A Study of GSK256073 in Subjects With Type 2 Diabetes Mel... | NCT01376323

Label	Type	Description	Intervention Names
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

Name	Type	Description	Arm Group Labels	Other Names
GSK256073 1mg	Drug	GSK256073 1mg capsule	GSK256073 1mg bid GSK256073 2mg qd

Measure	Description	Time Frame
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.

Measure	Description	Time Frame
Change From Baseline in 12 Hour Non-esterified Fatty Acids (NEFA) and Glucose Weighted Mean Concentration Value at Day 2 and at Week 6	Change from Baseline was calculated by subtracting the Baseline values from the corresponding post-treatment values. Baseline was defined as weighted mean value at Day 1 visit. Statistics is provided for least square mean at Week 6. It was assessed on Baseline (Day 1), Day 2 and Week 6.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

A diagnosis of T2DM as determined by a responsible physician based on a medical evaluation including medical history, physical examination, and laboratory tests, with onset at least 6 months prior to Screening. Subjects may be entered if they have stable hypertension or dyslipidemia on therapy. Subjects with other conditions except as noted in the Exclusion criteria may be included only if the investigator and GSK medical monitor agree that the condition is unlikely to introduce additional risk factors and will not interfere with study procedures
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

Exclusion Criteria:

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
Any concurrent serious illness (e.g., severe COPD, history of malignancy other than skin cancer within 5 years of initial diagnosis or with evidence of recurrence) that may interfere with a subject completing the study
Laboratory values as defined per protocol
ECG criteria as defined per protocol
Systolic blood pressure greater than 160 mmHg, or diastolic blood pressure greater than 100 mmHg at Screening
History of uric acid kidney stone, and being treated with drugs for hyperuricemia including Allopurinol or Probenecid
History of peptic ulcer disease (PUD) and/or other gastrointestinal bleeding within the 12 months prior to screening
Use of certain blood pressure medications or certain other medications that are renally excreted as defined per protocol
History of myopathy or CPK value greater than 3 times upper limit of normal at screening
The subject has participated in a clinical trial and has received an investigational product within 30 days or 5 half-lives or twice the biological effect (whichever is longer)
Exposure to more than four new chemical entities within 12 months prior to the first dosing day
Any change in diet, exercise habits or smoking status within six weeks prior to screening. Any subject that cannot refrain from smoking while in the unit must be excluded
History of sensitivity to any of the study medications, including sitagliptin or metformin, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation
The subject has a positive pre-study drug screen
History of regular alcohol consumption within 6 months of the study as defined per protocol
Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period
Pregnant females as determined by positive serum and/or urine hCG test at screening and prior to dosing
Lactating females
Subjects who are unwilling or unable to follow the procedures outlined in the protocol
Subject is mentally or legally incapacitated

Name	Affiliation	Role
GSK Clinical Trials	GlaxoSmithKline	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
GSK Investigational Site		Anniston	Alabama	36207	United States
GSK Investigational Site

Label	URL
Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.	View source

ID	Type	URL	Comment
114728	Statistical Analysis Plan	View IPD

ID	Title	Description
FG000	Placebo (Pooled)	Eligible participants in this arm received GSK256073 matching placebo capsules twice a day (BID) and once daily orally as directed with water for 12 weeks in a fed state. According to the randomized dose regimen, participants either took 2 capsules in the morning (once daily arm) or 1 capsule each in the morning and evening (BID arms). The data for placebos-GSK256073 matched placebo BID and GSK256073 matched placebo once daily was pooled into one placebo group.

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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.

Safety population was used which was defined as all participants who received at least one dose of study drug.

Posted

Count of Participants

Participants

Up to Week 12

ID	Title	Description
OG000	Placebo (Pooled)	Eligible participants in this arm received GSK256073 matching placebo capsules BID and once daily orally as directed with water for 12 weeks in a fed state. According to the randomized dose regimen, participants either took 2 capsules in the morning (once daily arm) or 1 capsule each in the morning and evening (BID arms). The data for placebos-GSK256073 matched placebo BID and GSK256073 matched placebo once daily was pooled into one placebo group.
OG001	GSK256073 5 mg BID	Eligible participants in this arm received GSK256073 5 mg capsules BID orally as directed with water for 12 weeks in a fed state.
OG002	GSK256073 10 mg Once Daily	Eligible participants in this arm received GSK256073 10 mg capsules once daily orally as directed with water for 12 weeks in a fed state.
OG003	GSK256073 25 mg BID	Eligible participants in this arm received GSK256073 25 mg capsules BID orally as directed with water for 12 weeks in a fed state.
OG004	GSK256073 50 mg Once Daily	Eligible participants in this arm received GSK256073 50 mg capsules once daily orally as directed with water for 12 weeks in a fed state.

