Effect of renal and hepatic impairment on the pharmacokinetics of pritelivir and its metabolites

“Two trials were performed to evaluate the effect of renal and hepatic impairment on the pharmacokinetics of pritelivir and its metabolites.” (opens the source at this quote in a new tab)
“Therefore, 2 trials were performed to evaluate the pharmacokinetics of pritelivir and its metabolites in subjects with impaired renal or hepatic function, compared with subjects with normal renal or hepatic function.” (opens the source at this quote in a new tab)
“The results of these trials may inform dosing in clinical practice for subjects with impaired renal or hepatic function.” (opens the source at this quote in a new tab)

Elimination pathways and protein binding as the reasons for both trials

“Both renal and hepatic pathways play a role in the elimination and excretion of pritelivir and its metabolites.” (opens the source at this quote in a new tab)
“In addition, due to the high plasma protein binding (mainly to albumin), lower albumin levels in patients with hepatic impairment may lead to higher systemic exposure of unbound pritelivir.” (opens the source at this quote in a new tab)
“As both renal and hepatic pathways are involved in the elimination of pritelivir and its metabolites, renal and hepatic impairment trials were performed to provide guidance on potential dose adjustments of pritelivir in subjects with impaired renal or hepatic function.” (opens the source at this quote in a new tab)

Intended population of pritelivir

“Pritelivir is being developed for the treatment of resistant HSV infection in immunocompromised patients, a vulnerable population often with multiple comorbidities.” (opens the source at this quote in a new tab)

Trial site of AIC316-03-I-04 and AIC316-03-I-05

“Both trials, AIC316-03-I-04 (Trial 04) and AIC316-03-I-05 (Trial 05), were conducted by CRS Clinical Research Services Kiel GmbH (Kiel, Germany).” (opens the source at this quote in a new tab)

Regulatory and ethics approval in both trials

“Trial protocols were approved by the German Health Authority Bundesinstitut für Arzneimittel und Medizinprodukte, and a favorable opinion was obtained from the independent ethics committee (IEC) Ethikkommission bei der Ärztekammer Schleswig-Holstein (Bad Segeberg, Germany).” (opens the source at this quote in a new tab)
“An IEC–approved written informed consent was obtained from each subject prior to the start of the trial.” (opens the source at this quote in a new tab)
“The trials were conducted in accordance with ethical principles that have their origins in the Declaration of Helsinki, Good Clinical Practice (GCP), International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines, and applicable laws and regulations.” (opens the source at this quote in a new tab)

Trial AIC316-03-I-04: single-center, open-label phase 1 design in four renal function groups

“This was a single-center, open-label, Phase 1 trial in 32 subjects including renally impaired male and female subjects and their matching controls.” (opens the source at this quote in a new tab)
“Subjects were assigned to one of 4 groups (n = 8 each) according to the individual eGFR” (opens the source at this quote in a new tab)

Trial AIC316-03-I-04: matching of the control group on age and body mass index

“The control group was matched to the average age and BMI of subjects in the mild, moderate, and severe renal impairment groups (combined) as follows: For subjects in the control group, the mean age of subjects did not differ by more than 10 years, and the mean BMI did not differ by more than 15% compared with the mean values for subjects in the combined mild, moderate, and severe renal impairment groups.” (opens the source at this quote in a new tab)

Trial AIC316-03-I-05: single-center, open-label phase 1 design in moderate hepatic impairment

“This was a single-center, open-label, Phase 1 trial in 16 male and female subjects total including 8 with moderate hepatic impairment (stage B according to the Child-Pugh classification) and their matching controls (n = 8).” (opens the source at this quote in a new tab)
“The subjects in the control group were individually matched for sex, age (±10 years), body weight (±10 kg), and ethnic origin to the subjects in the moderate hepatic impairment group.” (opens the source at this quote in a new tab)

Screening, confinement, and follow-up in both trials

“For each subject, the screening examination took place within 3 weeks before trial meditrition.” (opens the source at this quote in a new tab)
“Subjects were hospitalized from Day −1 until Day 7 (at least 144 hours after the last pritelivir administration).” (opens the source at this quote in a new tab)
“Subjects returned to the clinic for further PK and safety measurements up to 360 hours after dosing and an end-of-trial visit between Days 16 and 18.” (opens the source at this quote in a new tab)

Pharmacokinetic sampling schedule in both trials

“Serial blood samples for PK analysis of pritelivir and metabolites PPA, ATS, and PPA-acyl glucuronide in plasma and blood (3 mL at each time point per matrix) were collected before dosing on Day 1 and after dosing at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144, 216, 288, and 360 hours.” (opens the source at this quote in a new tab)

Single-dose design and its justification

“In both trials, the effect of impairment was evaluated after administration of a single oral dose of 100 mg of pritelivir.” (opens the source at this quote in a new tab)
“As pritelivir exhibits time-independent and linear PK (up to 480 mg following single and up to 400 mg following multiple once-daily doses), a single-dose trial was considered sufficient to accurately describe the PK in subjects with renal and hepatic impairment.” (opens the source at this quote in a new tab)

Trial AIC316-03-I-05: restriction to moderate hepatic impairment

“While the renal impairment trial included subjects with mild, moderate, and severe renal impairment, the hepatic impairment trial included subjects with moderate hepatic impairment only, which is generally considered appropriate” (opens the source at this quote in a new tab)
“and observations from the moderate hepatic impairment group could be applied to subjects with mild hepatic impairment as well.” (opens the source at this quote in a new tab)

Matched control groups in both trials

“Both trials included a matched control group, that is, subjects were matched for age and BMI between groups and at least 2 (of 8) subjects per sex were included in each group.” (opens the source at this quote in a new tab)
“There was no potential for confounding due to differences in baseline covariates such as age, weight, and sex.” (opens the source at this quote in a new tab)

Bioanalytical methods and lower limits of quantification

“All analyses were undertaken using fully validated procedures.” (opens the source at this quote in a new tab)
“Plasma concentrations of pritelivir, PPA, ATS, and PPA-acyl glucuronide were determined using a validated mass spectrometry, high-performance liquid chromatography (HPLC)–tandem mass spectrometry method by A&M Labor für Analytik und Metabolismusforschung Service GmbH (Bergheim, Germany).” (opens the source at this quote in a new tab)
“The lower limit of quantification (LLOQ) for pritelivir, PPA, ATS, and PPA-acyl glucuronide in plasma was 10.0, 2.00, 2.00, and 0.100 ng/mL, respectively.” (opens the source at this quote in a new tab)

