A 2-Part Trial in Subjects With Type 2 Diabetes and in Healthy Subjects to Evaluate GSK1614235, a New Glucose Lowering Drug to Treat Type 2 Diabetes

NCT00976261 | Completed Phase 1

• 1 other identifier: 112534
• Study Type: interventional
• Target: 72
• Locations: 4 countries
• Sites: 9

Brief Summary

The purpose of Part A of this study is to test whether repeated doses of the study drug (GSK1614235) are safe and well tolerated (i.e. do not produce unacceptable side effects) and whether we can obtain some preliminary information as to whether it works in lowering blood glucose levels. We will do this by comparing the effect of the study drug with placebo (no drug present) and against a drug (sitagliptin) known to control blood glucose in the treatment of diabetes. The purpose of Part B of this study is to determine the how the timing of dosing, relative to meals, affects the response to study drug.

Conditions

Diabetes Mellitus, Type 2

Keywords

type 2 diabetes; single dose; 3-O-methylglucose; healthy volunteer; repeat dose

Outcome Measures

Primary Outcomes (2)

• Part A: Safety, tolerability parameters: adverse events, gastro-intestinal side effects, subject reported outcomes, clinical laboratory results, ECGs and vital signs

  6 days

• Part B: Safety, tolerability parameters: adverse events, gastro-intestinal side effects, subject reported outcomes, clinical laboratory results, ECGs and vital signs

  1 day

Secondary Outcomes (5)

• Part A: Pharmacokinetics

  6 days

• Part A: Pharmacodynamics

  6 days

• Part B: Pharmacokinetics

  1 day

• Part B: Pharmacodynamics

  1 day

• Part B: 3-O-Methyl-Glucose Kinetics

  1 day

Study Arms (3)

GSK1614235

EXPERIMENTAL

Glucose lowering agent under investigation.

Drug: GSK1614235

Sitagliptin

ACTIVE COMPARATOR

Glucose lowering comparator

Drug: Sitagliptin

Placebo

PLACEBO COMPARATOR

Placebo to match GSK1614235 and placebo to match Sitagliptin

Other: Placebo

Interventions

GSK1614235 DRUG

Glucose lowering in Type 2 Diabetes Mellitus

Also known as: Type 2 Diabetes Mellitus

GSK1614235

Sitagliptin DRUG

Glucose lowering in Type 2 Diabetes Mellitus

Also known as: Type 2 Diabetes Mellitus

Sitagliptin

Placebo OTHER

Comparator

Also known as: Type 2 Diabetes Mellitus

Placebo

Eligibility Criteria

• Age: 30 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects with documented type 2 diabetes mellitus diagnosis whose HbA1c levels are \>7 and at or less than 9.5%; at screening, who are either controlled by diet alone, or are on monotherapy with oral sulfonylureas, DPP-IV inhibitors (e.g. sitagliptin), or metformin.
• Men and women 30 - 65 years of age, inclusive, at screening.
• Women: post-menopausal or surgically sterile, i.e. women of non-childbearing potential.
• Male subjects must agree to use a contraception method
• Body weight 50kg for men and 45kg for women and BMI within the range 22 35kg/m2, inclusive.
• Subjects taking stable regimens of aspirin, ACE inhibitors, beta-blockers, calcium channel blockers, thyroid replacement hormone, and HMG-CoA reductase inhibitors (statins) will be allowed if their dose regimen(s) remain constant throughout the study period.
• Signed and dated written informed consent prior to enrollment into the study, including performance of any screening procedures.
• The subject is able to understand and comply with protocol requirements

You may not qualify if:

• Requiring insulin therapy or use of combination oral antidiabetic medications or use of monotherapy other than oral sulfonylureas, DPP-IV inhibitors (e.g. sitagliptin), or metformin within the 3 months prior to screening.
• Medically unable or unwilling to discontinue current anti-diabetic therapy for 72 hours prior to admission to the research facility and remain off medication until the follow-up visit.
• Past or present disease (other than type 2 diabetes mellitus) including, but are not limited to, cardiovascular disease, malignancy, hepatic disease, renal disease, haematological disease, neurological disease and endocrine disease.
• Past or present history of irritable bowel syndrome, gastrointestinal surgeries, or any other gastrointestinal complaints, history of GI intolerance to sitagliptin, lactose intolerance or hepatobiliary conditions that may interfere with the absorption of GSK1614235 or interfere with the objectives and endpoints of the study.
• History or presence of sensitivity or allergy to the study drug or drugs, GSK 1614235 or sitagliptin, their components, or drugs of these classes or a history of drug or other allergy that contraindicates participation.
• Subjects with laboratory results that are not clinically significant may be included in the study
• Significant renal disease as manifested by one of the following:
• Creatinine clearance \<60mL/min Urine albumin concentration at or \>300ug/mg of creatinine. Known loss of a kidney, either by surgical ablation, injury, or disease.
• Positive test results for hepatitis C antibodies, hepatitis B surface antigen, and HIV at screening.
• Abuse of alcohol
• A positive pre-study urine drug screen
• No significant concomitant health problems other than type 2 diabetes mellitus and otherwise healthy. Subjects with the following clinical laboratory values are excluded:
• ALT or AST \> 2 times the upper limit of normal at screening. Bilirubin \> 1.5 times the upper limit of normal at screening (total; subjects above this limit may only be included if direct bilirubin is within normal limits).
• Fasting triglycerides \> 400mg/dL (22.2mmol/L) at screening. Fasting LDL cholesterol \> 160mg/dL (3.3mmol/L). Participation in a study trial with any investigational new drug (new chemical entity) within 90 days prior to the start of the study.
• For ECG rates and intervals, the average of 3 ECG assessments, separated by 5 minutes is used. Significant ECG abnormalities include but are not limited to:

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (9)

GSK Investigational Site

Miami, Florida, 33169, United States

Location

GSK Investigational Site

Baton Rouge, Louisiana, 70808, United States

Location

GSK Investigational Site

Cincinnati, Ohio, 45212, United States

Location

GSK Investigational Site

Gières, 38610, France

Location

GSK Investigational Site

Rueil-Malmaison, 92502, France

Location

GSK Investigational Site

Neuss, North Rhine-Westphalia, 41460, Germany

Location

GSK Investigational Site

Berlin, 14050, Germany

Location

GSK Investigational Site

Hamburg, 22769, Germany

Location

GSK Investigational Site

Cambridge, Cambridgeshire, CB2 2GG, United Kingdom

Location

Related Publications (1)

• Dobbins RL, Greenway FL, Chen L, Liu Y, Breed SL, Andrews SM, Wald JA, Walker A, Smith CD. Selective sodium-dependent glucose transporter 1 inhibitors block glucose absorption and impair glucose-dependent insulinotropic peptide release. Am J Physiol Gastrointest Liver Physiol. 2015 Jun 1;308(11):G946-54. doi: 10.1152/ajpgi.00286.2014. Epub 2015 Mar 12.

  PMID: 25767259 DERIVED

Related Links

• Results for study 112534 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Sitagliptin Phosphate

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: September 11, 2009
• First Posted: September 14, 2009
• Study Start: October 17, 2009
• Primary Completion: September 5, 2010
• Study Completion: September 5, 2010
• Last Updated: June 8, 2017

Record last verified: 2017-06

Locations

US (3); FR (2); GB (1); DE (3)