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

NCT02385071 | Completed Phase 1

• 3 other identifiers: CR106516TMC435HPC10102014-005448-17
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Keywords

Healthy; Simeprevir; Bioavailability

Outcome Measures

Primary Outcomes (6)

• Maximum Plasma Concentration (Cmax) of Simeprevir (SMV)

  The Cmax is the maximum observed plasma concentration of SMV.

  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.

  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.

  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.

  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.

  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).

  Baseline up to 72 hours post-administration of study drug

Secondary Outcomes (2)

• Number of Participants within Each Category of Taste Questionnaire

  5 to 15 minutes post administration of study drug (up to Day 19)

• Number of Participants with Adverse Events (AEs) and Serious AEs

  Screening up to follow-up (7 days after last dose administration)

Study Arms (12)

Panel1: Sequence 1 (ABC)

EXPERIMENTAL

Participants will receive Treatment A (150 milligram (mg) simeprevir (SMV) capsule with water under fed conditions) in Period 1; followed by Treatment B (3\*50 mg capsules of SMV \[including 50 mini-tablets of 1 mg each\] with water under fed conditions) in Period 2; followed by Treatment C (3\*50 mg dispersible SMV tablets dispersed in water under fed conditions) in Period 3. A washout period of at least 7 days will be maintained between each treatment period.

Drug: Treatment A; Drug: Treatment B; Drug: Treatment C

Panel1: Sequence 2 (BCA)

EXPERIMENTAL

Participants will receive Treatment B in Period 1; followed by Treatment C in Period 2; followed by Treatment A in Period 3. A washout period of at least 7 days will be maintained between each treatment period.

Drug: Treatment A; Drug: Treatment B; Drug: Treatment C

Panel1: Sequence 3 (CAB)

EXPERIMENTAL

Participants will receive Treatment C in Period 1; followed by Treatment A in Period 2; followed by Treatment B in Period 3. A washout period of at least 7 days will be maintained between each treatment period.

Drug: Treatment A; Drug: Treatment B; Drug: Treatment C

Panel1: Sequence 4 (CBA)

EXPERIMENTAL

Participants will receive Treatment C in Period 1; followed by Treatment B in Period 2; followed by Treatment A in Period 3. A washout period of at least 7 days will be maintained between each treatment period.

Drug: Treatment A; Drug: Treatment B; Drug: Treatment C

Panel1: Sequence 5 (BAC)

EXPERIMENTAL

Participants will receive Treatment B in Period 1; followed by Treatment A in Period 2; followed by Treatment C in Period 3. A washout period of at least 7 days will be maintained between each treatment period.

Drug: Treatment A; Drug: Treatment B; Drug: Treatment C

Panel1: Sequence 6 (ACB)

EXPERIMENTAL

Participants will receive Treatment A in Period 1; followed by Treatment C in Period 2; followed by Treatment B in Period 3. A washout period of at least 7 days will be maintained between each treatment period.

Drug: Treatment A; Drug: Treatment B; Drug: Treatment C

Panel 2: Sequence 1 (DEF)

EXPERIMENTAL

Participants will receive Treatment D (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 fed conditions) in Period 1; followed by Treatment E (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) in Period 2; followed by Treatment F (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) in Period 3. A washout period of at least 7 days will be maintained between each treatment period.

Drug: Treatment D; Drug: Treatment E; Drug: Treatment F

Panel 2: Sequence 2 (EFD)

EXPERIMENTAL

Participants will receive Treatment E in Period 1; followed by Treatment F in Period 2; followed by Treatment D in Period 3. A washout period of at least 7 days will be maintained between each treatment period.

Drug: Treatment D; Drug: Treatment E; Drug: Treatment F

Panel 2: Sequence 3 (FDE)

EXPERIMENTAL

Participants will receive Treatment F in Period 1; followed by Treatment D in Period 2; followed by Treatment E in Period 3. A washout period of at least 7 days will be maintained between each treatment period.

