Clinical trial NCT00002096: A Phase I Pharmacokinetic Study in HIV-Positive Subjects of Oral Ganciclovir and Concomitant Antiretroviral Zidovudine and Didanosine
Official title: A Phase I Pharmacokinetic Study in HIV-Positive Subjects of Oral Ganciclovir and Concomitant Antiretroviral Zidovudine and Didanosine
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cytomegalovirus Infections
HIV Infections
Keywords: Didanosine
Ganciclovir
Drug Interactions
Cytomegalovirus Infections
Acquired Immunodeficiency Syndrome
Zidovudine
Lead sponsor: NIH AIDS Clinical Trials Information Service
Sponsor class: INDUSTRY
First posted: 2001-08-31
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: Patients currently on either AZT or ddI receive ganciclovir therapy.

Eligibility 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).

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Irvine
country: United States
facility: Ctr for Special Immunology
state: California
city: Washington
country: United States
facility: Georgetown Univ Med Ctr
state: District of Columbia
city: Galveston
country: United States
facility: Univ TX Galveston Med Branch
state: Texas
Study officials:
References:
citation: Gaines K, Wong R, Jung D, Cimoch P, Lavelle J, Pollard R. Pharmacokinetic interactions with oral ganciclovir: zidovudine, didanosine, probenecid. Int Conf AIDS. 1994 Aug 7-12;10(1):7 (abstract no 004B)