A Weight Loss Study in Overweight Men and Women | NCT00993421

ID	Type	Description	Link
I1L-MC-GAEB	Other Identifier	Eli Lilly and Company

Label	Type	Intervention Names
placebo	Placebo Comparator	Drug: Placebo sibutramine Drug: Placebo Metoprolol Drug: Placebo LY377604
LY377604 (75 mg)	Experimental	Drug: LY377604 Drug: Placebo sibutramine Drug: Placebo Metoprolol
sibutramine (30 mg)/metoprolol (200 mg)	Active Comparator	Drug: Sibutramine Drug: Metoprolol
LY377604 (40 mg)/sibutramine (30 mg)	Experimental	Drug: LY377604 Drug: Sibutramine Drug: Placebo Metoprolol
LY377604 (75 mg)/sibutramine (30 mg)	Experimental	Drug: LY377604 Drug: Sibutramine Drug: Placebo Metoprolol
LY377604 (15 mg)/sibutramine (30 mg)	Experimental	Drug: LY377604 Drug: Sibutramine Drug: Placebo Metoprolol
LY377604 (75 mg)/sibutramine (15 mg)

Name	Type	Description	Arm Group Labels	Other Names
LY377604	Drug	Given daily, orally for 24 weeks	LY377604 (15 mg)/sibutramine (30 mg) LY377604 (40 mg)/sibutramine (30 mg) LY377604 (75 mg)

Measure	Description	Time Frame
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.	Baseline, 24 weeks

Measure	Description	Time Frame
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.	Baseline, 24 weeks

Eligibility Module

Eligibility Criteria

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).

Name	Affiliation	Role
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon-Fri 9 AM-5 PM Eastern time (UTC/GMT-5 hours, EST)	Eli Lilly and Company	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.		Mesa	Arizona	85201

ID	Title	Description
FG000	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.
FG001	LY377604 (75 mg)

Arm/Group Information

ID	Title	Description
BG000	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.
BG001	LY377604 (75 mg)	Given orally, daily for 24 weeks.
BG002	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.
BG003	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.
BG004	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.
BG005	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.
BG006	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.
BG007	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00042.71± 10.86 BG00143.89± 11.02 BG00244.68± 12.00 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00041 BG00142 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG002

Region of Enrollment

Number

participants

Title

Denominators

Categories

United States

Title	Measurements
	BG00049 BG00149 BG002

Height

Mean

Standard Deviation

centimeters (cm)

Title

Denominators

Categories

Title	Measurements
	BG000166.10± 8.02 BG001166.86± 8.40 BG002

Weight

Mean

Standard Deviation

kilograms (kg)

Title

Denominators

Categories

Title	Measurements
	BG00097.92± 18.73 BG00197.15± 15.67 BG002

Body Mass Index (BMI)

Body mass index is an estimate of body fat based on body weight (kilograms) divided by height (meters) squared.

Mean

Standard Deviation

kilograms/square meters (kg/m^2)

Title

Denominators

Categories

Title	Measurements
	BG00035.22± 4.96 BG00134.78

Blood Pressure

Mean

Standard Deviation

mm Hg

Title

Denominators

Categories

Systolic Blood Pressure (SBP)

Title	Measurements
	BG000117.11± 11.53 BG001115.72± 10.78 BG002

Waist and Hip Circumference

Mean

Standard Deviation

centimeters (cm)

Title

Denominators

Categories

Waist Circumference

Title	Measurements
	BG000109.13± 14.10 BG001107.42± 10.70 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

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.

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.

Posted

Least Squares Mean

Standard Error

percent change

Baseline, 24 weeks

ID	Title	Description
OG000	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.
OG001	LY377604 (75 mg)	Given orally, daily for 24 weeks.
OG002	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.
OG003	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.
OG004	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.
OG005	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.
OG006	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.

Units	Counts
Participants	OG00028 OG00126 OG00224 OG003

Title

Denominators

Categories

Title	Measurements
	OG000-2.21± 0.81 OG0010.48± 0.84 OG002-6.12± 0.86 OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG001 OG003	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.	Mixed Models Analysis		<0.001							95						No	Superiority or Other
OG001 OG004	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.

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.

Posted

Least Squares Mean

Standard Error

kilograms

Baseline, 24 weeks

ID	Title	Description
OG000	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.
OG001	LY377604 (75 mg)	Given orally, daily for 24 weeks.
OG002	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.

Secondary

Percentage of Participants Who Achieve a Minimum of 10% Weight Loss From Baseline at 24 Weeks

Posted

Number

percentage of participants

24 weeks

ID	Title	Description
OG000	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.
OG001	LY377604 (75 mg)	Given orally, daily for 24 weeks.
OG002	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.
OG003	LY377604 (15 mg)/Sibutramine (30 mg)

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.

Posted

Least Squares Mean

Standard Error

beats per minute (bpm)

Baseline, 24 weeks

ID	Title	Description
OG000	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.
OG001	LY377604 (75 mg)	Given orally, daily for 24 weeks.
OG002	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.

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.

ITT

Posted

Least Squares Mean

Standard Error

mm Hg

Baseline, 24 weeks

ID	Title	Description
OG000	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.
OG001	LY377604 (75 mg)	Given orally, daily for 24 weeks.
OG002	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.
OG003

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.

Posted

Least Squares Mean

Standard Error

kilograms (kg)

Baseline, 24 weeks

ID	Title	Description
OG000	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.
OG001	LY377604 (75 mg)	Given orally, daily for 24 weeks.
OG002	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.

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.

Posted

Least Squares Mean

Standard Error

centimeter (cm)

Baseline, 24 weeks

ID	Title	Description
OG000	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.
OG001	LY377604 (75 mg)	Given orally, daily for 24 weeks.
OG002	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.

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.

ITT

Posted

Least Squares Mean

Standard Deviation

percent change

Baseline, 24 weeks

ID	Title	Description
OG000	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.
OG001	LY377604 (75 mg)	Given orally, daily for 24 weeks.
OG002	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.
OG003

Secondary

Change in Total Cholesterol From Baseline to 24 Weeks Endpoint

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).

Posted

Mean

Standard Deviation

millimole/Liter (mmol/L)

Baseline, 24 weeks

ID	Title	Description
OG000	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.
OG001	LY377604 (75 mg)	Given orally, daily for 24 weeks.
OG002	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.
OG003	LY377604 (15 mg)/Sibutramine (30 mg)

Secondary

Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to 24 Weeks Endpoint

Posted

Mean

Standard Deviation

millimole/Liter (mmol/L)

Baseline, 24 weeks

ID	Title	Description
OG000	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.
OG001	LY377604 (75 mg)	Given orally, daily for 24 weeks.
OG002	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.
OG003

Secondary

Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline to 24 Weeks Endpoint

Posted

Mean

Standard Deviation

millimole/Liter (mmol/L)

Baseline, 24 weeks

ID	Title	Description
OG000	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.
OG001	LY377604 (75 mg)	Given orally, daily for 24 weeks.
OG002	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.
OG003

Secondary

Change in Triglycerides From Baseline to 24 Weeks Endpoint

Posted

Mean

Standard Deviation

millimole/Liter (mmol/L)

Baseline, 24 weeks

ID	Title	Description
OG000	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.
OG001	LY377604 (75 mg)	Given orally, daily for 24 weeks.
OG002	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.
OG003	LY377604 (15 mg)/Sibutramine (30 mg)

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].

ITT

Posted

Least Squares Mean

Standard Error

units on a scale

Baseline, 24 weeks

ID	Title	Description
OG000	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.
OG001	LY377604 (75 mg)	Given orally, daily for 24 weeks.
OG002	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.

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.

Posted

Least Squares Mean

Standard Error

units on a scale

Baseline, 24 weeks

ID	Title	Description
OG000	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.
OG001	LY377604 (75 mg)	Given orally, daily for 24 weeks.
OG002	Sibutramine (30 mg)/Metoprolol (200 mg)

Secondary

Change in Glycated Hemoglobin A1c (HbA1c) From Baseline

Analysis of change in HbA1c was not conducted due to an inadequate number of samples.

Zero participants were analyzed due to the small sample size.

Posted

Mean

Standard Deviation

percent glycated hemoglobin

Baseline, 24 weeks

ID	Title	Description
OG000	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.
OG001	LY377604 (75 mg)	Given orally, daily for 24 weeks.
OG002	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.
OG003	LY377604 (15 mg)/Sibutramine (30 mg)

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.

Zero participants were analyzed due to an inadequate number of samples.

Posted

Mean

Standard Deviation

millimoles per Liter (mmol/L)

Baseline, 24 weeks

ID	Title	Description
OG000	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.
OG001	LY377604 (75 mg)	Given orally, daily for 24 weeks.
OG002	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.
OG003	LY377604 (15 mg)/Sibutramine (30 mg)

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.

Zero participants were analyzed due to an inadequate number of samples.

Posted

Mean

Standard Deviation

micro Units/milliliter (μU/mL)

Baseline, 24 weeks

ID	Title	Description
OG000	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.
OG001	LY377604 (75 mg)	Given orally, daily for 24 weeks.
OG002	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.
OG003	LY377604 (15 mg)/Sibutramine (30 mg)

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.

Zero participants were analyzed due to inadequate number of samples.

Posted

Mean

Standard Deviation

Units of Insulin/Day

Baseline, 24 weeks

ID	Title	Description
OG000	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.
OG001	LY377604 (75 mg)	Given orally, daily for 24 weeks.
OG002	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.
OG003	LY377604 (15 mg)/Sibutramine (30 mg)

Secondary

Pharmacokinetics: Area Under the Concentration Time Curve (AUC)

Analysis of AUC was not conducted due to an inadequate number of samples collected.

Zero participants were analyzed because of the low sample size.

Posted

Geometric Mean

Standard Error

nanograms*hour per milliliter (ng*hr/mL)

4 weeks, 12 weeks, and 24 weeks

ID	Title	Description
OG000	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.
OG001	LY377604 (75 mg)	Given orally, daily for 24 weeks.
OG002	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.
OG003	LY377604 (15 mg)/Sibutramine (30 mg)

Secondary

Pharmacokinetics: Maximum Concentration (Cmax)

Analysis of Cmax was not conducted due to an inadequate number of samples collected.

Zero participants were analyzed due to the small sample size.

Posted

Geometric Mean

Standard Error

nanograms per milliliter (ng/mL)

4 weeks, 12 weeks, and 24 weeks

ID	Title	Description
OG000	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.
OG001	LY377604 (75 mg)	Given orally, daily for 24 weeks.
OG002	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.
OG003	LY377604 (15 mg)/Sibutramine (30 mg)

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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.	0	49	41	49
EG001	LY377604 (75 mg)	Given orally, daily for 24 weeks.	0	49	39	49
EG002	Sibutramine (30mg)/Metoprolol (200mg)	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 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.	2	48	38	48
EG003	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, followed by 2 week taper.	2	49	44	49
EG004	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.	0	52	43	52
EG005	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.	1	50	46	50
EG006	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.	2	46	33	46

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Haemorrhoids	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment		EG0000 events0 affected49 at risk EG0010 events0 affected49 at risk EG0021 events1 affected48 at risk EG0030 events0 affected49 at risk EG0040 events0 affected52 at risk EG0050 events0 affected50 at risk EG0060 events0 affected46 at risk
Vomiting	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment		EG0000 events0 affected49 at risk EG0010 events0 affected49 at risk EG0020 events0 affected48 at risk EG003
Cholecystitis	Hepatobiliary disorders	MedDRA 13.0	Systematic Assessment		EG0000 events0 affected49 at risk EG0010 events0 affected49 at risk EG0020 events0 affected48 at risk EG003
Meningitis viral	Infections and infestations	MedDRA 13.0	Systematic Assessment		EG0000 events0 affected49 at risk EG0010 events0 affected49 at risk EG0021 events1 affected48 at risk EG003
Head injury	Injury, poisoning and procedural complications	MedDRA 13.0	Systematic Assessment	This event (result of automobile accident) resulted in death.	EG0000 events0 affected49 at risk EG0010 events0 affected49 at risk EG0020 events0 affected48 at risk EG003
Blood pressure decreased	Investigations	MedDRA 13.0	Systematic Assessment		EG0000 events0 affected49 at risk EG0010 events0 affected49 at risk EG0020 events0 affected48 at risk EG003
Paraesthesia	Nervous system disorders	MedDRA 13.0	Systematic Assessment		EG0000 events0 affected49 at risk EG0010 events0 affected49 at risk EG0020 events0 affected48 at risk EG003
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment		EG0000 events0 affected49 at risk EG0010 events0 affected49 at risk EG0020 events0 affected48 at risk EG003
Hypoaesthesia facial	Skin and subcutaneous tissue disorders	MedDRA 13.0	Systematic Assessment		EG0000 events0 affected49 at risk EG0010 events0 affected49 at risk EG0020 events0 affected48 at risk EG003
Deep vein thrombosis	Vascular disorders	MedDRA 13.0	Systematic Assessment		EG0000 events0 affected49 at risk EG0010 events0 affected49 at risk EG0020 events0 affected48 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Vision blurred	Eye disorders	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected49 at risk EG0011 events1 affected49 at risk EG0021 events1 affected48 at risk EG0030 events0 affected49 at risk EG0041 events1 affected52 at risk EG0050 events0 affected50 at risk EG0063 events3 affected46 at risk
Abdominal discomfort	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0002 events2 affected49 at risk EG0012 events2 affected49 at risk EG0020 events0 affected48 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0004 events4 affected49 at risk EG0012 events2 affected49 at risk EG00211 events11 affected48 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0002 events2 affected49 at risk EG0013 events3 affected49 at risk EG0021 events1 affected48 at risk EG003
Dry mouth	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0001 events1 affected49 at risk EG0014 events4 affected49 at risk EG0026 events6 affected48 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0005 events3 affected49 at risk EG0010 events0 affected49 at risk EG0023 events3 affected48 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0005 events5 affected49 at risk EG0010 events0 affected49 at risk EG0021 events1 affected48 at risk EG003
Asthenia	General disorders	MedDRA 13.0	Systematic Assessment	EG0001 events1 affected49 at risk EG0010 events0 affected49 at risk EG0021 events1 affected48 at risk EG003
Fatigue	General disorders	MedDRA 13.0	Systematic Assessment	EG0002 events2 affected49 at risk EG0015 events5 affected49 at risk EG0022 events2 affected48 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0005 events5 affected49 at risk EG0015 events5 affected49 at risk EG0022 events2 affected48 at risk EG003
Sinusitis	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0003 events2 affected49 at risk EG0012 events2 affected49 at risk EG0022 events2 affected48 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0005 events5 affected49 at risk EG0019 events6 affected49 at risk EG0024 events4 affected48 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0003 events3 affected49 at risk EG0012 events2 affected49 at risk EG0023 events3 affected48 at risk EG003
Viral infection	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0001 events1 affected49 at risk EG0012 events1 affected49 at risk EG0021 events1 affected48 at risk EG003
Muscle strain	Injury, poisoning and procedural complications	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected49 at risk EG0010 events0 affected49 at risk EG0020 events0 affected48 at risk EG003
Blood creatine phosphokinase increased	Investigations	MedDRA 13.0	Systematic Assessment	EG0002 events2 affected49 at risk EG0011 events1 affected49 at risk EG0020 events0 affected48 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA 13.0	Systematic Assessment	EG0001 events1 affected49 at risk EG0011 events1 affected49 at risk EG0021 events1 affected48 at risk EG003
Increased appetite	Metabolism and nutrition disorders	MedDRA 13.0	Systematic Assessment	EG0001 events1 affected49 at risk EG0013 events3 affected49 at risk EG0020 events0 affected48 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Systematic Assessment	EG0001 events1 affected49 at risk EG0014 events4 affected49 at risk EG0023 events3 affected48 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Systematic Assessment	EG0001 events1 affected49 at risk EG0010 events0 affected49 at risk EG0023 events3 affected48 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Systematic Assessment	EG0004 events4 affected49 at risk EG0011 events1 affected49 at risk EG0021 events1 affected48 at risk EG003
Dizziness	Nervous system disorders	MedDRA 13.0	Systematic Assessment	EG0002 events2 affected49 at risk EG0013 events3 affected49 at risk EG0024 events4 affected48 at risk EG003
Dysgeusia	Nervous system disorders	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected49 at risk EG0011 events1 affected49 at risk EG0021 events1 affected48 at risk EG003
Headache	Nervous system disorders	MedDRA 13.0	Systematic Assessment	EG0004 events4 affected49 at risk EG0013 events3 affected49 at risk EG0025 events5 affected48 at risk EG003
Hypoaesthesia	Nervous system disorders	MedDRA 13.0	Systematic Assessment	EG0003 events2 affected49 at risk EG0015 events3 affected49 at risk EG0020 events0 affected48 at risk EG003
Migraine	Nervous system disorders	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected49 at risk EG0013 events3 affected49 at risk EG0021 events1 affected48 at risk EG003
Sinus headache	Nervous system disorders	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected49 at risk EG0010 events0 affected49 at risk EG0020 events0 affected48 at risk EG003
Anxiety	Psychiatric disorders	MedDRA 13.0	Systematic Assessment	EG0003 events2 affected49 at risk EG0010 events0 affected49 at risk EG0022 events2 affected48 at risk EG003
Insomnia	Psychiatric disorders	MedDRA 13.0	Systematic Assessment	EG0002 events2 affected49 at risk EG0015 events5 affected49 at risk EG0023 events3 affected48 at risk EG003
Stress	Psychiatric disorders	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected49 at risk EG0010 events0 affected49 at risk EG0020 events0 affected48 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0002 events2 affected49 at risk EG0012 events2 affected49 at risk EG0021 events1 affected48 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected49 at risk EG0011 events1 affected49 at risk EG0020 events0 affected48 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected49 at risk EG0010 events0 affected49 at risk EG0021 events1 affected48 at risk EG003
Sinus congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0001 events1 affected49 at risk EG0011 events1 affected49 at risk EG0020 events0 affected48 at risk EG003
Hyperhidrosis	Skin and subcutaneous tissue disorders	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected49 at risk EG0010 events0 affected49 at risk EG0020 events0 affected48 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA 13.0	Systematic Assessment	EG0000 events0 affected49 at risk EG0010 events0 affected49 at risk EG0021 events1 affected48 at risk EG003

ID	Term
D050177	Overweight
D044343	Overnutrition
D009748	Nutrition Disorders
D009750	Nutritional and Metabolic Diseases
D001835	Body Weight
D012816	Signs and Symptoms
D013568	Pathological Conditions, Signs and Symptoms

ID	Term
D050198	Phenoxypropanolamines
D011412	Propanolamines
D000605	Amino Alcohols
D000438	Alcohols
D009930	Organic Chemicals
D020005	Propanols
D000588	Amines