Primary objective in the trial protocol

“to define the effects of pritelivir on the QTcF interval derived from 12-lead ECGs in comparison with placebo in male and female subjects” (opens the source at this quote in a new tab)

Secondary objectives in the trial protocol

“to assess pharmacokinetic properties of multiple doses of pritelivir and to examine the correlations between pritelivir plasma concentration and its effects, if any, on the QTcF interval” (opens the source at this quote in a new tab)
“to evaluate additional electrocardiographic effects of pritelivir” (opens the source at this quote in a new tab)
“to show the trial’s assay sensitivity by assessing the effects of moxifloxacin (positive control vs. placebo) on the QTcF interval” (opens the source at this quote in a new tab)
“to investigate the safety and tolerability of pritelivir” (opens the source at this quote in a new tab)

Purpose of the thorough QT/QTc trial

“the present thorough QT/QTc trial is designed to investigate the potential of pritelivir to cause QT/QTc prolongation.” (opens the source at this quote in a new tab)
“It will be analyzed to determine whether oral pritelivir has a potential risk of causing QT/QTc prolongation after a multiple-dose administration of pritelivir and a single dose administration of moxifloxacin (positive control) as well as the corresponding matching placebos.” (opens the source at this quote in a new tab)

Registry dates and status

Field	Quoted record
Study start (actual)	“2022-12-04”
Primary completion (actual)	“2023-05-18”
Study completion (actual)	“2023-05-18”
First submitted	“2022-12-12”
First posted	“2023-01-04”
Results first submitted	“2024-04-09”
Results first posted	“2025-03-14”
Last update posted	“2025-03-14”
Recruitment status	“Completed”

Registry study site

Field	Quoted record
Number of locations	“This study has 1 location”
Location	“London, United Kingdom, SE1 1YR”
Facility	“Richmond Pharmacology Ltd”

Protocol identifiers, version, and planned trial period

Field	Quoted record
Sponsor	“AiCuris Anti-infective Cures AG”
EudraCT number	“2022-000203-12”
Protocol version	“V2.0”
Protocol date	“25 Nov 2022”
Study center	“Richmond Pharmacology”
Planned trial period	“Q4 2022 to Q2 2023”
Phase of development	“Phase 1”

Single-center conduct in a clinical pharmacology unit

“This will be a single-center trial.” (opens the source at this quote in a new tab)
“This trial will be conducted in a specialized early phase Clinical Pharmacology Unit with on site resuscitation equipment and medication, in addition to access to an acute hospital with Critical Care facilities, thus ensuring direct access to equipment and staff for resuscitating and stabilizing subjects in acute medical conditions and emergencies.” (opens the source at this quote in a new tab)

Protocol version 2 and comments from the United Kingdom regulator

“The protocol V2.0 was primarily issued to address comments from the MHRA.” (opens the source at this quote in a new tab)
“The selection criteria for the trial population were modified with regard to core laboratory parameters and concomitant medications.” (opens the source at this quote in a new tab)
“The rules for suspension of dosing in case of adverse reactions were modified for severe adverse reactions, hematological reactions, liver reactions, and dermatological reactions.” (opens the source at this quote in a new tab)

Protocol version used for the statistical analysis plan

“The protocol dated 25 November 2022, version 2.0 was used to prepare this SAP.” (opens the source at this quote in a new tab)

Design summary in the registry record

“This Phase 1 clinical trial was a double-blind, single-center, randomized and placebo-controlled trial in which healthy male and female subjects received in 2 parallel-groups daily oral doses of pritelivir (Group 1) or matching placebo (Group 2).” (opens the source at this quote in a new tab)
“Within Group 2, a single oral administration of moxifloxacin (positive control) and corresponding matching placebo was administered in a 2-sequence crossover design (nested crossover).” (opens the source at this quote in a new tab)

Registry design fields

Field	Quoted record
Study type	“Interventional”
Phase	“Phase 1”
Allocation	“Randomized”
Interventional model	“Parallel Assignment”
Masking	“Double”
Primary purpose	“Prevention”
Enrollment (actual)	“64”

Overall design in the trial protocol

“This Phase 1 clinical trial is a double-blind, single-center, randomized, placebo- and positive-controlled, parallel-group, ‘nested crossover’ trial with multiple oral dose administration of pritelivir or matching placebo as well as a single oral administration of moxifloxacin (positive control) and corresponding matching placebo in healthy male and female subjects.” (opens the source at this quote in a new tab)
“Subjects will be in-house from Day -2 to Day 20 and will be randomized to one of the 2 parallel treatment groups: Group 1 will receive a therapeutic and a supra-therapeutic dose of pritelivir plus moxifloxacin placebo.” (opens the source at this quote in a new tab)
“Group 2 will receive pritelivir placebo as well as moxifloxacin and matching placebo (nested crossover: Group 2a and Group 2b).” (opens the source at this quote in a new tab)

Randomization ratio and schedule

“Subjects will be randomly assigned to Group 1, Group 2a, or Group 2b at a 2:1:1 ratio.” (opens the source at this quote in a new tab)
“All subjects in this trial will be assigned to a treatment regimen according to a randomization schedule generated by a statistician using PROC Plan.” (opens the source at this quote in a new tab)

Blinding of participants, site staff, and sponsor

“Subjects and all trial personnel, except for pharmacy staff at Richmond Pharmacology, and A&M for assignment of bioanalytical samples, will be blinded with respect to the assignment to group 1 (pritelivir) and 2 (matched placebo to pritelivir) as well as the treatment sequence of moxifloxacin and respective matching placebo in group 2.” (opens the source at this quote in a new tab)
“To maintain blinding, matching placebos (pritelivir or moxifloxacin, as appropriate) will be used at equivalent timepoints to verum treatment in other treatment sequences, so that all subjects receive the same number of tablets or capsules, with the same appearance, at equivalent timepoints in their respective treatment sequence.” (opens the source at this quote in a new tab)
“Over-encapsulated moxifloxacin- and matching placebo will be used to maintain double-blindness.” (opens the source at this quote in a new tab)
“The pharmacy staff preparing the IMP will not be blinded to trial drug assignment.” (opens the source at this quote in a new tab)
“Administrative and operational staff of the trial site, including Principal Investigator and trial manager as well as monitors, AiCuris staff and data managers will remain blinded during the course of the trial until Database Lock and finalization of the Statistical Analysis Plan.” (opens the source at this quote in a new tab)

Electrocardiogram recording days and Holter backup

“12-lead ECG triplicates will be recorded from the bedside 12-lead-ECG on the Days -1, 1, 2, 6, 16, and 17 and will be analyzed afterwards in each group for these 6 days of documentation by a blinded reader.” (opens the source at this quote in a new tab)
“It is of note that Holter ECG data will be collected in parallel at screening to exclude anyone with pre-existing cardiac problems as well as on Days -1, 1, 2, 6, 16, and 17 as a back-up for the bedside 12-lead-ECGs.” (opens the source at this quote in a new tab)
“From 1 hour prior to dosing until 8 h (Day 2 and Day 17) or 24 h (Day -1, 1, Day 6 and Day 16) after dosing, a Holter-ECG will be carried out in all subjects.” (opens the source at this quote in a new tab)