Units	Counts
Participants	OG00020 OG00118 OG00219 OG003

Title

Denominators

Categories

Any AE

Title	Measurements
	OG00011 OG00112 OG00212 OG003

Primary

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.

Safety population. Only those participants available at the specified time points were analyzed.

Posted

Mean

Standard Deviation

Millimeters of mercury

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

ID	Title	Description
OG000	Placebo (Pooled)	Eligible participants in this arm received GSK256073 matching placebo capsules BID and once daily orally as directed with water for 12 weeks in a fed state. According to the randomized dose regimen, participants either took 2 capsules in the morning (once daily arm) or 1 capsule each in the morning and evening (BID arms). The data for placebos-GSK256073 matched placebo BID and GSK256073 matched placebo once daily was pooled into one placebo group.
OG001	GSK256073 5mg BID	Eligible participants in this arm received GSK256073 5 mg capsules BID orally as directed with water for 12 weeks in a fed state.
OG002

Primary

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.

Safety population. Only those participants available at the specified time points were analyzed.

Posted

Mean

Standard Deviation

Beats per minute

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

ID	Title	Description
OG000	Placebo (Pooled)	Eligible participants in this arm received GSK256073 matching placebo capsules BID and once daily orally as directed with water for 12 weeks in a fed state. According to the randomized dose regimen, participants either took 2 capsules in the morning (once daily arm) or 1 capsule each in the morning and evening (BID arms). The data for placebos-GSK256073 matched placebo BID and GSK256073 matched placebo once daily was pooled into one placebo group.
OG001	GSK256073 5mg BID	Eligible participants in this arm received GSK256073 5 mg capsules BID orally as directed with water for 12 weeks in a fed state.
OG002	GSK256073 10mg Once Daily

Primary

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.

Safety population. Only those participants available at the specified time points were analyzed.

Posted

Count of Participants

Participants

Up to Week 20

ID	Title	Description
OG000	Placebo (Pooled)	Eligible participants in this arm received GSK256073 matching placebo capsules BID and once daily orally as directed with water for 12 weeks in a fed state. According to the randomized dose regimen, participants either took 2 capsules in the morning (once daily arm) or 1 capsule each in the morning and evening (BID arms). The data for placebos-GSK256073 matched placebo BID and GSK256073 matched placebo once daily was pooled into one placebo group.
OG001	GSK256073 5 mg BID	Eligible participants in this arm received GSK256073 5 mg capsules BID orally as directed with water for 12 weeks in a fed state.
OG002	GSK256073 10 mg Once Daily

Primary

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.

Safety population

Posted

Count of Participants

Participants

Up to Week 12

ID	Title	Description
OG000	Placebo (Pooled)	Eligible participants in this arm received GSK256073 matching placebo capsules BID and once daily orally as directed with water for 12 weeks in a fed state. According to the randomized dose regimen, participants either took 2 capsules in the morning (once daily arm) or 1 capsule each in the morning and evening (BID arms). The data for placebos-GSK256073 matched placebo BID and GSK256073 matched placebo once daily was pooled into one placebo group.
OG001	GSK256073 5 mg BID	Eligible participants in this arm received GSK256073 5 mg capsules BID orally as directed with water for 12 weeks in a fed state.

Primary

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.

Safety population

Posted

Count of Participants

Participants

Up to Week 12

ID	Title	Description
OG000	Placebo (Pooled)	Eligible participants in this arm received GSK256073 matching placebo capsules BID and once daily orally as directed with water for 12 weeks in a fed state. According to the randomized dose regimen, participants either took 2 capsules in the morning (once daily arm) or 1 capsule each in the morning and evening (BID arms). The data for placebos-GSK256073 matched placebo BID and GSK256073 matched placebo once daily was pooled into one placebo group.
OG001	GSK256073 5 mg BID	Eligible participants in this arm received GSK256073 5 mg capsules BID orally as directed with water for 12 weeks in a fed state.
OG002	GSK256073 10 mg Once Daily

Primary

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).

