| Primary | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUCinf] | AUCinf is the area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time. | The pharmacokinetic (PK) parameter analysis population included all randomized participants who received at least 1 dose of PF-04937319 and who had at least 1 of the PK parameters of interest measured and available in at least 1 period; number of participants analyzed (N) is number of evaluable participants for this outcome measure. | Posted | | Geometric Mean | Geometric Coefficient of Variation | nanogram*hour/milliliter (ng*hr/mL) | | 0 (pre-dose) and 1, 2, 3, 4, 5, 6, 7, 8, 11, 12.5, 14, 16, 20, 24, 36, 48, and 72 hours post-dose | | | | ID | Title | Description |
|---|
| OG000 | PF-04937319 150+100 mg IR | Participants received immediate-release material sparing tablet (IR MST) administered orally at 150 mg with morning meal and 100 mg with lunch. There was a 5 to 10-day washout between dosing across the 4 regimens. | | OG001 | PF-04937319 250 mg MR1 | Participants received modified-release formulation #1 administered orally at 250 mg tablet with morning meal. There was a 5 to 10-day washout between dosing across the 4 regimens. | | OG002 | PF-04937319 300 mg MR2 | Participants received modified-release formulation#2 administered orally at 300 mg with morning meal. There was a 5 to 10-day washout between dosing across the 4 regimens. | | OG003 | PF-04937319 330 mg MR3 | Participants received modified-release formulation#3 administered orally at 330 mg with morning meal. There was a 5 to 10-day washout between dosing across the 4 regimens. |
| | Units | Counts |
|---|
| Participants | - OG00038
- OG00131
- OG00237
- OG003
|
| | Title | Denominators | Categories |
|---|
| | | Title | Measurements |
|---|
| - OG00010690± 26
- OG0013187± 59
- OG0022725± 35
- OG003
|
|
| | Group IDs | Group Description | Statistical Method | Statistical Comment | P-Value | P-Value Comment | Parameter Type | Parameter Value | Dispersion Type | Dispersion Value | Confidence Interval Sides | Confidence Interval % | CI Lower Limit | CI Upper Limit | CI Lower Limit Comment | CI Upper Limit Comment | Estimate Comment | Tested Non-Inferiority | Non-Inferiority Type | Non-Inferiority Comment | Other Analysis Description |
|---|
| | | | | | Adjusted Geometric Mean Ratio MR1/IR | 31.27 | | | 2-Sided | 90 | 28.09 | 34.80 | | | | No | Superiority or Other | | | | | | | | |
|
| Primary | Change From Reference in Weighted-Mean-Daily-Glucose (WMDG) on Day 1 | MWG was calculated as the area under the curve (AUC) for the full 24 hours expressed. | The pharmacodynamic analysis included participants who had taken at least 1 dose of PF-04937319 and who had WMDG assessment for at least 1 modified-release formulation and the Reference (IR MST) formulation; n=number of participants evaluated in respective arms for category. | Posted | | Mean | Standard Deviation | milligrams per deciliter (mg/dL) | | 0 (pre-dose) and 1, 2, 3, 4, 5, 6, 7, 8, 11, 12.5, 14, 16, 20, and 24 hours post-dose | | | | ID | Title | Description |
|---|
| OG000 | PF-04937319 150+100 mg IR | Participants received immediate-release material sparing tablet (IR MST) administered orally at 150 mg with morning meal and 100 mg with lunch. There was a 5 to 10-day washout between dosing across the 4 regimens. | | OG001 | PF-04937319 250 mg MR1 | Participants received modified-release formulation #1 administered orally at 250 mg tablet with morning meal. There was a 5 to 10-day washout between dosing across the 4 regimens. | | OG002 | PF-04937319 300 mg MR2 | Participants received modified-release formulation#2 administered orally at 300 mg with morning meal. There was a 5 to 10-day washout between dosing across the 4 regimens. |
|
| Secondary | Maximum Observed PF-04937319 Plasma Concentration (Cmax) | | The PK parameter analysis population included all randomized participants who received at least 1 dose of PF-04937319 and who had at least 1 of the PK parameters of interest measured and available in at least 1 period. | Posted | | Geometric Mean | Geometric Coefficient of Variation | ng/mL | | 0 (pre-dose) and 1, 2, 3, 4, 5, 6, 7, 8, 11, 12.5, 14, 16, 20, 24, 36, 48, and 72 hours post-dose | | | | ID | Title | Description |
|---|
| OG000 | PF-04937319 150+100 mg IR | Participants received immediate-release material sparing tablet (IR MST) administered orally at 150 mg with morning meal and 100 mg with lunch. There was a 5 to 10-day washout between dosing across the 4 regimens. | | OG001 | PF-04937319 250 mg MR1 | Participants received modified-release formulation #1 administered orally at 250 mg tablet with morning meal. There was a 5 to 10-day washout between dosing across the 4 regimens. | | OG002 | PF-04937319 300 mg MR2 | Participants received modified-release formulation#2 administered orally at 300 mg with morning meal. There was a 5 to 10-day washout between dosing across the 4 regimens. | | OG003 |
