A Phase I/II Study to Evaluate Single Agent and Combination Therapy With Megestrol Acetate and Dronabinol for the Treatment of HIV-Wasting Syndrome

Launched by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES (NIAID) · Aug 30, 2001

Keywords

ClinConnect Summary

HIV-wasting syndrome, which is characterized by severely debilitating anorexia and weight loss, is of particular concern because it can exacerbate the primary illness and is associated with a poor prognosis. Attempts at maintaining body mass through the use of megestrol acetate and dronabinol, two anti-cachectic drugs, may prolong survival.

Fifty-six patients are randomized to one of four treatment arms, as follows: high-dose megestrol acetate alone; dronabinol alone; high-dose megestrol acetate combined with dronabinol; or low-dose megestrol acetate combined with dronabinol. Treatment con...

Gender

ALL

Eligibility criteria

• • Inclusion Criteria
• Concurrent Medication:
• Allowed:
• • Zidovudine (AZT), didanosine (ddI), and dideoxycytidine (ddC). If initiating new antiretroviral therapy, patient must have been on a stable dose for at least 4 weeks prior to study entry.
• * Maintenance or suppressive therapy with any of the following, provided patient has been on a stable dose for at least 1 week prior to study entry:
• • Ganciclovir or foscarnet for CMV retinitis.
• • Fluconazole, amphotericin B, or flucytosine for cryptococcosis.
• • Amphotericin B for disseminated histoplasmosis.
• • Pyrimethamine, sulfadiazine, dapsone, or clindamycin for toxoplasmosis.
• • Amikacin, clarithromycin, clofazimine, ethambutol, ciprofloxacin, or rifampin for disseminated Mycobacterium avium complex.
• • Isoniazid, rifampin, ethambutol, or pyrazinamide for M. tuberculosis.
• * Any of the following provided patient is on a stable dose for at least 1 week prior to study entry:
• • Trimethoprim-sulfamethoxazole, aerosolized pentamidine, or dapsone for Pneumocystis carinii prophylaxis.
• • Clotrimazole troches, nystatin suspension, ketoconazole, or fluconazole for oral candidiasis.
• • Oral acyclovir for mucocutaneous herpes simplex.
• • Narcotic analgesics, tranquilizers, sedative-hypnotics, or anticholinergic agents provided patient is on a stable dose for at least 1 week prior to study entry.
• Patients must have:
• • HIV infection.
• • HIV-wasting syndrome and anorexia.
• • Life expectancy of at least 4 months.
• • Ability to tolerate oral therapy, feed themselves, and have access to as much food as they desire with no dietary restrictions.
• Prior Medication:
• Allowed:
• • Prior zidovudine (AZT), didanosine (ddI), and dideoxycytidine (ddC).
• * Prior maintenance or suppressive therapy for certain opportunistic infections, as follows:
• • Ganciclovir or foscarnet for CMV retinitis.
• • Fluconazole, amphotericin B, or flucytosine for cryptococcosis.
• • Amphotericin B for disseminated histoplasmosis.
• • Pyrimethamine, sulfadiazine, dapsone, or clindamycin for toxoplasmosis.
• • Amikacin, clarithromycin, clofazimine, ethambutol, ciprofloxacin, or rifampin for disseminated Mycobacterium avium complex.
• • Isoniazid, rifampin, ethambutol, or pyrazinamide for M. tuberculosis.
• • Exclusion Criteria
• Co-existing Condition:
• Patients with the following symptoms or conditions are excluded:
• • Major, acute opportunistic infections.
• • Active neoplasms other than Kaposi's sarcoma or localized skin carcinoma.
• • Diabetes, congestive heart failure, clinical ascites, or uncontrolled hypertension.
• • Persistent grade 3/4 diarrhea.
• • Impaired oral intake, such as occurs with Candida esophagitis or severe mouth ulcers.
• • Clinically significant cardiac arrhythmias.
• • Requirement for anticonvulsants for seizure disorder.
• Concurrent Medication:
• Excluded:
• • Marijuana use.
• • Anabolic steroids.
• • Anticonvulsants for seizure disorders.
• • Alcohol or barbiturates.
• Patients with the following prior conditions are excluded:
• • Diagnosis of a major, acute opportunistic infection within 2 months prior to study entry.
• • Hospitalization within 2 weeks prior to study entry.
• • History of hypersensitivity reactions to megestrol acetate, dronabinol, or sesame oil (a component of the dronabinol capsules).
• • History of thromboembolic events.
• • History of psychiatric disorder other than depression.
• Prior Medication:
• Excluded:
• • Prior dronabinol.
• • Megestrol acetate within 2 months prior to study entry.
• • Marijuana within 1 month prior to study entry.
• • Anabolic steroids within 3 months prior to study entry.
• • Current drug or alcohol abuse (patients with a history of occasional marijuana use are eligible provided they have abstained from its use for 1 month prior to study entry and agree to refrain from marijuana use for the study period).