Type 2 Diabetes Mellitus
Conditions
Keywords
phase 1, safety and tolerability, PK, PD, type 2 diabetes mellitus, T2DM
Brief summary
The purpose of this study is to characterize the safety, tolerability, pharmacokinetics, and pharmacodynamics of PF-04937319 following single escalating oral doses in adult subjects with Type 2 Diabetes Mellitus (T2DM).
Detailed description
The purpose of this phase 1 study is to characterize the safety, tolerability, pharmacokinetics, and pharmacodynamics of PF04937319 following single escalating oral doses in adult subjects with T2DM.
Interventions
DRUGPlacebo
Placebo to match PF-04937319 will be provided.
DRUGPF-04937319
The initial planned dosing schedule is: 10, 30, 100, 200, and 400 mg, with one cohort to be determined. Doses shown may be adjusted upwards or downwards and may be adjusted to include intermediate doses. All doses will be administered as a single oral dose as a powder-in-capsule (PIC) formulation. PF-04937319 will be supplied as 10 mg and 80 mg (and potentially 1 mg) PIC.
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Patients with type 2 diabetes mellitus who are taking stable doses of metformin only. Subjects treated with a sulfonylurea (SU) or a dipeptidyl peptidase-IV inhibitor (DPP-IVi) in combination with metformin may be eligible if washed off the SU or DPP-IVi to metformin only for a minimum of 4 weeks before dosing. * Male and/or female subjects (females will be women of non childbearing potential) between the ages of 18 and 65 years, inclusive, with a body mass index (BMI) of 18.5 to 45.0 kg/m2 and C-peptide \>0.8 ng/mL. * Screening and Day -2 troponin I concentration \</=0.05 ng/mL as measured by the Bayer Centaur Ultra assay. * HbA1c \>/=7% and \</=11%. If the patient requires to be washed off an SU or DPP-IVi, the HbA1c limits will be \>/=7% and \</=9.5%.
Exclusion criteria
* Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing). * Evidence or history of diabetic complications with significant end organ damage, eg, proliferative retinopathy and/or macular edema, creatinine clearance \</=60 mL/min based on the Cockcroft-Gault equation, diabetic neuropathy complicated by neuropathic ulcers. * History of stroke, transient ischemic attack, or myocardial infarction within the past 6 months. Additionally, history of coronary artery bypass graft or stent implantation, clinically significant peripheral vascular disease, or congestive heart failure (NYHA Classes II-IV). Furthermore, a current history of angina/unstable angina. Also, 12 lead electrocardiogram (ECG) demonstrating QTc \>450 msec at screening, ECG findings suggestive of asymptomatic myocardial ischemia, or supine blood pressure \>/=160 mm Hg (systolic) or \</=100 mm Hg (diastolic). * One or more self reported episodes of hypoglycemia within the last 3 months, or two or more self reported episodes of hypoglycemia within the last 6 months. * Screening or Day -2 fasting (\>/=8 hours) blood glucose, \</=70 or \>/=270 mg/dL, confirmed by a single repeat if deemed necessary.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) | 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose | AUCinf is the area under the plasma concentration versus time curve from time zero to extrapolated infinite time. |
| Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | Day 1 up to 10 days after last dose of study medication (up to 11 days) | 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. |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) | 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose | Area under the plasma concentration-time curve from zero to the last measured concentration (AUClast). |
| Maximum Observed Plasma Concentration (Cmax) | 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose | — |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) | 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose | — |
| Apparent Oral Clearance (CL/F) | 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose | Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. |
| Apparent Volume of Distribution (Vz/F) | 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose | 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. |
| Plasma Decay Half-Life (t1/2) | 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose | Plasma decay half-life (t1/2) is the time measured for the plasma concentration to decrease by one half. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | -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 | 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. |
| 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 | -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 | 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. |
| 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 | -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 | 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. |
| Change From Baseline in Ratio of Insulin Delta C30 to Glucose Delta C30 After a Mixed Meal Tolerance Test (MMTT) on Day 1 | -46, -45.5 hrs pre-dose on Day -1; 2, 2.5 hrs post-dose on Day 1 | 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. |
| Change From Baseline in Ratio of C-peptide Delta C30 to Glucose Delta C30 After a Mixed Meal Tolerance Test (MMTT) | -46, -45.5 hrs pre-dose on Day -1; 2, 2.5 hrs post-dose on Day 1 | 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. |
| Change From Baseline in Ratio of Insulin Area Under Curve (Insulin AUC) to Glucose Area Under Curve (Glucose AUC) After a Mixed Meal Tolerance Test (MMTT) on Day 1 | -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 | 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. |
| 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 | -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 | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PF-04937319 10 mg Participants received single oral dose of PF-04937319 10 milligram (mg) capsule on Day 1. | 6 |
| PF-04937319 30 mg Participants received single oral dose of PF-04937319 30 mg (3 capsules of 10 mg) on Day 1. | 6 |
| 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. | 6 |
| 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. | 6 |
| PF-04937319 480 mg Participants received single oral dose of PF-04937319 480 mg (6 capsules of 80 mg) on Day 1. | 5 |
| PF-04937319 640 mg Participants received single oral dose of PF-04937319 640 mg (8 capsules of 80 mg) on Day 1. | 5 |
| Placebo Participants received single oral dose of placebo matched to PF-04937319 capsule on Day 1. | 16 |
| Total | 50 |
Baseline characteristics
| Characteristic | PF-04937319 10 mg | PF-04937319 30 mg | PF-04937319 100 mg | PF-04937319 300 mg | PF-04937319 480 mg | PF-04937319 640 mg | Placebo | Total |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 55.0 years STANDARD_DEVIATION 9 | 52.2 years STANDARD_DEVIATION 8.8 | 52.0 years STANDARD_DEVIATION 6.8 | 58.8 years STANDARD_DEVIATION 4.6 | 55.0 years STANDARD_DEVIATION 8.1 | 49.0 years STANDARD_DEVIATION 10 | 53.7 years STANDARD_DEVIATION 7.8 | 53.7 years STANDARD_DEVIATION 7.9 |
| Sex: Female, Male Female | 4 Participants | 2 Participants | 3 Participants | 2 Participants | 0 Participants | 1 Participants | 4 Participants | 16 Participants |
| Sex: Female, Male Male | 2 Participants | 4 Participants | 3 Participants | 4 Participants | 5 Participants | 4 Participants | 12 Participants | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 6 | 4 / 6 | 1 / 6 | 3 / 6 | 3 / 5 | 3 / 5 | 0 / 16 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 5 | 0 / 5 | 0 / 16 |
Outcome results
Primary
Apparent Oral Clearance (CL/F)
Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-04937319 10 mg | Apparent Oral Clearance (CL/F) | 344.8 milliliter per minute (mL/min) | Geometric Coefficient of Variation 13 |
| PF-04937319 30 mg | Apparent Oral Clearance (CL/F) | 360.9 milliliter per minute (mL/min) | Geometric Coefficient of Variation 37 |
| PF-04937319 100 mg | Apparent Oral Clearance (CL/F) | 364.4 milliliter per minute (mL/min) | Geometric Coefficient of Variation 26 |
| PF-04937319 300 mg | Apparent Oral Clearance (CL/F) | 464.2 milliliter per minute (mL/min) | Geometric Coefficient of Variation 40 |
| PF-04937319 480 mg | Apparent Oral Clearance (CL/F) | 690.3 milliliter per minute (mL/min) | Geometric Coefficient of Variation 28 |
| PF-04937319 640 mg | Apparent Oral Clearance (CL/F) | 481.8 milliliter per minute (mL/min) | Geometric Coefficient of Variation 10 |
Primary
Apparent Volume of Distribution (Vz/F)
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.
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-04937319 10 mg | Apparent Volume of Distribution (Vz/F) | 154.0 liter | Geometric Coefficient of Variation 12 |
| PF-04937319 30 mg | Apparent Volume of Distribution (Vz/F) | 204.6 liter | Geometric Coefficient of Variation 42 |
| PF-04937319 100 mg | Apparent Volume of Distribution (Vz/F) | 254.4 liter | Geometric Coefficient of Variation 25 |
| PF-04937319 300 mg | Apparent Volume of Distribution (Vz/F) | 284.1 liter | Geometric Coefficient of Variation 76 |
| PF-04937319 480 mg | Apparent Volume of Distribution (Vz/F) | 379.2 liter | Geometric Coefficient of Variation 25 |
| PF-04937319 640 mg | Apparent Volume of Distribution (Vz/F) | 399.3 liter | Geometric Coefficient of Variation 23 |
Primary
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf)
AUCinf is the area under the plasma concentration versus time curve from time zero to extrapolated infinite time.
