HIV Infections
Conditions
Keywords
Acquired Immunodeficiency Syndrome, AIDS-Related Complex, HIV Protease Inhibitors
Brief summary
PRIMARY: To evaluate the safety, tolerability, pharmacokinetics, and ethanol exposure of two dose regimens and formulations of SC-52151. SECONDARY: To evaluate the preliminary anti-HIV activity of these treatment regimens and the relationship between day 14 plasma concentrations of SC-52151 and immunological and virological markers and toxicity. Since viral isolates with decreased susceptibility to the protease inhibitor SC-52151 occur in vitro after multiple passages, and since prolonged post infectious effects occur in vitro, comparison of two formulations, an elixir and a self-emulsifying drug delivery system (SEDDS), is needed to determine the appropriate dose formulation for Phase II studies.
Detailed description
Since viral isolates with decreased susceptibility to the protease inhibitor SC-52151 occur in vitro after multiple passages, and since prolonged post infectious effects occur in vitro, comparison of two formulations, an elixir and a self-emulsifying drug delivery system (SEDDS), is needed to determine the appropriate dose formulation for Phase II studies. Patients are randomized to four treatment arms to receive SC-52151 elixir or SEDDS formulation at 1 of 2 doses for 2 weeks, with follow-up for 14 days.
Interventions
DRUGTelinavir
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Primary purpose
TREATMENT
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Concurrent Medication: Required for patients with CD4 count \<= 200 cells/mm3: * PCP prophylaxis using TMP/SMX or aerosolized pentamidine. Allowed: * Topical antifungal agents. * Up to 1000 mg/day acyclovir as maintenance therapy for herpes simplex virus. * Antibiotics for bacterial infections. * Antipyretics, analgesics, nonsteroidal anti-inflammatory agents, antiemetics, and methadone for symptomatic treatment. Patients must have: * HIV infection. * CD4 count 150 - 500 cells/mm3.
Exclusion criteria
Co-existing Condition: Patients with the following symptoms or conditions are excluded: * Unable to tolerate the standard diet required for the study. * Unable to give informed consent. Concurrent Medication: Excluded: * Antiretrovirals and biologic response modifiers (including HIV vaccines). * Maintenance with ketoconazole, fluconazole, itraconazole, ganciclovir, foscarnet, pyrimethamine, sulfadiazine, clindamycin, azithromycin, isoniazid, rifampin, rifabutin, ethambutol, pyrazinamide, clofazimine, or clarithromycin. * Prophylaxis for Mycobacterial infection or fungal infections other than Candidiasis. * Allopurinol. * Omeprazole. * Astemizole. * Terfenadine. * Loratadine. * Psychotropics. * Phenylbutazone. * Barbiturates. * Benzodiazepines. * Monoamine oxidase inhibitors. * H-2 blockers. * Anticonvulsants. * Coumadin anticoagulants. * Oral contraceptives. * Antiarrhythmics. * Diltiazem. * Metronidazole. * Erythromycin. * Chloramphenicol. * Fluoroquinolones. * Disulfiram. * Erythropoietin. * G-CSF or GM-CSF. * Systemic corticosteroids. * Alcohol, including alcohol-containing medications. Patients with the following prior conditions are excluded: * Unexplained temperature \>= 38.5 C for any 7 days within the 30 days prior to study entry. * Chronic diarrhea (\>= three stools per day) for any 15 days within the 30 days prior to study entry. * Malignancy other than basal or squamous cell carcinoma of the skin, cervical intraepithelial neoplasia, and minimal Kaposi's sarcoma. Prior Medication: Excluded at any time: * Prior HIV protease inhibitor. Excluded within 30 days prior to study entry: * Investigational drugs. * Recombinant erythropoietin. * G-CSF or GM-CSF. * Interferon or interleukin. * Any HIV-1 vaccine. Excluded within 14 days prior to study entry: * Antiretrovirals. * Acute therapy for any opportunistic or other serious infection. * Therapy for malignancy. * Maintenance with ketoconazole, fluconazole, itraconazole, ganciclovir, foscarnet, pyrimethamine, sulfadiazine, clindamycin, azithromycin, isoniazid, rifampin, rifabutin, ethambutol, pyrazinamide, clofazimine, or clarithromycin. * Prophylaxis for Mycobacterial infection or fungal infections other than Candidiasis. Excluded within 7 days prior to study entry: * Allopurinol. * Omeprazole. * Astemizole. * Terfenadine. * Loratadine. * Psychotropics. * Phenylbutazone. * Barbiturates. * Benzodiazepines. * Monoamine oxidase inhibitors. * H-2 blockers. * Anticonvulsants. * Coumadin anticoagulants. * Oral contraceptives. * Antiarrhythmics. * Diltiazem. * Metronidazole. * Erythromycin. * Chloramphenicol. * Fluoroquinolones. * Disulfiram. Risk Behavior: Excluded: * History of substance or alcohol abuse. * Ingestion of more than 50 g alcohol daily within 6 months prior to study entry. * Recovered alcoholic.
Countries
United States
Outcome results
None listed