Trial Outcomes & Findings for A Phase 1 Study In Japanese Subjects With Type 2 Diabetes Mellitus As Monotherapy (NCT NCT02292433)
NCT ID: NCT02292433
Last Updated: 2016-03-15
Results Overview
An AE was any untoward medical occurrence in a participant who received study drug 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 drug and up to 14 days after last dose that were absent before treatment or that worsened relative to pre-treatment state.
COMPLETED
PHASE1
12 participants
Baseline up to 14 days after the last dose of study drug (minimum 8 weeks to maximum of 17 weeks)
2016-03-15
Participant Flow
Participant milestones
| Measure |
PF-04937319 100 mg Then PF-04937319 250 mg Then Placebo
Participants received PF-04937319 100 milligram (mg) orally per day in 2 divided doses (split dose regimen of 50 mg with morning meal and 50 mg with afternoon meal at approximately 5 hours of interval) for 7 days in the first intervention period followed by PF-04937319 250 mg orally per day in 2 divided doses (split dose regimen of 150 mg with morning meal and 100 mg with afternoon meal at approximately 5 hours of interval) for 7 days in the second intervention period, and then placebo matched to PF-04937319 administered orally with morning and afternoon meals for 7 days in the third intervention period. A washout period of 7 to 14 days was maintained between each intervention.
|
PF-04937319 100 mg Then Placebo Then PF-04937319 250 mg
Participants received PF-04937319 100 mg orally per day in 2 divided doses (split dose regimen of 50 mg with morning meal and 50 mg with afternoon meal at approximately 5 hours of interval) for 7 days in the first intervention period followed by placebo matched to PF-04937319 administered orally with morning and afternoon meals for 7 days in the second intervention period, and then PF-04937319 250 mg orally per day in 2 divided doses (split dose regimen of 150 mg with morning meal and 100 mg with afternoon meal at approximately 5 hours of interval) for 7 days in the third intervention period. A washout period of 7 to 14 days was maintained between each intervention.
|
Placebo Then PF-04937319 100 mg Then PF-04937319 250 mg
Participants received placebo matched to PF-04937319 administered orally with morning and afternoon meals for 7 days in the first intervention period followed by PF-04937319 100 mg orally per day in 2 divided doses (split dose regimen of 50 mg with morning meal and 50 mg with afternoon meal at approximately 5 hours of interval) for 7 days in the second intervention period, and then PF-04937319 250 mg orally per day in 2 divided doses (split dose regimen of 150 mg with morning meal and 100 mg with afternoon meal at approximately 5 hours of interval) for 7 days in the third intervention period. A washout period of 7 to 14 days was maintained between each intervention.
|
|---|---|---|---|
|
First Intervention Period (7 Days)
STARTED
|
4
|
4
|
4
|
|
First Intervention Period (7 Days)
COMPLETED
|
4
|
4
|
4
|
|
First Intervention Period (7 Days)
NOT COMPLETED
|
0
|
0
|
0
|
|
First Washout Period (7 to 14 Days)
STARTED
|
4
|
4
|
4
|
|
First Washout Period (7 to 14 Days)
COMPLETED
|
4
|
4
|
4
|
|
First Washout Period (7 to 14 Days)
NOT COMPLETED
|
0
|
0
|
0
|
|
Second Intervention Period (7 Days)
STARTED
|
4
|
4
|
4
|
|
Second Intervention Period (7 Days)
COMPLETED
|
4
|
4
|
4
|
|
Second Intervention Period (7 Days)
NOT COMPLETED
|
0
|
0
|
0
|
|
Second Washout Period (7 to 14 Days)
STARTED
|
4
|
4
|
4
|
|
Second Washout Period (7 to 14 Days)
COMPLETED
|
4
|
4
|
4
|
|
Second Washout Period (7 to 14 Days)
NOT COMPLETED
|
0
|
0
|
0
|
|
Third Intervention Period (7 Days)
STARTED
|
4
|
4
|
4
|
|
Third Intervention Period (7 Days)
COMPLETED
|
4
|
4
|
4
|
|
Third Intervention Period (7 Days)
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Phase 1 Study In Japanese Subjects With Type 2 Diabetes Mellitus As Monotherapy
Baseline characteristics by cohort
| Measure |
PF-04937319 100 mg Then PF-04937319 250 mg Then Placebo
n=4 Participants
Participants received PF-04937319 100 milligram (mg) orally per day in 2 divided doses (split dose regimen of 50 mg with morning meal and 50 mg with afternoon meal at approximately 5 hours of interval) for 7 days in the first intervention period followed by PF-04937319 250 mg orally per day in 2 divided doses (split dose regimen of 150 mg with morning meal and 100 mg with afternoon meal at approximately 5 hours of interval) for 7 days in the second intervention period, and then placebo matched to PF-04937319 administered orally with morning and afternoon meals for 7 days in the third intervention period. A washout period of 7 to 14 days was maintained between each intervention.
|
PF-04937319 100 mg Then Placebo Then PF-04937319 250 mg
n=4 Participants
Participants received PF-04937319 100 mg orally per day in 2 divided doses (split dose regimen of 50 mg with morning meal and 50 mg with afternoon meal at approximately 5 hours of interval) for 7 days in the first intervention period followed by placebo matched to PF-04937319 administered orally with morning and afternoon meals for 7 days in the second intervention period, and then PF-04937319 250 mg orally per day in 2 divided doses (split dose regimen of 150 mg with morning meal and 100 mg with afternoon meal at approximately 5 hours of interval) for 7 days in the third intervention period. A washout period of 7 to 14 days was maintained between each intervention.
|
Placebo Then PF-04937319 100 mg Then PF-04937319 250 mg
n=4 Participants
Participants received placebo matched to PF-04937319 administered orally with morning and afternoon meals for 7 days in the first intervention period followed by PF-04937319 100 mg orally per day in 2 divided doses (split dose regimen of 50 mg with morning meal and 50 mg with afternoon meal at approximately 5 hours of interval) for 7 days in the second intervention period, and then PF-04937319 250 mg orally per day in 2 divided doses (split dose regimen of 150 mg with morning meal and 100 mg with afternoon meal at approximately 5 hours of interval) for 7 days in the third intervention period. A washout period of 7 to 14 days was maintained between each intervention.
|
Total
n=12 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
49.3 years
STANDARD_DEVIATION 6.6 • n=5 Participants
|
52.5 years
STANDARD_DEVIATION 10.5 • n=7 Participants
|
53.8 years
STANDARD_DEVIATION 6.2 • n=5 Participants
|
51.8 years
STANDARD_DEVIATION 7.5 • n=4 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
12 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Baseline up to 14 days after the last dose of study drug (minimum 8 weeks to maximum of 17 weeks)Population: Safety analysis set included all participants who received at least 1 dose of study medication (including placebo) in at least 1 period.
An AE was any untoward medical occurrence in a participant who received study drug 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 drug and up to 14 days after last dose that were absent before treatment or that worsened relative to pre-treatment state.
