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

September 4, 2017 updated by: Janssen Sciences Ireland UC

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
48

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 55 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Panel1: Sequence 1 (ABC)
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
150 milligram (mg) SMV capsule with water under fed conditions.
Other Names:
  • simeprevir
Drug: Treatment B
Treatment B (3*50 mg capsules of SMV (including 50 mini-tablets of 1 mg each) with water under fed conditions.
Other Names:
  • simeprevir
Drug: Treatment C
Treatment C (3*50 mg dispersible SMV tablets dispersed in water under fed conditions).
Other Names:
  • simeprevir
Experimental: Panel1: Sequence 2 (BCA)
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
150 milligram (mg) SMV capsule with water under fed conditions.
Other Names:
  • simeprevir
Drug: Treatment B
Treatment B (3*50 mg capsules of SMV (including 50 mini-tablets of 1 mg each) with water under fed conditions.
Other Names:
  • simeprevir
Drug: Treatment C
Treatment C (3*50 mg dispersible SMV tablets dispersed in water under fed conditions).
Other Names:
  • simeprevir
Experimental: Panel1: Sequence 3 (CAB)
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
150 milligram (mg) SMV capsule with water under fed conditions.
Other Names:
  • simeprevir
Drug: Treatment B
Treatment B (3*50 mg capsules of SMV (including 50 mini-tablets of 1 mg each) with water under fed conditions.
Other Names:
  • simeprevir
Drug: Treatment C
Treatment C (3*50 mg dispersible SMV tablets dispersed in water under fed conditions).
Other Names:
  • simeprevir
Experimental: Panel1: Sequence 4 (CBA)
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
150 milligram (mg) SMV capsule with water under fed conditions.
Other Names:
  • simeprevir
Drug: Treatment B
Treatment B (3*50 mg capsules of SMV (including 50 mini-tablets of 1 mg each) with water under fed conditions.
Other Names:
  • simeprevir
Drug: Treatment C
Treatment C (3*50 mg dispersible SMV tablets dispersed in water under fed conditions).
Other Names:
  • simeprevir
Experimental: Panel1: Sequence 5 (BAC)
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
150 milligram (mg) SMV capsule with water under fed conditions.
Other Names:
  • simeprevir
Drug: Treatment B
Treatment B (3*50 mg capsules of SMV (including 50 mini-tablets of 1 mg each) with water under fed conditions.
Other Names:
  • simeprevir
Drug: Treatment C
Treatment C (3*50 mg dispersible SMV tablets dispersed in water under fed conditions).
Other Names:
  • simeprevir
Experimental: Panel1: Sequence 6 (ACB)
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
150 milligram (mg) SMV capsule with water under fed conditions.
Other Names:
  • simeprevir
Drug: Treatment B
Treatment B (3*50 mg capsules of SMV (including 50 mini-tablets of 1 mg each) with water under fed conditions.
Other Names:
  • simeprevir
Drug: Treatment C
Treatment C (3*50 mg dispersible SMV tablets dispersed in water under fed conditions).
Other Names:
  • simeprevir
Experimental: Panel 2: Sequence 1 (DEF)
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
*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.
Other Names:
  • simeprevir
Drug: 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.
Other Names:
  • simeprevir
Drug: 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.
Other Names:
  • simeprevir
Experimental: Panel 2: Sequence 2 (EFD)
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
*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.
Other Names:
  • simeprevir
Drug: 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.
Other Names:
  • simeprevir
Drug: 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.
Other Names:
  • simeprevir
Experimental: Panel 2: Sequence 3 (FDE)
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
*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.
Other Names:
  • simeprevir
Drug: 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.
Other Names:
  • simeprevir
Drug: 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.
Other Names:
  • simeprevir
Experimental: Panel 2: Sequence 4 (FED)
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
*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.
Other Names:
  • simeprevir
Drug: 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.
Other Names:
  • simeprevir
Drug: 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.
Other Names:
  • simeprevir
Experimental: Panel 2: Sequence 5 (EDF)
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
*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.
Other Names:
  • simeprevir
Drug: 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.
Other Names:
  • simeprevir
Drug: 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.
Other Names:
  • simeprevir
Experimental: Panel 2: Sequence 6 (DFE)
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
*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.
Other Names:
  • simeprevir
Drug: 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.
Other Names:
  • simeprevir
Drug: 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.
Other Names:
  • simeprevir

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Maximum Plasma Concentration (Cmax) of Simeprevir (SMV)
Time Frame: Baseline up to 72 hours post-administration of study drug
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
Time Frame: Baseline up to 72 hours post-administration of study drug
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
Time Frame: Baseline up to 72 hours post-administration of study drug
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
Time Frame: Baseline up to 72 hours post-administration of study drug
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
Time Frame: Baseline up to 72 hours post-administration of study drug
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
Time Frame: Baseline up to 72 hours post-administration of study drug
The t(1/2) is defined as 0.693/Lambda (z).
Baseline up to 72 hours post-administration of study drug

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Number of Participants within Each Category of Taste Questionnaire
Time Frame: 5 to 15 minutes post administration of study drug (up to Day 19)
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).
5 to 15 minutes post administration of study drug (up to Day 19)
Number of Participants with Adverse Events (AEs) and Serious AEs
Time Frame: Screening up to follow-up (7 days after last dose administration)
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.
Screening up to follow-up (7 days after last dose administration)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Janssen Sciences Ireland UC

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 28, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 9, 2015

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 9, 2015

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 5, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 10, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 11, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 7, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 4, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CR106516
  • TMC435HPC1010 (Other Identifier: Janssen Sciences Ireland UC)
  • 2014-005448-17 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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