Type 2 Diabetes Mellitus
Conditions
Keywords
Phase 1b, type 2 diabetes, metformin background, PF-04937319
Brief summary
Study B1621019 will assess efficacy and safety of two different dosing regimens of an investigational agent (PF-04937319) compared to an approved drug (sitagliptin) in patients with type 2 diabetes
Interventions
DRUGPF-04937319 once-daily
Tablets, 300 mg once-daily with breakfast, 14-days
DRUGPF-04937319 split-dose
tablets, 150 mg with breakfast plus 100 mg with lunch, 14-days
DRUGSitagliptin once-daily
tablets, 100 mg once-daily with breakfast, 14-days
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Patients with type 2 diabetes, on background metformin therapy either alone or with 1 other oral anti-diabetic agent (excluding Actos)
Exclusion criteria
* Patients with cardiovascular event within 6-months of screening * Patients with diabetic complications * Female subjects who are pregnant or planning to become pregnant * Subjects with unstable medical conditions (eg, hypertension)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Weighted Mean Daily Glucose (WMDG) at Day 14 | Prior to morning dose (Hour 0) and at 1.5, 3, 5, 6.5, 8, 11, 12.5, 14, 16, 20, and 24 hours post morning dose on Days 0 (baseline) and Day 14 | Plasma glucose concentration was determined predose (Hour 0) and at 1.5, 3, 5, 6.5, 8, 11, 12.5, 14, 16, 20, and 24 hours postdose on Days 0 (baseline) and 14. WMDG was calculated as the area under the curve (AUC) of the 12-point plasma glucose concentration-time profile divided by 24 hours. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Pre-meal C-Peptide on Day 14 | Day 14 | Blood samples for measurement of glucose to permit derivation of pre-meal collections of blood samples for C-peptide at the pre-specified nominal timepoints at predose, 5 and 11 hours on Day 0 (baseline) and Day 14. |
| Change From Baseline in Pre-meal Insulin on Day 14 | Day 14 | Blood samples for measurement of glucose to permit derivation of pre-meal collections of blood samples for insulin at 0, 5 and 11 hours on Day 0 (baseline) and Day 14. |
| Incidence of All Causality Treatment-Emergent Adverse Event by Preferred Term (Frequency Rate >5%) | Day 1 up to Day 14 | — |
| Frequency of Laboratory Test Abnormalities Reported in Any Treatment Group | Day 1 up to Day 14 | The total number of participants with laboratory test abnormalities (without regard to baseline abnormality) was assessed. |
| Change From Baseline in Body Weight (kg) | Day 1 up to Day 14 | — |
| Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern | Day 1 up to Day 14 | Vital signs included blood pressure (BP; supine, sitting and standing) and pulse rate. Vital signs criteria of potential clinical concern were 1), BP: sitting systolic BP (SBP) greater than or equal to (\>=) 30 millimeters of mercury (mm Hg) change from baseline, sitting SBP =\<20 mmHg change from baseline, supine/sitting/standing SBP less than (\<) 90 mm Hg; sitting diastolic BP (DBP) \>=20 mm Hg change from baseline, sitting SBP =\<20 mmHg change from baseline, supine/sitting/standing DBP \<50 mm Hg; 2), pulse rate (supine): \<40 or greater than (\>) 120 beats per minute (bpm). |
| Change From Baseline in Fasting Plasma Glucose (FPG) at Day 14 | Day 14 | Blood samples for measurement of glucose to permit derivation of pre-meal collections at the pre-specified nominal timepoints of each period: predose (ie, time 0), 1.5, 3, 5, 6.5, 8, 11, 12.5, 14, 16 and 20 hours on Day 0 (baseline) and Day 14; and predose on Days 1 and 15. |
| Plasma PF-04937319 Area Under the Concentration Time Curve From Time 0 to 24 Hours (AUC24) of PF-04937319 at Day 14 | Predose, 1.5, 3, 5, 6.5, 8, 11, 12.5, and 14 hours on Days 0 and 14; and predose on Days 7 and 15. | The PK parameters were summarized descriptively by treatment as appropriate. Two (2) PK parameters specified in the protocol and SAP were not reported: AUClast was not reported since it was the same as AUC24 in this study, and apparent volume of distribution (Vz/F) was not reported since the log-linear terminal phase of the concentration-time profiles was not consistently well characterized in the 24-hour sampling period. |
| Plasma PF-04937319 Apparent Clearance (CL/F) on Day 14 | Predose, 1.5, 3, 5, 6.5, 8, 11, 12.5, and 14 hours on Days 0 and 14; and predose on Days 7 and 15. | The PK parameters were summarized descriptively by treatment as appropriate. Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population PK modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. |
| Plasma PF-04937319 Average Concentration Over the 24-hour Period (Cav) on Day 14 | Predose, 1.5, 3, 5, 6.5, 8, 11, 12.5, and 14 hours on Days 0 and 14; and predose on Days 7 and 15. | Cav was average concentration over the 24-hour period. The PK parameters were summarized descriptively by treatment as appropriate. |
| Plasma PF-04937319 Highest Observed Concentration (Cmax) on Day 14 | Predose, 1.5, 3, 5, 6.5, 8, 11, 12.5, and 14 hours on Days 0 and 14; and predose on Days 7 and 15. | Cmax was highest observed concentration. The PK parameters were summarized descriptively by treatment as appropriate. |
| Plasma PF-04937319 Lowest Observed Concentration During the 24-hour Period (Cmin) on Day 14 | Predose, 1.5, 3, 5, 6.5, 8, 11, 12.5, and 14 hours on Days 0 and 14; and predose on Days 7 and 15. | Cmin lowest observed concentration during the 24-hour period. The PK parameters were summarized descriptively by treatment as appropriate. |
| Plasma PF-04937319 Time for Cmax (Tmax) on Day 14 | Predose, 1.5, 3, 5, 6.5, 8, 11, 12.5, and 14 hours on Days 0 and 14; and predose on Days 7 and 15. | Tmax was time of maximum concentration. The PK parameters were summarized descriptively by treatment as appropriate. |
| Number of Participants With Post-baseline Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern | Day 1 up to Day 14 | ECG criteria of potential clinical concern were 1), PR interval: \>=300 milliseconds (msec); \>=25% increase when baseline \>200 msec; or increase \>=50% when baseline \<=200 msec; 2), QRS interval: \>=140 msec; \>=50% increase from baseline; 3), QTc interval using Fridericia's formula (QTcF interval): absolute value \>=450 - \<480 msec, \>=480-\<500 msec, \>500 msec; absolute change 30 - \<60, \>=60 msec. |
Countries
United States
Participant flow
Recruitment details
A total of 90 participants with type 2 diabetes mellitus (T2DM) consented for this study; of these, 47 participants were ineligible at screening visit, 43 (47.8%) transitioned into run-in phase where participants were standardized on Sponsor-provided metformin.