Electrocardiogram acquisition and central reading

“12-lead standard ECGs according to Einthoven, Goldberger and Wilson will be recorded each time after 10 minutes rest in a supine position.” (opens the source at this quote in a new tab)
“At each timepoint, the ECG will be recorded in triplicate, to reduce variance and improve the precision of measurement.” (opens the source at this quote in a new tab)
“The triplicates will be performed at approximately 1-minute intervals.” (opens the source at this quote in a new tab)
“Each ECG recording (trace) will last 10 seconds.” (opens the source at this quote in a new tab)
“Blinding of the ECGs with respect to subject number, treatment period, trial day and time will be performed before ECG analysis by the central ECG laboratory.” (opens the source at this quote in a new tab)
“All ECGs from one subject should be read by the same person at the central ECG laboratory.” (opens the source at this quote in a new tab)

Rationale for the design and the control groups

“adequate methods of trial control including double-blinded administration using matching placebos, randomization, and concurrent use of a positive control group are enforced to reduce bias produced by subjects’ and Investigators’ expectations.” (opens the source at this quote in a new tab)
“The multiple-dose regimen was chosen to achieve an adequate exposure of pritelivir (Group 1) with a parallel-group comparison versus placebo (Group 2) due to a known long half-life of pritelivir.” (opens the source at this quote in a new tab)
“The positive control using moxifloxacin (Group 2) will serve for the demonstration of assay sensitivity and will account for sequence effects based on a ‘nested’, placebo-controlled,” (opens the source at this quote in a new tab)
“crossover design within Group 2 (ie, 2a vs. 2b).” (opens the source at this quote in a new tab)

FDA review of the proposed design

“The proposed trial design has been discussed with the FDA who provided some additional points for consideration.” (opens the source at this quote in a new tab)
“Overall, the proposed study design and analysis plan appear acceptable to characterize the effects of pritelivir on the QTc interval.” (opens the source at this quote in a new tab)
“In addition to primary analysis, we recommend that you conduct the by-time analysis using a linear mixed model and perform categorical analysis for all ECG biomarkers (QTc, ΔQTc, HR, PR, QRS, and T-wave morphology).” (opens the source at this quote in a new tab)

Duration of participation

“The maximum total period of subject participation in the trial will be 58 days from Screening, through Admission, inpatient treatment period, outpatient treatment period and up to the EoT safety follow-up visit” (opens the source at this quote in a new tab)
“The End of Trial examination (EoT) will be performed 14 to 21 days after last dosing, on Day 30 up to Day 37.” (opens the source at this quote in a new tab)

Period	Days	Duration
Screening period	“Day -21 to Day -1”	“21 days”
Treatment period (inpatient)	“Day 1 to Day 20”	“20 days”
Follow-up period (to end of trial)	“Up to Day 30 to 37”	“17 days”

Risk Benefit Committee and adaptive dose feature

“A Risk Benefit Committee (RBC) consisting of at least the Principal Investigator, AiCuris Responsible Physician, and the Pharmacovigilance Manager will meet to decide in cases where (non-emergency) unblinding or reductions in supratherapeutic dose levels may be necessary, or any other case where the Sponsor or PI consider this necessary.” (opens the source at this quote in a new tab)
“If AEs interfere with adequate ECG recording, a Risk Benefit Committee (participants from AiCuris as well as the Principal Investigator) might decide to lower the (supra-therapeutic) dose in individual subjects.” (opens the source at this quote in a new tab)
“This trial incorporates the use of an adaptive design.” (opens the source at this quote in a new tab)

Age, sex, and healthy volunteer status in the registry record

Field	Quoted record
Ages eligible for study	“18 Years to 45 Years”
Sexes eligible for study	“All”
Accepts healthy volunteers	“Yes”

Inclusion criteria: health status and consent

“Healthy male and female subjects of any ethnic origin, aged between 18 and 45 years (inclusive).” (opens the source at this quote in a new tab)
“Assessed as healthy based on a Screening examination including medical history, physical examination, blood pressure, pulse rate, ECG assessment, and clinical laboratory results.” (opens the source at this quote in a new tab)
“Subject had been informed both verbally and in writing about the objectives of the clinical trial, the methods, the anticipated benefits and potential risks and the discomfort to which they may be exposed and had given written consent to participation in the trial prior to trial start and any trial-related procedure.” (opens the source at this quote in a new tab)

Inclusion criteria: body weight, tablet burden, and screening tests

“Normal body weight as evidenced by a Body Mass Index (BMI) ≥18.0 and ≤25.0 kg/m2, and a body weight ≥50.0 kg at Screening.” (opens the source at this quote in a new tab)
“Subject had to be willing and able to swallow up to 4 tablets (pritelivir or matching placebo) and 1 capsule (over-encapsulated moxifloxacin or matching placebo) at least twice during the trial.” (opens the source at this quote in a new tab)
“Subjects must have a negative test result for HIV-I- and -II-antibody, HBsAg, anti-hepatitis B core antigen (HBc) (IgG + IgM) and anti-hepatitis C virus (HCV) at Screening.” (opens the source at this quote in a new tab)
“Subjects had to have negative urine tests for drugs of abuse (benzodiazepines, opiates, amphetamines, methadone, cocaine, cannabinoids, barbiturates, cotinine) and negative breath alcohol tests at Screening and Admission for the in-house phase (Day -2).” (opens the source at this quote in a new tab)
“In women, negative serum β-HCG (beta-human chorionic gonadotropin) test at Screening and negative urine β-HCG test on Day -2.” (opens the source at this quote in a new tab)
“Subject agreed to pharmacogenomic blood sampling.” (opens the source at this quote in a new tab)

Inclusion criteria: electrocardiographic requirements

“Normal triplicate 12-lead ECG measured after 10 minutes in the supine position at screening and on admission on Day -2 showing regular sinus rhythm with a well-defined end of T.” (opens the source at this quote in a new tab)
“Normal 24-hour 12-lead ECG at screening.” (opens the source at this quote in a new tab)

