Safety, Tolerability, and Effect of TMC207 and Efavirenz in Healthy Volunteers

• Status: Completed
• Trial end date: 2010-12-01
• Target enrollment: 0
• Participant gender: All

Summary

Common treatments for tuberculosis (TB) can interfere with certain antiretroviral (ARV) medications used to treat HIV. People whose immune systems are weakened by HIV infection are susceptible to TB, so it is important to find treatments for both that can be given in combination. This study will test the safety of combining a new medication for TB with an already approved HIV medication in healthy adults.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Treatments: Bedaquiline; Diarylquinolines; Efavirenz

Criteria

Inclusion Criteria:

• Females not of reproductive potential, defined as women who have been postmenopausal for at least 24 consecutive months or women who have undergone hysterectomy, bilateral oophorectomy, or bilateral tubal ligation

• Females who have been surgically sterilized and all males must agree to use contraceptives if participating in sexual activity that could lead to pregnancy while receiving the protocol-specified medications and for 4 weeks after stopping the medication

• Absence of HIV-1 infection, as documented by any licensed enzyme-linked immunosorbent assay (ELISA) test kit, within 21 days prior to study entry

• Estimated creatinine clearance of more than 50 ml/min, within 21 days prior to study entry, calculated by the Cockcroft-Gault method

• Laboratory test results obtained within 21 days prior to entry, including negative pregnancy test, negative hepatitis B and C tests, and certain blood values

Exclusion Criteria:

• Use of any prescription medication known to inhibit or induce CYP3A metabolizing enzymes within 30 days prior to entry

• Planned use during the study, from day 0 through the last PK blood draw, of any of the following: prescription medication(s), herbal supplement(s), nutritional supplement(s), or over-the-counter medication(s). Multivitamins and acetaminophen, up to 650 mg every 6 hours as an analgesic, are permitted.

• Hospitalization for any reason, pharmacotherapy for serious illness, or use of any prescription medication(s) within 14 days prior to study entry

• Receipt of any investigational study drug within 21 days prior to study entry

• Known allergy, sensitivity, or hypersensitivity to EFV or TMC207 or components of their formulations, including cyclodextrin allergy

• Significant previous or active history of cardiovascular, renal, liver, hematologic, neurologic, gastrointestinal, psychiatric, endocrine, or immunologic disease(s), as determined by the site investigator. This is inclusive of chronic illnesses or gastrointestinal conditions that may affect drug absorption, etc. Additionally, any medical condition that, in the opinion of the site investigator, would interfere with the volunteer's ability to participate in the protocol will exclude participation.

• Active illicit drug use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements

• Suspicion of active tuberculosis (TB) by the site investigator

• Inability to abstain from alcoholic beverages, grapefruit, and grapefruit juice for the duration of the study

• For smokers, inability to smoke 5 cigarettes per day or less for the duration of the study

• Breastfeeding

• Electrocardiogram (ECG) showing first-degree or greater heart block or QT interval (QTc) greater than 440 ms within 21 days prior to study entry. First-degree heart block is defined as PR interval greater than 200 ms.