Determination of unbound pritelivir by rapid equilibrium dialysis

“The determination of unbound pritelivir in plasma was based on rapid equilibrium dialysis (RED), matrix match, precipitation, and quantification of pritelivir in matrix matched samples as follows.” (opens the source at this quote in a new tab)
“The LLOQ for pritelivir was 0.200 ng/mL.” (opens the source at this quote in a new tab)
“The fraction of unbound pritelivir was calculated as follows: fraction unbound (%) = 100% * concentration buffer side (ng/mL)/concentration plasma side (ng/mL).” (opens the source at this quote in a new tab)
“Unbound PK parameters (pritelivir only) were calculated by correcting total PK parameters for the mean fraction unbound, which was determined at 3 and 144 hours postdose.” (opens the source at this quote in a new tab)

Control groups in both trials: age, body mass index, and body weight

“For the control groups, male and female subjects of any ethnic origin, aged 18 years or older (79 years or younger for the hepatic impairment Trial 05) with a body mass index (BMI) between 18.0 kg/m2 or greater and 36.0 kg/m2 or less and weighing 50 kg or greater were eligible for enrollment.” (opens the source at this quote in a new tab)

Trial AIC316-03-I-04: estimated glomerular filtration rate by group

“Subjects in the control group had an individual estimated glomerular filtration rate (eGFR) of 90 mL/min or greater as determined by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation for body surface area (BSA) standardized eGFR” (opens the source at this quote in a new tab)
“Subjects in the mild, moderate, and severe renal impairment group had an individual eGFR of 60-89, 30-59, and 15-29 mL/min, respectively.” (opens the source at this quote in a new tab)

Trial AIC316-03-I-04: definition of stable renal impairment

“Stable renal impairment was defined as no clinically significant change in eGFR within 3 months or longer prior to screening, as determined by the investigator.” (opens the source at this quote in a new tab)

Trial AIC316-03-I-05: Child-Pugh stage B

“Subjects in the moderate hepatic impairment group had Child-Pugh stage B (7-9 points), in accordance with the Child-Pugh classification” (opens the source at this quote in a new tab)
“as based on the signs and symptoms of hepatic encephalopathy, abdominal ultrasound evaluation of abdominal ascites (documented evaluation not older than 4 weeks before dosing), serum bilirubin and albumin levels, and prothrombin international normalized ratio (INR) time.” (opens the source at this quote in a new tab)

Stable health status and exclusion criteria in both trials

“Subjects had no clinically relevant unstable disease as assessed by the investigator, and renally impaired subjects had stable renal impairment based on a screening examination including medical history, physical examination, blood pressure, pulse rate, electrocardiogram (ECG) assessment, and clinical laboratory results.” (opens the source at this quote in a new tab)
“Subjects with a history or current evidence of any clinically relevant cardiovascular, pulmonary, hepatic (Trial 04), renal (Trial 05), gastrointestinal, hematological, endocrinological, metabolic, neurological, psychiatric, or other disease or malignancy were excluded.” (opens the source at this quote in a new tab)
“Subjects were also excluded in case of any clinically relevant abnormalities in ECG; vital signs; or clinical chemical, hematological, or any other laboratory values.” (opens the source at this quote in a new tab)

Prior medication, diet, smoking, and alcohol restrictions in both trials

“Subjects were not allowed to use any medication (including 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.” (opens the source at this quote in a new tab)
“Subjects were not allowed to consume any enzyme-inducing or inhibiting aliments and beverages within 2 weeks before dosing.” (opens the source at this quote in a new tab)
“Consumption of any methylxanthine-containing product was not allowed within 24 hours before dosing until discharge.” (opens the source at this quote in a new tab)
“Subjects were excluded when smoking more than 10 cigarettes per day and taking more than 12 units of alcohol per week for male subjects and 7 units for female subjects.” (opens the source at this quote in a new tab)
“Subjects were not allowed to consume any alcohol 2 days prior to submission (both trials) until the end-of-trial visit (subjects in renal impairment Trial 04 only) or smoke cigarettes within 1 day prior to administration until 24 hours after administration (both trials).” (opens the source at this quote in a new tab)

Single oral dose of pritelivir 100 mg under fasted conditions in both trials

“In both trials, the effect of impairment was evaluated after administration of a single oral dose of 100 mg of pritelivir.” (opens the source at this quote in a new tab)
“Pritelivir was administered orally with 240 mL of tap water (for subjects with severe renal impairment a reduction to 120 mL was acceptable) after an overnight fast and subjects were fasted until 4 hours after dosing.” (opens the source at this quote in a new tab)

Concomitant medication permitted for control participants

“For control subjects, concomitant medications were not allowed except for paracetamol (not exceeding 2 g/day), topical dermatological products, hormonal contraceptives, and hormone replacement therapy if taken at least 2 hours before or 4 hours after pritelivir administration.” (opens the source at this quote in a new tab)

Concomitant medication permitted for participants with renal or hepatic impairment

“For impaired subjects, concomitant medications were not allowed throughout the trial, other than stable doses of medically required medication (including over-the-counter medication), except for paracetamol (not exceeding 2 g/day or ibuprofen not exceeding 1200 mg per day [hepatically impaired subjects only]), topical dermatological products, hormonal contraceptives, hormone replacement therapy, proton pump inhibitors (had to be stopped from 3 days prior to dosing until after the 24 hours postdose PK sampling), H2 blockers (had to be stopped from 2 days prior to dosing until after the 24 hours postdose PK sampling), and other concomitant medication, including antacids and phosphate-binding drugs if taken at least 2 hours before or 4 hours after pritelivir administration.” (opens the source at this quote in a new tab)

Interruption of proton pump inhibitors around the pritelivir dose

“As per protocol, for the subjects in the renal impairment groups taking proton pump inhibitors (PPIs; 29.2%), PPI dosing was interrupted from 3 days prior to 24 hours after administration of pritelivir.” (opens the source at this quote in a new tab)
“As per protocol, for the subjects in the hepatic impairment group taking PPIs (25%), PPI dosing was interrupted from 3 days prior to 24 hours after administration of pritelivir.” (opens the source at this quote in a new tab)

