AIDS Wasting Syndrome, Anorexia, Cachexia, HIV Infections, HIV Wasting Syndrome
Conditions
Keywords
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
Brief summary
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
Interventions
DRUGMegestrol acetate oral suspension nanocrystal dispersion 115 mg/mL
Megestrol acetate oral suspension nanocrystal dispersion 115 mg/mL administered as 575 mg once per day (5 mL dose)
DRUGMegestrol acetate oral suspension 40 mg/mL
Megestrol acetate oral suspension 40 mg/mL administered as 800 mg once per day (20 mL dose)
Sponsors
Quintiles, Inc.
Endo Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Body Weight | Baseline (Day 1) to Week 12 | Weight gain in adult HIV positive subjects who have weight loss with AIDS related wasting within the first 12 weeks of treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Impedance | Baseline (Day 1) to Week 12 | 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. |
| 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 From Baseline in Lean Mass | Baseline (Day 1) to Week 12 | — |
| Change in Mid-arm Circumference | Baseline (Day 1) to Week 12 | — |
| Change in Total Energy | Baseline (Day 1) to Week 12 | Food intake was quantified by the 24-hour recall food diary |
| Appetite at Baseline (Day 3) and Week 12 | Baseline (Day 3) to 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). |
| Quality of Life (QoL) Via Bristol-Myers Anorexia/Cachexia Recovery Instrument (BACRI) at Baseline (Day 3) and Week 12 (BACRI) | Baseline (Day 3) to Week 12 | 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. |
| Change in Tricep Skinfold | Baseline (Day 1) to Week 12 | — |
Countries
India, South Africa, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Megestrol Acetate Oral Suspension Nanocrystal Dispersion Subjects were treated with 575 mg per as single-dose for 12 weeks | 32 |
| Megestrol Acetate Oral Suspension Micronized Formulation Subjects were treated with 800 mg per as single-dose for 12 weeks | 31 |
| Total | 63 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 |
| Overall Study | Death | 0 | 1 |
| Overall Study | Illicit Drug Use | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Physician Decision | 1 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 2 |
Baseline characteristics
| Characteristic | Megestrol Acetate Oral Suspension Nanocrystal Dispersion | Megestrol Acetate Oral Suspension Micronized Formulation | Total |
|---|---|---|---|
| Age, Continuous | 37.3 years STANDARD_DEVIATION 7.32 | 36.3 years STANDARD_DEVIATION 7.22 | 36.8 years STANDARD_DEVIATION 7.23 |
| Sex: Female, Male Female | 11 Participants | 16 Participants | 27 Participants |
| Sex: Female, Male Male | 21 Participants | 15 Participants | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 30 / 32 | 30 / 31 |
| serious Total, serious adverse events | 14 / 32 | 14 / 31 |
Outcome results
Primary
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
Time frame: Baseline (Day 1) to Week 12
Population: Analysis is based on Intent-To-Treat-Population (ITT); all randomized subjects who were dispensed medication and had at least one post-randomization visit
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Megestrol Acetate Oral Suspension Nanocrystal Dispersion | Change in Body Weight | Overall | 5.4 kg | Standard Deviation 5.32 |
| Megestrol Acetate Oral Suspension Nanocrystal Dispersion | Change in Body Weight | Male | 7.0 kg | Standard Deviation 3.16 |
| Megestrol Acetate Oral Suspension Nanocrystal Dispersion | Change in Body Weight | Female | 2.3 kg | Standard Deviation 7.18 |
| Megestrol Acetate Oral Suspension Micronized Formulation | Change in Body Weight | Overall | 3.5 kg | Standard Deviation 4.03 |
| Megestrol Acetate Oral Suspension Micronized Formulation | Change in Body Weight | Male | 3.5 kg | Standard Deviation 4.72 |
| Megestrol Acetate Oral Suspension Micronized Formulation | Change in Body Weight | Female | 3.5 kg | Standard Deviation 3.42 |
Secondary
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).
