NCT01376323

Brief Summary

The aim of this combined, two part study is to evaluate the safety and glucose lowering effects of GSK256073 when administered to diabetic subjects for 12 weeks.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
92

participants targeted

Target at P25-P50 for phase_2 diabetes-mellitus-type-2

Timeline
Completed

Started Jul 2011

Typical duration for phase_2 diabetes-mellitus-type-2

Geographic Reach
4 countries

15 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

June 16, 2011

Completed
4 days until next milestone

First Posted

Study publicly available on registry

June 20, 2011

Completed
23 days until next milestone

Study Start

First participant enrolled

July 13, 2011

Completed
1.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 16, 2012

Completed
1 day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 17, 2012

Completed
5.1 years until next milestone

Results Posted

Study results publicly available

October 11, 2017

Completed
Last Updated

October 11, 2017

Status Verified

August 1, 2017

Enrollment Period

1.2 years

First QC Date

June 16, 2011

Results QC Date

August 10, 2017

Last Update Submit

September 11, 2017

Conditions

Keywords

SafetyDose RangingEfficacy

Outcome Measures

Primary Outcomes (8)

  • Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)

    An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, may jeopardize the participant or require medical or surgical intervention to prevent one of the other outcomes listed in the definition above, or is an event of possible drug-induced liver injury.

    Up to Week 12

  • Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)

    Mean of triplicate measurements at each time point was considered for the summary. Baseline was defined as pre-dose of Day 1 visit. Change from Baseline was calculated by subtracting the Baseline values from the corresponding post-treatment values. It was assessed on Baseline, Day 1 (12 hours), Day 2 (pre-dose and 12 hours), Week 3, 6 (pre-dose and 12 hours), 9 and 12.

    Baseline (pre-dose Day 1) and up to Week 12

  • Change From Baseline in Heart Rate

    Mean of triplicate measurements at each time point was considered for the summary. Baseline was defined as pre-dose of Day 1 visit. Change from Baseline was calculated by subtracting the Baseline values from the corresponding post-treatment values. It was assessed on Baseline (pre-dose Day 1), Day 1 (12 hours), Day 2, Week 3, 6, 9 and 12.

    Baseline (pre-dose Day 1) and up to Week 12

  • Number of Participants With Abnormal Electrocardiograms (ECGs) Findings

    Single 12-lead ECGs were obtained at each time point during the study using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, and QTc intervals. It was assessed at Baseline (pre-dose Day 1), Day 2, Week 3, Week 6 and 12. Participants with normal, abnormal not clinically significant and abnormal clinically significant ECG were presented.

    Up to Week 20

  • Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance (PCI)

    Clinical chemistry parameters included blood urea nitrogen (BUN), potassium, aspartate aminotransferase (AST), total bilirubin, direct bilirubin, creatinine, chloride, alanine aminotransferase (ALT), uric acid, fasting glucose, total carbon dioxide, gamma glutamyltransferase (GGT), albumin, sodium, calcium, alkaline phosphatase (ALP), total protein, creatine phosphokinase (CPK) and fasting lipid panel including total cholesterol, triglycerides, high density lipoprotein (HDL) cholesterol and low density lipoprotein (LDL) cholesterol. It was assessed on Baseline (pre-dose Day 1), Week 3 and 12. Data for parameters with high and low of PCI is provided.

    Up to Week 12

  • Number of Participants With Hematology Abnormalities of Potential Clinical Importance (PCI)

    Hematology parameters included platelet, red blood cell (RBC) count, mean corpuscular volume (MCV), neutrophils, white blood cell (WBC) count (absolute), mean corpuscular hemoglobin (MCH), lymphocytes, reticulocyte count, mean corpuscular hemoglobin concentration (MCHC), monocytes, hemoglobin, eosinophils, hematocrit and basophils. It was assessed on Baseline (pre-dose Day 1) and 12. Data for parameters with high and low of PCI is provided.

    Up to Week 12

  • Number of Participants With Abnormal Urinalysis: Glucose, Protein, Blood and Ketones by Dipstick

    Urinalysis parameters included glucose, protein, blood and ketones by dipstick. It was assessed on Baseline (Day -1) and 12. Urine glucose was measured as grams per deciliter (G/dL).

    Up to Week 12

  • Change From Baseline in Glycated Hemoglobin (HbA1c) at Week 12

    Blood samples for analysis of HbA1c were collected at Baseline (Day -1), Day 41, Week 9 and Week 12. Change from Baseline was calculated by subtracting the Baseline values from the corresponding post-treatment values. Baseline was defined as Day -1 visit. Statistics is provided for least square mean at Week 12.

    Baseline (Day -1) and up to Week 12

Secondary Outcomes (7)

  • Change From Baseline in 12 Hour Non-esterified Fatty Acids (NEFA) and Glucose Weighted Mean Concentration Value at Day 2 and at Week 6

    Baseline (Day 1) and up to Week 6

  • GSK256073 AUC and HbA1c at Week 12 Was Evaluated to Establish the Exposure-response Pharmacokinetic/Pharmacodynamic (PK/PD) Relationship

    Up to Week 12

  • Change From Baseline in Fasting Plasma Glucose at Week 12

    Baseline (Day 1) and up to Week 12

  • Change From Baseline in Fasting Insulin at Week 12

    Baseline (Day 1) and up to Week 12

  • Summary of Homeostatic Model Assessment (HOMA) Index Calculated From Change From Baseline in Fasting Insulin and Fasting Glucose at Week 12

    Baseline (Day 1) and up to Week 12

  • +2 more secondary outcomes

Study Arms (10)