Safety population. Only those participants available at the specified time points were analyzed.

Posted

Count of Participants

Participants

Up to Week 12

ID	Title	Description
OG000	Placebo (Pooled)	Eligible participants in this arm received GSK256073 matching placebo capsules BID and once daily orally as directed with water for 12 weeks in a fed state. According to the randomized dose regimen, participants either took 2 capsules in the morning (once daily arm) or 1 capsule each in the morning and evening (BID arms). The data for placebos-GSK256073 matched placebo BID and GSK256073 matched placebo once daily was pooled into one placebo group.
OG001	GSK256073 5 mg BID	Eligible participants in this arm received GSK256073 5 mg capsules BID orally as directed with water for 12 weeks in a fed state.
OG002	GSK256073 10 mg Once Daily	Eligible participants in this arm received GSK256073 10 mg capsules once daily orally as directed with water for 12 weeks in a fed state.

Primary

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.

Pharmacodynamic (PD) population comprised of all participants who provide pharmacodynamic data. Only those participants available at the specified time points were analyzed.

Posted

Mean

Standard Deviation

Percentage of Glycosylated Hemoglobin

Baseline (Day -1) and up to Week 12

ID	Title	Description
OG000	Placebo (Pooled)	Eligible participants in this arm received GSK256073 matching placebo capsules BID and once daily orally as directed with water for 12 weeks in a fed state. According to the randomized dose regimen, participants either took 2 capsules in the morning (once daily arm) or 1 capsule each in the morning and evening (BID arms). The data for placebos-GSK256073 matched placebo BID and GSK256073 matched placebo once daily was pooled into one placebo group.
OG001	GSK256073 5 mg BID	Eligible participants in this arm received GSK256073 5 mg capsules BID orally as directed with water for 12 weeks in a fed state.
OG002

Secondary

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

Change from Baseline was calculated by subtracting the Baseline values from the corresponding post-treatment values. Baseline was defined as weighted mean value at Day 1 visit. Statistics is provided for least square mean at Week 6. It was assessed on Baseline (Day 1), Day 2 and Week 6.

PD population. Only those participants available at the specified time points were analyzed.

Posted

Mean

Standard Deviation

Millimoles per liter

Baseline (Day 1) and up to Week 6

ID	Title	Description
OG000	Placebo (Pooled)	Eligible participants in this arm received GSK256073 matching placebo capsules BID and once daily orally as directed with water for 12 weeks in a fed state. According to the randomized dose regimen, participants either took 2 capsules in the morning (once daily arm) or 1 capsule each in the morning and evening (BID arms). The data for placebos-GSK256073 matched placebo BID and GSK256073 matched placebo once daily was pooled into one placebo group.
OG001	GSK256073 5 mg Bid	Eligible participants in this arm received GSK256073 5 mg capsules BID orally as directed with water for 12 weeks in a fed state.
OG002	GSK256073 10 mg qd

Secondary

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

The relationships between drug exposure and HbA1c and relative PD endpoints of interest was planned to be plotted graphically. The data for this outcome measure was not collected.

PD population. The data for this outcome measure was not collected.

Posted

Up to Week 12

ID	Title	Description
OG000	Placebo (Pooled)	Eligible participants in this arm received GSK256073 matching placebo capsules BID and once daily orally as directed with water for 12 weeks in a fed state. According to the randomized dose regimen, participants either took 2 capsules in the morning (once daily arm) or 1 capsule each in the morning and evening (BID arms). The data for placebos-GSK256073 matched placebo BID and GSK256073 matched placebo once daily was pooled into one placebo group.
OG001	GSK256073 5 mg BID	Eligible participants in this arm received GSK256073 5 mg capsules BID orally as directed with water for 12 weeks in a fed state.
OG002	GSK256073 10 mg Once Daily	Eligible participants in this arm received GSK256073 10 mg capsules once daily orally as directed with water for 12 weeks in a fed state.