Pre-assignment details
A total of 33 (33/90; 36.7%) participants completed metformin run-in period and were randomized and received to at least one regimen (PF-04937319 split-dose, PF-04937319 once daily, or sitagliptin).
Participants by arm
| Arm | Count |
|---|---|
| All* A total of 90 participants with T2DM were consented for this study; of these, 43 transitioned into run-in with Sponsor-provided metformin and a total of 33 participants were randomized. | 33 |
| Total | 33 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| First Intervention Period (12-16 Days) | Lost to Follow-up | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| First Intervention Period (12-16 Days) | Other | 0 | 0 | 1 | 0 | 0 | 1 | 0 |
| Metformin Run-in Period | Adverse Event | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Metformin Run-in Period | No longer meets eligibility criteria | 4 | 0 | 0 | 0 | 0 | 0 | 0 |
| Metformin Run-in Period | Other | 5 | 0 | 0 | 0 | 0 | 0 | 0 |
| Second Intervention Period (12-16 Days) | Other | 0 | 1 | 1 | 0 | 0 | 0 | 0 |
| Third Intervention Period (12-16 Days) | Lost to Follow-up | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Third Intervention Period (12-16 Days) | Withdrawal by Subject | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | All* |
|---|---|
| Age, Continuous | 56.5 years STANDARD_DEVIATION 8.3 |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 43 | 16 / 31 | 19 / 30 | 12 / 30 |
| serious Total, serious adverse events | 0 / 43 | 0 / 31 | 0 / 30 | 0 / 30 |
Outcome results
Primary
Change From Baseline in Weighted Mean Daily Glucose (WMDG) at Day 14
Plasma glucose concentration was determined predose (Hour 0) and at 1.5, 3, 5, 6.5, 8, 11, 12.5, 14, 16, 20, and 24 hours postdose on Days 0 (baseline) and 14. WMDG was calculated as the area under the curve (AUC) of the 12-point plasma glucose concentration-time profile divided by 24 hours.
Time frame: Prior to morning dose (Hour 0) and at 1.5, 3, 5, 6.5, 8, 11, 12.5, 14, 16, 20, and 24 hours post morning dose on Days 0 (baseline) and Day 14
Population: Full analysis set defined as all randomized subjects who had taken at least 1 dose of blinded study medication and who had both a baseline and a post-baseline WMDG assessment. Number of participants analyzed was the evaluable participants with a measurement at both baseline and on Day 14.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| PF-04937319 Split-Dose (150+100 mg) | Change From Baseline in Weighted Mean Daily Glucose (WMDG) at Day 14 | -31.24 milligram/deciliter (mg/dL) | Standard Error 3.952 |
| PF-04937319 Once-Daily (300 mg) | Change From Baseline in Weighted Mean Daily Glucose (WMDG) at Day 14 | -31.33 milligram/deciliter (mg/dL) | Standard Error 4.604 |
| Sitagliptin 100 mg | Change From Baseline in Weighted Mean Daily Glucose (WMDG) at Day 14 | -19.24 milligram/deciliter (mg/dL) | Standard Error 4.437 |
Comparison: Change from baseline80% CI: [-36.35, -26.12]
Comparison: Change from baseline80% CI: [-37.29, -25.37]
Comparison: Change from baseline80% CI: [-24.99, -13.5]
Comparison: There was no hypothesis to be tested. Difference in change from baseline in WMDG between the 2 treatment groups was calculated based on the mixed effects repeated measures model.80% CI: [-19.81, -4.17]
Comparison: There was no hypothesis to be tested. Difference in change from baseline in WMDG between the 2 treatment groups was calculated based on the mixed effects repeated measures model.80% CI: [-19.81, -4.17]
Secondary
Change From Baseline in Body Weight (kg)
Time frame: Day 1 up to Day 14
Population: The safety analysis set was all participants who received at least one dose of randomized study treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PF-04937319 Split-Dose (150+100 mg) | Change From Baseline in Body Weight (kg) | 0.50 kg | Standard Error 0.313 |
| PF-04937319 Once-Daily (300 mg) | Change From Baseline in Body Weight (kg) | 0.30 kg | Standard Error 0.545 |
| Sitagliptin 100 mg | Change From Baseline in Body Weight (kg) | 0.05 kg | Standard Error 0.215 |
Comparison: Compared with baseline80% CI: [0.21, 1.39]
Comparison: Compared with baseline80% CI: [-0.43, 0.93]
Comparison: Compared with baseline80% CI: [-0.92, 0.4]
80% CI: [0.17, 1.95]
80% CI: [-0.45, 1.47]
Secondary
Change From Baseline in Fasting Plasma Glucose (FPG) at Day 14
Blood samples for measurement of glucose to permit derivation of pre-meal collections at the pre-specified nominal timepoints of each period: predose (ie, time 0), 1.5, 3, 5, 6.5, 8, 11, 12.5, 14, 16 and 20 hours on Day 0 (baseline) and Day 14; and predose on Days 1 and 15.
Time frame: Day 14
Population: Full analysis set defined as all randomized subjects who had taken at least 1 dose of blinded study medication and who had both a baseline and a post-baseline WMDG assessment. Number of participants analyzed was the evaluable participants with a measurement on Day 14.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| PF-04937319 Split-Dose (150+100 mg) | Change From Baseline in Fasting Plasma Glucose (FPG) at Day 14 | -21.92 mg/dL | Standard Error 3.909 |
| PF-04937319 Once-Daily (300 mg) | Change From Baseline in Fasting Plasma Glucose (FPG) at Day 14 | -20.70 mg/dL | Standard Error 4.324 |
| Sitagliptin 100 mg | Change From Baseline in Fasting Plasma Glucose (FPG) at Day 14 | -16.51 mg/dL | Standard Error 4.419 |
Comparison: Compared with Baseline80% CI: [-27, -16.85]
Comparison: Compared with Baseline80% CI: [-26.3, -15.1]
Comparison: Compared with Baseline80% CI: [-22.24, -10.78]
Comparison: Change from baseline in FPG was analyzed in a mixed model analysis of covariance (ANCOVA) with regimen, period, sequence, treatment × period, and carryover as fixed effects. Subjects within sequences were modelled as random effects, with each subject's period-specific baseline response included, as fixed covariates.80% CI: [-11.74, 0.92]
Comparison: Change from baseline in FPG was analyzed in a mixed model analysis of covariance (ANCOVA) with regimen, period, sequence, treatment × period, and carryover as fixed effects. Subjects within sequences were modelled as random effects, with each subject's period-specific baseline response included, as fixed covariates.80% CI: [-10.86, 2.49]
Secondary
Change From Baseline in Pre-meal C-Peptide on Day 14
Blood samples for measurement of glucose to permit derivation of pre-meal collections of blood samples for C-peptide at the pre-specified nominal timepoints at predose, 5 and 11 hours on Day 0 (baseline) and Day 14.
