A Weight Loss Study in Overweight Men and Women

This study has been terminated.
(Clinical trial terminated due to results from recent nonclinical studies)
Sponsor:
Information provided by:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00993421
First received: October 9, 2009
Last updated: June 2, 2011
Last verified: June 2011
  Purpose

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


Condition Intervention Phase
Obesity
Drug: LY377604
Drug: Sibutramine
Drug: Metoprolol
Drug: Placebo sibutramine
Drug: Placebo Metoprolol
Drug: Placebo LY377604
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: LY377604 + Sibutramine Hydrochloride Monohydrate: A Phase 2 Weight Loss Efficacy Study in Overweight/Obese Men and Women

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Percent Change in Body Weight From Baseline to 24 Week Endpoint [ Time Frame: Baseline, 24 weeks ] [ Designated as safety issue: No ]
    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 Outcome Measures:
  • The Mean Change in Body Weight From Baseline to 24 Week Endpoint [ Time Frame: Baseline, 24 weeks ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants Who Achieve a Minimum of 10% Weight Loss From Baseline at 24 Weeks [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Change in Heart Rate From Baseline to 24 Week Endpoint [ Time Frame: Baseline, 24 weeks ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Baseline, 24 weeks ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Baseline, 24 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, 24 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, 24 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, 24 weeks ] [ Designated as safety issue: No ]
  • Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to 24 Weeks Endpoint [ Time Frame: Baseline, 24 weeks ] [ Designated as safety issue: No ]
  • Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline to 24 Weeks Endpoint [ Time Frame: Baseline, 24 weeks ] [ Designated as safety issue: No ]
  • Change in Triglycerides From Baseline to 24 Weeks Endpoint [ Time Frame: Baseline, 24 weeks ] [ Designated as safety issue: No ]
  • Change From Baseline for Obesity Weight Loss Quality of Life Instrument (OWL-QoL) [ Time Frame: Baseline, 24 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, 24 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, 24 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, 24 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, 24 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, 24 weeks ] [ Designated as safety issue: No ]
    Analysis of change in insulin resistance was not conducted due to an inadequate number of samples.

  • Pharmacokinetics: Area Under the Concentration Time Curve (AUC) [ Time Frame: 4 weeks, 12 weeks, and 24 weeks ] [ Designated as safety issue: No ]
    Analysis of AUC was not conducted due to an inadequate number of samples collected.

  • Pharmacokinetics: Maximum Concentration (Cmax) [ Time Frame: 4 weeks, 12 weeks, and 24 weeks ] [ Designated as safety issue: No ]
    Analysis of Cmax was not conducted due to an inadequate number of samples collected.


Enrollment: 343
Study Start Date: October 2009
Study Completion Date: June 2010
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: placebo Drug: Placebo sibutramine
given daily, orally for 24 weeks
Drug: Placebo Metoprolol
given daily, orally for 26 weeks (24 weeks plus 2 weeks of taper)
Drug: Placebo LY377604
given daily, orally for 24 weeks
Experimental: LY377604 (75 mg) Drug: LY377604
Given daily, orally for 24 weeks
Drug: Placebo sibutramine
given daily, orally for 24 weeks
Drug: Placebo Metoprolol
given daily, orally for 26 weeks (24 weeks plus 2 weeks of taper)
Active Comparator: sibutramine (30 mg)/metoprolol (200 mg) Drug: Sibutramine
given daily, orally for 24 weeks
Drug: Metoprolol
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).
Experimental: LY377604 (40 mg)/sibutramine (30 mg) Drug: LY377604
Given daily, orally for 24 weeks
Drug: Sibutramine
given daily, orally for 24 weeks
Drug: Placebo Metoprolol
given daily, orally for 26 weeks (24 weeks plus 2 weeks of taper)
Experimental: LY377604 (75 mg)/sibutramine (30 mg) Drug: LY377604
Given daily, orally for 24 weeks
Drug: Sibutramine
given daily, orally for 24 weeks
Drug: Placebo Metoprolol
given daily, orally for 26 weeks (24 weeks plus 2 weeks of taper)
Experimental: LY377604 (15 mg)/sibutramine (30 mg) Drug: LY377604
Given daily, orally for 24 weeks
Drug: Sibutramine
given daily, orally for 24 weeks
Drug: Placebo Metoprolol
given daily, orally for 26 weeks (24 weeks plus 2 weeks of taper)
Experimental: LY377604 (75 mg)/sibutramine (15 mg) Drug: LY377604
Given daily, orally for 24 weeks
Drug: Sibutramine
given daily, orally for 24 weeks
Drug: Placebo Metoprolol
given daily, orally for 26 weeks (24 weeks plus 2 weeks of taper)

  Eligibility

Ages Eligible for Study:   21 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00993421

  Show 21 Study Locations
Sponsors and Collaborators
Eli Lilly and Company
Investigators
Study Director: 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
  More Information

No publications provided

Responsible Party: Chief Medical Officer, Eli Lilly
ClinicalTrials.gov Identifier: NCT00993421     History of Changes
Other Study ID Numbers: 11892, I1L-MC-GAEB
Study First Received: October 9, 2009
Results First Received: May 11, 2011
Last Updated: June 2, 2011
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Obesity
Weight Loss
Overweight
Overnutrition
Nutrition Disorders
Body Weight
Signs and Symptoms
Body Weight Changes
Metoprolol
Metoprolol succinate
Sibutramine
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Antihypertensive Agents
Sympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Adrenergic beta-1 Receptor Antagonists
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Appetite Depressants
Anti-Obesity Agents
Central Nervous System Agents
Antidepressive Agents

ClinicalTrials.gov processed this record on July 20, 2014