An Efficacy Study of 2',3'-Dideoxyinosine (ddI) (BMY-40900) Administered Orally Twice Daily to Zidovudine Intolerant Patients With AIDS or AIDS-Related Complex

Completed · Phase 2

Conditions studied: HIV Infections

In brief

AMENDED: 8/29/90 Inclusion of asymptomatic patients with CD4 counts less than 200 cells/mm3. Standardization of baseline evaluation schedule to allow 14 days prior to study dosing. Reduction in frequency and intensity of follow-up evaluations. Standardization of study endpoints. Inclusion of toxicity scoring and management for amylase and triglyceride elevations. Clarification of concomitant medication use. Original design: To determine the effectiveness of didanosine (ddI) in patients with AIDS or advanced AIDS related complex (ARC) who have documented hematologic intolerance to zidovudine (AZT) therapy. To determine if the efficacy of ddI increases with increasing doses. AZT is effective in reducing mortality in patients with AIDS who receive the drug after the first episode of Pneumocystis carinii pneumonia (PCP) and in patients with advanced ARC. However, AZT therapy has been associated with significant toxicities. In addition, the effectiveness of AZT appears to decrease during the second and third years of therapy. For these reasons, the development of alternative therapy that would be at least as effective but less toxic is of great importance. The drug ddI is an antiviral agent that inhibits replication (reproduction) of HIV with less apparent toxicity than AZT. The major dose-limiting toxicities found in the Phase I studies have been pains in the feet and legs of 2 patients initially receiving 12 mg/kg/day and 12 patients receiving daily doses of 25.8 to 51.2 mg/kg; symptoms began 8 to 27 weeks after initiating ddI treatment. These neuropathy-like symptoms have generally not been associated with significant abnormalities in nerve conduction studies and patients have reported marked improvement in symptoms within 1 to 2 weeks of discontinuing ddI. Some patients have resumed ddI treatment at a reduced dose after resolution of their symptoms. Studies indicate that ddI remains active in the body for at least 12 hours. This indicates that benefits of ddI might be achieved with a low frequency of drug administration.

Key facts

Study ID: NCT00000672
Run by: National Institute of Allergy and Infectious Diseases (NIAID)
People needed: 660
Last updated by the study team: 2011-03-14

Who can join

Age: 12 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

Concurrent Medication:
Required:
Aerosolized pentamidine (300 mg every 4 weeks). In the event of physiological intolerance, alternative PCP prophylaxis may be trimethoprim/sulfamethoxazole 1 DS tab per day or dapsone 50 - 100 mg per day.
Allowed:
Chronic suppressive treatment for toxoplasmosis, Pneumocystis carinii pneumonia (PCP), cryptococcal meningitis, herpes simplex virus, cytomegalovirus, coccidioidomycosis, and histoplasmosis (absorption of ketoconazole or dapsone may be inhibited if given at the same time as the buffered solution of ddI, and should be taken 2 hours before or 2 hours after taking ddI; oral acidifying agents are not allowed). Isoniazid is permitted only if no acceptable alternative therapy is available. Metronidazole may be used for single courses not to exceed 14 days within consecutive 90 day intervals, the first of which begins at the initiation of the study. Erythropoietin for patients under the relevant treatment IND. Intravenous acyclovir for short courses of therapy.
Patients must:
Have documented hematologic intolerance to zidovudine (AZT).
Have the diagnosis of AIDS or advanced AIDS related complex (ARC).
Have ended treatment for acute Pneumocystis carinii pneumonia (PCP) at least 2 weeks before study entry.
Have previous intolerance on at least two courses of AZT therapy (one of which must have been at daily doses of 500 mg of AZT or less).
Be able to provide informed consent (and/or guardian as appropriate).
Be available for follow-up for at least 6 months.
Have baseline laboratory values as measured within 7 days before initial drug dosing.
Allowed:
Development of new opportunistic infections during the study - patients remain in the protocol.
Prior Medication:
Required:
Prior use and intolerance to zidovudine (AZT).
Allowed:
Intralesional agents.