Time frame: Day 14
Population: Full analysis set defined as all randomized subjects who had taken at least 1 dose of blinded study medication and who had both a baseline and a post-baseline WMDG assessment. Number of participants analyzed was the evaluable participants with a measurement on Day 14.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| PF-04937319 Split-Dose (150+100 mg) | Change From Baseline in Pre-meal C-Peptide on Day 14 | Pre-lunch change from baseline | 0.20 nanograms/milliliter (ng/mL) | Standard Error 0.218 |
| PF-04937319 Split-Dose (150+100 mg) | Change From Baseline in Pre-meal C-Peptide on Day 14 | Pre-breakfast change from baseline | -0.06 nanograms/milliliter (ng/mL) | Standard Error 0.101 |
| PF-04937319 Split-Dose (150+100 mg) | Change From Baseline in Pre-meal C-Peptide on Day 14 | Pre-dinner change from baseline | 0.36 nanograms/milliliter (ng/mL) | Standard Error 0.251 |
| PF-04937319 Once-Daily (300 mg) | Change From Baseline in Pre-meal C-Peptide on Day 14 | Pre-lunch change from baseline | 0.70 nanograms/milliliter (ng/mL) | Standard Error 0.249 |
| PF-04937319 Once-Daily (300 mg) | Change From Baseline in Pre-meal C-Peptide on Day 14 | Pre-breakfast change from baseline | 0.06 nanograms/milliliter (ng/mL) | Standard Error 0.115 |
| PF-04937319 Once-Daily (300 mg) | Change From Baseline in Pre-meal C-Peptide on Day 14 | Pre-dinner change from baseline | 0.30 nanograms/milliliter (ng/mL) | Standard Error 0.289 |
| Sitagliptin 100 mg | Change From Baseline in Pre-meal C-Peptide on Day 14 | Pre-breakfast change from baseline | 0.30 nanograms/milliliter (ng/mL) | Standard Error 0.112 |
| Sitagliptin 100 mg | Change From Baseline in Pre-meal C-Peptide on Day 14 | Pre-dinner change from baseline | 0.32 nanograms/milliliter (ng/mL) | Standard Error 0.28 |
| Sitagliptin 100 mg | Change From Baseline in Pre-meal C-Peptide on Day 14 | Pre-lunch change from baseline | 0.06 nanograms/milliliter (ng/mL) | Standard Error 0.242 |
Comparison: Compared with Baseline （Pre-breakfast）80% CI: [-0.19, 0.07]
Comparison: Compared with Baseline (Pre-breakfast)80% CI: [-0.09, 0.21]
Comparison: Compared with Baseline (Pre-breakfast)80% CI: [0.16, 0.45]
Comparison: Pre-breakfast; Time-matched change from baseline in pre-meal C-peptide on Day 14 was analyzed using a mixed effects model with sequence, period, treatment, the treatment by-time interaction, period-specific baseline and carryover as fixed effects. Subjects within sequences were modeled as random effects.80% CI: [-0.56, -0.36]
Comparison: Pre-breakfast; Time-matched change from baseline in pre-meal C-peptide on Day 14 was analyzed using a mixed effects model with sequence, period, treatment, the treatment by-time interaction, period-specific baseline and carryover as fixed effects. Subjects within sequences were modeled as random effects.80% CI: [-0.45, -0.03]
Comparison: Compared with Baseline (Pre-lunch)80% CI: [-0.08, 0.48]
Comparison: Compared with Baseline (Pre-lunch)80% CI: [0.38, 1.03]
Comparison: Compared with Baseline (Pre-lunch)80% CI: [-0.26, 0.37]
Comparison: Pre-lunch; Time-matched change from baseline in pre-meal C-peptide on Day 14 was analyzed using a mixed effects model with sequence, period, treatment, the treatment by-time interaction, period-specific baseline and carryover as fixed effects. Subjects within sequences were modeled as random effects.80% CI: [-0.28, 0.57]
Comparison: Pre-lunch; Time-matched change from baseline in pre-meal C-peptide on Day 14 was analyzed using a mixed effects model with sequence, period, treatment, the treatment by-time interaction, period-specific baseline and carryover as fixed effects. Subjects within sequences were modeled as random effects.80% CI: [0.19, 1.11]
Comparison: Compared with Baseline (Pre-dinner)80% CI: [0.03, 0.68]
Comparison: Compared with Baseline (Pre-dinner)80% CI: [-0.08, 0.67]
Comparison: Compared with Baseline (Pre-dinner)80% CI: [-0.05, 0.68]
Comparison: Pre-dinner; Time-matched change from baseline in pre-meal C-peptide on Day 14 was analyzed using a mixed effects model with sequence, period, treatment, the treatment by-time interaction, period-specific baseline and carryover as fixed effects. Subjects within sequences were modeled as random effects.80% CI: [-0.45, 0.53]
Comparison: Pre-dinner; Time-matched change from baseline in pre-meal C-peptide on Day 14 was analyzed using a mixed effects model with sequence, period, treatment, the treatment by-time interaction, period-specific baseline and carryover as fixed effects. Subjects within sequences were modeled as random effects.80% CI: [-0.55, 0.51]
Secondary
Change From Baseline in Pre-meal Insulin on Day 14
Blood samples for measurement of glucose to permit derivation of pre-meal collections of blood samples for insulin at 0, 5 and 11 hours on Day 0 (baseline) and Day 14.