Outcome measures
| Measure |
PF--04937319 250 mg
n=12 Participants
All participants who received PF-04937319 250 mg orally per day in 2 divided doses (split dose regimen of 150 mg with morning meal and 100 mg with afternoon at approximately 5 hours of interval) for 7 days in either second or third intervention period.
|
Placebo
n=12 Participants
All participants who received placebo matched to PF-04937319 administered orally with morning meal and with afternoon meal for 7 days in either first, second or third intervention period.
|
PF--04937319 100 mg
n=12 Participants
All participants who received PF-04937319 100 mg orally per day in 2 divided doses (split dose regimen of 50 mg with morning meal and 50 mg with afternoon meal at approximately 5 hours of interval) for 7 days in either first or second intervention period.
|
|---|---|---|---|
|
Number of Participants With Treatment Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)
AEs
|
6 participants
|
1 participants
|
1 participants
|
|
Number of Participants With Treatment Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)
SAEs
|
0 participants
|
0 participants
|
0 participants
|
PRIMARY outcome
Timeframe: Baseline up to 14 days after the last dose of study drug (minimum 8 weeks to maximum of 17 weeks)Population: Safety analysis set included all participants who received at least 1 dose of study medication (including placebo) in at least 1 period.
A hypoglycemic event (HAE) was identified by characteristic symptoms or blood glucose levels. HAE was defined as 1 of the given definitions: 1) Characteristic symptoms of HAE with no home glucose monitoring performed where clinical picture included prompt resolution with food intake, subcutaneous glucagon, or intravenous glucose; 2) Characteristic symptoms of HAE with home glucose monitoring measurement of less than or equal to (=\<) 70 milligram per deciliter (mg/dL) using sponsor-provided, plasma-referenced, home glucometers (or central laboratory); 3) any glucose value =\<49 mg/dL using sponsor-provided, plasma-referenced, home glucometers (or central laboratory) with or without accompanying symptoms.
Outcome measures
| Measure |
PF--04937319 250 mg
n=12 Participants
All participants who received PF-04937319 250 mg orally per day in 2 divided doses (split dose regimen of 150 mg with morning meal and 100 mg with afternoon at approximately 5 hours of interval) for 7 days in either second or third intervention period.
|
Placebo
n=12 Participants
All participants who received placebo matched to PF-04937319 administered orally with morning meal and with afternoon meal for 7 days in either first, second or third intervention period.
|
PF--04937319 100 mg
n=12 Participants
All participants who received PF-04937319 100 mg orally per day in 2 divided doses (split dose regimen of 50 mg with morning meal and 50 mg with afternoon meal at approximately 5 hours of interval) for 7 days in either first or second intervention period.
|
|---|---|---|---|
|
Number of Participants With Protocol Defined Hypoglycaemic Adverse Events (HAEs)
|
4 participants
|
0 participants
|
1 participants
|
PRIMARY outcome
Timeframe: 0 hour (pre-dose), 1.5, 3, 5, 6.5, 8, 11, 12.5, 14, 24 hours post morning dose on Day 1Population: 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 PK parameters of interest calculated and available in at least 1 period.
Outcome measures
| Measure |
PF--04937319 250 mg
n=12 Participants
All participants who received PF-04937319 250 mg orally per day in 2 divided doses (split dose regimen of 150 mg with morning meal and 100 mg with afternoon at approximately 5 hours of interval) for 7 days in either second or third intervention period.
|
Placebo
All participants who received placebo matched to PF-04937319 administered orally with morning meal and with afternoon meal for 7 days in either first, second or third intervention period.
|
PF--04937319 100 mg
n=12 Participants
All participants who received PF-04937319 100 mg orally per day in 2 divided doses (split dose regimen of 50 mg with morning meal and 50 mg with afternoon meal at approximately 5 hours of interval) for 7 days in either first or second intervention period.
|
|---|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) on Day 1 for PF-04937319
|
614.6 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 20
|
—
|
345.8 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 13
|
PRIMARY outcome
Timeframe: 0 hour (pre-dose), 1.5, 3, 5, 6.5, 8, 11, 12.5, 14, 24 hours post morning dose on Day 1Population: PK parameter analysis population included all randomized participants who received at least 1 dose of PF-04937319 and who had at least 1 of PK parameters of interest calculated and available in at least 1 period.
Outcome measures
| Measure |
PF--04937319 250 mg
n=12 Participants
All participants who received PF-04937319 250 mg orally per day in 2 divided doses (split dose regimen of 150 mg with morning meal and 100 mg with afternoon at approximately 5 hours of interval) for 7 days in either second or third intervention period.
|
Placebo
All participants who received placebo matched to PF-04937319 administered orally with morning meal and with afternoon meal for 7 days in either first, second or third intervention period.
|
PF--04937319 100 mg
n=12 Participants
All participants who received PF-04937319 100 mg orally per day in 2 divided doses (split dose regimen of 50 mg with morning meal and 50 mg with afternoon meal at approximately 5 hours of interval) for 7 days in either first or second intervention period.
|
|---|---|---|---|
|
Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 1 for PF-04937319
|
6.50 hour
Full Range 20 • Interval 6.5 to 8.0
|
—
|
6.50 hour
Full Range 13 • Interval 6.5 to 6.5
|
PRIMARY outcome
Timeframe: 0 hour (pre-dose), 1.5, 3, 5, 6.5, 8, 11, 12.5, 14, 24 hours post-dose on Day 1Population: PK parameter analysis population included all randomized participants who received at least 1 dose of PF-04937319 and who had at least 1 of PK parameters of interest calculated and available in at least 1 period.
AUC24 is the area under the plasma concentration versus time curve from time zero (pre-dose) to 24 hours post-dose (0 to 24).
Outcome measures
| Measure |
PF--04937319 250 mg
n=12 Participants
All participants who received PF-04937319 250 mg orally per day in 2 divided doses (split dose regimen of 150 mg with morning meal and 100 mg with afternoon at approximately 5 hours of interval) for 7 days in either second or third intervention period.
|
Placebo
All participants who received placebo matched to PF-04937319 administered orally with morning meal and with afternoon meal for 7 days in either first, second or third intervention period.
|
PF--04937319 100 mg
n=12 Participants
All participants who received PF-04937319 100 mg orally per day in 2 divided doses (split dose regimen of 50 mg with morning meal and 50 mg with afternoon meal at approximately 5 hours of interval) for 7 days in either first or second intervention period.
|
|---|---|---|---|
|
Area Under the Concentration-Time Curve (AUC24) From Time Zero to 24 Hour on Day 1 for PF-04937319
|
6379 nanogram*hour per milliliter (ng*hr/mL)
Geometric Coefficient of Variation 22 • Interval 6.5 to 8.0
|
—
|
3308 nanogram*hour per milliliter (ng*hr/mL)
Geometric Coefficient of Variation 16 • Interval 6.5 to 6.5
|
PRIMARY outcome
Timeframe: 0 hour (pre-dose), 1.5, 3, 5, 6.5, 8, 11, 12.5, 14, 24, 36, 48 hours post morning dose on Day 7Population: PK parameter analysis population included all randomized participants who received at least 1 dose of PF-04937319 and who had at least 1 of PK parameters of interest calculated and available in at least 1 period.