Primary and secondary pharmacokinetic variables in both trials

“To evaluate the effect of mild, moderate, and severe renal impairment (Trial 04) and moderate hepatic impairment (Trial 05) on the PK of pritelivir and its metabolites (PPA, ATS, and PPA-acyl glucuronide), a linear mixed-effects model was applied on the log-transformed parameters AUC0-inf, AUC0-last, and Cmax (primary variables for pritelivir and secondary variables for its metabolites) and AUC0-inf,u, AUC0-last,u, and Cmax,u (secondary variables, pritelivir only) with group as fixed effect.” (opens the source at this quote in a new tab)

Pharmacokinetic parameters calculated

“For both trials, PK analyses were performed with standard noncompartmental methods using the validated computer program Phoenix WinNonlin (version 8.1.1; Certara LP, USA).” (opens the source at this quote in a new tab)
“For pritelivir, PPA, ATS, and PPA–acyl glucuronide: maximum plasma concentration (Cmax), time to maximum concentration, area under the plasma concentration-time curve (AUC) from time 0 to the last quantifiable concentration (AUC0-last), AUC from time 0 to infinity (AUC0-inf), terminal elimination half-life (t1/2z), apparent clearance (CL/F; pritelivir only), and fraction unbound (fu; pritelivir only).” (opens the source at this quote in a new tab)
“For pritelivir, the unbound parameters Cmax,u, AUC0-last,u, AUC0-inf,u, and CLu/F.” (opens the source at this quote in a new tab)
“For the metabolites, PPA, ATS, and PPA-acyl glucuronide metabolite-to-parent ratios were calculated for AUC0-last and AUC0-inf (AUC0-last,m/p and AUC0-inf,m/p).” (opens the source at this quote in a new tab)

Unbound exposure measured because impairment can change protein binding

“As disease states (such as hepatic impairment or renal impairment) may change protein binding of drugs, PK parameters based on total drug concentrations may be misleading.” (opens the source at this quote in a new tab)
“Therefore, in these trials, both total and unbound PK parameters were estimated for pritelivir.” (opens the source at this quote in a new tab)

Metabolites measured on the basis of urinary excretion

“Although the metabolites of pritelivir are pharmacologically inactive, PPA, ATS, and PPA-acyl glucuronide were measured in these trials on the basis of their urinary excretion profile.” (opens the source at this quote in a new tab)
“The metabolites PPA and ATS were tested to be pharmacologically inactive on HSV replication.” (opens the source at this quote in a new tab)

Safety and tolerability assessments in both trials

“Safety assessments in both trials consisted of adverse events (AEs) monitoring, vital signs, ECG, physical examination, and laboratory tests.” (opens the source at this quote in a new tab)
“All AEs were coded according to the Medical Dictionary for Regulatory Activities (Version 24.1 for Trial 04 and Version 25.0 for Trial 05).” (opens the source at this quote in a new tab)
“Incidences of treatment-emergent adverse events (TEAEs, beginning after the start of treatment) were summarized by primary system organ class and preferred term (PT) level.” (opens the source at this quote in a new tab)

Trial AIC316-03-I-04: participants planned by group

“This was a single-center, open-label, Phase 1 trial in 32 subjects including renally impaired male and female subjects and their matching controls.” (opens the source at this quote in a new tab)
“Subjects were assigned to one of 4 groups (n = 8 each) according to the individual eGFR” (opens the source at this quote in a new tab)

Trial AIC316-03-I-04: participants enrolled and analyzed

“In total, 32 healthy subjects (20 men, 12 women) were enrolled in the trial, with 8 subjects included in each of the following groups: control, mild, moderate, and severe renal impairment.” (opens the source at this quote in a new tab)
“All enrolled subjects received the planned treatment, completed the trial, and were included in the safety and PK population.” (opens the source at this quote in a new tab)

Trial AIC316-03-I-05: participants planned by group

“This was a single-center, open-label, Phase 1 trial in 16 male and female subjects total including 8 with moderate hepatic impairment (stage B according to the Child-Pugh classification) and their matching controls (n = 8).” (opens the source at this quote in a new tab)

Trial AIC316-03-I-05: participants enrolled and analyzed

“In total, 16 healthy subjects (8 men, 8 women) were enrolled in the trial, with 8 subjects included in each of the following groups: control and moderate hepatic impairment.” (opens the source at this quote in a new tab)
“All enrolled subjects received the planned treatment, completed the trial, and were included in the safety and PK population.” (opens the source at this quote in a new tab)

Safety and pharmacokinetic population in both trials

“All enrolled subjects received the planned treatment, completed the trial, and were included in the safety and PK population.” (opens the source at this quote in a new tab)
“Demographics and baseline characteristics of the safety population are summarized in Table 1.” (opens the source at this quote in a new tab)

Least square means ratios of impaired groups against the control group

“From that model, least square (LS) means ratios and 90% confidence intervals were computed for mild, moderate, and severe renal impairment (Trial 04) and the moderate hepatic impairment group (Trial 05) as test and the control group as reference.” (opens the source at this quote in a new tab)
“Both the difference between the LS means and the 90% confidence intervals were retransformed to the original scale.” (opens the source at this quote in a new tab)

Linear regression against renal and hepatic function

“For pritelivir and its metabolites, the relationship between AUC0-inf, CL/F, CLu/F, and apparent unbound volume of distribution (as applicable) and the continuous variable of renal function (eGFR) in Trial 04 and the relationship between AUC0-inf, CL/F, and CLu/F (as applicable) and baseline hepatic function abnormalities, such as bilirubin and albumin serum concentrations and prothrombin INR time in Trial 05 were investigated in using a linear regression model.” (opens the source at this quote in a new tab)

Descriptive statistics and handling of concentrations below the limit of quantification

“PK parameters for pritelivir and metabolites (PPA, ATS, and PPA-acyl glucuronide) were calculated based on the individual plasma concentration versus time data using the actual sampling time.” (opens the source at this quote in a new tab)
“Descriptive statistics were calculated for the PK parameters and included sample size (n), mean, standard deviation (SD), coefficient of variation (% CV), geometric mean, median, minimum, and maximum.” (opens the source at this quote in a new tab)
“All samples below the LLOQ have been entered as 0 and included as such in the calculation of means.” (opens the source at this quote in a new tab)

Safety analysis by descriptive statistics

“The results of these safety measurements and AEs were listed by subject and treatment group and analyzed by descriptive statistics.” (opens the source at this quote in a new tab)

Trial AIC316-03-I-04: all 32 participants completed

“In total, 32 healthy subjects (20 men, 12 women) were enrolled in the trial, with 8 subjects included in each of the following groups: control, mild, moderate, and severe renal impairment.” (opens the source at this quote in a new tab)
“All enrolled subjects received the planned treatment, completed the trial, and were included in the safety and PK population.” (opens the source at this quote in a new tab)

