Open-Label Extension (OLE) Study for Safety and Efficacy of Velneperit (S-2367) in Obese Subjects
Open-Label Extension (OLE) Study for Safety and Efficacy of Velneperit (S-2367) in Obese Subjects
The purpose of this open-label extension study is to evaluate the safety and efficacy of
 velneperit (S-2367) in obese subjects.
Inclusion Criteria:

 -  Must have completed all randomized treatment visits in the reduced calorie diet (RCD,
 Shionogi protocol 0701A2823) or low calorie diet (LCD, Shionogi protocol 0702A2824)
 study up to and including Visit 13

 -  Medically stable throughout the controlled clinical trial treatment period and in
 otherwise good health, with no clinically significant findings from medical history,
 physical examination, 12-lead 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 and Homeostatic Model Assessment of Insulin Sensitivity
 Index within the reference range for the test laboratory, unless deemed not clinically
 significant by the Investigator

 -  Males will be sterile or agree to continue 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 13/20) 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 13/20 and
 during study) oral, implantable, transdermal, or injectable 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 13/20, or agree to use an approved method of contraception. Some of the approved
 methods of contraception for females includes a sterile (for at least 3 months prior
 to Visit 13/20) male sexual partner; use of oral, implantable, transdermal, or
 injectable 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

 -  Current abnormal ECG, which, in the Investigator's opinion, is clinically significant

 -  Current 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 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

 -  A score above 10 in either the Anxiety or Depression portions of the Hospital Anxiety
 and Depression Scale (HADS) at Visit 13/20. Subjects whose HADS score at Visit 13/20
 exceeds 10 in either the Anxiety or Depression portions of the HADS will be allowed in
 the study only after they are examined and it is determined that the symptoms of
 anxiety and/or depression are not of a severity that is incompatible with further
 treatment with velneperit. Permission must also be obtained from the Sponsor or
 Sponsor's designated medical representative for subjects with scores above 10 on these
 HADS subscores

 -  Current obesity of endocrine origin

 -  Current Type 1 or Type 2 diabetes mellitus

 -  Current clinically significant hypertension, defined as blood pressure >160/90 mmHg
 for either the systolic or diastolic values in either the untreated or treated state

 -  Current or planned clinically significant GI surgery. Note: Appendectomy and
 cholecystectomy will be allowed

 -  Current or planned gastric bypass surgery, stomach banding surgery, or any other
 surgical procedure(s) that attempt to promote/aid weight loss. Note: Liposuction will
 be allowed if done more than 3 months prior to Study Visit 20

 -  Current polycystic ovarian syndrome

 -  Current or planned participation in any weight loss program outside of the program
 described in this open-label extension (OLE) study

 -  Current alcoholism or drug addiction/substance abuse. Note: Alcohol use during the
 study is allowed provided "routine" daily consumption is less than or equal to 2
 units/day (1 unit is the equivalent of 12 oz. of beer, 5 oz. of wine, or 1.5 oz. of
 80-proof distilled spirits [or equivalent]) and except that no alcohol consumption is
 allowed within 48 hours prior to blood collections for analysis of lipid profiles

 -  Current use of any tobacco-containing or nicotine-containing product (including
 cigarette, pipe, cigar, chewing, nicotine patch, or nicotine gum

 -  Current or planned participation in any other investigational study drug trial in
 which receipt of investigational study drug will occur

 -  Current or planned participation in any weight loss medication/product study in which
 receipt of weight loss medication/product will occur

 -  Current or planned use of any prescription or nonprescription over-the-counter (OTC)
 medication/product or herbal/phytotherapeutic/plant-derived medications/products 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, etc.
 Note: Use of any other medications/products for weight control, appetite suppression,
 treatment of obesity is prohibited during the course of this OLE study

 -  Current or planned use of chronic medications/products that are known to cause weight
 gain during the entire OLE study. The list includes but is not limited to
 amitriptyline (ELAVIL), paroxetine (PAXIL), setraline (ZOLOFT), and mirtazepine
 (REMERON). Additional clarification is provided in the concomitant medications section
 and Appendix B and updates or clarifications to these sections. Investigators are to
 discuss with the Sponsor's Medical Monitor any concomitant medications about which
 they are uncertain

 -  Current or planned use of any prescription or non-prescription OTC
 medications/product, unless deemed acceptable by the Investigator. Some examples of
 allowed medications are stable use (during RCD or LCD Study) of: hormone replacement
 therapy (e.g., for postmenopausal women); antihypertensive agents (e.g., for
 hypertensive subjects); statins (e.g., for hyperlipidemia); thyroid replacement
 therapy (e.g., for hypothyroid subjects and provided thyroid replacement therapy has
 been stable during the RCD or LCD study 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 also be
 allowed. Continued, stable, moderate use (during the RCD or LCD study) 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

 -  Planned donation of blood or blood products during the entire OLE study

 -  Current poor peripheral venous access that would preclude blood collection

 -  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