Outcome measures
| Measure |
PF--04937319 250 mg
n=12 Participants
All participants who received PF-04937319 250 mg orally per day in 2 divided doses (split dose regimen of 150 mg with morning meal and 100 mg with afternoon at approximately 5 hours of interval) for 7 days in either second or third intervention period.
|
Placebo
All participants who received placebo matched to PF-04937319 administered orally with morning meal and with afternoon meal for 7 days in either first, second or third intervention period.
|
PF--04937319 100 mg
n=12 Participants
All participants who received PF-04937319 100 mg orally per day in 2 divided doses (split dose regimen of 50 mg with morning meal and 50 mg with afternoon meal at approximately 5 hours of interval) for 7 days in either first or second intervention period.
|
|---|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) on Day 7 for PF-04937319
|
692.0 ng/mL
Geometric Coefficient of Variation 22
|
—
|
361.3 ng/mL
Geometric Coefficient of Variation 16
|
PRIMARY outcome
Timeframe: 0 hour (pre-dose), 1.5, 3, 5, 6.5, 8, 11, 12.5, 14, 24, 36, 48 hours post morning dose on Day 7Population: PK parameter analysis population included all randomized participants who received at least 1 dose of PF-04937319 and who had at least 1 of PK parameters of interest calculated and available in at least 1 period.
Outcome measures
| Measure |
PF--04937319 250 mg
n=12 Participants
All participants who received PF-04937319 250 mg orally per day in 2 divided doses (split dose regimen of 150 mg with morning meal and 100 mg with afternoon at approximately 5 hours of interval) for 7 days in either second or third intervention period.
|
Placebo
All participants who received placebo matched to PF-04937319 administered orally with morning meal and with afternoon meal for 7 days in either first, second or third intervention period.
|
PF--04937319 100 mg
n=12 Participants
All participants who received PF-04937319 100 mg orally per day in 2 divided doses (split dose regimen of 50 mg with morning meal and 50 mg with afternoon meal at approximately 5 hours of interval) for 7 days in either first or second intervention period.
|
|---|---|---|---|
|
Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 7 for PF-04937319
|
6.50 hour
Full Range 20 • Interval 1.5 to 8.0
|
—
|
6.50 hour
Full Range 13 • Interval 6.5 to 8.0
|
PRIMARY outcome
Timeframe: 0 hour (pre-dose), 1.5, 3, 5, 6.5, 8, 11, 12.5, 14, 24 hours post morning dose on Day 7Population: PK parameter analysis population included all randomized participants who received at least 1 dose of PF-04937319 and who had at least 1 of PK parameters of interest calculated and available in at least 1 period.
AUC24 is the area under the plasma concentration versus time curve from time zero (pre-dose) to 24 hours post-dose (0 to 24).
Outcome measures
| Measure |
PF--04937319 250 mg
n=12 Participants
All participants who received PF-04937319 250 mg orally per day in 2 divided doses (split dose regimen of 150 mg with morning meal and 100 mg with afternoon at approximately 5 hours of interval) for 7 days in either second or third intervention period.
|
Placebo
All participants who received placebo matched to PF-04937319 administered orally with morning meal and with afternoon meal for 7 days in either first, second or third intervention period.
|
PF--04937319 100 mg
n=12 Participants
All participants who received PF-04937319 100 mg orally per day in 2 divided doses (split dose regimen of 50 mg with morning meal and 50 mg with afternoon meal at approximately 5 hours of interval) for 7 days in either first or second intervention period.
|
|---|---|---|---|
|
Area Under the Concentration-Time Curve (AUC24) From Time Zero to 24 Hour on Day 7 for PF-04937319
|
7937 ng*hr/mL
Geometric Coefficient of Variation 27 • Interval 6.5 to 8.0
|
—
|
3840 ng*hr/mL
Geometric Coefficient of Variation 21 • Interval 6.5 to 6.5
|
PRIMARY outcome
Timeframe: 0 hour (pre-dose) on Day 7Population: PK parameter analysis population included all randomized participants who received at least 1 dose of PF-04937319 and who had at least 1 of PK parameters of interest calculated and available in at least 1 period.
Ctrough is the concentration prior to study drug administration.
Outcome measures
| Measure |
PF--04937319 250 mg
n=12 Participants
All participants who received PF-04937319 250 mg orally per day in 2 divided doses (split dose regimen of 150 mg with morning meal and 100 mg with afternoon at approximately 5 hours of interval) for 7 days in either second or third intervention period.
|
Placebo
All participants who received placebo matched to PF-04937319 administered orally with morning meal and with afternoon meal for 7 days in either first, second or third intervention period.
|
PF--04937319 100 mg
n=12 Participants
All participants who received PF-04937319 100 mg orally per day in 2 divided doses (split dose regimen of 50 mg with morning meal and 50 mg with afternoon meal at approximately 5 hours of interval) for 7 days in either first or second intervention period.
|
|---|---|---|---|
|
Pre-dose Plasma Concentration (Ctrough) on Day 7 for PF-04937319
|
106.3 ng/mL
Geometric Coefficient of Variation 29 • Interval 6.5 to 8.0
|
—
|
44.82 ng/mL
Geometric Coefficient of Variation 30 • Interval 6.5 to 6.5
|
PRIMARY outcome
Timeframe: 0 hour (pre-dose), 1.5, 3, 5, 6.5, 8, 11, 12.5, 14, 24 hours post morning dose on Day 7Population: PK parameter analysis population included all randomized participants who received at least 1 dose of PF-04937319 and who had at least 1 of PK parameters of interest calculated and available in at least 1 period.
Cav is the average plasma concentration during the 0 to 24 hour time period.
Outcome measures
| Measure |
PF--04937319 250 mg
n=12 Participants
All participants who received PF-04937319 250 mg orally per day in 2 divided doses (split dose regimen of 150 mg with morning meal and 100 mg with afternoon at approximately 5 hours of interval) for 7 days in either second or third intervention period.
|
Placebo
All participants who received placebo matched to PF-04937319 administered orally with morning meal and with afternoon meal for 7 days in either first, second or third intervention period.
|
PF--04937319 100 mg
n=12 Participants
All participants who received PF-04937319 100 mg orally per day in 2 divided doses (split dose regimen of 50 mg with morning meal and 50 mg with afternoon meal at approximately 5 hours of interval) for 7 days in either first or second intervention period.
|
|---|---|---|---|
|
Average Plasma Concentration (Cav) on Day 7 for PF-04937319
|
330.6 ng/mL
Geometric Coefficient of Variation 27 • Interval 6.5 to 8.0
|
—
|
159.9 ng/mL
Geometric Coefficient of Variation 21 • Interval 6.5 to 6.5
|
PRIMARY outcome
Timeframe: 0 hour (pre-dose), 1.5, 3, 5, 6.5, 8, 11, 12.5, 14, 24 hours post morning dose on Day 7Population: PK parameter analysis population included all randomized participants who received at least 1 dose of PF-04937319 and who had at least 1 of PK parameters of interest calculated and available in at least 1 period.
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 oral bioavailability. It is calculated as the total oral daily dose divided by AUC24, where AUC24 is the area under the plasma concentration-time profile from time 0 to 24 hours.
