Obesity, Overweight
Conditions
Keywords
overweight, orlistat, body composition
Brief summary
The purpose of this study is to determine if a 24 week weight loss program with orlistat 60 mg will produce greater changes in body composition compared to placebo.
Detailed description
Large amounts of VAT (adipose tissue surrounding the viscera of the organs), is known to be associated with increased risk of heart disease and diabetes. Orlistat (tetrahydrolipstatin or THL) inhibits gastrointestinal lipase and reduces the absorption of dietary fat. The purpose of this study is to to determine if a 24 week weight loss program with orlistat 60 mg would produce greater changes in adipose tissue depots (specifically VAT) compared to placebo. This study will use the Echo MRI technology across multiple sites to measure total fat mass. EchoMRI is a non invasive method ideally suited for studies which track changes in human body composition over time, with measuring times of less than 3 minutes and no radiation exposure.
Interventions
DRUGOrlistat
Weight loss treatment
DRUGPlacebo
Inactive
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
* Aged 18-60 years inclusive * Body Mass Index (BMI): BMI in the range of 25.0-34.9 kg/m\^2 * Waist circumference: Females: \> 35 inches Males: \> 40 inches * Diet: 1. Normal eating habits, consuming 3 meals a day (breakfast, lunch and dinner) 2. Willing to follow a hypocaloric diet during the study to achieve weight loss 3. Willing to take a daily multivitamin for the duration of the study. * General Health:Good general health with (in the opinion of the investigator) no clinically significant and relevant abnormalities of medical history or physical examination
Exclusion criteria
* Pregnant and/ or Breast-feeding women * Diet/Exercise:Currently on a special diet or who cannot fulfill the dietary requirements of the study. * Smoking History:a) Smoking cessation within the past 6 months b) Current Smokers * Allergy/Intolerance: Known or suspected intolerance or hypersensitivity to the study materials and study foods (or closely related compounds) or any of their stated ingredients. * Medication: a) Currently taking medication for weight loss or appetite control. b) Previous Xenical® (orlistat) or alli® use within 3 months of screening date c) Currently taking medication or supplements that influence intestinal transit time and other stool formation parameters or influences cramping (e.g., Anticholinergics (such as atropine) or cholinergics (such as physostigmine), phenothiazines, tricyclic antidepressants, opioid analgesics (including loperamide), calcium channel antagonists, clonidine, cisapride, octreotide. Also, any laxative or antidiarrheal product). d) Currently taking or withdrawn during the past 6 months any drugs with significant impact on body weight (e.g. serotoninergically acting drugs, antidepressants, central adrenergically acting drugs, drugs inhibiting digestion and absorption, appetite suppressants, metformin) e) Currently taking Cyclosporine, Warfarin or Amiodarone HCL * Disease/Surgery: a) History of gastrointestinal disease (e.g., irritable bowel syndrome, diarrhea, inflamed bowel, steatorrhea/fat malabsorption, hemorrhoids, incontinence, pancreatitis). b) History of psychological disorder, including eating disorders such as anorexia nervosa and bulimia c) History of neurological disorder (e.g. seizures, parkinson's disease, Alzheimer's disease) d) History of hypo/hyperthyroidism unless euthyroid and controlled on a stable dose of medication for at least 6 months. e) History of surgery for weight loss f) Uncontrolled hypertension g) Heart Disease h) Diabetes Mellitus (Type 1 and 2) (Fasting Blood Glucose \>126 mg/dL) * Participant has a known history of panic attacks and/or claustrophobia or other conditions precluding safe EchoMRI, CT or other scanning modalities according to local guidelines, (e.g., pacemaker, hearing aid, metallic body piercing and/or other metal implants) or in the opinion of the Investigator the participant exceeds size limitations for the instruments. * Participant has had a weight loss or gain of greater than or equal to 3 kg in the 3 months prior to screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 24 in Abdominal VAT Mass | Baseline to week 24 | VAT was measured by the computed tomography (CT) scan. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 24 in Body Weight | Baseline to week 24 | Participants were weighed at least twice until two consecutive measurements were within 0.5 kg of each other and the average of the two measurements was recorded. |