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-04937319 10 mg | Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) | 483.3 nanogram*hour per milliliter | Geometric Coefficient of Variation 13 |
| PF-04937319 30 mg | Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) | 1385 nanogram*hour per milliliter | Geometric Coefficient of Variation 34 |
| PF-04937319 100 mg | Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) | 4570 nanogram*hour per milliliter | Geometric Coefficient of Variation 23 |
| PF-04937319 300 mg | Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) | 10770 nanogram*hour per milliliter | Geometric Coefficient of Variation 35 |
| PF-04937319 480 mg | Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) | 11590 nanogram*hour per milliliter | Geometric Coefficient of Variation 28 |
| PF-04937319 640 mg | Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) | 22130 nanogram*hour per milliliter | Geometric Coefficient of Variation 9 |
Primary
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)
Area under the plasma concentration-time curve from zero to the last measured concentration (AUClast).
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-04937319 10 mg | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) | 475.2 nanogram*hour per milliliter | Geometric Coefficient of Variation 13 |
| PF-04937319 30 mg | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) | 1362 nanogram*hour per milliliter | Geometric Coefficient of Variation 34 |
| PF-04937319 100 mg | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) | 4418 nanogram*hour per milliliter | Geometric Coefficient of Variation 21 |
| PF-04937319 300 mg | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) | 10640 nanogram*hour per milliliter | Geometric Coefficient of Variation 33 |
| PF-04937319 480 mg | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) | 10830 nanogram*hour per milliliter | Geometric Coefficient of Variation 29 |
| PF-04937319 640 mg | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) | 19970 nanogram*hour per milliliter | Geometric Coefficient of Variation 11 |
Primary
Maximum Observed Plasma Concentration (Cmax)
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-04937319 10 mg | Maximum Observed Plasma Concentration (Cmax) | 72.29 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 25 |
| PF-04937319 30 mg | Maximum Observed Plasma Concentration (Cmax) | 124.9 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 17 |
| PF-04937319 100 mg | Maximum Observed Plasma Concentration (Cmax) | 339.8 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 34 |
| PF-04937319 300 mg | Maximum Observed Plasma Concentration (Cmax) | 756.6 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 59 |
| PF-04937319 480 mg | Maximum Observed Plasma Concentration (Cmax) | 769.9 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 50 |
| PF-04937319 640 mg | Maximum Observed Plasma Concentration (Cmax) | 1050 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 24 |
Primary
Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)
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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PF-04937319 10 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | AEs | 1 participants |
| PF-04937319 10 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | SAEs | 0 participants |
| PF-04937319 30 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | AEs | 4 participants |
| PF-04937319 30 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | SAEs | 0 participants |
| PF-04937319 100 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | AEs | 1 participants |
| PF-04937319 100 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | SAEs | 0 participants |
| PF-04937319 300 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | AEs | 3 participants |
| PF-04937319 300 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | SAEs | 0 participants |
| PF-04937319 480 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | AEs | 3 participants |
| PF-04937319 480 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | SAEs | 0 participants |
| PF-04937319 640 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | AEs | 3 participants |
| PF-04937319 640 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | SAEs | 0 participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | AEs | 0 participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | SAEs | 0 participants |
Primary
Plasma Decay Half-Life (t1/2)
Plasma decay half-life (t1/2) is the time measured for the plasma concentration to decrease by one half.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PF-04937319 10 mg | Plasma Decay Half-Life (t1/2) | 5.203 hour | Standard Deviation 0.74888 |
| PF-04937319 30 mg | Plasma Decay Half-Life (t1/2) | 6.592 hour | Standard Deviation 0.79893 |
| PF-04937319 100 mg | Plasma Decay Half-Life (t1/2) | 8.632 hour | Standard Deviation 3.3756 |
| PF-04937319 300 mg | Plasma Decay Half-Life (t1/2) | 7.366 hour | Standard Deviation 2.4225 |
| PF-04937319 480 mg | Plasma Decay Half-Life (t1/2) | 6.410 hour | Standard Deviation 1.0422 |
| PF-04937319 640 mg | Plasma Decay Half-Life (t1/2) | 12.79 hour | Standard Deviation 6.3392 |
Primary
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PF-04937319 10 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 2.48 hour |
| PF-04937319 30 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 2.50 hour |
| PF-04937319 100 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 3.00 hour |
| PF-04937319 300 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 3.50 hour |
| PF-04937319 480 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 6.00 hour |
| PF-04937319 640 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 7.98 hour |
Secondary
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
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.
