Thorough QT/QTc of Pritelivir in Healthy Subjects
brief summary
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). 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).
detailed description
Subjects were in-house from Day -2 to Day 20 and were randomized to one of the 2 parallel treatment groups (as part of the blind, both groups received the same number of tablets and capsules at the same timepoints, though some were verum and some were placebo depending on the randomized regimen). Group 1 received a therapeutic and a supra-therapeutic dose of pritelivir plus moxifloxacin placebo. Group 2 received pritelivir placebo as well as one dose of moxifloxacin and one dose of matching placebo in a 2-sequence crossover design (nested crossover). 12-lead electrocardiogram (ECG) triplicates were recorded from the bedside 12-lead ECG on the Days -1, 1, 2, 6, 16, and 17 and were analyzed afterwards in each group for these 6 days of documentation by a blinded reader.
It is of note that Holter ECG data was collected in parallel at Screening to exclude anyone with pre-existing cardiac abnormalities as well as on Days -1, 1, 2, 6, 16, and 17 as a back-up for the bedside 12-lead ECGs.
In Group 1, 32 male and female subjects (at least 12 subjects per sex) received a loading dose of 400 mg pritelivir on Day 1. Afterwards they received 100 mg pritelivir qd from Day 2 to 6 and 400 mg pritelivir qd from Day 7 to 16. Furthermore, these subjects received matching moxifloxacin placebo on the Days 2 and 17.
In Group 2, 32 male and female subjects (at least 12 subjects per sex) receive the respective amounts of tablets of matching pritelivir placebo from Day 1 to Day 16 in Group 2 as verum tablets in Group 1. Furthermore, subjects in Group 2a (16 male and female subjects) received 400 mg moxifloxacin on Day 2 and matching moxifloxacin placebo on Day 17 and subjects in Group 2b (16 male and female subjects) received 400 mg moxifloxacin on Day 17 and matching moxifloxacin placebo on Day 2.
To maintain double-blinding the following measures were needed, and data evaluations generated for Group 1 and Group 2:
* 12-lead ten second ECG triplicates were digitally recorded and analyzed (from the bedside 12-lead-ECG devices) in subjects of both groups on the Days -1, 1, 2, 6, 16 and 17. * PK samples were 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. * Over-encapsulated moxifloxacin- and matching placebo were used.
official title
A Double-blind, Single-center, Randomized, Placebo- and Positive-controlled, Parallel-group Trial With a Nested Crossover Part on the Electrocardiographic Effects 100 and 400 mg Pritelivir Per Day in Healthy Subjects: a Thorough QT/QTc Trial