Clinical trial NCT00000737: A Phase I/II Study to Evaluate Single Agent and Combination Therapy With Megestrol Acetate and Dronabinol for the Treatment of HIV-Wasting Syndrome
Official title: A Phase I/II Study to Evaluate Single Agent and Combination Therapy With Megestrol Acetate and Dronabinol for the Treatment of HIV-Wasting Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cachexia
HIV Infections
HIV Wasting Syndrome
Keywords: Weight Loss
Megestrol
Cachexia
Eating Disorders
Tetrahydrocannabinol
Appetite
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Roxane Laboratories
name: Bristol-Myers Squibb
First posted: 2001-08-31
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: To obtain data on the safety of administering megestrol acetate and dronabinol as single agents or in combination to patients with human immunodeficiency virus (HIV)-wasting syndrome. To obtain preliminary data on the efficacy of single agent and combination therapy with megestrol acetate and dronabinol with regard to weight gain, appetite increase and quality of life in this patient population. To obtain steady-state pharmacokinetics data when megestrol acetate and dronabinol are administered as single agents and in combination.

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.

Detailed description: 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 continues for 12 weeks. Patients are evaluated for toxicity, preliminary evidence of response (e.g., weight gain), and steady-state pharmacokinetics of drug therapies.

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).

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Denver
country: United States
facility: Denver Public Health Dept
state: Colorado
city: Chicago
country: United States
facility: Univ of Illinois
state: Illinois
city: Wichita
country: United States
facility: Univ of Kansas School of Medicine
state: Kansas
city: New Orleans
country: United States
facility: Tulane Univ Med School
state: Louisiana
city: Baltimore
country: United States
facility: Univ of Maryland at Baltimore / Veterans Adm
state: Maryland
city: St Louis
country: United States
facility: Washington Univ
state: Missouri
city: Brooklyn
country: United States
facility: SUNY / Health Sciences Ctr at Brooklyn
state: New York
city: Portland
country: United States
facility: Portland Veterans Adm Med Ctr / Rsch & Education Grp
state: Oregon
city: Providence
country: United States
facility: Univ of Rhode Island / College of Pharmacy
state: Rhode Island
Study officials:
name: Galetto G
role: STUDY_CHAIR
name: Egorin M
role: STUDY_CHAIR
References:
citation: Timpone JG, Wright DJ, Li N, Egorin MJ, Enama ME, Mayers J, Galetto G. The safety and pharmacokinetics of single-agent and combination therapy with megestrol acetate and dronabinol for the treatment of HIV wasting syndrome. The DATRI 004 Study Group. Division of AIDS Treatment Research Initiative. AIDS Res Hum Retroviruses. 1997 Mar 1;13(4):305-15. doi: 10.1089/aid.1997.13.305.