The purpose of this study is to assess the relative bioavailability (the extent to which a drug or other substance becomes available to the body) of simeprevir (SMV) following single dose administration of age-appropriate oral formulation candidates compared to the 150 milligram (mg) capsule, and to assess the effect of food on the bioavailability of SMV following single dose administration of a selected age-appropriate oral formulation candidate.
This is a Phase 1, open-label (all people know the identity of the intervention), randomized (study medication assigned to participants by chance), 2-panel, 3-way crossover (participants will receive different interventions sequentially during the trial) study in healthy adult participants. Participants will be equally divided over 2 panels, and will not be randomized between panels. Participants will not be allowed to switch panels. The study consists of 3 parts: Screening Phase (that is, 28 days before study commences on Day 1); Open-label Treatment (in subsequent 3-treatment periods in each Panel, each separated with washout period of 7 days); and Post-Treatment Phase (up to 7 days after last study drug intake). The duration of the study per participant will be at least 19 days, screening and follow-up not included. All the eligible participants will be randomly assigned to 1 of the 6 treatment sequences in each Panel. In fasted conditions, study drug will be administered following a 10-hour overnight fast. In fed conditions, participants will also fast from food for 10 hours, but will consume a high fat/high calorie breakfast within a 30-minute period. Study drug will be administered 30 minutes after the start of breakfast. Participants will not be allowed to have food until at least 4 hours after study drug administration. Blood samples will be collected for evaluation of pharmacokinetics at pre-dose and post-dose of study treatment. Relative bioavailability of SMV formulations will be evaluated primarily. Participants' safety will be monitored throughout the study.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
48
150 milligram (mg) SMV capsule with water under fed conditions.
Treatment B (3\*50 mg capsules of SMV (including 50 mini-tablets of 1 mg each) with water under fed conditions.
Treatment C (3\*50 mg dispersible SMV tablets dispersed in water under fed conditions).
\*50 mg SMV capsules (including 50 mini-tablets of 1 mg each) with water or 3\*50 mg dispersible SMV tablets dispersed in water under fed conditions.
3\*50 mg SMV capsules (including 50 mini-tablets of 1 mg each) with water or 3\*50 mg dispersible SMV tablets dispersed in water under fasted conditions.
3\*50 mg SMV capsules (including 50 mini-tablets of 1 mg each) with yoghurt or 3\*50 mg dispersible SMV tablets dispersed in apple juice under fed conditions.
Unnamed facility
Harrow, United Kingdom
Maximum Plasma Concentration (Cmax) of Simeprevir (SMV)
The Cmax is the maximum observed plasma concentration of SMV.
Time frame: Baseline up to 72 hours post-administration of study drug
Time to Reach the Maximum Plasma Concentration (Tmax) of SMV
The Tmax is the time to reach the maximum observed plasma concentration of SMV.
Time frame: Baseline up to 72 hours post-administration of study drug
Area Under the Plasma Concentration-Time Curve From 0 to last (AUC[0-last]) Post Dose of SMV
AUC (0-last) from time 0 to the time of the last measurable (non-below quantification limit \[BQL\]) concentration, calculated by linear-linear trapezoidal summation.
Time frame: Baseline up to 72 hours post-administration of study drug
Area Under the Plasma Concentration-Time Curve From 0 to Infinite Time (AUC[0-infinity]) Post Dose of SMV
The AUC (0-infinity) is the area under the plasma concentration-time curve from time 0 to infinite time, calculated as the sum of AUC (0-last) and C(last)/lambda(z), in which AUC(0-last) is area under the plasma concentration-time curve from time zero to time of the last quantifiable concentration, C(last) is the last observed quantifiable concentration and lambda(z) is elimination rate constant.
Time frame: Baseline up to 72 hours post-administration of study drug
Elimination Rate Constant (Lambda [z]) of SMV
The Lambda (z) determined by linear regression of the terminal points of the ln-linear plasma concentration-time curve.
Time frame: Baseline up to 72 hours post-administration of study drug
Terminal Half-life (t[1/2]) of SMV
The t(1/2) is defined as 0.693/Lambda (z).
Time frame: Baseline up to 72 hours post-administration of study drug
Number of Participants within Each Category of Taste Questionnaire
Participants will assess the palatability of the SMV formulations by Taste Questionnaire, Question 1 will assess sweetness, bitterness, flavor and overall taste of the formulation; and Question 2 consists of visual analog scale wherein participants will put a cross in the box beneath the scores, corresponding to the 5-point hedonic scale (dislike it very much; dislike it a little; not sure, like it a little, like it very much).
Time frame: 5 to 15 minutes post administration of study drug (up to Day 19)
Number of Participants with Adverse Events (AEs) and Serious AEs
An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Time frame: Screening up to follow-up (7 days after last dose administration)
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