Fixed Dose Combination of Fluoxetin and Metformin in the Management of Overweight and Obesity (Metfluo)

• ClinicalTrials.gov Identifier: NCT03051451
• Recruitment Status: Suspended
• First Posted: February 13, 2017
• Last Update Posted: September 1, 2017
• Sponsor: Laboratorios Silanes S.A. de C.V.
• Collaborators: INTEC Instituto de Terapéutica Experimental y Clínica, Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara.; OSMO (OAXACA SITE MANAGEMENT ORGANIZATION, SC); IBIOMED INVESTIGACIÓN BIOMÉDICA PARA EL DESARROLLO DE FÁRMACOS, S.A. DE C.V.
• Information provided by (Responsible Party): Laboratorios Silanes S.A. de C.V.

Study Description

Brief Summary:

Clinical trial, multicenter, double-blind, placebo-controlled, comparative of three parallel groups, randomized treatment to assess the efficacy and safety using a fixed dose combination of metformin hydrochloride with fluoxetine as adjunctive treatment in patient with obesity or overweight in order to generate new knowledge and give a greater number of therapeutic options to the clinicians, one group will receive metformin 1700 mg and 40 mg of fluoxetine; Another group will receive metformin 1000 mg with 40 mg of fluoxetine, and a third group called control will receive placebo.

The above described treatments will be administered according to the "Dosage Schedule" The three groups will receive tablets of physical characteristics equal to the reference drug to preserve the blinding.

Condition or disease	Intervention/treatment	Phase
Overweight and Obesity	Drug: combination metformin hydrochloride/ fluoxetine 500/20 mg; Drug: combination metformin hydrochloride/ fluoxetine 1000/20mg; Drug: Placebo Oral Tablet	Phase 2

Detailed Description:

Overweight and obesity are serious health problems that affect population around the world. According to information of the World Health Organization (WHO) in 2014 more than 1.9 billion of inhabitants older than 18 years had overweight, of which 600 million were obese, i.e., 39% of adults at global level present overweight and 13% of adults suffer obesity.

Overweight and obesity are considered complex and multifactorial diseases associated with the development of multiple co-morbidities such as certain types of cancer, cardiovascular diseases (CVD), disability, diabetes mellitus type 2 (DM2), disease of gallbladder, osteoarthritis, high blood pressure (Hypertension), sleep apnea and cerebrovascular disease (CD), making it the fifth leading cause of death worldwide , and is therefore considered a pandemic.

Obesity is defined as the increase of the weight body associated to an imbalance in the proportions of the different components of the body, in which mainly, the mass fat increases with abnormal distribution in the body.The Body Mass Index (BMI) is the standard most widely used for the classification of the somatotype in the people, and therefore the identification of obesity. BMI is obtained through by dividing the weight in kilograms between heights in squared meters. The classification of the BMI for White, Hispanic, and African-American adult people has been approved by the National Institute of Heart, Lung and Blood, the WHO, the American Association of Heart, the American College of Cardiology and the Obesity Society, whose classification is the following:

The weight body is determined by the balance energy, which represents the difference between the intake of energy through the food and the expenditure of energy coming of physical activity of an individual. For the maintenance of a stable body weight, the energy intake must be equal to energy expenditure, that's when weight gain happens, when the intake exceeds expenditure, which produces a positive energy balance. On the other hand, weight loss occurs when energy expenditure exceeds the caloric intake.

Although the low expenditure of energy represents one of the main factors that produce an increase in the weight, there are multiple factors that play an important role. These factors include genetic predisposition of the individual, physical inactivity and sedentary behavior, socio-economic factors, as well as emotional factors and consumption of certain types of drugs.

Due to the multiple factors that have an influence in the development of overweight and obesity, the treatment is complex, because there must be some type of treatment by a multidisciplinary team that achieve the control of each one of the factors that condition obesity of each individual.

Traditional treatments for loss weight have been given in the education of the individual on the preference for healthy foods, prescription diets and the implementation of programs of physical activity. However, various studies have shown that this type of intervention has few effects in long term, so the incorporation of new strategies as adjuvants in the loss of weight have been developed, which include surgical techniques and pharmacological therapies.