Time frame: Baseline (Day 3) to Week 12
Population: Analysis is based on Intent-To-Treat-Population (ITT); all randomized subjects who were dispensed medication and had at least one post-randomization visit. Only 29 subjects were analyzed in the micronized formulation treatment group based on available baseline measurements.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Megestrol Acetate Oral Suspension Nanocrystal Dispersion | Appetite at Baseline (Day 3) and Week 12 | Baseline Day 3 | 6.1 cm | Standard Deviation 1.81 |
| Megestrol Acetate Oral Suspension Nanocrystal Dispersion | Appetite at Baseline (Day 3) and Week 12 | Week 12 | 8.4 cm | Standard Deviation 1.3 |
| Megestrol Acetate Oral Suspension Micronized Formulation | Appetite at Baseline (Day 3) and Week 12 | Baseline Day 3 | 5.8 cm | Standard Deviation 1.16 |
| Megestrol Acetate Oral Suspension Micronized Formulation | Appetite at Baseline (Day 3) and Week 12 | Week 12 | 8.0 cm | Standard Deviation 2.14 |
Secondary
Change From Baseline in Body Fat Mass
Time frame: Baseline (Day 1) to Week 12
Population: Analysis is based on Intent-To-Treat-Population (ITT); all randomized subjects who were dispensed medication and had at least one post-randomization visit. Only 31 subjects were analyzed for the megestrol acetate oral suspension nanocrystal dispersion group based on available baseline measurements.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Megestrol Acetate Oral Suspension Nanocrystal Dispersion | Change From Baseline in Body Fat Mass | 3.2 kg | Standard Deviation 4.1 |
| Megestrol Acetate Oral Suspension Micronized Formulation | Change From Baseline in Body Fat Mass | 2.2 kg | Standard Deviation 3.4 |
Secondary
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.
Time frame: Baseline (Day 1) to Week 12
Population: Analysis is based on Intent-To-Treat-Population (ITT); all randomized subjects who were dispensed medication and had at least one post-randomization visit. Only 31 subjects were analyzed for the megestrol acetate oral suspension nanocrystal dispersion group based on available baseline measurements.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Megestrol Acetate Oral Suspension Nanocrystal Dispersion | Change From Baseline in Impedance | 21.6 ohms | Standard Deviation 77.2 |
| Megestrol Acetate Oral Suspension Micronized Formulation | Change From Baseline in Impedance | 12.2 ohms | Standard Deviation 54.2 |
Secondary
Change From Baseline in Lean Mass
Time frame: Baseline (Day 1) to Week 12
Population: Analysis is based on Intent-To-Treat-Population (ITT); all randomized subjects who were dispensed medication and had at least one post-randomization visit. Only 31 subjects were analyzed for the megestrol acetate oral suspension nanocrystal dispersion group based on available baseline measurements.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Megestrol Acetate Oral Suspension Nanocrystal Dispersion | Change From Baseline in Lean Mass | 2.1 kg | Standard Deviation 3.74 |
| Megestrol Acetate Oral Suspension Micronized Formulation | Change From Baseline in Lean Mass | 1.3 kg | Standard Deviation 2.82 |
Secondary
Change in Hip Circumference
Time frame: Baseline (Day 1) to Week 12
Population: Analysis is based on Intent-To-Treat-Population (ITT); all randomized subjects who were dispensed medication and had at least one post-randomization visit. Only 31 subjects and 29 subjects were analyzed, respectively based on available baseline measurements.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Megestrol Acetate Oral Suspension Nanocrystal Dispersion | Change in Hip Circumference | 2.5 cm | Standard Deviation 3.7 |
| Megestrol Acetate Oral Suspension Micronized Formulation | Change in Hip Circumference | 1.8 cm | Standard Deviation 3.6 |
Secondary
Change in Mid-arm Circumference