Time frame: -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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PF-04937319 10 mg | 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 (ng*dL*hour)/(mg*mL*hour) | Standard Deviation 0.012 |
| PF-04937319 10 mg | 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 (ng*dL*hour)/(mg*mL*hour) | Standard Deviation 0.002 |
| PF-04937319 30 mg | 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) | 0.03 (ng*dL*hour)/(mg*mL*hour) | Standard Deviation 0.014 |
| PF-04937319 30 mg | 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 (ng*dL*hour)/(mg*mL*hour) | Standard Deviation 0.004 |
| PF-04937319 100 mg | 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) | 0.03 (ng*dL*hour)/(mg*mL*hour) | Standard Deviation 0.02 |
| PF-04937319 100 mg | 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 (ng*dL*hour)/(mg*mL*hour) | Standard Deviation 0.013 |
| PF-04937319 300 mg | 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) | 0.03 (ng*dL*hour)/(mg*mL*hour) | Standard Deviation 0.009 |
| PF-04937319 300 mg | 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) | 0.01 (ng*dL*hour)/(mg*mL*hour) | Standard Deviation 0.003 |
| PF-04937319 480 mg | 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) | 0.03 (ng*dL*hour)/(mg*mL*hour) | Standard Deviation 0.009 |
| PF-04937319 480 mg | 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) | 0.01 (ng*dL*hour)/(mg*mL*hour) | Standard Deviation 0.005 |
| PF-04937319 640 mg | 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) | 0.03 (ng*dL*hour)/(mg*mL*hour) | Standard Deviation 0.009 |
| PF-04937319 640 mg | 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) | 0.01 (ng*dL*hour)/(mg*mL*hour) | Standard Deviation 0.008 |
| Placebo | 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) | 0.03 (ng*dL*hour)/(mg*mL*hour) | Standard Deviation 0.013 |
| Placebo | 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 (ng*dL*hour)/(mg*mL*hour) | Standard Deviation 0.005 |
Secondary
Change From Baseline in Ratio of C-peptide Delta C30 to Glucose Delta C30 After a Mixed Meal Tolerance Test (MMTT)
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.