|
| Secondary | PF-04937319 Plasma Concentration at 5 Hours After Morning Dose (C5) | | The PK parameter analysis population included all randomized participants who received at least 1 dose of PF-04937319 and who had at least 1 of the PK parameters of interest measured and available in at least 1 period. | Posted | | Geometric Mean | Geometric Coefficient of Variation | ng/mL | | 0 (pre-dose) and 1, 2, 3, 4, 5, 6, 7, 8, 11, 12.5, 14, 16, 20, 24, 36, 48, and 72 hours post-dose | | | | ID | Title | Description |
|---|
| OG000 | PF-04937319 150+100 mg IR | Participants received immediate-release material sparing tablet (IR MST) administered orally at 150 mg with morning meal and 100 mg with lunch. There was a 5 to 10-day washout between dosing across the 4 regimens. | | OG001 | PF-04937319 250 mg MR1 | Participants received modified-release formulation #1 administered orally at 250 mg tablet with morning meal. There was a 5 to 10-day washout between dosing across the 4 regimens. | | OG002 | PF-04937319 300 mg MR2 | Participants received modified-release formulation#2 administered orally at 300 mg with morning meal. There was a 5 to 10-day washout between dosing across the 4 regimens. | | OG003 |
|
| Secondary | PF-04937319 Plasma Concentration at 16 Hours After Morning Dose (C16) | | The PK parameter analysis population included all randomized participants who received at least 1 dose of PF-04937319 and who had at least 1 of the PK parameters of interest measured and available in at least 1 period. | Posted | | Geometric Mean | Geometric Coefficient of Variation | ng/mL | | 0 (pre-dose) and 1, 2, 3, 4, 5, 6, 7, 8, 11, 12.5, 14, 16, 20, 24, 36, 48, and 72 hours post-dose | | | | ID | Title | Description |
|---|
| OG000 | PF-04937319 150+100 mg IR | Participants received immediate-release material sparing tablet (IR MST) administered orally at 150 mg with morning meal and 100 mg with lunch. There was a 5 to 10-day washout between dosing across the 4 regimens. | | OG001 | PF-04937319 250 mg MR1 | Participants received modified-release formulation #1 administered orally at 250 mg tablet with morning meal. There was a 5 to 10-day washout between dosing across the 4 regimens. | | OG002 | PF-04937319 300 mg MR2 | Participants received modified-release formulation#2 administered orally at 300 mg with morning meal. There was a 5 to 10-day washout between dosing across the 4 regimens. | | OG003 |
|
| Secondary | PF-04937319 Plasma Concentration at 24 Hours After Morning Dose (C24) | | The PK parameter analysis population included all randomized participants who received at least 1 dose of PF-04937319 and who had at least 1 of the PK parameters of interest measured and available in at least 1 period. | Posted | | Geometric Mean | Geometric Coefficient of Variation | ng/dL | | 0 (pre-dose) and 1, 2, 3, 4, 5, 6, 7, 8, 11, 12.5, 14, 16, 20, 24, 36, 48, and 72 hours post-dose | | | | ID | Title | Description |
|---|
| OG000 | PF-04937319 150+100 mg IR | Participants received immediate-release material sparing tablet (IR MST) administered orally at 150 mg with morning meal and 100 mg with lunch. There was a 5 to 10-day washout between dosing across the 4 regimens. | | OG001 | PF-04937319 250 mg MR1 | Participants received modified-release formulation #1 administered orally at 250 mg tablet with morning meal. There was a 5 to 10-day washout between dosing across the 4 regimens. | | OG002 | PF-04937319 300 mg MR2 | Participants received modified-release formulation#2 administered orally at 300 mg with morning meal. There was a 5 to 10-day washout between dosing across the 4 regimens. | | OG003 |
|
| Secondary | Ratio of Maximum to Approximate Trough PF-04937319 Concentration (Cmax/C24) | Cmax/C24 is the ratio of maximum to approximate trough concentration, where Cmax is the overall maximum observed plasma concentration and C24 is the plasma concentration at 24 hours after the morning dose. | The PK parameter analysis population included all randomized participants who received at least 1 dose of PF-04937319 and who had at least 1 of the PK parameters of interest measured and available in at least 1 period. | Posted | | Geometric Mean | Geometric Coefficient of Variation | ratio | | 0 (pre-dose) and 1, 2, 3, 4, 5, 6, 7, 8, 11, 12.5, 14, 16, 20, 24, 36, 48, and 72 hours post-dose | | | | ID | Title | Description |
|---|
| OG000 | PF-04937319 150+100 mg IR | Participants received immediate-release material sparing tablet (IR MST) administered orally at 150 mg with morning meal and 100 mg with lunch. There was a 5 to 10-day washout between dosing across the 4 regimens. | | OG001 | PF-04937319 250 mg MR1 | Participants received modified-release formulation #1 administered orally at 250 mg tablet with morning meal. There was a 5 to 10-day washout between dosing across the 4 regimens. | | OG002 | PF-04937319 300 mg MR2 | Participants received modified-release formulation#2 administered orally at 300 mg with morning meal. There was a 5 to 10-day washout between dosing across the 4 regimens. |
