The purpose of this study is to determine if LY377604 + sibutramine work better than
LY377604 or sibutramine alone in the treatment of obesity.
The mean change in body weight from baseline to 24 week endpointChange in Heart Rate from baseline to 24 week endpoint
Change in Blood Pressure from baseline to 24 week endpoint
Change in Waist Circumference from baseline to 24 week endpoint
Proportion of participants who achieve a minimum of 10% weight loss
Pharmacokinetics AUC
Percentage change in waist circumference from baseline to 24 week endpoint
Change in Glycated hemoglobin A1c (HbA1c) from baseline
Change from baseline for OWL-QOL [Obesity weight loss quality of life instrument including weight-related symptoms measurement (WRSM)]
Change from baseline in Vitality Scale of Medical Outcomes Short Form - 36 (SF-36) scale
Change in body Composition using Dual Energy X-ray Absorptiometry (DXA) from baseline to 24 week endpoint
Change in Total cholesterol from baseline to 24 weeks endpoint
Change in High-density lipoprotein Cholesterol (HDL-C) from baseline to 24 weeks endpoint
Change in Trigylcerides from baseline to 24 weeks endpoint
Change in fasting glucose from baseline to 24 weeks endpoint
Change in fasting insulin from baseline to 24 weeks endpoint
Change in Low-density lipoprotein Cholesterol (LDL-C) from baseline to 24 weeks endpoint
Change in insulin resistance from baseline to 24 weeks endpoint
Pharmacokinetics Cmax
Inclusion Criteria:
- Are between the body mass index (BMI) of 27 and 45 kg/m2, 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 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).
There may be multiple sites in this clinical trial 1-877-CTLILLY (1-877-285-4559) or, Phone: 1-317-615-4559
