A Study to Test How SB756050 Affects Subjects With Type 2 Diabetes Mellitus After 6 Days of Dosing.

NCT00733577 | Completed Phase 1

• 1 other identifier: 111829
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 4

Brief Summary

This is an escalating dose study in subjects with T2DM, which will consist of four overlapping cohorts receiving 6 days of SB756050 to assess safety, pharmacokinetics, and pharmacodynamics.

Conditions

Diabetes Mellitus, Type 2

Keywords

diabetes; pharmacodynamics; safety; pharmacokinetics

Outcome Measures

Primary Outcomes (1)

• Safety measures including: AEs daily; laboratory testing: day -1,2,5,7 and follow up; ECG: day -1, 2, 5, 6, 7 and follow-up; vital signs: daily; PK parameters day -1,5, and 6.

  6 days of dosing

Secondary Outcomes (3)

• Pharmacodynamic endpoints will include fasting and meal or OGTT-related weighted mean AUC for glucose, GLP-1 (total and active), glucagon, insulin, PYY (active) and C-peptide levels.

  6 days of dosing

• Safety and tolerability parameters including adverse events, clinical laboratory, ECGs and vital signs assessments.

  6 days of dosing

• Subject reports of hunger and craving as reported on the Hunger and Craving questionnaire

  6 days of dosing

Study Arms (4)

Cohort 1

EXPERIMENTAL

15 mg SB756050 or placebo

Drug: SB756050

Cohort 2

EXPERIMENTAL

Planned dose for Cohorts 2 50mg SB756050 or placebo

Drug: SB756050

Cohort 3

EXPERIMENTAL

Planned dose for Cohort 3 150mg SB756050 or placebo

Drug: SB756050

Cohort 4

EXPERIMENTAL

Planned dose for Cohort 4 600mg SB756050 or placebo

Drug: SB756050

Interventions

SB756050 DRUG

doses are planned to be 15mg to 600mg doses may be altered based on plasma concentrations

Cohort 1; Cohort 2; Cohort 3; Cohort 4

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female subjects, 18 - 60 years of age, inclusive, at the time of signing the informed consent
• A female subject is eligible to participate if she is of non-childbearing potential, defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea. FSH and estradiol levels will be checked at Screening for postmenopausal women. Simultaneous follicle stimulating hormone (FSH) \> 40 MlU/ml and estradiol \< 40 pg/ml (\<140 pmol/L) is confirmatory.

You may not qualify if:

• BMI (body mass index) within the range 25-35 kg/m2, inclusive.
• T2DM diagnosed at least 3 months prior to Screening
• Subjects must be treating their T2DM using one of the following regimens: Diet and exercise therapy, Metformin as monotherapy, Sulfonylurea as monotherapy, Metformin and sulfonylurea in combination, DPP-IV inhibitors, either as monotherapy or in combination with other agent(s) on this list at half maximal dose or less, Exenatide, either as monotherapy or in combination with other agent(s) on this list All doses of anti-diabetic medication must have been stable for at least 3 months prior to Screening, and the subject must be willing to wash out from their antidiabetic medications from Day -7 through Day 7.
• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
• Has positive pre-study Hepatitis B surface antigen or positive Hepatitis C, result within 3 months of screening. Positive test for HIV antibody. History of uncorrected thyroid dysfunction. ALT and/or AST \> 2 times the upper limit of normal at screening. Fasting triglycerides \> 450mg/dL at screening. Total Bilirubin \> 1.5 times the upper limit of normal at screening. A positive pre-study drug/urine screen and tobacco screen.
• Significant renal disease
• Significant ECG abnormalities
• Systolic pressure \> 150 mmHg or \<80 mmHg or diastolic blood pressure \> 95 mmHg or \<60 mmHg at screening.
• Previous use of insulin as a treatment within 3 months of Screening, or for \>2 weeks when used for acute illness in the last 12 months prior to Screening, or if used for more than 1 year when associated with GDM.
• Has a history of gastrointestinal disease that could affect absorption within the past year, Gastrointestinal surgery, Chronic or acute pancreatitis.
• History of regular alcohol consumption
• Smoked or used tobacco or nicotine-containing products within the previous 6 months.
• Has participated in a clinical trial and has received a drug or a new chemical entity within 30 days or 5 half-lives, or twice the duration of the biological effect of any drug (whichever is longer) prior to the first dose of current study medication.
• Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
• Is taking prohibited medications.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (4)

GSK Investigational Site

Miami, Florida, 33169, United States

Location

GSK Investigational Site

Orlando, Florida, 32809, United States

Location

GSK Investigational Site

Hackensack, New Jersey, 07601, United States

Location

GSK Investigational Site

San Antonio, Texas, 78209, United States

Location

Related Publications (1)

• Hodge RJ, Lin J, Vasist Johnson LS, Gould EP, Bowers GD, Nunez DJ; SB-756050 Project Team. Safety, Pharmacokinetics, and Pharmacodynamic Effects of a Selective TGR5 Agonist, SB-756050, in Type 2 Diabetes. Clin Pharmacol Drug Dev. 2013 Jul;2(3):213-22. doi: 10.1002/cpdd.34. Epub 2013 May 14.

  PMID: 27121782 DERIVED

Related Links

• Results for study 111829 can be found on the GSK Clinical Study Register.
• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Diabetes Mellitus

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 12, 2008
• First Posted: August 13, 2008
• Study Start: August 11, 2008
• Primary Completion: March 3, 2009
• Study Completion: March 3, 2009
• Last Updated: July 13, 2017

Record last verified: 2017-07

Data Sharing

• IPD Sharing: Will share

Locations

US (4)