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

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

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)

Study Overview

• Status: Completed
• Conditions: Obesity
• Intervention / Treatment: Drug: Sibutramine; Drug: Orlistat

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 174
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Korea, Republic of
  • Namdong-gu
    • Inchon, Namdong-gu, Korea, Republic of
      • GachonGill Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

MAOInclusion Criteria:

1. A patient who gave one's voluntary written consent to participate in this clinical study
2. Aged ≥ 18 and < 50 years old
3. An obese patient with a body mass index (BMI) ≥ 27 kg/m2
4. In case of a women, premenopausal woman

Exclusion Criteria:

1. A patient with the weight change ≥ 5% over the past 3 months
2. A patient who was receiving a MAO(monoamine oxldase) inhibitor within 1 months of screening
3. A patient with an active acute or chronic disease at the participation of the study
4. A patient with the malignancy history within the past 5 years
5. A patient diagnosed with secondary obesity (Cushing's syndrome, thyroid disease, etc.)
6. 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
7. 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
8. A patient with clear unexplained abnormal findings in chest X-ray, urinalysis, electrocardiogram
9. A pregnant women or breastfeeding mother
10. A patient participating in another clinical study other than this study
11. Other patient who is legally and mentally not appropriate to participate in a clinical study, at the judgment of the investigator
12. A person who participated in other clinical study within the past 3 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sibutramine + 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; ○ 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; Drug: Orlistat; ○ 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
Placebo Comparator: Sibutramine + Orlistat(Placebo); 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; ○ 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; Drug: Orlistat; ○ 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Gachon University Gil Medical Center
• Investigators: Principal Investigator: Kim Kyoungkon, GachonGill Medical Center

Publications and helpful links

General Publications

• Ko KD, Kim KK, Suh HS, Hwang IC. Associations between the GNB3 C825T polymorphism and obesity-related metabolic risk factors in Korean obese women. J Endocrinol Invest. 2014 Nov;37(11):1117-20. doi: 10.1007/s40618-014-0182-6. Epub 2014 Oct 4.
• Kim KK, Suh HS, Hwang IC, Ko KD. Influence of eating behaviors on short-term weight loss by orlistat and anorectic agent. Eat Behav. 2014 Jan;15(1):87-90. doi: 10.1016/j.eatbeh.2013.10.019. Epub 2013 Oct 31.
• Hwang IC, Park JY, Ahn HY, Kim KK, Suh HS, Ko KD, Kim KA. Effects of CYP3A5, CYP2C19, and CYP2B6 on the clinical efficacy and adverse outcomes of sibutramine therapy: a crucial role for the CYP2B6*6 allele. Clin Chim Acta. 2014 Jan 20;428:77-81. doi: 10.1016/j.cca.2013.11.007. Epub 2013 Nov 19.
• Hwang IC, Kim KK, Ahn HY, Suh HS, Oh SW. Effect of the G-protein beta3 subunit 825T allele on the change of body adiposity in obese female. Diabetes Obes Metab. 2013 Mar;15(3):284-6. doi: 10.1111/dom.12023. Epub 2012 Nov 8.

Study record dates

Study Major Dates

• Study Start: February 1, 2010
• Primary Completion (Actual): July 1, 2010
• Study Completion (Actual): July 1, 2010

Study Registration Dates

• First Submitted: August 16, 2010
• First Submitted That Met QC Criteria: August 18, 2010
• First Posted (Estimate): August 19, 2010

Study Record Updates

• Last Update Posted (Estimate): August 19, 2010
• Last Update Submitted That Met QC Criteria: August 18, 2010
• Last Verified: October 1, 2009

More Information

Terms related to this study

• Keywords: obesity
• Additional Relevant MeSH Terms: Body Weight; Body Weight Changes; Weight Loss; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Lipid Regulating Agents; Psychotropic Drugs; Antidepressive Agents; Appetite Depressants; Anti-Obesity Agents; Sibutramine; Orlistat
• Other Study ID Numbers: HM-OPS