Double-Blind, Multi-Center, Randomized Study to Assess the Efficacy and Safety of Velneperit (S-2367) and Orlistat Administered Individually or Combined With a Reduced Calorie Diet (RCD) in Obese Subjects

NCT01126970 | Completed Phase 2 DMC

• 1 other identifier: 1002A2828
• Study Type: interventional
• Target: 486
• Locations: 1 country
• Sites: 25

Brief Summary

To evaluate the weight loss effect and safety of 400 mg velneperit and 120 mg orlistat administered individually or combined three times per day for 24 weeks while on a reduced calorie diet (RCD) and also to evaluate the steady-state trough concentrations of velneperit (S-2367), velneperit (S-2367) tert-butyl OH, and velneperit (S-2367) tert-butyl OH-O glucuronide following 400 mg of velneperit (S-2367) three times per day and 120 mg of orlistat, either combined or separate.

Conditions

Obesity

Keywords

reduced calorie diet; orlistat; velneperit

Outcome Measures

Primary Outcomes (1)

• The primary efficacy endpoint was the change from baseline in body weight (kg) over the 168-day (24-week) double-blind treatment period, where baseline body weight was defined as the last measurement prior to randomization

  Change in body weight from baseline to 24 weeks

  168 days (24 weeks)

Secondary Outcomes (4)

• Efficacy analysis: The proportion of subjects with (a) a 5% decrease in body weight at Visit 7 and Visit 10 and (b) percent change in body weight from baseline to each study visit was summarized by treatment group

  change from baseline to each study visit

• Efficacy analysis: The change in waist & hip circumference (cm) from baseline to each study visit was summarized by treatment group

  Change from baseline to each study visit

• Efficacy analysis: The proportion of subjects with a decrease equal to or greater than 1 BMI unit at Visit 7 and Visit 10 was summarized by treatment group

  Baseline to Visits 7 and 10

• Safety analysis: (a) Treatment-emergent adverse events and (b) monitoring clinical laboratory evaluations, vital signs, 12-lead electrocardiograms, and physical examinations

  Baseline to each visit and to Week 24

Study Arms (4)

Placebos.

PLACEBO COMPARATOR

Velneperit Placebo q.d.+ Orlistat Placebo t.i.d.

Drug: Orlistat Placebo; Drug: Velneperit Placebo; Other: Reduced Calorie Diet

Velneperit 400 mg

EXPERIMENTAL

Velneperit 400 mg q.d.

Drug: Velneperit 400 mg; Drug: Orlistat Placebo; Other: Reduced Calorie Diet

Orlistat 120 mg

ACTIVE COMPARATOR

Orlistat 120 mg t.i.d.

Drug: Orlistat 120 mg; Drug: Velneperit Placebo; Other: Reduced Calorie Diet

Velneperit 400 mg + Orlistat 120 mg

EXPERIMENTAL

Velneperit 400 mg q.d.and Orlistat 120 mg t.i.d

Drug: Velneperit 400 mg; Drug: Orlistat 120 mg; Other: Reduced Calorie Diet

Interventions

Velneperit 400 mg DRUG

Velneperit 400 mg q.d.

Also known as: S-2367

Velneperit 400 mg; Velneperit 400 mg + Orlistat 120 mg

Orlistat 120 mg DRUG

Orlistat 120 mg t.i.d

Also known as: Xenical

Orlistat 120 mg; Velneperit 400 mg + Orlistat 120 mg

Orlistat Placebo DRUG

Orlistat Placebo t.i.d.

Placebos.; Velneperit 400 mg

Velneperit Placebo DRUG

Velneperit Placebo q.d

Orlistat 120 mg; Placebos.

Reduced Calorie Diet OTHER

Reduced calorie diet

Orlistat 120 mg; Placebos.; Velneperit 400 mg; Velneperit 400 mg + Orlistat 120 mg

