A Phase I Trial to Evaluate the Safety and Pharmacokinetics of 1592U89

To assess the safety of single oral doses of 1592U89 (abacavir succinate, ABC) administered to HIV-positive individuals. To determine the pharmacokinetics of 1592U89 after single oral doses. To determine the effects of food on the bioavailability of 1592U89.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Abacavir sulfate

Detailed Description

Patients are randomized in a double-blinded manner, with 12 patients entering the treatment arm and 6 patients entering the control arm. Patients in the treatment arm receive 6 single escalating doses of 1592U89 separated by at least a 6-day washout period. Patients in the control arm receive 6 single oral doses of placebo at least 6 days apart. The second and third doses of 1592U89 are equivalent. During these doses, investigators study the effects of food on the pharmacokinetics of 1592U89 by giving half of the patients the second dose with a standardized, high-fat breakfast and giving the other half the dose in a fasted state. During the third dose, patients are crossed over so that patients who received the second dose with a meal now receive it in a fasted state, and vice versa. Following the sixth dose, investigators break the blind. Patients who received 1592U89 take a seventh dose in solution form and return for follow-up at least 7 days later; patients who received placebo receive no further treatment or follow-up. Serial blood and urine samples are collected before and after each administration of 1592U89 (or placebo) for determination of plasma and urine concentrations of 1592U89, and investigators monitor patients closely for adverse events or abnormal laboratory test findings.

• Study Type: Interventional
• Enrollment: 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown Univ Med Ctr
  • Kansas
    • Wichita, Kansas, United States, 67214
      • Ctr for Phase I Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years to 55 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

Patients must have:

• HIV infection, as documented by ELISA/Western blot detection of HIV antibody, positive p24 antigen assay, positive viral culture, or other accepted technique.
• Written informed consent of parent or legal guardian if under age 18.

Exclusion Criteria

Co-existing Condition:

Excluded:

• Debilitating disease, as a result of HIV or associated therapies, that, in the opinion of the investigator, might prevent the patient from completing 6-week dosing period.
• Malabsorption syndrome or other gastrointestinal dysfunction that might interfere with drug absorption.

Concurrent Medication:

Excluded:

• Prescription or over-the-counter medication that cannot be withheld for 48 hours prior to dosing and during the 6 dosing periods. (Note:
• Antiretrovirals must be withheld for 24 hours prior to dosing and during the day of dosing.)
• Other investigational treatments (treatments available through a Treatment IND or other expanded access mechanism is evaluated individually in consultation with the sponsor).
• Alcoholic beverages within 48 hours before dosing and during the day of dosing.
• Coffee, tea, and other xanthine-containing beverages and foods on the day of dosing.

Patients with the following symptoms or conditions are excluded:

History of hepatitis, pancreatitis, or cardiomyopathy within the last 5 years.

Risk Behavior:

Excluded:

Current alcohol or illicit drug use that might interfere with the patient's ability to comply with the dosing schedule and protocol evaluations, as determined by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Masking: Double

Collaborators and Investigators

• Sponsor: Burroughs Wellcome

Study record dates

Study Major Dates

• Study Start: July 1, 1994

Study Registration Dates

• First Submitted: November 2, 1999
• First Submitted That Met QC Criteria: August 30, 2001
• First Posted (Estimate): August 31, 2001

Study Record Updates

• Last Update Posted (Estimate): June 24, 2005
• Last Update Submitted That Met QC Criteria: June 23, 2005
• Last Verified: October 1, 1994

More Information

Terms related to this study

• Keywords: Reverse Transcriptase Inhibitors; abacavir; Biological Availability; Food-Drug Interactions
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Abacavir
• Other Study ID Numbers: 238A; 001 (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES))