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

This study has been completed.
Sponsor:
Collaborators:
Roxane Laboratories
Bristol-Myers Squibb
Information provided by:
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000737
First received: November 2, 1999
Last updated: August 22, 2008
Last verified: January 1994
  Purpose

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.


Condition Intervention Phase
Cachexia
HIV Infections
HIV Wasting Syndrome
Drug: Dronabinol
Drug: Megestrol acetate
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 56
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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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).

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00000737

Locations
United States, Colorado
Denver Public Health Dept
Denver, Colorado, United States, 802044507
United States, Illinois
Univ of Illinois
Chicago, Illinois, United States, 60612
United States, Kansas
Univ of Kansas School of Medicine
Wichita, Kansas, United States, 67214
United States, Louisiana
Tulane Univ Med School
New Orleans, Louisiana, United States, 701122699
United States, Maryland
Univ of Maryland at Baltimore / Veterans Adm
Baltimore, Maryland, United States, 21201
United States, Missouri
Washington Univ
St Louis, Missouri, United States, 63110
United States, New York
SUNY / Health Sciences Ctr at Brooklyn
Brooklyn, New York, United States, 11203
United States, Oregon
Portland Veterans Adm Med Ctr / Rsch & Education Grp
Portland, Oregon, United States, 972109951
United States, Rhode Island
Univ of Rhode Island / College of Pharmacy
Providence, Rhode Island, United States, 02908
Sponsors and Collaborators
Roxane Laboratories
Bristol-Myers Squibb
Investigators
Study Chair: Galetto G
Study Chair: Egorin M
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT00000737     History of Changes
Other Study ID Numbers: DATRI 004
Study First Received: November 2, 1999
Last Updated: August 22, 2008
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Weight Loss
Megestrol
Cachexia
Eating Disorders
Tetrahydrocannabinol
Appetite

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Syndrome
Cachexia
Wasting Syndrome
HIV Wasting Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Disease
Pathologic Processes
Emaciation
Weight Loss
Body Weight Changes
Body Weight
Signs and Symptoms
Metabolic Diseases
Nutrition Disorders
Megestrol
Megestrol Acetate
Dronabinol
Contraceptives, Oral, Synthetic
Contraceptives, Oral
Contraceptive Agents, Female

ClinicalTrials.gov processed this record on September 18, 2014