Outcome measures
| Measure |
PF--04937319 250 mg
n=12 Participants
All participants who received PF-04937319 250 mg orally per day in 2 divided doses (split dose regimen of 150 mg with morning meal and 100 mg with afternoon at approximately 5 hours of interval) for 7 days in either second or third intervention period.
|
Placebo
All participants who received placebo matched to PF-04937319 administered orally with morning meal and with afternoon meal for 7 days in either first, second or third intervention period.
|
PF--04937319 100 mg
n=12 Participants
All participants who received PF-04937319 100 mg orally per day in 2 divided doses (split dose regimen of 50 mg with morning meal and 50 mg with afternoon meal at approximately 5 hours of interval) for 7 days in either first or second intervention period.
|
|---|---|---|---|
|
Apparent Oral Clearance on Day 7 for PF-04937319
|
525.0 milliliter per minute (mL/min)
Geometric Coefficient of Variation 27 • Interval 6.5 to 8.0
|
—
|
434.0 milliliter per minute (mL/min)
Geometric Coefficient of Variation 21 • Interval 6.5 to 6.5
|
PRIMARY outcome
Timeframe: 0 hour (pre-dose), 1.5, 3, 5, 6.5, 8, 11, 12.5, 14, 24, 36, 48 hours post morning dose on Day 7Population: PK parameter analysis population included all randomized participants who received at least 1 dose of PF-04937319 and who had at least 1 of PK parameters of interest calculated and available in at least 1 period.
Terminal half-life is the time measured for the plasma concentration to decrease by one half. Terminal half-life is calculated by dividing the natural logarithm to the base e (Log e) multiplied by (\*) 2/k el, where 'k el' is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Only those data points judged to describe the terminal log-linear decline were used in the regression.
Outcome measures
| Measure |
PF--04937319 250 mg
n=12 Participants
All participants who received PF-04937319 250 mg orally per day in 2 divided doses (split dose regimen of 150 mg with morning meal and 100 mg with afternoon at approximately 5 hours of interval) for 7 days in either second or third intervention period.
|
Placebo
All participants who received placebo matched to PF-04937319 administered orally with morning meal and with afternoon meal for 7 days in either first, second or third intervention period.
|
PF--04937319 100 mg
n=12 Participants
All participants who received PF-04937319 100 mg orally per day in 2 divided doses (split dose regimen of 50 mg with morning meal and 50 mg with afternoon meal at approximately 5 hours of interval) for 7 days in either first or second intervention period.
|
|---|---|---|---|
|
Terminal Half-Life (t1/2) on Day 7 for PF-04937319
|
10.01 hour
Standard Deviation 4.5216 • Interval 6.5 to 8.0
|
—
|
8.006 hour
Standard Deviation 3.5291 • Interval 6.5 to 6.5
|
PRIMARY outcome
Timeframe: 0 hour (pre-dose), 1.5, 3, 5, 6.5, 8, 11, 12.5, 14, 24 hours post morning dose on Day 7Population: PK parameter analysis population included all randomized participants who received at least 1 dose of PF-04937319 and who had at least 1 of PK parameters of interest calculated and available in at least 1 period.
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. Apparent volume of distribution after oral dose is influenced by the oral bioavailability. It is calculated as the total oral daily dose divided by AUC24\* k el, where AUC24 is the area under the plasma concentration-time profile from time 0 to 24 hours and terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
Outcome measures
| Measure |
PF--04937319 250 mg
n=12 Participants
All participants who received PF-04937319 250 mg orally per day in 2 divided doses (split dose regimen of 150 mg with morning meal and 100 mg with afternoon at approximately 5 hours of interval) for 7 days in either second or third intervention period.
|
Placebo
All participants who received placebo matched to PF-04937319 administered orally with morning meal and with afternoon meal for 7 days in either first, second or third intervention period.
|
PF--04937319 100 mg
n=12 Participants
All participants who received PF-04937319 100 mg orally per day in 2 divided doses (split dose regimen of 50 mg with morning meal and 50 mg with afternoon meal at approximately 5 hours of interval) for 7 days in either first or second intervention period.
|
|---|---|---|---|
|
Apparent Volume of Distribution on Day 7 for PF-04937319
|
414.6 liter
Geometric Coefficient of Variation 40 • Interval 6.5 to 8.0
|
—
|
280.5 liter
Geometric Coefficient of Variation 48 • Interval 6.5 to 6.5
|
PRIMARY outcome
Timeframe: 0 hour (pre-dose), 1.5, 3, 5, 6.5, 8, 11, 12.5, 14, 24 hours post morning dose on Day 7Population: PK parameter analysis population included all randomized participants who received at least 1 dose of PF-04937319 and who had at least 1 of PK parameters of interest calculated and available in at least 1 period.
Rac is based on AUC24. It is the ratio of AUC24 of Day 7 and AUC24 of Day 1, where AUC24 is the area under the plasma concentration-time profile from time 0 to 24 hours.
Outcome measures
| Measure |
PF--04937319 250 mg
n=12 Participants
All participants who received PF-04937319 250 mg orally per day in 2 divided doses (split dose regimen of 150 mg with morning meal and 100 mg with afternoon at approximately 5 hours of interval) for 7 days in either second or third intervention period.
|
Placebo
All participants who received placebo matched to PF-04937319 administered orally with morning meal and with afternoon meal for 7 days in either first, second or third intervention period.
|
PF--04937319 100 mg
n=12 Participants
All participants who received PF-04937319 100 mg orally per day in 2 divided doses (split dose regimen of 50 mg with morning meal and 50 mg with afternoon meal at approximately 5 hours of interval) for 7 days in either first or second intervention period.
|
|---|---|---|---|
|
Accumulation Ratio (Rac) on Day 7 for PF-04937319
|
1.244 ratio
Geometric Coefficient of Variation 19 • Interval 6.5 to 8.0
|
—
|
1.159 ratio
Geometric Coefficient of Variation 16 • Interval 6.5 to 6.5
|
SECONDARY outcome
Timeframe: 0 hour (pre-dose), 1.5, 3, 5, 6.5, 8, 11, 12.5, 14, 24 hours post morning dose on Day 1Population: PK parameter analysis population included all randomized participants who received at least 1 dose of PF-04937319 and who had at least 1 of PK parameters of interest calculated and available in at least 1 period.
PF-06455349 is a metabolite of PF-04937319.
Outcome measures
| Measure |
PF--04937319 250 mg
n=12 Participants
All participants who received PF-04937319 250 mg orally per day in 2 divided doses (split dose regimen of 150 mg with morning meal and 100 mg with afternoon at approximately 5 hours of interval) for 7 days in either second or third intervention period.
|
Placebo
All participants who received placebo matched to PF-04937319 administered orally with morning meal and with afternoon meal for 7 days in either first, second or third intervention period.
|
PF--04937319 100 mg
n=12 Participants
All participants who received PF-04937319 100 mg orally per day in 2 divided doses (split dose regimen of 50 mg with morning meal and 50 mg with afternoon meal at approximately 5 hours of interval) for 7 days in either first or second intervention period.
|
|---|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) on Day 1 for PF-06455349
|
583.7 ng/mL
Geometric Coefficient of Variation 22
|
—
|
310.5 ng/mL
Geometric Coefficient of Variation 21
|
SECONDARY outcome
Timeframe: 0 hour (pre-dose), 1.5, 3, 5, 6.5, 8, 11, 12.5, 14, 24 hours post morning dose on Day 1Population: PK parameter analysis population included all randomized participants who received at least 1 dose of PF-04937319 and who had at least 1 of PK parameters of interest calculated and available in at least 1 period.