Drug: Treatment D; Drug: Treatment E; Drug: Treatment F

Panel 2: Sequence 4 (FED)

EXPERIMENTAL

Participants will receive Treatment F in Period 1; followed by Treatment E in Period 2; followed by Treatment D in Period 3. A washout period of at least 7 days will be maintained between each treatment period.

Drug: Treatment D; Drug: Treatment E; Drug: Treatment F

Panel 2: Sequence 5 (EDF)

EXPERIMENTAL

Participants will receive Treatment E in Period 1; followed by Treatment D in Period 2; followed by Treatment F in Period 3. A washout period of at least 7 days will be maintained between each treatment period.

Drug: Treatment D; Drug: Treatment E; Drug: Treatment F

Panel 2: Sequence 6 (DFE)

EXPERIMENTAL

Participants will receive Treatment D in Period 1; followed by Treatment F in Period 2; followed by Treatment E in Period 3. A washout period of at least 7 days will be maintained between each treatment period.

Drug: Treatment D; Drug: Treatment E; Drug: Treatment F

Interventions

Treatment A DRUG

150 milligram (mg) SMV capsule with water under fed conditions.

Also known as: simeprevir

Panel1: Sequence 1 (ABC); Panel1: Sequence 2 (BCA); Panel1: Sequence 3 (CAB); Panel1: Sequence 4 (CBA); Panel1: Sequence 5 (BAC); Panel1: Sequence 6 (ACB)

Treatment B DRUG

Treatment B (3\*50 mg capsules of SMV (including 50 mini-tablets of 1 mg each) with water under fed conditions.

Also known as: simeprevir

Panel1: Sequence 1 (ABC); Panel1: Sequence 2 (BCA); Panel1: Sequence 3 (CAB); Panel1: Sequence 4 (CBA); Panel1: Sequence 5 (BAC); Panel1: Sequence 6 (ACB)

Treatment C DRUG

Treatment C (3\*50 mg dispersible SMV tablets dispersed in water under fed conditions).

Also known as: simeprevir

Panel1: Sequence 1 (ABC); Panel1: Sequence 2 (BCA); Panel1: Sequence 3 (CAB); Panel1: Sequence 4 (CBA); Panel1: Sequence 5 (BAC); Panel1: Sequence 6 (ACB)

Treatment D DRUG

\*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.

Also known as: simeprevir

Panel 2: Sequence 1 (DEF); Panel 2: Sequence 2 (EFD); Panel 2: Sequence 3 (FDE); Panel 2: Sequence 4 (FED); Panel 2: Sequence 5 (EDF); Panel 2: Sequence 6 (DFE)

Treatment E DRUG

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.

Also known as: simeprevir

Panel 2: Sequence 1 (DEF); Panel 2: Sequence 2 (EFD); Panel 2: Sequence 3 (FDE); Panel 2: Sequence 4 (FED); Panel 2: Sequence 5 (EDF); Panel 2: Sequence 6 (DFE)

Treatment F DRUG

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.

Also known as: simeprevir

Panel 2: Sequence 1 (DEF); Panel 2: Sequence 2 (EFD); Panel 2: Sequence 3 (FDE); Panel 2: Sequence 4 (FED); Panel 2: Sequence 5 (EDF); Panel 2: Sequence 6 (DFE)

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Sciences Ireland UC: lead

Study Sites (1)

Unknown Facility

Harrow, United Kingdom

Location

MeSH Terms

Interventions

Simeprevir

Intervention Hierarchy (Ancestors)

Sulfonamides; Sulfones; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Janssen Sciences Ireland UC Clinical Trial

  Janssen Sciences Ireland UC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 5, 2015
• First Posted: March 11, 2015
• Study Start: April 28, 2015
• Primary Completion: September 9, 2015
• Study Completion: September 9, 2015
• Last Updated: September 7, 2017

Record last verified: 2017-09

Locations

GB (1)