Objective of the trial of topical pritelivir 5% ointment in the protocol summary

“To assess the efficacy, tolerability and safety of pritelivir 5% w/w ointment applied 5 times daily for 4 days for the treatment of recurrent herpes labialis (rHL) in adults” (opens the source at this quote in a new tab)

Registry description of the topical ointment trial

“Randomized, double-blind, multi-center, three arm parallel group, comparative trial to assess pritelivir ointment safety and efficacy, ie, proportion of subjects with non-ulcerative lesions, in adult subjects with recurrent herpes labialis (RHL) in comparison with placebo or Zovirax® Cream.” (opens the source at this quote in a new tab)

Planned sites and study period in the protocol summary

“10 to 14 investigational sites in the US” (opens the source at this quote in a new tab)
“First Subject First Visit: 4th quarter 2016” (opens the source at this quote in a new tab)
“Last Subject Last Visit: 3rd quarter 2017” (opens the source at this quote in a new tab)

Study dates and status in the registry record

Field	Registry entry
Recruitment status	“Completed”
Study start (actual)	“2016-11-29”
Primary completion (actual)	“2017-09-29”
Study completion (actual)	“2017-10-16”
Results first posted	“2021-07-13”

Study locations in the registry record

“This study has 10 locations” (opens the source at this quote in a new tab)

State	Location
Arizona	“Scottsdale, Arizona, United States, 85251”
California	“Santa Rosa, California, United States, 95405”
Florida	“Pinellas Park, Florida, United States, 33781”
Minnesota	“Edina, Minnesota, United States, 55435”
Missouri	“St Louis, Missouri, United States, 63141”
Ohio	“Akron, Ohio, United States, 44311”
Ohio	“Cincinnati, Ohio, United States, 45236”
South Carolina	“Anderson, South Carolina, United States, 29621”
South Carolina	“Greer, South Carolina, United States, 29650”
Texas	“San Antonio, Texas, United States, 78229”

Topical pritelivir 5% ointment: randomized, double-blind, three-arm parallel-group design

“This is a randomized, double-blind, multi-center, three arm parallel group, comparative trial to assess the safety and efficacy, ie, proportion of subjects with non-ulcerative lesions, in adult subjects with rHL treated with pritelivir 5% w/w ointment.” (opens the source at this quote in a new tab)

Participant-initiated topical treatment at the first sign of a recurrence

“The start of treatment with trial medication will be initiated by the subject within one hour of noticing the first sign or symptom (eg, prodrome) of a recurrence of herpes labialis (HL). Trial medication will be applied to the affected area 5 times daily for 4 days.” (opens the source at this quote in a new tab)

Daily investigator assessment, diary, and follow-up after topical treatment

“After self-initiation of treatment with trial medication subjects will be assessed daily by the Investigator until complete healing for a maximum of 13 days. Subjects will document application of trial medication and the status of their lesion in a diary. There will also be blood sampling, ECG measurement and physical examination performed at the investigational site.” (opens the source at this quote in a new tab)

Lesion stages assessed by the investigator

“After self-initiation of treatment with trial medication subjects will be assessed daily for the following parameters by the Investigator until healing:” (opens the source at this quote in a new tab)
“prodrome (symptoms including itching, pain, tingling, but no physical evidence of disease by inspection or by palpation in the application area)” (opens the source at this quote in a new tab)
“papule (any elevation of skin without fluid in the application area)/edema” (opens the source at this quote in a new tab)
“vesicle (blister, fluid filled or collapsed, in the application area)” (opens the source at this quote in a new tab)
“ulcer/soft crust” (opens the source at this quote in a new tab)
“hard crust” (opens the source at this quote in a new tab)
“residual abnormalities (residual erythema/scaling)” (opens the source at this quote in a new tab)
“normal appearing skin.” (opens the source at this quote in a new tab)
“Maximum lesion area (length x width) in mm2” (opens the source at this quote in a new tab)

