Trial Outcomes & Findings for Study Of GW823093 In Japanese Subjects With Type 2 Diabetes Mellitus (NCT NCT00372957)

NCT ID: NCT00372957

Last Updated: 2018-09-04

Results Overview

PK parameters were calculated using data at the actual time of blood collection. Cmax was determined from plasma concentration-time data, using standard model independent methods.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 30 participants
• Primary outcome timeframe: Day 1 (at 0, 1, 1.5, 2, 3, 4, 6, 8, 12 hours [hr]), Day 2 (0 hr) and Day 7 (0, 0.5, 1, 1.5, 2, 4, 6, 8, 12 and 24 hr)
• Results posted on: 2018-09-04

Participant Flow

This study was conducted across two centers in Japan from 22 March 2006 to 28 June 2006.

A total of 30 participants were randomized in the study. After screening, participants were washed off of diabetes medications for two weeks prior to the first dose of study medication.

Participant milestones

Measure	Placebo Participants received two capsules of matching placebo orally once daily in the morning with 150 milliliter (mL) of water at least 15 minutes prior to breakfast for 7 Days.	GW823093C 15 mg Participants received one 15 milligrams (mg) of GW823093C capsule and one placebo capsule orally once daily in the morning with 150 mL of water at least 15 minutes prior to breakfast for 7 Days.	GW823093C 30 mg Participants received 30 mg (2x15 mg) of GW823093C capsules orally once daily in the morning with 150 mL of water at least 15 minutes prior to breakfast for 7 Days.
Overall Study STARTED	10	10	10
Overall Study COMPLETED	10	10	10
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study Of GW823093 In Japanese Subjects With Type 2 Diabetes Mellitus

Baseline characteristics by cohort

Measure	Placebo n=10 Participants Participants received two capsules of matching placebo orally once daily in the morning with 150 mL of water at least 15 minutes prior to breakfast for 7 Days.	GW823093C 15 mg n=10 Participants Participants received one 15 mg of GW823093C capsule and one placebo capsule orally once daily in the morning with 150 mL of water at least 15 minutes prior to breakfast for 7 Days.	GW823093C 30 mg n=10 Participants Participants received 30 mg (2x15 mg) of GW823093C capsules orally once daily in the morning with 150 mL of water at least 15 minutes prior to breakfast for 7 Days.	Total n=30 Participants Total of all reporting groups
Age, Customized 20 to 64 Years	10 Participants n=5 Participants	10 Participants n=7 Participants	10 Participants n=5 Participants	30 Participants n=4 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	5 Participants n=4 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	9 Participants n=7 Participants	8 Participants n=5 Participants	25 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	10 Participants n=5 Participants	10 Participants n=7 Participants	10 Participants n=5 Participants	30 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants

PRIMARY outcome

Timeframe: Day 1 (at 0, 1, 1.5, 2, 3, 4, 6, 8, 12 hours [hr]), Day 2 (0 hr) and Day 7 (0, 0.5, 1, 1.5, 2, 4, 6, 8, 12 and 24 hr)

Population: PK Parameter Population comprised of all participants who received an active dose of GW823093C and for whom PK data was collected.

PK parameters were calculated using data at the actual time of blood collection. Cmax was determined from plasma concentration-time data, using standard model independent methods.

Outcome measures

Measure	GW823093C 15 mg n=10 Participants Participants received one 15 mg of GW823093C capsule and one placebo capsule orally once daily in the morning with 150 mL of water at least 15 minutes prior to breakfast for 7 Days.	GW823093C 30 mg n=10 Participants Participants received 30 mg (2x15 mg) of GW823093C capsules orally once daily in the morning with 150 mL of water at least 15 minutes prior to breakfast for 7 Days.	GW823093C 30 mg Participants received 30 mg (2x15 mg) of GW823093C capsules orally once daily in the morning with 150 mL of water at least 15 minutes prior to breakfast for 7 Days.
Standard Pharmacokinetic (PK) Parameter: Maximum Observed Plasma Drug Concentration (Cmax) Day 1	238.166 Nanograms per milliliter (ng/mL) Interval 183.73 to 308.731	419.937 Nanograms per milliliter (ng/mL) Interval 358.461 to 491.957	—
Standard Pharmacokinetic (PK) Parameter: Maximum Observed Plasma Drug Concentration (Cmax) Day 7	262.523 Nanograms per milliliter (ng/mL) Interval 209.416 to 329.097	534.888 Nanograms per milliliter (ng/mL) Interval 486.074 to 588.604	—

PRIMARY outcome

Timeframe: Day 1 (at 0, 1, 1.5, 2, 3, 4, 6, 8, 12 hr), Day 2 (0 hr) and Day 7 (0, 0.5, 1, 1.5, 2, 4, 6, 8, 12 and 24 hr)

Population: PK Parameter Population.

PK parameters were calculated using data at the actual time of blood collection. Tmax was determined from plasma concentration-time data, using standard model independent methods.