Inclusion criteria: contraception

“Male subjects were not planning to father or to donate sperms for in vitro fertilization during the trial and for at least 3 months after dosing of trial medication.” (opens the source at this quote in a new tab)
“Women of childbearing potential had to perform adequate contraception.” (opens the source at this quote in a new tab)
“Adequate contraception was defined as a combination of a highly effective method of birth control and additional barrier contraception.” (opens the source at this quote in a new tab)
“Highly effective method of birth control was defined as follows: combined (estrogen and progesterone) oral contraceptives, combined hormonal vaginal rings, hormone implants, hormone injectables, or intrauterine device that needed to be in place for a period of at least 2 months prior to Screening and continue for at least 3 months after dosing of trial medication.” (opens the source at this quote in a new tab)
“A single barrier method alone or abstinence alone was not acceptable.” (opens the source at this quote in a new tab)
“Women of non-childbearing potential could be included if surgically sterile (documented complete hysterectomy, supracervical hysterectomy or bi-tubal ligations; partial hysterectomy was not sufficient) or if postmenopausal (who have a history of no menses of at least 24 months at screening and postmenopausal status was confirmed by follicle stimulating hormone [FSH] test at screening).” (opens the source at this quote in a new tab)

Exclusion criteria: cardiac history, vital signs, and electrocardiographic intervals

“The history or presence of any of the following cardiac conditions: known structural cardiac abnormalities; family history of long QT syndrome; cardiac syncope or recurrent, idiopathic syncope; exercise-related clinically significant cardiac events; known cardiovascular disease.” (opens the source at this quote in a new tab)
“Consistent abnormal interval readings for PR, QRS and QTc intervals (PR <120ms or >210ms, QRS >120ms or QTcF >450ms for males and >470ms for females).” (opens the source at this quote in a new tab)
“Transient fascicular blocks, undue ectopic burden, junctional rhythm and any other ECG findings which may in the opinion of the Investigator make a subject unsuitable for inclusion in this clinical trial.” (opens the source at this quote in a new tab)
“Has vital signs consistently outside of normal range at screening or Day -1.” (opens the source at this quote in a new tab)
“supine heart rate (HR) 40 - 100 bpm (after at least five minutes of supine rest)” (opens the source at this quote in a new tab)
“systolic blood pressure: 90 - 130 mmHg” (opens the source at this quote in a new tab)
“diastolic blood pressure: 40 - 90 mmHg” (opens the source at this quote in a new tab)

Exclusion criteria: medical history

“History or current evidence of clinically relevant allergies or idiosyncrasy to drugs or food.” (opens the source at this quote in a new tab)
“History of any moderate or severe allergy or any known allergy to any active or inactive ingredient(s) of moxifloxacin investigational medicinal product (IMP), pritelivir IMP, or their respective matching placebos.” (opens the source at this quote in a new tab)
“History or current evidence of any clinically relevant cardiovascular, pulmonary, hepatic, renal, gastrointestinal, hematologic, endocrine, metabolic, neurological, psychiatric, or other disease suspected to influence pharmacokinetics or safety of the IMP.” (opens the source at this quote in a new tab)
“History or any current evidence of a dermatological condition requiring treatment by a general practitioner (GP) or specialist (with the exception of burns, fungal infections, and/or warts).” (opens the source at this quote in a new tab)
“History of malignancy.” (opens the source at this quote in a new tab)
“Chronic or clinically relevant acute infections or febrile illness within 5 days prior to administration of the IMP.” (opens the source at this quote in a new tab)
“Diseases or surgery of the gastrointestinal tract which could have interfered with drug absorption (note: this is not applicable for minor abdominal surgery such as eg, appendectomy and herniotomy).” (opens the source at this quote in a new tab)
“Subject was lactating or breastfeeding.” (opens the source at this quote in a new tab)

Exclusion criteria: laboratory values

“Clinically relevant abnormalities in serum chemistry, haematology and coagulation parameters, urinalysis.” (opens the source at this quote in a new tab)
“Participants with transaminases (AST/ALT) above ULN or total bilirubin x1.5 ULN, at Screening.” (opens the source at this quote in a new tab)
“Hemoglobin below lower limit of normal (LLN) at Screening.” (opens the source at this quote in a new tab)
“Platelet count below LLN at Screening.” (opens the source at this quote in a new tab)
“White Blood Count above upper limit of normal (ULN) at Screening.” (opens the source at this quote in a new tab)
“Participants with urinalysis indicative of underlying infection/pathology at Screening.” (opens the source at this quote in a new tab)
“Magnesium or potassium outside normal range in safety laboratory” (opens the source at this quote in a new tab)

Exclusion criteria: medications, vaccination, and investigational drugs

“Use of any medication (incl. over-the-counter medication) within 2 weeks before dosing on Day 1 or within less than 10 times the elimination half-life of the respective drug, or anticipated concomitant medication during the treatment period.” (opens the source at this quote in a new tab)
“Exceptions may be the use of hormonal contraception and hormone replacement therapy as well as single intake of a drug if judged by the Investigators to have no clinical relevance and no relevance for the trial objectives.” (opens the source at this quote in a new tab)
“Subject had received or is planning to receive a COVID-19 vaccination within 4 weeks before first dose administration, or within one week after trial completion.” (opens the source at this quote in a new tab)
“Treatment with an investigational drug within 90 days or 5 half-lives preceding the first dose of trial medication (or as determined by the local requirement, whichever is the longer).” (opens the source at this quote in a new tab)
“Participation in an earlier clinical trial with pritelivir.” (opens the source at this quote in a new tab)
“Donation of blood or blood products (excluding plasma) within 90 days prior to trial medication administration.” (opens the source at this quote in a new tab)

Exclusion criteria: alcohol, tobacco, and substance use

“Consumption of alcohol and tobacco products within 48 h prior to admission to the clinic until discharge.” (opens the source at this quote in a new tab)
“Smoking of more than 10 cigarettes/cigars/pipes per day and/or inability to refrain from smoking during confinement.” (opens the source at this quote in a new tab)
“History or clinical evidence of substance and/or alcohol abuse within the 2 years before screening.” (opens the source at this quote in a new tab)
“Alcohol abuse was defined as regular weekly intake of more than 14 units (for both males and females)” (opens the source at this quote in a new tab)

Exclusion criteria: diet, communication, and vulnerable persons

“Any special dietary requirements that would have prevented the consumption of standardized meals.” (opens the source at this quote in a new tab)
“Not able to communicate meaningfully with the Investigator and site staff.” (opens the source at this quote in a new tab)
“Lack of ability or willingness to give informed consent.” (opens the source at this quote in a new tab)
“Vulnerable subjects (eg, persons kept in detention).” (opens the source at this quote in a new tab)

Withdrawal criteria in the trial protocol

“A subject may terminate participation in the trial at any time without providing a reason and without any personal disadvantage.” (opens the source at this quote in a new tab)
“Use of/need for a prohibited medication which in the opinion of the Sponsor or Investigator may jeopardize the trial results or represent a risk to the subject” (opens the source at this quote in a new tab)
“Subject meets the individual rules criteria (see Appendix 2)” (opens the source at this quote in a new tab)
“Subjects who are withdrawn from the trial are not allowed to re-enter at a later date.” (opens the source at this quote in a new tab)

Regimens by group in the registry record

Group	Pritelivir or matching placebo	Moxifloxacin or matching placebo
Group 1	“Subjects (32 male and female subjects) received 400 mg pritelivir on Day 1, 100 mg pritelivir from Day 2 to 6 and 400 mg pritelivir from Day 7 to 16.”	“Furthermore, these subjects received moxifloxacin matching placebo on the Days 2 and 17.”
Group 2a	“Subjects (16 male and female subjects) received the respective amounts of tablets of matching pritelivir matching placebo on Day 1 to Day 16 in Group 2a as verum tablets in Group1.”	“Furthermore, these subjects received 400 mg moxifloxacin on Day 2 and moxifloxacin matching placebo on Day 17.”
Group 2b	“Subjects (16 male and female subjects) received the respective amounts of tablets of matching pritelivir matching placebo on Day 1 to Day 16 in Group 2b as verum tablets in Group1.”	“Furthermore, these subjects received moxifloxacin matching placebo on Day 2 and 400 mg moxifloxacin on Day 17.”

Investigational products

“There are 4 IMPs in this clinical trial:” (opens the source at this quote in a new tab)
“Pritelivir 100 mg tablets” (opens the source at this quote in a new tab)
“Matching placebo to Pritelivir 100 mg tablets” (opens the source at this quote in a new tab)
“Encapsulated moxifloxacin tablets 400 mg” (opens the source at this quote in a new tab)
“Matching placebo to encapsulated moxifloxacin tablets 400 mg” (opens the source at this quote in a new tab)
“Pritelivir 100 mg tablets are provided as film-coated tablets for oral administration.” (opens the source at this quote in a new tab)

Pritelivir and pritelivir placebo dosing

“In Group 1: A loading dose of 400 mg on Day 1, followed by a once daily 100 mg dose regimen from Day 2 to Day 6, followed by a once daily 400 mg dose regimen from Day 7 to Day 16.” (opens the source at this quote in a new tab)
“In Group 2: The same number of corresponding pritelivir placebo tablets will be administered from Day 1 to Day 16 in Group 2 as verum tablets in Group 1.” (opens the source at this quote in a new tab)

Moxifloxacin and moxifloxacin placebo dosing

“A single oral dose of 400 mg moxifloxacin will be administered in Group 2a on Day 2 and in Group 2b on Day 17.” (opens the source at this quote in a new tab)
“A single oral dose of moxifloxacin placebo will be administered in Group 1 on Days 2 and 17 as well as on Day 17 in Group 2a and Day 2 in Group 2b.” (opens the source at this quote in a new tab)

Tablets and capsules dispensed for each dose

Group	Treatment	Product dispensed
Group 1	“400 mg or 100 mg pritelivir”	“4 or 1 x 100 mg pritelivir tablet”
Group 1	“Moxifloxacin placebo”	“1 x matched placebo to moxifloxacin capsule”
Group 2a and Group 2b	“Pritelivir placebo”	“4 or 1 x matched placebo to pritelivir tablet(s)”
Group 2a and Group 2b	“400 mg Moxifloxacin”	“1 x 400 mg moxifloxacin capsule”

Administration with water and fasting on electrocardiogram days

“Study treatments will be administered to each participant with 240 mL of water” (opens the source at this quote in a new tab)
“On Days -1, 1, 2, 6, 16 and 17, in order to omit the effect of food subjects will fast from at least 10 h before until 4 h after dosing to have the same conditions on all Holter-ECG days.” (opens the source at this quote in a new tab)
“On all other days between Day 3 and 15 (except Day 6), subjects will be dosed 2 h after a standardized continental breakfast.” (opens the source at this quote in a new tab)

Selection of the therapeutic dose and the loading dose

“Pritelivir has already entered Phase 3 development stage and the therapeutic dose for pritelivir in the currently ongoing Phase 3 trial is 100 mg/day.” (opens the source at this quote in a new tab)
“Therefore, this is also the planned therapeutic dose for this TQT trial.” (opens the source at this quote in a new tab)
“Due to the long terminal elimination half-life, a loading dose of 400 mg will be administered on Day 1 to reach steady-state conditions immediately.” (opens the source at this quote in a new tab)
“This will also guarantee steady-state conditions on the planned PK- and ECG-Day 6.” (opens the source at this quote in a new tab)

Selection of the supratherapeutic dose

“Thus, a high supra-therapeutic dose of pritelivir, which results in an exposure in excess of what would be observed in patients, will be used in this TQT trial.” (opens the source at this quote in a new tab)
“Following the exposure to 400 mg pritelivir on Day 1 and 100 mg qd for the next 5 days, dosing of 400 mg qd pritelivir for 10 further days (Day 7 to Day 16) is sufficient (based on results of trial AIC316-01-I-05) to reach steady-state conditions for the planned pharmacokinetic sampling and ECG Day 16.” (opens the source at this quote in a new tab)
“Overall, a dosage of 400 mg qd pritelivir is considered to be the supra-therapeutic dose because of a lag of absorption at doses higher than 400 mg pritelivir, ie, no higher exposures can be reached by increasing the dose when administering pritelivir once daily.” (opens the source at this quote in a new tab)
“An about 4-fold higher exposure after 400 mg qd dosing compared to the therapeutic exposure after 100 mg qd dosing is also considered to cover intrinsic and extrinsic factors that may increase pritelivir exposure after a therapeutic dose of 100 mg pritelivir is given” (opens the source at this quote in a new tab)
“In conclusion, the expected highest pritelivir exposure in this TQT trial after 400 mg qd pritelivir dosing at steady state is already covered by previous clinical trial- and nonclinical data.” (opens the source at this quote in a new tab)

Selection of the moxifloxacin dose

“A single dose of 400 mg moxifloxacin will be administered in this trial to demonstrate the trial’s ability to detect a small effect on the QT interval (assay sensitivity).” (opens the source at this quote in a new tab)
“This dose is the standard dose in TQT trials” (opens the source at this quote in a new tab)

Concomitant medications

“Concomitant medication is prohibited throughout the trial, except for hormonal contraception and hormone replacement therapy as well as single intake of a drug if judged by the Investigators to have no clinical relevance and no relevance for the trial objectives.” (opens the source at this quote in a new tab)
“Limited amounts of paracetamol (not exceeding 2 g per day) are allowed on demand to treat painful intercurrent adverse events (eg, headache, migraine).” (opens the source at this quote in a new tab)

Dose reduction rules for the supratherapeutic dosing period

“In the unlikely case that adverse events from SOC skin and subcutaneous tissue disorders occur to such an extent or severity that subjects have to be withdrawn from the trial, the supratherapeutic dose may be reduced to 200 mg/day pritelivir i) in an individual subject for the rest of the dosing phase, or ii) it may even be decided to suspend further dosing of all subjects (see Appendix 2).” (opens the source at this quote in a new tab)
“Dose reduction is not possible if the adverse reaction occurs during D1 to D6 dosing.” (opens the source at this quote in a new tab)
“For adverse reactions that occur during the 400 mg/day supratherapeutic dosing period (D7 to D16), the following rules apply regarding reduction to 200 mg/day dosing.” (opens the source at this quote in a new tab)