According to the guidelines for obesity, the drug treatment therapy should be recommended in individuals with a BMI ≥30 kg/m2 or with a BMI of ≥27 kg/m2 and the presence of a comorbidity. 6. The use of pharmacological therapies must always be used as adjuvants to changes in lifestyle, and must be approved by health authorities of each country. Before 2012, phentermine and orlistat were the unique medications available for the treatment of obesity in the United States; however in 2015 the Repertoire of pharmacological agents available to treat the obesity was extended and incorporated 4 new drugs: lorcaserin, phentermine / topiramate of prolonged release, naltrexone / wellbutrin of prolonged release and liraglutide. These new drugs share a common strategy to promote weight loss that controls hunger and satiation at the level of the central nervous system (CNS), besides that most of them have been previously used for the treatment of a medical condition other than obesity. The amount of weight lost that is achieved through the use of these agents, usually goes from 3 to 10% of the initial weight and requires a continuous to hold the loss of weight. In addition, each of these drugs has a unique profile of adverse events that should be considered deeply prior to be indicated.

Due to the above, the search for new drug therapies for the obesity treatment is one of the priorities in the research. Some drugs developed for different therapeutic indications have shown significant effects on weight loss, which include metformin hydrochloride and fluoxetine

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 150 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Care Provider)
• Primary Purpose: Treatment
• Official Title: Multicenter, Randomized, Double-blind, Placebo-controlled Trial to Determine the Efficacy of Two Fixed Dose Combination of Metformin/Fluoxetin 1000/40 mg vs. 1700/40 mg in the Management of Overweight and Obesity
• Estimated Primary Completion Date: May 2018
• Estimated Study Completion Date: November 2018

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: combination metformin hydrochloride/ fluoxetine 500/20 mg; Dosage: The dose will depend on the period of treatment in which the patient is: Single dose treatment (from visit 2 (from day 0 to day 30 ± 7), the patient will take 1 metformin hydrochloride tablet 500 mg / fluoxetine 20 mg and 1 placebo tablet , every 24 hours in the morning for 30 days).; Treatment at double dose (from visit 3 and until visit 8), the patient will take 2 tablets of metformin hydrochloride 500 mg / fluoxetine 20 mg and 2 tablets of Placebo, every 24 hours in the morning for 150 days).	Drug: combination metformin hydrochloride/ fluoxetine 500/20 mg; Group A will receive metformin 1000 mg and 40 mg of fluoxetine; after the increment phase. All treatment groups will receive, in addition to the intervention, recommendations of a diet based on a hyper protein, hypo caloric and low carbohydrate diet as well as an exercise routine according to age and physical condition
Active Comparator: combination metformin hydrochloride/ fluoxetine 1000/20mg; Dosage: The dose will depend on the period of treatment in which the patient is: Single dose treatment (from visit 2 (from day 0 to day 30 ± 7), the patient will take 1 metformin hydrochloride tablet 850 mg / fluoxetine 20 mg and 1 placebo tablet , every 24 hours in the morning for 30 days).; Treatment at double dose (from visit 3 and until visit 8), the patient will take 2 tablets of metformin hydrochloride 850 mg / fluoxetine 20 mg and 2 tablets of Placebo, every 24 hours in the morning for 150 days).	Drug: combination metformin hydrochloride/ fluoxetine 1000/20mg; Group B will receive metformin 1700 mg and 40 mg of fluoxetine; after the increment phase. All treatment groups will receive, in addition to the intervention, recommendations of a diet based on a hyper protein, hypo caloric and low carbohydrate diet as well as an exercise routine according to age and physical condition
Placebo Comparator: Placebo Oral Tablet; Placebo	Drug: Placebo Oral Tablet; Group C will receive placebo oral tablet; All treatment groups will receive, in addition to the intervention, recommendations of a diet based on a hyper protein, hypo caloric and low carbohydrate diet as well as an exercise routine according to age and physical condition

Outcome Measures

Primary Outcome Measures :

1. Decrease of at least 5% of body weight and the reduction in the body mass index. [ Time Frame: six months ]
   Compare BMI after 6 months of treatment with hydrochloride of metformin / fluoxetine. In two doses (1000/40 mg) and (1700/40 mg) or placebo.