Trial AIC316-03-I-05: all 16 participants completed

“In total, 16 healthy subjects (8 men, 8 women) were enrolled in the trial, with 8 subjects included in each of the following groups: control and moderate hepatic impairment.” (opens the source at this quote in a new tab)
“All enrolled subjects received the planned treatment, completed the trial, and were included in the safety and PK population.” (opens the source at this quote in a new tab)

Trial AIC316-03-I-04: demographics by renal function group

Parameter	Control (n = 8)	Mild renal impairment (n = 8)	Moderate renal impairment (n = 8)	Severe renal impairment (n = 8)
Age (years), mean (range)	“69 (62-73)”	“68 (55-82)”	“68 (49-84)”	“69 (47-80)”
Height (cm), mean (range)	“172 (165-178)”	“170 (156-183)”	“170 (161-183)”	“169 (154-180)”
Weight (kg), mean (range)	“80.1 (66.5-92.0)”	“82.6 (61.5-105.5)”	“73.7 (57.0-100.2)”	“78.4 (61.0-93.5)”
BMI (kg/m2), mean (range)	“27.2 (23.8-31.8)”	“28.3 (21.1-31.5)”	“25.4 (21.9-33.5)”	“27.6 (21.8-34.7)”
eGFR (mL/min), mean (range)	“101.6 (91.5-118.6)”	“77.7 (60.7-89.3)”	“48.3 (31.0-58.2)”	“24.0 (16.2-28.9)”
Race, White, n (%)	“8 (100)”	“8 (100)”	“8 (100)”	“8 (100)”
Ethnicity, non-Hispanic or Latino, n (%)	“8 (100)”	“8 (100)”	“8 (100)”	“8 (100)”
Male, n (%)	“5 (62.5)”	“5 (62.5)”	“4 (50.0)”	“6 (75.0)”
Female, n (%)	“3 (37.5)”	“3 (37.5)”	“4 (50.0)”	“2 (25.0)”

Trial AIC316-03-I-04: matching and estimated glomerular filtration rate ranges

“Overall, renally impaired treatment groups were closely matched to the normal control group in terms of demographics (age, sex, race, and ethnicity), and all eGFR values were within the intended ranges for allocation to the specific groups.” (opens the source at this quote in a new tab)

Trial AIC316-03-I-04: concomitant diseases and medications

“No subject in the control group and all subjects in the renal impairment groups had at least 1 concomitant disease reported.” (opens the source at this quote in a new tab)
“The most commonly reported concurrent conditions besides chronic kidney disease were hypertension (95.8%), hyperlipidemia (45.8%), and diabetes mellitus type 2 (20.8%).” (opens the source at this quote in a new tab)
“No subject in the control group and all subjects in the renal impairment groups had at least 1 concomitant medication during the trial.” (opens the source at this quote in a new tab)
“The medications most commonly used during the trial were platelet aggregation inhibitors such as acetylsalicylic acid (ASS), angiotensin II receptor blockers, and statins.” (opens the source at this quote in a new tab)
“The proportion of subjects with concomitant use increased with the severity category of renal impairment.” (opens the source at this quote in a new tab)

Trial AIC316-03-I-05: demographics by hepatic function group

Parameter	Control (n = 8)	Moderate hepatic impairment (n = 8)
Age (years), mean (range)	“57 (44-74)”	“59 (40-72)”
Height (cm), mean (range)	“167 (150-183)”	“171 (158-182)”
Weight (kg), mean (range)	“72.9 (59.5-91.6)”	“76.8 (62.1-94.4)”
BMI (kg/m2), mean (range)	“26.1 (20.0-30.6)”	“26.6 (19.4-35.3)”
Race, White, n (%)	“8 (100)”	“8 (100)”
Ethnicity, non-Hispanic or Latino, n (%)	“8 (100)”	“8 (100)”
Male, n (%)	“4 (50.0)”	“4 (50.0)”
Female, n (%)	“4 (50.0)”	“4 (50.0)”
Child-Pugh score 7, n (%)	“0”	“4 (50.0)”
Child-Pugh score 8, n (%)	“0”	“2 (25.0)”
Child-Pugh score 9, n (%)	“0”	“2 (25.0)”

Trial AIC316-03-I-05: matching and Child-Pugh scores

“Overall, subjects in the moderate hepatic impairment group were closely matched to subjects in the normal control group in terms of demographics (age, sex, race, and ethnicity).” (opens the source at this quote in a new tab)
“All subjects in the hepatic impairment group had Child-Pugh total scores within the prespecified range (7-9), and the full range of scores representing moderate hepatic impairment was included.” (opens the source at this quote in a new tab)

Trial AIC316-03-I-05: concomitant diseases and medications

“No subject in the control group and all subjects in the moderate hepatic impairment group had at least 1 concomitant disease reported.” (opens the source at this quote in a new tab)
“The most commonly reported concurrent conditions besides hepatic impairment were ascites (100%), cirrhosis alcoholic (75%), and hepatic encephalopathy (62.5%).” (opens the source at this quote in a new tab)
“No subject in the control group and all subjects in the hepatic impairment groups had at least 1 concomitant medication during the trial.” (opens the source at this quote in a new tab)
“The medications most commonly used during the trial were spironolactone, loop diuretics, lactulose, and other medication for hepatic encephalopathy.” (opens the source at this quote in a new tab)

Trial AIC316-03-I-05: albumin, bilirubin, and prothrombin ranges in the impaired group

“However, the ranges of albumin, bilirubin, and prothrombin INR in subjects with moderate hepatic impairment were not very wide (2.5-4.6 g/dL, 0.3-3.0 mg/dL, and 1.03-1.34 seconds at Day −1, respectively).” (opens the source at this quote in a new tab)
“There were 2 subjects with lower albumin concentrations (ie, 2.5 and 3.4 g/dL), resulting in higher fu values for these subjects as described above.” (opens the source at this quote in a new tab)
“In addition, only 2 of 8 subjects with moderate hepatic impairment had abnormalities in these parameters; the other subjects were included because of the presence of mild or moderate ascites and encephalopathy.” (opens the source at this quote in a new tab)

Trial AIC316-03-I-04: least square means ratios for pritelivir, mild renal impairment against control

