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

Inclusion Criteria

Inclusion Criteria

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.

Exclusion Criteria

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:

Excluded:

- Chronic therapy for cytomegalovirus infection with ganciclovir.

- ddI.

- d4T.

- ddC.

Excluded within 2 weeks of study entry:

- Zidovudine (AZT).

Excluded within 1 month of study entry:

- Therapy with any other antiretroviral drug or investigational agent not specifically
allowed, including interferon and immunomodulating drugs.

- Ganciclovir.

- Neurotoxic drugs.

Excluded within 3 months of study entry:

- Ribavirin.

- Cytotoxic anticancer therapy.

Prior Treatment:

Excluded within 2 weeks of study randomization:

- Transfusion.

Active alcohol or drug abuse that is sufficient, in investigator's opinion, to prevent
adequate compliance with study therapy.