Participant diary

“Time of each application of trial treatment” (opens the source at this quote in a new tab)
“Pain intensity, changes in pain intensity, and cessation of pain at each application of trial treatment (at the first and last daily application as a minimum)” (opens the source at this quote in a new tab)
“Pain intensity, changes in pain intensity, and cessation of pain in the morning and evening on days after stop of application of trial treatment until pain disappeared” (opens the source at this quote in a new tab)
“Lesion stage at each application of trial treatment” (opens the source at this quote in a new tab)
“Lesion stage in the morning and evening on days after stop of application of trial treatment until lesion healing” (opens the source at this quote in a new tab)
“Lesion tenderness at each application of trial treatment” (opens the source at this quote in a new tab)
“Lesion tenderness in the morning and evening on days after stop of application of trial treatment until lesion tenderness disappeared.” (opens the source at this quote in a new tab)
“Subject diaries will be reviewed by the investigational site staff at each visit.” (opens the source at this quote in a new tab)

Safety measurements and pharmacokinetic blood sampling

“The following safety measures will be performed at screening and at Visit 5 (Day 5/6) and at the End of Trial Visit (Day 12±1) after initiation of treatment:” (opens the source at this quote in a new tab)
“Safety laboratory parameters, ie, serum chemistry, hematology, coagulation and urinalysis” (opens the source at this quote in a new tab)
“Vital signs, ie, systolic and diastolic blood pressure, pulse rate” (opens the source at this quote in a new tab)
“Standard 12-lead electrocardiogram (ECG) according to Einthoven, Goldberger and Wilson” (opens the source at this quote in a new tab)
“Blood sampling for pharmacokinetic analysis (one per day, in total seven samples) will be performed at randomization, daily at Visit 1 to Visit 5, and at the End of Trial Visit (Day 12±1). The time of PK blood sampling will be documented.” (opens the source at this quote in a new tab)

Design fields in the registry record

Field	Registry entry
Official title	“A Randomized, Double-blind, Multi-center, Three Arm (Pritelivir, Placebo and Zovirax®) Parallel Group, Comparative Trial to Assess the Efficacy and Safety of Pritelivir 5% w/w Ointment for the Treatment of Recurrent Herpes Labialis in Adults - LipP1”
Other study identifier	“AIC316-02-II-01”
Phase	“Phase 2”
Allocation	“Randomized”
Interventional model	“Parallel Assignment”
Masking	“Quadruple”
Primary purpose	“Treatment”
Sponsor	“AiCuris Anti-infective Cures AG”
Collaborator	“Novella Clinical”

Company statement on the start of the phase 2 trial of topical pritelivir

“Pritelivir (topical), designed for the treatment of recurrent labial herpes (mainly HSV-1), has just started a clinical phase 2 trial after reporting successful phase 1 clinical results.” (opens the source at this quote in a new tab)

Inclusion criteria for the topical ointment trial in the protocol summary

“Healthy men and women of any ethnic group aged ≥18 years” (opens the source at this quote in a new tab)
“Subjects should have experienced ≥4 recurrences of HL in the previous 12-month period” (opens the source at this quote in a new tab)
“Subjects should have experienced prodromal symptoms in at least 50% of rHL episodes and should have developed ulcerative lesions that have progressed through vesicle, ulcer, and crust stages in at least 50% of the episodes” (opens the source at this quote in a new tab)
“Willingness not to use any topical application (such as cosmetics, lip balm, sunscreens etc.) other than the trial medication in the area of lesion development from start of prodromal symptoms to healing” (opens the source at this quote in a new tab)
“Willingness not to use any systemic and topical anti-HSV agent during the trial participation including prescription and over-the-counter products” (opens the source at this quote in a new tab)
“Willingness not to use any systemic, anti-inflammatory or analgesic agents from start of prodromal symptoms to healing” (opens the source at this quote in a new tab)
“Willingness to refrain from mechanical disruption (ie, scrubbing, lancing, shaving) of the prodromal area or lesion after start of treatment with trial medication until end of the trial participation” (opens the source at this quote in a new tab)
“Women of child bearing potential and males must use adequate contraception” (opens the source at this quote in a new tab)
“Subject must give written informed consent.” (opens the source at this quote in a new tab)
“Subjects with current lesion may be enrolled, but must not to treat the lesion present at randomization with the trial medication; they should be instructed to wait for the next subsequent lesion.” (opens the source at this quote in a new tab)