Time frame: Day 14
Population: Full analysis set defined as all randomized subjects who had taken at least 1 dose of blinded study medication and who had both a baseline and a post-baseline WMDG assessment. Number of participants analyzed was the evaluable participants with a measurement on Day 14.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| PF-04937319 Split-Dose (150+100 mg) | Change From Baseline in Pre-meal Insulin on Day 14 | Pre-lunch (n=30,27,25) | 1.69 micro international unit/milliliter | Standard Error 1.69 |
| PF-04937319 Split-Dose (150+100 mg) | Change From Baseline in Pre-meal Insulin on Day 14 | Pre-breakfast (n=31,30,26) | 0.16 micro international unit/milliliter | Standard Error 0.704 |
| PF-04937319 Split-Dose (150+100 mg) | Change From Baseline in Pre-meal Insulin on Day 14 | Pre-dinner (n=30,28,24) | -0.70 micro international unit/milliliter | Standard Error 2.286 |
| PF-04937319 Once-Daily (300 mg) | Change From Baseline in Pre-meal Insulin on Day 14 | Pre-lunch (n=30,27,25) | 4.07 micro international unit/milliliter | Standard Error 1.939 |
| PF-04937319 Once-Daily (300 mg) | Change From Baseline in Pre-meal Insulin on Day 14 | Pre-breakfast (n=31,30,26) | 0.46 micro international unit/milliliter | Standard Error 0.81 |
| PF-04937319 Once-Daily (300 mg) | Change From Baseline in Pre-meal Insulin on Day 14 | Pre-dinner (n=30,28,24) | 5.06 micro international unit/milliliter | Standard Error 2.597 |
| Sitagliptin 100 mg | Change From Baseline in Pre-meal Insulin on Day 14 | Pre-breakfast (n=31,30,26) | 1.60 micro international unit/milliliter | Standard Error 0.793 |
| Sitagliptin 100 mg | Change From Baseline in Pre-meal Insulin on Day 14 | Pre-dinner (n=30,28,24) | 3.42 micro international unit/milliliter | Standard Error 2.714 |
| Sitagliptin 100 mg | Change From Baseline in Pre-meal Insulin on Day 14 | Pre-lunch (n=30,27,25) | -0.01 micro international unit/milliliter | Standard Error 1.864 |
Comparison: Compared with Baseline （Pre-breakfast）80% CI: [-0.75, 1.07]
Comparison: Compared with Baseline (Pre-breakfast)80% CI: [-0.58, 1.51]
Comparison: Compared with Baseline (Pre-breakfast)80% CI: [0.58, 2.63]
Comparison: Pre-breakfast; Time-matched change from baseline in pre-meal insulin on Day 14 was analyzed using a mixed effects model with sequence, period, treatment, the treatment by-time interaction, period-specific baseline and carryover as fixed effects. Subjects within sequences were modeled as random effects.80% CI: [-2.84, -0.05]
Comparison: Pre-breakfast; Time-matched change from baseline in pre-meal insulin on Day 14 was analyzed using a mixed effects model with sequence, period, treatment, the treatment by-time interaction, period-specific baseline and carryover as fixed effects. Subjects within sequences were modeled as random effects.80% CI: [-2.63, 0.35]
Comparison: Compared with Baseline (Pre-lunch)80% CI: [-0.5, 3.88]
Comparison: Compared with Baseline (Pre-lunch)80% CI: [1.56, 6.58]
Comparison: Compared with Baseline (Pre-lunch)80% CI: [-2.42, 2.4]
Comparison: Pre-lunch; Time-matched change from baseline in pre-meal insulin on Day 14 was analyzed using a mixed effects model with sequence, period, treatment, the treatment by-time interaction, period-specific baseline and carryover as fixed effects. Subjects within sequences were modeled as random effects.80% CI: [-1.62, 5.01]
Comparison: Pre-lunch; Time-matched change from baseline in pre-meal insulin on Day 14 was analyzed using a mixed effects model with sequence, period, treatment, the treatment by-time interaction, period-specific baseline and carryover as fixed effects. Subjects within sequences were modeled as random effects.80% CI: [0.54, 7.62]
Comparison: Compared with Baseline (Pre-dinner)80% CI: [-3.66, 2.27]
Comparison: Compared with Baseline (Pre-dinner)80% CI: [1.7, 8.43]
Comparison: Compared with Baseline (Pre-dinner)80% CI: [-0.1, 6.94]
Comparison: Pre-dinner; Time-matched change from baseline in pre-meal insulin on Day 14 was analyzed using a mixed effects model with sequence, period, treatment, the treatment by-time interaction, period-specific baseline and carryover as fixed effects. Subjects within sequences were modeled as random effects.80% CI: [-8.42, 0.18]
Comparison: Pre-dinner; Time-matched change from baseline in pre-meal insulin on Day 14 was analyzed using a mixed effects model with sequence, period, treatment, the treatment by-time interaction, period-specific baseline and carryover as fixed effects. Subjects within sequences were modeled as random effects.80% CI: [-2.6, 5.89]
Secondary
Frequency of Laboratory Test Abnormalities Reported in Any Treatment Group
The total number of participants with laboratory test abnormalities (without regard to baseline abnormality) was assessed.