Time frame: -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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PF-04937319 10 mg | 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 (ng*dL)/(mg*mL) | Standard Deviation 0.018 |
| PF-04937319 10 mg | Change From Baseline in Ratio of C-peptide Delta C30 to Glucose Delta C30 After a Mixed Meal Tolerance Test (MMTT) | Baseline | 0.04 (ng*dL)/(mg*mL) | Standard Deviation 0.034 |
| PF-04937319 30 mg | Change From Baseline in Ratio of C-peptide Delta C30 to Glucose Delta C30 After a Mixed Meal Tolerance Test (MMTT) | Baseline | 0.16 (ng*dL)/(mg*mL) | Standard Deviation 0.293 |
| PF-04937319 30 mg | 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 | -0.12 (ng*dL)/(mg*mL) | Standard Deviation 0.283 |
| PF-04937319 100 mg | 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 | -0.02 (ng*dL)/(mg*mL) | Standard Deviation 0.05 |
| PF-04937319 100 mg | Change From Baseline in Ratio of C-peptide Delta C30 to Glucose Delta C30 After a Mixed Meal Tolerance Test (MMTT) | Baseline | 0.05 (ng*dL)/(mg*mL) | Standard Deviation 0.064 |
| PF-04937319 300 mg | 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 (ng*dL)/(mg*mL) | Standard Deviation 0.006 |
| PF-04937319 300 mg | Change From Baseline in Ratio of C-peptide Delta C30 to Glucose Delta C30 After a Mixed Meal Tolerance Test (MMTT) | Baseline | 0.03 (ng*dL)/(mg*mL) | Standard Deviation 0.011 |
| PF-04937319 480 mg | Change From Baseline in Ratio of C-peptide Delta C30 to Glucose Delta C30 After a Mixed Meal Tolerance Test (MMTT) | Baseline | 0.02 (ng*dL)/(mg*mL) | Standard Deviation 0.008 |
| PF-04937319 480 mg | 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 | 0.13 (ng*dL)/(mg*mL) | Standard Deviation 0.24 |
| PF-04937319 640 mg | Change From Baseline in Ratio of C-peptide Delta C30 to Glucose Delta C30 After a Mixed Meal Tolerance Test (MMTT) | Baseline | 0.05 (ng*dL)/(mg*mL) | Standard Deviation 0.038 |
| PF-04937319 640 mg | 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 | 0.02 (ng*dL)/(mg*mL) | Standard Deviation 0.029 |
| Placebo | 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 | 0.00 (ng*dL)/(mg*mL) | Standard Deviation 0.025 |
| Placebo | Change From Baseline in Ratio of C-peptide Delta C30 to Glucose Delta C30 After a Mixed Meal Tolerance Test (MMTT) | Baseline | 0.04 (ng*dL)/(mg*mL) | Standard Deviation 0.023 |
Secondary
Change From Baseline in Ratio of Insulin Area Under Curve (Insulin AUC) to Glucose Area Under Curve (Glucose AUC) After a Mixed Meal Tolerance Test (MMTT) on Day 1
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.
Time frame: -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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PF-04937319 10 mg | Change From Baseline in Ratio of Insulin Area Under Curve (Insulin AUC) to Glucose Area Under Curve (Glucose AUC) After a Mixed Meal Tolerance Test (MMTT) on Day 1 | Baseline (n= 5,5,6,6,5,5,14) | 0.24 (mU*dL*hour)/(mg*liter*hour) | Standard Deviation 0.118 |
| PF-04937319 10 mg | Change From Baseline in Ratio of Insulin Area Under Curve (Insulin AUC) to Glucose Area Under Curve (Glucose AUC) After a Mixed Meal Tolerance Test (MMTT) on Day 1 | Change at Day 1 (n= 5,4,6,5,5,5,14) | 0.03 (mU*dL*hour)/(mg*liter*hour) | Standard Deviation 0.036 |
| PF-04937319 30 mg | Change From Baseline in Ratio of Insulin Area Under Curve (Insulin AUC) to Glucose Area Under Curve (Glucose AUC) After a Mixed Meal Tolerance Test (MMTT) on Day 1 | Baseline (n= 5,5,6,6,5,5,14) | 0.32 (mU*dL*hour)/(mg*liter*hour) | Standard Deviation 0.257 |
