Trial Outcomes & Findings for A Trial To Assess The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Of Single Doses Of PF-04937319 In Subjects With Type 2 Diabetes Mellitus (NCT NCT01044537)

Results Overview

An AE was any untoward medical occurrence in a participant who received study medication without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study medication and up to 10 days after last dose that were absent before treatment or that worsened relative to pretreatment state.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

50 participants

Primary outcome timeframe

Day 1 up to 10 days after last dose of study medication (up to 11 days)

Results posted on

2017-03-10

Participant Flow

Participant milestones

Participant milestones
Measure	PF-04937319 10 mg Participants received single oral dose of PF-04937319 10 milligram (mg) capsule on Day 1.	PF-04937319 30 mg Participants received single oral dose of PF-04937319 30 mg (3 capsules of 10 mg) on Day 1.	PF-04937319 100 mg Participants received single oral dose of PF-04937319 100 mg (1 capsule of 80 mg and 2 capsules of 10 mg) on Day 1.	PF-04937319 300 mg Participants received single oral dose of PF-04937319 300 mg (3 capsules of 80 mg and 6 capsules of 10 mg) on Day 1.	PF-04937319 480 mg Participants received single oral dose of PF-04937319 480 mg (6 capsules of 80 mg) on Day 1.	PF-04937319 640 mg Participants received single oral dose of PF-04937319 640 mg (8 capsules of 80 mg) on Day 1.	Placebo Participants received single oral dose of placebo matched to PF-04937319 capsule on Day 1.
Overall Study STARTED	6	6	6	6	5	5	16
Overall Study COMPLETED	6	6	6	6	5	5	16
Overall Study NOT COMPLETED	0	0	0	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Trial To Assess The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Of Single Doses Of PF-04937319 In Subjects With Type 2 Diabetes Mellitus

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	PF-04937319 10 mg n=6 Participants Participants received single oral dose of PF-04937319 10 milligram (mg) capsule on Day 1.	PF-04937319 30 mg n=6 Participants Participants received single oral dose of PF-04937319 30 mg (3 capsules of 10 mg) on Day 1.	PF-04937319 100 mg n=6 Participants Participants received single oral dose of PF-04937319 100 mg (1 capsule of 80 mg and 2 capsules of 10 mg) on Day 1.	PF-04937319 300 mg n=6 Participants Participants received single oral dose of PF-04937319 300 mg (3 capsules of 80 mg and 6 capsules of 10 mg) on Day 1.	PF-04937319 480 mg n=5 Participants Participants received single oral dose of PF-04937319 480 mg (6 capsules of 80 mg) on Day 1.	PF-04937319 640 mg n=5 Participants Participants received single oral dose of PF-04937319 640 mg (8 capsules of 80 mg) on Day 1.	Placebo n=16 Participants Participants received single oral dose of placebo matched to PF-04937319 capsule on Day 1.	Total n=50 Participants Total of all reporting groups
Age, Continuous	55.0 years STANDARD_DEVIATION 9.0 • n=5 Participants	52.2 years STANDARD_DEVIATION 8.8 • n=7 Participants	52.0 years STANDARD_DEVIATION 6.8 • n=5 Participants	58.8 years STANDARD_DEVIATION 4.6 • n=4 Participants	55.0 years STANDARD_DEVIATION 8.1 • n=21 Participants	49.0 years STANDARD_DEVIATION 10.0 • n=10 Participants	53.7 years STANDARD_DEVIATION 7.8 • n=115 Participants	53.7 years STANDARD_DEVIATION 7.9 • n=6 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants	2 Participants n=4 Participants	0 Participants n=21 Participants	1 Participants n=10 Participants	4 Participants n=115 Participants	16 Participants n=6 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	4 Participants n=7 Participants	3 Participants n=5 Participants	4 Participants n=4 Participants	5 Participants n=21 Participants	4 Participants n=10 Participants	12 Participants n=115 Participants	34 Participants n=6 Participants

PRIMARY outcome

Timeframe: Day 1 up to 10 days after last dose of study medication (up to 11 days)

Population: Safety analysis set included all participants who received at least 1 dose of study medication.

An AE was any untoward medical occurrence in a participant who received study medication without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study medication and up to 10 days after last dose that were absent before treatment or that worsened relative to pretreatment state.

Outcome measures

Outcome measures
Measure	PF-04937319 10 mg n=6 Participants Participants received single oral dose of PF-04937319 10 milligram (mg) capsule on Day 1.	PF-04937319 30 mg n=6 Participants Participants received single oral dose of PF-04937319 30 mg (3 capsules of 10 mg) on Day 1.	PF-04937319 100 mg n=6 Participants Participants received single oral dose of PF-04937319 100 mg (1 capsule of 80 mg and 2 capsules of 10 mg) on Day 1.	PF-04937319 300 mg n=6 Participants Participants received single oral dose of PF-04937319 300 mg (3 capsules of 80 mg and 6 capsules of 10 mg) on Day 1.	PF-04937319 480 mg n=5 Participants Participants received single oral dose of PF-04937319 480 mg (6 capsules of 80 mg) on Day 1.	PF-04937319 640 mg n=5 Participants Participants received single oral dose of PF-04937319 640 mg (8 capsules of 80 mg) on Day 1.	Placebo n=16 Participants Participants received single oral dose of placebo matched to PF-04937319 capsule on Day 1.
Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) AEs	1 participants	4 participants	1 participants	3 participants	3 participants	3 participants	0 participants
Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) SAEs	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants

PRIMARY outcome

Timeframe: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose

Population: Pharmacokinetic (PK) parameter analysis population included all enrolled participants who received study medication and had at least 1 of the PK parameters of interest.

Area under the plasma concentration-time curve from zero to the last measured concentration (AUClast).

Outcome measures

Outcome measures
Measure	PF-04937319 10 mg n=6 Participants Participants received single oral dose of PF-04937319 10 milligram (mg) capsule on Day 1.	PF-04937319 30 mg n=6 Participants Participants received single oral dose of PF-04937319 30 mg (3 capsules of 10 mg) on Day 1.	PF-04937319 100 mg n=5 Participants Participants received single oral dose of PF-04937319 100 mg (1 capsule of 80 mg and 2 capsules of 10 mg) on Day 1.	PF-04937319 300 mg n=6 Participants Participants received single oral dose of PF-04937319 300 mg (3 capsules of 80 mg and 6 capsules of 10 mg) on Day 1.	PF-04937319 480 mg n=5 Participants Participants received single oral dose of PF-04937319 480 mg (6 capsules of 80 mg) on Day 1.	PF-04937319 640 mg n=5 Participants Participants received single oral dose of PF-04937319 640 mg (8 capsules of 80 mg) on Day 1.	Placebo Participants received single oral dose of placebo matched to PF-04937319 capsule on Day 1.
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)	475.2 nanogram*hour per milliliter Geometric Coefficient of Variation 13	1362 nanogram*hour per milliliter Geometric Coefficient of Variation 34	4418 nanogram*hour per milliliter Geometric Coefficient of Variation 21	10640 nanogram*hour per milliliter Geometric Coefficient of Variation 33	10830 nanogram*hour per milliliter Geometric Coefficient of Variation 29	19970 nanogram*hour per milliliter Geometric Coefficient of Variation 11	—

PRIMARY outcome

Timeframe: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose

Population: PK parameter analysis population included all enrolled participants who received study medication and had at least 1 of the PK parameters of interest.

Outcome measures

Outcome measures
Measure	PF-04937319 10 mg n=6 Participants Participants received single oral dose of PF-04937319 10 milligram (mg) capsule on Day 1.	PF-04937319 30 mg n=6 Participants Participants received single oral dose of PF-04937319 30 mg (3 capsules of 10 mg) on Day 1.	PF-04937319 100 mg n=5 Participants Participants received single oral dose of PF-04937319 100 mg (1 capsule of 80 mg and 2 capsules of 10 mg) on Day 1.	PF-04937319 300 mg n=6 Participants Participants received single oral dose of PF-04937319 300 mg (3 capsules of 80 mg and 6 capsules of 10 mg) on Day 1.	PF-04937319 480 mg n=5 Participants Participants received single oral dose of PF-04937319 480 mg (6 capsules of 80 mg) on Day 1.	PF-04937319 640 mg n=5 Participants Participants received single oral dose of PF-04937319 640 mg (8 capsules of 80 mg) on Day 1.	Placebo Participants received single oral dose of placebo matched to PF-04937319 capsule on Day 1.
Maximum Observed Plasma Concentration (Cmax)	72.29 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 25	124.9 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 17	339.8 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 34	756.6 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 59	769.9 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 50	1050 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 24	—

PRIMARY outcome

Timeframe: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose

Population: PK parameter analysis population included all enrolled participants who received study medication and had at least 1 of the PK parameters of interest.

