Overview
A Phase II Double-Blind Study of Delavirdine Mesylate ( U-90152 ) in Combination With Zidovudine ( AZT ) and/or Didanosine ( ddI ) Versus AZT and ddI Combination Therapy
Status:
Completed
Completed
Trial end date:
1997-03-01
1997-03-01
Target enrollment:
0
0
Participant gender:
All
All
Summary
To determine the safety and anti-HIV activity of delavirdine mesylate ( U-90152 ) in combination with zidovudine ( AZT ) and/or didanosine ( ddI ) versus AZT/ddI combination. U-90152 has demonstrated anti-HIV activity. Since the combination of this drug with either AZT or ddI has synergistic inhibitory activity against HIV-1 in vitro, and triple therapy appears to have greater inhibitory activity against HIV-1 in vitro than dual therapy, the use of U-90152 in combination with AZT and/or ddI may improve the benefits of these drugs in persons with HIV disease.Phase:
Phase 2Accepts Healthy Volunteers?
NoDetails
Lead Sponsor:
National Institute of Allergy and Infectious Diseases (NIAID)Treatments:
Delavirdine
Didanosine
Zidovudine
Criteria
Inclusion CriteriaConcurrent Medication:
Required:
- PCP prophylaxis for patients with CD4 count <= 200 cells/mm3.
Allowed:
- Topical antifungal agents.
- Oral ketoconazole, fluconazole, and itraconazole for candidiasis or disseminated
fungal infections.
- Isoniazid, ethambutol, pyrazinamide, clofazimine, ciprofloxacin, and clarithromycin
for acute or maintenance therapy for mycobacterial disease (also clarithromycin for
MAC prophylaxis).
- Acute or maintenance therapy for toxoplasmosis.
- Acute or maintenance therapy with acyclovir (no more than 1000 mg/day) for herpes
simplex virus infection.
- rEPO and rG-CSF.
- Antibiotics for bacterial infections (except rifampin and rifabutin).
- Antipyretics, analgesics, nonsteroidal anti-inflammatory agents, antiemetics, and
methadone.
Concurrent Treatment:
Allowed for cutaneous Kaposi's sarcoma:
- Localized radiation therapy.
- Limited intralesional therapy.
Patients must have:
- HIV infection.
- CD4 count 100 - 500 cells/mm3.
- Prior cumulative monotherapy of <= 6 months (may have taken either AZT or ddI, but not
both) OR no prior antiretroviral therapy.
Exclusion Criteria
Co-existing Condition:
Patients with the following symptoms or conditions are excluded:
- Malignancy (other than basal or squamous cell carcinoma of the skin, Stage 1 or 2
cervical intraepithelial neoplasia, or minimal Kaposi's sarcoma).
- Considered to be unlikely to comply with study requirements.
Concurrent Medication:
Excluded:
- Antiretroviral therapies and biologic response modifiers (except for study
medications, rEPO, and rG-CSF).
- Rifampin.
- Rifabutin.
- Terfenadine.
- Astemizole.
- Loratadine.
- Quinidine.
- Digitoxin.
- Systemic corticosteroids for more than 21 consecutive days.
- Foscarnet.
- Systemic cytotoxic chemotherapy for a malignancy.
Patients with the following prior conditions are excluded:
- History of intolerance to AZT at <= 600 mg/day or ddI at <= 400 mg/day or
discontinuation of either drug for toxicity.
- History of intolerance to trifluoperazine or piperazine citrate (per amendment).
- History of pancreatitis.
- History of grade 2 or worse peripheral neuropathy.
- Unexplained temperature >= 38.5 C on any 7 days within the past 30 days.
- Chronic diarrhea on any 15 days during the past 30 days.
Prior Medication:
Excluded:
- Prior foscarnet as induction or maintenance therapy.
- Prior U-90152.
- Prior ddC or d4T.
- Prior AZT/ddI in combination or taken separately at different times.
- Prior non-nucleoside reverse transcriptase inhibitors (nevirapine, atevirdine, etc.).
- Prior protease inhibitors (although patients from ACTG 282 are eligible).
- HIV-1 vaccine within the past 21 days.
- Acute treatment for a serious infection or for any opportunistic infection within the
past 14 days.
Excluded within the past 30 days:
- Interferon or interleukin.
- Rifampin.
- Rifabutin.
- Terfenadine.
- Astemizole.
- Loratadine.
- Recombinant EPO or G-CSF.
- Hydroxyurea.
- SPV-30.
- Any other investigational drug.
Active drug or alcohol use.