Clinical trial NCT00946842: A Study to Determine the Relative Oral Bioavailability of Single Dose Administration of TMC207, Under Fed and Fasted Conditions in Healthy Participants
Official title: A Phase I, Two-Panel, Open-Label, Randomized, 3-way Crossover Trial in Healthy Subjects to Determine the Relative Oral Bioavailability of TMC207 After Single Dose Administration of TMC207 100 mg as the Phase II Clinical Trial Tablet Formulation and as a Newly Developed Tablet Formulation, Under Fed and Fasted Conditions
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Healthy
Bioavailability
Relative bioavailability
TMC207
Fed condition
Fasted condition
Lead sponsor: Tibotec BVBA
Sponsor class: INDUSTRY
First posted: 2009-07-27
Enrollment: 28
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 determine the relative oral bioavailability (the extent to which a medication or other substance becomes available to the body as compared with another form of medication or other substance) of TMC207 after single-dose oral administration of the Phase II clinical study tablet formulation, and a newly developed tablet formulations, under fed (with food) and fasted (without food) conditions.

Detailed description: This is a 2-panel (2 groups), open-label (all people know the identity of the intervention), randomized (the study medication is assigned by chance), 3- way crossover (method used to switch participants from one treatment arm to another in a clinical study) study. The study consists of 3 phases including, the screening phase (less than or equal to 21 days before administration of study medication), treatment phase (84 days), and the follow-up phase (up to 30 to 35 days after the last blood sample in the last treatment session is collected). Approximately 24 healthy participants will be allocated to one of two panels: Panel A (participants will receive study medication under fed condition); and Panel B (participants will receive study medication under fasted condition). Participants in Panel A will be randomly assigned to 1 of 6 treatment sequences (Treatment sequences ABC, ACB, BAC, BCA, CBA, and CAB) to receive the following 3 formulations of TMC207 with food: Treatments A: the Phase II tablet formulation; Treatment B: newly developed tablet formulation with fine particle size distribution; and Treatment C: newly developed tablet formulation with coarse particle size distribution. Participants in Panel B will be randomly assigned to 1 of 6 treatment sequences (Treatment sequences DEF, DFE, EDF, EFD, FDE, and FED) to receive the following 3 formulations of TMC207 without food: Treatments D: the Phase II tablet formulation; Treatment E: newly developed tablet formulation with fine particle size distribution; and Treatment F: newly developed tablet formulation with coarse particle size distribution. Subsequent treatments will be separated by a period of 4 weeks. The total duration of the study for each participant will be approximately 20 weeks. Safety evaluations will include assessment of adverse events, clinical laboratory tests, vital signs, electrocardiogram, physical examination, and alcohol urine medicine screen which will be monitored throughout the study.

Eligibility criteria: Inclusion Criteria:

* Non-smoker or smokers with no more than 10 cigarettes or 2 cigars or 2 pipes per day for at least 3 months prior selection
* Normal weight as defined by a body mass index (weight in kilograms divided by the square of height in meters) of 18 to 30 kg/m2, extremes included
* Healthy on the basis of a medical evaluation that reveals the absence of any clinically relevant abnormality

Exclusion Criteria:

* Positive tests for Human Immunodeficiency Virus 1 (HIV type 1) or HIV 2; hepatitis A, hepatitis B, or hepatitis C infection; and urine drug tests at screening
* Female with no childbearing potential
* History or current use of alcohol, barbiturate, amphetamine, recreational or narcotic drug use
* Relevant medical history or presence of systemic disease (gastrointestinal, cardiovascular, neurologic, psychiatric, metabolic, renal, hepatic, respiratory, inflammatory, infectious disease), or significant skin disease
* History or presence of clinically significant electrocardiogram at screening
* Abnormal laboratory values at screening

Primary outcomes:
measure: Time to Reach the Maximum Plasma Concentration of TMC207
timeFrame: 0 hour predose to 672 hours postdose, after each of the 3 single-dose administration
measure: Maximum Plasma Concentration of TMC207
timeFrame: 0 hour predose to 672 hours postdose, after each of the 3 single-dose administration
measure: Area Under Curve From Time of Administration up to 72 Hours Post Dosing of TMC207
timeFrame: 0 hour predose to 672 hours postdose, after each of the 3 single-dose administration
Secondary outcomes:
measure: Time to Reach the Maximum Plasma Concentration of M2 Metabolite of TMC207
timeFrame: 0 hour predose to 672 hours postdose, after each of the 3 single-dose administration
measure: Maximum Plasma Concentration of M2 Metabolite of TMC207
timeFrame: 0 hour predose to 672 hours postdose, after each of the 3 single-dose administration
measure: Area Under Curve From Time of Administration up to 72 Hours Post Dosing of M2 Metabolite of TMC207
timeFrame: 0 hour predose to 672 hours postdose, after each of the 3 single-dose administration
measure: Area Under Curve From Time of Administration up to the Last Time Point With a Measurable Concentration Post Dosing of M2 Metabolite of TMC207
timeFrame: 0 hour predose to 672 hours postdose, after each of the 3 single-dose administration
measure: Area Under Curve Extrapolated to Infinity of M2 Metabolite of TMC207
timeFrame: 0 hour predose to 672 hours postdose, after each of the 3 single-dose administration
measure: Elimination Rate Constant of a Sequential Elimination Phase of the Plasma Concentration-Time Curve of M2 Metabolite of TMC207
timeFrame: 0 hour predose to 672 hours postdose, after each of the 3 single-dose administration
measure: Elimination Half-Life of M2 Metabolite of TMC207
timeFrame: 0 hour predose to 672 hours postdose, after each of the 3 single-dose administration
measure: Number of Participants With Adverse Events
timeFrame: Up to 20 weeks
Other outcomes:
Locations:
Study officials:
affiliation: Tibotec BVBA
name: Tibotec-Virco Virology BVBA Clinical Trial
role: STUDY_DIRECTOR
References: