Clinical trial NCT05513625
Conditions: HSV Infection
Sponsor: AiCuris Anti-infective Cures AG
Start date: 2020-07-13; Completion date: 2020-10-13
Enrollment: 16 participants; Allocation: NON_RANDOMIZED; Intervention model: SEQUENTIAL

Brief summary:
To investigate the effect of esomeprazole (ESO) on the pharmacokinetics of pritelivir (PTV), and to investigate the safety and tolerability of PTV.

Detailed description:
This was a single-center, open-label, 2-period, fixed-sequence Phase 1 trial in 16 healthy adult male and female subjects (at least 7 subjects per sex). In the first period, subjects received treatment 1 (T1; single dose of 100 mg PTV on Day 1). In the second period, subjects received treatment 2 (T2: 40 mg qd ESO from Day -3 to Day 1 followed by a single dose of 100 mg PTV on Day 1). The wash-out period between PTV administrations in T1 and T2 was at least 4 weeks.

Arms: arm 1: Single dose 100 mg pritelivir (PTV) administered day 1 arm 2: 40 mg qd ESO Day -3 to Day1. Single dose of 100 mg PTV on Day 1
Interventions: intervention 1: Pritelivir intervention 2: ESO and pritelivir
Intervention descriptions: intervention 1: oral administration intervention 2: oral administration

Protocol documents:
Prot_SAP_000.pdf: 
 
 
CONFIDENTIAL 
 
 
 
AIC316-03-I-01  
Summary of the Clinical Trial Protocol  
and Statistical Plan 
 
A single-center, open-label, 2-period, fixed-sequence Phase 1 trial  
to evaluate the effect of esomeprazole on the pharmacokinetics of pritelivir 
 
NCT number: 
NCT05513625 
Investigational drug: 
Pritelivir 
 
 
Sponsor: 
Address: 
 
AiCuris Anti-infective Cures AG 
Friedrich-Ebert Str. 475 
DE-42117 Wuppertal 
Germany 
Finalization dates: 
 
Summary of the Clinical Trial 
Protocol and Statistical Plan, V1.0: 
16Sep2022 
Clinical Trial Protocol,  
V1.0: 
04Jun2020 
Safety Statistical Analysis Plan, 
V2.0: 
21Jul2020 
Pharmacokinetic Statistical 
Analysis Plan, V1.0: 
01Jul2020 


 
Summary of the Clinical Trial 
Protocol and Statistical Plan 
AIC316-03-I-01 
V1.0 
16Sep2022 
 
 
 
CONFIDENTIAL 
2 of 4 
 
SUMMARY OF THE CLINICAL TRIAL PROTOCOL AND STATISTICAL 
PLAN 
Name of Sponsor/Company: 
AiCuris Anti-infective Cures GmbH  
Title of the trial: A single-center, open-label, 2-period, fixed-sequence Phase 1 trial to evaluate the effect 
of esomeprazole on the pharmacokinetics of pritelivir 
Principal Investigator: Dr. Leela Vrishabhendra 
Trial center(s): 
Medpace Clinical Pharmacology 
5355 Medpace Way, Cincinnati, Ohio 45227, USA 
Planned trial period: 
First Subject First Visit:  
Last Subject Last Visit 
 
Jul 2020 
Sep 2020 
Phase of development: 
Phase 1 
Objectives: 
• 
To investigate the effect of esomeprazole on the pharmacokinetics of pritelivir  
• 
To investigate the pharmacokinetics of pritelivir metabolites AIC090015, AIC090105 and 
AIC090015-acylglucuronides 
• 
To investigate the safety and tolerability of pritelivir 
Trial design: 
This will be a single-center, open-label, 2-period, fixed-sequence Phase 1 trial in 18 healthy adult male 
and female subjects (at least 7 subjects per sex). All subjects will receive treatment 1 (T1; single dose of 
100 mg pritelivir will be administered on Day 1) in the first period, followed by treatment 2 (T2; single 
dose of 100 mg pritelivir will be administered on Day 1 and 40 mg esomeprazole will be administered qd 
from Day -3 to Day 1) in the second period. The wash-out period between pritelivir administrations in T1 
and T2 is at least 4 weeks. 
Number of subjects (planned): 
18 
Diagnosis and main criteria for inclusion: 
Healthy adult male and female subjects (at least 7 subjects per sex) of any ethnic origin, aged 18 to 
45 years inclusive. 
Test product, dose and mode of administration: 
Oral 100 mg pritelivir tablets 
Oral 40 mg esomeprazole tablets (Nexium®) 
Duration of treatment: 
In Treatment Period 1: 
Pritelivir:  
single dose of 100 mg on Day 1 
 


 
Summary of the Clinical Trial 
Protocol and Statistical Plan 
AIC316-03-I-01 
V1.0 
16Sep2022 
 
 
 
CONFIDENTIAL 
3 of 4 
 
In Treatment Period 2: 
4 days 
Esomeprazole: 40 mg qd from Day -3 to Day 1, inclusive 
Pritelivir:  
single dose of 100 mg on Day 1 
Reference therapy, dose and mode of administration, batch number(s): 
Not applicable. 
Criteria for evaluation: 
Efficacy 
Not applicable. 
 