Outcome measures

Outcome measures
Measure	PF-04937319 10 mg n=6 Participants Participants received single oral dose of PF-04937319 10 milligram (mg) capsule on Day 1.	PF-04937319 30 mg n=6 Participants Participants received single oral dose of PF-04937319 30 mg (3 capsules of 10 mg) on Day 1.	PF-04937319 100 mg n=5 Participants Participants received single oral dose of PF-04937319 100 mg (1 capsule of 80 mg and 2 capsules of 10 mg) on Day 1.	PF-04937319 300 mg n=6 Participants Participants received single oral dose of PF-04937319 300 mg (3 capsules of 80 mg and 6 capsules of 10 mg) on Day 1.	PF-04937319 480 mg n=5 Participants Participants received single oral dose of PF-04937319 480 mg (6 capsules of 80 mg) on Day 1.	PF-04937319 640 mg n=5 Participants Participants received single oral dose of PF-04937319 640 mg (8 capsules of 80 mg) on Day 1.	Placebo Participants received single oral dose of placebo matched to PF-04937319 capsule on Day 1.
Time to Reach Maximum Observed Plasma Concentration (Tmax)	2.48 hour Interval 1.95 to 3.0	2.50 hour Interval 1.0 to 6.0	3.00 hour Interval 1.95 to 8.0	3.50 hour Interval 3.0 to 6.0	6.00 hour Interval 1.92 to 6.0	7.98 hour Interval 3.0 to 12.0	—

PRIMARY outcome

Timeframe: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose

Population: PK parameter analysis population included all enrolled participants who received study medication and had at least 1 of the PK parameters of interest. Here 'N' (number of participants analyzed) signifies participants evaluable for this measure.

Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.

Outcome measures

Outcome measures
Measure	PF-04937319 10 mg n=6 Participants Participants received single oral dose of PF-04937319 10 milligram (mg) capsule on Day 1.	PF-04937319 30 mg n=6 Participants Participants received single oral dose of PF-04937319 30 mg (3 capsules of 10 mg) on Day 1.	PF-04937319 100 mg n=5 Participants Participants received single oral dose of PF-04937319 100 mg (1 capsule of 80 mg and 2 capsules of 10 mg) on Day 1.	PF-04937319 300 mg n=4 Participants Participants received single oral dose of PF-04937319 300 mg (3 capsules of 80 mg and 6 capsules of 10 mg) on Day 1.	PF-04937319 480 mg n=4 Participants Participants received single oral dose of PF-04937319 480 mg (6 capsules of 80 mg) on Day 1.	PF-04937319 640 mg n=3 Participants Participants received single oral dose of PF-04937319 640 mg (8 capsules of 80 mg) on Day 1.	Placebo Participants received single oral dose of placebo matched to PF-04937319 capsule on Day 1.
Apparent Oral Clearance (CL/F)	344.8 milliliter per minute (mL/min) Geometric Coefficient of Variation 13	360.9 milliliter per minute (mL/min) Geometric Coefficient of Variation 37	364.4 milliliter per minute (mL/min) Geometric Coefficient of Variation 26	464.2 milliliter per minute (mL/min) Geometric Coefficient of Variation 40	690.3 milliliter per minute (mL/min) Geometric Coefficient of Variation 28	481.8 milliliter per minute (mL/min) Geometric Coefficient of Variation 10	—

PRIMARY outcome

Timeframe: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose

Population: PK parameter analysis population included all enrolled participants who received study medication and had at least 1 of the PK parameters of interest. Here 'N' (number of participants analyzed) signifies participants evaluable for this measure.

Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.

Outcome measures

Outcome measures
Measure	PF-04937319 10 mg n=6 Participants Participants received single oral dose of PF-04937319 10 milligram (mg) capsule on Day 1.	PF-04937319 30 mg n=6 Participants Participants received single oral dose of PF-04937319 30 mg (3 capsules of 10 mg) on Day 1.	PF-04937319 100 mg n=5 Participants Participants received single oral dose of PF-04937319 100 mg (1 capsule of 80 mg and 2 capsules of 10 mg) on Day 1.	PF-04937319 300 mg n=4 Participants Participants received single oral dose of PF-04937319 300 mg (3 capsules of 80 mg and 6 capsules of 10 mg) on Day 1.	PF-04937319 480 mg n=4 Participants Participants received single oral dose of PF-04937319 480 mg (6 capsules of 80 mg) on Day 1.	PF-04937319 640 mg n=3 Participants Participants received single oral dose of PF-04937319 640 mg (8 capsules of 80 mg) on Day 1.	Placebo Participants received single oral dose of placebo matched to PF-04937319 capsule on Day 1.
Apparent Volume of Distribution (Vz/F)	154.0 liter Geometric Coefficient of Variation 12	204.6 liter Geometric Coefficient of Variation 42	254.4 liter Geometric Coefficient of Variation 25	284.1 liter Geometric Coefficient of Variation 76	379.2 liter Geometric Coefficient of Variation 25	399.3 liter Geometric Coefficient of Variation 23	—