Time frame: Day 1 up to Day 14
Population: The safety analysis set was all participants who received at least one dose of randomized study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PF-04937319 Split-Dose (150+100 mg) | Frequency of Laboratory Test Abnormalities Reported in Any Treatment Group | Total neutrophils (abs) (10^3/mm^3) <0.8 × LLN | 1 participants |
| PF-04937319 Split-Dose (150+100 mg) | Frequency of Laboratory Test Abnormalities Reported in Any Treatment Group | Eosinophils (abs) (10^3/mm^3) >1.2 × ULN | 0 participants |
| PF-04937319 Split-Dose (150+100 mg) | Frequency of Laboratory Test Abnormalities Reported in Any Treatment Group | Triglycerides (mg/dL) >1.3 × ULN | 2 participants |
| PF-04937319 Split-Dose (150+100 mg) | Frequency of Laboratory Test Abnormalities Reported in Any Treatment Group | Phosphate (mg/dL)<0.8 × LLN | 1 participants |
| PF-04937319 Split-Dose (150+100 mg) | Frequency of Laboratory Test Abnormalities Reported in Any Treatment Group | Glucose (mg/dL)>1.5 × ULN | 16 participants |
| PF-04937319 Split-Dose (150+100 mg) | Frequency of Laboratory Test Abnormalities Reported in Any Treatment Group | Creatine kinase (U/L) >2.0 × ULN | 1 participants |
| PF-04937319 Split-Dose (150+100 mg) | Frequency of Laboratory Test Abnormalities Reported in Any Treatment Group | Urine glucose (qual) ≥1 | 8 participants |
| PF-04937319 Split-Dose (150+100 mg) | Frequency of Laboratory Test Abnormalities Reported in Any Treatment Group | Urine nitrite ≥1 | 2 participants |
| PF-04937319 Split-Dose (150+100 mg) | Frequency of Laboratory Test Abnormalities Reported in Any Treatment Group | Urine leukocyte esterase ≥1 | 1 participants |
| PF-04937319 Split-Dose (150+100 mg) | Frequency of Laboratory Test Abnormalities Reported in Any Treatment Group | Urine WBC (/HPF) ≥20 | 1 participants |
| PF-04937319 Once-Daily (300 mg) | Frequency of Laboratory Test Abnormalities Reported in Any Treatment Group | Urine leukocyte esterase ≥1 | 1 participants |
| PF-04937319 Once-Daily (300 mg) | Frequency of Laboratory Test Abnormalities Reported in Any Treatment Group | Total neutrophils (abs) (10^3/mm^3) <0.8 × LLN | 0 participants |
| PF-04937319 Once-Daily (300 mg) | Frequency of Laboratory Test Abnormalities Reported in Any Treatment Group | Creatine kinase (U/L) >2.0 × ULN | 1 participants |
| PF-04937319 Once-Daily (300 mg) | Frequency of Laboratory Test Abnormalities Reported in Any Treatment Group | Glucose (mg/dL)>1.5 × ULN | 12 participants |
| PF-04937319 Once-Daily (300 mg) | Frequency of Laboratory Test Abnormalities Reported in Any Treatment Group | Eosinophils (abs) (10^3/mm^3) >1.2 × ULN | 0 participants |
| PF-04937319 Once-Daily (300 mg) | Frequency of Laboratory Test Abnormalities Reported in Any Treatment Group | Urine WBC (/HPF) ≥20 | 1 participants |
| PF-04937319 Once-Daily (300 mg) | Frequency of Laboratory Test Abnormalities Reported in Any Treatment Group | Urine nitrite ≥1 | 3 participants |
| PF-04937319 Once-Daily (300 mg) | Frequency of Laboratory Test Abnormalities Reported in Any Treatment Group | Triglycerides (mg/dL) >1.3 × ULN | 0 participants |
| PF-04937319 Once-Daily (300 mg) | Frequency of Laboratory Test Abnormalities Reported in Any Treatment Group | Urine glucose (qual) ≥1 | 4 participants |
| PF-04937319 Once-Daily (300 mg) | Frequency of Laboratory Test Abnormalities Reported in Any Treatment Group | Phosphate (mg/dL)<0.8 × LLN | 0 participants |
| Sitagliptin 100 mg | Frequency of Laboratory Test Abnormalities Reported in Any Treatment Group | Urine nitrite ≥1 | 1 participants |
| Sitagliptin 100 mg | Frequency of Laboratory Test Abnormalities Reported in Any Treatment Group | Phosphate (mg/dL)<0.8 × LLN | 0 participants |
| Sitagliptin 100 mg | Frequency of Laboratory Test Abnormalities Reported in Any Treatment Group | Glucose (mg/dL)>1.5 × ULN | 14 participants |
| Sitagliptin 100 mg | Frequency of Laboratory Test Abnormalities Reported in Any Treatment Group | Creatine kinase (U/L) >2.0 × ULN | 0 participants |
| Sitagliptin 100 mg | Frequency of Laboratory Test Abnormalities Reported in Any Treatment Group | Urine leukocyte esterase ≥1 | 2 participants |
| Sitagliptin 100 mg | Frequency of Laboratory Test Abnormalities Reported in Any Treatment Group | Urine glucose (qual) ≥1 | 5 participants |
| Sitagliptin 100 mg | Frequency of Laboratory Test Abnormalities Reported in Any Treatment Group | Total neutrophils (abs) (10^3/mm^3) <0.8 × LLN | 0 participants |
| Sitagliptin 100 mg | Frequency of Laboratory Test Abnormalities Reported in Any Treatment Group | Urine WBC (/HPF) ≥20 | 1 participants |
| Sitagliptin 100 mg | Frequency of Laboratory Test Abnormalities Reported in Any Treatment Group | Eosinophils (abs) (10^3/mm^3) >1.2 × ULN | 1 participants |
| Sitagliptin 100 mg | Frequency of Laboratory Test Abnormalities Reported in Any Treatment Group | Triglycerides (mg/dL) >1.3 × ULN | 2 participants |
Secondary
Incidence of All Causality Treatment-Emergent Adverse Event by Preferred Term (Frequency Rate >5%)
Time frame: Day 1 up to Day 14
Population: The safety analysis set was all participants who received at least one dose of randomized study treatment. HAEs meeting protocol definition were summarized descriptively by treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PF-04937319 Split-Dose (150+100 mg) | Incidence of All Causality Treatment-Emergent Adverse Event by Preferred Term (Frequency Rate >5%) | Participants with Musculoskeletal pain | 0 participants |
| PF-04937319 Split-Dose (150+100 mg) | Incidence of All Causality Treatment-Emergent Adverse Event by Preferred Term (Frequency Rate >5%) | Participants with Diarrhoea | 1 participants |
| PF-04937319 Split-Dose (150+100 mg) | Incidence of All Causality Treatment-Emergent Adverse Event by Preferred Term (Frequency Rate >5%) | Participants with Cough | 0 participants |
| PF-04937319 Split-Dose (150+100 mg) | Incidence of All Causality Treatment-Emergent Adverse Event by Preferred Term (Frequency Rate >5%) | Participants with Headache | 0 participants |
| PF-04937319 Split-Dose (150+100 mg) | Incidence of All Causality Treatment-Emergent Adverse Event by Preferred Term (Frequency Rate >5%) | Participants with hypoglycaemia | 2 participants |
