A Phase I Pharmacokinetic Study in HIV-Positive Subjects of Oral Ganciclovir and Concomitant Antiretroviral Zidovudine and Didanosine

Roche

Status and phase: Completed; Phase 1

Conditions: HIV Infections; Cytomegalovirus Infections

Treatments: Drug: Zidovudine; Drug: Ganciclovir; Drug: Didanosine

Study type: Interventional

Funder types: Industry

Identifiers

NCT00002096

059E

ICM 1776

Details and patient eligibility

About

To determine whether there is a pharmacokinetic drug interaction between oral ganciclovir and oral zidovudine (AZT) and between oral ganciclovir and oral didanosine (ddI). To determine whether concurrent administration of probenecid affects the pharmacokinetics of oral ganciclovir. To obtain data on the short-term safety of oral ganciclovir administered concurrently with AZT, ddI, or probenecid in HIV-positive patients.

Full description

Patients currently on either AZT or ddI receive ganciclovir therapy.

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

Concurrent Medication:

Required:

• Concomitant AZT or ddI.

Allowed:

• Probenecid.
• Aerosolized pentamidine.

Patients must have:

• Asymptomatic HIV infection.
• CMV seropositivity or CMV culture positivity at present or at any time in the past.
• No history of CMV disease (e.g., retinitis, colitis) or any other AIDS-defining illness.
• Treatment with AZT or ddI for at least 1 month prior to study entry.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms and conditions are excluded:

• Uncontrolled diarrhea (three or more loose stools/day).
• Clinically significant gastrointestinal symptoms including persistent nausea or abdominal pain.
• AZT patients only:
• Deficiency in glucose-6-phosphate dehydrogenase.
• ddI patients only:
• Grade 2 or worse peripheral neuropathy.

Concurrent Medication:

Excluded:

• Combination antiretroviral therapy.
• G-CSF or GM-CSF.
• Acyclovir.
• Amphotericin B.
• Amikacin.
• Captopril.
• Carbamazepine.
• Cimetidine.
• Cyclosporine.
• Glutethimide.
• Gentamicin.
• Griseofulvin.
• Ibuprofen.
• Imipenem-Cilastatin.
• Lithium.
• Methicillin.
• Methotrexate.
• Naproxen.
• Pentamidine (Pentam 300) (Aerosolized drug permitted).
• Phenacetin.
• Phenobarbital.
• Phenytoin.
• Piroxicam.
• Ribavirin.
• Rifampin.
• Tobramycin.
• Vidarabine.
• Zalcitabine.
• Other investigational drugs.

Patients with the following prior conditions are excluded:

• History of hypersensitivity to acyclovir or ganciclovir.
• AZT patients only:
• History of gout, uric acid, kidney stones, peptic ulcer or porphyria.
• ddI patients only:
• History of pancreatitis or alcoholism, or seizures within 6 months prior to study entry or prior need for anticonvulsant therapy.

Prior Medication:

Excluded:

• Combination antiretroviral therapy within 1 month prior to study entry.

Required:

• AZT at 500 mg/day for at least 1 month prior to study entry (with 100 mg administered five times per day for at least 1 week prior to study entry). OR
• ddI at recommended dose for at least 1 month prior to study entry (with 250 mg administered every 12 hours for at least 1 week prior to study entry).

History of alcoholism (in ddI patients).