PRIMARY outcome

Timeframe: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose

Population: PK parameter analysis population included all enrolled participants who received study medication and had at least 1 of the PK parameters of interest. Here 'N' (number of participants analyzed) signifies participants evaluable for this measure.

Plasma decay half-life (t1/2) is the time measured for the plasma concentration to decrease by one half.

Outcome measures

Outcome measures
Measure	PF-04937319 10 mg n=6 Participants Participants received single oral dose of PF-04937319 10 milligram (mg) capsule on Day 1.	PF-04937319 30 mg n=6 Participants Participants received single oral dose of PF-04937319 30 mg (3 capsules of 10 mg) on Day 1.	PF-04937319 100 mg n=5 Participants Participants received single oral dose of PF-04937319 100 mg (1 capsule of 80 mg and 2 capsules of 10 mg) on Day 1.	PF-04937319 300 mg n=5 Participants Participants received single oral dose of PF-04937319 300 mg (3 capsules of 80 mg and 6 capsules of 10 mg) on Day 1.	PF-04937319 480 mg n=4 Participants Participants received single oral dose of PF-04937319 480 mg (6 capsules of 80 mg) on Day 1.	PF-04937319 640 mg n=4 Participants Participants received single oral dose of PF-04937319 640 mg (8 capsules of 80 mg) on Day 1.	Placebo Participants received single oral dose of placebo matched to PF-04937319 capsule on Day 1.
Plasma Decay Half-Life (t1/2)	5.203 hour Standard Deviation 0.74888	6.592 hour Standard Deviation 0.79893	8.632 hour Standard Deviation 3.3756	7.366 hour Standard Deviation 2.4225	6.410 hour Standard Deviation 1.0422	12.79 hour Standard Deviation 6.3392	—

PRIMARY outcome

Timeframe: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose

Population: PK parameter analysis population included all enrolled participants who received study medication and had at least 1 of the PK parameters of interest. Here 'N' (number of participants analyzed) signifies participants evaluable for this measure.

AUCinf is the area under the plasma concentration versus time curve from time zero to extrapolated infinite time.

Outcome measures

Outcome measures
Measure	PF-04937319 10 mg n=6 Participants Participants received single oral dose of PF-04937319 10 milligram (mg) capsule on Day 1.	PF-04937319 30 mg n=6 Participants Participants received single oral dose of PF-04937319 30 mg (3 capsules of 10 mg) on Day 1.	PF-04937319 100 mg n=5 Participants Participants received single oral dose of PF-04937319 100 mg (1 capsule of 80 mg and 2 capsules of 10 mg) on Day 1.	PF-04937319 300 mg n=4 Participants Participants received single oral dose of PF-04937319 300 mg (3 capsules of 80 mg and 6 capsules of 10 mg) on Day 1.	PF-04937319 480 mg n=4 Participants Participants received single oral dose of PF-04937319 480 mg (6 capsules of 80 mg) on Day 1.	PF-04937319 640 mg n=3 Participants Participants received single oral dose of PF-04937319 640 mg (8 capsules of 80 mg) on Day 1.	Placebo Participants received single oral dose of placebo matched to PF-04937319 capsule on Day 1.
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf)	483.3 nanogram*hour per milliliter Geometric Coefficient of Variation 13	1385 nanogram*hour per milliliter Geometric Coefficient of Variation 34	4570 nanogram*hour per milliliter Geometric Coefficient of Variation 23	10770 nanogram*hour per milliliter Geometric Coefficient of Variation 35	11590 nanogram*hour per milliliter Geometric Coefficient of Variation 28	22130 nanogram*hour per milliliter Geometric Coefficient of Variation 9	—

SECONDARY outcome

Timeframe: -46, -45.75, -45.5, -45, -44.5, -44, -43, -42 hours pre-dose on Day -1; 2, 2.25, 2.5, 3, 3.5, 4, 5, 6 hours post-dose on Day 1

Population: PD analysis population included all enrolled participants who received at least 1 dose of study medication and had at least 1 of the PD parameters of interest. 'N' (number of participants analyzed) signifies participants evaluable for this measure and 'n' signifies participants evaluable at specified time point for each arm group, respectively.

