Obesity
Conditions
Brief summary
The purpose of this study is to determine if LY377604 + sibutramine work better than LY377604 or sibutramine alone in the treatment of obesity.
Interventions
DRUGLY377604
Given daily, orally for 24 weeks
DRUGSibutramine
given daily, orally for 24 weeks
DRUGMetoprolol
given daily, orally for 24 weeks (100 mg for 1 week followed by 200 mg for 23 weeks. Patients unable to tolerate 200 mg will be dose reduced to 100 mg), followed by a 2 week taper (1 week at 100 mg/day followed by 1 week at 50 mg/day).
DRUGPlacebo sibutramine
given daily, orally for 24 weeks
DRUGPlacebo Metoprolol
given daily, orally for 26 weeks (24 weeks plus 2 weeks of taper)
DRUGPlacebo LY377604
given daily, orally for 24 weeks
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
21 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Are between the body mass index (BMI) of 27 and 45 kg/m\^2, inclusive, at the time of screening.
Exclusion criteria
* Have a Diastolic Blood Pressure (DBP) greater than 90 mm Hg or less than 55 mm Hg, and/or Systolic Blood Pressure (SBP) \>140 mm Hg or \<90 mmHg, confirmed by at least 1 repeat measurement. Subjects with hypertension treated with antihypertensive medication are not excluded if blood pressure is within the prescribed limits and they are not treated with excluded medications. Changes in antihypertensive medication are not permitted within 30 days prior to randomization * Previous history of poorly controlled hypertension, (that is, \>160/100 or hypertension which requires more than 2 drugs for control). * Have a pulse rate \>90 bpm or \<50 bpm. * Evidence or history of prior significant cardiovascular disease, coronary artery disease, cardiovascular surgery, significant valvular disease, heart failure, arrhythmias, sick sinus syndrome or stroke. * Current treatment with β-blockers, calcium channel blockers, digitalis glycosides (for example, digoxin, etc), or clonidine. * Recent treatment (within 2 weeks prior to randomization) with catecholamine-depleting drugs (such as reserpine or tetrabenazine, monoamine oxidase inhibitors (MAOIs). * Current treatment with serotonergic drugs, such as selective serotonin reuptake inhibitors (SSRI), any drug that is a serotonin, norepinephrine, or dopamine reuptake inhibitor, triptan or ergot therapies for migraine or nausea, or serotonin-releasing agents. * Treatment with significant inhibitors of Cytochrome P2D6 (CYP2D6), such as bupropion, fluoxetine, paroxetine, quinidine, duloxetine, amiodarone, cimetidine, chlorpheniramine, clomipramine, doxepin, haloperidol, methadone, mibefradil, and ritonavir. * Participants with bronchospastic diseases or who are treated with bronchodilators or other prescription or nonprescription beta adrenergic agonists. * Peripheral vascular disease * History of thyrotoxicosis * History of seizures (except for childhood febrile convulsion) or at increased risk of seizures (for example, history of significant head trauma or intracranial surgery). * Have had a significant change in weight, defined as a gain or loss of at least 4 kg (9 lb) in the 90 days prior to randomization * Have had bariatric surgery (for example, gastric banding or gastric bypass) * Have had liposuction within 90 days prior to randomization * Have a disease that affects adipose mass or distribution of energy balance (for example, Cushing's syndrome, uncontrolled hyper- or hypothyroidism). * Have taken in the 30 days prior to randomization, a medication, herbal product, or nutritional supplement that affects adipose mass or distribution or energy balance, such as glucocorticoids, antiretrovirals, atypical antipsychotics, lithium, valproic acid, lamotrigine, or other anticonvulsants, mirtazapine, bupropion, phentermine, sibutramine, orlistat, rimonabant, amphetamine, or ephedra-containing supplements. Note: Medications that have small and transient effects on weight or medications that may affect weight independent of adipose mass (for example, estrogens or diuretics), may be continued, but may not be started, stopped, or changed during the course of the study. * Have been diagnosed with an eating disorder, such as anorexia, bulimia, binge eating disorder, or nocturnal eating disorder. * Have diabetes mellitus treated with medication, or type 2 diabetes mellitus managed with diet and exercise with hemoglobin A1c (HbA1C) \>7.0%. * Symptomatic cholelithiasis in the 90 days prior to randomization. * Any lifetime history of suicide attempt. * History of major depressive disorder in the last 2 years or any lifetime history of severe psychiatric disorders (for example, schizophrenia or bipolar disorder).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Body Weight From Baseline to 24 Week Endpoint | Baseline, 24 weeks | Body weight percentage change from baseline is presented as Least Squares Mean (LSMean) with treatment, visit, and their interaction as fixed effects, subject as a random effect, baseline body weight, age, gender were used as covariates. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieve a Minimum of 10% Weight Loss From Baseline at 24 Weeks | 24 weeks | — |
| Change in Heart Rate From Baseline to 24 Week Endpoint | Baseline, 24 weeks | Heart rate change from baseline is presented as Least Squares Mean (LSMean) with treatment, visit, and their interaction as fixed effects, subject as a random effect, baseline heart rate, age, gender were used as covariates. |
| Change in Blood Pressure From Baseline to 24 Week Endpoint | Baseline, 24 weeks | Blood pressure change from baseline is presented as Least Squares Mean (LSMean) with treatment, visit, and their interaction as fixed effects, subject as a random effect, baseline blood pressure, age, gender were used as covariates. |