Outcome measures

Measure	GW823093C 15 mg n=10 Participants Participants received one 15 mg of GW823093C capsule and one placebo capsule orally once daily in the morning with 150 mL of water at least 15 minutes prior to breakfast for 7 Days.	GW823093C 30 mg n=10 Participants Participants received 30 mg (2x15 mg) of GW823093C capsules orally once daily in the morning with 150 mL of water at least 15 minutes prior to breakfast for 7 Days.	GW823093C 30 mg Participants received 30 mg (2x15 mg) of GW823093C capsules orally once daily in the morning with 150 mL of water at least 15 minutes prior to breakfast for 7 Days.
Standard PK Parameter: Time at Which Cmax Was Observed (Tmax) Tmax, Day 1	2.50 Hour Interval 0.5 to 4.0	3.50 Hour Interval 0.5 to 6.0	—
Standard PK Parameter: Time at Which Cmax Was Observed (Tmax) Tmax, Day 7	3.00 Hour Interval 0.5 to 4.0	2.00 Hour Interval 0.5 to 4.0	—

PRIMARY outcome

Timeframe: Day 1 (at 0, 1, 1.5, 2, 3, 4, 6, 8, 12 hr), Day 2 (0 hr) and Day 7 (0, 0.5, 1, 1.5, 2, 4, 6, 8, 12 and 24 hr)

Population: PK Parameter Population.

PK parameters were calculated using data at the actual time of blood collection. T1/2 was determined from plasma concentration-time data, using standard model independent methods.

Outcome measures

Measure	GW823093C 15 mg n=10 Participants Participants received one 15 mg of GW823093C capsule and one placebo capsule orally once daily in the morning with 150 mL of water at least 15 minutes prior to breakfast for 7 Days.	GW823093C 30 mg n=10 Participants Participants received 30 mg (2x15 mg) of GW823093C capsules orally once daily in the morning with 150 mL of water at least 15 minutes prior to breakfast for 7 Days.	GW823093C 30 mg Participants received 30 mg (2x15 mg) of GW823093C capsules orally once daily in the morning with 150 mL of water at least 15 minutes prior to breakfast for 7 Days.
Standard PK Parameter: Half Life of Terminal Elimination Phase (t1/2) Day 1	6.662 Hour Interval 5.884 to 7.543	8.788 Hour Interval 8.094 to 9.541	—
Standard PK Parameter: Half Life of Terminal Elimination Phase (t1/2) Day 7	7.127 Hour Interval 6.372 to 7.971	9.648 Hour Interval 8.674 to 10.731	—

PRIMARY outcome

Timeframe: Day 1 (at 0, 1, 1.5, 2, 3, 4, 6, 8, 12 hr), Day 2 (0 hr) and Day 7 (0, 0.5, 1, 1.5, 2, 4, 6, 8, 12 and 24 hr)

Population: PK Parameter Population.

PK parameters were calculated using data at the actual time of blood collection. AUC[0-inf] and AUC[0-t] was determined from plasma concentration-time data, using standard model independent methods.

Outcome measures

Measure	GW823093C 15 mg n=10 Participants Participants received one 15 mg of GW823093C capsule and one placebo capsule orally once daily in the morning with 150 mL of water at least 15 minutes prior to breakfast for 7 Days.	GW823093C 30 mg n=10 Participants Participants received 30 mg (2x15 mg) of GW823093C capsules orally once daily in the morning with 150 mL of water at least 15 minutes prior to breakfast for 7 Days.	GW823093C 30 mg Participants received 30 mg (2x15 mg) of GW823093C capsules orally once daily in the morning with 150 mL of water at least 15 minutes prior to breakfast for 7 Days.
Standard PK Parameter: Area Under the Plasma Drug Concentration Versus Time Curve Extrapolated to Infinity (AUC[0-inf]), AUC From 0 to the Last Measurable Concentration (AUC[0-t]) AUC(0-t), Day 1	2261.076 Hr.ng/mL Interval 1944.959 to 2628.572	4800.677 Hr.ng/mL Interval 4451.224 to 5177.565	—
Standard PK Parameter: Area Under the Plasma Drug Concentration Versus Time Curve Extrapolated to Infinity (AUC[0-inf]), AUC From 0 to the Last Measurable Concentration (AUC[0-t]) AUC(0-t), Day 7	2545.651 Hr.ng/mL Interval 2155.396 to 3006.567	6129.987 Hr.ng/mL Interval 5801.218 to 6477.387	—
Standard PK Parameter: Area Under the Plasma Drug Concentration Versus Time Curve Extrapolated to Infinity (AUC[0-inf]), AUC From 0 to the Last Measurable Concentration (AUC[0-t]) AUC(0-inf), Day 1	2508.608 Hr.ng/mL Interval 2114.506 to 2976.163	5786.001 Hr.ng/mL Interval 5449.326 to 6143.477	—
Standard PK Parameter: Area Under the Plasma Drug Concentration Versus Time Curve Extrapolated to Infinity (AUC[0-inf]), AUC From 0 to the Last Measurable Concentration (AUC[0-t]) AUC(0-inf), Day 7	2870.716 Hr.ng/mL Interval 2374.654 to 3470.405	7562.008 Hr.ng/mL Interval 7132.565 to 8017.307	—

PRIMARY outcome

Timeframe: Day 1 (at 0, 1, 1.5, 2, 3, 4, 6, 8, 12 hr), Day 2 (0 hr) and Day 7 (0, 0.5, 1, 1.5, 2, 4, 6, 8, 12 and 24 hr)

Population: PK Parameter Population.

PK parameters were calculated using data at the actual time of blood collection. %AUCex was determined from plasma concentration-time data, using standard model independent methods.

Outcome measures

Measure	GW823093C 15 mg n=10 Participants Participants received one 15 mg of GW823093C capsule and one placebo capsule orally once daily in the morning with 150 mL of water at least 15 minutes prior to breakfast for 7 Days.	GW823093C 30 mg n=10 Participants Participants received 30 mg (2x15 mg) of GW823093C capsules orally once daily in the morning with 150 mL of water at least 15 minutes prior to breakfast for 7 Days.	GW823093C 30 mg Participants received 30 mg (2x15 mg) of GW823093C capsules orally once daily in the morning with 150 mL of water at least 15 minutes prior to breakfast for 7 Days.
Standard PK Parameter: Percentage of AUC(0-inf) Obtained by Extrapolation (%AUCex) Day 1	9.029 Percentage of AUCex Interval 6.625 to 12.305	16.645 Percentage of AUCex Interval 14.331 to 19.333	—
Standard PK Parameter: Percentage of AUC(0-inf) Obtained by Extrapolation (%AUCex) Day 7	10.704 Percentage of AUCex Interval 8.425 to 13.601	18.442 Percentage of AUCex Interval 15.817 to 21.503	—

PRIMARY outcome

Timeframe: Day 1 (at 0, 1, 1.5, 2, 3, 4, 6, 8, 12 hr), Day 2 (0 hr) and Day 7 (0, 0.5, 1, 1.5, 2, 4, 6, 8, 12 and 24 hr)

Population: PK Parameter Population.

PK parameters were calculated using data at the actual time of blood collection. Lambda_z was determined from plasma concentration-time data, using standard model independent methods.

Outcome measures

Measure	GW823093C 15 mg n=10 Participants Participants received one 15 mg of GW823093C capsule and one placebo capsule orally once daily in the morning with 150 mL of water at least 15 minutes prior to breakfast for 7 Days.	GW823093C 30 mg n=10 Participants Participants received 30 mg (2x15 mg) of GW823093C capsules orally once daily in the morning with 150 mL of water at least 15 minutes prior to breakfast for 7 Days.	GW823093C 30 mg Participants received 30 mg (2x15 mg) of GW823093C capsules orally once daily in the morning with 150 mL of water at least 15 minutes prior to breakfast for 7 Days.
Standard PK Parameter: Constant Rate of Elimination (lambda_z) Day 1	0.10403 1/hr Interval 0.09188 to 0.11779	0.07887 1/hr Interval 0.07266 to 0.08562	—
Standard PK Parameter: Constant Rate of Elimination (lambda_z) Day 7	0.09727 1/hr Interval 0.08697 to 0.10879	0.07184 1/hr Interval 0.06458 to 0.07992	—

PRIMARY outcome

Timeframe: Day 1 (at 0, 1, 1.5, 2, 3, 4, 6, 8, 12 hr), Day 2 (0 hr) and Day 7 (0, 0.5, 1, 1.5, 2, 4, 6, 8, 12 and 24 hr)

Population: PK Parameter Population.

PK parameters were calculated using data at the actual time of blood collection. CL/F was determined from plasma concentration-time data, using standard model independent methods.

Outcome measures

Measure	GW823093C 15 mg n=10 Participants Participants received one 15 mg of GW823093C capsule and one placebo capsule orally once daily in the morning with 150 mL of water at least 15 minutes prior to breakfast for 7 Days.	GW823093C 30 mg n=10 Participants Participants received 30 mg (2x15 mg) of GW823093C capsules orally once daily in the morning with 150 mL of water at least 15 minutes prior to breakfast for 7 Days.	GW823093C 30 mg Participants received 30 mg (2x15 mg) of GW823093C capsules orally once daily in the morning with 150 mL of water at least 15 minutes prior to breakfast for 7 Days.
Standard PK Parameter: Total Clearance (CL/F) Day 1	5.979 Liter per hour (L/hr) Interval 5.04 to 7.094	5.185 Liter per hour (L/hr) Interval 4.883 to 5.505	—
Standard PK Parameter: Total Clearance (CL/F) Day 7	5.225 Liter per hour (L/hr) Interval 4.322 to 6.317	3.967 Liter per hour (L/hr) Interval 3.742 to 4.206	—

PRIMARY outcome

Timeframe: Day 1 (at 0, 1, 1.5, 2, 3, 4, 6, 8, 12 hr), Day 2 (0 hr) and Day 7 (0, 0.5, 1, 1.5, 2, 4, 6, 8, 12 and 24 hr)

Population: PK Parameter Population.

PK parameters were calculated using data at the actual time of blood collection. Vz/F was determined from plasma concentration-time data, using standard model independent methods.

