HIV Clinical Trial
Official title:
A Phase I, Safety, Tolerability, and Pharmacokinetic Interaction Study of Single-Dose TMC207 and Efavirenz in Healthy Volunteers
Verified date | October 2021 |
Source | National Institute of Allergy and Infectious Diseases (NIAID) |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Completed |
Enrollment | 37 |
Est. completion date | December 2010 |
Est. primary completion date | December 2010 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | All |
Age group | 18 Years to 65 Years |
Eligibility | 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. |
Country | Name | City | State |
---|---|---|---|
United States | Johns Hopkins Adult AIDS CRS | Baltimore | Maryland |
United States | Unc Aids Crs | Chapel Hill | North Carolina |
United States | The Ohio State Univ. AIDS CRS | Columbus | Ohio |
United States | Vanderbilt Therapeutics CRS | Nashville | Tennessee |
United States | Ucsf Aids Crs | San Francisco | California |
Lead Sponsor | Collaborator |
---|---|
National Institute of Allergy and Infectious Diseases (NIAID) |
United States,
Diacon AH, Pym A, Grobusch M, Patientia R, Rustomjee R, Page-Shipp L, Pistorius C, Krause R, Bogoshi M, Churchyard G, Venter A, Allen J, Palomino JC, De Marez T, van Heeswijk RP, Lounis N, Meyvisch P, Verbeeck J, Parys W, de Beule K, Andries K, Mc Neeley DF. The diarylquinoline TMC207 for multidrug-resistant tuberculosis. N Engl J Med. 2009 Jun 4;360(23):2397-405. doi: 10.1056/NEJMoa0808427. — View Citation
Goldman RC, Plumley KV, Laughon BE. The evolution of extensively drug resistant tuberculosis (XDR-TB): history, status and issues for global control. Infect Disord Drug Targets. 2007 Jun;7(2):73-91. Review. — View Citation
McIlleron H, Meintjes G, Burman WJ, Maartens G. Complications of antiretroviral therapy in patients with tuberculosis: drug interactions, toxicity, and immune reconstitution inflammatory syndrome. J Infect Dis. 2007 Aug 15;196 Suppl 1:S63-75. Review. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Area under curve (AUC) over 336 hours of TMC207, measured when dosed alone and when dosed together with efavirenz (EFV) 600 mg daily | Measured at baseline and Days 1 to 15, 28, and 29 to 43 | ||
Primary | Signs or symptoms of toxicity ranked Grade 2 or higher, according to the DAIDS adverse event (AE) grading table | Throughout study | ||
Secondary | 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 | Measured at baseline and Days 1 to 15, 28, and 29 to 43 | ||
Secondary | 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 | Measured at baseline and on Day 28 | ||
Secondary | Correlation between AUC over 24 hours of EFV and AUC over 336 hours of TMC207 | Measured at baseline and Days 1 to 15, 28, and 29 to 43 |
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