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Comparison of 2',3'-Dideoxyinosine (ddI) (BMY-40900) and Zidovudine in Therapy of Patients With HIV Infection

Phase 2
12 Years
Not Enrolling
HIV Infections

Thank you

Trial Information

Comparison of 2',3'-Dideoxyinosine (ddI) (BMY-40900) and Zidovudine in Therapy of Patients With HIV Infection

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.

AMENDED: 9/28/90 Patients are assigned to one of 2 treatments under a double-blind, randomly
allocated, experimental design if their duration of prior AZT therapy is 0 to 16 weeks.
(Patients who entered with no more than 16 weeks prior AZT and who were randomized to ddI
will continue to be dosed at that level, adjusted for weight, and followed as originally
planned.) Patients are assigned to one of 3 treatments as explained prior to this amendment
if their duration of prior to AZT therapy is greater than 16 weeks. Original design:
Patients are assigned to one of three treatments under a double-blind randomly allocated
experimental design. ddI will be administered at two dose levels.

It is anticipated that patients will be seen as outpatients every 2 weeks for the first 4
weeks of the study and monthly thereafter. This study continues for at least 18 months after
the entry of the first subject.

Inclusion Criteria

Inclusion Criteria

Concurrent Medication:


- Aerosolized pentamidine (300 mg every 4 weeks using a Respirgard II nebulizer). In
the event of physiological intolerance, alternative prophylaxis may be: Trimethoprim
/ sulfamethoxazole 1 DS tab per day or dapsone 50 - 100 mg/day.


Maintenance therapy for active AIDS defining opportunistic infections for patients with 9
to 47 weeks' experience with zidovudine (AZT).

Treatment of opportunistic infections with other than sulfonamide containing drugs:

- Pyrimethamine and sulfadiazine or clindamycin for suppression of toxoplasmosis
acquired after study entry; fluconazole or amphotericin B for suppression of
cryptococcosis or ketoconazole for candidiasis.

Intravenous acyclovir for up to 10 days. Erythropoietin for patients under the relevant
treatment IND. Analgesics, antihistamines, antiemetics, antidiarrheal agents for
symptomatic therapy for toxicities.

Isoniazid (INH) if no other acceptable therapy is available.

Metronidazole may be used for single courses of therapy not to exceed 14 days within
consecutive 90 day intervals. Note:

- Ketoconazole and dapsone should be taken 2 hours before or 2 hours after taking ddI
(amendment 5/20/91).

Concurrent Treatment:


- Blood transfusions for hemoglobin toxicity.

Patients must:

- Have a diagnosis of AIDS or advanced AIDS related complex (ARC), or per 8/09/90
amendment, asymptomatic HIV infection with CD4 count = or < 200 cells/mm3.

- Be either naive to zidovudine (AZT) or have taken AZT for = or < 48 weeks.

- Have ended treatment for acute Pneumocystis carinii pneumonia (PCP) at least 2 weeks
before study entry. For patients with 2 months or less experience with AZT, PCP
infection will be the single and only AIDS-defining infection and must have been
within 120 days of study entry. Per amendment, other AIDS-defining conditions are
allowed in the 8 weeks prior to study entry (for patients in the AZT stratum).Only
one episode of PCP is permitted unless patient has > 2 months AZT experience in which
case > 1 prior episode of PCP infection is allowed.

- Not have experienced a major intolerance to AZT at doses of at least 500 mg if the
patient was on AZT therapy for = or < 48 weeks. A major intolerance is defined as
recurrent grade 3 or greater toxicity which results in discontinuation of drug.


- Basal cell carcinoma.

- In situ carcinoma of the cervix.

- Occasional premature atrial or ventricular contraction.

- Patients developing new opportunistic infections after study entry will remain on
this protocol.

- Patients whose AIDS-defining condition is Kaposi's sarcoma alone must have CD4 cell
counts < 300 cells/mm3.

Prior Medication:


- Previous treatment with zidovudine (AZT) up to 48 weeks.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or diseases are excluded:

- Kaposi's sarcoma (KS) with evidence of visceral disease or where KS requires
chemotherapy; subjects with localized KS having CD4 counts = or > 200 cells/mm3.

- AIDS-dementia complex = or > stage 2.

- Prior history of acute pancreatitis within past 2 years or chronic pancreatitis.

- Intractable diarrhea.

- History of seizures within past 6 months or currently requiring anticonvulsants for

- History of past or current heart disease.

- Presence of a malignancy likely in the investigators opinion to require cytotoxic
myelosuppressive chemotherapy during the expected course of this trial.

Concurrent Medication:


- Oral acidifying agents.

- Neurotoxic drugs. NOTE: If patients require therapy for PCP with IV pentamidine,
study mediation is stopped.

Patients with the following are excluded:

- Active AIDS defining events. Maintenance therapy for prior AIDS-defining
opportunistic infections is permitted.

- Intolerance to AZT at doses of 500 mg because of recurrent grade 3 toxicity or
greater which resulted in discontinuation of drug.

- Neoplasms not specifically allowed.

- Previous enrollment in any study of ddI, ddC or d4T.

- > 48 weeks of AZT therapy.

- An opportunistic infection not adequately controlled with suppressive therapies
allowed in the protocol.

- Psychological or emotional problems sufficient, in the investigator's opinion, to
prevent adequate compliance study therapy.

- Life expectancy = or < 6 months.

Prior Medication:


- Ganciclovir.

- AZT for = or > 48 weeks.

Excluded within 14 days of study entry:

- Erythropoietin (Eprex).

Excluded within 30 days of study entry:

- Anti-HIV therapy other than AZT.

- Biologic response modifiers.

- Other investigational drugs.

- Corticosteroids.

- Neurotoxic drugs.

Excluded within 90 days of study entry:

- Ribavirin.

Prior Treatment:

Excluded within 14 days of study entry:

- Transfusion.

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

Type of Study:


Study Design:

Primary Purpose: Treatment

Principal Investigator

R Dolin

Investigator Role:

Study Chair


United States: Federal Government

Study ID:

ACTG 116



Start Date:

Completion Date:

Related Keywords:

  • HIV Infections
  • Didanosine
  • Zidovudine
  • HIV Infections
  • Acquired Immunodeficiency Syndrome



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