PF-06455349 is a metabolite of PF-04937319.
Outcome measures
| Measure |
PF--04937319 250 mg
n=12 Participants
All participants who received PF-04937319 250 mg orally per day in 2 divided doses (split dose regimen of 150 mg with morning meal and 100 mg with afternoon at approximately 5 hours of interval) for 7 days in either second or third intervention period.
|
Placebo
All participants who received placebo matched to PF-04937319 administered orally with morning meal and with afternoon meal for 7 days in either first, second or third intervention period.
|
PF--04937319 100 mg
n=12 Participants
All participants who received PF-04937319 100 mg orally per day in 2 divided doses (split dose regimen of 50 mg with morning meal and 50 mg with afternoon meal at approximately 5 hours of interval) for 7 days in either first or second intervention period.
|
|---|---|---|---|
|
Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 1 for PF-06455349
|
11.0 hour
Full Range 20 • Interval 8.0 to 12.5
|
—
|
11.0 hour
Full Range 13 • Interval 11.0 to 14.0
|
SECONDARY outcome
Timeframe: 0 hour (pre-dose), 1.5, 3, 5, 6.5, 8, 11, 12.5, 14, 24 hours post morning dose on Day 1Population: PK parameter analysis population included all randomized participants who received at least 1 dose of PF-04937319 and who had at least 1 of PK parameters of interest calculated and available in at least 1 period.
AUC24 is the area under the plasma concentration versus time curve from time zero (pre-dose) to 24 hours post-dose (0 to 24). PF-06455349 is a metabolite of PF-04937319.
Outcome measures
| Measure |
PF--04937319 250 mg
n=12 Participants
All participants who received PF-04937319 250 mg orally per day in 2 divided doses (split dose regimen of 150 mg with morning meal and 100 mg with afternoon at approximately 5 hours of interval) for 7 days in either second or third intervention period.
|
Placebo
All participants who received placebo matched to PF-04937319 administered orally with morning meal and with afternoon meal for 7 days in either first, second or third intervention period.
|
PF--04937319 100 mg
n=12 Participants
All participants who received PF-04937319 100 mg orally per day in 2 divided doses (split dose regimen of 50 mg with morning meal and 50 mg with afternoon meal at approximately 5 hours of interval) for 7 days in either first or second intervention period.
|
|---|---|---|---|
|
Area Under the Concentration-Time Curve (AUC24) From Time Zero to 24 Hour on Day 1 for PF--06455349
|
10180 ng*hr/mL
Geometric Coefficient of Variation 19 • Interval 6.5 to 8.0
|
—
|
5326 ng*hr/mL
Geometric Coefficient of Variation 18 • Interval 6.5 to 6.5
|
SECONDARY outcome
Timeframe: 0 hour (pre-dose), 1.5, 3, 5, 6.5, 8, 11, 12.5, 14, 24 hours post morning dose on Day 1Population: PK parameter analysis population included all randomized participants who received at least 1 dose of PF-04937319 and who had at least 1 of PK parameters of interest calculated and available in at least 1 period.
MRAUC24 is the ratio of AUC24 of PF-06455349 (metabolite) to AUC24 of PF-04937319 (parent drug) \* ratio of molecular weight of PF-04937319 to molecular weight of PF-06455349, where AUC24 is the area under the plasma concentration-time profile from time 0 to 24 hours.
Outcome measures
| Measure |
PF--04937319 250 mg
n=12 Participants
All participants who received PF-04937319 250 mg orally per day in 2 divided doses (split dose regimen of 150 mg with morning meal and 100 mg with afternoon at approximately 5 hours of interval) for 7 days in either second or third intervention period.
|
Placebo
All participants who received placebo matched to PF-04937319 administered orally with morning meal and with afternoon meal for 7 days in either first, second or third intervention period.
|
PF--04937319 100 mg
n=12 Participants
All participants who received PF-04937319 100 mg orally per day in 2 divided doses (split dose regimen of 50 mg with morning meal and 50 mg with afternoon meal at approximately 5 hours of interval) for 7 days in either first or second intervention period.
|
|---|---|---|---|
|
Metabolite to Parent Ratio for AUC24 (MRAUC24) on Day 1
|
1.649 ratio
Geometric Coefficient of Variation 23 • Interval 6.5 to 8.0
|
—
|
1.664 ratio
Geometric Coefficient of Variation 24 • Interval 6.5 to 6.5
|
SECONDARY outcome
Timeframe: 0 hour (pre-dose), 1.5, 3, 5, 6.5, 8, 11, 12.5, 14, 24, 36, 48 hours post morning dose on Day 7Population: PK parameter analysis population included all randomized participants who received at least 1 dose of PF-04937319 and who had at least 1 of PK parameters of interest calculated and available in at least 1 period.
PF-06455349 is a metabolite of PF-04937319.
Outcome measures
| Measure |
PF--04937319 250 mg
n=12 Participants
All participants who received PF-04937319 250 mg orally per day in 2 divided doses (split dose regimen of 150 mg with morning meal and 100 mg with afternoon at approximately 5 hours of interval) for 7 days in either second or third intervention period.
|
Placebo
All participants who received placebo matched to PF-04937319 administered orally with morning meal and with afternoon meal for 7 days in either first, second or third intervention period.
|
PF--04937319 100 mg
n=12 Participants
All participants who received PF-04937319 100 mg orally per day in 2 divided doses (split dose regimen of 50 mg with morning meal and 50 mg with afternoon meal at approximately 5 hours of interval) for 7 days in either first or second intervention period.
|
|---|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) on Day 7 for PF--06455349
|
978.6 ng/mL
Geometric Coefficient of Variation 17
|
—
|
464.0 ng/mL
Geometric Coefficient of Variation 9
|
SECONDARY outcome
Timeframe: 0 hour (pre-dose), 1.5, 3, 5, 6.5, 8, 11, 12.5, 14, 24, 36, 48 hours post morning dose on Day 7Population: PK parameter analysis population included all randomized participants who received at least 1 dose of PF-04937319 and who had at least 1 of PK parameters of interest calculated and available in at least 1 period.
PF-06455349 is a metabolite of PF-04937319.
Outcome measures
| Measure |
PF--04937319 250 mg
n=12 Participants
All participants who received PF-04937319 250 mg orally per day in 2 divided doses (split dose regimen of 150 mg with morning meal and 100 mg with afternoon at approximately 5 hours of interval) for 7 days in either second or third intervention period.
|
Placebo
All participants who received placebo matched to PF-04937319 administered orally with morning meal and with afternoon meal for 7 days in either first, second or third intervention period.
|
PF--04937319 100 mg
n=12 Participants
All participants who received PF-04937319 100 mg orally per day in 2 divided doses (split dose regimen of 50 mg with morning meal and 50 mg with afternoon meal at approximately 5 hours of interval) for 7 days in either first or second intervention period.
|
|---|---|---|---|
|
Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 7 for PF-06455349
|
11.0 hour
Full Range 20 • Interval 6.5 to 12.5
|
—
|
11.0 hour
Full Range 13 • Interval 6.5 to 12.5
|
SECONDARY outcome
Timeframe: 0 hour (pre-dose), 1.5, 3, 5, 6.5, 8, 11, 12.5, 14, 24 hours post morning dose on Day 7Population: PK parameter analysis population included all randomized participants who received at least 1 dose of PF-04937319 and who had at least 1 of PK parameters of interest calculated and available in at least 1 period.