Exclusion criteria for the topical ointment trial in the protocol summary

“Known intolerance to pritelivir or any of the ointment ingredients (ie, butylated hydroxytoluene (BHT), PEG-400, PEG-4000, propylene glycol)” (opens the source at this quote in a new tab)
“Known intolerance to Zovirax® Cream or any of the ingredients (ie, acyclovir, cetostearyl alcohol, mineral oil, poloxamer 407, propylene glycol, sodium lauryl sulfate, and white petrolatum) or valacyclovir” (opens the source at this quote in a new tab)
“Any skin conditions that could interfere with the assessment of HL recurrences (eg, eczema, psoriasis, acne)” (opens the source at this quote in a new tab)
“Any other condition which in the opinion of the Investigator would interfere with successful completion of this clinical trial” (opens the source at this quote in a new tab)
“Pregnant and/or breastfeeding women” (opens the source at this quote in a new tab)
“Participation in any investigational drug trial within the last 30 days before randomization for this clinical trial” (opens the source at this quote in a new tab)
“Previous treatment with pritelivir tablets” (opens the source at this quote in a new tab)
“Previous participation in a HSV vaccination trial (unless having received placebo)” (opens the source at this quote in a new tab)
“Clinically relevant ECG abnormalities (eg, QTc according to Fridericia: QTcF > 450ms for males and QTcF > 470ms for females; PR > 220 ms) at screening” (opens the source at this quote in a new tab)
“Clinically relevant abnormalities in laboratory indices at screening which in the opinion of the investigator might have an impact on the safety and evaluability of the subject” (opens the source at this quote in a new tab)
“Known chronic infections which in the opinion of the investigator might have an impact on the safety and evaluability of the subject” (opens the source at this quote in a new tab)
“Evidence of active malignancy or immunodeficiency disease, or require chronic use of immunosuppressive drugs (eg, systemic steroids) or topical steroids, or chronically use antiviral medication with activity against HSV” (opens the source at this quote in a new tab)
“HIV positive based on screening labs.” (opens the source at this quote in a new tab)

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

Field	Registry entry
Ages eligible for study	“18 Years and older (Adult, Older Adult )”
Sexes eligible for study	“All”
Accepts healthy volunteers	“No”

Test product: topical pritelivir 5% w/w ointment

“Pritelivir 5% w/w ointment, 5 times daily, topical application.” (opens the source at this quote in a new tab)
“Four days (20 applications).” (opens the source at this quote in a new tab)

Reference therapies: topical placebo ointment and Zovirax cream

“Pritelivir placebo ointment, 5 times daily, topical application” (opens the source at this quote in a new tab)
“Zovirax® Cream, 5 times daily, topical application.” (opens the source at this quote in a new tab)

Topical treatment arms in the registry record

Arm	Regimen
“Experimental: Pritelivir 5% w/w ointment”	“Topical treatment (20 applications), 5 times daily for 4 days”
“Placebo Comparator: Pritelivir ointment matching placebo”	“Topical treatment (20 applications), 5 times daily for 4 days”
“Active Comparator: Zovirax® cream”	“Topical treatment (20 applications), 5 times daily for 4 days”

Calculation of compliance with topical applications

“The percentage compliance will be calculated as the number of doses applied documented in the diary divided by 20 times 100.” (opens the source at this quote in a new tab)

Primary endpoint of the topical ointment trial in the protocol summary

“The percentage of subjects with non-ulcerative lesions in each treatment group.” (opens the source at this quote in a new tab)

Primary outcome measure and lesion stage scale in the registry record

“Efficacy Measured by Percentage of Subjects With Non-ulcerative Lesions Based on Principal Investigator's Assessment” (opens the source at this quote in a new tab)
“The Investigator assessed subjects for lesion stage at every visit as long as lesions were present from Visit 1 to the End of Trial Visit (Day 12± 1) as a maximum. Percentage of subjects with non-ulcerative lesions (i.e, scoring below 3) based on the Principal Investigators Assessment. Lesion stages were defined as follows: 1-Prodrome; 2a-Redness; 2b-Erythema-Redness; 3-Small Blister; 4-Ulcer; 5-Crust; 6-Drying up and healing; 0-Resolved” (opens the source at this quote in a new tab)

