A Phase I/II Study to Evaluate Single Agent and Combination Therapy With Megestrol Acetate and Dronabinol for the Treatment of HIV-Wasting Syndrome
Information source: National Institute of Allergy and Infectious Diseases (NIAID)
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Cachexia; HIV Infections; HIV Wasting Syndrome
Intervention: Dronabinol (Drug); Megestrol acetate (Drug)
Phase: Phase 1
Status: Completed
Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID) Official(s) and/or principal investigator(s):
Galetto G, Study Chair
Egorin M, Study Chair
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.
Clinical Details
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 design: Treatment, Open Label, Pharmacokinetics Study
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
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
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).
Locations and Contacts
Denver Public Health Dept, Denver, Colorado 802044507, United States
Univ of Illinois, Chicago, Illinois 60612, United States
Univ of Kansas School of Medicine, Wichita, Kansas 67214, United States
Tulane Univ Med School, New Orleans, Louisiana 701122699, United States
Univ of Maryland at Baltimore / Veterans Adm, Baltimore, Maryland 21201, United States
Washington Univ, St. Louis, Missouri 63110, United States
SUNY / Health Sciences Ctr at Brooklyn, Brooklyn, New York 11203, United States
Portland Veterans Adm Med Ctr / Rsch & Education Grp, Portland, Oregon 972109951, United States
Univ of Rhode Island / College of Pharmacy, Providence, Rhode Island 02908, United States
Additional Information
Click here for more information about Megestrol acetate Click here for more information about Dronabinol
Related publications: 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.
Last updated: June 23, 2005
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