A Weight Loss Study in Overweight Men and Women

Lilly

Status and phase: Terminated; Phase 2

Conditions: Obesity

Treatments: Drug: Metoprolol; Drug: Placebo LY377604; Drug: Placebo Metoprolol; Drug: Placebo sibutramine; Drug: LY377604; Drug: Sibutramine

Study type: Interventional

Funder types: Industry

Identifiers

NCT00993421

11892

I1L-MC-GAEB (Other Identifier)

Details and patient eligibility

About

The purpose of this study is to determine if LY377604 + sibutramine work better than LY377604 or sibutramine alone in the treatment of obesity.

Enrollment: 343 patients

Sex: All

Ages: 21 to 65 years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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343 participants in 7 patient groups, including a placebo group

placebo

Placebo Comparator group

Treatment:

Drug: Placebo sibutramine

Drug: Placebo Metoprolol

Drug: Placebo LY377604

LY377604 (75 mg)

Experimental group

Treatment:

Drug: Placebo sibutramine

Drug: Placebo Metoprolol

Drug: LY377604

sibutramine (30 mg)/metoprolol (200 mg)

Active Comparator group

Treatment:

Drug: Sibutramine

Drug: Metoprolol

LY377604 (40 mg)/sibutramine (30 mg)

Experimental group

Treatment:

Drug: Placebo Metoprolol

Drug: LY377604

Drug: Sibutramine

LY377604 (75 mg)/sibutramine (30 mg)

Experimental group

Treatment:

Drug: Placebo Metoprolol

Drug: LY377604

Drug: Sibutramine

LY377604 (15 mg)/sibutramine (30 mg)

Experimental group

Treatment:

Drug: Placebo Metoprolol

Drug: LY377604

Drug: Sibutramine

LY377604 (75 mg)/sibutramine (15 mg)

Experimental group

Treatment:

Drug: Placebo Metoprolol

Drug: LY377604

Drug: Sibutramine