Treatment compliance

“All trial medication administrations will be performed by the Investigator or appropriately trained designee (for example a Research Physician) and the dosing will be verified by another member of the Investigator’s staff.” (opens the source at this quote in a new tab)
“After oral administration, a thorough hand and mouth check will be performed to ensure proper oral ingestion of the trial medication.” (opens the source at this quote in a new tab)
“The blood concentrations of pritelivir and moxifloxacin will serve as an additional measure of treatment compliance.” (opens the source at this quote in a new tab)

Primary endpoint defined in the statistical analysis plan

“QTc using Fridericia correction method (QTcF).” (opens the source at this quote in a new tab)
“The primary endpoint is defined as the model based QTcF change from baseline (ΔQTcF), where baseline is the average of the 3 pre-dose measurements of Day 1.” (opens the source at this quote in a new tab)
“ECGs from Day 1, Day 6 and Day 16 will be used for comparison against baseline.” (opens the source at this quote in a new tab)

Primary outcome measure in the registry record

Field	Quoted record
Outcome measure	“Effects of Pritelivir on the QTcF Interval (QTc Using Fridericia Correction Method) in Comparison With Placebo in Male and Female Subjects.”
Description	“Mean QTcF values using the Frederica correction method derived from 12-lead ECGs were used to define the effects of pritelivir in comparison with placebo in male and female subjects.”
Time frame	“Day -2 to Day 20”

Threshold of regulatory concern for the change in QTcF

“Predictions of the effect of pritelivir and metabolites at the concentrations seen at tmax of each of the moieties involved will be used to exclude an effect of regulatory concern (ie, a one-sided 95% confidence interval for ΔQTcF completely below 10 ms).” (opens the source at this quote in a new tab)

Regulatory guidance behind the endpoint and the Fridericia correction

“Statistical analyses of ECG variables will be performed according to the recommendations provided by the guideline ICH-E14 and its Q&A documents.” (opens the source at this quote in a new tab)
“If your product is likely to increase or decrease the heart rate significantly (e.g., >10 bpm) in the study, you will need to consider the use of alternative methods for assessing changes in the QT interval, such as QTcI (individualized QT correction).” (opens the source at this quote in a new tab)
“In the absence of significant heart rate effects, we recommend the use of QTcF for the primary analysis.” (opens the source at this quote in a new tab)

Planned replacement of QTcF by an individual correction after a heart rate effect

“If there are indications that pritelivir has an effect on HR exceeding 10 bpm, HR will also be submitted to a similar analysis as QTcF.” (opens the source at this quote in a new tab)
“If this confirms an effect exceeding 10 bpm, then an individual correction will be determined based on the ECG data from Day -1, and QT values corrected according to this method (QTcI) will replace QTcF in the primary analyses.” (opens the source at this quote in a new tab)

Role of moxifloxacin as the positive control

“The role of moxifloxacin in this trial is to demonstrate the trial’s ability to detect a small effect on the QT interval (assay sensitivity), since moxifloxacin is known to have a mild QT prolonging effect that has been used in the majority of thorough QT/QTc trials” (opens the source at this quote in a new tab)

Nonclinical and earlier clinical electrocardiographic findings cited in the trial protocol

“Nonclinical safety pharmacology studies in Beagle dogs showed no adverse cardiac effects” (opens the source at this quote in a new tab)
“No evidence was noted for a prolongation of the QT interval.” (opens the source at this quote in a new tab)
“revealed a concentration-dependent inhibition of hERG-mediated tail current amplitude (IC50 ~156 µM).” (opens the source at this quote in a new tab)
“However, since the IC50 (hERG) is more than 100-fold greater than the mean therapeutic Cmax values when corrected for free fraction (from 109-fold for the 400 mg/day to 355-fold for the 100 mg/day dose group at steady state), the interaction between pritelivir and hERG is of negligible clinical relevance in humans.” (opens the source at this quote in a new tab)
“No effect on any ECG parameter, including QT and QTcF, could be detected in clinical trials by classical 12-lead safety ECGs so far for doses up to 400 mg pritelivir per day.” (opens the source at this quote in a new tab)

Secondary electrocardiographic variables

“Heart rate” (opens the source at this quote in a new tab)
“PR interval” (opens the source at this quote in a new tab)
“QRS interval” (opens the source at this quote in a new tab)
“Uncorrected QT interval” (opens the source at this quote in a new tab)
“Change in ECG morphological patterns” (opens the source at this quote in a new tab)

Categorical analyses of QTcF

“QTcF interval >450 ms to ≤480 ms” (opens the source at this quote in a new tab)
“QTcF interval >480 ms to ≤500 ms” (opens the source at this quote in a new tab)
“QTcF interval >500 ms” (opens the source at this quote in a new tab)
“QTcF interval increases from baseline >30 msec to ≤60 msec” (opens the source at this quote in a new tab)
“QTcF interval increases from baseline >60 ms” (opens the source at this quote in a new tab)
“Fulfilling both, absolute QTcF values >500 ms and ΔQTcF >60 ms;” (opens the source at this quote in a new tab)

Categorical analyses of PR interval, QRS duration, and heart rate

“Absolute PR values >200 ms, >220 ms, with a pre-dose value below the respective threshold” (opens the source at this quote in a new tab)
“Absolute QRS duration >110 ms and >120 ms” (opens the source at this quote in a new tab)
“Absolute HR of <50 bpm or ≥100 bpm” (opens the source at this quote in a new tab)

Pharmacokinetic sampling and plasma concentration endpoints

“PK samples will be collected from subjects of both groups on the Days 1, 6, and 16 for pritelivir and the metabolites AIC090015 and AIC090105 as well as for moxifloxacin on the Days 2 and 17.” (opens the source at this quote in a new tab)

“Plasma concentrations of pritelivir and its metabolites AIC090015 and AIC090105 will be determined for the purpose of the concentration-effect analysis (described in this document) as well as for standard pharmacokinetic evaluation (described in the separate PK SAP).” (opens the source at this quote in a new tab)
“The concentrations will be reported, but no pharmacokinetic parameters will be determined.” (opens the source at this quote in a new tab)

Blood sampling times for pritelivir and its metabolites

“Day 1: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, and 24 h post-dose” (opens the source at this quote in a new tab)
“Day 3 to 5: pre-dose (trough),” (opens the source at this quote in a new tab)
“Day 6: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, and 24 h post-dose” (opens the source at this quote in a new tab)
“Day 13 to 15: pre-dose (trough),” (opens the source at this quote in a new tab)
“Day 16: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, and 24 h post-dose” (opens the source at this quote in a new tab)

Reference ranges for electrocardiographic parameters

Parameter	Quoted normal range
Heart rate (supine)	“40-100 bpm”
PR interval	“120–210 ms”
QRS duration	“≤120 ms”
QTcF	“≤450 ms (Males); ≤470 ms (Females)”