| PF-04937319 Split-Dose (150+100 mg) | Incidence of All Causality Treatment-Emergent Adverse Event by Preferred Term (Frequency Rate >5%) | Participants with AEs having a frequency rate >5% | 3 participants |
| PF-04937319 Split-Dose (150+100 mg) | Incidence of All Causality Treatment-Emergent Adverse Event by Preferred Term (Frequency Rate >5%) | Participants with Pain in extremity | 0 participants |
| PF-04937319 Split-Dose (150+100 mg) | Incidence of All Causality Treatment-Emergent Adverse Event by Preferred Term (Frequency Rate >5%) | Participants with Back pain | 0 participants |
| PF-04937319 Split-Dose (150+100 mg) | Incidence of All Causality Treatment-Emergent Adverse Event by Preferred Term (Frequency Rate >5%) | Participants evaluable for AEs | 43 participants |
| PF-04937319 Once-Daily (300 mg) | Incidence of All Causality Treatment-Emergent Adverse Event by Preferred Term (Frequency Rate >5%) | Participants with Back pain | 2 participants |
| PF-04937319 Once-Daily (300 mg) | Incidence of All Causality Treatment-Emergent Adverse Event by Preferred Term (Frequency Rate >5%) | Participants with Musculoskeletal pain | 1 participants |
| PF-04937319 Once-Daily (300 mg) | Incidence of All Causality Treatment-Emergent Adverse Event by Preferred Term (Frequency Rate >5%) | Participants with Diarrhoea | 0 participants |
| PF-04937319 Once-Daily (300 mg) | Incidence of All Causality Treatment-Emergent Adverse Event by Preferred Term (Frequency Rate >5%) | Participants with AEs having a frequency rate >5% | 16 participants |
| PF-04937319 Once-Daily (300 mg) | Incidence of All Causality Treatment-Emergent Adverse Event by Preferred Term (Frequency Rate >5%) | Participants evaluable for AEs | 31 participants |
| PF-04937319 Once-Daily (300 mg) | Incidence of All Causality Treatment-Emergent Adverse Event by Preferred Term (Frequency Rate >5%) | Participants with hypoglycaemia | 11 participants |
| PF-04937319 Once-Daily (300 mg) | Incidence of All Causality Treatment-Emergent Adverse Event by Preferred Term (Frequency Rate >5%) | Participants with Cough | 1 participants |
| PF-04937319 Once-Daily (300 mg) | Incidence of All Causality Treatment-Emergent Adverse Event by Preferred Term (Frequency Rate >5%) | Participants with Pain in extremity | 1 participants |
| PF-04937319 Once-Daily (300 mg) | Incidence of All Causality Treatment-Emergent Adverse Event by Preferred Term (Frequency Rate >5%) | Participants with Headache | 4 participants |
| Sitagliptin 100 mg | Incidence of All Causality Treatment-Emergent Adverse Event by Preferred Term (Frequency Rate >5%) | Participants with Back pain | 1 participants |
| Sitagliptin 100 mg | Incidence of All Causality Treatment-Emergent Adverse Event by Preferred Term (Frequency Rate >5%) | Participants evaluable for AEs | 30 participants |
| Sitagliptin 100 mg | Incidence of All Causality Treatment-Emergent Adverse Event by Preferred Term (Frequency Rate >5%) | Participants with AEs having a frequency rate >5% | 19 participants |
| Sitagliptin 100 mg | Incidence of All Causality Treatment-Emergent Adverse Event by Preferred Term (Frequency Rate >5%) | Participants with hypoglycaemia | 14 participants |
| Sitagliptin 100 mg | Incidence of All Causality Treatment-Emergent Adverse Event by Preferred Term (Frequency Rate >5%) | Participants with Headache | 4 participants |
| Sitagliptin 100 mg | Incidence of All Causality Treatment-Emergent Adverse Event by Preferred Term (Frequency Rate >5%) | Participants with Diarrhoea | 2 participants |
| Sitagliptin 100 mg | Incidence of All Causality Treatment-Emergent Adverse Event by Preferred Term (Frequency Rate >5%) | Participants with Musculoskeletal pain | 2 participants |
| Sitagliptin 100 mg | Incidence of All Causality Treatment-Emergent Adverse Event by Preferred Term (Frequency Rate >5%) | Participants with Pain in extremity | 2 participants |
| Sitagliptin 100 mg | Incidence of All Causality Treatment-Emergent Adverse Event by Preferred Term (Frequency Rate >5%) | Participants with Cough | 0 participants |
| Sitagliptin 100 mg | Incidence of All Causality Treatment-Emergent Adverse Event by Preferred Term (Frequency Rate >5%) | Participants with Musculoskeletal pain | 1 participants |
| Sitagliptin 100 mg | Incidence of All Causality Treatment-Emergent Adverse Event by Preferred Term (Frequency Rate >5%) | Participants with Headache | 4 participants |
| Sitagliptin 100 mg | Incidence of All Causality Treatment-Emergent Adverse Event by Preferred Term (Frequency Rate >5%) | Participants with hypoglycaemia | 4 participants |
| Sitagliptin 100 mg | Incidence of All Causality Treatment-Emergent Adverse Event by Preferred Term (Frequency Rate >5%) | Participants with Cough | 2 participants |
| Sitagliptin 100 mg | Incidence of All Causality Treatment-Emergent Adverse Event by Preferred Term (Frequency Rate >5%) | Participants with Pain in extremity | 1 participants |
| Sitagliptin 100 mg | Incidence of All Causality Treatment-Emergent Adverse Event by Preferred Term (Frequency Rate >5%) | Participants with AEs having a frequency rate >5% | 12 participants |
| Sitagliptin 100 mg | Incidence of All Causality Treatment-Emergent Adverse Event by Preferred Term (Frequency Rate >5%) | Participants with Diarrhoea | 2 participants |
| Sitagliptin 100 mg | Incidence of All Causality Treatment-Emergent Adverse Event by Preferred Term (Frequency Rate >5%) | Participants with Back pain | 2 participants |
| Sitagliptin 100 mg | Incidence of All Causality Treatment-Emergent Adverse Event by Preferred Term (Frequency Rate >5%) | Participants evaluable for AEs | 30 participants |
Secondary
Number of Participants With Post-baseline Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern
ECG criteria of potential clinical concern were 1), PR interval: \>=300 milliseconds (msec); \>=25% increase when baseline \>200 msec; or increase \>=50% when baseline \<=200 msec; 2), QRS interval: \>=140 msec; \>=50% increase from baseline; 3), QTc interval using Fridericia's formula (QTcF interval): absolute value \>=450 - \<480 msec, \>=480-\<500 msec, \>500 msec; absolute change 30 - \<60, \>=60 msec.