GSK256073 1mg bid

EXPERIMENTAL

GSK256073 1mg capsule taken orally twice a day

Drug: GSK256073 1mg

GSK256073 2mg qd

EXPERIMENTAL

GSK256073 2 x 1mg capsule taken orally once a day

Drug: GSK256073 1mg

GSK256073 5mg bid

EXPERIMENTAL

GSK256073 5mg capsule taken orally twice a day

Drug: GSK256073 5mg

GSK256073 10mg qd

EXPERIMENTAL

GSK256073 2 x 5mg capsule taken orally once a day

Drug: GSK256073 5mg

GSK256073 10mg bid

EXPERIMENTAL

GSK256073 10mg capsule taken orally twice a day

Drug: GSK256073 10mg

GSK256073 20mg qd

EXPERIMENTAL

GSK256073 2x 10mg capsule taken orally once a day

Drug: GSK256073 10mg

GSK256073 25mg bid

EXPERIMENTAL

GSK256073 25mg capsule taken orally twice a day

Drug: GSK256073 25mg

GSK256073 50mg qd

EXPERIMENTAL

GSK256073 2x 25mg capsule taken orally once a day

Drug: GSK256073 25mg

Placebo

PLACEBO COMPARATOR

Matching placebo capsules taken orally either once a day or twice a day

Drug: Placebo

Sitagliptin 100mg qd

ACTIVE COMPARATOR

Commercially available Sitagliptin 100mg capsules taken once a day

Drug: Sitagliptin 100mg

Interventions

GSK256073 1mg capsule

GSK256073 1mg bidGSK256073 2mg qd

GSK256073 5mg capsule

GSK256073 10mg qdGSK256073 5mg bid

GSK256073 10mg capsule

GSK256073 10mg bidGSK256073 20mg qd

GSK256073 25mg capsule

GSK256073 25mg bidGSK256073 50mg qd

placebo capsule

Placebo

Sitagliptin 100mg capsule

Sitagliptin 100mg qd

Eligibility Criteria

Age20 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may not qualify if:

  • HbA1c levels greater than or equal to 7.0 % and less than or equal to 9.5% at Screening
  • On monotherapy with metformin at the time of screening, and at a maximum tolerated dose greater than or equal to 1000 mg for at least 2 months prior to dosing.
  • Fasting plasma glucose level less than 13.3 mmol/L (240 mg/dL) at Screening
  • Male or female between 20 and 70 years of age, inclusive, at the time of signing the informed consent
  • Fasting Triglycerides lower than 4.52 mmol/L (400 mg/dL)
  • A female subject is able to participate is she if of non-child bearing potential
  • Male subjects must agree to use one of the contraception methods listed in the protocol. This criterion must be followed from the time of the first dose of study medication until 3 days after last dose of the study medication
  • Overweight with BMI greater than or equal to 25 kg/m2 for non-Asian Indians and greater than or equal to 24 kg/m2 for Asian-Indian, and less than 40 kg/m2
  • The subject is capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form
  • Subjects in France will be eligible only if they are affiliated to or a beneficiary of a social security category
  • Subjects in other countries must meet all local and/or country-specific requirements for registration and reimbursement, as applicable
  • Requiring insulin therapy or use of combination oral antidiabetic medications or use of monotherapy other than metformin within the 3 months prior to screening
  • Past or present disease (other than type 2 diabetes mellitus) that in the opinion of the Investigator may affect the outcome of this study
  • A positive pre-study Hepatitis B surface antigen, or positive Hepatitis C result within 3 months of screening
  • Renal impairment as defined by a calculated GFR less than 60 mL/min
  • +19 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (15)

GSK Investigational Site

Anniston, Alabama, 36207, United States

Location

GSK Investigational Site

Miami, Florida, 33169, United States

Location

GSK Investigational Site

Miramar, Florida, 33025, United States

Location

GSK Investigational Site

Nantes, 44093, France

Location

GSK Investigational Site

Pierre-Bénite, 69495, France

Location

GSK Investigational Site

Rennes, 35046, France

Location

GSK Investigational Site

Rueil-Malmaison, 92502, France

Location

GSK Investigational Site

Alicante, 03114, Spain

Location

GSK Investigational Site

Badalona, 08916, Spain

Location

GSK Investigational Site

Granada, 18004, Spain

Location

GSK Investigational Site

Madrid, 28046, Spain

Location

GSK Investigational Site

Edinburgh, Midlothian, EH4 2XU, United Kingdom

Location

GSK Investigational Site

Cambridge, CB2 0GG, United Kingdom

Location

GSK Investigational Site

Coventry, CV2 2DX, United Kingdom

Location

GSK Investigational Site

Newcastle upon Tyne, NE1 4LP, United Kingdom

Location

Related Links

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

8-chloro-3-pentyl-1H-purine-2,6(3H,7H)-dioneSitagliptin Phosphate

Condition Hierarchy (Ancestors)

Diabetes MellitusGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System Diseases

Intervention Hierarchy (Ancestors)

TriazolesAzolesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsPyrazines

Results Point of Contact

Title
GSK Response Center
Organization
GlaxoSmithKline

Study Officials

  • GSK Clinical Trials

    GlaxoSmithKline

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

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

Study Record Dates

First Submitted

June 16, 2011

First Posted

June 20, 2011

Study Start

July 13, 2011

Primary Completion

September 16, 2012

Study Completion

September 17, 2012

Last Updated

October 11, 2017

Results First Posted

October 11, 2017

Record last verified: 2017-08

Data Sharing

IPD Sharing
Will share

Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Available IPD Datasets

Statistical Analysis Plan (114728)Access
Individual Participant Data Set (114728)Access
Informed Consent Form (114728)Access
Study Protocol (114728)Access
Dataset Specification (114728)Access
Annotated Case Report Form (114728)Access
Clinical Study Report (114728)Access

Locations