Parameter	n	Control (reference)	Impaired (test)	LS means ratio (%)	90% CI (%)	%CV
Total Cmax (ng/mL)	“8”	“1141”	“1021”	“89.5”	“52.0-153.9”	“70.9”
Total AUC0-last (ng•h/mL)	“8”	“76,079”	“67,492”	“88.7”	“60.4-130.3”	“47.7”
Total AUC0-inf (ng•h/mL)	“8”	“77,595”	“68,905”	“88.8”	“61.2-128.7”	“45.9”
Unbound Cmax,u (ng/mL)	“8”	“6.84”	“5.99”	“87.6”	“51.3-149.5”	“69.6”
Unbound AUC0-last,u (ng•h/mL)	“8”	“456”	“396”	“86.9”	“57.4-131.4”	“51.8”
Unbound AUC0-inf,u (ng•h/mL)	“8”	“465”	“404”	“86.9”	“58.1-130.0”	“50.2”

Trial AIC316-03-I-04: least square means ratios for pritelivir, moderate renal impairment against control

Parameter	n	Control (reference)	Impaired (test)	LS means ratio (%)	90% CI (%)	%CV
Total Cmax (ng/mL)	“8”	“1141”	“1141”	“100.0”	“58.1-171.9”	“70.9”
Total AUC0-last (ng•h/mL)	“8”	“76,079”	“80,558”	“105.9”	“72.0-155.6”	“47.7”
Total AUC0-inf (ng•h/mL)	“8”	“77,595”	“82,946”	“106.9”	“73.7-155.0”	“45.9”
Unbound Cmax,u (ng/mL)	“8”	“6.8”	“6.9”	“101.0”	“59.2-172.4”	“69.6”
Unbound AUC0-last,u (ng•h/mL)	“8”	“456”	“488”	“107.0”	“70.7-162.0”	“51.8”
Unbound AUC0-inf,u (ng•h/mL)	“8”	“465”	“502”	“108.0”	“72.2-161.6”	“50.2”

Trial AIC316-03-I-04: least square means ratios for pritelivir, severe renal impairment against control

Parameter	n	Control (reference)	Impaired (test)	LS means ratio (%)	90% CI (%)	%CV
Total Cmax (ng/mL)	“8”	“1141”	“1834”	“160.7”	“93.4-276.4”	“70.9”
Total AUC0-last (ng•h/mL)	“8”	“76,079”	“119,294”	“156.8”	“106.6-230.4”	“47.7”
Total AUC0-inf (ng•h/mL)	“8”	“77,595”	“121,560”	“156.7”	“108.0-227.1”	“45.9”
Unbound Cmax,u (ng/mL)	“8”	“6.84”	“11.3”	“166.0”	“97.2-283.2”	“69.6”
Unbound AUC0-last,u (ng•h/mL)	“8”	“456”	“738”	“162.0”	“106.9-245.1”	“51.8”
Unbound AUC0-inf,u (ng•h/mL)	“8”	“465”	“752”	“161.8”	“108.1-242.1”	“50.2”

Trial AIC316-03-I-05: least square means ratios for pritelivir, moderate hepatic impairment against control

Parameter	n	Control (reference)	Impaired (test)	LS means ratio (%)	90% CI (%)	%CV
Total Cmax (ng/mL)	“8”	“1297”	“1465”	“113.0”	“66.4-192.1”	“66.2”
Total AUC0-last (ng•h/mL)	“8”	“79,928”	“76,300”	“95.5”	“69.1-131.8”	“37.9”
Total AUC0-inf (ng•h/mL)	“8”	“81,666”	“77,995”	“95.5”	“69.7-130.8”	“36.9”
Unbound Cmax,u (ng/mL)	“8”	“7.11”	“10.4”	“145.7”	“86.4-245.8”	“65.0”
Unbound AUC0-last,u (ng•h/mL)	“8”	“438”	“540”	“123.2”	“84.6-179.2”	“44.6”
Unbound AUC0-inf,u (ng•h/mL)	“8”	“448”	“552”	“123.2”	“85.1-178.4”	“44.0”

Trial AIC316-03-I-04: pritelivir exposure by degree of renal impairment

“The LS means ratios for Cmax and AUC0-inf of pritelivir in subjects with mild renal impairment compared with matched control subjects were 89.5% and 88.8%, respectively.” (opens the source at this quote in a new tab)
“The LS means ratios for Cmax and AUC0-inf of pritelivir in subjects with moderate renal impairment compared with matched control subjects were 100.0% and 106.9%, respectively, and the LS means ratios for Cmax and AUC0-inf of pritelivir in subjects with severe renal impairment compared with matched control subjects were 160.7% and 156.7%, respectively.” (opens the source at this quote in a new tab)
“As fu was comparable between the matched control subjects and renal impairment categories (range, 0.591%-0.641%), similar results were obtained for unbound PK parameters.” (opens the source at this quote in a new tab)

Trial AIC316-03-I-04: half-life and apparent clearance of pritelivir

“Mean t1/2z for pritelivir and metabolites were comparable among the matched control subjects and all renal impairment categories (range, 54.9-56.3 hours).” (opens the source at this quote in a new tab)
“CL/F of pritelivir was similar (range, 1.4-1.6 L/h) among control, mild, and moderate renal impairment categories and lower for subjects with severe renal impairment (0.8 L/h).” (opens the source at this quote in a new tab)

Trial AIC316-03-I-04: metabolite exposure by degree of renal impairment

“For the metabolite PPA, the LS means ratios for AUCinf were 94.6%, 132.8%, and 296.9% for subjects with mild, moderate, and severe renal impairment compared with matched control subjects, respectively.” (opens the source at this quote in a new tab)
“For the metabolite ATS, the LS means ratios for AUCinf were 96.1%, 167.3%, and 259.7% and for the metabolite PPA-acyl glucuronide, the LS means ratios for AUC0-inf were 104.2%, 201.7%, and 559.4% for subjects with mild, moderate, and severe renal impairment compared with matched control subjects, respectively.” (opens the source at this quote in a new tab)
“Mean metabolite-to-parent ratios of AUC0-inf appeared to increase with severity level of renal impairment for all metabolites, this was most pronounced for PPA in the severe renal impairment group (Tables S2-S4).” (opens the source at this quote in a new tab)

Trial AIC316-03-I-04: correlation of exposure and clearance with estimated glomerular filtration rate

