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

NCT ID: NCT00000806

Last Updated: 2005-06-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL

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.

Conditions

HIV Infections

Study Design

• Allocation Method: RANDOMIZED
• Primary Study Purpose: TREATMENT

Interventions

Telinavir

Intervention Type: DRUG

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.

• Minimum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Principal Investigators

Fischl MA

Role: STUDY_CHAIR

Richman DD

Role: STUDY_CHAIR

Flexner C

Role: STUDY_CHAIR

Para MF

Role: STUDY_CHAIR

Locations

Univ of California / San Diego Treatment Ctr

San Diego, California, United States

Univ of Miami School of Medicine

Miami, Florida, United States

Johns Hopkins Hosp

Baltimore, Maryland, United States

Ohio State Univ Hosp Clinic

Columbus, Ohio, United States

Countries

United States

References

Fischl MA, Richman DD, Flexner C, Meehan P, Para MF, Haubrich R, Cook J, Wood K, Karim A. Phase I study of two formulations and dose schedules of SC- 521151, A protease inhibitor. Natl Conf Hum Retroviruses Relat Infect (2nd). 1995 Jan 29-Feb 2:88

Reference Type: BACKGROUND

Other Identifiers

ACTG 282

Identifier Type: -

Identifier Source: org_study_id