Phase IIb One Year Efficacy and Safety Study of S-2367 in Obese Subjects With Initial 6-Week Low Calorie Diet

NCT00748605 | Completed Phase 2

• 1 other identifier: 0702A2824 revised
• Study Type: interventional
• Target: 842
• Locations: 1 country
• Sites: 40

Brief Summary

1. 1.To evaluate the weight loss effect of 1600 mg/day S-2367 administered orally once daily with the morning meal after a 6-week low calorie diet (LCD) of 950 kcal/day with or without S-2367 followed by 54 weeks while on a 800 kcal deficit reduced calorie diet (RCD) compared with placebo in medically stable and otherwise healthy obese male and female subjects
2. 2.To evaluate the safety and tolerability of 1600 mg/day S-2367 administered orally once daily with the morning meal after a 6-week LCD with or without S-2367 followed by 54 weeks on a RCD compared with placebo in medically stable and otherwise healthy obese male and female subjects
3. 3.To evaluate the steady-state/trough pharmacokinetics of 1600 mg/day S-2367 administered orally once daily with the morning meal after a 6-week LCD with or without S-2367 followed by 54 weeks on a RCD in obese male and female subjects
4. 4.To evaluate the weight loss effect of 1600 mg/day S-2367 administered orally once daily with the morning meal during an initial 6-week LCD compared with placebo in medically stable and otherwise healthy obese male and female subjects

Conditions

Obesity

Keywords

Obesity

Outcome Measures

Primary Outcomes (1)

• The change in body weight over the 60-week active therapy phase of the study

  60 weeks

Secondary Outcomes (3)

• Change in body composition: calculated body mass index, waist circumference, hip circumference, and calculated waist-to-hip ratio

  Throughout the study

• Steady-state/trough pharmacokinetic analysis

  After 9, 18, 30, 42, and 60 weeks of study drug treatment

• Safety and tolerability of S-2367: treatment emergent adverse events, clinical laboratory data, vital signs, and 12-lead electrocardiogram parameters at each visit

  Throughout the study

Study Arms (3)

Placebo

PLACEBO COMPARATOR

S-2367 placebo + LCD (Low Calorie Diet) +RCD (Reduced Calorie Diet)

Drug: S-2367 Placebo; Other: LCD (low calorie diet); Other: RCD (reduced calorie diet)

S-2367 1600 mg q.d. 54 weeks

EXPERIMENTAL

S-2367 placebo + LCD for 6 weeks and 1600 mg S-2367 + RCD for 54 weeks

Drug: S-2367 Placebo; Drug: S-2367 1600 mg q.d. 54 Weeks; Other: LCD (low calorie diet); Other: RCD (reduced calorie diet)

S-2367 1600 mg q.d. 60 weeks

EXPERIMENTAL

S-23671600 mg q.d. + LCD for 6 weeks and S-2367 1600 mg q.d + RCD for 54 weeks

Drug: S-2367 1600 mg q.d. 60 weeks; Other: LCD (low calorie diet); Other: RCD (reduced calorie diet)

Interventions

S-2367 Placebo DRUG

Four placebo tablets (total dose = 0 mg/day S-2367) administered orally once daily with AM (ante meridiem) meal while on both LCD (low calorie diet for 6 weeks) and RCD (reduced calorie diet for 54 weeks) for a total of 60 weeks

Placebo; S-2367 1600 mg q.d. 54 weeks

S-2367 1600 mg q.d. 54 Weeks DRUG

Four 400 mg S- 2367 tablets (total dose = 1600 mg/day S-2367) administered orally once daily with AM meal while on RCD for a total of 54 weeks

Also known as: Velneperit

S-2367 1600 mg q.d. 54 weeks

S-2367 1600 mg q.d. 60 weeks DRUG

Four 400 mg S- 2367 tablets (total dose = 1600 mg/day S-2367) administered orally once daily with AM meal while on both LCD and RCD for a total of 60 weeks

Also known as: Velneperit

S-2367 1600 mg q.d. 60 weeks

LCD (low calorie diet) OTHER

A low calorie diet was utilized during the first 6 weeks of the study

Placebo; S-2367 1600 mg q.d. 54 weeks; S-2367 1600 mg q.d. 60 weeks

RCD (reduced calorie diet) OTHER

A reduced calorie diet was used during the last 54 weeks for the study

Placebo; S-2367 1600 mg q.d. 54 weeks; S-2367 1600 mg q.d. 60 weeks

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 (ECGs), 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

You may not qualify if:

• 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 within 1 year prior to Visit 1

Sponsors & Collaborators

• Shionogi: lead

Study Sites (40)

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Birmingham, Alabama, 35209, United States

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Huntsville, Alabama, 35801, United States

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Phoenix, Arizona, 85014, United States

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Fountain Valley, California, 92708, United States

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San Diego, California, 92108, United States

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San Francisco, California, 94102, United States

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Waterbury, Connecticut, 06708, United States

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Jacksonville, Florida, 32259, United States

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Ocala, Florida, 34471, United States

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Orlando, Florida, 32809, United States

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South Miami, Florida, 33143, United States

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Atlanta, Georgia, 30338, United States

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Augusta, Georgia, 30904, United States

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Boise, Idaho, 83704, United States

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Chicago, Illinois, 60610, United States

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Gurnee, Illinois, 60031, United States

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Wichita, Kansas, 67207, United States

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Lexington, Kentucky, 40509, United States

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Boston, Massachusetts, 02135, United States

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South Dartmouth, Massachusetts, 02747, United States

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Brooklyn Center, Minnesota, 55430, United States

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Kansas City, Missouri, 64114, United States

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St Louis, Missouri, 63141, United States

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Lincoln, Nebraska, 68510, United States

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Las Vegas, Nevada, 89146, United States

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Edison, New Jersey, 08817, United States

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Endwell, New York, 13760, United States

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Burlington, North Carolina, 27215, United States

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Winston-Salem, North Carolina, 27103, United States

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Cincinnati, Ohio, 45219, United States

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Columbus, Ohio, 43212, United States

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Yukon, Oklahoma, 73099, United States

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Bensalem, Pennsylvania, 19020, United States

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Mt. Pleasant, South Carolina, 29464, United States

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Nashville, Tennessee, 37203, United States

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Fort Worth, Texas, 76135, United States

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New Braunfels, Texas, 78130, United States

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San Antonio, Texas, 78229, United States

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West Jordan, Utah, 84088, United States

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Wauwatosa, Wisconsin, 53226, United States

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MeSH Terms

Conditions

Obesity

Interventions

Caloric Restriction; Apoptosis

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Diet Therapy; Nutrition Therapy; Therapeutics; Energy Intake; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena; Regulated Cell Death; Cell Death; Cell Physiological Phenomena

Study Officials

• Shionogi Clinical Trials Administrator Clinical Support Help Line

  Shionogi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 5, 2008
• First Posted: September 8, 2008
• Study Start: June 1, 2007
• Primary Completion: November 1, 2008
• Study Completion: January 1, 2009
• Last Updated: May 11, 2018

Record last verified: 2018-05

Locations

US (40)