“The correlation plots showed a slight increase for AUC0-inf with decreasing eGFR values and a slight decrease for CL/F with decreasing eGFR values for pritelivir.” (opens the source at this quote in a new tab)
“For pritelivir and its metabolites, the correlation plot showed an increase for AUC0-inf with decreasing eGFR values.” (opens the source at this quote in a new tab)
“The R2 value for all regression lines was relatively low (Figures S3, S4).” (opens the source at this quote in a new tab)

Trial AIC316-03-I-04: authors' interpretation of pritelivir exposure in renal impairment

“For pritelivir, systemic exposure (total and unbound) was similar in subjects with mild and moderate renal impairment compared with matched control subjects (LS means ratios between 86.9% and 108.0% for Cmax and AUC), suggesting that mild and moderate renal impairment did not have a clinically relevant effect on the pharmacokinetics of pritelivir.” (opens the source at this quote in a new tab)
“This result was expected as the percentage of unchanged pritelivir excreted in urine was previously shown to be negligible (approximately 0.5% of the recovered dose).” (opens the source at this quote in a new tab)
“For severe renal impairment, systemic exposure was higher compared with matched control subjects (LS means ratios between 156.7% and 166.0% for Cmax and AUC).” (opens the source at this quote in a new tab)
“This could not be attributed to a lower renal excretion or altered plasma protein binding but was more likely due to changes in drug metabolism and transport pathways in the liver and intestine, which is more pronounced in subjects with severe renal impairment.” (opens the source at this quote in a new tab)
“In line with these results, mean CL/F and CLu/F were comparable in all groups except for the severely renally impaired group.” (opens the source at this quote in a new tab)

Trial AIC316-03-I-04: authors' interpretation of metabolite exposure in renal impairment

“For the metabolites PPA, ATS, and PPA-acyl glucuronide, the systemic exposure in subjects with mild renal impairment was similar compared with matched control subjects (LS means ratios for AUC0-inf between 94.6% and 104.2% for AUC), suggesting that mild renal impairment does not have a clinically relevant effect on the pharmacokinetics of the metabolites of pritelivir.” (opens the source at this quote in a new tab)
“For subjects with moderate and severe renal impairment, the systemic exposure was higher compared with matched control subjects, which was most prominent for PPA-acyl glucuronide with an LS means ratio of 201.7% and 559.4% for moderate and severe renal impairment, respectively.” (opens the source at this quote in a new tab)
“For PPA and ATS, the increase in AUC0-inf was similar in subjects with moderate (LS means ratio of 132.8% for PPA and 167.3% for ATS) and severe renal impairment (LS means ratio of 296.9% for PPA and 259.7% for ATS).” (opens the source at this quote in a new tab)
“These results were not unexpected, as the primary route of excretion for metabolites is renal and about 77% of pritelivir-related material was recovered in urine.” (opens the source at this quote in a new tab)

Trial AIC316-03-I-05: pritelivir exposure in moderate hepatic impairment

“The LS means ratios for Cmax and AUC0-inf of pritelivir in subjects with moderate hepatic impairment compared with matched control subjects were 113.0% and 95.5%, respectively.” (opens the source at this quote in a new tab)
“As mean fu was slightly higher for subjects with moderate hepatic impairment compared with matched control subjects, the LS means ratios for unbound Cmax and AUC0-inf of pritelivir were also higher with 145.7% for Cmax and 123.2% for AUC0-inf.” (opens the source at this quote in a new tab)
“For pritelivir, mean t1/2z and CL/F were comparable for subjects with moderate hepatic impairment (45.9 hours and 1.3 L/h, respectively) and matched control subjects (52.0 hours and 1.3 L/h, respectively) with overlapping ranges.” (opens the source at this quote in a new tab)

Trial AIC316-03-I-05: fraction unbound in moderate hepatic impairment

“Mean fu was slightly higher for subjects with moderate hepatic impairment (0.738%) compared with matched control subjects (0.551%).” (opens the source at this quote in a new tab)
“This was mainly due to 2 subjects in the moderate hepatic impairment group with high mean fu values of 1.14% both, while the range for the remaining subjects was 0.532%-0.666%.” (opens the source at this quote in a new tab)
“Therefore, the unbound PK parameter CLu/F showed some differences between the mean values of both groups but overlapping ranges were observed.” (opens the source at this quote in a new tab)
“The highest fu values were observed in the 2 subjects with abnormalities in albumin and bilirubin levels.” (opens the source at this quote in a new tab)
“These high fu values could be explained by the low albumin concentration in these 2 subjects.” (opens the source at this quote in a new tab)

Trial AIC316-03-I-05: metabolite exposure in moderate hepatic impairment

“For the metabolites PPA, ATS, and PPA-acyl glucuronide, the LS means ratios for AUC0-inf were 122.2%, 168.8%, and 95.1%, respectively, for subjects with moderate hepatic impairment compared with matched control subjects.” (opens the source at this quote in a new tab)
“Mean metabolite-to-parent ratio AUC0-inf was higher for the subjects with moderate hepatic impairment for PPA and ATS and comparable for PPA-acyl glucuronide.” (opens the source at this quote in a new tab)

Trial AIC316-03-I-05: correlation of exposure with albumin, bilirubin, and prothrombin time

“Correlation plots showed that there was no clear relationship between AUC0-inf of pritelivir and its metabolites and albumin and bilirubin serum concentrations and prothrombin INR (Figures S5-S8).” (opens the source at this quote in a new tab)
“Similarly, there was no clear relationship between pritelivir CL/F and CLu/F, albumin and bilirubin serum concentrations, and prothrombin INR (figures not shown).” (opens the source at this quote in a new tab)

Trial AIC316-03-I-05: authors' interpretation of exposure in moderate hepatic impairment

“In subjects with moderate hepatic impairment, pritelivir systemic exposure was similar compared with matched control subjects (LS means ratios between 113.0% and 95.5% for Cmax and AUC), suggesting that moderate hepatic impairment does not have a clinically relevant effect on the pharmacokinetics of pritelivir.” (opens the source at this quote in a new tab)
“Since pritelivir metabolites are mainly formed by nonenzymatic biotransformation (hydrolysis) and partly by enzymatic (hydroxylation, glucuronidation) biotransformation, the effect of hepatic impairment on pritelivir exposure was expected to be limited.” (opens the source at this quote in a new tab)
“The fu appeared to be higher and the unbound clearance CLu/F appeared to be lower in subjects with moderate hepatic impairment.” (opens the source at this quote in a new tab)
“As a result, unbound systemic exposure of pritelivir was higher compared with matched control subjects (LS means ratios between 145.7% and 123.2% for Cmax and AUC), suggesting that moderate impairment has a modest effect on the pharmacokinetics of unbound pritelivir.” (opens the source at this quote in a new tab)
“For the pharmacologically inactive metabolites PPA and ATS, a modest effect of moderate hepatic impairment was observed on the systemic exposure (LS means ratios of 122.2% and 168.8%, respectively).” (opens the source at this quote in a new tab)
“For PPA-acyl glucuronide systemic exposure was similar (LS means ratio of 95.1%) and thus suggesting no clinically relevant effect.” (opens the source at this quote in a new tab)

