Phase IIb One Year Efficacy and Safety Study of S-2367 in Obese Subjects With Reduced Calorie Diet

Study Overview
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Brief Summary
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To evaluate the effect of S-2367 on body weight when administered following a 6-week placebo lead-in period and then a 54-week 800 kilocalorie deficit reduced calorie diet compared to placebo in healthy obese male and female subjects To evaluate the safety and tolerability of S-2367 during 54 weeks of drug exposure To evaluate the steady-state/trough pharmacokinetics of S-2367

Official Title
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A Double-Blind, Multi-Center, Randomized, Parallel-Group, Yearlong Study to Assess the Efficacy and Safety of 0, 800, or 1600 mg/Day of S-2367 Administered Orally Once Daily With a Reduced Calorie Diet in Obese Males and Females

Conditions
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Obesity

Intervention / Treatment
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* Drug: S-2367 Placebo
* Drug: S-2367 800 mg
* Drug: S-2367 1600 mg
* Other: Reduced Calorie Diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females between 18 and 65 years of age and body mass index between 30.0 to 45.0 kg/m2, inclusive, and a weight that has not fluctuated by more than 3% for the last 3 months Medically stable for 3 months prior to Visit 1 and in otherwise good health, with no clinically significant findings from medical history, physical examination, 12-lead electrocardiograms (ECG), and vital signs Clinical laboratory evaluations (including clinical chemistry [fasted at least 8 hours], complete blood count, urinalysis, including creatine phosphokinase, amylase, lipase, lipid profile, insulin, Homeostatic Model Assessment of Insulin Sensitivity Index, hemoglobin A1c, thyroid stimulating hormone, free thyroxine, cortisol, iron, and ferritin) within the reference range for the test laboratory, unless deemed not clinically significant by the investigator Males will be sterile or agree to use an approved method of contraception. Some of the approved methods of contraception for males includes a surgically sterile (for at least 3 months prior to Visit 1) female sexual partner; a postmenopausal (for at least 1 year since last menstrual cycle) female sexual partner; a female sexual partner who uses (for at least previous 3 months prior to Visit 1 and during study) oral, implantable, transdermal, or injectable oral contraceptives; or use of the following double-barrier method: male condom with spermicide Females will be non-pregnant, non-lactating, and either postmenopausal for at least 1 year since last menstrual period, surgically sterile for at least 3 months prior to Visit 1, or agree to use an approved method of contraception. Some of the approved methods of contraception for females include a sterile (for at least 3 months prior to Visit 1) male sexual partner; use of oral, implantable, transdermal, or injectable oral contraceptives; or use of one of the following double-barrier methods: intrauterine device with spermicide, diaphragm with spermicide, cervical cap with spermicide, female condom with spermicide, or a male condom with spermicide by the male sexual partner Able to understand and willing to sign an informed consent form and comply with all study procedures Exclusion Criteria: History or clinical manifestations of significant metabolic, hepatic, immunological (e.g., human immunodeficiency virus/ acquired immunodeficiency syndrome), renal, hematological, pulmonary, cardiovascular, gastrointestinal (GI), urological, neurological, or psychiatric disorders History or presence of an abnormal ECG, which in the investigator's opinion, is clinically significant History or evidence of a psychological disorder, other than stable or controlled anxiety or depression, including but not limited to the schizophrenias. Treatment with an antidepressant or anxiolytic drug(s) will be permitted if the dose and form has remained stable for at least the previous 3 months and the medication is not precluded/ excluded by this protocol because of potential effects on body weight and is not expected to change during the remainder of this clinical protocol History or evidence of an eating disorder with a compensatory behavior such as purging bulimia nervosa or non-purging bulimia nervosa History of obesity of endocrine origin History of type 1 or type 2 diabetes mellitus Clinically significant hypertension defined as blood pressure > 160/90 mm Hg for either the systolic or diastolic values in either the untreated or treated state Clinically significant GI history or surgery. NOTE: Appendectomy and cholecystectomy will be allowed Gastric bypass surgery, stomach banding surgery, or any other surgical procedure(s) that attempt to promote/aid weight loss History of polycystic ovarian syndrome