Outcome measures

Measure	GW823093C 15 mg n=10 Participants Participants received one 15 mg of GW823093C capsule and one placebo capsule orally once daily in the morning with 150 mL of water at least 15 minutes prior to breakfast for 7 Days.	GW823093C 30 mg n=10 Participants Participants received 30 mg (2x15 mg) of GW823093C capsules orally once daily in the morning with 150 mL of water at least 15 minutes prior to breakfast for 7 Days.	GW823093C 30 mg Participants received 30 mg (2x15 mg) of GW823093C capsules orally once daily in the morning with 150 mL of water at least 15 minutes prior to breakfast for 7 Days.
Standard PK Parameter: Apparent Volume of Distribution (Vz/F) Day 1	57.470 L Interval 51.466 to 64.175	65.735 L Interval 58.465 to 73.91	—
Standard PK Parameter: Apparent Volume of Distribution (Vz/F) Day 7	53.724 L Interval 48.155 to 59.938	55.221 L Interval 50.088 to 60.881	—

PRIMARY outcome

Timeframe: Day 1 (at 0, 1, 1.5, 2, 3, 4, 6, 8, 12 hr), Day 2 (0 hr) and Day 7 (0, 0.5, 1, 1.5, 2, 4, 6, 8, 12 and 24 hr)

Population: PK Parameter Population.

PK parameters were calculated using data at the actual time of blood collection. R[Cmax], Ro and Rs were determined from plasma concentration-time data, using standard model independent methods. R[Cmax] = Cmax (Day 7)/Cmax (Day 1), Ro = AUC(0-tau) (Day 7)/ AUC(0-tau) (Day 1) and Rs = AUC(0-tau) (Day 7)/ AUC(0-inf) (Day 1).

Outcome measures

Measure	GW823093C 15 mg n=10 Participants Participants received one 15 mg of GW823093C capsule and one placebo capsule orally once daily in the morning with 150 mL of water at least 15 minutes prior to breakfast for 7 Days.	GW823093C 30 mg n=10 Participants Participants received 30 mg (2x15 mg) of GW823093C capsules orally once daily in the morning with 150 mL of water at least 15 minutes prior to breakfast for 7 Days.	GW823093C 30 mg Participants received 30 mg (2x15 mg) of GW823093C capsules orally once daily in the morning with 150 mL of water at least 15 minutes prior to breakfast for 7 Days.
Standard PK Parameter: R[Cmax], Extent of Accumulation (Ro), Steady State Accumulation Ratio (Rs) R[Cmax]	1.102 Ratio Interval 0.946 to 1.284	1.274 Ratio Interval 1.11 to 1.461	—
Standard PK Parameter: R[Cmax], Extent of Accumulation (Ro), Steady State Accumulation Ratio (Rs) Ro	1.126 Ratio Interval 1.082 to 1.171	1.277 Ratio Interval 1.183 to 1.379	—
Standard PK Parameter: R[Cmax], Extent of Accumulation (Ro), Steady State Accumulation Ratio (Rs) Rs	1.015 Ratio Interval 0.987 to 1.044	1.059 Ratio Interval 0.988 to 1.136	—

PRIMARY outcome

Timeframe: Day 7

Population: Pharmacodynamic (PD) Parameter Population comprised of all participants who received study medication (active or placebo) and for whom PD data was available.

For analysis of DPP-IV activity, approximately 2 mL of whole blood was collected into a vacuum tube containing ethylenediamine tetraacetic acid (EDTA2K) and centrifuged at approximately 4 degree Celsius, at approximately 2500 revolution per minute (rpm) for 15 minutes. Samples were stored in a freezer at -70 degree Celsius or lower. DPP-IV inhibition was estimated by using the percent change from pre-dose of DPP-IV activity. DPP-IV inhibition was done at pre-dose, 0.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr and 24 hr.

Outcome measures

Measure	GW823093C 15 mg n=10 Participants Participants received one 15 mg of GW823093C capsule and one placebo capsule orally once daily in the morning with 150 mL of water at least 15 minutes prior to breakfast for 7 Days.	GW823093C 30 mg n=10 Participants Participants received 30 mg (2x15 mg) of GW823093C capsules orally once daily in the morning with 150 mL of water at least 15 minutes prior to breakfast for 7 Days.	GW823093C 30 mg n=10 Participants Participants received 30 mg (2x15 mg) of GW823093C capsules orally once daily in the morning with 150 mL of water at least 15 minutes prior to breakfast for 7 Days.
Percent Dipeptidyl-peptidase IV (DPP-IV) Inhibition by Dose (Day 7) Pre-dose	0.000 Percent inhibition	69.565 Percent inhibition	88.854 Percent inhibition
Percent Dipeptidyl-peptidase IV (DPP-IV) Inhibition by Dose (Day 7) 0.5hr	2.273 Percent inhibition	83.612 Percent inhibition	88.854 Percent inhibition
Percent Dipeptidyl-peptidase IV (DPP-IV) Inhibition by Dose (Day 7) 1hr	-1.724 Percent inhibition	91.107 Percent inhibition	91.033 Percent inhibition
Percent Dipeptidyl-peptidase IV (DPP-IV) Inhibition by Dose (Day 7) 1.5hr	0.000 Percent inhibition	91.304 Percent inhibition	91.033 Percent inhibition
Percent Dipeptidyl-peptidase IV (DPP-IV) Inhibition by Dose (Day 7) 2hr	-1.724 Percent inhibition	91.304 Percent inhibition	92.593 Percent inhibition
Percent Dipeptidyl-peptidase IV (DPP-IV) Inhibition by Dose (Day 7) 3hr	-2.273 Percent inhibition	91.304 Percent inhibition	92.593 Percent inhibition
Percent Dipeptidyl-peptidase IV (DPP-IV) Inhibition by Dose (Day 7) 4hr	-3.448 Percent inhibition	91.304 Percent inhibition	92.593 Percent inhibition
Percent Dipeptidyl-peptidase IV (DPP-IV) Inhibition by Dose (Day 7) 6 hr	-5.721 Percent inhibition	91.107 Percent inhibition	91.609 Percent inhibition
Percent Dipeptidyl-peptidase IV (DPP-IV) Inhibition by Dose (Day 7) 8 hr	-9.091 Percent inhibition	91.107 Percent inhibition	92.593 Percent inhibition
Percent Dipeptidyl-peptidase IV (DPP-IV) Inhibition by Dose (Day 7) 12 hr	-9.091 Percent inhibition	91.107 Percent inhibition	91.033 Percent inhibition
Percent Dipeptidyl-peptidase IV (DPP-IV) Inhibition by Dose (Day 7) 24 hr	-4.105 Percent inhibition	68.783 Percent inhibition	88.562 Percent inhibition