| Change From Baseline to Week 24 in Total Fat Mass | Baseline to week 24 | Change in total fat mass was calculated from an average of three measurements at each visit from Echo Magnetic Resonance Imaging (EchoMRI). |
| Change From Baseline to Week 24 in Percentage Body Fat | Baseline to week 24 | Body fat was assessed through Bioelectrical Impedance Analysis (BIA). |
| Change From Baseline to Week 24 in Waist Circumference | Baseline to week 24 | Waist circumference was measured against the skin, without interference from clothing, at the level midway between the lateral lower rib margin and the iliac crest in standing position. |
| Change From Baseline to Week 12 in Abdominal VAT Mass | Baseline to week 12 | Abdominal VAT mass from baseline to week 12 was measured by CT scan. |
| Change From Baseline to Week 24 in Liver Fat | Baseline to week 24 | The liver fat was measured by CT scan in Hounsfield Units (HU). |
| Change From Baseline to Week 24 in Total Calories Expended for Physical Activity | Baseline to week 24 | Measurement of physical activity from Paffenbarger questionnaire. The number of caloried expended was representation of activity level: Higher calorie counts indicate higher activity |
| Change From Baseline to Week 24 in Quality of Life (QoL) Scores. | Baseline to week 24 | QoL scores were measured using an Impact of Weight Quality of Life (IWQoL) Questionnaire, which scored the responses at a scale of 1 to 5(1, never true, to 5, always true): QoL scales for physical function, self-esteem, sexual life, public distress, and work were evaluated, and summarized in a total score. A higher value indicated a better quality of life. |
| Selectivity Index at Week 24 | Baseline to week 24 | The selectivity index (SI) was used as a measure of orlistat's ability to target abdominal VAT loss compared to total adipose tissue lost. SI was calculated using the following equation: Mean % change in VAT divided by Mean % change in total fat mass. |
| Change From Baseline to Week 24 in Percentage Liver Fat | Baseline to week 24 | For Liver fat, Intrahepatic lipids (IHL) were measured by Magnetic Resonance Spectroscopy (MRS). |
Countries
Sweden, United States
Participant flow
Recruitment details
This multicentric clinical study was conducted in 2 countries; 2 centres in United States of America (USA) and 1 centre in Sweden.
Pre-assignment details
Out of 267 screened participants, 131 were randomized, while 136 participants were considered as screen failures.
Participants by arm
| Arm | Count |
|---|---|
| Orlistat 60 mg Orlistat 60 mg capsules taken orally with meals 3 times per day. Intent-to-treat (ITT) population was considered for baseline measures. | 62 |
| Placebo Placebo to match Orlistat 60 mg capsules taken orally with meals 3 times per day. ITT population was considered for baseline measures. | 61 |
| Total | 123 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 0 |
| Overall Study | Lost to Follow-up | 2 | 1 |
| Overall Study | Other Reason | 1 | 2 |
| Overall Study | Withdrawal by Subject | 5 | 10 |
Baseline characteristics
| Characteristic | Orlistat 60 mg | Placebo | Total |
|---|---|---|---|
| Age Continuous | 42.92 Year STANDARD_DEVIATION 9.031 | 43.84 Year STANDARD_DEVIATION 11.682 | 43.37 Year STANDARD_DEVIATION 10.397 |
| Body Mass Index (BMI) | 31.03 Kilogram per meter square (kg/m^2) STANDARD_DEVIATION 2.259 | 31.04 Kilogram per meter square (kg/m^2) STANDARD_DEVIATION 2.064 | 31.03 Kilogram per meter square (kg/m^2) STANDARD_DEVIATION 2.155 |
| Body Weight | 88.10 Kilogram (kg) STANDARD_DEVIATION 10.705 | 87.79 Kilogram (kg) STANDARD_DEVIATION 9.354 | 87.95 Kilogram (kg) STANDARD_DEVIATION 10.018 |
| Height | 168.30 Centimeter (cm) STANDARD_DEVIATION 8.275 | 168.08 Centimeter (cm) STANDARD_DEVIATION 8.117 | 168.19 Centimeter (cm) STANDARD_DEVIATION 8.164 |
| Sex: Female, Male Female | 51 Participants | 51 Participants | 102 Participants |
| Sex: Female, Male Male | 11 Participants | 10 Participants | 21 Participants |
| Visceral Abdominal Tissue (VAT) Mass | 3.75 kg STANDARD_DEVIATION 1.87 | 3.92 kg STANDARD_DEVIATION 1.806 | 3.83 kg STANDARD_DEVIATION 1.832 |
| Waist Circumference | 100.10 cm STANDARD_DEVIATION 7.967 | 100.60 cm STANDARD_DEVIATION 6.892 | 100.35 cm STANDARD_DEVIATION 7.427 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 57 / 63 | 52 / 64 |
| serious Total, serious adverse events | 2 / 63 | 1 / 64 |
Outcome results
Primary
Change From Baseline to Week 24 in Abdominal VAT Mass
VAT was measured by the computed tomography (CT) scan.
