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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000740
First received: November 2, 1999
Last updated: March 30, 2012
Last verified: March 2012

November 2, 1999
March 30, 2012
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Complete list of historical versions of study NCT00000740 on ClinicalTrials.gov Archive Site
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Escalating Multiple-Dose Safety and Tolerance of WR 6026 Hydrochloride in HIV-Infected Subjects
Escalating Multiple-Dose Safety and Tolerance of WR 6026 Hydrochloride in HIV-Infected Subjects

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.

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.

Interventional
Phase 1
Endpoint Classification: Pharmacokinetics Study
Masking: Double-Blind
Primary Purpose: Treatment
  • Pneumonia, Pneumocystis Carinii
  • HIV Infections
Drug: Sitamaquine
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*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
44
September 1993
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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.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00000740
ACTG 173, 11148
Not Provided
National Institute of Allergy and Infectious Diseases (NIAID)
National Institute of Allergy and Infectious Diseases (NIAID)
Not Provided
Study Chair: Petty BG
National Institute of Allergy and Infectious Diseases (NIAID)
March 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP