a phase i randomized dose/formulation comparison study of sc-52151

Conditions: HIV Infections

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.

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.

Eligibility criteria:
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.

Keywords: acquired immunodeficiency syndrome aids-related complex hiv protease inhibitors