Ratio of area under the plasma C-peptide concentration-time curve from time 2 to 6 hrs (in terms of nanogram\*deciliter\*hour \[ng\*dL\*hour\]) to area under the plasma glucose concentration-time curve from time 2 to 6 hrs (in terms of milligram\*milliliter\*hour \[mg\*mL\*hour\]) was calculated. Linear trapezoidal method was used to compute AUC. The change in ratio from baseline (Day -1) was calculated at Day 1.

Outcome measures

Outcome measures
Measure	PF-04937319 10 mg n=5 Participants Participants received single oral dose of PF-04937319 10 milligram (mg) capsule on Day 1.	PF-04937319 30 mg n=6 Participants Participants received single oral dose of PF-04937319 30 mg (3 capsules of 10 mg) on Day 1.	PF-04937319 100 mg n=6 Participants Participants received single oral dose of PF-04937319 100 mg (1 capsule of 80 mg and 2 capsules of 10 mg) on Day 1.	PF-04937319 300 mg n=6 Participants Participants received single oral dose of PF-04937319 300 mg (3 capsules of 80 mg and 6 capsules of 10 mg) on Day 1.	PF-04937319 480 mg n=5 Participants Participants received single oral dose of PF-04937319 480 mg (6 capsules of 80 mg) on Day 1.	PF-04937319 640 mg n=5 Participants Participants received single oral dose of PF-04937319 640 mg (8 capsules of 80 mg) on Day 1.	Placebo n=15 Participants Participants received single oral dose of placebo matched to PF-04937319 capsule on Day 1.
Change From Baseline in Ratio of C-peptide Area Under Curve (C-peptide AUC) to Glucose Area Under Curve (Glucose AUC) After a Mixed Meal Tolerance Test (MMTT) on Day 1 Baseline (n= 5,6,6,6,5,5,15)	0.02 (ngdLhour)/(mgmLhour) Standard Deviation 0.012	0.03 (ngdLhour)/(mgmLhour) Standard Deviation 0.014	0.03 (ngdLhour)/(mgmLhour) Standard Deviation 0.020	0.03 (ngdLhour)/(mgmLhour) Standard Deviation 0.009	0.03 (ngdLhour)/(mgmLhour) Standard Deviation 0.009	0.03 (ngdLhour)/(mgmLhour) Standard Deviation 0.009	0.03 (ngdLhour)/(mgmLhour) Standard Deviation 0.013
Change From Baseline in Ratio of C-peptide Area Under Curve (C-peptide AUC) to Glucose Area Under Curve (Glucose AUC) After a Mixed Meal Tolerance Test (MMTT) on Day 1 Change at Day 1 (n= 5,5,6,6,5,5,15)	0.00 (ngdLhour)/(mgmLhour) Standard Deviation 0.002	0.00 (ngdLhour)/(mgmLhour) Standard Deviation 0.004	0.00 (ngdLhour)/(mgmLhour) Standard Deviation 0.013	0.01 (ngdLhour)/(mgmLhour) Standard Deviation 0.003	0.01 (ngdLhour)/(mgmLhour) Standard Deviation 0.005	0.01 (ngdLhour)/(mgmLhour) Standard Deviation 0.008	0.00 (ngdLhour)/(mgmLhour) Standard Deviation 0.005

SECONDARY outcome

Timeframe: -46, -45.75, -45.5, -45, -44.5, -44, -43, -42 hrs pre-dose on Day -1; 2, 2.25, 2.5, 3, 3.5, 4, 5, 6 hrs post-dose on Day 1

Population: PD analysis population included all enrolled participants who received at least 1 dose of study medication and had at least 1 of the PD parameters of interest. Here 'N' (number of participants analyzed) signifies participants evaluable for this measure.

Percent change from baseline in post-prandial area under the plasma glucose concentration-time curve as determined by standardized MMTT. Linear trapezoidal method was used to compute AUC. Baseline value was the AUC (2-6) calculated on Day -1.