Trial AIC316-03-I-04: descriptive pharmacokinetic parameters of pritelivir by renal function group

Parameter	Control (n = 8)	Mild renal impairment (n = 8)	Moderate renal impairment (n = 8)	Severe renal impairment (n = 8)
Total Cmax (ng/mL)	“1380 (853)”	“1117 (449)”	“1437 (841)”	“1961 (687)”
tmax (hour)	“4.0 (1.0-16.0)”	“4.0 (0.5-12.0)”	“4.0 (0.8-36.0)”	“3.0 (1.5-5.0)”
Total AUC0-last (ng•h/mL)	“82,380 (33,004)”	“70,286 (20,356)”	“93,935 (41,743)”	“121,005 (22,119)”
Total AUC0-inf (ng•h/mL)	“83,789 (32,999)”	“71,640 (20,422)”	“95,677 (41,641)”	“123,232 (22,021)”
t1/2z (hour)	“54.9 (9.7)”	“55.9 (5.9)”	“55.7 (8.3)”	“56.3 (11)”
CL/F (L/h)	“1.4 (0.7)”	“1.5 (0.5)”	“1.6 (1.6)”	“0.8 (0.1)”
fu (%)	“0.607 (0.11)”	“0.591 (0.085)”	“0.641 (0.27)”	“0.626 (0.10)”
Unbound Cmax,u (ng/mL)	“7.9 (4.5)”	“6.4 (2.5)”	“9.1 (5.5)”	“12.2 (4.5)”
Unbound AUC0-last,u (ng•h/mL)	“484 (173)”	“406 (97)”	“624 (420)”	“757 (191)”
Unbound AUC0-inf,u (ng•h/mL)	“493 (174)”	“414 (97)”	“637 (432)”	“770 (190)”
CLu/F (L/h)	“229 (90)”	“254 (60)”	“275 (282)”	“136 (29)”

Trial AIC316-03-I-05: descriptive pharmacokinetic parameters of pritelivir by hepatic function group

Parameter	Control (n = 8)	Moderate hepatic impairment (n = 8)
Total Cmax (ng/mL)	“1532 (776)”	“1638 (832)”
tmax (hour)	“4.0 (0.8-36.0)”	“3.5 (0.5-16.0)”
Total AUC0-last (ng•h/mL)	“85,236 (28,944)”	“79,517 (22,578)”
Total AUC0-inf (ng•h/mL)	“86,739 (28,726)”	“81,269 (23,268)”
t1/2z (hour)	“52.0 (9.3)”	“45.9 (16)”
CL/F (L/h)	“1.3 (0.6)”	“1.3 (0.5)”
fu (%)	“0.551 (0.057)”	“0.738 (0.25)”
Unbound Cmax,u (ng/mL)	“8.5 (4.8)”	“11.2 (4.2)”
Unbound AUC0-last,u (ng•h/mL)	“472 (178)”	“586 (280)”
Unbound AUC0-inf,u (ng•h/mL)	“480 (177)”	“601 (296)”
CLu/F (L/h)	“242 (109)”	“195 (81)”

Statistics shown in the descriptive parameter tables

“Mean (SD); tmax, median (range)” (opens the source at this quote in a new tab)

Authors' conclusions for both trials

“Mild and moderate renal impairment and moderate hepatic impairment did not have a clinically relevant effect on the pharmacokinetics of pritelivir.” (opens the source at this quote in a new tab)
“In subjects with severe renal impairment, systemic exposure (based on AUC0-inf) was 57% higher compared with matched control subjects.” (opens the source at this quote in a new tab)
“The free fraction was similar among renally impaired and matched control subjects.” (opens the source at this quote in a new tab)
“Free fraction was higher for subjects with moderate hepatic impairment compared with matched control subjects, resulting in a 23% higher systemic exposure of unbound pritelivir.” (opens the source at this quote in a new tab)
“For the metabolites PPA, ATS, and PPA-acyl glucuronide, higher systemic exposure was observed with increasing degree of moderate (33%-102%) to severe (160%-459%) renal impairment, but not with mild renal impairment.” (opens the source at this quote in a new tab)
“For the metabolites PPA and ATS, a modest effect of moderate hepatic impairment was observed (22% and 69% higher exposure) but not for PPA-acyl glucuronide.” (opens the source at this quote in a new tab)

Prescribing information: pharmacokinetics in renal impairment

“In a single-dose pharmacokinetic study, pritelivir exposure (AUC and Cmax) was comparable between participants with mild (eGFR 60–89 mL/min) or moderate (eGFR 30–59 mL/min) renal impairment and those with normal renal function (eGFR ≥90 mL/min).” (opens the prescribing information at this quote)
“Pritelivir exposure (AUC and Cmax) were approximately 1.6-fold higher in participants with severe renal impairment (eGFR 15–29 mL/min, not on hemodialysis) relative to those with normal renal function.” (opens the prescribing information at this quote)
“Pritelivir pharmacokinetics in patients on hemodialysis is unknown.” (opens the prescribing information at this quote)

Prescribing information: dosing in renal impairment

“No dose adjustment is recommended for patients with mild, moderate, or severe renal impairment.” (opens the prescribing information at this quote)
“The pharmacokinetics and safety of pritelivir in patients requiring hemodialysis have not been evaluated” (opens the prescribing information at this quote)

Prescribing information: pharmacokinetics in hepatic impairment

“In a single-dose pharmacokinetic study, pritelivir exposure (AUC and Cmax) was comparable in participants with moderate hepatic impairment (Child-Pugh Class B) relative to those with normal hepatic function.” (opens the prescribing information at this quote)
“The effect of severe hepatic impairment (Child-Pugh Class C) on pritelivir pharmacokinetics is unknown.” (opens the prescribing information at this quote)