| Change in Body Composition Using Dual Energy X-ray Absorptiometry (DXA) From Baseline to 24 Week Endpoint | Baseline, 24 weeks | Change in body composition (lean body mass and fat mass) was assessed using dual energy x-ray absorptiometry (DXA) and is presented as LSMEAN values with treatment, visit, and their interaction as fixed effects, subject as a random effect, baseline body composition, age, gender were used as covariates. |
| Change in Waist Circumference From Baseline to 24 Week Endpoint | Baseline, 24 weeks | Change from baseline to endpoint is presented as LSMEAN with treatment, visit, and their interaction as fixed effects, subject as a random effect, baseline waist circumference, age, gender were used as covariates. |
| Percentage Change in Waist Circumference From Baseline to 24 Week Endpoint | Baseline, 24 weeks | Percentage change from baseline to endpoint is presented as LSMEAN with treatment, visit, and their interaction as fixed effects, subject as a random effect, baseline waist circumference, age, gender were used as covariates. |
| Change in Total Cholesterol From Baseline to 24 Weeks Endpoint | Baseline, 24 weeks | — |
| Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to 24 Weeks Endpoint | Baseline, 24 weeks | — |
| Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline to 24 Weeks Endpoint | Baseline, 24 weeks | — |
| The Mean Change in Body Weight From Baseline to 24 Week Endpoint | Baseline, 24 weeks | Body weight change from baseline is presented as Least Squares Mean (LSMean) with treatment, visit, and their interaction as fixed effects, subject as a random effect, baseline body weight, age, gender were used as covariates. |
| Change in Triglycerides From Baseline to 24 Weeks Endpoint | Baseline, 24 weeks | — |
| Change From Baseline for Obesity Weight Loss Quality of Life Instrument (OWL-QoL) | Baseline, 24 weeks | Results presented as Least Squares Mean with treatment, visit, and their interaction as fixed effects, subject as random effect, baseline body mass index used as covariate. OWL-QoL consists of 17 items on scale ranging from 0 (Not at all) to 6 (A very great deal). Before calculating scores, each item is reversed. A single quality of life score is computed by summing each item and transforming this raw score onto standardized scale of 0 (greatest impact) to 100 (lowest impact) using formula: score = \[(sum of component items score (minus) lowest possible score/ possible raw score range)\*100\]. |
| Change From Baseline in Vitality Scale of Medical Outcomes Short Form - 36 (SF-36) Scale | Baseline, 24 weeks | Vitality change from baseline is presented as Least Squares Mean (LSMean) with treatment, visit, and their interaction as fixed effects, subject as a random effect, baseline body mass index was used as covariate. SF-36 is a self-reported questionnaire that consists of 36 questions covering 8 health domains including vitality. The vitality domain results are presented. The vitality domain is scored by summing the individual items and transforming the scores into a 0 to 100 scale, with higher scores indicating better health status or functioning. |
| Change in Glycated Hemoglobin A1c (HbA1c) From Baseline | Baseline, 24 weeks | Analysis of change in HbA1c was not conducted due to an inadequate number of samples. |
| Change in Fasting Glucose From Baseline to 24 Weeks Endpoint | Baseline, 24 weeks | Analysis of change in fasting glucose was not conducted due to an inadequate number of samples. |
| Change in Fasting Insulin From Baseline to 24 Weeks Endpoint | Baseline, 24 weeks | Analysis of change in fasting insulin was not conducted due to an inadequate number of samples. |
| Change in Insulin Resistance From Baseline to 24 Weeks Endpoint | Baseline, 24 weeks | Analysis of change in insulin resistance was not conducted due to an inadequate number of samples. |
| Pharmacokinetics: Area Under the Concentration Time Curve (AUC) | 4 weeks, 12 weeks, and 24 weeks | Analysis of AUC was not conducted due to an inadequate number of samples collected. |
| Pharmacokinetics: Maximum Concentration (Cmax) | 4 weeks, 12 weeks, and 24 weeks | Analysis of Cmax was not conducted due to an inadequate number of samples collected. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo LY377604: given orally, daily for 24 weeks.
Placebo sibutramine: given orally, daily for 24 weeks.
Placebo metoprolol: given orally, daily for 24 weeks, followed by 2 week taper. | 49 |
| LY377604 (75 mg) Given orally, daily for 24 weeks. | 49 |
| Sibutramine (30 mg)/Metoprolol (200 mg) sibutramine (30 mg): Given orally, daily for 24 weeks.
metoprolol (200 mg): Given orally, daily 100 mg for 1 week followed by 200 mg for 23 weeks (Patients unable to tolerate 200 mg will be dose reduced to 100 mg), followed by a 2 week taper - 1 week at 100 mg/day followed by 1 week at 50 mg/day.
Placebo LY377604: given orally, daily for 24 weeks. | 48 |
| LY377604 (15 mg)/Sibutramine (30 mg) LY377604 (15 mg): Given orally, daily for 24 weeks.
sibutramine (30 mg): Given orally, daily for 24 weeks.
Placebo metoprolol: Given orally, daily for 24 weeks. | 49 |
| LY377604 (40 mg)/Sibutramine (30 mg) LY377604 (40 mg): Given orally, daily for 24 weeks.
sibutramine (30 mg): Given orally, daily for 24 weeks.
Placebo metoprolol: Given orally, daily for 24 weeks, followed by 2 week taper. | 52 |
| LY377604 (75 mg)/Sibutramine (30 mg) LY377604 (75 mg): Given orally, daily for 24 weeks.
sibutramine (30 mg): Given orally, daily for 24 weeks.
Placebo metoprolol: Given orally, daily for 24 weeks, followed by 2 week taper. | 50 |
| LY377604 (75 mg)/Sibutramine (15 mg) LY377604 (75 mg): Given orally, daily for 24 weeks.
sibutramine (15 mg): Given orally, daily for 24 weeks.