Assumed percentages of non-ulcerative lesions without treatment and with topical pritelivir

“The percentage of subjects with non-ulcerative lesions if left untreated with HL is estimated as 26%. The percentage of subjects with non-ulcerative lesions is assumed to be 50% when applying pritelivir 5% w/w ointment as compared to placebo.” (opens the source at this quote in a new tab)

Secondary efficacy endpoints: episode duration and lesion area

“Duration of lesion episode (DOE), defined as time from treatment initiation to the healing of the primary lesion (loss of crust) for subjects who experienced a vesicular lesion. For subjects whose primary lesions were not vesicular in nature, DOE is the time from the treatment initiation to the return to normal skin or to the cessation of symptoms, whichever occurs last” (opens the source at this quote in a new tab)
“Maximum lesion area (length x width) for ulcerative lesions during the vesicular, ulcerative and hard crust stages” (opens the source at this quote in a new tab)
“Cumulative lesion area (sum of daily maximum lesion areas)” (opens the source at this quote in a new tab)

Secondary efficacy endpoints: participant-assessed pain and tenderness

“Pain rate, defined as number of days with pain at lesion site relative to the total number of days with analyzable pain through daily subject self-assessment” (opens the source at this quote in a new tab)
“Subject-assessed duration of lesion pain, defined as the time from first dose of trial medication until pain is no longer reported by the subject (date and time)” (opens the source at this quote in a new tab)
“Subject-assessed severity of lesion pain defined as the average daily NUMERICAL RATING SCALE (NRS) pain score using a single-dimensional scale assessing pain intensity at lesion site, 11 intensities [no pain (0) to worst pain imaginable (10)]” (opens the source at this quote in a new tab)
“Duration of lesion tenderness (unpleasantness upon touching the affected area).” (opens the source at this quote in a new tab)

Safety and pharmacokinetic endpoints

“An overall summary of adverse events (AEs) will be provided including the number and percentage of subjects with any AE, treatment emergent AE (TEAE), related TEAE, serious AE, severe AE, and TEAE leading to early termination” (opens the source at this quote in a new tab)
“Safety signals such as hematological changes, lymphadenopathy, CRP increase, cutaneous adverse events and changes in (a)PTT” (opens the source at this quote in a new tab)
“Cmax, Tmax, AUC, if feasible” (opens the source at this quote in a new tab)

Planned enrollment

“approx. 360 subjects should be enrolled resulting in at least 71 subjects dosed in each treatment arm.” (opens the source at this quote in a new tab)

Sample size calculation

“The following table shows the total number of subjects with recurrences needed to show superiority of pritelivir compared with placebo with 80% power and assuming a type I error rate of 5%.” (opens the source at this quote in a new tab)
“In order to obtain 213 evaluable HL recurrences, 360 subjects need to be randomized in a 1:1:1 randomization scheme to cover the rate of approx. 40% of subjects which do not develop a recurrence or drop out.” (opens the source at this quote in a new tab)

Quantity	Value in the protocol summary
Proportion with non-ulcerative lesions, placebo	“26%”
Proportion with non-ulcerative lesions, pritelivir	“50%”
Evaluable recurrences needed per arm	“71”
Total evaluable recurrences needed	“213”
Total number of subjects needed, including 40% who do not develop a recurrence	“360”

Participants randomized and participants who treated a recurrence

“Overall, 362 subjects were enrolled and randomized. 223 started the self-initiated treatment due to an outbreak. The remaining 139 subjects did not have an outbreak and were not treated.” (opens the source at this quote in a new tab)

Participants started, analyzed for the primary outcome, and at risk for adverse events by topical treatment arm

Measure	Pritelivir 5% w/w ointment	Placebo ointment	Zovirax cream
Started	“73”	“73”	“77”
Analyzed for the primary outcome	“71”	“72”	“75”
At risk for adverse events	“73”	“73”	“77”

