A Phase I Randomized Dose/Formulation Comparison Study of SC-52151

• Status: Completed
• Trial end date: 1969-12-31
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

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.