Placebo metoprolol: Given orally, daily for 24 weeks, followed by 2 week taper. | 46 |
| Total | 343 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 7 | 6 | 9 | 5 | 7 | 1 |
| Overall Study | Death | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Entry Criteria Exclusion | 0 | 0 | 1 | 3 | 0 | 1 | 0 |
| Overall Study | Lost to Follow-up | 3 | 5 | 5 | 0 | 0 | 0 | 6 |
| Overall Study | Physician Decision | 0 | 0 | 0 | 0 | 0 | 1 | 1 |
| Overall Study | Protocol Violation | 0 | 0 | 0 | 0 | 0 | 2 | 1 |
| Overall Study | Sponsor Decision | 36 | 31 | 28 | 30 | 38 | 30 | 29 |
| Overall Study | Withdrawal by Subject | 3 | 2 | 3 | 3 | 3 | 5 | 3 |
Baseline characteristics
| Characteristic | LY377604 (75 mg) | Sibutramine (30 mg)/Metoprolol (200 mg) | LY377604 (15 mg)/Sibutramine (30 mg) | LY377604 (40 mg)/Sibutramine (30 mg) | Placebo | LY377604 (75 mg)/Sibutramine (30 mg) | LY377604 (75 mg)/Sibutramine (15 mg) | Total |
|---|---|---|---|---|---|---|---|---|
| Age Continuous | 43.89 years STANDARD_DEVIATION 11.02 | 44.68 years STANDARD_DEVIATION 12 | 43.42 years STANDARD_DEVIATION 11.06 | 44.15 years STANDARD_DEVIATION 10.71 | 42.71 years STANDARD_DEVIATION 10.86 | 45.80 years STANDARD_DEVIATION 9.15 | 43.93 years STANDARD_DEVIATION 10.15 | 44.09 years STANDARD_DEVIATION 10.68 |
| Blood Pressure Diastolic Blood Pressure (DBP) | 74.40 mm Hg STANDARD_DEVIATION 7.7 | 75.83 mm Hg STANDARD_DEVIATION 6.76 | 76.61 mm Hg STANDARD_DEVIATION 7.07 | 76.94 mm Hg STANDARD_DEVIATION 6.31 | 75.12 mm Hg STANDARD_DEVIATION 7.31 | 77.87 mm Hg STANDARD_DEVIATION 6.82 | 78.38 mm Hg STANDARD_DEVIATION 6.23 | 76.44 mm Hg STANDARD_DEVIATION 6.97 |
| Blood Pressure Systolic Blood Pressure (SBP) | 115.72 mm Hg STANDARD_DEVIATION 10.78 | 117.35 mm Hg STANDARD_DEVIATION 10.13 | 118.67 mm Hg STANDARD_DEVIATION 11.11 | 118.34 mm Hg STANDARD_DEVIATION 11.37 | 117.11 mm Hg STANDARD_DEVIATION 11.53 | 119.86 mm Hg STANDARD_DEVIATION 11.42 | 120.72 mm Hg STANDARD_DEVIATION 11.36 | 118.24 mm Hg STANDARD_DEVIATION 11.13 |
| Body Mass Index (BMI) | 34.78 kilograms/square meters (kg/m^2) STANDARD_DEVIATION 4.53 | 36.34 kilograms/square meters (kg/m^2) STANDARD_DEVIATION 5.36 | 35.12 kilograms/square meters (kg/m^2) STANDARD_DEVIATION 4.55 | 34.86 kilograms/square meters (kg/m^2) STANDARD_DEVIATION 4.39 | 35.22 kilograms/square meters (kg/m^2) STANDARD_DEVIATION 4.96 | 35.30 kilograms/square meters (kg/m^2) STANDARD_DEVIATION 4.44 | 35.22 kilograms/square meters (kg/m^2) STANDARD_DEVIATION 4.87 | 35.26 kilograms/square meters (kg/m^2) STANDARD_DEVIATION 4.71 |
| Height | 166.86 centimeters (cm) STANDARD_DEVIATION 8.4 | 167.51 centimeters (cm) STANDARD_DEVIATION 9.22 | 165.23 centimeters (cm) STANDARD_DEVIATION 8.93 | 168.13 centimeters (cm) STANDARD_DEVIATION 7.88 | 166.10 centimeters (cm) STANDARD_DEVIATION 8.02 | 168.99 centimeters (cm) STANDARD_DEVIATION 8.18 | 168.38 centimeters (cm) STANDARD_DEVIATION 7.5 | 167.32 centimeters (cm) STANDARD_DEVIATION 8.34 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 8 Participants | 10 Participants | 8 Participants | 12 Participants | 6 Participants | 7 Participants | 56 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 3 Participants | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 10 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 43 Participants | 39 Participants | 34 Participants | 43 Participants | 36 Participants | 42 Participants | 36 Participants | 273 Participants |
| Region of Enrollment United States | 49 participants | 48 participants | 49 participants | 52 participants | 49 participants | 50 participants | 46 participants | 343 participants |
| Sex: Female, Male Female | 42 Participants | 38 Participants | 39 Participants | 40 Participants | 41 Participants | 41 Participants | 34 Participants | 275 Participants |
| Sex: Female, Male Male | 7 Participants | 10 Participants | 10 Participants | 12 Participants | 8 Participants | 9 Participants | 12 Participants | 68 Participants |
| Waist and Hip Circumference Hip Circumference | 118.55 centimeters (cm) STANDARD_DEVIATION 9.42 | 120.29 centimeters (cm) STANDARD_DEVIATION 11.51 | 117.65 centimeters (cm) STANDARD_DEVIATION 11.13 | 117.30 centimeters (cm) STANDARD_DEVIATION 14.96 | 119.76 centimeters (cm) STANDARD_DEVIATION 12.36 | 119.43 centimeters (cm) STANDARD_DEVIATION 11.45 | 118.01 centimeters (cm) STANDARD_DEVIATION 11.43 | 118.70 centimeters (cm) STANDARD_DEVIATION 11.83 |
| Waist and Hip Circumference Waist Circumference | 107.42 centimeters (cm) STANDARD_DEVIATION 10.7 | 111.47 centimeters (cm) STANDARD_DEVIATION 12.58 | 107.31 centimeters (cm) STANDARD_DEVIATION 12.06 | 110.18 centimeters (cm) STANDARD_DEVIATION 10.8 | 109.13 centimeters (cm) STANDARD_DEVIATION 14.1 | 109.99 centimeters (cm) STANDARD_DEVIATION 11.49 | 109.15 centimeters (cm) STANDARD_DEVIATION 12.95 | 109.24 centimeters (cm) STANDARD_DEVIATION 12.1 |
| Weight | 97.15 kilograms (kg) STANDARD_DEVIATION 15.67 | 102.25 kilograms (kg) STANDARD_DEVIATION 17.8 | 96.36 kilograms (kg) STANDARD_DEVIATION 18.08 | 99.09 kilograms (kg) STANDARD_DEVIATION 17.73 | 97.92 kilograms (kg) STANDARD_DEVIATION 18.73 | 100.96 kilograms (kg) STANDARD_DEVIATION 17.2 | 100.09 kilograms (kg) STANDARD_DEVIATION 17.11 | 99.10 kilograms (kg) STANDARD_DEVIATION 17.46 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 41 / 49 | 39 / 49 | 38 / 48 | 44 / 49 | 43 / 52 | 46 / 50 | 33 / 46 |
| serious Total, serious adverse events | 0 / 49 | 0 / 49 | 2 / 48 | 2 / 49 | 0 / 52 | 1 / 50 | 2 / 46 |
Outcome results
Primary
Percent Change in Body Weight From Baseline to 24 Week Endpoint
Body weight percentage change from baseline is presented as Least Squares Mean (LSMean) with treatment, visit, and their interaction as fixed effects, subject as a random effect, baseline body weight, age, gender were used as covariates.
Time frame: Baseline, 24 weeks
Population: ITT population: all randomized participants receiving at least 1 dose of the study drug according to the treatment the participants actually received. Participants with baseline and a measurement at endpoint were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change in Body Weight From Baseline to 24 Week Endpoint | -2.21 percent change | Standard Error 0.81 |
| LY377604 (75 mg) | Percent Change in Body Weight From Baseline to 24 Week Endpoint | 0.48 percent change | Standard Error 0.84 |
| Sibutramine (30 mg)/Metoprolol (200 mg) | Percent Change in Body Weight From Baseline to 24 Week Endpoint | -6.12 percent change | Standard Error 0.86 |
| LY377604 (15 mg)/Sibutramine (30 mg) | Percent Change in Body Weight From Baseline to 24 Week Endpoint | -8.53 percent change | Standard Error 0.8 |
| LY377604 (40 mg)/Sibutramine (30 mg) | Percent Change in Body Weight From Baseline to 24 Week Endpoint | -6.61 percent change | Standard Error 0.79 |
| LY377604 (75 mg)/Sibutramine (30 mg) | Percent Change in Body Weight From Baseline to 24 Week Endpoint | -7.05 percent change | Standard Error 0.85 |
| LY377604 (75 mg)/Sibutramine (15 mg) | Percent Change in Body Weight From Baseline to 24 Week Endpoint | -4.71 percent change | Standard Error 0.86 |
Comparison: Hypothesis: Treatment with a combination of LY377604 + sibutramine for 24 weeks would result in weight loss that was significantly greater than treatment with either sibutramine or LY377604 alone.p-value: <0.001Mixed Models Analysis
Comparison: Hypothesis: Treatment with a combination of LY377604 + sibutramine for 24 weeks would result in weight loss that was significantly greater than treatment with either sibutramine or LY377604 alone.p-value: <0.001Mixed Models Analysis
Comparison: Hypothesis: Treatment with a combination of LY377604 + sibutramine for 24 weeks would result in weight loss that was significantly greater than treatment with either sibutramine or LY377604 alone.p-value: <0.001Mixed Models Analysis
Comparison: Hypothesis: Treatment with a combination of LY377604 + sibutramine for 24 weeks would result in weight loss that was significantly greater than treatment with either sibutramine or LY377604 alone.p-value: <0.001Mixed Models Analysis
Comparison: Hypothesis: Treatment with a combination of LY377604 + sibutramine for 24 weeks would result in weight loss that was significantly greater than treatment with either sibutramine or LY377604 alone.p-value: 0.041Mixed Models Analysis
Comparison: Hypothesis: Treatment with a combination of LY377604 + sibutramine for 24 weeks would result in weight loss that was significantly greater than treatment with either sibutramine or LY377604 alone.p-value: 0.668Mixed Models Analysis
Comparison: Hypothesis: Treatment with a combination of LY377604 + sibutramine for 24 weeks would result in weight loss that was significantly greater than treatment with either sibutramine or LY377604 alone.p-value: 0.437Mixed Models Analysis
Comparison: Hypothesis: Treatment with a combination of LY377604 + sibutramine for 24 weeks would result in weight loss that was significantly greater than treatment with either sibutramine or LY377604 alone.p-value: 0.249Mixed Models Analysis
Secondary
Change From Baseline for Obesity Weight Loss Quality of Life Instrument (OWL-QoL)
Results presented as Least Squares Mean with treatment, visit, and their interaction as fixed effects, subject as random effect, baseline body mass index used as covariate. OWL-QoL consists of 17 items on scale ranging from 0 (Not at all) to 6 (A very great deal). Before calculating scores, each item is reversed. A single quality of life score is computed by summing each item and transforming this raw score onto standardized scale of 0 (greatest impact) to 100 (lowest impact) using formula: score = \[(sum of component items score (minus) lowest possible score/ possible raw score range)\*100\].
Time frame: Baseline, 24 weeks
Population: ITT
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline for Obesity Weight Loss Quality of Life Instrument (OWL-QoL) | 11.71 units on a scale | Standard Error 4.93 |
| LY377604 (75 mg) | Change From Baseline for Obesity Weight Loss Quality of Life Instrument (OWL-QoL) | 2.67 units on a scale | Standard Error 5.3 |
| Sibutramine (30 mg)/Metoprolol (200 mg) | Change From Baseline for Obesity Weight Loss Quality of Life Instrument (OWL-QoL) | 13.96 units on a scale | Standard Error 5.26 |
| LY377604 (15 mg)/Sibutramine (30 mg) | Change From Baseline for Obesity Weight Loss Quality of Life Instrument (OWL-QoL) | 16.52 units on a scale | Standard Error 5.27 |
| LY377604 (40 mg)/Sibutramine (30 mg) | Change From Baseline for Obesity Weight Loss Quality of Life Instrument (OWL-QoL) | 17.44 units on a scale | Standard Error 5.17 |
| LY377604 (75 mg)/Sibutramine (30 mg) | Change From Baseline for Obesity Weight Loss Quality of Life Instrument (OWL-QoL) | 13.53 units on a scale | Standard Error 5.35 |
| LY377604 (75 mg)/Sibutramine (15 mg) | Change From Baseline for Obesity Weight Loss Quality of Life Instrument (OWL-QoL) | 14.02 units on a scale | Standard Error 5.23 |
Secondary
Change From Baseline in Vitality Scale of Medical Outcomes Short Form - 36 (SF-36) Scale
Vitality change from baseline is presented as Least Squares Mean (LSMean) with treatment, visit, and their interaction as fixed effects, subject as a random effect, baseline body mass index was used as covariate. SF-36 is a self-reported questionnaire that consists of 36 questions covering 8 health domains including vitality. The vitality domain results are presented. The vitality domain is scored by summing the individual items and transforming the scores into a 0 to 100 scale, with higher scores indicating better health status or functioning.
Time frame: Baseline, 24 weeks
Population: Intent to Treat (IIT) population: all randomized participants who received at least one dose of study drug and received the intended study drug. Participants with baseline and at least one post-baseline measurement were included in the analysis (LOCF).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Vitality Scale of Medical Outcomes Short Form - 36 (SF-36) Scale | 10.79 units on a scale | Standard Error 5.24 |
| LY377604 (75 mg) | Change From Baseline in Vitality Scale of Medical Outcomes Short Form - 36 (SF-36) Scale | 5.83 units on a scale | Standard Error 5.66 |
| Sibutramine (30 mg)/Metoprolol (200 mg) | Change From Baseline in Vitality Scale of Medical Outcomes Short Form - 36 (SF-36) Scale | 16.81 units on a scale | Standard Error 5.63 |
| LY377604 (15 mg)/Sibutramine (30 mg) | Change From Baseline in Vitality Scale of Medical Outcomes Short Form - 36 (SF-36) Scale | 10.69 units on a scale | Standard Error 5.69 |
| LY377604 (40 mg)/Sibutramine (30 mg) | Change From Baseline in Vitality Scale of Medical Outcomes Short Form - 36 (SF-36) Scale | 7.35 units on a scale | Standard Error 5.53 |
| LY377604 (75 mg)/Sibutramine (30 mg) | Change From Baseline in Vitality Scale of Medical Outcomes Short Form - 36 (SF-36) Scale | 10.62 units on a scale | Standard Error 5.72 |
| LY377604 (75 mg)/Sibutramine (15 mg) | Change From Baseline in Vitality Scale of Medical Outcomes Short Form - 36 (SF-36) Scale | 13.61 units on a scale | Standard Error 5.58 |
Secondary
Change in Blood Pressure From Baseline to 24 Week Endpoint
Blood pressure change from baseline is presented as Least Squares Mean (LSMean) with treatment, visit, and their interaction as fixed effects, subject as a random effect, baseline blood pressure, age, gender were used as covariates.
Time frame: Baseline, 24 weeks
Population: ITT
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change in Blood Pressure From Baseline to 24 Week Endpoint | Systolic Blood Pressure | -2.84 mm Hg | Standard Error 1.67 |
| Placebo | Change in Blood Pressure From Baseline to 24 Week Endpoint | Diastolic Blood Pressure | -2.25 mm Hg | Standard Error 1.28 |
| LY377604 (75 mg) | Change in Blood Pressure From Baseline to 24 Week Endpoint | Diastolic Blood Pressure | -3.84 mm Hg | Standard Error 1.35 |
| LY377604 (75 mg) | Change in Blood Pressure From Baseline to 24 Week Endpoint | Systolic Blood Pressure | -3.59 mm Hg | Standard Error 1.75 |
| Sibutramine (30 mg)/Metoprolol (200 mg) | Change in Blood Pressure From Baseline to 24 Week Endpoint | Diastolic Blood Pressure | -2.51 mm Hg | Standard Error 1.41 |
| Sibutramine (30 mg)/Metoprolol (200 mg) | Change in Blood Pressure From Baseline to 24 Week Endpoint | Systolic Blood Pressure | -3.77 mm Hg | Standard Error 1.84 |
| LY377604 (15 mg)/Sibutramine (30 mg) | Change in Blood Pressure From Baseline to 24 Week Endpoint | Systolic Blood Pressure | 3.25 mm Hg | Standard Error 1.76 |
| LY377604 (15 mg)/Sibutramine (30 mg) | Change in Blood Pressure From Baseline to 24 Week Endpoint | Diastolic Blood Pressure | 2.03 mm Hg | Standard Error 1.34 |
| LY377604 (40 mg)/Sibutramine (30 mg) | Change in Blood Pressure From Baseline to 24 Week Endpoint | Diastolic Blood Pressure | 0.13 mm Hg | Standard Error 1.22 |
| LY377604 (40 mg)/Sibutramine (30 mg) | Change in Blood Pressure From Baseline to 24 Week Endpoint | Systolic Blood Pressure | -1.17 mm Hg | Standard Error 1.59 |
| LY377604 (75 mg)/Sibutramine (30 mg) | Change in Blood Pressure From Baseline to 24 Week Endpoint | Diastolic Blood Pressure | -2.87 mm Hg | Standard Error 1.45 |
| LY377604 (75 mg)/Sibutramine (30 mg) | Change in Blood Pressure From Baseline to 24 Week Endpoint | Systolic Blood Pressure | -0.43 mm Hg | Standard Error 1.9 |
| LY377604 (75 mg)/Sibutramine (15 mg) | Change in Blood Pressure From Baseline to 24 Week Endpoint | Systolic Blood Pressure | 0.95 mm Hg | Standard Error 1.8 |
| LY377604 (75 mg)/Sibutramine (15 mg) | Change in Blood Pressure From Baseline to 24 Week Endpoint | Diastolic Blood Pressure | -0.38 mm Hg | Standard Error 1.38 |
Secondary
Change in Body Composition Using Dual Energy X-ray Absorptiometry (DXA) From Baseline to 24 Week Endpoint
Change in body composition (lean body mass and fat mass) was assessed using dual energy x-ray absorptiometry (DXA) and is presented as LSMEAN values with treatment, visit, and their interaction as fixed effects, subject as a random effect, baseline body composition, age, gender were used as covariates.
Time frame: Baseline, 24 weeks
Population: ITT population: all randomized participants receiving at least 1 dose of the study drug according to the treatment the participants actually received. Participants with baseline and a measurement at endpoint were included in the analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change in Body Composition Using Dual Energy X-ray Absorptiometry (DXA) From Baseline to 24 Week Endpoint | Lean Mass | -0.55 kilograms (kg) | Standard Error 0.41 |
| Placebo | Change in Body Composition Using Dual Energy X-ray Absorptiometry (DXA) From Baseline to 24 Week Endpoint | Fat Mass | -2.40 kilograms (kg) | Standard Error 0.72 |
| LY377604 (75 mg) | Change in Body Composition Using Dual Energy X-ray Absorptiometry (DXA) From Baseline to 24 Week Endpoint | Lean Mass | 0.15 kilograms (kg) | Standard Error 0.45 |
| LY377604 (75 mg) | Change in Body Composition Using Dual Energy X-ray Absorptiometry (DXA) From Baseline to 24 Week Endpoint | Fat Mass | 0.54 kilograms (kg) | Standard Error 0.76 |
| Sibutramine (30 mg)/Metoprolol (200 mg) | Change in Body Composition Using Dual Energy X-ray Absorptiometry (DXA) From Baseline to 24 Week Endpoint | Lean Mass | -1.92 kilograms (kg) | Standard Error 0.45 |
| Sibutramine (30 mg)/Metoprolol (200 mg) | Change in Body Composition Using Dual Energy X-ray Absorptiometry (DXA) From Baseline to 24 Week Endpoint | Fat Mass | -3.00 kilograms (kg) | Standard Error 0.75 |
| LY377604 (15 mg)/Sibutramine (30 mg) | Change in Body Composition Using Dual Energy X-ray Absorptiometry (DXA) From Baseline to 24 Week Endpoint | Lean Mass | -1.85 kilograms (kg) | Standard Error 0.43 |
| LY377604 (15 mg)/Sibutramine (30 mg) | Change in Body Composition Using Dual Energy X-ray Absorptiometry (DXA) From Baseline to 24 Week Endpoint | Fat Mass | -6.13 kilograms (kg) | Standard Error 0.71 |
| LY377604 (40 mg)/Sibutramine (30 mg) | Change in Body Composition Using Dual Energy X-ray Absorptiometry (DXA) From Baseline to 24 Week Endpoint | Fat Mass | -4.80 kilograms (kg) | Standard Error 0.67 |
| LY377604 (40 mg)/Sibutramine (30 mg) | Change in Body Composition Using Dual Energy X-ray Absorptiometry (DXA) From Baseline to 24 Week Endpoint | Lean Mass | -0.71 kilograms (kg) | Standard Error 0.39 |
| LY377604 (75 mg)/Sibutramine (30 mg) | Change in Body Composition Using Dual Energy X-ray Absorptiometry (DXA) From Baseline to 24 Week Endpoint | Fat Mass | -4.29 kilograms (kg) | Standard Error 0.77 |
| LY377604 (75 mg)/Sibutramine (30 mg) | Change in Body Composition Using Dual Energy X-ray Absorptiometry (DXA) From Baseline to 24 Week Endpoint | Lean Mass | -1.08 kilograms (kg) | Standard Error 0.47 |
| LY377604 (75 mg)/Sibutramine (15 mg) | Change in Body Composition Using Dual Energy X-ray Absorptiometry (DXA) From Baseline to 24 Week Endpoint | Lean Mass | -1.48 kilograms (kg) | Standard Error 0.43 |
| LY377604 (75 mg)/Sibutramine (15 mg) | Change in Body Composition Using Dual Energy X-ray Absorptiometry (DXA) From Baseline to 24 Week Endpoint | Fat Mass | -2.55 kilograms (kg) | Standard Error 0.73 |
Secondary
Change in Fasting Glucose From Baseline to 24 Weeks Endpoint
Analysis of change in fasting glucose was not conducted due to an inadequate number of samples.
Time frame: Baseline, 24 weeks
Population: Zero participants were analyzed due to an inadequate number of samples.
Secondary
Change in Fasting Insulin From Baseline to 24 Weeks Endpoint
Analysis of change in fasting insulin was not conducted due to an inadequate number of samples.
Time frame: Baseline, 24 weeks
Population: Zero participants were analyzed due to an inadequate number of samples.
Secondary
Change in Glycated Hemoglobin A1c (HbA1c) From Baseline
Analysis of change in HbA1c was not conducted due to an inadequate number of samples.
Time frame: Baseline, 24 weeks
Population: Zero participants were analyzed due to the small sample size.
Secondary
Change in Heart Rate From Baseline to 24 Week Endpoint
Heart rate change from baseline is presented as Least Squares Mean (LSMean) with treatment, visit, and their interaction as fixed effects, subject as a random effect, baseline heart rate, age, gender were used as covariates.
Time frame: Baseline, 24 weeks
Population: ITT population: all randomized participants receiving at least 1 dose of the study drug according to the treatment the participants actually received. Participants with baseline and a measurement at endpoint were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Heart Rate From Baseline to 24 Week Endpoint | -0.69 beats per minute (bpm) | Standard Error 1.51 |
| LY377604 (75 mg) | Change in Heart Rate From Baseline to 24 Week Endpoint | -3.34 beats per minute (bpm) | Standard Error 1.6 |
| Sibutramine (30 mg)/Metoprolol (200 mg) | Change in Heart Rate From Baseline to 24 Week Endpoint | -1.37 beats per minute (bpm) | Standard Error 1.67 |
| LY377604 (15 mg)/Sibutramine (30 mg) | Change in Heart Rate From Baseline to 24 Week Endpoint | 6.11 beats per minute (bpm) | Standard Error 1.6 |
| LY377604 (40 mg)/Sibutramine (30 mg) | Change in Heart Rate From Baseline to 24 Week Endpoint | 2.19 beats per minute (bpm) | Standard Error 1.44 |
| LY377604 (75 mg)/Sibutramine (30 mg) | Change in Heart Rate From Baseline to 24 Week Endpoint | -2.66 beats per minute (bpm) | Standard Error 1.72 |
| LY377604 (75 mg)/Sibutramine (15 mg) | Change in Heart Rate From Baseline to 24 Week Endpoint | -2.46 beats per minute (bpm) | Standard Error 1.63 |
Secondary
Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to 24 Weeks Endpoint
Time frame: Baseline, 24 weeks
Population: Intent to Treat (IIT) population: all randomized participants who received at least one dose of study drug and received the intended study drug. Participants with baseline and at least one post-baseline measurement were included in the analysis (LOCF).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to 24 Weeks Endpoint | -0.02 millimole/Liter (mmol/L) | Standard Deviation 0.16 |
| LY377604 (75 mg) | Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to 24 Weeks Endpoint | -0.05 millimole/Liter (mmol/L) | Standard Deviation 0.19 |
| Sibutramine (30 mg)/Metoprolol (200 mg) | Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to 24 Weeks Endpoint | -0.03 millimole/Liter (mmol/L) | Standard Deviation 0.15 |
| LY377604 (15 mg)/Sibutramine (30 mg) | Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to 24 Weeks Endpoint | 0.01 millimole/Liter (mmol/L) | Standard Deviation 0.15 |
| LY377604 (40 mg)/Sibutramine (30 mg) | Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to 24 Weeks Endpoint | 0.06 millimole/Liter (mmol/L) | Standard Deviation 0.21 |
| LY377604 (75 mg)/Sibutramine (30 mg) | Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to 24 Weeks Endpoint | 0.01 millimole/Liter (mmol/L) | Standard Deviation 0.17 |
| LY377604 (75 mg)/Sibutramine (15 mg) | Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to 24 Weeks Endpoint | -0.04 millimole/Liter (mmol/L) | Standard Deviation 0.17 |
Secondary
Change in Insulin Resistance From Baseline to 24 Weeks Endpoint
Analysis of change in insulin resistance was not conducted due to an inadequate number of samples.
Time frame: Baseline, 24 weeks
Population: Zero participants were analyzed due to inadequate number of samples.
Secondary
Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline to 24 Weeks Endpoint
Time frame: Baseline, 24 weeks
Population: Intent to Treat (IIT) population: all randomized participants who received at least one dose of study drug and received the intended study drug. Participants with baseline and at least one post-baseline measurement were included in the analysis (LOCF).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline to 24 Weeks Endpoint | -0.07 millimole/Liter (mmol/L) | Standard Deviation 0.57 |
| LY377604 (75 mg) | Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline to 24 Weeks Endpoint | -0.03 millimole/Liter (mmol/L) | Standard Deviation 0.44 |
| Sibutramine (30 mg)/Metoprolol (200 mg) | Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline to 24 Weeks Endpoint | 0.00 millimole/Liter (mmol/L) | Standard Deviation 0.62 |
| LY377604 (15 mg)/Sibutramine (30 mg) | Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline to 24 Weeks Endpoint | -0.00 millimole/Liter (mmol/L) | Standard Deviation 0.58 |
| LY377604 (40 mg)/Sibutramine (30 mg) | Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline to 24 Weeks Endpoint | -0.07 millimole/Liter (mmol/L) | Standard Deviation 0.5 |
| LY377604 (75 mg)/Sibutramine (30 mg) | Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline to 24 Weeks Endpoint | 0.16 millimole/Liter (mmol/L) | Standard Deviation 0.65 |
| LY377604 (75 mg)/Sibutramine (15 mg) | Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline to 24 Weeks Endpoint | -0.16 millimole/Liter (mmol/L) | Standard Deviation 0.67 |
Secondary
Change in Total Cholesterol From Baseline to 24 Weeks Endpoint
Time frame: Baseline, 24 weeks
Population: Intent to Treat (IIT) population: all randomized participants who received at least one dose of study drug and received the intended study drug. Participants with baseline and at least one post-baseline measurement were included in the analysis (LOCF).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Total Cholesterol From Baseline to 24 Weeks Endpoint | -0.12 millimole/Liter (mmol/L) | Standard Deviation 0.68 |
| LY377604 (75 mg) | Change in Total Cholesterol From Baseline to 24 Weeks Endpoint | -0.13 millimole/Liter (mmol/L) | Standard Deviation 0.47 |
| Sibutramine (30 mg)/Metoprolol (200 mg) | Change in Total Cholesterol From Baseline to 24 Weeks Endpoint | -0.04 millimole/Liter (mmol/L) | Standard Deviation 0.69 |
| LY377604 (15 mg)/Sibutramine (30 mg) | Change in Total Cholesterol From Baseline to 24 Weeks Endpoint | -0.01 millimole/Liter (mmol/L) | Standard Deviation 0.67 |
| LY377604 (40 mg)/Sibutramine (30 mg) | Change in Total Cholesterol From Baseline to 24 Weeks Endpoint | 0.00 millimole/Liter (mmol/L) | Standard Deviation 0.68 |
| LY377604 (75 mg)/Sibutramine (30 mg) | Change in Total Cholesterol From Baseline to 24 Weeks Endpoint | 0.17 millimole/Liter (mmol/L) | Standard Deviation 0.7 |
| LY377604 (75 mg)/Sibutramine (15 mg) | Change in Total Cholesterol From Baseline to 24 Weeks Endpoint | -0.13 millimole/Liter (mmol/L) | Standard Deviation 0.76 |
Secondary
Change in Triglycerides From Baseline to 24 Weeks Endpoint
Time frame: Baseline, 24 weeks
Population: Intent to Treat (IIT) population: all randomized participants who received at least one dose of study drug and received the intended study drug. Participants with baseline and at least one post-baseline measurement were included in the analysis (LOCF).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Triglycerides From Baseline to 24 Weeks Endpoint | -0.06 millimole/Liter (mmol/L) | Standard Deviation 0.61 |
| LY377604 (75 mg) | Change in Triglycerides From Baseline to 24 Weeks Endpoint | -0.11 millimole/Liter (mmol/L) | Standard Deviation 0.48 |
| Sibutramine (30 mg)/Metoprolol (200 mg) | Change in Triglycerides From Baseline to 24 Weeks Endpoint | -0.04 millimole/Liter (mmol/L) | Standard Deviation 0.66 |
| LY377604 (15 mg)/Sibutramine (30 mg) | Change in Triglycerides From Baseline to 24 Weeks Endpoint | 0.04 millimole/Liter (mmol/L) | Standard Deviation 0.6 |
| LY377604 (40 mg)/Sibutramine (30 mg) | Change in Triglycerides From Baseline to 24 Weeks Endpoint | 0.04 millimole/Liter (mmol/L) | Standard Deviation 0.55 |
| LY377604 (75 mg)/Sibutramine (30 mg) | Change in Triglycerides From Baseline to 24 Weeks Endpoint | 0.03 millimole/Liter (mmol/L) | Standard Deviation 0.72 |
| LY377604 (75 mg)/Sibutramine (15 mg) | Change in Triglycerides From Baseline to 24 Weeks Endpoint | 0.22 millimole/Liter (mmol/L) | Standard Deviation 0.94 |
Secondary
Change in Waist Circumference From Baseline to 24 Week Endpoint
Change from baseline to endpoint is presented as LSMEAN with treatment, visit, and their interaction as fixed effects, subject as a random effect, baseline waist circumference, age, gender were used as covariates.