Secondary

Change From Baseline in Fasting Plasma Glucose at Week 12

Mean of triplicate measurements at pre-dose time point were considered for the summary. Change from Baseline was calculated by subtracting the Baseline values from the corresponding post-treatment values. Baseline was defined as mean of Day 1 pre-dose visit. Statistics is provided for least square mean at Week 12. It was assessed on Day 1 (pre-dose), 2 (pre-dose), Week 6 (pre-dose) and Week 12.

PD population. Only those participants available at the specified time points were analyzed.

Posted

Mean

Standard Deviation

Millimoles per liter

Baseline (Day 1) and up to Week 12

ID	Title	Description
OG000	Placebo (Pooled)	Eligible participants in this arm received GSK256073 matching placebo capsules BID and once daily orally as directed with water for 12 weeks in a fed state. According to the randomized dose regimen, participants either took 2 capsules in the morning (once daily arm) or 1 capsule each in the morning and evening (BID arms). The data for placebos-GSK256073 matched placebo BID and GSK256073 matched placebo once daily was pooled into one placebo group.
OG001	GSK256073 5 mg BID	Eligible participants in this arm received GSK256073 5 mg capsules BID orally as directed with water for 12 weeks in a fed state.
OG002	GSK256073 10 mg Once Daily

Secondary

Change From Baseline in Fasting Insulin at Week 12

PD population. Only those participants available at the specified time points were analyzed.

Posted

Mean

Standard Deviation

Picomoles per liter

Baseline (Day 1) and up to Week 12

ID	Title	Description
OG000	Placebo (Pooled)	Eligible participants in this arm received GSK256073 matching placebo capsules BID and once daily orally as directed with water for 12 weeks in a fed state. According to the randomized dose regimen, participants either took 2 capsules in the morning (once daily arm) or 1 capsule each in the morning and evening (BID arms). The data for placebos-GSK256073 matched placebo BID and GSK256073 matched placebo once daily was pooled into one placebo group.
OG001	GSK256073 5 mg BID	Eligible participants in this arm received GSK256073 5 mg capsules BID orally as directed with water for 12 weeks in a fed state.
OG002	GSK256073 10 mg qd

Secondary

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

Mean of triplicate measurements at pre-dose time point was considered for the summary. HOMA was calculated by multiplying insulin concentration with glucose concentration divided by 22.5. Change from Baseline for insulin and glucose was calculated by subtracting the Baseline values from the corresponding post-treatment values. Baseline was defined as mean of Day 1 pre-dose visit. Statistics is provided for least square mean. It was assessed on Day 1 (pre-dose), 2 (pre-dose), Week 6 (pre-dose) and Week 12.

PD population. Only those participants available at the specified time points were analyzed.

Posted

Mean

Standard Deviation

Index

Baseline (Day 1) and up to Week 12

ID	Title	Description
OG000	Placebo (Pooled)	Eligible participants in this arm received GSK256073 matching placebo capsules BID and once daily orally as directed with water for 12 weeks in a fed state. According to the randomized dose regimen, participants either took 2 capsules in the morning (once daily arm) or 1 capsule each in the morning and evening (BID arms). The data for placebos-GSK256073 matched placebo BID and GSK256073 matched placebo once daily was pooled into one placebo group.
OG001	GSK256073 5 mg BID	Eligible participants in this arm received GSK256073 5 mg capsules BID orally as directed with water for 12 weeks in a fed state.

Secondary

Change From Baseline in Fructosamine at Week 6 and Week 12

Change from Baseline was calculated by subtracting the Baseline values from the corresponding post-treatment values. Baseline was defined as mean of Day -1 visit. Statistics is provided for least square mean. It was assessed on Baseline (Day -1), Day 41 and Week 12.

PD population. Only those participants available at the specified time points were analyzed.

