Escalating Multiple-Dose Safety and Tolerance of WR 6026 Hydrochloride in HIV-Infected Subjects

NCT ID: NCT00000740

Last Updated: 2021-11-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Completion Date: 1993-09-30

Brief Summary

To determine the maximum tolerated dose (MTD) of WR 6026 in HIV-infected patients. To determine whether any unexpected toxicities are caused by WR 6026 in HIV-infected patients. To determine whether there is additional toxicity when WR 6026 is given for 21 days rather than 14 days. To further investigate the pharmacokinetics and pharmacodynamics of WR 6026, and in particular to examine potential correlations between the area under the concentration-time curve and methemoglobinemia or other toxicities.

In recent animal studies, WR 6026 demonstrated inhibitory activity against Pneumocystis carinii pneumonia (PCP). This study will assess the safety and tolerance of this drug in HIV-infected patients who do not have PCP.

Detailed Description

In recent animal studies, WR 6026 demonstrated inhibitory activity against Pneumocystis carinii pneumonia (PCP). This study will assess the safety and tolerance of this drug in HIV-infected patients who do not have PCP.

Escalating doses of WR 6026 will be studied in successive patient cohorts. Four patients will be randomized to active drug or placebo in a 3:1 ratio at each dose level until moderate toxicity is demonstrated. If one patient at a given dose level experiences WR 6026-related moderate or worse toxicity, the sample size for all subsequent dose levels will be doubled. If two or more patients at a given dose level experience moderate or dose-limiting toxicity, an additional four patients (randomized in the same 3:1 ratio) will be entered at that level, and sample size at all subsequent dose levels will be doubled. Dose escalation will continue until three of six patients receiving active drug at a given dose level experience dose-limiting or worse toxicity, or until two of six patients at a given dose level experience life-threatening toxicity. The MTD will be defined as the dose immediately below the highest dose studied. Eight additional patients will be studied at the presumed MTD to confirm tolerance.

Conditions

Pneumonia, Pneumocystis Carinii; HIV Infections

Keywords

Pneumonia, Pneumocystis carinii; Acquired Immunodeficiency Syndrome; AIDS-Related Complex; WR 6026

Study Design

• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Interventions

Sitamaquine

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

Patients must have:

• HIV antibody positive.
• CD4 cell counts less than 500/mm3.
• Adequate general health.
• No significant deterioration in performance status within the past month.
• Prior treatment with a stable regimen of antiretroviral medication for at least 4 weeks prior to study.

Prior Medication:

Required:

• Stable regimen of antiretroviral medication for at least 4 weeks prior to study entry.

Allowed:

• Aerosolized pentamidine for PCP prophylaxis.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

• Intercurrent infection.
• Clinically significant abnormality on EKG.
• Known hypersensitivity to quinolines.
• Known hemoglobin M abnormality.
• Known NADH methemoglobin reductase deficiency.
• Positive test for G6PD deficiency.
• Fever.

Prior Medication:

Excluded:

• Other systemic medication (other than AZT, ddC, ddI, methadone, acyclovir, and NSAIDs) within 3 days prior to study entry.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Petty BG

Role: STUDY_CHAIR

Locations

Indiana Univ. School of Medicine, Infectious Disease Research Clinic

Indianapolis, Indiana, United States

Johns Hopkins Adult AIDS CRS

Baltimore, Maryland, United States

Countries

United States

References

Petty BG, Black JR, Hendrix CW, Lewis LD, Basiakos Y, Feinberg J, Pattison DG, Hafner R. Escalating multiple-dose safety and tolerance study of oral WR 6026 in HIV-infected subjects: AIDS clinical trials group 173. J Acquir Immune Defic Syndr. 1999 May 1;21(1):26-32. doi: 10.1097/00126334-199905010-00004.

Reference Type: BACKGROUND

PMID: 10235511 (View on PubMed)

Other Identifiers

11148

Identifier Type: REGISTRY

Identifier Source: secondary_id

ACTG 173

Identifier Type: -

Identifier Source: org_study_id