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

NCT00000710 | Completed Phase 1

• 2 other identifiers: ACTG 06411038
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

HIV Infections

Keywords

Injections, Intravenous; Didanosine; Dose-Response Relationship, Drug; Drug Evaluation; Acquired Immunodeficiency Syndrome; AIDS-Related Complex

Interventions

Didanosine DRUG

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

SUNY - Buffalo, Erie County Medical Ctr.

Buffalo, New York, 14215, United States

Location

Related Publications (9)

• 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

  BACKGROUND

• Valentine FT, Seidlin M, Hochster H, Laverty M. Phase I study of 2',3'-dideoxyinosine: experience with 19 patients at New York University Medical Center. Rev Infect Dis. 1990 Jul-Aug;12 Suppl 5:S534-9. doi: 10.1093/clinids/12.supplement_5.s534.

  PMID: 1974725 BACKGROUND

• 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)

  BACKGROUND

• Seidlin M, Lambert JS, Dolin R, Valentine FT. Pancreatitis and pancreatic dysfunction in patients taking dideoxyinosine. AIDS. 1992 Aug;6(8):831-5. doi: 10.1097/00002030-199208000-00011.

  PMID: 1418780 BACKGROUND

• Lambert JS, Seidlin M, Valentine FT, Reichman RC, Dolin R. Didanosine: long-term follow-up of patients in a phase 1 study. Clin Infect Dis. 1993 Feb;16 Suppl 1:S40-5. doi: 10.1093/clinids/16.supplement_1.s40.

  PMID: 8093846 BACKGROUND

• Dolin R, Lambert JS, Morse GD, Reichman RC, Plank CS, Reid J, Knupp C, McLaren C, Pettinelli C. 2',3'-Dideoxyinosine in patients with AIDS or AIDS-related complex. Rev Infect Dis. 1990 Jul-Aug;12 Suppl 5:S540-9; discussion S549-51.

  PMID: 1974726 BACKGROUND

• Lambert JS, Seidlin M, Reichman RC, Plank CS, Laverty M, Morse GD, Knupp C, McLaren C, Pettinelli C, Valentine FT, et al. 2',3'-dideoxyinosine (ddI) in patients with the acquired immunodeficiency syndrome or AIDS-related complex. A phase I trial. N Engl J Med. 1990 May 10;322(19):1333-40. doi: 10.1056/NEJM199005103221901.

  PMID: 2139173 BACKGROUND

• Demeter LM, Nawaz T, Morse G, Dolin R, Dexter A, Gerondelis P, Reichman RC. Development of zidovudine resistance mutations in patients receiving prolonged didanosine monotherapy. J Infect Dis. 1995 Dec;172(6):1480-5. doi: 10.1093/infdis/172.6.1480.

  PMID: 7594706 BACKGROUND

• Kieburtz KD, Seidlin M, Lambert JS, Dolin R, Reichman R, Valentine F. Extended follow-up of peripheral neuropathy in patients with AIDS and AIDS-related complex treated with dideoxyinosine. J Acquir Immune Defic Syndr (1988). 1992;5(1):60-4.

  PMID: 1346633 BACKGROUND

MeSH Terms

Conditions

HIV Infections; Acquired Immunodeficiency Syndrome; AIDS-Related Complex

Interventions

Didanosine

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases

Intervention Hierarchy (Ancestors)

Inosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Dideoxynucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Dolin R

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 1999
• First Posted: August 31, 2001
• Study Completion: May 1, 1990
• Last Updated: November 4, 2021

Record last verified: 2021-10

Locations

US (1)