A Weight Loss Study in Overweight Men and Women
Condition: Obesity
MeSH terms: Overweight; Weight Loss
Intervention: LY377604; Sibutramine; Metoprolol; Placebo sibutramine; Placebo Metoprolol; Placebo LY377604
Intervention description: Given daily, orally for 24 weeks; given daily, orally for 24 weeks; 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).; given daily, orally for 24 weeks; given daily, orally for 26 weeks (24 weeks plus 2 weeks of taper); given daily, orally for 24 weeks
Intervention MeSH terms: Sibutramine; Metoprolol
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 343.0
Sex: All
Minimum age: 21 Years
Maximum age: 65 Years
Healthy volunteers: No

Summary:

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

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).