Clinical trial NCT02385071: A Crossover Study to Evaluate Relative Bioavailability of Simeprevir Age-appropriate Oral Formulation Candidates Compared With 150-milligram (mg) Oral Capsule in Healthy Adult Participants
Official title: A Phase 1, Open-label, Randomized, 2-panel, 3-way Crossover Study in Healthy Adult Subjects to Assess the Relative Bioavailability of Simeprevir Following Single Dose Administration of Age-appropriate Oral Formulation Candidates, Compared to the 150-mg Oral Capsule, and to Assess the Effect of Food on the Bioavailability of Simeprevir Following Single Dose Administration of a Selected Age-appropriate Oral Formulation Candidate
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Healthy
Simeprevir
Bioavailability
Lead sponsor: Janssen Sciences Ireland UC
Sponsor class: INDUSTRY
First posted: 2015-03-11
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Participants must be healthy on the basis of physical examination, medical history, 12-lead electrocardiogram (ECG) and vital signs performed at screening (after signing the ICF), and on Day -1 of the first treatment session, if applicable. If there are abnormalities, the participant may be included only if the Investigator judges the abnormalities or deviations from normal to be not clinically significant. This determination must be recorded in the participant's source documents
* Participants must be willing and able to adhere to the prohibitions and restrictions specified in the protocol and study procedures
* Female participants, except for postmenopausal women, should have a negative serum pregnancy test at screening
* All female participants should have a negative urine pregnancy test on Day -1 of the first treatment session
* Male participants heterosexually active with a woman of childbearing potential must agree to use two effective methods of birth control and all men must not donate sperm during the study and for at least 30 days after receiving the last dose of study drug

Exclusion Criteria:

* Female participants who are pregnant or breast feeding at screening or on Day -1 of the first treatment session
* Participants with current hepatitis A infection (confirmed by hepatitis A antibody immunoglobulin \[IgM\]), or hepatitis B infection (confirmed by hepatitis B surface antigen \[HBsAg\]), or hepatitis C infection (confirmed by HCV antibody), or human immunodeficiency virus type 1 (HIV-1) or HIV-2 infection
* Participants with a history or evidence of current or past abuse of alcohol, or recreational or narcotic drugs, which in the Investigator's opinion would compromise the participant's safety and/or compliance with the study procedures
* Participants with any history of clinically relevant skin disease such as, but not limited to, dermatitis, eczema, drug rash, psoriasis, food allergy, and urticaria
* Participants with known allergies, hypersensitivity, or intolerance to simeprevir (SMV) or any of the excipients

Primary outcomes:
measure: Maximum Plasma Concentration (Cmax) of Simeprevir (SMV)
timeFrame: Baseline up to 72 hours post-administration of study drug
measure: Time to Reach the Maximum Plasma Concentration (Tmax) of SMV
timeFrame: Baseline up to 72 hours post-administration of study drug
measure: Area Under the Plasma Concentration-Time Curve From 0 to last (AUC[0-last]) Post Dose of SMV
timeFrame: Baseline up to 72 hours post-administration of study drug
measure: Area Under the Plasma Concentration-Time Curve From 0 to Infinite Time (AUC[0-infinity]) Post Dose of SMV
timeFrame: Baseline up to 72 hours post-administration of study drug
measure: Elimination Rate Constant (Lambda [z]) of SMV
timeFrame: Baseline up to 72 hours post-administration of study drug
measure: Terminal Half-life (t[1/2]) of SMV
timeFrame: Baseline up to 72 hours post-administration of study drug
Secondary outcomes:
measure: Number of Participants within Each Category of Taste Questionnaire
timeFrame: 5 to 15 minutes post administration of study drug (up to Day 19)
measure: Number of Participants with Adverse Events (AEs) and Serious AEs
timeFrame: Screening up to follow-up (7 days after last dose administration)
Other outcomes:
Locations:
city: Harrow
country: United Kingdom
Study officials:
affiliation: Janssen Sciences Ireland UC
name: Janssen Sciences Ireland UC Clinical Trial
role: STUDY_DIRECTOR
References: