Safety and Anti-HIV Activity of Capravirine Alone and in Combination With Other Anti-HIV Drugs
This 2-part study will test the safety and anti-HIV activity of capravirine alone, and the safety, anti-HIV activity, and drug interactions of capravirine combined with other anti-HIV drugs. Capravirine belongs to a class of drugs called non-nucleoside reverse transcriptase inhibitors (NNRTIs), which are effective when used together with other drugs, including nucleoside reverse transcriptase inhibitors (NRTIs) and protease inhibitors.
Normal volunteers 18 years of age and older may enroll in Part 1 of the study. HIV-infected patients 18 years of age and older who have not previously been treated with a NNRTI (efavirenz, nevirapine, and delavirdine) may participate in Part 2. All prospective study participants will be screened for eligibility with a physical examination, blood tests, a urine test and an electrocardiogram (ECG).
Part 1 - Volunteers will be randomly assigned to one of two treatment groups as follows:
Group 1 will receive capravirine alone for 7 days and capravirine plus efavirenz (another NNRTI) for an additional 10 days. On day 1, participants will have a physical examination, urine test and laboratory blood tests. Blood samples will be collected just before the first dose of capravirine is given and again at 0.5, 1, 2, 4, 6, 8 and 12 hours after the dose. A small plastic tube will be placed in a vein to avoid multiple needle sticks. On day 8, participants will have another physical examination and laboratory blood tests. Blood samples will be drawn again as described above. In the evening of day 8, efavirenz will be added to the regimen. On day 18 (the last day of the study), participants will have another physical examination and blood tests. Blood will again be collected as described above.
Group 2 will take capravirine alone for 8) days and capravirine plus ritonavir (a protease inhibitor) for an additional 8 days. Physical examinations, urine tests, and blood collections will be done as described above on day 1, day 8 and day 16 (the last day) of the study.
Part 2 - Patients will take capravirine alone for 7 days. On day 1, patients will have a physical examination, urine test and laboratory blood tests. Blood samples will be collected just before the first dose of capravirine is given and again at 0.5, 1, 2, 4, 6, 8 and 12 hours after the dose. A small plastic tube will be placed in a vein to avoid multiple needle sticks. On day 8, patients will have another physical examination and laboratory blood tests. Blood samples will be drawn again as described above. Additional drugs will then be added to the regimen (in varying doses according to group), as follows:
Group 1 - efavirenz plus abacavir
Group 2 - ritonavir plus efavirenz plus abacavir
Group 3 - ritonavir plus efavirenz plus abacavir
On day 15, the procedures performed on day 8 will be repeated.
Patients will have the option of having blood drawn daily on days 2 through 7 to measure HIV-1 viral load and of having a lumbar puncture (spinal tap) done between days 2 and 7 to measure how well capravirine gets into the central nervous system.
After day 15, patients in all groups will continue with their drug regimen until week 48 or until it is determined that the treatment is not effective for the patient. Physical examinations, viral load measurements, white blood cell counts and other blood tests will be done periodically throughout the trial. Within 4 weeks after the end of the study, patients will be followed with another physical examination, blood and urine tests, and an ECG.
|Study Design:||Endpoint Classification: Safety Study
Primary Purpose: Treatment
|Official Title:||Safety and Pharmacokinetic Study of Capravirine. Part I. Pharmacokinetics of Capravirine in HIV-Negative Volunteers. Part II. Antiviral Activity of Capravirine, Efavirenz, and Abacavir in HIV-Infected Patients|
|Study Start Date:||May 2000|
|Estimated Study Completion Date:||May 2002|
This is an open-label, phase I study examining the safety and anti-HIV activity of an investigational non-nucleoside reverse transcriptase inhibitor, capravirine. The primary objectives of the study are 1) To evaluate the safety and pharmacokinetics of capravirine when combined with efavirenz and (low-dose) ritonavir in non-HIV-infected volunteers; 2) To evaluate the safety, virologic activity, and pharmacokinetics of capravirine when combined with efavirenz, (low-dose) ritonavir, and abacavir in HIV-infected patients; and 3) To evaluate the safety, virologic activity, and pharmacokinetics of a once-daily regimen with capravirine, efavirenz, (low-dose) ritonavir, and abacavir in HIV-infected patients. The study will be conducted in 2 parts. Part I will examine the safety, pharmacokinetics, and potential drug interactions of capravirine with other antiretroviral agents in non-HIV-infected volunteers. Sixteen volunteers (8 per group) will receive capravirine monotherapy (7 days), followed by the addition of either: 1) efavirenz (10 days); or 2) ritonavir (8 days). Part II will examine the safety, virologic activity, pharmacokinetics, and potential drug interactions of capravirine in HIV-infected patients. Thirty patients (10 per group) will receive of capravirine monotherapy (7 days), followed by the randomized addition of: 1) efavirenz/abacavir (7 days); 2) ritonavir/efavirenz/abacavir (7 days) twice-daily regimen; or 3) ritonavir/efavirenz/abacavir (7 days) once-daily regimen. [Doses of capravirine may be changed depending upon pharmacokinetic data obtained from Part I of the study.] The primary efficacy endpoint is the time-to-virologic-failure.
|United States, Maryland|
|National Institute of Allergy and Infectious Diseases (NIAID)|
|Bethesda, Maryland, United States, 20892|