Outcome measures

Outcome measures
Measure	PF-04937319 10 mg n=6 Participants Participants received single oral dose of PF-04937319 10 milligram (mg) capsule on Day 1.	PF-04937319 30 mg n=5 Participants Participants received single oral dose of PF-04937319 30 mg (3 capsules of 10 mg) on Day 1.	PF-04937319 100 mg n=6 Participants Participants received single oral dose of PF-04937319 100 mg (1 capsule of 80 mg and 2 capsules of 10 mg) on Day 1.	PF-04937319 300 mg n=6 Participants Participants received single oral dose of PF-04937319 300 mg (3 capsules of 80 mg and 6 capsules of 10 mg) on Day 1.	PF-04937319 480 mg n=5 Participants Participants received single oral dose of PF-04937319 480 mg (6 capsules of 80 mg) on Day 1.	PF-04937319 640 mg n=5 Participants Participants received single oral dose of PF-04937319 640 mg (8 capsules of 80 mg) on Day 1.	Placebo n=16 Participants Participants received single oral dose of placebo matched to PF-04937319 capsule on Day 1.
Percent Change From Baseline in Post-Prandial Glucose Area Under the Curve From Time 2 to 6 Hours (AUC [2-6]) After a Mixed Meal Tolerance Test (MMTT) on Day 1	8.58 percent change Standard Deviation 8.428	-15.22 percent change Standard Deviation 8.887	4.96 percent change Standard Deviation 31.567	-11.72 percent change Standard Deviation 8.350	-10.81 percent change Standard Deviation 10.017	-23.21 percent change Standard Deviation 10.207	-0.45 percent change Standard Deviation 13.041

SECONDARY outcome

Timeframe: -46, -45.75, -45.5, -45, -44.5, -44, -43, -42 hrs pre-dose on Day -1; 2, 2.25, 2.5, 3, 3.5, 4, 5, 6 hrs post-dose on Day 1

Population: PD analysis population included all enrolled participants who received at least 1 dose of study medication and had at least 1 of the PD parameters of interest. Here 'N' (number of participants analyzed) signifies participants evaluable for this measure.

Percent change from baseline in post-prandial area under the plasma insulin concentration-time curve as determined by standardized MMTT. Linear trapezoidal method was used to compute AUC. Baseline value was the AUC (2-6) calculated on Day -1.

Outcome measures

Outcome measures
Measure	PF-04937319 10 mg n=5 Participants Participants received single oral dose of PF-04937319 10 milligram (mg) capsule on Day 1.	PF-04937319 30 mg n=5 Participants Participants received single oral dose of PF-04937319 30 mg (3 capsules of 10 mg) on Day 1.	PF-04937319 100 mg n=6 Participants Participants received single oral dose of PF-04937319 100 mg (1 capsule of 80 mg and 2 capsules of 10 mg) on Day 1.	PF-04937319 300 mg n=5 Participants Participants received single oral dose of PF-04937319 300 mg (3 capsules of 80 mg and 6 capsules of 10 mg) on Day 1.	PF-04937319 480 mg n=5 Participants Participants received single oral dose of PF-04937319 480 mg (6 capsules of 80 mg) on Day 1.	PF-04937319 640 mg n=5 Participants Participants received single oral dose of PF-04937319 640 mg (8 capsules of 80 mg) on Day 1.	Placebo n=14 Participants Participants received single oral dose of placebo matched to PF-04937319 capsule on Day 1.
Percent Change From Baseline in Post-Prandial Insulin Area Under the Curve From Time 2 to 6 Hours (AUC [2-6]) After a Mixed Meal Tolerance Test (MMTT) on Day 1	30.98 percent change Standard Deviation 21.327	10.72 percent change Standard Deviation 13.424	0.22 percent change Standard Deviation 26.086	2.03 percent change Standard Deviation 15.622	35.61 percent change Standard Deviation 28.235	9.30 percent change Standard Deviation 38.556	6.35 percent change Standard Deviation 25.752

SECONDARY outcome

Timeframe: -46, -45.75, -45.5, -45, -44.5, -44, -43, -42 hrs pre-dose on Day -1; 2, 2.25, 2.5, 3, 3.5, 4, 5, 6 hrs post-dose on Day 1

Population: PD analysis population included all enrolled participants who received at least 1 dose of study medication and had at least 1 of the PD parameters of interest. Here 'N' (number of participants analyzed) signifies participants evaluable for this measure.

Percent change from baseline in post-prandial area under the plasma C-peptide concentration-time curve as determined by standardized MMTT. Linear trapezoidal method was used to compute AUC. Baseline value was the AUC (2-6) calculated on Day -1.