AUC24 is the area under the plasma concentration versus time curve from time zero (pre-dose) to 24 hours post-dose (0 to 24). PF-06455349 is a metabolite of PF-04937319.
Outcome measures
| Measure |
PF--04937319 250 mg
n=12 Participants
All participants who received PF-04937319 250 mg orally per day in 2 divided doses (split dose regimen of 150 mg with morning meal and 100 mg with afternoon at approximately 5 hours of interval) for 7 days in either second or third intervention period.
|
Placebo
All participants who received placebo matched to PF-04937319 administered orally with morning meal and with afternoon meal for 7 days in either first, second or third intervention period.
|
PF--04937319 100 mg
n=12 Participants
All participants who received PF-04937319 100 mg orally per day in 2 divided doses (split dose regimen of 50 mg with morning meal and 50 mg with afternoon meal at approximately 5 hours of interval) for 7 days in either first or second intervention period.
|
|---|---|---|---|
|
Area Under the Concentration-Time Curve (AUC24) From Time Zero to 24 Hour on Day 7 for PF--06455349
|
19380 ng*hr/mL
Geometric Coefficient of Variation 15 • Interval 6.5 to 8.0
|
—
|
9346 ng*hr/mL
Geometric Coefficient of Variation 11 • Interval 6.5 to 6.5
|
SECONDARY outcome
Timeframe: 0 hour (pre-dose) on Day 7Population: PK parameter analysis population included all randomized participants who received at least 1 dose of PF-04937319 and who had at least 1 of PK parameters of interest calculated and available in at least 1 period.
Ctrough is the concentration prior to study drug administration. PF-06455349 is a metabolite of PF-04937319.
Outcome measures
| Measure |
PF--04937319 250 mg
n=12 Participants
All participants who received PF-04937319 250 mg orally per day in 2 divided doses (split dose regimen of 150 mg with morning meal and 100 mg with afternoon at approximately 5 hours of interval) for 7 days in either second or third intervention period.
|
Placebo
All participants who received placebo matched to PF-04937319 administered orally with morning meal and with afternoon meal for 7 days in either first, second or third intervention period.
|
PF--04937319 100 mg
n=12 Participants
All participants who received PF-04937319 100 mg orally per day in 2 divided doses (split dose regimen of 50 mg with morning meal and 50 mg with afternoon meal at approximately 5 hours of interval) for 7 days in either first or second intervention period.
|
|---|---|---|---|
|
Pre-dose Plasma Concentration (Ctrough) on Day 7 for PF--06455349
|
649.9 ng/mL
Geometric Coefficient of Variation 15 • Interval 6.5 to 12.5
|
—
|
321.8 ng/mL
Geometric Coefficient of Variation 15 • Interval 6.5 to 12.5
|
SECONDARY outcome
Timeframe: 0 hour (pre-dose), 1.5, 3, 5, 6.5, 8, 11, 12.5, 14, 24 hours post morning dose on Day 7Population: PK parameter analysis population included all randomized participants who received at least 1 dose of PF-04937319 and who had at least 1 of PK parameters of interest calculated and available in at least 1 period.
Cav is the average plasma concentration during the 0 to 24 hour time period. PF-06455349 is a metabolite of PF-04937319.
Outcome measures
| Measure |
PF--04937319 250 mg
n=12 Participants
All participants who received PF-04937319 250 mg orally per day in 2 divided doses (split dose regimen of 150 mg with morning meal and 100 mg with afternoon at approximately 5 hours of interval) for 7 days in either second or third intervention period.
|
Placebo
All participants who received placebo matched to PF-04937319 administered orally with morning meal and with afternoon meal for 7 days in either first, second or third intervention period.
|
PF--04937319 100 mg
n=12 Participants
All participants who received PF-04937319 100 mg orally per day in 2 divided doses (split dose regimen of 50 mg with morning meal and 50 mg with afternoon meal at approximately 5 hours of interval) for 7 days in either first or second intervention period.
|
|---|---|---|---|
|
Average Plasma Concentration (Cav) on Day 7 for PF--06455349
|
807.0 ng/mL
Geometric Coefficient of Variation 15 • Interval 6.5 to 8.0
|
—
|
389.5 ng/mL
Geometric Coefficient of Variation 11 • Interval 6.5 to 6.5
|
SECONDARY outcome
Timeframe: 0 hour (pre-dose), 1.5, 3, 5, 6.5, 8, 11, 12.5, 14, 24, 36, 48 hours post morning dose on Day 7Population: PK parameter analysis population included all randomized participants who received at least 1 dose of PF-04937319 and who had at least 1 of PK parameters of interest calculated and available in at least 1 period. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure.
Terminal half-life is the time measured for the plasma concentration to decrease by one half. Terminal half-life is calculated by dividing the natural logarithm to the base e (Log e) \* 2/k el, where 'k el' is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Only those data points judged to describe the terminal log-linear decline were used in the regression. PF-06455349 is a metabolite of PF-04937319.
Outcome measures
| Measure |
PF--04937319 250 mg
n=5 Participants
All participants who received PF-04937319 250 mg orally per day in 2 divided doses (split dose regimen of 150 mg with morning meal and 100 mg with afternoon at approximately 5 hours of interval) for 7 days in either second or third intervention period.
|
Placebo
All participants who received placebo matched to PF-04937319 administered orally with morning meal and with afternoon meal for 7 days in either first, second or third intervention period.
|
PF--04937319 100 mg
n=9 Participants
All participants who received PF-04937319 100 mg orally per day in 2 divided doses (split dose regimen of 50 mg with morning meal and 50 mg with afternoon meal at approximately 5 hours of interval) for 7 days in either first or second intervention period.
|
|---|---|---|---|
|
Terminal Half-Life (t1/2) on Day 7 for PF-06455349
|
NA hour
Standard Deviation NA • Interval 14.1 to 17.3
Data was not reported because as per planned analysis, the summary statistics was not assessed if data was missing for more than 50 percent of participants.
|
—
|
15.80 hour
Standard Deviation 1.9026 • Interval 13.2 to 18.6
|
SECONDARY outcome
Timeframe: 0 hour (pre-dose), 1.5, 3, 5, 6.5, 8, 11, 12.5, 14, 24 hours post morning dose on Day 7Population: PK parameter analysis population included all randomized participants who received at least 1 dose of PF-04937319 and who had at least 1 of PK parameters of interest calculated and available in at least 1 period.
Rac is based on AUC24. It is the ratio of AUC24 of Day 7 and AUC24 of Day 1, where AUC24 is the area under the plasma concentration-time profile from time 0 to 24 hours. PF-06455349 is a metabolite of PF-04937319.