| PF-04937319 30 mg | Change From Baseline in Ratio of Insulin Area Under Curve (Insulin AUC) to Glucose Area Under Curve (Glucose AUC) After a Mixed Meal Tolerance Test (MMTT) on Day 1 | Change at Day 1 (n= 5,4,6,5,5,5,14) | 0.10 (mU*dL*hour)/(mg*liter*hour) | Standard Deviation 0.104 |
| PF-04937319 100 mg | Change From Baseline in Ratio of Insulin Area Under Curve (Insulin AUC) to Glucose Area Under Curve (Glucose AUC) After a Mixed Meal Tolerance Test (MMTT) on Day 1 | Baseline (n= 5,5,6,6,5,5,14) | 0.48 (mU*dL*hour)/(mg*liter*hour) | Standard Deviation 0.452 |
| PF-04937319 100 mg | Change From Baseline in Ratio of Insulin Area Under Curve (Insulin AUC) to Glucose Area Under Curve (Glucose AUC) After a Mixed Meal Tolerance Test (MMTT) on Day 1 | Change at Day 1 (n= 5,4,6,5,5,5,14) | -0.12 (mU*dL*hour)/(mg*liter*hour) | Standard Deviation 0.235 |
| PF-04937319 300 mg | Change From Baseline in Ratio of Insulin Area Under Curve (Insulin AUC) to Glucose Area Under Curve (Glucose AUC) After a Mixed Meal Tolerance Test (MMTT) on Day 1 | Baseline (n= 5,5,6,6,5,5,14) | 0.36 (mU*dL*hour)/(mg*liter*hour) | Standard Deviation 0.142 |
| PF-04937319 300 mg | Change From Baseline in Ratio of Insulin Area Under Curve (Insulin AUC) to Glucose Area Under Curve (Glucose AUC) After a Mixed Meal Tolerance Test (MMTT) on Day 1 | Change at Day 1 (n= 5,4,6,5,5,5,14) | 0.04 (mU*dL*hour)/(mg*liter*hour) | Standard Deviation 0.062 |
| PF-04937319 480 mg | Change From Baseline in Ratio of Insulin Area Under Curve (Insulin AUC) to Glucose Area Under Curve (Glucose AUC) After a Mixed Meal Tolerance Test (MMTT) on Day 1 | Baseline (n= 5,5,6,6,5,5,14) | 0.29 (mU*dL*hour)/(mg*liter*hour) | Standard Deviation 0.085 |
| PF-04937319 480 mg | Change From Baseline in Ratio of Insulin Area Under Curve (Insulin AUC) to Glucose Area Under Curve (Glucose AUC) After a Mixed Meal Tolerance Test (MMTT) on Day 1 | Change at Day 1 (n= 5,4,6,5,5,5,14) | 0.16 (mU*dL*hour)/(mg*liter*hour) | Standard Deviation 0.104 |
| PF-04937319 640 mg | Change From Baseline in Ratio of Insulin Area Under Curve (Insulin AUC) to Glucose Area Under Curve (Glucose AUC) After a Mixed Meal Tolerance Test (MMTT) on Day 1 | Baseline (n= 5,5,6,6,5,5,14) | 0.38 (mU*dL*hour)/(mg*liter*hour) | Standard Deviation 0.31 |
| PF-04937319 640 mg | Change From Baseline in Ratio of Insulin Area Under Curve (Insulin AUC) to Glucose Area Under Curve (Glucose AUC) After a Mixed Meal Tolerance Test (MMTT) on Day 1 | Change at Day 1 (n= 5,4,6,5,5,5,14) | 0.10 (mU*dL*hour)/(mg*liter*hour) | Standard Deviation 0.169 |
| Placebo | Change From Baseline in Ratio of Insulin Area Under Curve (Insulin AUC) to Glucose Area Under Curve (Glucose AUC) After a Mixed Meal Tolerance Test (MMTT) on Day 1 | Baseline (n= 5,5,6,6,5,5,14) | 0.34 (mU*dL*hour)/(mg*liter*hour) | Standard Deviation 0.222 |
| Placebo | Change From Baseline in Ratio of Insulin Area Under Curve (Insulin AUC) to Glucose Area Under Curve (Glucose AUC) After a Mixed Meal Tolerance Test (MMTT) on Day 1 | Change at Day 1 (n= 5,4,6,5,5,5,14) | 0.01 (mU*dL*hour)/(mg*liter*hour) | Standard Deviation 0.071 |
Secondary
Change From Baseline in Ratio of Insulin Delta C30 to Glucose Delta C30 After a Mixed Meal Tolerance Test (MMTT) on Day 1
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.