Time frame: Baseline to week 24
Population: This analysis was carried out for the observed ITT population, who had this post-baseline efficacy assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Orlistat 60 mg | Change From Baseline to Week 24 in Abdominal VAT Mass | -0.630 kg | Standard Deviation 0.6887 |
| Placebo | Change From Baseline to Week 24 in Abdominal VAT Mass | -0.403 kg | Standard Deviation 0.7249 |
Comparison: The null hypothesis considered no difference in the change from baseline to week 24 between the two treatment groups.p-value: 0.024495% CI: [0.035, 0.491]ANCOVA
Secondary
Change From Baseline to Week 12 in Abdominal VAT Mass
Abdominal VAT mass from baseline to week 12 was measured by CT scan.
Time frame: Baseline to week 12
Population: This analysis was carried out for the observed ITT population, who had this post-baseline efficacy assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Orlistat 60 mg | Change From Baseline to Week 12 in Abdominal VAT Mass | -0.496 kg | Standard Deviation 0.4943 |
| Placebo | Change From Baseline to Week 12 in Abdominal VAT Mass | -0.351 kg | Standard Deviation 0.5904 |
Comparison: The null hypothesis considered no difference in the change from baseline to week 12 between the two treatment groups.p-value: 0.041595% CI: [0.007, 0.337]ANCOVA
Secondary
Change From Baseline to Week 24 in Body Weight
Participants were weighed at least twice until two consecutive measurements were within 0.5 kg of each other and the average of the two measurements was recorded.
Time frame: Baseline to week 24
Population: This analysis was carried out for the observed ITT population, who had this post-baseline efficacy assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Orlistat 60 mg | Change From Baseline to Week 24 in Body Weight | -5.96 kg | Standard Deviation 4.743 |
| Placebo | Change From Baseline to Week 24 in Body Weight | -3.91 kg | Standard Deviation 5.375 |
Comparison: The null hypothesis considered no difference in the change from baseline to week 24 between the two treatment groups.p-value: 0.02695% CI: [0.25, 3.74]ANCOVA
Secondary
Change From Baseline to Week 24 in Liver Fat
The liver fat was measured by CT scan in Hounsfield Units (HU).
Time frame: Baseline to week 24
Population: This analysis was carried out for the observed ITT population, who had this post-baseline efficacy assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Orlistat 60 mg | Change From Baseline to Week 24 in Liver Fat | 0.06 Hounsfield Units (HU) | Standard Deviation 0.169 |
| Placebo | Change From Baseline to Week 24 in Liver Fat | 0.02 Hounsfield Units (HU) | Standard Deviation 0.174 |
Comparison: The null hypothesis considered no difference in the change from baseline to week 24 between the two treatment groups.p-value: 0.323595% CI: [-0.069, 0.023]ANCOVA
Secondary
Change From Baseline to Week 24 in Percentage Body Fat
Body fat was assessed through Bioelectrical Impedance Analysis (BIA).
Time frame: Baseline to week 24
Population: This analysis was carried out for the observed ITT population, who had this post-baseline efficacy assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Orlistat 60 mg | Change From Baseline to Week 24 in Percentage Body Fat | -1.70 Percentage (%) body fat | Standard Deviation 3.434 |
| Placebo | Change From Baseline to Week 24 in Percentage Body Fat | -0.38 Percentage (%) body fat | Standard Deviation 4.232 |
Comparison: The null hypothesis considered no difference in the change from baseline to week 24 between the two treatment groups.p-value: 0.03995% CI: [0.07, 2.87]ANCOVA
Secondary
Change From Baseline to Week 24 in Percentage Liver Fat
For Liver fat, Intrahepatic lipids (IHL) were measured by Magnetic Resonance Spectroscopy (MRS).
