Assess the Additional Weight Loss Effect of Orlistat Used in Combination With Sibutramine

Study Overview
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Brief Summary
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The purpose of this study, conducted academic Pilot research purposes, this is not clear as to permit. when orlistat to sibutramine merge if there are additional effects of BMI and group, which has an attribute that is greater for the combined effect is to analyze. Study phase: Investigator-initiated clinical study (Pilot study) Method of blinding: Double-blind Control: Placebo-controlled Assignment method: Randomization (Sibutramine monotherapy group: Orlistat and Sibutramine combination group = 1 : 1) Studied disease: Obesity Study population: Subjects eligible for inclusion/exclusion criteria Dosing period: Total 18 weeks Run-in period (2 weeks), dosing period (12 weeks) and post-dosing observation period (4 weeks)

Detailed Description
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After the screening period, patients eligible for inclusion/exclusion criteria would administer Sibutramine placebo and Orlistat placebo during 2 weeks of the run-in period, Subsequently, subjects are randomized to 2 groups of the Sibutramine monotherapy group and the Orlistat and Sibutramine combination group. Sibutramine monotherapy group would receive Sibutramine 10mg once daily and Orlistat placebo three times daily for 12 weeks; the Orlistat and Sibutramine combination group would receive Sibutramine 10mg once daily and Orlistat 120mg three times daily for 12 weeks. After completing the dosing period, the occurrence of adverse events would be checked for 4 weeks and the study would be completed. Body weight, abdominal CT(Computed Tomography)(visceral fat examination), body fat analysis, etc. would be measured before the study initiation and after 14 weeks of treatment, and comparatively analyzed. A two sample t-test is conducted for the inter-group comparison and a paired t-rest is conducted for the comparison between baseline and after 14 weeks after the study initiation.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Investigator-initiated Study to Assess the Additional Weight Loss Effect of Orlistat Used in Combination With Sibutramine

Conditions
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Obesity

Intervention / Treatment
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* Drug: Sibutramine
* Drug: Orlistat


Participation Criteria
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Eligibility Criteria
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MAOInclusion Criteria: A patient who gave one's voluntary written consent to participate in this clinical study Aged ≥ 18 and < 50 years old An obese patient with a body mass index (BMI) ≥ 27 kg/m2 In case of a women, premenopausal woman Exclusion Criteria: A patient with the weight change ≥ 5% over the past 3 months A patient who was receiving a MAO(monoamine oxldase) inhibitor within 1 months of screening A patient with an active acute or chronic disease at the participation of the study A patient with the malignancy history within the past 5 years A patient diagnosed with secondary obesity (Cushing's syndrome, thyroid disease, etc.) A patient with a significant cardiovascular disease (coronary vascular disease, congestive heart failure, peripheral arterial obstructive disease, arrhythmia, cerebrovascular disease, etc.), poorly controlled hypertension defined by JNC(Joint National Committee) 7 guidelines, diabetes, severe hepatic/renal disease and CNS(Central Nervous System) disease, drug abuse, psychiatric disorder, positive prostatic hyperplasia concurrent with urinary retention and glaucoma within the past 1 year according to medical records A patient falling under the followings from screening test results Hemoglobin < 10g/L or platelets < 100* 103/μL Total bilirubin > 2.0mg/dL Serum GOT(Glutamate oxaloacetate transaminase) or GPT(glutamic pyruvate transaminase) > 120 IU/L Serum creatinine > 1.4mg/dL Serum uric acid > 10mg/dL Thyroid stimulating hormone < 0.1μIU/mL or > 6.5 μIU/mL A patient with clear unexplained abnormal findings in chest X-ray, urinalysis, electrocardiogram A pregnant women or breastfeeding mother A patient participating in another clinical study other than this study Other patient who is legally and mentally not appropriate to participate in a clinical study, at the judgment of the investigator A person who participated in other clinical study within the past 3 months

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sibutramine + Orlistat<br>A lipase inhibitor used for weight loss. Lipase is an enzyme found in the bowel that assists in lipid absorption by the body. Orlistat blocks this enzyme, reducing the amount of fat the body absorbs by about 30%. It is known as a fat blocker. Because more oily fat is left in the bowel to be excreted, Orlistat can cause an oily anal leakage and fecal incontinence | Drug: Sibutramine<br>* ○ Dosing standard Run-in period: All subjects would administer Sibutramine placebo 1 capsule (once daily) and Orlistat placebo 1 capsule (three times daily). The total dosing period is 2 weeks. Treatment period: The total dosing period is 12 weeks. Sibutramine monotherapy group: Sibutramine 1 capsule once daily + Orlistat placebo 1 capsule three times daily Orlistat and Sibutramine combination group: Sibutramine 1 capsule once daily + Orlistat 1 capsule three times daily<br>Drug: Orlistat<br>* ○ Dosing standard Run-in period: All subjects would administer Sibutramine placebo 1 capsule (once daily) and Orlistat placebo 1 capsule (three times daily). The total dosing period is 2 weeks. Treatment period: The total dosing period is 12 weeks. Sibutramine monotherapy group: Sibutramine 1 capsule once daily + Orlistat placebo 1 capsule three times daily Orlistat and Sibutramine combination group: Sibutramine 1 capsule once daily + Orlistat 1 capsule three times daily<br>|
| Placebo Comparator: Sibutramine + Orlistat(Placebo)<br>Sibutramine : one of components included into Diet Pills. This reduces appetite, normalizes amount of cholesterol in blood, and reduces abdominal fat. Orlistat : A lipase inhibitor used for weight loss. Lipase is an enzyme found in the bowel that assists in lipid absorption by the body. Orlistat blocks this enzyme, reducing the amount of fat the body absorbs by about 30%. It is known as a fat blocker. Because more oily fat is left in the bowel to be excreted, Orlistat can cause an oily anal leakage and fecal incontinence. | Drug: Sibutramine<br>* ○ Dosing standard Run-in period: All subjects would administer Sibutramine placebo 1 capsule (once daily) and Orlistat placebo 1 capsule (three times daily). The total dosing period is 2 weeks. Treatment period: The total dosing period is 12 weeks. Sibutramine monotherapy group: Sibutramine 1 capsule once daily + Orlistat placebo 1 capsule three times daily Orlistat and Sibutramine combination group: Sibutramine 1 capsule once daily + Orlistat 1 capsule three times daily<br>Drug: Orlistat<br>* ○ Dosing standard Run-in period: All subjects would administer Sibutramine placebo 1 capsule (once daily) and Orlistat placebo 1 capsule (three times daily). The total dosing period is 2 weeks. Treatment period: The total dosing period is 12 weeks. Sibutramine monotherapy group: Sibutramine 1 capsule once daily + Orlistat placebo 1 capsule three times daily Orlistat and Sibutramine combination group: Sibutramine 1 capsule once daily + Orlistat 1 capsule three times daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Weight | Weight | with in 18weeks | 
| BMI(Body Mass Index) | BMI(Body Mass Index) | with in 18weeks | 
| waist circumference | waist circumference | with in 18weeks | 
| blood pressure | blood pressure | with in 18weeks | 
| fat mass | fat mass | with in 18weeks | 
| visceral fat mass improvement | visceral fat mass improvement | with in 18weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lipid profile | Total cholesterol, HDL-C(high-density lipoprotein-cholesterol), LDL-C(low-density lipoprotein-cholesterol), Triglyceride improvement | with in 18weeks | 
| Adipokines improvement | Serum insulin, adiponectin, leptin, ghrelin, serum ostecalcin, urine deoxypyridinolin | with in 18weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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obesity