Safety and tolerability endpoints

“Overall tolerability” (opens the source at this quote in a new tab)
“Nature, frequency, duration, intensity, seriousness, and causality of adverse events” (opens the source at this quote in a new tab)
“Physical examination, vital signs, and body temperature” (opens the source at this quote in a new tab)
“Clinical laboratory parameters: serum chemistry, hematology and coagulation parameters, urinalysis” (opens the source at this quote in a new tab)
“Standard 12-lead ECG collected using a 12-lead ECG device” (opens the source at this quote in a new tab)

Planned number of participants

“64 (32 subjects per group; at least 12 of each sex in each group)” (opens the source at this quote in a new tab)

Sample size rationale

“Simulations by Huang et al suggest that using concentration-response analysis, assay sensitivity can be shown with at least 24 subjects” (opens the source at this quote in a new tab)
“Since in this trial, the time between the 2 periods of the nested crossover is 14 days, it seems prudent to allow for a slightly higher variability of ΔQTc and, therefore, a sample size of 32 subjects has been planned.” (opens the source at this quote in a new tab)
“Assuming a true effect of at most 3 ms, ie, a margin of 7 ms, the power to show absence of an effect of pritelivir is higher than that to show assay sensitivity where the margin may be assumed to be 5 ms.” (opens the source at this quote in a new tab)
“Therefore, 32 subjects in the active group were chosen.” (opens the source at this quote in a new tab)

Reserve participants at screening

“Additional subjects will be screened as reserve subjects.” (opens the source at this quote in a new tab)

Participants enrolled and included in the baseline analysis

Population	Group 1	Group 2a	Group 2b	Total
Overall number of baseline participants	“32”	“16”	“16”	“64”

Participants analyzed for the primary outcome measure

Population	Group 1	Group 2a	Group 2b
Participants analyzed	“32”	“16”	“16”

Safety set and pharmacokinetic set

“The safety set (SS) will consist of all randomised subjects who received at least one dose of the trial medication.” (opens the source at this quote in a new tab)
“The Pharmacokinetic Set (PKS) will include all subjects in SS who had at least 1 valid plasma concentration-time point to be included in the PK analysis.” (opens the source at this quote in a new tab)

Electrocardiogram set

“The ECG set will include all subjects in the SS that have at least one valid pre-dose ECG assessment and one valid post-dose assessment ECGs are considered valid if they are based on at least 2 replicates with measurable QTc and RR.” (opens the source at this quote in a new tab)

Analysis set for the concentration-QTc analysis

“The analysis set for concentration-QTc analysis will be a subset of the intersection of the PK set and the ECG set.” (opens the source at this quote in a new tab)
“The concentration-ECG analyses will be performed on the set for concentration-QTc analysis, all other analyses not requiring PK data will be performed on the ECG-Set.” (opens the source at this quote in a new tab)

“Only those pairs of ECG and PK data where samples were taken within these time windows will be included in this analysis set.” (opens the source at this quote in a new tab)
“Note that a dose reduction is not a reason to exclude a subject from this analysis set.” (opens the source at this quote in a new tab)

Maximum time between blood sampling and electrocardiogram for a paired measurement

Postdose time point	Deviation above which the pair is excluded
15 minutes to 1 hour	“11 min for timepoints 15 min to 1 h post dose”
2 hours to 4 hours	“16 min for timepoints 2 h to 4 h post dose”
5 hours	“18 min for timepoint 5 h post dose”
6 hours to 12 hours	“33 min for timepoints 6 h to 12 h post dose.”

Analysis populations posted with the registry results

Analysis	Quoted population description
Baseline characteristics	“Safety Set”

Analysis	Quoted population description
Primary outcome measure	“Time course of the drug effect on QTcF: Model based estimates (ECG Set).”

Baseline for electrocardiographic variables

“Baseline for quantitative ECG variables will be the average of the 3 pre-dose values measured on Day 1 (which in turn are the average over the individual triplicates).” (opens the source at this quote in a new tab)

Concentration-QTc models for the primary analysis

“a series of 7 linear mixed effect models relating the change from baseline to the concentrations of pritelivir and the metabolites AIC090015 and AIC090105, together or separately, will be fitted” (opens the source at this quote in a new tab)
“Random effects per subject for the intercept and, if feasible, for the concentrations included in the respective models will be given.” (opens the source at this quote in a new tab)
“Selection of the primary model will be based on model fit and the Akaike Information Criterion.” (opens the source at this quote in a new tab)
“More specifically, among the models with no significant (at the two sided 5% level) treatment intercept, the one with lowest AIC will be selected as primary.” (opens the source at this quote in a new tab)
“The groups 2a and 2b will be pooled for analysis.” (opens the source at this quote in a new tab)

“Apart from these concentrations, the models will include fixed effects for time and treatment (Active or placebo) and baseline as a covariate.” (opens the source at this quote in a new tab)

Assay sensitivity analysis

“A comparison between moxifloxacin and matching placebo will be done in groups 2a and 2b to demonstrate assay sensitivity using a similar model to the model M1 described above.” (opens the source at this quote in a new tab)
“Assay sensitivity will be concluded if the lower limit of the one-sided 95% CI for the predicted effect will be >5 ms.” (opens the source at this quote in a new tab)

Time course analysis of electrocardiographic variables

“All quantitative ECG variables and their change from baseline will be summarized by timepoint and treatment group.” (opens the source at this quote in a new tab)
“In addition, they will be analysed with respect to their time course using a mixed effects linear model.” (opens the source at this quote in a new tab)
“This model will have treatment (pritelivir, placebo) and time as well as their interaction as fixed effects and a random intercept per subject.” (opens the source at this quote in a new tab)
“The time course of the drug effect will be estimated from the contrast using treatment and time by treatment interaction.” (opens the source at this quote in a new tab)

Safety analysis, pharmacokinetic analysis, and interim analysis

“Safety analyses will be performed on the safety set, unless otherwise stated.” (opens the source at this quote in a new tab)
“No formal statistical analysis will be performed.” (opens the source at this quote in a new tab)
“No interim analysis is planned for this trial.” (opens the source at this quote in a new tab)
“PK parameter analysis and report are out of scope for this SAP and details on this analysis will be provided by Venn Life Sciences.” (opens the source at this quote in a new tab)

Participant flow

Milestone	Group 1	Group 2a	Group 2b
Started	“32”	“16”	“16”
Completed	“32”	“16”	“16”
Not completed	“0”	“0”	“0”

Age

Characteristic	Group 1	Group 2a	Group 2b	Total
Participants	“32”	“16”	“16”	“64”
Age in years, mean (standard deviation)	“27.5 (4.74)”	“27.3 (4.78)”	“30.8 (6.23)”	“28.2 (5.28)”