Intent-to-treat, per-protocol, and safety sets in the protocol summary

“The primary efficacy analysis will be performed in the ITT (Intend to Treat Set) and the PPS (Per-Protocol Set). ITT includes the results from all randomized subjects who applied the trial medication at least once and had at least one lesion status assessment done/reported after start of treatment. PPS is a subset of the ITT excluding subjects with major protocol violations.” (opens the source at this quote in a new tab)
“The secondary efficacy analyses will be performed in the ITT and the PPS.” (opens the source at this quote in a new tab)
“All safety analyses will be performed in the Safety Set (= all randomized subjects who applied at least one dose of trial medication).” (opens the source at this quote in a new tab)

Superiority test against placebo and descriptive comparison with the active comparator

“The statistical superiority will be tested against placebo and a descriptive comparison with Zovirax® Cream will be made.” (opens the source at this quote in a new tab)

Analysis population and method for the primary outcome in the registry results

“Primary analysis for the ITT ( intent to treat) population; multiple imputation.” (opens the source at this quote in a new tab)
“Cochran-Mantel-Haenszel” (opens the source at this quote in a new tab)

Recruitment relative to the planned number of evaluable recurrences

“Patients with labial HSV develop an outbreak only a few times per year. Therefore, more patients need to be enrolled to obtain the planned number of evaluable herpes labialis recurrences, as roughly 40% of subjects do not develop a recurrence.” (opens the source at this quote in a new tab)

Participant flow among participants who started topical treatment

Milestone	Pritelivir 5% w/w ointment	Placebo ointment	Zovirax cream
Started	“73”	“73”	“77”
Completed	“67”	“70”	“71”
Not completed	“6”	“3”	“6”
Lost to follow-up	“6”	“3”	“5”
Withdrawal by subject	“0”	“0”	“1”

Demographics of participants who started topical treatment, by arm

Characteristic	Pritelivir 5% w/w ointment, n = 73	Placebo ointment, n = 73	Zovirax cream, n = 77	Total, n = 223
Age, median (full range), years	“54 (21 to 74)”	“49 (20 to 77)”	“51 (18 to 79)”	“51 (18 to 79)”
Female, count (%)	“52”( “71.2%”)	“53”( “72.6%”)	“56”( “72.7%”)	“161”( “72.2%”)
Male, count (%)	“21”( “28.8%”)	“20”( “27.4%”)	“21”( “27.3%”)	“62”( “27.8%”)
American Indian or Alaska Native, count (%)	“0”( “0.0%”)	“1”( “1.4%”)	“0”( “0.0%”)	“1”( “0.4%”)
Asian, count (%)	“1”( “1.4%”)	“1”( “1.4%”)	“1”( “1.3%”)	“3”( “1.3%”)
Native Hawaiian or other Pacific Islander, count (%)	“0”( “0.0%”)	“0”( “0.0%”)	“0”( “0.0%”)	“0”( “0.0%”)
Black or African American, count (%)	“8”( “11.0%”)	“6”( “8.2%”)	“10”( “13.0%”)	“24”( “10.8%”)
White, count (%)	“63”( “86.3%”)	“65”( “89.0%”)	“65”( “84.4%”)	“193”( “86.5%”)
More than one race, count (%)	“1”( “1.4%”)	“0”( “0.0%”)	“1”( “1.3%”)	“2”( “0.9%”)
Enrolled in the United States, count (%)	“73”( “100.0%”)	“73”( “100.0%”)	“77”( “100.0%”)	“223”( “100.0%”)
Body mass index, median (full range), kg/m2	“27.8 (19.3 to 48.5)”	“27.3 (19.4 to 56.7)”	“28.1 (17.1 to 47.7)”	“27.8 (17.1 to 56.7)”

Primary endpoint for topical pritelivir 5% ointment: percentage of participants with non-ulcerative recurrences

Measure	Pritelivir 5% w/w ointment	Placebo ointment	Zovirax cream
Participants analyzed	“71”	“72”	“75”
Non-ulcerative recurrences, percentage of participants	“21.8”	“16.4”	“19.9”
Ulcerative recurrences, percentage of participants	“78.2”	“83.6”	“80.1”

Statistical comparison of topical pritelivir ointment with placebo ointment

Field	Registry entry
Comparison type	“SUPERIORITY”
Method	“Cochran-Mantel-Haenszel”
P value	“0.4294”

