Escalating multiple-dose safety and tolerance study of oral WR 6026 in HIV-infected subjects: AIDS clinical trials group 173

Brent G. Petty, John R. Black, Craig W. Hendrix, Lionel D. Lewis, Yiannis Basiakos, Judith Feinberg, David G. Pattison, Richard Hafner

Research output: Contribution to journalArticle

Abstract

WR 6026 is an 8-aminoquinoline with activity against Pneumocystis carinii in vitro and in an animal model of P. carinii pneumonia that has predicted the clinical utility of related compounds. This study was conducted to assess the safety and tolerance of WR 6026 given once daily for 21 days to HIV-infected subjects with CD4 counts <500 cells/μl. This double-blind, placebo-controlled study employed WR 6026 doses starting at 30 mg once daily and increasing to 60, 90, 120, or 150 mg once daily. Weekly visits for clinical and laboratory monitoring were conducted. Forty-nine study subjects, including 25 subjects with CD4 counts <200 cells/μl and 12 subjects with CD4 counts <100 cells/μl, entered the study. The maximum tolerated dose was 120 mg/day. Dose-limiting methemoglobinemia (>20%) was seen in 3 of 6 study subjects who received 150 mg/day for ≥19 days. Methemoglobin level was correlated with peak plasma WR 6026 concentrations. Three other study subjects developed skin rashes that may have been drug-related, and two developed asymptomatic serum triglyceride levels >1000 mg/dl. We conclude that WR 6026 is well tolerated at doses up to 120 mg/day for 21 days in HIV- infected volunteers including those with CD4 counts <200 cells/μl. Methemoglobinemia appears to be the primary dose-limiting toxicity.

Original languageEnglish (US)
Pages (from-to)26-32
Number of pages7
JournalJournal of Acquired Immune Deficiency Syndromes and Human Retrovirology
Volume21
Issue number1
DOIs
StatePublished - May 1 1999

Keywords

  • HIV
  • Pneumocystis carinii pneumonia
  • Safety
  • Tolerance
  • WR 6026

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Virology

Fingerprint Dive into the research topics of 'Escalating multiple-dose safety and tolerance study of oral WR 6026 in HIV-infected subjects: AIDS clinical trials group 173'. Together they form a unique fingerprint.

  • Cite this