Phase I Trial of S-1153 in Patients With HIV Infection

This study has been completed.
Sponsor:
Information provided by:
NIH AIDS Clinical Trials Information Service
ClinicalTrials.gov Identifier:
NCT00002214
First received: November 2, 1999
Last updated: June 23, 2005
Last verified: July 1998
  Purpose

To assess the toxicity profile and determine the maximum tolerated dose (MTD), if possible, of S-1153 administered orally 3 times daily for 14 days. To investigate the clinical pharmacokinetic parameters for S-1153. To assess anti-HIV activity associated with S-1153 administration through evaluation of CD4 and viral load measurements.


Condition Intervention Phase
HIV Infections
Drug: Capravirine
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Primary Purpose: Treatment
Official Title: Phase I Trial of S-1153 in Patients With HIV Infection

Resource links provided by NLM:


Further study details as provided by NIH AIDS Clinical Trials Information Service:

Estimated Enrollment: 40
Detailed Description:

Two separate schedules of S-1153 are administered on this study: single dose (2 dose levels/cohorts) and repeated dose administration over 14 days (escalation through 4 dose levels/cohorts). All doses are determined by body weight.

Single-dose study (Cohort 1):

(4 patients) low-dose po, following a standardized morning meal. (4 patients) low-dose po, fasting.

Single-dose study (Cohort 2), administered during the first 3 levels of the repeated dose study and prior to the initiation of the 4th repeated dose level:

(4 patients): intermediate-dose po, following a standardized morning meal. (4 patients): intermediate-dose po, fasted. Following treatment with S-1153, all single-dose patients (Cohorts 1and 2) are observed for 21 days.

Repeated dose (escalation) study:

All doses are administered for 14 days. Three patients are entered at the starting dose of S-1153. In the absence of dose-limiting toxicity (DLT), subsequent 3-patient cohorts are entered at 3 escalating doses.

The last patient at any given dose level must be observed for 21 days prior to entry of patient at the next dose. If 1 of the initial 3 patients experiences DLT at a given level, 3 additional patients will be added at that dose; if no additional toxicity occurs, escalation resumes. If 2 or more patients at a given dose exhibit DLT, the previous dose is declared the maximum tolerated dose (MTD) and 3 additional patients (6 total) are treated at that dose.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

Concurrent Medication:

1. Required for patients with CD4 cell count lower than 200:

  • PCP prophylaxis with aerosolized pentamidine, trimethoprim/sulfamethoxazole, mepron, or dapsone.
  • Allowed:
  • Continuation on an approved antiretroviral agent other than non-nucleoside reverse transcriptase inhibitors (e.g., Nevirapine) or other specifically excluded prior medications, if received without complications for at least 4 weeks prior to study entry.

Patients must have:

  • Serologically documented HIV infection.
  • Single-dose patients:
  • CD4 cell count greater than 50 (no upper limit for single-dose cohorts). Repeated-dose patients:
  • CD4 count from 50 to 500 within 35 days prior to entrance on study.
  • No active opportunistic infection.

Prior Medication:

Allowed for entry onto multiple-dose study:

  • Single-dose portion of S-1153 study, provided all study visits and evaluations are completed, all eligibility criteria are met, and a minimum of 30 days has elapsed before Day 1 of the repeated-dose administration.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

Active opportunistic infection.

Concurrent Medication:

Excluded:

Concomitant use (within 5 half-lives prior to administration and for at least 24 hours following cessation of treatment with S-1153) of highly plasma-bound drugs with narrow therapeutic indices, including but not limited to coumadin and dilantin.

Prior Medication:

1. Investigational new drugs.

  • Excluded within 30 days prior to study entry:
  • Chronic (greater than 7 days) use of drugs known to affect or be extensively metabolized by cytochromes P450, including but not limited to ketoconazole, fluconazole, itraconazole, isoniazid, rifampin, rifabutin, astemizole, terfenadine, or protease inhibitors.

Prior Treatment:

Excluded within 3 weeks prior to study entry:

  • Cytotoxic chemotherapy.
  • Interferon treatment.
  • Radiation therapy.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00002214

Locations
United States, Massachusetts
Beth Israel Deaconess Med Ctr
Boston, Massachusetts, United States, 02215
Sponsors and Collaborators
Lexigen Pharmaceuticals
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00002214     History of Changes
Other Study ID Numbers: 286A, 9616T0311, 51,197
Study First Received: November 2, 1999
Last Updated: June 23, 2005
Health Authority: United States: Food and Drug Administration

Keywords provided by NIH AIDS Clinical Trials Information Service:
Dose-Response Relationship, Drug
Reverse Transcriptase Inhibitors

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 17, 2014