A Study to Assess the Relative Bioavailability of TMC207 Following Single-Dose Administrations of Two Pediatric Formulations in Healthy Adult Participants

Healthy Clinical Trial

Official title:

A Phase I, Open-label, Randomized, 3-way Crossover Study in 3 Panels of Healthy, Adult Subjects to Assess the Relative Bioavailability of TMC207 Following Single-dose Administration of Two Pediatric Formulations Using a 100 mg Tablet Formulation as the Reference, With and Without Food.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01803373
• Other study ID #: CR100987
• Secondary ID: TMC207TBC1002201
• Status: Completed
• Phase: Phase 1
• First received: March 1, 2013
• Last updated: March 16, 2014
• Start date: April 2013
• Est. completion date: August 2013

Study information

• Verified date: March 2014
• Source: Janssen Infectious Diseases BVBA
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to test the relative bioavailability (extent and rate to which a drug is taken up by the body) of TMC207 following the administration of two pediatric formulations of TMC207 taken with and without food in healthy adult participants.

Description:

This is an open-label (all study staff and participants know the identity of treatments assigned), 3-way cross-over (method used to switch participants from one treatment to another treatment) study. Three panels of 12 healthy adult participants each will be enrolled. Within each panel, participants will be randomly (by chance) assigned to 1 of 6 treatment sequences to receive each of the 3 formulations of TMC207 in a randomized order. The 3 formulations of TMC207 will be referred to as Treatments A, B, and C. In Treatment A, participants will receive a single 100-mg dose of TMC207 formulated as a 100-mg tablet (reference formulation). In Treatment B, participants will receive a single 100-mg dose of TMC207 formulated as 20-mg water dispersible (dissolvable) tablets (i.e. 5 tablets) (pediatric formulation 1). In Treatment C, participants will receive a single 100-mg dose of TMC207 formulated as granules 5 grams (20 mg/g) (pediatric formulation 2). Each treatment will be separated by 4 weeks. Participants in Panel 1 will receive each treatment with a standardized breakfast, Panel 2 will receive each treatment with yogurt, and Panel 3 will receive each treatment after a 10-hour overnight fast (without food). The duration of the treatment period in this study will be 8.5 weeks (includes 4 weeks between treatments).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: August 2013
• Est. primary completion date: August 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• Healthy participant on the basis of physical examination, medical history, vital signs, and electrocardiogram (ECG), and the results of blood biochemistry and hematology tests and a urinalysis performed at screening

• Must have a Body Mass Index (BMI, weight in kg divided by the square of height in meters) of 18.5 to 30.0 kg/m2, extremes included

• Women must be postmenopausal for at least 2 years and have a negative serum pregnancy test at screening and a negative urine pregnancy test at Day -1

• Men must agree to use a highly effective method of birth control (eg., male condom with either female intrauterine device, diaphragm, cervical cap or hormone based contraceptives by their female partner) when having sexual intercourse with a female partner of childbearing potential, and to not donate sperm during the study and for 6 months after receiving the last dose of study drug. Men who have had a vasectomy and have a female partner of childbearing potential must agree to use a male condom during the study and for 6 months after receiving the last dose of study drug

• Participants must be non-smokers for at least 3 months prior to screening

Exclusion Criteria:

• Human immunodeficiency virus - type 1 (HIV-1) or type 2 (HIV-2) infection confirmed at screening

• Hepatitis A, B or C infection confirmed at screening

• A positive urine drug test or alcohol breath test at screening. Urine will be tested for the presence of amphetamines, barbiturates, benzodiazepines, cocaine, methadone, and opioids

• History or any currently active disease or condition that the Investigator considers to be clinically significant for which, in the opinion of the Investigator, participation would not be in the best interest of the participant (eg, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments

Study Design

Allocation: Randomized, Endpoint Classification: Bio-availability Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Biological Availability
• Healthy

Intervention

Drug:
• Treatment A (reference)
One tablet equivalent to a single 100-mg dose of TMC207 taken orally (by mouth) once.
• Treatment B
Five 20-mg water dispersable tablets equivalent to a single 100-mg dose of TMC207 taken orally (by mouth) once.
• Treatment C
5 grams (ie,20mg/g) equivalent to a single 100-mg dose of TMC207 taken orally (by mouth) once.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Infectious Diseases BVBA

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Plasma concentrations of TMC207	Protocol-specified pharmacokinetic parameters will be determined from plasma samples collected after each administration of study drug to assess the relative bioavailability of TMC207.	Up to 72 hours after study drug intake during 3 treatment sessions	No
Secondary	The plasma concentration of the primary metabolite in TMC207	Protocol-specified pharmacokinetic parameters will be determined from plasma samples collected after each administration of study drug to assess the concentration of the primary metabolite in TMC207.	Up to 72 hours after each study drug intake during 3 treatment sessions	No
Secondary	The effect of food on the relative bioavailability of TMC207	The effect of food will be determined by comparing, across panels, each formulation taken after eating a standardized breakfast versus after eating yoghurt, and versus no food (ie, in the fasted state).	Up to 72 hours after study drug intake during 3 treatment sessions	No
Secondary	The number of participants reporting adverse events as a measure of safety and tolerability	Includes up to 30-32 days after the last plasma sample in the last treatment session for participants who complete the study (or up to 30-32 days after a participant withdraws from the study).	Up to approximately 12.5 weeks	No
Secondary	The taste of TMC207	The taste of each formulation will be assessed by having study participants complete a 5-item questionnaire after they take study drug.	On Day 1 after study drug administration during 3 treatment sessions.	No