Time frame: Baseline to week 24
Population: ITT subset (participants who had this post-baseline efficacy assessment) from one study site was analysed for this parameter.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Orlistat 60 mg | Change From Baseline to Week 24 in Percentage Liver Fat | -0.0008 Percentage (%) IHL | Standard Deviation 0.00609 |
| Placebo | Change From Baseline to Week 24 in Percentage Liver Fat | -0.0112 Percentage (%) IHL | Standard Deviation 0.03642 |
Secondary
Change From Baseline to Week 24 in Quality of Life (QoL) Scores.
QoL scores were measured using an Impact of Weight Quality of Life (IWQoL) Questionnaire, which scored the responses at a scale of 1 to 5(1, never true, to 5, always true): QoL scales for physical function, self-esteem, sexual life, public distress, and work were evaluated, and summarized in a total score. A higher value indicated a better quality of life.
Time frame: Baseline to week 24
Population: This analysis was carried out for the observed ITT population, i.e. ITT subjects who had this post-baseline efficacy assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Orlistat 60 mg | Change From Baseline to Week 24 in Quality of Life (QoL) Scores. | 5.29 Score on a Scale | Standard Deviation 8.009 |
| Placebo | Change From Baseline to Week 24 in Quality of Life (QoL) Scores. | 8.78 Score on a Scale | Standard Deviation 10.429 |
Comparison: The null hypothesis considered no difference in the change from baseline to week 24 between the treatment groups.p-value: 0.284795% CI: [-1.4, 4.72]ANCOVA
Secondary
Change From Baseline to Week 24 in Total Calories Expended for Physical Activity
Measurement of physical activity from Paffenbarger questionnaire. The number of caloried expended was representation of activity level: Higher calorie counts indicate higher activity
Time frame: Baseline to week 24
Population: This analysis was carried out for the observed ITT population, who had this post-baseline efficacy assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Orlistat 60 mg | Change From Baseline to Week 24 in Total Calories Expended for Physical Activity | -498 Kilocalorie (kcal)/week | Standard Deviation 6627 |
| Placebo | Change From Baseline to Week 24 in Total Calories Expended for Physical Activity | 517 Kilocalorie (kcal)/week | Standard Deviation 4873 |
Comparison: The null hypothesis considered no difference in the change from baseline to week 24 between the two treatment groups.p-value: 0.2895% CI: [-657.3, 2224.9]ANCOVA
Secondary
Change From Baseline to Week 24 in Total Fat Mass
Change in total fat mass was calculated from an average of three measurements at each visit from Echo Magnetic Resonance Imaging (EchoMRI).
Time frame: Baseline to week 24
Population: This analysis was carried out for the observed ITT population, who had this post-baseline efficacy assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Orlistat 60 mg | Change From Baseline to Week 24 in Total Fat Mass | -4.69 kg | Standard Deviation 3.691 |
| Placebo | Change From Baseline to Week 24 in Total Fat Mass | -3.16 kg | Standard Deviation 4.248 |
Comparison: The null hypothesis considered no difference in the change from baseline to week 24 between the two treatment groups.p-value: 0.024295% CI: [0.219, 3.065]ANCOVA
Secondary
Change From Baseline to Week 24 in Waist Circumference
Waist circumference was measured against the skin, without interference from clothing, at the level midway between the lateral lower rib margin and the iliac crest in standing position.
Time frame: Baseline to week 24
Population: This analysis was carried out for the observed ITT population, who had this post-baseline efficacy assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Orlistat 60 mg | Change From Baseline to Week 24 in Waist Circumference | -6.65 cm | Standard Deviation 0.692 |
| Placebo | Change From Baseline to Week 24 in Waist Circumference | -4.95 cm | Standard Deviation 0.704 |
Comparison: The null hypothesis considered no difference in the change from baseline to week 24 between the two treatment groups.p-value: 0.08595% CI: [-0.24, 3.63]ANCOVA
Secondary
Selectivity Index at Week 24
The selectivity index (SI) was used as a measure of orlistat's ability to target abdominal VAT loss compared to total adipose tissue lost. SI was calculated using the following equation: Mean % change in VAT divided by Mean % change in total fat mass.
Time frame: Baseline to week 24
Population: This analysis was carried out for the observed ITT population, who had this post-baseline efficacy assessment, only in Orlistat 60 mg group. This analysis was not carried out for placebo group.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Orlistat 60 mg | Selectivity Index at Week 24 | 1.155 Ratio |