PK Interaction Between Rifapentine or Rifampicin and a Single Dose of TMC207 in Healthy Subjects (TMC207-CL002)
| Status: | Completed |
|---|---|
| Conditions: | Infectious Disease |
| Therapuetic Areas: | Immunology / Infectious Diseases |
| Healthy: | No |
| Age Range: | 19 - 55 |
| Updated: | 4/21/2016 |
| Start Date: | March 2010 |
| End Date: | May 2010 |
A Phase I Open-label Trial to Investigate the Pharmacokinetic Interaction Between Rifapentine or Rifampicin and a Single Dose of TMC207 in Healthy Subjects
This is a open-label study, 2-treatment, 2-period, single sequence design. Period 1 will
examine the pharmacokinetics of TMC207 in the absence of rifapentine or rifampicin. Subjects
will receive a single 400-mg dose of TMC207 administered alone on Study Day 1. Period 2 will
examine the effects of repeated doses of either rifapentine or rifampicin on TMC207
pharmacokinetics and will begin on Study Day 20. During Period 2, subjects will receive 22
daily doses of either 600 mg rifapentine or rifampicin from Study Day 20 through Study Day
41. A single 400-mg dose of TMC207 will be administered on Study Day 29. Subjects will be
confined to the clinic from Study Day-1 to Study Day 2 in the morning of Period 1, and Study
Day 19 to Study Day 30 in the morning of Period 2. The study hypothesis is to determine
whether Rifapentine affects the pharmacokinetics of TMC207 as measured by effects on Cmax
and AUC(0-t) to a lesser degree than rifampicin.
examine the pharmacokinetics of TMC207 in the absence of rifapentine or rifampicin. Subjects
will receive a single 400-mg dose of TMC207 administered alone on Study Day 1. Period 2 will
examine the effects of repeated doses of either rifapentine or rifampicin on TMC207
pharmacokinetics and will begin on Study Day 20. During Period 2, subjects will receive 22
daily doses of either 600 mg rifapentine or rifampicin from Study Day 20 through Study Day
41. A single 400-mg dose of TMC207 will be administered on Study Day 29. Subjects will be
confined to the clinic from Study Day-1 to Study Day 2 in the morning of Period 1, and Study
Day 19 to Study Day 30 in the morning of Period 2. The study hypothesis is to determine
whether Rifapentine affects the pharmacokinetics of TMC207 as measured by effects on Cmax
and AUC(0-t) to a lesser degree than rifampicin.
Inclusion Criteria:
- Aged between 19 and 55 years, extremes included.
- Non tobacco/nicotine using (at least 3 months prior to screening).
- Body Mass Index (BMI, weight in kg divided by the square of height in meters) of 18.0
to 32.0 kg/m2, inclusive.
- Informed Consent Form (ICF) signed voluntarily before the first trial-related
activity.
- Able to comply with protocol requirements.
- Healthy on the basis of a medical evaluation or history that reveals the absence of
any clinically relevant abnormality and includes a physical examination, medical
history, electrocardiogram (ECG), vital signs, and the results of blood biochemistry,
and hematology tests and a urinalysis carried out at screening (See Section 6.1).
Exclusion Criteria:
- Female, except if postmenopausal since more than 2 years, or post-hysterectomy, or
post surgical sterilization, i.e., tubal ligation (without reversal operation) or
total hysterectomy.
- History or evidence of current use of alcohol, barbiturate, amphetamine, recreational
or narcotic drug use, which in the investigator's opinion would compromise subject's
safety and/or compliance with the trial procedures.
- Any clinically significant (as deemed by the Principle Investigator) history acute
illness (resolved within 4 weeks of screening), or presence of cardiovascular,
pulmonary, hepatic, renal, hematologic, gastrointestinal (including eating
disorders), endocrine, metabolic, immunologic, dermatologic, neurologic,
psychological, or psychiatric disease.
- Currently significant diarrhea, gastric stasis, or constipation that in the
investigator's opinion could influence drug absorption or bioavailability.
- Any history of significant skin disease such as, but not limited to, rash or
eruptions, drug allergies, food allergy, dermatitis, eczema, psoriasis, or urticaria.
Subjects with a history of skin disease may be enrolled into the study after
consultation with the Sponsor Medical Monitor.
- Previously demonstrated clinically significant allergy or hypersensitivity to any of
the excipients of the investigational medication administered in this trial (i.e.
rifapentine, rifampicin, and TMC207).
- Subjects with QTcF [Fredericia correction] interval > 450 msec (based on the average
of the triplicate ECGs) at screening (and confirmed by repeat ECG).
- Subjects with any other clinically significant ECG abnormality at screening, such as
arrhythmia, ischemia, or evidence of heart failure or with a family history of Long
QT Syndrome.
- Use of concomitant medication, including over-the-counter products and dietary
supplements, except for ibuprofen and paracetamol up to 7 days before the first dose
of trial medication and all prescribed medication must have been discontinued at
least 14 days before first intake of trial medication.
- Participation in an investigational drug trial within 60 days prior to the first
intake of trial medication.
- Donation of blood or significant loss of blood within 56 days or plasma donation
within 7 days preceding the first intake of trial medication.
- Having received TMC207 in a previous trial.
- Positive HIV-1 or HIV-2 test at screening
- Hepatitis A, B, or C infection (confirmed by hepatitis A antibody IgM, hepatitis B
surface antigen, or hepatitis C virus antibody, respectively) at screening.
- A positive urine drug test at screening. Urine will be tested to check the current
use of alcohol, amphetamines, benzodiazepines, cocaine, cannabinoids, and opioids.
- Subjects with the following laboratory abnormalities at screening as defined by the
NIH, NIAID, Division of Microbiology and Infectious Diseases (DMID) Adult Toxicity
Table and in accordance with the normal ranges of the clinical laboratory: Serum
creatinine grade 1 or greater (> 1.0 x ULN); Pancreatic lipase grade 1 or greater (>
1.0 x ULN); Hemoglobin grade 1 or greater (≤ 10.5 g/dL); Platelet count grade 1 or
greater (≤ 99000/mm3); Absolute neutrophil count grade 1 or greater (≤ 1500/mm3);
Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) grade 1 or greater
(> 1.0 x ULN); Total bilirubin grade 1 or greater (> 1.0 x ULN); Any other toxicity
grade 2 or above, including: proteinuria (spot urine) > 1+ and gross hematuria.
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