All-cause mortality, serious adverse events, and other adverse events by topical treatment arm

Category	Pritelivir 5% w/w ointment	Placebo ointment	Zovirax cream
All-cause mortality	“0/73 (0.00%)”	“0/73 (0.00%)”	“0/77 (0.00%)”
Serious adverse events	“0/73 (0.00%)”	“0/73 (0.00%)”	“0/77 (0.00%)”
Other (not including serious) adverse events	“30/73 (41.10%)”	“27/73 (36.99%)”	“27/77 (35.06%)”

Adverse events by term for topical pritelivir ointment, placebo ointment, and Zovirax cream, participants affected of participants at risk

System organ class	Term	Pritelivir 5% w/w ointment	Placebo ointment	Zovirax cream
Blood and lymphatic system disorders	Anaemia	“1/73 (1.37%)”	“1/73 (1.37%)”	“0/77 (0.00%)”
Cardiac disorders	Palpitations	“1/73 (1.37%)”	“0/73 (0.00%)”	“0/77 (0.00%)”
Ear and labyrinth disorders	Ear Pain	“1/73 (1.37%)”	“0/73 (0.00%)”	“0/77 (0.00%)”
Ear and labyrinth disorders	Eustachian tube dysfunction	“0/73 (0.00%)”	“1/73 (1.37%)”	“0/77 (0.00%)”
Gastrointestinal disorders	Abdominal discomfort	“1/73 (1.37%)”	“0/73 (0.00%)”	“0/77 (0.00%)”
Gastrointestinal disorders	Abdominal pain lower	“0/73 (0.00%)”	“0/73 (0.00%)”	“1/77 (1.30%)”
Gastrointestinal disorders	Chapped lips	“1/73 (1.37%)”	“0/73 (0.00%)”	“1/77 (1.30%)”
Gastrointestinal disorders	Diarrhoea	“1/73 (1.37%)”	“1/73 (1.37%)”	“0/77 (0.00%)”
Gastrointestinal disorders	Lip blister	“0/73 (0.00%)”	“1/73 (1.37%)”	“0/77 (0.00%)”
Gastrointestinal disorders	Nausea	“1/73 (1.37%)”	“1/73 (1.37%)”	“0/77 (0.00%)”
Gastrointestinal disorders	Toothache	“1/73 (1.37%)”	“0/73 (0.00%)”	“0/77 (0.00%)”
General disorders	Application site inflammation	“0/73 (0.00%)”	“1/73 (1.37%)”	“0/77 (0.00%)”
General disorders	Application site pain	“0/73 (0.00%)”	“1/73 (1.37%)”	“0/77 (0.00%)”
General disorders	Induration	“0/73 (0.00%)”	“0/73 (0.00%)”	“1/77 (1.30%)”
General disorders	Pain	“0/73 (0.00%)”	“0/73 (0.00%)”	“1/77 (1.30%)”
General disorders	Pyrexia	“0/73 (0.00%)”	“0/73 (0.00%)”	“1/77 (1.30%)”
Infections and infestations	Bronchitis	“1/73 (1.37%)”	“0/73 (0.00%)”	“0/77 (0.00%)”
Infections and infestations	Gastroenteritis	“1/73 (1.37%)”	“0/73 (0.00%)”	“1/77 (1.30%)”
Infections and infestations	Oral herpes	“10/73 (13.70%)”	“5/73 (6.85%)”	“3/77 (3.90%)”
Infections and infestations	Pharyngitis streptococcal	“0/73 (0.00%)”	“0/73 (0.00%)”	“1/77 (1.30%)”
Infections and infestations	Pyuria	“0/73 (0.00%)”	“0/73 (0.00%)”	“1/77 (1.30%)”
Infections and infestations	Respiratory tract infection	“1/73 (1.37%)”	“0/73 (0.00%)”	“0/77 (0.00%)”
Infections and infestations	Rhinitis	“0/73 (0.00%)”	“0/73 (0.00%)”	“1/77 (1.30%)”
Infections and infestations	Sinusitis	“1/73 (1.37%)”	“0/73 (0.00%)”	“0/77 (0.00%)”
Infections and infestations	Upper respiratory tract infection	“1/73 (1.37%)”	“1/73 (1.37%)”	“1/77 (1.30%)”
Infections and infestations	Viral upper respiratory tract infection	“2/73 (2.74%)”	“2/73 (2.74%)”	“0/77 (0.00%)”
Injury, poisoning and procedural complications	Arthropod bite	“0/73 (0.00%)”	“0/73 (0.00%)”	“2/77 (2.60%)”
Injury, poisoning and procedural complications	Brain contusion	“0/73 (0.00%)”	“0/73 (0.00%)”	“1/77 (1.30%)”
Injury, poisoning and procedural complications	Limb crushing injury	“0/73 (0.00%)”	“1/73 (1.37%)”	“0/77 (0.00%)”
Injury, poisoning and procedural complications	Muscle strain	“1/73 (1.37%)”	“0/73 (0.00%)”	“0/77 (0.00%)”
Injury, poisoning and procedural complications	Thermal burn	“0/73 (0.00%)”	“0/73 (0.00%)”	“1/77 (1.30%)”
Injury, poisoning and procedural complications	Wound complication	“0/73 (0.00%)”	“0/73 (0.00%)”	“1/77 (1.30%)”
Investigations	Blood creatine phosphokinase increased	“0/73 (0.00%)”	“1/73 (1.37%)”	“2/77 (2.60%)”
Investigations	Blood pressure increased	“1/73 (1.37%)”	“1/73 (1.37%)”	“1/77 (1.30%)”
Investigations	Blood sodium decreased	“0/73 (0.00%)”	“0/73 (0.00%)”	“1/77 (1.30%)”
Investigations	C-reactive protein increased	“0/73 (0.00%)”	“1/73 (1.37%)”	“0/77 (0.00%)”
Investigations	Cardiac murmur	“0/73 (0.00%)”	“0/73 (0.00%)”	“1/77 (1.30%)”
Investigations	Electrocardiogram ST-T change	“0/73 (0.00%)”	“1/73 (1.37%)”	“0/77 (0.00%)”
Investigations	Electrocardiogram T wave inversion	“0/73 (0.00%)”	“0/73 (0.00%)”	“1/77 (1.30%)”
Investigations	Eosinophil count increased	“0/73 (0.00%)”	“1/73 (1.37%)”	“0/77 (0.00%)”
Investigations	Haptoglobin increased	“0/73 (0.00%)”	“1/73 (1.37%)”	“0/77 (0.00%)”
Investigations	Lipase increased	“0/73 (0.00%)”	“1/73 (1.37%)”	“0/77 (0.00%)”
Investigations	Platelet count increased	“0/73 (0.00%)”	“0/73 (0.00%)”	“1/77 (1.30%)”
Investigations	Urine analysis abnormal	“2/73 (2.74%)”	“0/73 (0.00%)”	“1/77 (1.30%)”
Investigations	White blood cell count increased	“0/73 (0.00%)”	“0/73 (0.00%)”	“1/77 (1.30%)”
Musculoskeletal and connective tissue disorders	Arthralgia	“1/73 (1.37%)”	“0/73 (0.00%)”	“0/77 (0.00%)”
Musculoskeletal and connective tissue disorders	Back pain	“1/73 (1.37%)”	“0/73 (0.00%)”	“0/77 (0.00%)”
Musculoskeletal and connective tissue disorders	Muscle spasms	“0/73 (0.00%)”	“1/73 (1.37%)”	“0/77 (0.00%)”
Musculoskeletal and connective tissue disorders	Musculoskeletal pain	“0/73 (0.00%)”	“1/73 (1.37%)”	“0/77 (0.00%)”
Musculoskeletal and connective tissue disorders	Musculoskeletal stiffness	“1/73 (1.37%)”	“0/73 (0.00%)”	“0/77 (0.00%)”
Musculoskeletal and connective tissue disorders	Myalgia	“0/73 (0.00%)”	“0/73 (0.00%)”	“1/77 (1.30%)”
Musculoskeletal and connective tissue disorders	Pain in extremity	“1/73 (1.37%)”	“1/73 (1.37%)”	“1/77 (1.30%)”
Nervous system disorders	Dizziness	“1/73 (1.37%)”	“0/73 (0.00%)”	“1/77 (1.30%)”
Nervous system disorders	Headache	“1/73 (1.37%)”	“1/73 (1.37%)”	“3/77 (3.90%)”
Nervous system disorders	Sinus headache	“0/73 (0.00%)”	“0/73 (0.00%)”	“1/77 (1.30%)”
Renal and urinary disorders	Haematuria	“1/73 (1.37%)”	“0/73 (0.00%)”	“1/77 (1.30%)”
Renal and urinary disorders	Proteinuria	“0/73 (0.00%)”	“1/73 (1.37%)”	“0/77 (0.00%)”
Reproductive system and breast disorders	Vaginal haemorrhage	“1/73 (1.37%)”	“0/73 (0.00%)”	“0/77 (0.00%)”
Respiratory, thoracic and mediastinal disorders	Oropharyngeal pain	“1/73 (1.37%)”	“0/73 (0.00%)”	“1/77 (1.30%)”
Respiratory, thoracic and mediastinal disorders	Rhinorrhoea	“1/73 (1.37%)”	“0/73 (0.00%)”	“0/77 (0.00%)”
Respiratory, thoracic and mediastinal disorders	Sinus congestion	“0/73 (0.00%)”	“1/73 (1.37%)”	“3/77 (3.90%)”
Respiratory, thoracic and mediastinal disorders	Throat irritation	“0/73 (0.00%)”	“0/73 (0.00%)”	“1/77 (1.30%)”
Respiratory, thoracic and mediastinal disorders	Upper-airway cough syndrome	“0/73 (0.00%)”	“1/73 (1.37%)”	“0/77 (0.00%)”
Skin and subcutaneous tissue disorders	Acne	“0/73 (0.00%)”	“2/73 (2.74%)”	“0/77 (0.00%)”
Skin and subcutaneous tissue disorders	Ecchymosis	“0/73 (0.00%)”	“1/73 (1.37%)”	“0/77 (0.00%)”
Skin and subcutaneous tissue disorders	Papule	“1/73 (1.37%)”	“0/73 (0.00%)”	“0/77 (0.00%)”
Skin and subcutaneous tissue disorders	Pruritus	“0/73 (0.00%)”	“0/73 (0.00%)”	“1/77 (1.30%)”
Skin and subcutaneous tissue disorders	Rash	“0/73 (0.00%)”	“1/73 (1.37%)”	“1/77 (1.30%)”
Skin and subcutaneous tissue disorders	Skin mass	“0/73 (0.00%)”	“0/73 (0.00%)”	“1/77 (1.30%)”
Vascular disorders	Hypertension	“1/73 (1.37%)”	“0/73 (0.00%)”	“0/77 (0.00%)”