|
| Secondary | Time to Reach Maximum Observed PF-04937319 Plasma Concentration (Tmax) | | The PK parameter analysis population included all randomized participants who received at least 1 dose of PF-04937319 and who had at least 1 of the PK parameters of interest measured and available in at least 1 period. | Posted | | Median | Full Range | hours | | 0 (pre-dose) and 1, 2, 3, 4, 5, 6, 7, 8, 11, 12.5, 14, 16, 20, 24, 36, 48, and 72 hours post-dose | | | | ID | Title | Description |
|---|
| OG000 | PF-04937319 150+100 mg IR | Participants received immediate-release material sparing tablet (IR MST) administered orally at 150 mg with morning meal and 100 mg with lunch. There was a 5 to 10-day washout between dosing across the 4 regimens. | | OG001 | PF-04937319 250 mg MR1 | Participants received modified-release formulation #1 administered orally at 250 mg tablet with morning meal. There was a 5 to 10-day washout between dosing across the 4 regimens. | | OG002 | PF-04937319 300 mg MR2 | Participants received modified-release formulation#2 administered orally at 300 mg with morning meal. There was a 5 to 10-day washout between dosing across the 4 regimens. | | OG003 |
|
| Secondary | Area Under the Curve From Time Zero to Last Quantifiable PF-04937319 Concentration (AUClast) | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) | The PK parameter analysis population included all randomized participants who received at least 1 dose of PF-04937319 and who had at least 1 of the PK parameters of interest measured and available in at least 1 period. | Posted | | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | | 0 (pre-dose) and 1, 2, 3, 4, 5, 6, 7, 8, 11, 12.5, 14, 16, 20, 24, 36, 48, and 72 hours post-dose | | | | ID | Title | Description |
|---|
| OG000 | PF-04937319 150+100 mg IR | Participants received immediate-release material sparing tablet (IR MST) administered orally at 150 mg with morning meal and 100 mg with lunch. There was a 5 to 10-day washout between dosing across the 4 regimens. | | OG001 | PF-04937319 250 mg MR1 | Participants received modified-release formulation #1 administered orally at 250 mg tablet with morning meal. There was a 5 to 10-day washout between dosing across the 4 regimens. | | OG002 | PF-04937319 300 mg MR2 | Participants received modified-release formulation#2 administered orally at 300 mg with morning meal. There was a 5 to 10-day washout between dosing across the 4 regimens. |
|
| Secondary | Terminal Elimination Half-Life (t1/2) | t1/2 is the time measured for the plasma concentration to decrease by one half. | The PK parameter analysis population included all randomized participants who received at least 1 dose of PF-04937319 and who had at least 1 of the PK parameters of interest measured and available in at least 1 period; number of participants analyzed (N) is number of evaluable participants for this outcome measure. | Posted | | Mean | Standard Deviation | hour | | 0 (pre-dose) and 1, 2, 3, 4, 5, 6, 7, 8, 11, 12.5, 14, 16, 20, 24, 36, 48, and 72 hours post-dose | | | | ID | Title | Description |
|---|
| OG000 | PF-04937319 150+100 mg IR | Participants received immediate-release material sparing tablet (IR MST) administered orally at 150 mg with morning meal and 100 mg with lunch. There was a 5 to 10-day washout between dosing across the 4 regimens. | | OG001 | PF-04937319 250 mg MR1 | Participants received modified-release formulation #1 administered orally at 250 mg tablet with morning meal. There was a 5 to 10-day washout between dosing across the 4 regimens. | | OG002 | PF-04937319 300 mg MR2 | Participants received modified-release formulation#2 administered orally at 300 mg with morning meal. There was a 5 to 10-day washout between dosing across the 4 regimens. |
|
| Secondary | 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 drug. 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 drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pre-treatment state. AEs included both SAEs and non-SAEs. | The safety analysis population included all participants who received at least 1 dose of open-label, sponsor-provided metformin. | Posted | | Number | | participants | | Baseline up to 28 days after last study drug administration in Period 4 | | | | ID | Title | Description |
|---|
| OG000 | Metformin Run-In | Participants received open-label, sponsor-provided metformin tablet(s) orally at a dose in multiples of 500 mg (minimum dose 500 mg, maximum dose 2500 mg). Participants who met eligibility criteria on metformin were then randomized to 1 of 4 treatment regimens. | | OG001 | PF-04937319 150+100 mg IR | Participants received immediate-release material sparing tablet (IR MST) administered orally at 150 mg with morning meal and 100 mg with lunch. There was a 5 to 10-day washout between dosing across the 4 regimens. |
|