Pharmacokinetics 
Primary variables: 
• 
AUC0-∞, AUC0-last, Cmax of pritelivir in plasma 
 
Secondary variables: 
• 
tmax, tlag, t1/2z, CL/F, Vd /F, MRT of pritelivir in plasma 
• 
AUC0-∞, AUC0-last, Cmax, tmax, tlag, t1/2z, MRT of metabolites AIC090015, AIC090105 and AIC090015-
acyl glucuronides in plasma 
• 
The ratio between each of the metabolites AIC090015, AIC090105 and AIC090015-acyl 
glucuronides versus pritelivir will be calculated for AUC0-∞, AUC0-last 
 
Pharmacokinetic profile will be determined in each period on Day 1 for 360 hours. 
 
Pharmacogenomics/gene expression: 
• 
Post-hoc analysis of alleles associated with altered drug metabolism/ disposition may be determined. 
 
Safety 
• 
Overall tolerability 
• 
Nature, frequency, duration, severity and causality of adverse events 
• 
Clinical laboratory parameters 
• 
Vital signs (blood pressure, pulse rate) 
• 
Standard 12-lead ECG 


 
Summary of the Clinical Trial 
Protocol and Statistical Plan 
AIC316-03-I-01 
V1.0 
16Sep2022 
 
 
 
CONFIDENTIAL 
4 of 4 
 
Statistical methods: 
Pharmacokinetic data 
The Pharmacokinetic Set (PKS) will include all subjects in the Safety Set (SS) with at least 1 plasma 
concentration time point for inclusion in the PK analysis. The PKS will be used for the PK analyses. 
Descriptive statistics will be calculated for plasma concentrations of pritelivir and derived PK parameters. 
Statistics include sample size (n), mean, standard deviation (SD), %CV, geometric mean, median, 
minimum and maximum. 
The relative bioavailability of pritelivir with respect to the primary variables AUC0-∞, AUC0-last and Cmax 
will be explored based on the log transformed data with an analysis of variance model with treatment (as 
fixed effect) and subject (as random effect). Point estimates (GMR) and 90% confidence intervals (90% 
CIs) will be computed for the ratio T2 (test) /T1 (reference) to evaluate the effect of esomeprazole on 
pritelivir PK under fasted conditions. 
Safety data 
Safety data analysis will be conducted on the Safety Set. Statistical analysis of the safety data will be 
limited to descriptive summaries. 
The results of AE recording, vital signs, 12-lead ECGs, clinical laboratory investigations, and physical 
examinations will be listed by subject and analyzed by descriptive statistics as appropriate. 
All adverse events will be coded according to the Medical Dictionary for Regulatory Activities 
(MedDRA). Incidences of treatment-emergent adverse events (TEAE) that began after the start of trial 
treatment (post-dose on Day 1 to End of trial examination) will be summarized at 3 levels: the overall 
subject level (occurrence of at least one TEAE), primary System Organ Class level, and preferred term 
level. All adverse events will be listed together with information on onset, duration, frequency, intensity, 
seriousness, relationship to IMP, outcome, and action taken. 
Laboratory data will be presented in summary statistics of raw data and change from baseline values 
(mean, median, standard deviation, minimum, maximum), and by flagging values outside the reference 
range in data listings. Vital signs will be summarized presenting statistics of raw data and change from 
baseline values (mean, median, standard deviation, minimum and maximum). 
ECG data will be summarized presenting statistics of raw data and change from baseline values (mean, 
median, standard deviation, minimum and maximum). In addition, 12-lead ECGs will be analyzed with a 
focus on the incidence and extent of QTc prolongation. QTc will be calculated according to Fridericia 
formula. Frequencies for classes of absolute values and differences from baseline will be provided 
according to the classifications defined by ICH-E14. 
The World Health Organization Drug Dictionary (WHO-DD) will be used for coding of concomitant 
medications (except IMPs).