Time frame: -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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PF-04937319 10 mg | 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 (mU*dL)/(mg*Liter) | Standard Deviation 0.627 |
| PF-04937319 10 mg | 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 (mU*dL)/(mg*Liter) | Standard Deviation 0.427 |
| PF-04937319 30 mg | Change From Baseline in Ratio of Insulin Delta C30 to Glucose Delta C30 After a Mixed Meal Tolerance Test (MMTT) on Day 1 | Baseline | 4.59 (mU*dL)/(mg*Liter) | Standard Deviation 6.935 |
| PF-04937319 30 mg | 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 | -3.20 (mU*dL)/(mg*Liter) | Standard Deviation 7.093 |
| PF-04937319 100 mg | Change From Baseline in Ratio of Insulin Delta C30 to Glucose Delta C30 After a Mixed Meal Tolerance Test (MMTT) on Day 1 | Baseline | 1.92 (mU*dL)/(mg*Liter) | Standard Deviation 2.759 |
| PF-04937319 100 mg | 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 | -0.81 (mU*dL)/(mg*Liter) | Standard Deviation 1.891 |
| PF-04937319 300 mg | Change From Baseline in Ratio of Insulin Delta C30 to Glucose Delta C30 After a Mixed Meal Tolerance Test (MMTT) on Day 1 | Baseline | 0.77 (mU*dL)/(mg*Liter) | Standard Deviation 0.289 |
| PF-04937319 300 mg | 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 | 0.25 (mU*dL)/(mg*Liter) | Standard Deviation 0.09 |
| PF-04937319 480 mg | Change From Baseline in Ratio of Insulin Delta C30 to Glucose Delta C30 After a Mixed Meal Tolerance Test (MMTT) on Day 1 | Baseline | 0.73 (mU*dL)/(mg*Liter) | Standard Deviation 0.265 |
| PF-04937319 480 mg | 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 | 1.89 (mU*dL)/(mg*Liter) | Standard Deviation 3.894 |
| PF-04937319 640 mg | Change From Baseline in Ratio of Insulin Delta C30 to Glucose Delta C30 After a Mixed Meal Tolerance Test (MMTT) on Day 1 | Baseline | 0.85 (mU*dL)/(mg*Liter) | Standard Deviation 0.631 |
| PF-04937319 640 mg | 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 | 0.74 (mU*dL)/(mg*Liter) | Standard Deviation 0.675 |
| Placebo | Change From Baseline in Ratio of Insulin Delta C30 to Glucose Delta C30 After a Mixed Meal Tolerance Test (MMTT) on Day 1 | Baseline | 1.15 (mU*dL)/(mg*Liter) | Standard Deviation 0.798 |
| Placebo | 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 | -0.05 (mU*dL)/(mg*Liter) | Standard Deviation 0.607 |
Secondary
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
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.
Time frame: -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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PF-04937319 10 mg | 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 |
| PF-04937319 30 mg | 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 | -0.63 percent change | Standard Deviation 14.664 |
| PF-04937319 100 mg | 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 | 1.79 percent change | Standard Deviation 17.426 |
| PF-04937319 300 mg | 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 | 8.23 percent change | Standard Deviation 8.101 |
| PF-04937319 480 mg | 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 | 21.13 percent change | Standard Deviation 8.037 |
| PF-04937319 640 mg | 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 | 12.51 percent change | Standard Deviation 19.188 |
| Placebo | 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 | 6.09 percent change | Standard Deviation 18.625 |
Secondary
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
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.
Time frame: -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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PF-04937319 10 mg | 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 |
| PF-04937319 30 mg | 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 | -15.22 percent change | Standard Deviation 8.887 |
| PF-04937319 100 mg | 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 | 4.96 percent change | Standard Deviation 31.567 |
| PF-04937319 300 mg | 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 | -11.72 percent change | Standard Deviation 8.35 |
| PF-04937319 480 mg | 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 | -10.81 percent change | Standard Deviation 10.017 |
| PF-04937319 640 mg | 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 | -23.21 percent change | Standard Deviation 10.207 |
| Placebo | 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 | -0.45 percent change | Standard Deviation 13.041 |
Secondary
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
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.
Time frame: -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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PF-04937319 10 mg | 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 |
| PF-04937319 30 mg | 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 | 10.72 percent change | Standard Deviation 13.424 |
| PF-04937319 100 mg | 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 | 0.22 percent change | Standard Deviation 26.086 |
| PF-04937319 300 mg | 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 | 2.03 percent change | Standard Deviation 15.622 |
| PF-04937319 480 mg | 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 | 35.61 percent change | Standard Deviation 28.235 |
| PF-04937319 640 mg | 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 | 9.30 percent change | Standard Deviation 38.556 |
| Placebo | 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 | 6.35 percent change | Standard Deviation 25.752 |