Time frame: Day 1 up to Day 14
Population: The safety analysis set was all participants who received at least one dose of randomized study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PF-04937319 Split-Dose (150+100 mg) | Number of Participants With Post-baseline Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern | QTcF interval 480-500 msec, n=31,30,29 | 0 participants |
| PF-04937319 Split-Dose (150+100 mg) | Number of Participants With Post-baseline Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern | QTcF increase >=60 msec, n=31,30,29 | 0 participants |
| PF-04937319 Split-Dose (150+100 mg) | Number of Participants With Post-baseline Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern | PR interval increase >=25%/50%, n=31,30,29 | 0 participants |
| PF-04937319 Split-Dose (150+100 mg) | Number of Participants With Post-baseline Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern | QTcF interval >=500 msec, n=31,30,29 | 0 participants |
| PF-04937319 Split-Dose (150+100 mg) | Number of Participants With Post-baseline Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern | PR interval >=300 msec, n=31,30,29 | 0 participants |
| PF-04937319 Split-Dose (150+100 mg) | Number of Participants With Post-baseline Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern | QTcF increase 30-60 msec, n=31,30,29 | 0 participants |
| PF-04937319 Split-Dose (150+100 mg) | Number of Participants With Post-baseline Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern | QTcF interval 450-480 msec, n=31,30,29 | 2 participants |
| PF-04937319 Split-Dose (150+100 mg) | Number of Participants With Post-baseline Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern | QRS interval >=140 msec, n=31,30,29 | 0 participants |
| PF-04937319 Split-Dose (150+100 mg) | Number of Participants With Post-baseline Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern | QRS interval increase >=50%, n=31,30,29 | 0 participants |
| PF-04937319 Once-Daily (300 mg) | Number of Participants With Post-baseline Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern | QTcF interval >=500 msec, n=31,30,29 | 0 participants |
| PF-04937319 Once-Daily (300 mg) | Number of Participants With Post-baseline Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern | PR interval >=300 msec, n=31,30,29 | 0 participants |
| PF-04937319 Once-Daily (300 mg) | Number of Participants With Post-baseline Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern | QRS interval >=140 msec, n=31,30,29 | 0 participants |
| PF-04937319 Once-Daily (300 mg) | Number of Participants With Post-baseline Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern | QTcF interval 450-480 msec, n=31,30,29 | 1 participants |
| PF-04937319 Once-Daily (300 mg) | Number of Participants With Post-baseline Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern | QTcF interval 480-500 msec, n=31,30,29 | 0 participants |
| PF-04937319 Once-Daily (300 mg) | Number of Participants With Post-baseline Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern | PR interval increase >=25%/50%, n=31,30,29 | 0 participants |
| PF-04937319 Once-Daily (300 mg) | Number of Participants With Post-baseline Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern | QRS interval increase >=50%, n=31,30,29 | 0 participants |
| PF-04937319 Once-Daily (300 mg) | Number of Participants With Post-baseline Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern | QTcF increase 30-60 msec, n=31,30,29 | 0 participants |
| PF-04937319 Once-Daily (300 mg) | Number of Participants With Post-baseline Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern | QTcF increase >=60 msec, n=31,30,29 | 0 participants |
| Sitagliptin 100 mg | Number of Participants With Post-baseline Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern | QTcF interval 450-480 msec, n=31,30,29 | 1 participants |
| Sitagliptin 100 mg | Number of Participants With Post-baseline Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern | PR interval >=300 msec, n=31,30,29 | 0 participants |
| Sitagliptin 100 mg | Number of Participants With Post-baseline Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern | QRS interval increase >=50%, n=31,30,29 | 0 participants |
| Sitagliptin 100 mg | Number of Participants With Post-baseline Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern | QRS interval >=140 msec, n=31,30,29 | 0 participants |
| Sitagliptin 100 mg | Number of Participants With Post-baseline Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern | QTcF increase >=60 msec, n=31,30,29 | 0 participants |
| Sitagliptin 100 mg | Number of Participants With Post-baseline Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern | QTcF interval >=500 msec, n=31,30,29 | 0 participants |
| Sitagliptin 100 mg | Number of Participants With Post-baseline Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern | QTcF interval 480-500 msec, n=31,30,29 | 0 participants |
| Sitagliptin 100 mg | Number of Participants With Post-baseline Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern | QTcF increase 30-60 msec, n=31,30,29 | 0 participants |
| Sitagliptin 100 mg | Number of Participants With Post-baseline Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern | PR interval increase >=25%/50%, n=31,30,29 | 0 participants |
Secondary
Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern
Vital signs included blood pressure (BP; supine, sitting and standing) and pulse rate. Vital signs criteria of potential clinical concern were 1), BP: sitting systolic BP (SBP) greater than or equal to (\>=) 30 millimeters of mercury (mm Hg) change from baseline, sitting SBP =\<20 mmHg change from baseline, supine/sitting/standing SBP less than (\<) 90 mm Hg; sitting diastolic BP (DBP) \>=20 mm Hg change from baseline, sitting SBP =\<20 mmHg change from baseline, supine/sitting/standing DBP \<50 mm Hg; 2), pulse rate (supine): \<40 or greater than (\>) 120 beats per minute (bpm).
Time frame: Day 1 up to Day 14
Population: The safety analysis set was all participants who received at least one dose of randomized study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PF-04937319 Split-Dose (150+100 mg) | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern | Sitting SBP <90 mm Hg | 0 participants |
| PF-04937319 Split-Dose (150+100 mg) | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern | Sitting DBP <50 mm Hg | 0 participants |
| PF-04937319 Split-Dose (150+100 mg) | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern | Sitting Pulse Rate <40 bpm | 0 participants |
| PF-04937319 Split-Dose (150+100 mg) | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern | Sitting Pulse Rate >120 bpm | 0 participants |
| PF-04937319 Split-Dose (150+100 mg) | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern | Increase:sitting SBP≥30 mm Hg | 1 participants |
| PF-04937319 Split-Dose (150+100 mg) | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern | Increase:sitting DBP≥20 mm Hg | 0 participants |
| PF-04937319 Split-Dose (150+100 mg) | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern | Decrease:sitting SBP≥30 mm Hg | 2 participants |
| PF-04937319 Split-Dose (150+100 mg) | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern | Decrease:sitting DBP≥30 mm Hg | 0 participants |
| PF-04937319 Once-Daily (300 mg) | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern | Sitting Pulse Rate <40 bpm | 0 participants |
| PF-04937319 Once-Daily (300 mg) | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern | Decrease:sitting SBP≥30 mm Hg | 2 participants |
| PF-04937319 Once-Daily (300 mg) | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern | Sitting Pulse Rate >120 bpm | 0 participants |
| PF-04937319 Once-Daily (300 mg) | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern | Increase:sitting SBP≥30 mm Hg | 1 participants |
| PF-04937319 Once-Daily (300 mg) | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern | Increase:sitting DBP≥20 mm Hg | 1 participants |
| PF-04937319 Once-Daily (300 mg) | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern | Sitting SBP <90 mm Hg | 0 participants |
| PF-04937319 Once-Daily (300 mg) | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern | Sitting DBP <50 mm Hg | 0 participants |
| PF-04937319 Once-Daily (300 mg) | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern | Decrease:sitting DBP≥30 mm Hg | 0 participants |
| Sitagliptin 100 mg | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern | Sitting Pulse Rate <40 bpm | 0 participants |
| Sitagliptin 100 mg | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern | Sitting DBP <50 mm Hg | 1 participants |
| Sitagliptin 100 mg | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern | Sitting SBP <90 mm Hg | 0 participants |
| Sitagliptin 100 mg | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern | Sitting Pulse Rate >120 bpm | 0 participants |
| Sitagliptin 100 mg | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern | Decrease:sitting SBP≥30 mm Hg | 2 participants |
| Sitagliptin 100 mg | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern | Increase:sitting DBP≥20 mm Hg | 0 participants |
| Sitagliptin 100 mg | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern | Increase:sitting SBP≥30 mm Hg | 2 participants |
| Sitagliptin 100 mg | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern | Decrease:sitting DBP≥30 mm Hg | 2 participants |
Secondary
Plasma PF-04937319 Apparent Clearance (CL/F) on Day 14
The PK parameters were summarized descriptively by treatment as appropriate. Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population PK modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Time frame: Predose, 1.5, 3, 5, 6.5, 8, 11, 12.5, and 14 hours on Days 0 and 14; and predose on Days 7 and 15.