Secondary Outcome Measures :

1. Body weight [ Time Frame: six months ]
   the mass of the body in kilograms
2. Height [ Time Frame: six months ]
   expressed in meters
3. Body Mass Index [ Time Frame: six months ]
   relationship between weight and height, used to classify underweight, overweight and obesity, calculated by dividing the weight in kilograms by the square of the height in meters
4. Waist-hip index (hip circumference) [ Time Frame: six months ]
   The waist hip index will be obtained by measuring the waist perimeter in centimeters at the last floating rib level and the maximum hip perimeter at the gluteal level.
5. Blood pressure measurement [ Time Frame: six months ]
   The blood pressure measurement will be performed with a calibrated and verified sphygmomanometer in mm/Hg
6. Fasting glucose concentration [ Time Frame: six months ]
   Glucose concentrations in mg/dl from blood serum will be determined in patients in fasting condition
7. Insulin levels [ Time Frame: six months ]
   Serum insulin levels in µl/ml will be quantified using an enzyme immunoassay technique
8. concentrations of lipid profile [ Time Frame: six months ]
   Percentage of reduction of cholesterol levels in mg/dl after 6 months of treatment.
9. fat mass [ Time Frame: six months ]
   Measured by bioimpedance
10. concentrations of lipid profile [ Time Frame: six months ]
    Percentage of reduction LDL-C and / or triglycerides in mg/dl after 6 months of treatment

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Signature of consent informed
• Men and Women.
• ≥ 18 years old proven through a current official identification.
• BMI ≥ 30 kg/m2 with or without Comorbidities.
• BMI ≥ 27 kg/m2 with a diagnosis of comorbidities by patient's clinical record associated with overweight (DM2's recent diagnosis without treatment, hypertension, dyslipidemia, sleep apnea or secondary heart disease) defined as follows:
• DM2 of current diagnosis study inclusion unless not receive drug treatment, with a HbA1c ≥6. 5 and and < 8.5%.
• Arterial Systemic Hypertension with figures < 140 / 90 mmHg.
• Dyslipidemia with total cholesterol levels> 200 mg / dl and <240 mg / dl, and / or LDL-C> 100 and <160 mg / dl and / or triglycerides> 150 mg / dl and <400 mg / dl.
• In case of have drug treatment for hypertension or dyslipidemia, the participants must have a stable dose for at least 3 months prior to the elective visit.
• Women in childbearing age must use a reliable method of birth control, such as barrier methods (condom, diaphragm), fallopian tube obstruction, intrauterine device.

Exclusion Criteria:

• Endogenous obesity (endocrine diseases that condition gain of weight, such as hypothyroidism, syndrome of Cushing).
• Background of patient's clinical record history of iatrogenic obesity (use of drugs that determine weight gain, such as corticosteroids, antipsychotic and antiepileptic).
• Thyroid stimulating Hormone (TSH) is out of range.
• Prolongation of the QT interval corrected for rate (QTc) segment by electrocardiogram with the formula of prolonged Bazett (greater than 450 msec. in males and 470 msec in women).
• Creatinine ≥1. 3 mg/dl in women and ≥1. 5 mg/dl in men.
• Alanine transaminase(ALT) or Aspartate Aminotransferase (AST) > 2 times above from the normal value.
• Background of patient's clinical record of depressive disorder or anxiety that - may require therapy with psychiatric drugs.
• Intolerance known to drugs in the study.
• Pregnancy or breastfeeding.
• Use of medications, supplements or other techniques whose objective is the reduction of weight.
• Use of medications contraindicated with drugs study.

Contacts and Locations

Locations

Mexico

Laboratorios SIlanes S.A. de C.V,

Mexico Distrito Federal, Mexico City, Mexico, 03100

Sponsors and Collaborators

Laboratorios Silanes S.A. de C.V.

INTEC Instituto de Terapéutica Experimental y Clínica, Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara.

OSMO (OAXACA SITE MANAGEMENT ORGANIZATION, SC)

IBIOMED INVESTIGACIÓN BIOMÉDICA PARA EL DESARROLLO DE FÁRMACOS, S.A. DE C.V.

Investigators

• Principal Investigator: Manuel González, PhD; Instituto de Terapéutica Experimental y Clínica, Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara.

More Information

Additional Information:

Efficacy and safety using fluoxetin 

• Responsible Party: Laboratorios Silanes S.A. de C.V.
• ClinicalTrials.gov Identifier: NCT03051451
• Other Study ID Numbers: 30050/II/16
• First Posted: February 13, 2017
• Last Update Posted: September 1, 2017
• Last Verified: August 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Laboratorios Silanes S.A. de C.V.:

Hydrochloride of Metformin / Fluoxetine; Placebo; Obesity

Additional relevant MeSH terms:

Obesity; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Metformin; Fluoxetine; Hypoglycemic Agents; Physiological Effects of Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Serotonin Agents; Antidepressive Agents, Second-Generation; Antidepressive Agents; Psychotropic Drugs; Cytochrome P-450 CYP2D6 Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Enzyme Inhibitors