PRIMARY outcome

Timeframe: Baseline (Day -1) and Day 7

Population: Pharmacodynamic (PD) Parameter Population comprised of all participants who received study medication (active or placebo) and for whom PD data was available.

For analysis of DPP-IV activity, approximately 2 mL of whole blood was collected into a vacuum tube containing EDTA2K and centrifuged at approximately 4 degree Celsius, at approximately 2500 rpm for 15 minutes. Samples were stored in a freezer at -70 degree Celsius or lower. Double-delta represented active treatment within participant change from Baseline summarized across participants, subtracted from placebo within participant change from Baseline summarized across participants. AUC with respect to these time interval was calculated using linear trapezoidal rule by sum of the areas between each chronological pair of assessments (using observed times). Weighted mean was then determined by dividing AUC by observed length of collection interval (time of last assessment - time of first assessment in hr). Double-delta analysis has been presented in analysis. Unit of measure: Nano mole per minute per milliliter (nmol/min/mL).

Outcome measures

Measure	GW823093C 15 mg n=10 Participants Participants received one 15 mg of GW823093C capsule and one placebo capsule orally once daily in the morning with 150 mL of water at least 15 minutes prior to breakfast for 7 Days.	GW823093C 30 mg n=10 Participants Participants received 30 mg (2x15 mg) of GW823093C capsules orally once daily in the morning with 150 mL of water at least 15 minutes prior to breakfast for 7 Days.	GW823093C 30 mg n=10 Participants Participants received 30 mg (2x15 mg) of GW823093C capsules orally once daily in the morning with 150 mL of water at least 15 minutes prior to breakfast for 7 Days.
DPP-IV Activity Weighted Mean AUCs at Baseline (Day -1) and Day 7 AUC(0-12 hr), Day -1	2.34 nmol/min/mL Standard Deviation 0.38	2.43 nmol/min/mL Standard Deviation 0.25	2.41 nmol/min/mL Standard Deviation 0.70
DPP-IV Activity Weighted Mean AUCs at Baseline (Day -1) and Day 7 AUC(0-12 hr), Day 7	2.35 nmol/min/mL Standard Deviation 0.35	0.27 nmol/min/mL Standard Deviation 0.08	0.21 nmol/min/mL Standard Deviation 0.02
DPP-IV Activity Weighted Mean AUCs at Baseline (Day -1) and Day 7 AUC(0-24 hr), Day -1	2.35 nmol/min/mL Standard Deviation 0.38	2.44 nmol/min/mL Standard Deviation 0.28	2.42 nmol/min/mL Standard Deviation 0.71
DPP-IV Activity Weighted Mean AUCs at Baseline (Day -1) and Day 7 AUC(0-24 hr), Day 7	2.34 nmol/min/mL Standard Deviation 0.32	0.37 nmol/min/mL Standard Deviation 0.12	0.23 nmol/min/mL Standard Deviation 0.06

PRIMARY outcome

Timeframe: Baseline (Day -1) and Day 7

Population: PD Parameter Population.

For the analysis of active GLP-1 concentrations, approximately 3 mL of whole blood was collected into a vacuum tube containing DPP-IV inhibitor, and then centrifuged in a refrigerated centrifuge at approximately 4 degree Celsius, at approximately 2500 rpm for 15 minutes. Samples were stored in a freezer at -70 degree Celsius or lower. Double-delta represented the active treatment within participant change from Baseline summarized across participants, subtracted from placebo within participant change from Baseline summarized across participants. AUC with respect to these time interval was calculated using linear trapezoidal rule by sum of the areas between each chronological pair of assessments (using observed times). Weighted mean was then determined by dividing AUC by observed length of collection interval (time of last assessment - time of first assessment in hr). Double-delta analysis for weighted mean AUCs has been presented in the statistical analysis section.