You may not qualify if…

Co-existing Condition:
Patients with the following are excluded:
Presence of Kaposi's sarcoma (KS) with known or suspected visceral disease or where KS requires chemotherapy.
Active AIDS defining opportunistic infections not specifically allowed.
Intractable diarrhea.
Stage 2 AIDS-dementia complex.
History of intolerance to aerosolized pentamidine.
Grade 2 neuropathy, based on the Neuropathy Targeted Symptom Questionnaire, or any moderate abnormality indicative of peripheral neuropathy, particularly impaired sensation of sharp pain, light touch, or vibration in the lower extremities, distal extremity weakness, or distal extremity hyporeflexia.
Prior history of acute or chronic pancreatitis.
History of seizures within past 2 years or currently requiring anticonvulsants for control.
Any other clinical conditions or prior therapy which, in the opinion of the investigator, would make the patient unsuitable for study or unable to comply with the dosing requirements.
Concurrent Medication:
Excluded:
Isoniazid (INH).
Patients with the following are excluded:
Active AIDS-defining opportunistic infections not specifically allowed.
Intractable diarrhea.
AIDS-dementia complex = or > stage 2.
History of intolerance to aerosolized pentamidine. Grade 2 neuropathy, based on the Neuropathy Targeted Symptom Questionnaire, or any moderate abnormality indicative of peripheral neuropathy, particularly impaired sensation of sharp pain, light touch, or vibration in the lower extremities, distal extremity weakness, or distal extremity hyporeflexia.
Prior history of acute or chronic pancreatitis.
History of seizures within past 2 years or currently requiring anticonvulsants for control.
Any other clinical conditions or prior therapy which, in the opinion of the investigator, would make the patient unsuitable for study or unable to comply with the dosing requirements.
Previous participation in any Phase I ddI study.
Life expectancy < 6 months.
Prior Medication:

Where it is running

Cedars Sinai / UCLA Med Ctr — Los Angeles, California, United States
UCLA Med Ctr / Pediatric — Los Angeles, California, United States
Harbor - UCLA Med Ctr / UCLA School of Medicine — Los Angeles, California, United States
Palo Alto Veterans Adm Med Ctr / Stanford Univ — Palo Alto, California, United States
Univ of California / San Diego Treatment Ctr — San Diego, California, United States
Stanford Univ School of Medicine — Stanford, California, United States
Olive View Med Ctr — Sylmar, California, United States
Sepulveda Veterans Adm Med Ctr / Olive View Med Ctr — Sylmar, California, United States
Harbor UCLA Med Ctr — Torrance, California, United States
Mountain States Regional Hemophilia Ctr / Univ of Colorado — Denver, Colorado, United States
Univ of Colorado Health Sciences Ctr — Denver, Colorado, United States
George Washington Univ Med Ctr — Washington D.C., District of Columbia, United States
G E Morey Jr — Fort Lauderdale, Florida, United States
Univ of Miami School of Medicine — Miami, Florida, United States
Univ of South Florida — Tampa, Florida, United States
Northwestern Univ Med School — Chicago, Illinois, United States
Edward Hines Veterans Administration Hosp — Hines, Illinois, United States
Indiana Univ Hosp — Indianapolis, Indiana, United States
Univ of Kansas School of Medicine — Wichita, Kansas, United States
Louisiana Comprehensive Hemophilia Care Ctr — New Orleans, Louisiana, United States
Louisiana State Univ Med Ctr / Tulane Med School — New Orleans, Louisiana, United States
Tulane Univ School of Medicine — New Orleans, Louisiana, United States
Johns Hopkins Hosp — Baltimore, Maryland, United States
Harvard (Massachusetts Gen Hosp) — Boston, Massachusetts, United States
Los Angeles County - USC Med Ctr — Los Angeles, California, United States

Full record on ClinicalTrials.gov

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