Outcome measures

Outcome measures
Measure	PF-04937319 10 mg n=5 Participants Participants received single oral dose of PF-04937319 10 milligram (mg) capsule on Day 1.	PF-04937319 30 mg n=6 Participants Participants received single oral dose of PF-04937319 30 mg (3 capsules of 10 mg) on Day 1.	PF-04937319 100 mg n=6 Participants Participants received single oral dose of PF-04937319 100 mg (1 capsule of 80 mg and 2 capsules of 10 mg) on Day 1.	PF-04937319 300 mg n=6 Participants Participants received single oral dose of PF-04937319 300 mg (3 capsules of 80 mg and 6 capsules of 10 mg) on Day 1.	PF-04937319 480 mg n=5 Participants Participants received single oral dose of PF-04937319 480 mg (6 capsules of 80 mg) on Day 1.	PF-04937319 640 mg n=5 Participants Participants received single oral dose of PF-04937319 640 mg (8 capsules of 80 mg) on Day 1.	Placebo n=15 Participants Participants received single oral dose of placebo matched to PF-04937319 capsule on Day 1.
Percent Change From Baseline in Post-Prandial C-peptide Area Under the Curve From Time 2 to 6 Hours (AUC [2-6]) After a Mixed Meal Tolerance Test (MMTT) on Day 1	14.10 percent change Standard Deviation 3.749	-0.63 percent change Standard Deviation 14.664	1.79 percent change Standard Deviation 17.426	8.23 percent change Standard Deviation 8.101	21.13 percent change Standard Deviation 8.037	12.51 percent change Standard Deviation 19.188	6.09 percent change Standard Deviation 18.625

SECONDARY outcome

Timeframe: -46, -45.5 hrs pre-dose on Day -1; 2, 2.5 hrs post-dose on Day 1

Population: PD analysis population included all enrolled participants who received at least 1 dose of study medication and had at least 1 of the PD parameters of interest. Here 'N' (number of participants analyzed) signifies participants evaluable for this measure.

Ratio of insulin delta C30 (in terms of milliunits\*deciliter \[mU\*dL\]) to glucose delta C30 (in terms of milligram\*liter \[mg\*liter\]) was calculated. The change in ratio from baseline (Day -1) was calculated at Day 1.

Outcome measures

Outcome measures
Measure	PF-04937319 10 mg n=5 Participants Participants received single oral dose of PF-04937319 10 milligram (mg) capsule on Day 1.	PF-04937319 30 mg n=5 Participants Participants received single oral dose of PF-04937319 30 mg (3 capsules of 10 mg) on Day 1.	PF-04937319 100 mg n=6 Participants Participants received single oral dose of PF-04937319 100 mg (1 capsule of 80 mg and 2 capsules of 10 mg) on Day 1.	PF-04937319 300 mg n=6 Participants Participants received single oral dose of PF-04937319 300 mg (3 capsules of 80 mg and 6 capsules of 10 mg) on Day 1.	PF-04937319 480 mg n=5 Participants Participants received single oral dose of PF-04937319 480 mg (6 capsules of 80 mg) on Day 1.	PF-04937319 640 mg n=5 Participants Participants received single oral dose of PF-04937319 640 mg (8 capsules of 80 mg) on Day 1.	Placebo n=15 Participants Participants received single oral dose of placebo matched to PF-04937319 capsule on Day 1.
Change From Baseline in Ratio of Insulin Delta C30 to Glucose Delta C30 After a Mixed Meal Tolerance Test (MMTT) on Day 1 Baseline	0.70 (mUdL)/(mgLiter) Standard Deviation 0.627	4.59 (mUdL)/(mgLiter) Standard Deviation 6.935	1.92 (mUdL)/(mgLiter) Standard Deviation 2.759	0.77 (mUdL)/(mgLiter) Standard Deviation 0.289	0.73 (mUdL)/(mgLiter) Standard Deviation 0.265	0.85 (mUdL)/(mgLiter) Standard Deviation 0.631	1.15 (mUdL)/(mgLiter) Standard Deviation 0.798
Change From Baseline in Ratio of Insulin Delta C30 to Glucose Delta C30 After a Mixed Meal Tolerance Test (MMTT) on Day 1 Change at Day 1	-0.04 (mUdL)/(mgLiter) Standard Deviation 0.427	-3.20 (mUdL)/(mgLiter) Standard Deviation 7.093	-0.81 (mUdL)/(mgLiter) Standard Deviation 1.891	0.25 (mUdL)/(mgLiter) Standard Deviation 0.090	1.89 (mUdL)/(mgLiter) Standard Deviation 3.894	0.74 (mUdL)/(mgLiter) Standard Deviation 0.675	-0.05 (mUdL)/(mgLiter) Standard Deviation 0.607

