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

Primary Purpose

HIV Infections

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Didanosine
Sponsored by
National Institute of Allergy and Infectious Diseases (NIAID)
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for HIV Infections focused on measuring Injections, Intravenous, Didanosine, Dose-Response Relationship, Drug, Drug Evaluation, Acquired Immunodeficiency Syndrome, AIDS-Related Complex

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • SUNY - Buffalo, Erie County Medical Ctr.

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 2, 1999
Last Updated
October 27, 2021
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
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1. Study Identification

Unique Protocol Identification Number
NCT00000710
Brief 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
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2021
Overall Recruitment Status
Completed
Study Start Date
undefined (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
May 1990 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)

4. Oversight

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections
Keywords
Injections, Intravenous, Didanosine, Dose-Response Relationship, Drug, Drug Evaluation, Acquired Immunodeficiency Syndrome, AIDS-Related Complex

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Masking
None (Open Label)
Enrollment
42 (false)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Didanosine

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dolin R
Official's Role
Study Chair
Facility Information:
Facility Name
SUNY - Buffalo, Erie County Medical Ctr.
City
Buffalo
State/Province
New York
ZIP/Postal Code
14215
Country
United States

12. IPD Sharing Statement

Citations:
Citation
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
Results Reference
background
PubMed Identifier
1974725
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. doi: 10.1093/clinids/12.supplement_5.s534.
Results Reference
background
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)
Results Reference
background
PubMed Identifier
1418780
Citation
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.
Results Reference
background
PubMed Identifier
8093846
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. doi: 10.1093/clinids/16.supplement_1.s40.
Results Reference
background
PubMed Identifier
1974726
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.
Results Reference
background
PubMed Identifier
2139173
Citation
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.
Results Reference
background
PubMed Identifier
7594706
Citation
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.
Results Reference
background
PubMed Identifier
1346633
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.
Results Reference
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A Phase I Safety, Efficacy, and Pharmacokinetic Study of 2',3'-Dideoxyinosine (ddI) Administered Twice Daily to Patients With AIDS or AIDS Related Complex

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