Prescribing information: dosing in hepatic impairment

“No dose adjustment is recommended for patients with mild (Child-Pugh Class A) or moderate (Child-Pugh Class B) hepatic impairment.” (opens the prescribing information at this quote)
“The pharmacokinetics and safety of pritelivir in patients with severe hepatic impairment (Child-Pugh Class C) have not been evaluated” (opens the prescribing information at this quote)

Trial AIC316-03-I-04: treatment-emergent adverse events by renal function group

“No TEAEs were reported in the control group.” (opens the source at this quote in a new tab)
“In the renal impairment groups treated with pritelivir, 6 subjects had a total of 6 TEAEs (1 per subject), of which 1 of 8 subjects (12.5%) each was in the mild and moderate impairment groups and 4 of 8 subjects (50.0%) were in the severe renal impairment group.” (opens the source at this quote in a new tab)
“All events were of mild (50%) or moderate (50.0%) severity and all events were reported as resolved by the end of the trial.” (opens the source at this quote in a new tab)

Trial AIC316-03-I-04: events by group and severity

Group	Severity	Event as reported
Mild renal impairment	Moderate	“headache”
Moderate renal impairment	Moderate	“back pain”
Severe renal impairment	Moderate	“first-degree atrioventricular block”
Severe renal impairment	Mild	“nasopharyngitis”
Severe renal impairment	Mild, reported twice	“C-reactive protein increased”

“Single moderate TEAEs were reported in each of the renal impairment groups” (opens the source at this quote in a new tab)
“Mild TEAEs were reported in the severe renal impairment group” (opens the source at this quote in a new tab)

Trial AIC316-03-I-04: pattern of events and relatedness to pritelivir

“a slight increase in the overall incidence of TEAEs in the severe renal impairment group, which are not unexpected in this group, no further pattern was apparent from comparison of the TEAE profiles by system organ class or PT.” (opens the source at this quote in a new tab)
“Only 1 subject (12.5%) in the mild renal impairment group had 1 TEAE (headache) considered to be possibly related to pritelivir.” (opens the source at this quote in a new tab)

Trial AIC316-03-I-04: laboratory parameters, vital signs, and electrocardiograms

“Pritelivir had no apparent effect on clinical laboratory parameters, vital signs, ECG, or physical examination parameters in any of the treatment groups, regardless of the extent of accompanying renal impairment.” (opens the source at this quote in a new tab)

Trial AIC316-03-I-05: treatment-emergent adverse events by hepatic function group

“No TEAEs were reported in the control group.” (opens the source at this quote in a new tab)
“In the hepatic impairment group treated with pritelivir, 4 of 8 subjects (50%) had a total of 4 TEAEs (1 per subject).” (opens the source at this quote in a new tab)
“All events were reported recovered/resolved by the end of the trial.” (opens the source at this quote in a new tab)
“The events were generally consistent with the selected hepatically impaired population and none of the TEAEs were considered to be related to pritelivir.” (opens the source at this quote in a new tab)

Trial AIC316-03-I-05: events by preferred term and intensity

Event (preferred term)	Intensity
“tachyarrhythmia”	“were of moderate intensity (75%)”
“diarrhea”	“were of moderate intensity (75%)”
“sciatica”	“were of moderate intensity (75%)”
“lipase increased”	“which was severe (25%)”

Trial AIC316-03-I-05: laboratory parameters, vital signs, and electrocardiograms

“Pritelivir administration had no apparent effect on clinical laboratory parameters, vital signs, ECGs, or physical examination parameters in either the healthy control group or the moderate hepatic impairment group.” (opens the source at this quote in a new tab)

Authors' conclusion on safety in both trials

“Pritelivir administration was safe and well tolerated in subjects with renal or hepatic impairment.” (opens the source at this quote in a new tab)

Summary

Both trials were single-center, open-label, single-dose trials with 8 participants per group, all White; the 90% confidence interval of the Cmax ratio in mild renal impairment spanned 52.0% to 153.9%. The hepatic trial enrolled Child-Pugh stage B only, and 2 of 8 impaired participants had abnormal albumin, bilirubin, or prothrombin values. Regression lines against eGFR had low R2 values. Fraction unbound measured ex vivo (0.551% to 0.607% in controls) differed from the earlier in vitro value of 2.8%. Hemodialysis and severe hepatic impairment were not evaluated. The sponsor funded both trials.

Trial AIC316-03-I-04: low coefficients of determination in the regression on renal function

“However, the R2 value for all regression lines was relatively low.” (opens the source at this quote in a new tab)

Trial AIC316-03-I-05: limited range of hepatic function abnormalities

“No clear relationship could be established for any of the investigated parameters.” (opens the source at this quote in a new tab)
“This is likely due to the inclusion of subjects with only moderate hepatic impairment, thus covering a limited range of hepatic function abnormalities.” (opens the source at this quote in a new tab)
“In addition, only 2 of 8 subjects with moderate hepatic impairment had abnormalities in these parameters; the other subjects were included because of the presence of mild or moderate ascites and encephalopathy.” (opens the source at this quote in a new tab)

Fraction unbound differing from earlier in vitro results

“It should be noted that the ex vivo results on the free fraction in these trials (ie, 0.607% and 0.551% for the control groups in the renal and hepatic impairment trials, respectively) were different from earlier in vitro results, as mentioned previously (2.8%).” (opens the source at this quote in a new tab)
“This can be explained by the different methods that were used throughout development.” (opens the source at this quote in a new tab)
“The results from the impairment trials were derived using the RED method, which was considered to be the most suitable method for a comparison of the different groups in these trials.” (opens the source at this quote in a new tab)

Populations not evaluated: hemodialysis and severe hepatic impairment

“The pharmacokinetics and safety of pritelivir in patients requiring hemodialysis have not been evaluated” (opens the prescribing information at this quote)
“The pharmacokinetics and safety of pritelivir in patients with severe hepatic impairment (Child-Pugh Class C) have not been evaluated” (opens the prescribing information at this quote)

Funding and author affiliations

“These trials were funded by AiCuris Anti-infective Cures AG.” (opens the source at this quote in a new tab)
“Dirk Kropeit, Susanne Bonsmann, Melanie Sumner, Alexander Birkmann, and Holger Zimmermann are employees of AiCuris Anti-infective Cures AG.” (opens the source at this quote in a new tab)
“Katharina Erb-Zohar is an independent clinical pharmacology consultant and owner of clinphase®, Schotten, Germany.” (opens the source at this quote in a new tab)
“Jörg Pausch was an employee of AiCuris Anti-infective Cures AG at the time of the studies.” (opens the source at this quote in a new tab)