SECONDARY outcome

Timeframe: -46, -45.5 hrs pre-dose on Day -1; 2, 2.5 hrs post-dose on Day 1

Population: PD analysis population included all enrolled participants who received at least 1 dose of study medication and had at least 1 of the PD parameters of interest. Here 'N' (number of participants analyzed) signifies participants evaluable for this measure.

Ratio of C-peptide Delta C30 (in terms of nanogram\*deciliter \[ng\*dL\]) to glucose delta C30 (in terms of milligram\*milliliter \[mg\*mL\]) was calculated. The change in ratio from baseline (Day -1) was calculated at Day 1.

Outcome measures

Outcome measures
Measure	PF-04937319 10 mg n=5 Participants Participants received single oral dose of PF-04937319 10 milligram (mg) capsule on Day 1.	PF-04937319 30 mg n=6 Participants Participants received single oral dose of PF-04937319 30 mg (3 capsules of 10 mg) on Day 1.	PF-04937319 100 mg n=6 Participants Participants received single oral dose of PF-04937319 100 mg (1 capsule of 80 mg and 2 capsules of 10 mg) on Day 1.	PF-04937319 300 mg n=6 Participants Participants received single oral dose of PF-04937319 300 mg (3 capsules of 80 mg and 6 capsules of 10 mg) on Day 1.	PF-04937319 480 mg n=5 Participants Participants received single oral dose of PF-04937319 480 mg (6 capsules of 80 mg) on Day 1.	PF-04937319 640 mg n=5 Participants Participants received single oral dose of PF-04937319 640 mg (8 capsules of 80 mg) on Day 1.	Placebo n=15 Participants Participants received single oral dose of placebo matched to PF-04937319 capsule on Day 1.
Change From Baseline in Ratio of C-peptide Delta C30 to Glucose Delta C30 After a Mixed Meal Tolerance Test (MMTT) Baseline	0.04 (ngdL)/(mgmL) Standard Deviation 0.034	0.16 (ngdL)/(mgmL) Standard Deviation 0.293	0.05 (ngdL)/(mgmL) Standard Deviation 0.064	0.03 (ngdL)/(mgmL) Standard Deviation 0.011	0.02 (ngdL)/(mgmL) Standard Deviation 0.008	0.05 (ngdL)/(mgmL) Standard Deviation 0.038	0.04 (ngdL)/(mgmL) Standard Deviation 0.023
Change From Baseline in Ratio of C-peptide Delta C30 to Glucose Delta C30 After a Mixed Meal Tolerance Test (MMTT) Change at Day 1	-0.01 (ngdL)/(mgmL) Standard Deviation 0.018	-0.12 (ngdL)/(mgmL) Standard Deviation 0.283	-0.02 (ngdL)/(mgmL) Standard Deviation 0.050	0.01 (ngdL)/(mgmL) Standard Deviation 0.006	0.13 (ngdL)/(mgmL) Standard Deviation 0.240	0.02 (ngdL)/(mgmL) Standard Deviation 0.029	0.00 (ngdL)/(mgmL) Standard Deviation 0.025

SECONDARY outcome

Timeframe: -46, -45.75, -45.5, -45, -44.5, -44, -43, -42 hrs pre-dose on Day -1; 2, 2.25, 2.5, 3, 3.5, 4, 5, 6 hrs post-dose on Day 1

Population: PD analysis population included all enrolled participants who received at least 1 dose of study medication and had at least 1 of the PD parameters of interest. 'N' (number of participants analyzed) signifies participants evaluable for this measure and 'n' signifies participants evaluable at specified time point for each arm group, respectively.

Ratio of area under the plasma insulin concentration-time curve from time 2 to 6 hrs (in terms of milliunit\*deciliter\*hour \[mU\*dL\*hour\]) to area under the plasma glucose concentration-time curve from time 2 to 6 hrs (in terms of milligram\*liter\*hour \[mg\*liter\*hour\]) was calculated. Linear trapezoidal method was used to compute AUC. The change in ratio from baseline (Day -1) was calculated at Day 1.