Adverse event collection, time frame, and coding dictionary

“Subjects were interviewed by the investigational site staff pre-dose and at every visit using nonleading questions.” (opens the source at this quote in a new tab)

Field	Registry entry
Time frame	“10 months”
Frequency threshold for reporting other adverse events	“0%”
Source vocabulary	“MedDRA 20.0”

Summary

LipP1 tested pritelivir 5% w/w ointment applied 5 times daily for 4 days, a topical formulation other than the approved 100 mg tablet. It enrolled healthy adults with recurrent herpes labialis and excluded immunodeficiency disease and HIV infection, a population outside the labeled indication. Of 362 randomized participants, 223 treated a recurrence and 139 had no outbreak. Non-ulcerative recurrences occurred in 21.8% of participants receiving pritelivir ointment and 16.4% receiving placebo ointment (P = 0.4294). The comparison with Zovirax cream was planned as descriptive. The registry posts no results for secondary endpoints and records an agreement that restricts publication without the sponsor's consent.

Basis for the descriptive comparison of topical pritelivir with the active comparator

“It is assumed that 71 recurrences in each arm are sufficient to allow for a descriptive comparison of pritelivir with Zovirax®.” (opens the source at this quote in a new tab)

Agreement on publication recorded in the registry

“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)
“The Institution and Investigator agree not to publish the results or other data of this Study without the prior written consent of Sponsor.” (opens the source at this quote in a new tab)