Safety, Tolerability, and Effect of TMC207 and Efavirenz in Healthy Volunteers
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I, Safety, Tolerability, and Pharmacokinetic Interaction Study of Single-Dose TMC207 and Efavirenz in Healthy Volunteers|
- Area under curve (AUC) over 336 hours of TMC207, measured when dosed alone and when dosed together with efavirenz (EFV) 600 mg daily [ Time Frame: Measured at baseline and Days 1 to 15, 28, and 29 to 43 ] [ Designated as safety issue: Yes ]
- Signs or symptoms of toxicity ranked Grade 2 or higher, according to the DAIDS adverse event (AE) grading table [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
- Maximum observed plasma or serum concentration (Cmax) and oral clearance (CL/F) of TMC207 and AUC, Cmax, and CL/F of the M2 metabolite of TMC207 when dosed alone and when dosed together with EFV 600 mg daily [ Time Frame: Measured at baseline and Days 1 to 15, 28, and 29 to 43 ] [ Designated as safety issue: Yes ]
- AUC over 24 hours, Cmax, Cmin, CL/F, and elimination half-life (T1/2) of EFV and host EFV metabolism genotype status (CYP2B6) obtained from whole blood samples taken at screening [ Time Frame: Measured at baseline and on Day 28 ] [ Designated as safety issue: Yes ]
- Correlation between AUC over 24 hours of EFV and AUC over 336 hours of TMC207 [ Time Frame: Measured at baseline and Days 1 to 15, 28, and 29 to 43 ] [ Designated as safety issue: Yes ]
|Study Start Date:||December 2009|
|Study Completion Date:||December 2010|
|Primary Completion Date:||December 2010 (Final data collection date for primary outcome measure)|
Experimental: TMC207 alone and with EFV
Participants will receive single-dose TMC207 alone and then single-dose TMC207 with EFV.
Drug: Efavirenz (EFV)
Oral dose of 600 mg daily, taken in the evening
Other Name: SustivaDrug: TMC207
Single oral dose of 400 mg in the morning
Tuberculosis (TB) is the second most deadly infectious disease after HIV. Multidrug-resistant TB (MDR-TB) has emerged as a worldwide epidemic, limiting treatment options. HIV infected people with suppressed immune systems are particularly susceptible to TB, and TB is the leading cause of death among people with HIV. Treating people infected with both HIV and TB is particularly problematic because rifamycins, the drug class usually used to treat TB, lower the effectiveness of certain anti-HIV medications. Studies of pharmacokinetics (PK), the interactions between drugs and body, are needed to determine which anti-TB and anti-HIV medications can be safely and effectively combined. This study will examine TMC207, a new anti-TB medication with the potential to shorten TB treatment time, combined with efavirenz (EFV), an antiretroviral (ARV) medication used in many first-line treatment regimens for HIV. The study will test PK and safety of this combination in healthy volunteers.
Participation in this study will last 49 days. At entry, participants will complete basic assessments, including taking a medical history and completing a physical exam, an eye exam, an electrocardiogram (ECG) to measure heartbeat, a pregnancy test, and a blood test. Certain behaviors and substances will be prohibited during the study, including consuming grapefruit, alcohol, or caffeine (on PK visit days); taking nutritional supplements, over-the-counter herbal medicines, and certain medicines and drugs from other studies; and excessive smoking. Participants will also be asked to keep a medication diary to record all medications they take during the study.
All participants will receive study medications on the same schedule: a single dose of TMC207 on Days 1 and 29, and daily dosing of EFV on Days 15 to 43.
Participants will complete two PK visits, one from Days 1 to 3, and one from Days 28 to 31. During PK visits, participants will have their vital signs checked and undergo an ECG, and they may also complete a limited physical exam, give a medication history, and report on symptoms. They will have multiple blood samples taken via a catheter left in place for the 3-day visit. Blood samples will be taken before receiving TMC207; 1, 2, 3, 4, 5, 6, 8, and 12 hours after receiving TMC207; and again on the mornings of Days 2 and 3.
Participants will complete six outpatient visits over the 11 days following each PK visit and one outpatient visit on Day 21, between PK visits. At outpatient visits participants will complete a blood draw and may complete a limited physical exam and medical history, record symptoms, and review their medication diaries.
On Day 49 participants will complete their last study visit, repeating many of the assessments from baseline testing. In the case of side effects or abnormal blood tests, participants may be monitored longer for safety reasons.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00992069
|United States, California|
|Ucsf Aids Crs|
|San Francisco, California, United States, 94110|
|United States, Maryland|
|Johns Hopkins Adult AIDS CRS|
|Baltimore, Maryland, United States, 21287|
|United States, North Carolina|
|Unc Aids Crs|
|Chapel Hill, North Carolina, United States, 27514|
|United States, Ohio|
|The Ohio State Univ. AIDS CRS|
|Columbus, Ohio, United States, 43210|
|United States, Tennessee|
|Vanderbilt Therapeutics CRS|
|Nashville, Tennessee, United States, 37232-2582|
|Study Chair:||Kelly Dooley, MD||Johns Hopkins University|