Outcome measures
| Measure |
PF--04937319 250 mg
n=12 Participants
All participants who received PF-04937319 250 mg orally per day in 2 divided doses (split dose regimen of 150 mg with morning meal and 100 mg with afternoon at approximately 5 hours of interval) for 7 days in either second or third intervention period.
|
Placebo
All participants who received placebo matched to PF-04937319 administered orally with morning meal and with afternoon meal for 7 days in either first, second or third intervention period.
|
PF--04937319 100 mg
n=12 Participants
All participants who received PF-04937319 100 mg orally per day in 2 divided doses (split dose regimen of 50 mg with morning meal and 50 mg with afternoon meal at approximately 5 hours of interval) for 7 days in either first or second intervention period.
|
|---|---|---|---|
|
Accumulation Ratio (Rac) on Day 7 for PF-06455349
|
1.903 ratio
Geometric Coefficient of Variation 16 • Interval 6.5 to 8.0
|
—
|
1.756 ratio
Geometric Coefficient of Variation 14 • Interval 6.5 to 6.5
|
SECONDARY outcome
Timeframe: 0 hour (pre-dose), 1.5, 3, 5, 6.5, 8, 11, 12.5, 14, 24 hours post morning dose on Day 7Population: PK parameter analysis population included all randomized participants who received at least 1 dose of PF-04937319 and who had at least 1 of PK parameters of interest calculated and available in at least 1 period.
MRAUC24 is the ratio of AUC24 of PF-06455349 (metabolite) to AUC24 of PF-04937319 (parent drug) \* ratio of molecular weight of PF-04937319 to molecular weight of PF-06455349, where AUC24 is the area under the plasma concentration-time profile from time 0 to 24 hours. PF-06455349 is a metabolite of PF-04937319.
Outcome measures
| Measure |
PF--04937319 250 mg
n=12 Participants
All participants who received PF-04937319 250 mg orally per day in 2 divided doses (split dose regimen of 150 mg with morning meal and 100 mg with afternoon at approximately 5 hours of interval) for 7 days in either second or third intervention period.
|
Placebo
All participants who received placebo matched to PF-04937319 administered orally with morning meal and with afternoon meal for 7 days in either first, second or third intervention period.
|
PF--04937319 100 mg
n=12 Participants
All participants who received PF-04937319 100 mg orally per day in 2 divided doses (split dose regimen of 50 mg with morning meal and 50 mg with afternoon meal at approximately 5 hours of interval) for 7 days in either first or second intervention period.
|
|---|---|---|---|
|
Metabolite to Parent Ratio for AUC24 (MRAUC24) on Day 7
|
2.523 ratio
Geometric Coefficient of Variation 27 • Interval 6.5 to 8.0
|
—
|
2.516 ratio
Geometric Coefficient of Variation 22 • Interval 6.5 to 6.5
|
SECONDARY outcome
Timeframe: Pre-morning meal, 1.5, 3, 5, 6.5, 8, 11, 12.5, 14, 16 and 20 hours post- morning meal on Day 0; pre-morning dose, 1.5, 3, 5, 6.5, 8, 11, 12.5, 14, 16, 20 hours post-morning dose on Day 7Population: The pharmacodynamic (PD) analysis population included all randomized participants who received at least 1 dose of study medication and had both a baseline and a post-baseline assessment for at least 1 PD parameter in at least 1 period.
WMDG was defined as time-weighted mean daily glucose. WMDG was calculated by as the time-weighted mean of glucose levels at actual time points for glucose sampling, for Day 0 (Baseline) and Day 7.
Outcome measures
| Measure |
PF--04937319 250 mg
n=12 Participants
All participants who received PF-04937319 250 mg orally per day in 2 divided doses (split dose regimen of 150 mg with morning meal and 100 mg with afternoon at approximately 5 hours of interval) for 7 days in either second or third intervention period.
|
Placebo
n=12 Participants
All participants who received placebo matched to PF-04937319 administered orally with morning meal and with afternoon meal for 7 days in either first, second or third intervention period.
|
PF--04937319 100 mg
n=12 Participants
All participants who received PF-04937319 100 mg orally per day in 2 divided doses (split dose regimen of 50 mg with morning meal and 50 mg with afternoon meal at approximately 5 hours of interval) for 7 days in either first or second intervention period.
|
|---|---|---|---|
|
Change From Baseline in Weighted Mean Daily Glucose (WMDG) at Day 7
Baseline
|
184.38 mg/dL
Standard Deviation 51.844
|
190.42 mg/dL
Standard Deviation 41.284
|
201.31 mg/dL
Standard Deviation 49.204
|
|
Change From Baseline in Weighted Mean Daily Glucose (WMDG) at Day 7
Change at Day 7
|
-28.61 mg/dL
Standard Deviation 17.983
|
4.88 mg/dL
Standard Deviation 18.182
|
-23.58 mg/dL
Standard Deviation 14.833
|
SECONDARY outcome
Timeframe: Pre-morning meal on Day 0, pre-morning dose on Day 1, pre-morning dose on Day 7, pre-morning meal on Day 8Population: PD analysis population included all randomized participants who received at least 1 dose of study medication and had both a baseline and a post-baseline assessment for at least 1 PD parameter in at least 1 period.
FPG was defined as plasma glucose measurements taken pre-breakfast, in the fasted state, and prior to dosing with study drug. Baseline was defined as the average of Hour 0 measurements taken on Day 0 and Day 1 in each intervention period. The measurement on the last day of treatment was defined as the average of Hour 0 measurements taken on Day 7 and Day 8 in each period.
Outcome measures
| Measure |
PF--04937319 250 mg
n=12 Participants
All participants who received PF-04937319 250 mg orally per day in 2 divided doses (split dose regimen of 150 mg with morning meal and 100 mg with afternoon at approximately 5 hours of interval) for 7 days in either second or third intervention period.
|
Placebo
n=12 Participants
All participants who received placebo matched to PF-04937319 administered orally with morning meal and with afternoon meal for 7 days in either first, second or third intervention period.
|
PF--04937319 100 mg
n=12 Participants
All participants who received PF-04937319 100 mg orally per day in 2 divided doses (split dose regimen of 50 mg with morning meal and 50 mg with afternoon meal at approximately 5 hours of interval) for 7 days in either first or second intervention period.
|
|---|---|---|---|
|
Change From Baseline in Fasting Plasma Glucose (FPG) at Last Day of Treatment
Baseline
|
156.96 mg/dL
Standard Deviation 37.388
|
159.25 mg/dL
Standard Deviation 30.716
|
164.42 mg/dL
Standard Deviation 32.389
|
|
Change From Baseline in Fasting Plasma Glucose (FPG) at Last Day of Treatment
Change at last day of treatment
|
-39.33 mg/dL
Standard Deviation 17.892
|
-13.92 mg/dL
Standard Deviation 17.142
|
-31.08 mg/dL
Standard Deviation 14.860
|
SECONDARY outcome
Timeframe: Pre-morning meal (pre-breakfast), 5 hours (pre-lunch), 11 hours (pre-dinner) after morning meal on Day 0 (Baseline); pre-morning dose (pre-breakfast), 5 hours (pre-lunch), 11 hours (pre-dinner) post-morning dose on Day 7Population: PD analysis population included all randomized participants who received at least 1 dose of study medication and had both a baseline and a post-baseline assessment for at least 1 PD parameter in at least 1 period.