History of fenfluramine or dexfenfluramine or fen-phen administration with abnormal findings on echocardiograms at the time of fen-phen discontinuation History of participation in any weight loss program within 3 months prior to Visit 1 History of body weight loss or gain greater than 3% within 3 months prior to Visit 1 History of alcoholism or drug addiction/ substance abuse within 1 year prior to Visit 1 History of any tobacco-containing or nicotine-containing product use (including cigarette, pipe, cigar, chewing, nicotine patch, or nicotine gum) within 1 year prior to Visit 1 Participation in any other investigational study drug trial in which receipt of investigational study drug occurred within 3 months prior to Visit 1 Previous use or participation in a study of S-2367 or any other neuropeptide Y5 agonist or antagonist Participation in any weight loss medication/product study in which receipt of weight loss medication/product occurred within 3 months prior to Visit 1 Use of any prescription or non-prescription over-the-counter (OTC) medication/product or herbal/phytotherapeutic/plant-derived medications/products within 3 months prior to Visit 1 that is intended to induce weight loss, appetite suppression, weight control, or treat obesity, including, but not limited to, phentermine, sibutramine, orlistat, ephedra, rimonabant and other anorexogenics and/or stimulants, as well as topiramate Use of chronic medications/products within 3 months prior to Visit 1 or during the study that are known to cause weight gain. The list includes but is not limited to amitriptyline (Elavil), paroxetine (Paxil), setraline (Zoloft), and mirtazepine (Remeron) Use of any prescription or non-prescription OTC medications/products within 1 month prior to Visit 1, unless deemed acceptable by the investigator. Some examples of allowed medications are stable use (over the 3-month period prior to Visit 1) of the following will be allowed: hormone replacement therapy (e.g., for postmenopausal women); antihypertensive agents (e.g., for hypertensive subjects); statins (e.g., for hyperlilidaemia); thyroid replacement therapy (e.g., for thyroid subjects and provided thyroid replacement therapy has been stable for 3 months and no clinically significant changes in thyroid stimulating hormone and/or free thyroxine occur[s] during the study); oral, implantable, transdermal, or injectable contraceptive(s), etc. Anticholinergics (if used acutely), centrally acting antihistamines, and anti-inflammatories will be also allowed. Continued, stable, moderate use (over 3 month period prior to Visit 1) of vitamins and minerals is allowed and additional use of multivitamin-mineral supplements (non-herbal) may be allowed by the investigator (or designee) as part of the study diet program Donation of blood or blood products 3 months prior to Visit 1 or during the entire study Any acute or chronic condition that, in the opinion of the investigator, would limit the subject's ability to complete and/ or participate in this clinical study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: S-2367 Placebo<br>Placebo + reduced calorie diet | Drug: S-2367 Placebo<br>* four placebo tablets (total dose = 0 mg/day S-2367) administered orally once-a-day with morning meal while on a reduced calorie diet for a total of 54 weeks,<br>Other: Reduced Calorie Diet<br>* A diet with restricted calorie content<br>|
| Experimental: S-2367 800 mg<br>S-2367 800 mg q.d. + reduced calorie diet | Drug: S-2367 800 mg<br>* two 400 mg S-2367 tablets (total dose = 800 mg/day S-2367) administered orally once-a-day with morning meal while on a reduced calorie diet for a total of 54 weeks<br>* Other names: Velneperit;Other: Reduced Calorie Diet<br>* A diet with restricted calorie content<br>|
| Experimental: S-2367 1600 mg<br>S-2367 1600 mg q.d. + reduced calorie diet | Drug: S-2367 1600 mg<br>* four 400 mg S-2367 tablets (total dose = 1600 mg/day S-2367) administered orally once-a-day with morning meal while on a reduced calorie diet for total of 54 weeks,<br>* Other names: Velneperit;Other: Reduced Calorie Diet<br>* A diet with restricted calorie content<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change in body weight over the 54-week active therapy phase of the study | body weight at 54 weeks compared to body weight at start of treatment | 54 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in body composition: calculated body mass index, waist circumference, hip circumference, and calculated waist-to-hip ratio | Change in body weight, waist measurement, and hip measurement | 54 weeks | 
| Steady-state/trough pharmacokinetic analysis | Trough plasma concentration at various times after start of treatment | After 3, 12, 24, 36, and 54 weeks | 
| Safety and tolerability of S-2367 | number of adverse events or changes in laboratory values | 54 weeks | 

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