Last updated: 11/07/2018 04:03:42
A study to test how SB756050 affects subjects with Type 2 Diabetes Mellitus after 6 days of dosing.
Clinicaltrials.gov ID
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Completed
Completed
Trial overview
Official title: A single-blinded randomized, placebo-controlled, staggered-parallel, escalating-dose study to investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of oral SB756050 administered for 6 days to Subjects with Type 2 Diabetes Mellitus
Trial description: 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.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Single (Participant)
Allocation:
Randomized
Primary outcomes:
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.
Timeframe: 6 days of dosing
Secondary outcomes:
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.
Timeframe: 6 days of dosing
Safety and tolerability parameters including adverse events, clinical laboratory, ECGs and vital signs assessments.
Timeframe: 6 days of dosing
Subject reports of hunger and craving as reported on the Hunger and Craving questionnaire
Timeframe: 6 days of dosing
Interventions:
Drug: SB756050
Enrollment:
48
Observational study model:
Not applicable
Primary completion date:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Hodge R, Lin J, Vasist L, Gould E, Bowers G, Nunez D, on behalf of the SB-756050 Project Team. Safety, Pharmacokinetics, and Pharmacodynamic Effects of a Selective TGR5 Agonist, SB-756050, in Type 2 Diabetes . Clin Pharmacol Drug Devel. 2013
Medical condition
Diabetes Mellitus, Type 2
Product
SB756050
Collaborators
Not applicable
Study date(s)
August 2008 to March 2009
Type
Interventional
Phase
1
Participation criteria
Sex
Female & Male
Age
18 - 60 years
Accepts healthy volunteers
No
- 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.
- 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
Inclusion and exclusion criteria
Inclusion criteria:
- 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.
- Except as noted elsewhere, subjects should have no significant known medical conditions other than T2DM, as determined by a responsible physician, based on a medical evaluation including medical history, physical examination, laboratory tests and ECGs. A subject with a clinical abnormality or laboratory parameters that meets exclusion criteria but is outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
- 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.
Exclusion criteria:
- 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.
- Unwilling to abstain from caffeine-or xanthine-containing products for 24 hours prior to dosing until Day 7, Use of illicit drugs or nicotine-containing products, Alcohol for 24 hours prior to dosing until Day 7, Consumption of red wine, Seville oranges, grapefruit or grapefruit juice from 7 days prior to the first dose of study medication until collection of the final pharmacokinetic blood samples
- History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the physician responsible, contraindicates their participation. This includes sensitivity to heparin, if heparin will be used to maintain catheter patency.
- Where participation in the study would result in donation of blood in excess of 500 mL within a 56 day period.
- Subject is either an immediate family member of a participating investigator, study coordinator, employee of an investigator; or is a member of the staff conducting the study.
- Unwillingness or inability to follow the procedures outlined in the protocol.
Trial location(s)
Location
GSK Investigational Site
Orlando, Florida, United States, 32809
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Hackensack, New Jersey, United States, 07601
Status
Study Complete
Location
GSK Investigational Site
San Antonio, Texas, United States, 78209
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Miami, Florida, United States, 33169
Status
Terminated/Withdrawn
Study documents
Clinical study report
Available language(s): English
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Refer to study documents
Recruitment status
Completed
Actual primary completion date
Not applicable
Actual study completion date
2009-03-03
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
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Additional information
Results for study 111829 can be found on the GSK Clinical Study Register.
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