Sex and ethnicity, count and percentage of participants

Characteristic	Group 1	Group 2a	Group 2b	Total
Female	“12”“37.5%”	“8”“50.0%”	“7”“43.8%”	“27”“42.2%”
Male	“20”“62.5%”	“8”“50.0%”	“9”“56.3%”	“37”“57.8%”
Hispanic or Latino	“3”“9.4%”	“0”“0.0%”	“2”“12.5%”	“5”“7.8%”
Not Hispanic or Latino	“29”“90.6%”	“16”“100.0%”	“14”“87.5%”	“59”“92.2%”
Ethnicity unknown or not reported	“0”“0.0%”	“0”“0.0%”	“0”“0.0%”	“0”“0.0%”

Race, count and percentage of participants

Characteristic	Group 1	Group 2a	Group 2b	Total
Asian	“4”“12.5%”	“0”“0.0%”	“1”“6.3%”	“5”“7.8%”
Black or African American	“2”“6.3%”	“2”“12.5%”	“2”“12.5%”	“6”“9.4%”
White	“20”“62.5%”	“12”“75.0%”	“11”“68.8%”	“43”“67.2%”
Other	“6”“18.8%”	“2”“12.5%”	“2”“12.5%”	“10”“15.6%”

Cardiac electrophysiology statement in the prescribing information

“At 4 times the recommended maintenance pritelivir dose, clinically significant QTc interval prolongation was not observed.” (opens the prescribing information at this quote)

Statistical analysis of the primary outcome measure posted on the registry

Field	Quoted record
Type of comparison	“NON_INFERIORITY”
Null hypothesis	“Null hypothesis: difference to placebo of change from baseline QTcF ≥ 10 ms.”
P value	“<0.05”
Statistical method	“Mixed Models Analysis”
Estimation parameter	“Prediction @ mean max concentration”
Estimated value	“0.8”
Confidence level, %	“90”
Number of sides	“TWO_SIDED”
Confidence interval, lower limit	“-1.3”
Confidence interval, upper limit	“2.9”
Unit of measure	“ms”

Mean QTcF in milliseconds by group and time point

Day and time relative to dosing	Group 1, mean	Group 1, standard deviation	Group 2a, mean	Group 2a, standard deviation	Group 2b, mean	Group 2b, standard deviation
Day 1, -1 hour	“402.66”	“15.198”	“405.23”	“17.208”	“401.94”	“16.989”
Day 1, -40 minutes	“404.55”	“15.043”	“408.19”	“17.040”	“404.21”	“17.782”
Day 1, -20 minutes	“405.66”	“15.781”	“409.10”	“15.934”	“405.19”	“19.805”
Day 1, 15 minutes	“405.86”	“15.653”	“407.06”	“14.679”	“406.23”	“16.081”
Day 1, 30 minutes	“400.94”	“14.466”	“403.96”	“15.311”	“398.56”	“17.347”
Day 1, 45 minutes	“401.82”	“13.891”	“405.48”	“17.832”	“402.13”	“17.295”
Day 1, 1 hr	“403.99”	“15.280”	“405.69”	“17.724”	“403.27”	“20.122”
Day 1, 2 hr	“403.34”	“13.638”	“406.42”	“16.724”	“404.06”	“19.436”
Day 1, 3 hr	“404.70”	“15.006”	“409.08”	“17.105”	“403.60”	“18.037”
Day 1, 4 hr	“405.84”	“14.719”	“407.63”	“16.228”	“403.75”	“19,248”
Day 1, 5 hr	“398.16”	“13.577”	“401.54”	“16.387”	“401.29”	“15.948”
Day 1, 6 hr	“396.48”	“13.705”	“397.56”	“15.982”	“396.98”	“16.573”
Day 1, 7 hr	“397.40”	“13.037”	“398.69”	“17,711”	“396.65”	“16.517”
Day 1, 8 hr	“398.92”	“14.727”	“401.81”	“16.308”	“397.98”	“17.455”
Day 1, 12 hr	“402.41”	“11.990”	“402.63”	“15.583”	“402.96”	“17.687”
Day 6, -1 hr	“406.43”	“14.456”	“404.94”	“13.207”	“404.63”	“20.971”
Day 6, -40 minutes	“405.40”	“16.410”	“407.56”	“16.518”	“406.60”	“18.966”
Day 6, -20 minutes	“407.01”	“16.483”	“405.33”	“14.640”	“407.94”	“16.662”
Day 6, 1 hr	“404.76”	“15.722”	“406.04”	“18.259”	“404.23”	“20.257”
Day 6, 2 hr	“405.93”	“15.895”	“404.54”	“17.555”	“404.29”	“19,128”
Day 6, 3 hr	“405.34”	“17.242”	“404.81”	“18.170”	“405.15”	“18.768”
Day 6, 4 hr	“404.73”	“16.959”	“406.44”	“18.839”	“405.63”	“22.097”
Day 6, 5 hr	“398.04”	“13.348”	“396.40”	“14.502”	“401.42”	“14.800”
Day 6, 6 hr	“395.97”	“14.423”	“396.48”	“15.856”	“397.83”	“18.350”
Day 6, 7 hr	“396.82”	“14.461”	“396.10”	“15.270”	“394.21”	“18.831”
Day 6, 8 hr	“400.02”	“13.161”	“397.63”	“17.160”	“398.40”	“16.213”
Day 6, 12 hr	“399.09”	“12.784”	“396.92”	“16.245”	“399.17”	“17.726”
Day 16, -1 hr	“403.56”	“15.159”	“405.54”	“13.995”	“404.79”	“15.734”
Day 16, -40 minutes	“404.81”	“15.116”	“405.54”	“17.129”	“405.52”	“15.714”
Day 16, -20 minutes	“405.36”	“13.483”	“408.75”	“15.479”	“406.38”	“14.649”
Day 16, 1 hr	“403.93”	“14.543”	“404.71”	“15.240”	“404.88”	“15.248”
Day 16, 2 hr	“404.14”	“14.856”	“407.85”	“15.755”	“405.15”	“18.643”
Day 16, 3 hr	“405.32”	“15.513”	“405.52”	“17.318”	“406.83”	“16.953”
Day 16, 4 hr	“405.74”	“15.966”	“406.85”	“17.257”	“405.38”	“16.946”
Day 16, 5 hr	“398.14”	“13.121”	“399.71”	“17.031”	“399.56”	“14.704”
Day 16, 6 hr	“395.29”	“12.566”	“397.60”	“16.424”	“396.04”	“16.262”
Day 16, 7 hr	“396.54”	“13.894”	“395.44”	“15.874”	“396.42”	“17.022”
Day 16, 8 hr	“400.52”	“16.196”	“399.52”	“16.536”	“398.46”	“15.975”
Day 16, 12 hr	“398.61”	“13.372”	“399.00”	“14.569”	“400.23”	“15.474”

