A Phase I Safety, Efficacy, and Pharmacokinetic Study of 2',3'-Dideoxyinosine (ddI) Administered Twice Daily to Patients With AIDS or AIDS Related Complex

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000710
First received: November 2, 1999
Last updated: March 28, 2012
Last verified: March 2012
  Purpose

To determine the safety, pharmacokinetics (blood levels), and effectiveness of didanosine (ddI) when administered both intravenously and orally. After the maximum tolerated dose (MTD) is determined, an appropriate dosage regimen will then be established for Phase II and Phase III trials.

Zidovudine (AZT) has produced the best clinical results in the drug therapy of AIDS to date, but it produces toxicity in approximately 50 percent of patients. Early data show that ddI possesses high antiviral activity and less toxicity than AZT. The most effective route and dose of ddI has yet to be determined.


Condition Intervention Phase
HIV Infections
Drug: Didanosine
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Safety, Efficacy, and Pharmacokinetic Study of 2',3'-Dideoxyinosine (ddI) Administered Twice Daily to Patients With AIDS or AIDS Related Complex

Resource links provided by NLM:


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

Estimated Enrollment: 42
Study Completion Date: May 1990
Detailed Description:

Zidovudine (AZT) has produced the best clinical results in the drug therapy of AIDS to date, but it produces toxicity in approximately 50 percent of patients. Early data show that ddI possesses high antiviral activity and less toxicity than AZT. The most effective route and dose of ddI has yet to be determined.

Patients are given intravenous drug for 14 days with a 1 day washout period, then 76 weeks of oral medication. To expedite this safety study and still be able to maintain close monitoring of the patient's health, an overlapping dosing regimen is used. After 6 patients have been enrolled and at least 4 have completed 4 weeks of dosing without significant toxic effects, a second group of patients is started at the next dose level.

AMENDED: An alternative oral dosing formulation of ddI will be provided as a buffer powder blend packaged in sealed foil sachets in several strengths.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

Concurrent Medication:

Recommended:

  • Allopurinol for consistent occurrence of hyperuricemia observed with 2',3'-dideoxyinosine (ddI) administration.

Allowed:

  • Aerosolized pentamidine for Pneumocystis carinii pneumonia (PCP) prophylaxis.
  • Oral acyclovir for herpes simplex infections provided ddI dosing is suspended during this time.
  • Ketoconazole for patients not responding to any other therapy and after consultation with the sponsor.
  • Symptomatic therapy such as analgesics, antihistamines, antiemetics, antidiarrheal agents, or other supportive therapy may be administered as deemed necessary by the principal investigator.
  • Aspirin rather than acetaminophen for fever.

Patients with the following will be included:

  • An absence of life-threatening opportunistic infection on enrollment.
  • A life expectancy less than 6 months.
  • Available for follow-up for at least 6 months.
  • Able to provide informed consent. Exclusion Criteria

Co-existing Condition:

Patients with the following are excluded:

  • Intractable diarrhea.
  • No venous access.
  • A history of or propensity for seizure disorders.
  • A history of past or current heart disease or other significant abnormality on routine EKG.

Concurrent Medication:

Excluded:

  • Adenine deaminase inhibitors.
  • Trimethoprim / sulfamethoxazole for Pneumocystis carinii pneumonia (PCP) infections.
  • Antibiotics.
  • Acetaminophen for therapy of fever.

Patients with the following are excluded:

  • Intractable diarrhea.
  • A life expectancy less than 6 months.
  • No venous access.
  • A history of or propensity for seizure disorders.
  • A history of past or current heart disease or other significant abnormality on routine EKG.

Prior Medication:

Excluded:

  • Any agent known as a potent inducer or inhibitor of drug-metabolizing enzymes.
  • Excluded within 2 weeks of study entry:
  • Trimethoprim / sulfamethoxazole.
  • Excluded within 1 month of study entry:
  • Any antiretroviral drug.
  • Investigational agents.
  • 2',3'-didanosine.
  • AL721.
  • Interferons.
  • Immunomodulating drugs.
  • Excluded within 3 months of study entry:
  • Ribavirin.
  • Cytotoxic agents.

Risk Behavior:

Excluded:

Active alcohol or drug abuse sufficient in the investigator's opinion to prevent adequate compliance.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00000710

Locations
United States, New York
SUNY - Buffalo, Erie County Medical Ctr.
Buffalo, New York, United States, 14215
Sponsors and Collaborators
Investigators
Study Chair: Dolin R
  More Information

Additional Information:
Publications:
Demeter L, Nawaz T, Morse G, Dolin R, Reichman R. AZT resistant (AZT-R) HIV-1 isolates obtained during DDI monotherapy from a patient with no history of AZT use. Natl Conf Hum Retroviruses Relat Infect (2nd). 1995 Jan 29-Feb 2:139
Lambert J, Dolin R, Seidlin M, Knupp C, McLaren C, Reichman RC. Phase I study of 2'3'dideoxyinosine(ddI) administered twice daily to patients with AIDS/AIDS related complex. Int Conf AIDS. 1989 Jun 4-9;5:563 (abstract no MCP130)

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000710     History of Changes
Other Study ID Numbers: ACTG 064, 11038
Study First Received: November 2, 1999
Last Updated: March 28, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Injections, Intravenous
Didanosine
Dose-Response Relationship, Drug
Drug Evaluation
Acquired Immunodeficiency Syndrome
AIDS-Related Complex

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
AIDS-Related Complex
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
Didanosine
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on September 16, 2014