Outcome measures

Measure	GW823093C 15 mg n=10 Participants Participants received one 15 mg of GW823093C capsule and one placebo capsule orally once daily in the morning with 150 mL of water at least 15 minutes prior to breakfast for 7 Days.	GW823093C 30 mg n=10 Participants Participants received 30 mg (2x15 mg) of GW823093C capsules orally once daily in the morning with 150 mL of water at least 15 minutes prior to breakfast for 7 Days.	GW823093C 30 mg n=10 Participants Participants received 30 mg (2x15 mg) of GW823093C capsules orally once daily in the morning with 150 mL of water at least 15 minutes prior to breakfast for 7 Days.
Active Glucagon-like Peptide-1 (GLP-1) Weighted Mean AUCs at Baseline (Day -1) and Day 7 AUC(0-12 hr), Day -1	4.64 Picomole (pM) Standard Deviation 3.68	3.21 Picomole (pM) Standard Deviation 1.06	5.48 Picomole (pM) Standard Deviation 3.04
Active Glucagon-like Peptide-1 (GLP-1) Weighted Mean AUCs at Baseline (Day -1) and Day 7 AUC(0-12 hr), Day 7	4.74 Picomole (pM) Standard Deviation 3.80	7.19 Picomole (pM) Standard Deviation 2.46	10.79 Picomole (pM) Standard Deviation 3.32
Active Glucagon-like Peptide-1 (GLP-1) Weighted Mean AUCs at Baseline (Day -1) and Day 7 AUC(0-24 hr), Day -1	4.25 Picomole (pM) Standard Deviation 3.34	2.77 Picomole (pM) Standard Deviation 0.80	4.99 Picomole (pM) Standard Deviation 2.64
Active Glucagon-like Peptide-1 (GLP-1) Weighted Mean AUCs at Baseline (Day -1) and Day 7 AUC(0-24 hr), Day 7	4.65 Picomole (pM) Standard Deviation 3.54	6.37 Picomole (pM) Standard Deviation 2.22	9.81 Picomole (pM) Standard Deviation 2.77

PRIMARY outcome

Timeframe: Baseline (Day -1) and Day 7

Population: PD Parameter Population.

For the analysis of plasma insulin, approximately 2 mL of whole blood was collected into a vacuum tube containing EDTA2Na, and then centrifuged in a refrigerated centrifuge at approximately 4 degree Celsius, at approximately 2500 rpm for 15 minutes. Samples were stored in a freezer at -70 degree Celsius or lower. Double-delta represented the active treatment within participant change from Baseline summarized across participants, subtracted from placebo within participant change from Baseline summarized across participants. AUC with respect to these time interval was calculated using linear trapezoidal rule by sum of the areas between each chronological pair of assessments (using observed times). Weighted mean was then determined by dividing AUC by observed length of collection interval (time of last assessment - time of first assessment in hr). Double-delta analysis for weighted mean AUCs has been presented in the statistical analysis section.

Outcome measures

Measure	GW823093C 15 mg n=10 Participants Participants received one 15 mg of GW823093C capsule and one placebo capsule orally once daily in the morning with 150 mL of water at least 15 minutes prior to breakfast for 7 Days.	GW823093C 30 mg n=10 Participants Participants received 30 mg (2x15 mg) of GW823093C capsules orally once daily in the morning with 150 mL of water at least 15 minutes prior to breakfast for 7 Days.	GW823093C 30 mg n=10 Participants Participants received 30 mg (2x15 mg) of GW823093C capsules orally once daily in the morning with 150 mL of water at least 15 minutes prior to breakfast for 7 Days.
Insulin Weighted Mean AUCs at Baseline (Day -1) and Day 7 AUC(0-12 hr), Day -1	17.35 Micro units per milliliter (µU/mL) Standard Deviation 7.37	17.55 Micro units per milliliter (µU/mL) Standard Deviation 7.72	21.28 Micro units per milliliter (µU/mL) Standard Deviation 12.06
Insulin Weighted Mean AUCs at Baseline (Day -1) and Day 7 AUC(0-12 hr), Day 7	18.07 Micro units per milliliter (µU/mL) Standard Deviation 9.28	16.70 Micro units per milliliter (µU/mL) Standard Deviation 6.75	22.79 Micro units per milliliter (µU/mL) Standard Deviation 11.95
Insulin Weighted Mean AUCs at Baseline (Day -1) and Day 7 AUC(0-24 hr), Day -1	16.60 Micro units per milliliter (µU/mL) Standard Deviation 6.75	17.87 Micro units per milliliter (µU/mL) Standard Deviation 7.68	21.72 Micro units per milliliter (µU/mL) Standard Deviation 12.66
Insulin Weighted Mean AUCs at Baseline (Day -1) and Day 7 AUC(0-24 hr), Day 7	16.89 Micro units per milliliter (µU/mL) Standard Deviation 7.73	16.64 Micro units per milliliter (µU/mL) Standard Deviation 6.91	22.81 Micro units per milliliter (µU/mL) Standard Deviation 11.90

PRIMARY outcome

Timeframe: Baseline (Day -1) and Day 7

Population: PD Parameter Population.

For the analysis of plasma glucagons concentrations, approximately 2 mL of whole blood was collected into a vacuum tube containing aprotinin, and then centrifuged in a refrigerated centrifuge at approximately 4 degree Celsius, at approximately 2500 rpm for 15 minutes. Samples were stored in a freezer at -70 degree Celsius or lower. Double-delta represented the active treatment within participant change from Baseline summarized across participants, subtracted from placebo within participant change from Baseline summarized across participants. AUC with respect to these time interval was calculated using linear trapezoidal rule by sum of the areas between each chronological pair of assessments (using observed times). Weighted mean was then determined by dividing AUC by observed length of collection interval (time of last assessment - time of first assessment in hr). Double-delta analysis for weighted mean AUCs has been presented in the statistical analysis section.

Outcome measures

Measure	GW823093C 15 mg n=10 Participants Participants received one 15 mg of GW823093C capsule and one placebo capsule orally once daily in the morning with 150 mL of water at least 15 minutes prior to breakfast for 7 Days.	GW823093C 30 mg n=10 Participants Participants received 30 mg (2x15 mg) of GW823093C capsules orally once daily in the morning with 150 mL of water at least 15 minutes prior to breakfast for 7 Days.	GW823093C 30 mg n=10 Participants Participants received 30 mg (2x15 mg) of GW823093C capsules orally once daily in the morning with 150 mL of water at least 15 minutes prior to breakfast for 7 Days.
Glucagon Weighted Mean AUCs at Baseline (Day -1) and Day 7 AUC(0-12 hr), Day -1	113.1 Picogram per milliliter (pg/mL) Standard Deviation 49.2	100.1 Picogram per milliliter (pg/mL) Standard Deviation 14.9	125.1 Picogram per milliliter (pg/mL) Standard Deviation 37.0
Glucagon Weighted Mean AUCs at Baseline (Day -1) and Day 7 AUC(0-12 hr), Day 7	113.9 Picogram per milliliter (pg/mL) Standard Deviation 34.4	97.3 Picogram per milliliter (pg/mL) Standard Deviation 17.3	105.6 Picogram per milliliter (pg/mL) Standard Deviation 27.2
Glucagon Weighted Mean AUCs at Baseline (Day -1) and Day 7 AUC(0-24 hr), Day -1	114.7 Picogram per milliliter (pg/mL) Standard Deviation 53.2	104.4 Picogram per milliliter (pg/mL) Standard Deviation 16.9	129.0 Picogram per milliliter (pg/mL) Standard Deviation 41.0
Glucagon Weighted Mean AUCs at Baseline (Day -1) and Day 7 AUC(0-24 hr), Day 7	113.4 Picogram per milliliter (pg/mL) Standard Deviation 32.5	97.0 Picogram per milliliter (pg/mL) Standard Deviation 16.3	105.6 Picogram per milliliter (pg/mL) Standard Deviation 24.3

PRIMARY outcome

Timeframe: Baseline (Day -1) and Day 7

Population: PD Parameter Population.

For the analysis of plasma C-peptide concentrations, approximately 2 mL of whole blood was collected into a vacuum tube containing EDTA2Na, and then centrifuged in a refrigerated centrifuge at approximately 4 degree Celsius, at approximately 2500 rpm for 15 minutes. Samples were stored in a freezer at -70 degree Celsius or lower. Double-delta represented the active treatment within participant change from Baseline summarized across participants, subtracted from placebo within participant change from Baseline summarized across participants. AUC with respect to these time interval was calculated using linear trapezoidal rule by sum of the areas between each chronological pair of assessments (using observed times). Weighted mean was then determined by dividing AUC by observed length of collection interval (time of last assessment - time of first assessment in hr). Double-delta analysis for weighted mean AUCs has been presented in the statistical analysis section.

Outcome measures

Measure	GW823093C 15 mg n=10 Participants Participants received one 15 mg of GW823093C capsule and one placebo capsule orally once daily in the morning with 150 mL of water at least 15 minutes prior to breakfast for 7 Days.	GW823093C 30 mg n=10 Participants Participants received 30 mg (2x15 mg) of GW823093C capsules orally once daily in the morning with 150 mL of water at least 15 minutes prior to breakfast for 7 Days.	GW823093C 30 mg n=10 Participants Participants received 30 mg (2x15 mg) of GW823093C capsules orally once daily in the morning with 150 mL of water at least 15 minutes prior to breakfast for 7 Days.
C-peptide Weighted Mean AUCs at Baseline (Day -1) and Day 7 AUC(0-12 hr), Day -1	4.29 ng/mL Standard Deviation 1.25	3.78 ng/mL Standard Deviation 1.54	4.73 ng/mL Standard Deviation 1.29
C-peptide Weighted Mean AUCs at Baseline (Day -1) and Day 7 AUC(0-12 hr), Day 7	4.46 ng/mL Standard Deviation 1.20	4.31 ng/mL Standard Deviation 1.27	5.25 ng/mL Standard Deviation 1.83
C-peptide Weighted Mean AUCs at Baseline (Day -1) and Day 7 AUC(0-24 hr), Day -1	3.88 ng/mL Standard Deviation 1.02	3.54 ng/mL Standard Deviation 1.41	4.40 ng/mL Standard Deviation 1.30
C-peptide Weighted Mean AUCs at Baseline (Day -1) and Day 7 AUC(0-24 hr), Day 7	4.01 ng/mL Standard Deviation 0.90	4.07 ng/mL Standard Deviation 1.18	4.94 ng/mL Standard Deviation 1.72

PRIMARY outcome

Timeframe: Baseline (Day -1) and Day 7

Population: PD Parameter Population.

For the analysis of plasma glucose concentrations, approximately 2 mL of whole blood was collected into a vacuum tube containing sodium fluoride, and then centrifuged in a refrigerated centrifuge at approximately 4 degree Celsius, at approximately 2500 rpm for 15 minutes. Samples were stored in a freezer at -70 degree Celsius or lower. Double-delta represented the active treatment within participant change from Baseline summarized across participants, subtracted from placebo within participant change from Baseline summarized across participants. AUC with respect to these time interval was calculated using linear trapezoidal rule by sum of the areas between each chronological pair of assessments (using observed times). Weighted mean was then determined by dividing AUC by observed length of collection interval (time of last assessment - time of first assessment in hr). Double-delta analysis for weighted mean AUCs has been presented in the statistical analysis section.

Outcome measures

Measure	GW823093C 15 mg n=10 Participants Participants received one 15 mg of GW823093C capsule and one placebo capsule orally once daily in the morning with 150 mL of water at least 15 minutes prior to breakfast for 7 Days.	GW823093C 30 mg n=10 Participants Participants received 30 mg (2x15 mg) of GW823093C capsules orally once daily in the morning with 150 mL of water at least 15 minutes prior to breakfast for 7 Days.	GW823093C 30 mg n=10 Participants Participants received 30 mg (2x15 mg) of GW823093C capsules orally once daily in the morning with 150 mL of water at least 15 minutes prior to breakfast for 7 Days.
Glucose Weighted Mean AUCs at Baseline (Day -1) and Day 7 AUC(0-12 hr), Day -1	218.9 Milligrams per deciliter (mg/dL) Standard Deviation 69.5	233.8 Milligrams per deciliter (mg/dL) Standard Deviation 68.7	227.5 Milligrams per deciliter (mg/dL) Standard Deviation 64.1
Glucose Weighted Mean AUCs at Baseline (Day -1) and Day 7 AUC(0-12 hr), Day 7	210.0 Milligrams per deciliter (mg/dL) Standard Deviation 73.5	203.2 Milligrams per deciliter (mg/dL) Standard Deviation 52.5	208.6 Milligrams per deciliter (mg/dL) Standard Deviation 62.1
Glucose Weighted Mean AUCs at Baseline (Day -1) and Day 7 AUC(0-24 hr), Day -1	211.4 Milligrams per deciliter (mg/dL) Standard Deviation 66.0	221.6 Milligrams per deciliter (mg/dL) Standard Deviation 58.2	219.1 Milligrams per deciliter (mg/dL) Standard Deviation 51.6
Glucose Weighted Mean AUCs at Baseline (Day -1) and Day 7 AUC(0-24 hr), Day 7	201.1 Milligrams per deciliter (mg/dL) Standard Deviation 67.2	194.6 Milligrams per deciliter (mg/dL) Standard Deviation 45.5	202.0 Milligrams per deciliter (mg/dL) Standard Deviation 55.5

SECONDARY outcome

Timeframe: Up to post-study screen (Follow-up [7 days after the last dose of study medication])

Population: Safety Population comprised of all participants who received study medication (active or placebo).

AE is defined as any untoward medical occurrence in a 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. SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is serious corresponding to those listed in above definition.

Outcome measures

Measure	GW823093C 15 mg n=10 Participants Participants received one 15 mg of GW823093C capsule and one placebo capsule orally once daily in the morning with 150 mL of water at least 15 minutes prior to breakfast for 7 Days.	GW823093C 30 mg n=10 Participants Participants received 30 mg (2x15 mg) of GW823093C capsules orally once daily in the morning with 150 mL of water at least 15 minutes prior to breakfast for 7 Days.	GW823093C 30 mg n=10 Participants Participants received 30 mg (2x15 mg) of GW823093C capsules orally once daily in the morning with 150 mL of water at least 15 minutes prior to breakfast for 7 Days.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Any AEs	1 Participants	0 Participants	0 Participants
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Any SAEs	0 Participants	0 Participants	0 Participants

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

GW823093C 15 mg

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

GW823093C 30 mg

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Placebo n=10 participants at risk Participants received two capsules of matching placebo orally once daily in the morning with 150 mL of water at least 15 minutes prior to breakfast for 7 Days.	GW823093C 15 mg n=10 participants at risk Participants received one 15 mg of GW823093C capsule and one placebo capsule orally once daily in the morning with 150 mL of water at least 15 minutes prior to breakfast for 7 Days.	GW823093C 30 mg n=10 participants at risk Participants received 30 mg (2x15 mg) of GW823093C capsules orally once daily in the morning with 150 mL of water at least 15 minutes prior to breakfast for 7 Days.
Infections and infestations Herpes zoster	10.0% 1/10 • AEs and SAEs were collected up to post-study screen (Follow-up [7 days after the last dose of study medication]). Safety Population was used for the analysis.	0.00% 0/10 • AEs and SAEs were collected up to post-study screen (Follow-up [7 days after the last dose of study medication]). Safety Population was used for the analysis.	0.00% 0/10 • AEs and SAEs were collected up to post-study screen (Follow-up [7 days after the last dose of study medication]). Safety Population was used for the analysis.

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

• Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
• Publication restrictions are in place

Restriction type: OTHER