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

Sponsor:	National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00000710

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 I

Study Type:	Interventional
Study Design:	Treatment, Open Label, Pharmacokinetics Study
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:

MedlinePlus related topics: AIDS

Drug Information available for: Didanosine

U.S. FDA Resources

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

Estimated Enrollment:

42

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

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

Locations

United States, New York
Univ of Rochester Medical Center
Rochester, New York, United States, 14642
Bellevue Hosp / New York Univ Med Ctr
New York, New York, United States, 10016
SUNY / Erie County Med Ctr at Buffalo
Buffalo, New York, United States, 14215

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

Study Chair:

Dolin R

More Information

Additional Information:

Click here for more information about Didanosine This link exits the ClinicalTrials.gov site

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

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.

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)

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

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.

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.

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.

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.

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. 1992;5(1):60-4.

Study ID Numbers:	ACTG 064
Study First Received:	November 2, 1999
Last Updated:	July 11, 2008
ClinicalTrials.gov Identifier:	NCT00000710 History of Changes
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:

Antimetabolites
Anti-Infective Agents
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Molecular Mechanisms of Pharmacological Action
Infection
Reverse Transcriptase Inhibitors
Anti-Retroviral Agents
Therapeutic Uses
Retroviridae Infections
Nucleic Acid Synthesis Inhibitors
RNA Virus Infections
Anti-HIV Agents

Immune System Diseases
Acquired Immunodeficiency Syndrome
AIDS-Related Complex
Enzyme Inhibitors
Antiviral Agents
Immunologic Deficiency Syndromes
Pharmacologic Actions
Virus Diseases
Didanosine
HIV Infections
Sexually Transmitted Diseases
Lentivirus Infections

ClinicalTrials.gov processed this record on November 09, 2009