Adverse event reporting period and group definitions

“Phase 1 trial primarily compares 2 parallel groups: Group 1 receiving pritelivir verum and Group 2 receiving matching pritelivir placebo and moxifloxacin.” (opens the source at this quote in a new tab)
“In Group 1 the different pritelivir doses were defined as one intervention with no differentiation between doses, to compare versus pritelivir placebo in Group 2 only.” (opens the source at this quote in a new tab)
“Group 2 (pritelivir placebo arm) was subdivided into subgroups 2a and 2b as subjects received 400 mg moxifloxacin on different days, Day 2 and Day 17, respectively.” (opens the source at this quote in a new tab)

Field	Quoted record
Time frame	“39 days”
Coding vocabulary	“MedDRA 26.0”

Deaths, serious adverse events, and other adverse events

Category	Group 1	Group 2a	Group 2b
All-cause mortality	“0/32 (0.00%)”	“0/16 (0.00%)”	“0/16 (0.00%)”
Serious adverse events	“0/32 (0.00%)”	“0/16 (0.00%)”	“0/16 (0.00%)”
Other (not including serious) adverse events	“20/32 (62.50%)”	“10/16 (62.50%)”	“10/16 (62.50%)”

Adverse events by system organ class and preferred term

System organ class	Preferred term	Group 1, affected / at risk	Group 1, events	Group 2a, affected / at risk	Group 2a, events	Group 2b, affected / at risk	Group 2b, events
Cardiac disorders	“dizziness”	“2/32 (6.25%)”	“2”	“1/16 (6.25%)”	“1”	“1/16 (6.25%)”	“1”
Cardiac disorders	“dizziness postural”	“1/32 (3.13%)”	“1”	“0/16 (0.00%)”	“0”	“0/16 (0.00%)”	“0”
Gastrointestinal disorders	“Constipation”	“0/32 (0.00%)”	“0”	“0/16 (0.00%)”	“0”	“3/16 (18.75%)”	“3”
Gastrointestinal disorders	“Dyspepsia”	“1/32 (3.13%)”	“1”	“0/16 (0.00%)”	“0”	“0/16 (0.00%)”	“0”
Gastrointestinal disorders	“Gastrooesophageal reflux disease”	“2/32 (6.25%)”	“2”	“0/16 (0.00%)”	“0”	“2/16 (12.50%)”	“2”
Gastrointestinal disorders	“Nausea”	“3/32 (9.38%)”	“3”	“2/16 (12.50%)”	“3”	“0/16 (0.00%)”	“0”
Gastrointestinal disorders	“Toothache”	“1/32 (3.13%)”	“1”	“0/16 (0.00%)”	“0”	“0/16 (0.00%)”	“0”
Infections and infestations	“Gastroenteritis”	“0/32 (0.00%)”	“0”	“1/16 (6.25%)”	“1”	“0/16 (0.00%)”	“0”
Infections and infestations	“Upper respiratory tract infection”	“2/32 (6.25%)”	“2”	“1/16 (6.25%)”	“1”	“0/16 (0.00%)”	“0”
Infections and infestations	“Urinary tract infection”	“1/32 (3.13%)”	“1”	“0/16 (0.00%)”	“0”	“0/16 (0.00%)”	“0”
Infections and infestations	“Viral upper respiratory tract infection”	“5/32 (15.63%)”	“5”	“0/16 (0.00%)”	“0”	“1/16 (6.25%)”	“1”
Injury, poisoning and procedural complications	“Neck Injury”	“1/32 (3.13%)”	“1”	“0/16 (0.00%)”	“0”	“0/16 (0.00%)”	“0”
Neoplasms benign, malignant and unspecified (incl cysts and polyps)	“Lipoma”	“0/32 (0.00%)”	“0”	“0/16 (0.00%)”	“0”	“1/16 (6.25%)”	“1”
Nervous system disorders	“Headache”	“2/32 (6.25%)”	“2”	“4/16 (25.00%)”	“4”	“2/16 (12.50%)”	“2”
Respiratory, thoracic and mediastinal disorders	“Epistaxis”	“2/32 (6.25%)”	“2”	“1/16 (6.25%)”	“1”	“0/16 (0.00%)”	“0”
Skin and subcutaneous tissue disorders	“Dermatitis atopic”	“0/32 (0.00%)”	“0”	“1/16 (6.25%)”	“1”	“0/16 (0.00%)”	“0”
Skin and subcutaneous tissue disorders	“Dermatitis contact”	“5/32 (15.63%)”	“6”	“4/16 (25.00%)”	“4”	“3/16 (18.75%)”	“5”
Skin and subcutaneous tissue disorders	“Erythema ab igne”	“1/32 (3.13%)”	“1”	“0/16 (0.00%)”	“0”	“0/16 (0.00%)”	“0”
Skin and subcutaneous tissue disorders	“Pruritus”	“0/32 (0.00%)”	“0”	“0/16 (0.00%)”	“0”	“1/16 (6.25%)”	“1”
Skin and subcutaneous tissue disorders	“Rash maculo-papular”	“2/32 (6.25%)”	“2”	“1/16 (6.25%)”	“1”	“0/16 (0.00%)”	“0”
Skin and subcutaneous tissue disorders	“Rash papular”	“0/32 (0.00%)”	“0”	“1/16 (6.25%)”	“1”	“0/16 (0.00%)”	“0”
Skin and subcutaneous tissue disorders	“Rash vesicular”	“1/32 (3.13%)”	“1”	“0/16 (0.00%)”	“0”	“0/16 (0.00%)”	“0”
Skin and subcutaneous tissue disorders	“Skin hyperpigmentation”	“1/32 (3.13%)”	“1”	“0/16 (0.00%)”	“0”	“0/16 (0.00%)”	“0”

Summary

AIC316-03-I-07 enrolled 64 healthy adults aged 18 to 45 years at 1 site; concomitant medication was an exclusion criterion, with exceptions for hormonal contraception, hormone replacement therapy, and a single intake judged to have no clinical relevance. The highest pritelivir dose was 400 mg once daily, given for 10 days. The registry posts mean QTcF by time point and one model-based prediction with its 90% confidence interval. It posts no moxifloxacin assay sensitivity result, no heart rate, PR interval, or QRS duration result, and no pharmacokinetic result. No journal publication of the trial was identified.

FDA comment on the adequacy of dose selection

“The adequacy of the dose selection is still a review issue and will depend on the highest therapeutic dose and whether the selected supratherapeutic dose covers the high clinical exposure scenario (i.e., increases in exposure due to drug interaction or organ impairment) of parent and any relevant metabolites for the therapeutic dose.” (opens the source at this quote in a new tab)

Hepatic and renal impairment trials in progress when the protocol was written

“The influence of hepatic and renal impairment is currently under investigation in parallel clinical trials, but no relevant effects are expected.” (opens the source at this quote in a new tab)

Agreement restricting investigator publication

“Principal Investigators are NOT employed by the organization sponsoring the study.” (opens the source at this quote in a new tab)
“There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed” (opens the source at this quote in a new tab)