Evaluate Weight Gain Using 2 Different Formulations of Megestrol Acetate Oral Suspension for AIDS-related Weight Loss

Study Overview
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Brief Summary
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Explore weight gain in HIV-positive patients who have weight loss associated with AIDS-related wasting (anorexia/cachexia). Patients are treated for 12 weeks with either megestrol acetate oral suspension nanocrystal dispersion formulation, or megestrol acetate oral suspension original formulation

Official Title
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A Randomized, Open-labeled, Pilot Study Comparing Weight Gain in Adults With AIDS-related Wasting Given Either Megestrol Acetate Oral Suspension Nanocrystal Dispersion (MA-NCD) or Megestrol Acetate Oral Suspension (Megace)

Conditions
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HIV Infections, Cachexia, Anorexia, AIDS Wasting Syndrome, HIV Wasting Syndrome

Intervention / Treatment
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* Drug: Megestrol acetate oral suspension nanocrystal dispersion 115 mg/mL
* Drug: Megestrol acetate oral suspension 40 mg/mL


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Capable of and willing to provide informed consent Evidence of HIV infection (either HIV-seropositive, CD4+ T-cell count of ≤350/mm3 or other clinically accepted indicator) An unintentional weight loss resulting in a weight 10% less than the lower limit of Ideal Body Weight for frame size, or a recent history of unintentional weight loss of 10% from the subjects baseline Weight losses was clinically associated with AIDS-related wasting and not related to any other disease process Women of childbearing potential had to agree to use effective contraception for the duration of the study and for two weeks after the last dose Clinical laboratory values had to be within normal limits or out-of-range limits must be designated as not clinically significant (some exceptions per protocol) Able to read and write in the study related documents translated into the primary local language Capable of and willing to return to the clinic regularly for study visits Must have been taking a stable regimen of accepted HIV anti-retroviral treatments for at least two weeks prior to study entry Capable of completing a 3-day food intake diary with instruction Willing to abstain from any illegal or recreational drug substances for the duration of the trial Willing to abstain from taking any other medications or substances known to affect appetite or weight gain (eg, steroids [other than those inhaled for treatment of asthmatic conditions], nutritional supplements [other than vitamins or minerals], dronabinol, recombinant human growth hormone, etc.) Exclusion Criteria: Weight loss due to factors other than AIDS-related wasting Enrollment in any other clinical trial Lack of access to regular meals Women of childbearing potential could not be pregnant or nursing Clinically severe depression evidenced by a baseline score of 17 or more on the Hamilton Depression Rating Scale (GRID-HAMD-17) Recent evidence of or history of significant psychiatric illness that may have compromised the subject's ability to comply with the study requirements Intractable or frequent vomiting that regularly interfered with eating Clinically significant diarrhea that would have interfered with absorption of foods or medications Clinically significant oral lesions or dental conditions that would have interfered with eating a regular diet History or evidence of thromboembolic events or any first degree relative with a history of thromboembolic events Active AIDS-defining illness or other clinically significant or uncontrolled medical problems Current evidence of or history of diabetes mellitus or hypoadrenalism Systemic treatment with glucocorticoids within the 12 months prior to study entry

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Megestrol acetate oral suspension nanocrystal dispersion<br>Megestrol acetate oral suspension nanocrystal dispersion formulation 115 mg/mL | Drug: Megestrol acetate oral suspension nanocrystal dispersion 115 mg/mL<br>* Megestrol acetate oral suspension nanocrystal dispersion 115 mg/mL administered as 575 mg once per day (5 mL dose)<br>* Other names: Megace ES;|
| Active Comparator: Megestrol acetate oral suspension micronized formulation<br>Megestrol acetate oral suspension micronized formulation 60 mg/mL | Drug: Megestrol acetate oral suspension 40 mg/mL<br>* Megestrol acetate oral suspension 40 mg/mL administered as 800 mg once per day (20 mL dose)<br>* Other names: Megace;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Body Weight | Weight gain in adult HIV positive subjects who have weight loss with AIDS related wasting within the first 12 weeks of treatment | Baseline (Day 1) to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Lean Mass |  | Baseline (Day 1) to Week 12 | 
| Change From Baseline in Impedance | Electrical impedance is a method for body composition assessment. The procedure involves sending a small current through the body and measuring the resistance in ohm. High resistance is associated with smaller amounts of fat-free mass. Smaller resistance is associated with large amounts of fat-free mass. | Baseline (Day 1) to Week 12 | 
| Change From Baseline in Body Fat Mass |  | Baseline (Day 1) to Week 12 | 
| Change in Hip Circumference |  | Baseline (Day 1) to Week 12 | 
| Change in Waist Circumference |  | Baseline (Day 1) to Week 12 | 
| Change in Tricep Skinfold |  | Baseline (Day 1) to Week 12 | 
| Change in Mid-arm Circumference |  | Baseline (Day 1) to Week 12 | 
| Change in Total Energy | Food intake was quantified by the 24-hour recall food diary | Baseline (Day 1) to Week 12 | 
| Quality of Life (QoL) Via Bristol-Myers Anorexia/Cachexia Recovery Instrument (BACRI) at Baseline (Day 3) and Week 12 (BACRI) | The BACRI instrument is used to measure the benefit of weight gain treatment provided to anorexic patients on health related quality of life aspects. The scale is composed of 9 subscales (0 to 10 [worse to better]). The response was captured on a VAS scale in cm. The total BACRI score is the sum with a minimum score 0=worse and maximum score 90=better. These subscales are: change in weight impacting health; concern about weight; appearance change; change feeling of appearance; change in appetite; enjoy eating; overall feeling; benefit of treatment; and quality of life. | Baseline (Day 3) to Week 12 | 
| Appetite at Baseline (Day 3) and Week 12 | Appetite was assessed via visual analogue scale (VAS) as part of the Bristol-Myers Anorexia/Cachexia Recovery Instrument (BACRI) (Question 5 only). The question was To what extent has your appetite changed since the start of treatment? The response was captured on a VAS scale in cm with a range from 0 ( much worse) to 10 (much better). | Baseline (Day 3) to Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Weight loss, Cachexia, Anorexia, Megestrol acetate oral suspension, Nanocrystal dispersion, Nanocrystal technology, Body weight changes, AIDS wasting, HIV wasting, Emaciation, Megace ES, Megace, Treatment Experienced