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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
History of Changes
  Purpose

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.


Condition Intervention Phase
Pneumonia, Pneumocystis Carinii
HIV Infections
 Drug: Sitamaquine
 Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: Escalating Multiple-Dose Safety and Tolerance of WR 6026 Hydrochloride in HIV-Infected Subjects

Resource links provided by NLM:

MedlinePlus related topics: HIV/AIDS Pneumonia
U.S. FDA Resources

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 44
Study Completion Date: September 1993
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00000740

Locations
United States, Indiana
Indiana Univ. School of Medicine, Infectious Disease Research Clinic
Indianapolis, Indiana, United States, 46202
United States, Maryland
Johns Hopkins Adult AIDS CRS
Baltimore, Maryland, United States, 21287
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
Study Chair: Petty BG
  More Information

Publications:
Petty B, Black J, Hendrix C, Bassiakos Y, Feinberg J, Hafner R. Escalating multiple-dose safety and tolerance of WR 6026 in HIV-infected subjects. Int Conf AIDS. 1993 Jun 6-11;9(1):498 (abstract no PO-B29-2180)

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000740     History of Changes
Other Study ID Numbers: ACTG 173, 11148
Study First Received: November 2, 1999
Last Updated: March 30, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Pneumonia, Pneumocystis carinii
Acquired Immunodeficiency Syndrome
AIDS-Related Complex
WR 6026

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Pneumonia
Pneumonia, Pneumocystis
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
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Lung Diseases, Fungal
Mycoses
Pneumocystis Infections

ClinicalTrials.gov processed this record on June 18, 2013