Posted

Mean

Standard Deviation

Micromoles per liter

Baseline (Day -1) and Week 12

ID	Title	Description
OG000	Placebo (Pooled)	Eligible participants in this arm received GSK256073 matching placebo capsules BID and once daily orally as directed with water for 12 weeks in a fed state. According to the randomized dose regimen, participants either took 2 capsules in the morning (once daily arm) or 1 capsule each in the morning and evening (BID arms). The data for placebos-GSK256073 matched placebo BID and GSK256073 matched placebo once daily was pooled into one placebo group.
OG001	GSK256073 5 mg BID	Eligible participants in this arm received GSK256073 5 mg capsules BID orally as directed with water for 12 weeks in a fed state.
OG002	GSK256073 10 mg Once Daily

Secondary

Number of Participants With HbA1c < 7.0% and < 6.5%

Data has been presented for number of participants with their corresponding percentages with HbA1c <7.0% and <6.5%.

PD population. Only those participants available at the specified time points were analyzed.

Posted

Count of Participants

Participants

Up to Week 12

ID	Title	Description
OG000	Placebo (Pooled)	Eligible participants in this arm received GSK256073 matching placebo capsules BID and once daily orally as directed with water for 12 weeks in a fed state. According to the randomized dose regimen, participants either took 2 capsules in the morning (once daily arm) or 1 capsule each in the morning and evening (BID arms). The data for placebos-GSK256073 matched placebo BID and GSK256073 matched placebo once daily was pooled into one placebo group.
OG001	GSK256073 5 mg BID	Eligible participants in this arm received GSK256073 5 mg capsules BID orally as directed with water for 12 weeks in a fed state.
OG002	GSK256073 10 mg Once Daily	Eligible participants in this arm received GSK256073 10 mg capsules once daily orally as directed with water for 12 weeks in a fed state.

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Nasopharyngitis	Infections and infestations	MedDRA version	Systematic Assessment	EG0003 events3 affected20 at risk EG0010 events0 affected18 at risk EG0021 events1 affected19 at risk EG0032 events2 affected19 at risk EG0043 events3 affected18 at risk
Headache	Nervous system disorders	MedDRA version	Systematic Assessment	EG0001 events1 affected20 at risk EG0011 events1 affected18 at risk EG0021 events1 affected19 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA version	Systematic Assessment	EG0001 events1 affected20 at risk EG0012 events2 affected18 at risk EG0021 events1 affected19 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA version	Systematic Assessment	EG0001 events1 affected20 at risk EG0011 events1 affected18 at risk EG0021 events1 affected19 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA version	Systematic Assessment	EG0000 events0 affected20 at risk EG0013 events2 affected18 at risk EG0021 events1 affected19 at risk EG003
Blood uric acid decreased	Investigations	MedDRA version	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected18 at risk EG0021 events1 affected19 at risk EG003
Dizziness	Nervous system disorders	MedDRA version	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected19 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA version	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected18 at risk EG0021 events1 affected19 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA version	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0021 events1 affected19 at risk EG003
Asthenia	General disorders	MedDRA version	Systematic Assessment	EG0002 events2 affected20 at risk EG0011 events1 affected18 at risk EG0020 events0 affected19 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA version	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected18 at risk EG0021 events1 affected19 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA version	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0022 events2 affected19 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA version	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0022 events2 affected19 at risk EG003
Enterocolitis	Gastrointestinal disorders	MedDRA version	Systematic Assessment	EG0002 events2 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected19 at risk EG003
Haemoglobin decreased	Investigations	MedDRA version	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected19 at risk EG003
Influenza	Infections and infestations	MedDRA version	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected18 at risk EG0021 events1 affected19 at risk EG003
Oedema peripheral	General disorders	MedDRA version	Systematic Assessment	EG0001 events1 affected20 at risk EG0011 events1 affected18 at risk EG0020 events0 affected19 at risk EG003
Pharyngitis	Infections and infestations	MedDRA version	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected19 at risk EG003
Reticulocyte count increased	Investigations	MedDRA version	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected19 at risk EG003
Rhinitis	Infections and infestations	MedDRA version	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0021 events1 affected19 at risk EG003
Sciatica	Nervous system disorders	MedDRA version	Systematic Assessment	EG0001 events1 affected20 at risk EG0011 events1 affected18 at risk EG0020 events0 affected19 at risk EG003
Sinus congestion	Respiratory, thoracic and mediastinal disorders	MedDRA version	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0021 events1 affected19 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA version	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected19 at risk EG003
Abdominal discomfort	Gastrointestinal disorders	MedDRA version	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected19 at risk EG003
Abdominal pain lower	Gastrointestinal disorders	MedDRA version	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected19 at risk EG003
Angina pectoris	Cardiac disorders	MedDRA version	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected18 at risk EG0020 events0 affected19 at risk EG003
Anxiety	Psychiatric disorders	MedDRA version	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0021 events1 affected19 at risk EG003
Asthmatic crisis	Respiratory, thoracic and mediastinal disorders	MedDRA version	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected19 at risk EG003
Atrial flutter	Cardiac disorders	MedDRA version	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0021 events1 affected19 at risk EG003
Blood creatine phosphokinase increased	Investigations	MedDRA version	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected19 at risk EG003
Blood creatinine increased	Investigations	MedDRA version	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected19 at risk EG003
Blood pressure increased	Investigations	MedDRA version	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected19 at risk EG003
Bronchitis	Infections and infestations	MedDRA version	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected18 at risk EG0020 events0 affected19 at risk EG003
Cheilitis	Gastrointestinal disorders	MedDRA version	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected19 at risk EG003
Cold sweat	Skin and subcutaneous tissue disorders	MedDRA version	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected19 at risk EG003
Contrast media reaction	Injury, poisoning and procedural complications	MedDRA version	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected19 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA version	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected19 at risk EG003
Dysaesthesia	Nervous system disorders	MedDRA version	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0021 events1 affected19 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA version	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0021 events1 affected19 at risk EG003
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	MedDRA version	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected18 at risk EG0020 events0 affected19 at risk EG003
Dysuria	Renal and urinary disorders	MedDRA version	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected19 at risk EG003
Eosinophil count increased	Investigations	MedDRA version	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected19 at risk EG003
Fatigue	General disorders	MedDRA version	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected19 at risk EG003
Feeling abnormal	General disorders	MedDRA version	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected19 at risk EG003
Folliculitis	Infections and infestations	MedDRA version	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected18 at risk EG0020 events0 affected19 at risk EG003
Haematocrit decreased	Investigations	MedDRA version	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected19 at risk EG003
Hepatitis	Hepatobiliary disorders	MedDRA version	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected19 at risk EG003
Hot flush	Vascular disorders	MedDRA version	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0021 events1 affected19 at risk EG003
Hyperhidrosis	Skin and subcutaneous tissue disorders	MedDRA version	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected19 at risk EG003
Hypertension	Vascular disorders	MedDRA version	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected18 at risk EG0020 events0 affected19 at risk EG003
Hyperuricaemia	Metabolism and nutrition disorders	MedDRA version	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected19 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA version	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0021 events1 affected19 at risk EG003
Influenza like illness	General disorders	MedDRA version	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected19 at risk EG003
Libido decreased	Psychiatric disorders	MedDRA version	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected18 at risk EG0020 events0 affected19 at risk EG003
Lower respiratory tract infection	Infections and infestations	MedDRA version	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected19 at risk EG003
Malaise	General disorders	MedDRA version	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected19 at risk EG003
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA version	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected18 at risk EG0020 events0 affected19 at risk EG003
Nasal obstruction	Respiratory, thoracic and mediastinal disorders	MedDRA version	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected19 at risk EG003
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA version	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected18 at risk EG0020 events0 affected19 at risk EG003
Nocturia	Renal and urinary disorders	MedDRA version	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected19 at risk EG003
Oral candidiasis	Infections and infestations	MedDRA version	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected19 at risk EG003
Oral herpes	Infections and infestations	MedDRA version	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected19 at risk EG003
Pain	General disorders	MedDRA version	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected19 at risk EG003
Paraesthesia	Nervous system disorders	MedDRA version	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected19 at risk EG003
Periarthritis	Musculoskeletal and connective tissue disorders	MedDRA version	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected19 at risk EG003
Presyncope	Nervous system disorders	MedDRA version	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected18 at risk EG0020 events0 affected19 at risk EG003
Prostate infection	Infections and infestations	MedDRA version	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected19 at risk EG003
Rash pruritic	Skin and subcutaneous tissue disorders	MedDRA version	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected18 at risk EG0020 events0 affected19 at risk EG003
Retinal haemorrhage	Eye disorders	MedDRA version	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0021 events1 affected19 at risk EG003
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA version	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected19 at risk EG003
Sensation of heaviness	Musculoskeletal and connective tissue disorders	MedDRA version	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected19 at risk EG003
Somnolence	Nervous system disorders	MedDRA version	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected18 at risk EG0020 events0 affected19 at risk EG003
Torticollis	Musculoskeletal and connective tissue disorders	MedDRA version	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected18 at risk EG0020 events0 affected19 at risk EG003
Tremor	Nervous system disorders	MedDRA version	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected19 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA version	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0021 events1 affected19 at risk EG003
Varicose vein	Vascular disorders	MedDRA version	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected18 at risk EG0020 events0 affected19 at risk EG003