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and females between 18 and 65 years of age at the time of informed consent
• Weight that has not fluctuated by more than 3% for the 90 days prior to Visit 1
• Non-smoker and no use of tobacco or nicotine products for at least 1 year prior to Visit 1
• Normotensive or acceptable level of hypertension, defined as systolic \<160 and diastolic \<95 mmHg
• No clinically significant laboratory abnormalities
• Negative urine drug screen for drugs of abuse
• No clinically significant findings on medical history, physical examination, and electrocardiogram (ECG) and no known history of clinically significant ECG abnormalities
• Negative serum pregnancy test in women of child-bearing potential (Females must be at least one year post-partum.)
• Males either should remain abstinent, be sterile or agree to use an approved method of contraception (which for males includes use of a condom with spermicide) Visit 1 through 12 weeks following the last dose, in addition to having a female partner use an effective form of contraception as noted below
• All female subjects must be non-pregnant (confirmed by a negative serum pregnancy test), have no plans of becoming pregnant during the study, and must be at least one year post-partum, non-lactating, postmenopausal, (defined as cessation of regular menstrual periods for at least one year and confirmed by a follicle-stimulating hormone test), or surgically sterile by hysterectomy and/or bilateral oophorectomy or tubal ligation. Females of child-bearing potential must agree to use acceptable forms of birth control including oral, implantable or transdermal 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 comply with all required study procedures and schedule
• Able to speak and read English
• Signed and dated informed consent form prior to any study-related procedures

You may not qualify if:

• Obesity of known endocrine or genetic origin (eg, hypothyroidism, Cushing's syndrome or diagnosed polycystic ovarian syndrome) meeting one of the following conditions:
• Menstrual irregularity due to oligo- or anovulation
• Evidence of hyperandrogenism, whether clinical (hirsutism, acne, or male pattern balding) or biochemical (high serum androgen concentrations)
• History of malignancy within the previous 5 years with the exception of non-melanoma skin cancer or surgically cured cervical cancer
• Human immunodeficiency virus (HIV) identified by history or previous HIV test
• Any serious medical condition that, in the opinion of the Investigator, would limit the subject's ability to complete and/or participate in this clinical study including any clinically significant findings from medical history, physical examination, 12-lead ECG, and vital signs
• Known history or evidence of a psychiatric disorder that in the opinion of the investigator would preclude the subject from participating in the trial. Stable or controlled anxiety or depression are permitted. Treatment with an antidepressant or anxiolytic drug is permitted if in accordance with Appendix 4. Subjects with a score of 11 or higher on the depression portion of the Hospital Anxiety and Depression Scale are excluded.
• Subjects with pancreatitis or chronic pancreatic inflammation
• History of Type 1 or Type 2 diabetes mellitus as defined by HbA1c \> 6.5% or blood glucose values of \> 126 mg/dl or treated Type 2 diabetes mellitus
• Any weight gain during the single-blind lead-in period (Visit 1 and Visit 3)
• History of surgical or device (eg, gastric bypass) intervention for obesity 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 90 days prior to screening
• History of alcoholism or drug addiction/substance abuse within 1 year of Visit 1. Note: No alcohol consumption is permitted within 48 hours prior to blood collections for analysis of lipid profiles.
• Abnormal thyroid stimulating hormone level at screening
• Subjects with hypothyroidism
• Subjects with genetic hematologic disease or trait with or without manifestation of disease.

Sponsors & Collaborators

• Shionogi: lead

Study Sites (25)

Unknown Facility

Santa Rosa, California, United States

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Waterbury, Connecticut, United States

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Clearwater, Florida, United States

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Jacksonville, Florida, United States

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Ocala, Florida, United States

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Ponte Vedra, Florida, United States

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Augusta, Georgia, United States

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Louisville, Kentucky, United States

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Boston, Massachusetts, United States

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Milford, Massachusetts, United States

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North Dartmouth, Massachusetts, United States

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St Louis, Missouri, United States

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Lincoln, Nebraska, United States

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Albuquerque, New Mexico, United States

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Manlius, New York, United States

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Rochester, New York, United States

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Cary, North Carolina, United States

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Raleigh, North Carolina, United States

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Cleveland, Ohio, United States

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Columbus, Ohio, United States

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Greenville, South Carolina, United States

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Nashville, Tennessee, United States

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New Braunfels, Texas, United States

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Renton, Washington, United States

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Wauwatosa, Wisconsin, United States

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MeSH Terms

Conditions

Obesity

Interventions

Orlistat

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Lactones; Organic Chemicals

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: May 17, 2010
• First Posted: May 20, 2010
• Study Start: April 1, 2010
• Primary Completion: January 1, 2011
• Study Completion: February 1, 2011
• Last Updated: May 9, 2018

Record last verified: 2018-05

Locations

US (25)