Double-Blind Comparison of the Efficacy of Continued Zidovudine Versus 2',3'-Dideoxyinosine (ddI) (BMY-40900) for the Treatment of Patients With AIDS or AIDS-Related Complex and Increasing Symptomatology Despite Treatment With Zidovudine

Bristol-Myers Squibb (BMS)

Status: Completed

Conditions: HIV Infections

Treatments: Drug: Didanosine; Drug: Zidovudine

Study type: Interventional

Funder types: Industry

Identifiers

NCT00002035

AI454-010

039B

Details and patient eligibility

About

To compare the efficacy and safety of orally administered didanosine (ddI) with orally administered zidovudine (AZT) in the treatment of patients who exhibit increasing clinical deterioration despite treatment with AZT.

Sex: All

Ages: 12+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

Concurrent Medication:

Allowed for Hematologic toxicity:

• Erythropoietin.
• Colony-Stimulating Factors.
• Allowed for prophylaxis of Pneumocystis carinii pneumonia (PCP):
• Aerosolized pentamidine.
• Trimethoprim/sulfamethoxazole.
• Dapsone.
• NOTE:
• If intravenous pentamidine is required for treatment of PCP, study drug should be suspended until one week after completion of intravenous pentamidine.
• Allowed:
• Prophylactic or suppressive therapy begun prior to study entry with the exception of neurotoxic agents (as defined in the protocol).

Concurrent Treatment:

Allowed:

• Transfusions for hematologic toxicity.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions or symptoms are excluded:

• Active acute AIDS defining infection.
• Clinical evidence of acute pancreatitis in the last two years or chronic pancreatitis.
• Dementia of such severity that patient cannot give informed consent.
• Grade 2 or worse peripheral neuropathy as defined by Targeted Neuropathy Score (Schaumberg).
• Prior Cytomegalovirus disease requiring ongoing systemic ganciclovir therapy.
• Extensive Kaposi's sarcoma or other malignancy requiring systemic cytotoxic myelosuppressive or neurotoxic chemotherapy.
• Cardiomyopathy or the need for antiarrhythmic therapy.
• Inability to tolerate at least 600 mg per day of zidovudine (AZT).
• Seizures within the last 6 months or the need for anticonvulsant therapy.

Concurrent Medication:

Excluded:

• Ganciclovir (DHPG).
• Myelosuppressive or neurotoxic chemotherapy.
• Antiarrhythmic therapy.
• Anticonvulsant therapy.
• Neurotoxic agents (as defined in the protocol).
• NOTE:
• If intravenous pentamidine is required for treatment of Pneumocystis carinii pneumonia (PCP), study drug should be suspended until 1 week after completion of intravenous pentamidine.

Patients with the following are excluded:

• Symptoms and conditions defined in the Patient Exclusion Co-Existing Conditions field.
• Average of two sequential CD4 counts from SciCor Clinical Laboratories in the 30 days prior to study entry > 300 cells/mm3.

Prior Medication:

Excluded, participation in studies using:

• Dideoxyinosine (ddI).
• 2',3'-Dideoxy-2',3'-didehydrothymidine (d4T).
• Dideoxycytidine (ddC).
• Excluded within one month of study entry:
• Any other experimental antiretroviral compounds.

Patients must:

• Have documented HIV positivity via ELISA.
• Meet CDC criteria for AIDS or AIDS related complex (ARC).
• Have received zidovudine (AZT) for = or > 6 months and tolerated a dose of at least 500 mg per day without significant hematologic toxicity.
• Have no acute AIDS defining opportunistic infection, but may be receiving suppressive therapy for such infections.
• Demonstrate at least one of the following criteria for clinical deterioration despite AZT therapy within 4 weeks prior to study entry (8 weeks prior for weight loss):
• involuntary weight loss of more than 5 percent of the body weight occurring over the 8 week period prior to study entry, Karnofsky score = or > 50 but demonstrating a fall = or > 20 from previous level of functioning (assessment must be persistent on two occasions at least 14 days apart), unexplained fever of = or > 38 degrees C (despite evaluation defined in protocol) for more than 7 days, appearance of newly diagnosed oral hairy leukoplakia or oral candidiasis, or recurrence of a previously quiescent multidermatomal varicella-zoster, appearance of dermatologic afflictions (e.g. psoriasis, molluscum contagiosum, or newly diagnosed seborrheic dermatitis), appearance of chronic herpetic ulcers not responsive to acyclovir therapy.

Required:

• Zidovudine (AZT) for = or > 6 months prior to study entry.