Population: The PK population was defined as all randomized participants who received at least 1 dose of PF 04937319 and who had at least 1 PK sample with reported concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-04937319 Split-Dose (150+100 mg) | Plasma PF-04937319 Apparent Clearance (CL/F) on Day 14 | 389.2 mL/min | Geometric Coefficient of Variation 43 |
| PF-04937319 Once-Daily (300 mg) | Plasma PF-04937319 Apparent Clearance (CL/F) on Day 14 | 423.3 mL/min | Geometric Coefficient of Variation 47 |
Secondary
Plasma PF-04937319 Area Under the Concentration Time Curve From Time 0 to 24 Hours (AUC24) of PF-04937319 at Day 14
The PK parameters were summarized descriptively by treatment as appropriate. Two (2) PK parameters specified in the protocol and SAP were not reported: AUClast was not reported since it was the same as AUC24 in this study, and apparent volume of distribution (Vz/F) was not reported since the log-linear terminal phase of the concentration-time profiles was not consistently well characterized in the 24-hour sampling period.
Time frame: Predose, 1.5, 3, 5, 6.5, 8, 11, 12.5, and 14 hours on Days 0 and 14; and predose on Days 7 and 15.
Population: The PK population was defined as all randomized participants who received at least 1 dose of PF 04937319 and who had at least 1 PK sample with reported concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-04937319 Split-Dose (150+100 mg) | Plasma PF-04937319 Area Under the Concentration Time Curve From Time 0 to 24 Hours (AUC24) of PF-04937319 at Day 14 | 10710 ng•hr/mL | Geometric Coefficient of Variation 43 |
| PF-04937319 Once-Daily (300 mg) | Plasma PF-04937319 Area Under the Concentration Time Curve From Time 0 to 24 Hours (AUC24) of PF-04937319 at Day 14 | 11810 ng•hr/mL | Geometric Coefficient of Variation 47 |
Secondary
Plasma PF-04937319 Average Concentration Over the 24-hour Period (Cav) on Day 14
Cav was average concentration over the 24-hour period. The PK parameters were summarized descriptively by treatment as appropriate.
Time frame: Predose, 1.5, 3, 5, 6.5, 8, 11, 12.5, and 14 hours on Days 0 and 14; and predose on Days 7 and 15.
Population: The PK population was defined as all randomized participants who received at least 1 dose of PF 04937319 and who had at least 1 PK sample with reported concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-04937319 Split-Dose (150+100 mg) | Plasma PF-04937319 Average Concentration Over the 24-hour Period (Cav) on Day 14 | 446.1 ng/mL | Geometric Coefficient of Variation 43 |
| PF-04937319 Once-Daily (300 mg) | Plasma PF-04937319 Average Concentration Over the 24-hour Period (Cav) on Day 14 | 492.0 ng/mL | Geometric Coefficient of Variation 47 |
Secondary
Plasma PF-04937319 Highest Observed Concentration (Cmax) on Day 14
Cmax was highest observed concentration. The PK parameters were summarized descriptively by treatment as appropriate.
Time frame: Predose, 1.5, 3, 5, 6.5, 8, 11, 12.5, and 14 hours on Days 0 and 14; and predose on Days 7 and 15.
Population: The PK population was defined as all randomized participants who received at least 1 dose of PF 04937319 and who had at least 1 PK sample with reported concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-04937319 Split-Dose (150+100 mg) | Plasma PF-04937319 Highest Observed Concentration (Cmax) on Day 14 | 776.6 ng/mL | Geometric Coefficient of Variation 39 |
| PF-04937319 Once-Daily (300 mg) | Plasma PF-04937319 Highest Observed Concentration (Cmax) on Day 14 | 980.5 ng/mL | Geometric Coefficient of Variation 38 |
Secondary
Plasma PF-04937319 Lowest Observed Concentration During the 24-hour Period (Cmin) on Day 14
Cmin lowest observed concentration during the 24-hour period. The PK parameters were summarized descriptively by treatment as appropriate.
Time frame: Predose, 1.5, 3, 5, 6.5, 8, 11, 12.5, and 14 hours on Days 0 and 14; and predose on Days 7 and 15.
Population: The PK population was defined as all randomized participants who received at least 1 dose of PF 04937319 and who had at least 1 PK sample with reported concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-04937319 Split-Dose (150+100 mg) | Plasma PF-04937319 Lowest Observed Concentration During the 24-hour Period (Cmin) on Day 14 | 101.9 ng/mL | Geometric Coefficient of Variation 602 |
| PF-04937319 Once-Daily (300 mg) | Plasma PF-04937319 Lowest Observed Concentration During the 24-hour Period (Cmin) on Day 14 | 131.0 ng/mL | Geometric Coefficient of Variation 265 |
Secondary
Plasma PF-04937319 Time for Cmax (Tmax) on Day 14
Tmax was time of maximum concentration. The PK parameters were summarized descriptively by treatment as appropriate.
Time frame: Predose, 1.5, 3, 5, 6.5, 8, 11, 12.5, and 14 hours on Days 0 and 14; and predose on Days 7 and 15.
Population: The PK population was defined as all randomized participants who received at least 1 dose of PF 04937319 and who had at least 1 PK sample with reported concentration.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| PF-04937319 Split-Dose (150+100 mg) | Plasma PF-04937319 Time for Cmax (Tmax) on Day 14 | 6.50 hour | Full Range 602 |
| PF-04937319 Once-Daily (300 mg) | Plasma PF-04937319 Time for Cmax (Tmax) on Day 14 | 5.00 hour | Full Range 265 |