ID	Term
D003920	Diabetes Mellitus
D044882	Glucose Metabolism Disorders
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases
D004700	Endocrine System Diseases

ID	Term
C000604188	8-chloro-3-pentyl-1H-purine-2,6(3H,7H)-dione
D000068900	Sitagliptin Phosphate

ID	Term
D014230	Triazoles
D001393	Azoles
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D011719	Pyrazines

ID	Title	Description
BG000	Placebo (Pooled)	Eligible participants in this arm received GSK256073 matching placebo capsules BID and once daily orally as directed with water for 12 weeks in a fed state. According to the randomized dose regimen, participants either took 2 capsules in the morning (once daily arm) or 1 capsule each in the morning and evening (BID arms). The data for placebos-GSK256073 matched placebo BID and GSK256073 matched placebo once daily was pooled into one placebo group.
BG001	GSK256073 5 mg BID	Eligible participants in this arm received GSK256073 5 mg capsules BID orally as directed with water for 12 weeks in a fed state.
BG002	GSK256073 10 mg Once Daily	Eligible participants in this arm received GSK256073 10 mg capsules once daily orally as directed with water for 12 weeks in a fed state.
BG003	GSK256073 25 mg BID	Eligible participants in this arm received GSK256073 25 mg capsules BID orally as directed with water for 12 weeks in a fed state.
BG004	GSK256073 50 mg Once Daily	Eligible participants in this arm received GSK256073 50 mg capsules once daily orally as directed with water for 12 weeks in a fed state.
BG005	Total	Total of all reporting groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo (Pooled)	Eligible participants in this arm received GSK256073 matching placebo capsules BID and once daily orally as directed with water for 12 weeks in a fed state. According to the randomized dose regimen, participants either took 2 capsules in the morning (once daily arm) or 1 capsule each in the morning and evening (BID arms). The data for placebos-GSK256073 matched placebo BID and GSK256073 matched placebo once daily was pooled into one placebo group.	20	1	20	11	20
EG001	GSK256073 5 mg BID	Eligible participants in this arm received GSK256073 5 mg capsules BID orally as directed with water for 12 weeks in a fed state.	18	0	18	12	18
EG002	GSK256073 10 mg Once Daily	Eligible participants in this arm received GSK256073 10 mg capsules once daily orally as directed with water for 12 weeks in a fed state.	19	0	19	12	19
EG003	GSK256073 25 mg BID	Eligible participants in this arm received GSK256073 25 mg capsules BID orally as directed with water for 12 weeks in a fed state.	19	2	19	10	19
EG004	GSK256073 50 mg Once Daily	Eligible participants in this arm received GSK256073 50 mg capsules once daily orally as directed with water for 12 weeks in a fed state.	18	0	18	10	18

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Atrial fibrillation	Cardiac disorders	MedDRA version	Systematic Assessment	EG0000 affected20 at risk EG0010 affected18 at risk EG0020 affected19 at risk EG0031 affected19 at risk EG0040 affected18 at risk
Joint dislocation	Injury, poisoning and procedural complications	MedDRA version	Systematic Assessment	EG0000 affected20 at risk EG0010 affected18 at risk EG0020 affected19 at risk EG003
Nephrotic syndrome	Renal and urinary disorders	MedDRA version	Systematic Assessment	EG0001 affected20 at risk EG0010 affected18 at risk EG0020 affected19 at risk EG003