Time frame: Baseline, 24 weeks
Population: ITT population: all randomized participants receiving at least 1 dose of the study drug according to the treatment the participants actually received. Participants with baseline and a measurement at endpoint were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Waist Circumference From Baseline to 24 Week Endpoint | -6.58 centimeter (cm) | Standard Error 2.44 |
| LY377604 (75 mg) | Change in Waist Circumference From Baseline to 24 Week Endpoint | -2.51 centimeter (cm) | Standard Error 2.62 |
| Sibutramine (30 mg)/Metoprolol (200 mg) | Change in Waist Circumference From Baseline to 24 Week Endpoint | -8.84 centimeter (cm) | Standard Error 2.77 |
| LY377604 (15 mg)/Sibutramine (30 mg) | Change in Waist Circumference From Baseline to 24 Week Endpoint | -6.76 centimeter (cm) | Standard Error 2.71 |
| LY377604 (40 mg)/Sibutramine (30 mg) | Change in Waist Circumference From Baseline to 24 Week Endpoint | -3.57 centimeter (cm) | Standard Error 2.38 |
| LY377604 (75 mg)/Sibutramine (30 mg) | Change in Waist Circumference From Baseline to 24 Week Endpoint | -3.55 centimeter (cm) | Standard Error 2.88 |
| LY377604 (75 mg)/Sibutramine (15 mg) | Change in Waist Circumference From Baseline to 24 Week Endpoint | -8.67 centimeter (cm) | Standard Error 2.68 |
Secondary
Percentage Change in Waist Circumference From Baseline to 24 Week Endpoint
Percentage change from baseline to endpoint is presented as LSMEAN with treatment, visit, and their interaction as fixed effects, subject as a random effect, baseline waist circumference, age, gender were used as covariates.
Time frame: Baseline, 24 weeks
Population: ITT
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percentage Change in Waist Circumference From Baseline to 24 Week Endpoint | -5.86 percent change | Standard Deviation 2.21 |
| LY377604 (75 mg) | Percentage Change in Waist Circumference From Baseline to 24 Week Endpoint | -2.22 percent change | Standard Deviation 2.38 |
| Sibutramine (30 mg)/Metoprolol (200 mg) | Percentage Change in Waist Circumference From Baseline to 24 Week Endpoint | -7.55 percent change | Standard Deviation 2.52 |
| LY377604 (15 mg)/Sibutramine (30 mg) | Percentage Change in Waist Circumference From Baseline to 24 Week Endpoint | -5.96 percent change | Standard Deviation 2.46 |
| LY377604 (40 mg)/Sibutramine (30 mg) | Percentage Change in Waist Circumference From Baseline to 24 Week Endpoint | -3.02 percent change | Standard Deviation 2.16 |
| LY377604 (75 mg)/Sibutramine (30 mg) | Percentage Change in Waist Circumference From Baseline to 24 Week Endpoint | -3.11 percent change | Standard Deviation 2.62 |
| LY377604 (75 mg)/Sibutramine (15 mg) | Percentage Change in Waist Circumference From Baseline to 24 Week Endpoint | -7.29 percent change | Standard Deviation 2.44 |
Secondary
Percentage of Participants Who Achieve a Minimum of 10% Weight Loss From Baseline at 24 Weeks
Time frame: 24 weeks
Population: ITT population: all randomized participants receiving at least 1 dose of the study drug according to the treatment the participants actually received. Participants with baseline and a measurement at endpoint were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Who Achieve a Minimum of 10% Weight Loss From Baseline at 24 Weeks | 10.2 percentage of participants |
| LY377604 (75 mg) | Percentage of Participants Who Achieve a Minimum of 10% Weight Loss From Baseline at 24 Weeks | 0.0 percentage of participants |
| Sibutramine (30 mg)/Metoprolol (200 mg) | Percentage of Participants Who Achieve a Minimum of 10% Weight Loss From Baseline at 24 Weeks | 18.8 percentage of participants |
| LY377604 (15 mg)/Sibutramine (30 mg) | Percentage of Participants Who Achieve a Minimum of 10% Weight Loss From Baseline at 24 Weeks | 34.7 percentage of participants |
| LY377604 (40 mg)/Sibutramine (30 mg) | Percentage of Participants Who Achieve a Minimum of 10% Weight Loss From Baseline at 24 Weeks | 21.2 percentage of participants |
| LY377604 (75 mg)/Sibutramine (30 mg) | Percentage of Participants Who Achieve a Minimum of 10% Weight Loss From Baseline at 24 Weeks | 18.0 percentage of participants |
| LY377604 (75 mg)/Sibutramine (15 mg) | Percentage of Participants Who Achieve a Minimum of 10% Weight Loss From Baseline at 24 Weeks | 6.5 percentage of participants |
Secondary
Pharmacokinetics: Area Under the Concentration Time Curve (AUC)
Analysis of AUC was not conducted due to an inadequate number of samples collected.
Time frame: 4 weeks, 12 weeks, and 24 weeks
Population: Zero participants were analyzed because of the low sample size.
Secondary
Pharmacokinetics: Maximum Concentration (Cmax)
Analysis of Cmax was not conducted due to an inadequate number of samples collected.
Time frame: 4 weeks, 12 weeks, and 24 weeks
Population: Zero participants were analyzed due to the small sample size.
Secondary
The Mean Change in Body Weight From Baseline to 24 Week Endpoint
Body weight change from baseline is presented as Least Squares Mean (LSMean) with treatment, visit, and their interaction as fixed effects, subject as a random effect, baseline body weight, age, gender were used as covariates.
Time frame: Baseline, 24 weeks
Population: ITT population: all randomized participants receiving at least 1 dose of the study drug according to the treatment the participants actually received. Participants with baseline and a measurement at endpoint were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | The Mean Change in Body Weight From Baseline to 24 Week Endpoint | -2.37 kilograms | Standard Error 0.82 |
| LY377604 (75 mg) | The Mean Change in Body Weight From Baseline to 24 Week Endpoint | 0.45 kilograms | Standard Error 0.85 |
| Sibutramine (30 mg)/Metoprolol (200 mg) | The Mean Change in Body Weight From Baseline to 24 Week Endpoint | -6.41 kilograms | Standard Error 0.87 |
| LY377604 (15 mg)/Sibutramine (30 mg) | The Mean Change in Body Weight From Baseline to 24 Week Endpoint | -8.15 kilograms | Standard Error 0.81 |
| LY377604 (40 mg)/Sibutramine (30 mg) | The Mean Change in Body Weight From Baseline to 24 Week Endpoint | -6.49 kilograms | Standard Error 0.79 |
| LY377604 (75 mg)/Sibutramine (30 mg) | The Mean Change in Body Weight From Baseline to 24 Week Endpoint | -7.06 kilograms | Standard Error 0.85 |
| LY377604 (75 mg)/Sibutramine (15 mg) | The Mean Change in Body Weight From Baseline to 24 Week Endpoint | -4.68 kilograms | Standard Error 0.87 |