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

HIV Infections Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00000710
• Other study ID #: ACTG 064
• Secondary ID: 11038
• Status: Completed
• Phase: Phase 1
• Est. completion date: May 1990

Study information

• Verified date: October 2021
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: May 1990
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• AIDS-Related Complex
• HIV Infections

Intervention

Drug:
• Didanosine

Locations

Country	Name	City	State
United States	SUNY - Buffalo, Erie County Medical Ctr.	Buffalo	New York

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

United States, 

References & 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

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. — View Citation

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. — View Citation

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. — View Citation

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)

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. — View Citation

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. — View Citation

Seidlin M, Lambert JS, Dolin R, Valentine FT. Pancreatitis and pancreatic dysfunction in patients taking dideoxyinosine. AIDS. 1992 Aug;6(8):831-5. — View Citation

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. — View Citation