Time frame: Baseline (Day 1) to Week 12
Population: Analysis is based on Intent-To-Treat-Population (ITT); all randomized subjects who were dispensed medication and had at least one post-randomization visit
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Megestrol Acetate Oral Suspension Nanocrystal Dispersion | Change in Mid-arm Circumference | -0.6 cm | Standard Deviation 11.5 |
| Megestrol Acetate Oral Suspension Micronized Formulation | Change in Mid-arm Circumference | 1.1 cm | Standard Deviation 1.5 |
Secondary
Change in Total Energy
Food intake was quantified by the 24-hour recall food diary
Time frame: Baseline (Day 1) to Week 12
Population: Analysis is based on Intent-To-Treat-Population (ITT); all randomized subjects who were dispensed medication and had at least one post-randomization visit. Only 27 subjects and 22 subjects were analyzed, respectively based on available baseline data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Megestrol Acetate Oral Suspension Nanocrystal Dispersion | Change in Total Energy | 215.9 kcal | Standard Deviation 830.3 |
| Megestrol Acetate Oral Suspension Micronized Formulation | Change in Total Energy | 150.6 kcal | Standard Deviation 1044.1 |
Secondary
Change in Tricep Skinfold
Time frame: Baseline (Day 1) to Week 12
Population: Analysis is based on Intent-To-Treat-Population (ITT); all randomized subjects who were dispensed medication and had at least one post-randomization visit
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Megestrol Acetate Oral Suspension Nanocrystal Dispersion | Change in Tricep Skinfold | 1.0 cm | Standard Deviation 2.6 |
| Megestrol Acetate Oral Suspension Micronized Formulation | Change in Tricep Skinfold | 1.5 cm | Standard Deviation 5.4 |
Secondary
Change in Waist Circumference
Time frame: Baseline (Day 1) to Week 12
Population: Analysis is based on Intent-To-Treat-Population (ITT); all randomized subjects who were dispensed medication and had at least one post-randomization visit. Only 31 subjects were analyzed for the megestrol acetate oral suspension nanocrystal dispersion group based on available data measurements.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Megestrol Acetate Oral Suspension Nanocrystal Dispersion | Change in Waist Circumference | 7.1 cm | Standard Deviation 4.9 |
| Megestrol Acetate Oral Suspension Micronized Formulation | Change in Waist Circumference | 5.4 cm | Standard Deviation 4.7 |
Secondary
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.
Time frame: Baseline (Day 3) to Week 12
Population: Analysis is based on Intent-To-Treat-Population (ITT); all randomized subjects who were dispensed medication and had at least one post-randomization visit. Only 29 subjects were analyzed in the micronized formulation treatment group based on available baseline measurements.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Megestrol Acetate Oral Suspension Nanocrystal Dispersion | Quality of Life (QoL) Via Bristol-Myers Anorexia/Cachexia Recovery Instrument (BACRI) at Baseline (Day 3) and Week 12 (BACRI) | Baseline (Day 3) | 52.3 cm | Standard Deviation 9.38 |
| Megestrol Acetate Oral Suspension Nanocrystal Dispersion | Quality of Life (QoL) Via Bristol-Myers Anorexia/Cachexia Recovery Instrument (BACRI) at Baseline (Day 3) and Week 12 (BACRI) | Week 12 | 67.6 cm | Standard Deviation 9.53 |
| Megestrol Acetate Oral Suspension Micronized Formulation | Quality of Life (QoL) Via Bristol-Myers Anorexia/Cachexia Recovery Instrument (BACRI) at Baseline (Day 3) and Week 12 (BACRI) | Baseline (Day 3) | 50.1 cm | Standard Deviation 7.31 |
| Megestrol Acetate Oral Suspension Micronized Formulation | Quality of Life (QoL) Via Bristol-Myers Anorexia/Cachexia Recovery Instrument (BACRI) at Baseline (Day 3) and Week 12 (BACRI) | Week 12 | 65.6 cm | Standard Deviation 14.78 |