Time-matched change from baseline in pre-meal serum insulin on Day 7 of each period was analyzed. Pre-meal insulin levels therefore, pre-breakfast, pre-lunch, and pre-dinner were analyzed.
Outcome measures
| Measure |
PF--04937319 250 mg
n=12 Participants
All participants who received PF-04937319 250 mg orally per day in 2 divided doses (split dose regimen of 150 mg with morning meal and 100 mg with afternoon at approximately 5 hours of interval) for 7 days in either second or third intervention period.
|
Placebo
n=12 Participants
All participants who received placebo matched to PF-04937319 administered orally with morning meal and with afternoon meal for 7 days in either first, second or third intervention period.
|
PF--04937319 100 mg
n=12 Participants
All participants who received PF-04937319 100 mg orally per day in 2 divided doses (split dose regimen of 50 mg with morning meal and 50 mg with afternoon meal at approximately 5 hours of interval) for 7 days in either first or second intervention period.
|
|---|---|---|---|
|
Change From Baseline in Pre-Meal Insulin at Day 7
Pre-breakfast: Baseline
|
9.038 micro international unit per milliliter
Standard Deviation 5.4983
|
8.378 micro international unit per milliliter
Standard Deviation 5.1908
|
8.577 micro international unit per milliliter
Standard Deviation 4.8132
|
|
Change From Baseline in Pre-Meal Insulin at Day 7
Pre-breakfast: Change at Day 7
|
-1.439 micro international unit per milliliter
Standard Deviation 1.5490
|
0.594 micro international unit per milliliter
Standard Deviation 1.8753
|
-0.828 micro international unit per milliliter
Standard Deviation 1.2970
|
|
Change From Baseline in Pre-Meal Insulin at Day 7
Pre-lunch: Baseline
|
9.093 micro international unit per milliliter
Standard Deviation 4.6060
|
9.781 micro international unit per milliliter
Standard Deviation 5.5415
|
10.548 micro international unit per milliliter
Standard Deviation 4.5632
|
|
Change From Baseline in Pre-Meal Insulin at Day 7
Pre-lunch: Change at Day 7
|
2.640 micro international unit per milliliter
Standard Deviation 2.8358
|
5.416 micro international unit per milliliter
Standard Deviation 5.6758
|
4.258 micro international unit per milliliter
Standard Deviation 7.1120
|
|
Change From Baseline in Pre-Meal Insulin at Day 7
Pre-dinner: Baseline
|
13.031 micro international unit per milliliter
Standard Deviation 7.0380
|
13.344 micro international unit per milliliter
Standard Deviation 9.6188
|
13.113 micro international unit per milliliter
Standard Deviation 6.1401
|
|
Change From Baseline in Pre-Meal Insulin at Day 7
Pre-dinner: Change at Day 7
|
-2.521 micro international unit per milliliter
Standard Deviation 2.8025
|
0.449 micro international unit per milliliter
Standard Deviation 4.9616
|
-1.625 micro international unit per milliliter
Standard Deviation 3.0286
|
SECONDARY outcome
Timeframe: Pre-morning meal (pre-breakfast), 5 hours (pre-lunch), 11 hours (pre-dinner) after morning meal on Day 0 (Baseline); pre-morning dose (pre-breakfast), 5 hours (pre-lunch), 11 hours (pre-dinner) post-morning dose on Day 7Population: PD analysis population included all randomized participants who received at least 1 dose of study medication and had both a baseline and a post-baseline assessment for at least 1 PD parameter in at least 1 period.
Time-matched change from baseline in pre-meal serum C-peptide on Day 7 of each period was analyzed. Pre-meal C-peptide levels therefore, pre-breakfast, pre-lunch, and pre-dinner were analyzed.
Outcome measures
| Measure |
PF--04937319 250 mg
n=12 Participants
All participants who received PF-04937319 250 mg orally per day in 2 divided doses (split dose regimen of 150 mg with morning meal and 100 mg with afternoon at approximately 5 hours of interval) for 7 days in either second or third intervention period.
|
Placebo
n=12 Participants
All participants who received placebo matched to PF-04937319 administered orally with morning meal and with afternoon meal for 7 days in either first, second or third intervention period.
|
PF--04937319 100 mg
n=12 Participants
All participants who received PF-04937319 100 mg orally per day in 2 divided doses (split dose regimen of 50 mg with morning meal and 50 mg with afternoon meal at approximately 5 hours of interval) for 7 days in either first or second intervention period.
|
|---|---|---|---|
|
Change From Baseline in Pre-Meal C-Peptide at Day 7
Pre-breakfast: Baseline
|
1.90 ng/mL
Standard Deviation 0.663
|
1.73 ng/mL
Standard Deviation 0.475
|
1.68 ng/mL
Standard Deviation 0.432
|
|
Change From Baseline in Pre-Meal C-Peptide at Day 7
Pre-breakfast: Change at Day 7
|
-0.38 ng/mL
Standard Deviation 0.325
|
-0.14 ng/mL
Standard Deviation 0.358
|
-0.38 ng/mL
Standard Deviation 0.374
|
|
Change From Baseline in Pre-Meal C-Peptide at Day 7
Pre-lunch: Baseline
|
2.18 ng/mL
Standard Deviation 0.666
|
2.28 ng/mL
Standard Deviation 0.845
|
2.35 ng/mL
Standard Deviation 0.674
|
|
Change From Baseline in Pre-Meal C-Peptide at Day 7
Pre-lunch: Change at Day 7
|
0.97 ng/mL
Standard Deviation 0.676
|
0.84 ng/mL
Standard Deviation 0.904
|
0.65 ng/mL
Standard Deviation 0.521
|
|
Change From Baseline in Pre-Meal C-Peptide at Day 7
Pre-dinner: Baseline
|
2.93 ng/mL
Standard Deviation 0.936
|
2.77 ng/mL
Standard Deviation 0.951
|
2.93 ng/mL
Standard Deviation 0.713
|
|
Change From Baseline in Pre-Meal C-Peptide at Day 7
Pre-dinner: Change at Day 7
|
-0.52 ng/mL
Standard Deviation 1.079
|
-0.16 ng/mL
Standard Deviation 0.608
|
-0.64 ng/mL
Standard Deviation 0.462
|
Adverse Events
PF--04937319 100 mg
PF--04937319 250 mg
Placebo
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
PF--04937319 100 mg
n=12 participants at risk
All participants who received PF-04937319 100 mg orally per day in 2 divided doses (split dose regimen of 50 mg with morning meal and 50 mg with afternoon meal at approximately 5 hours of interval) for 7 days in either first or second intervention period.
|
PF--04937319 250 mg
n=12 participants at risk
All participants who received PF-04937319 250 mg orally per day in 2 divided doses (split dose regimen of 150 mg with morning meal and 100 mg with afternoon at approximately 5 hours of interval) for 7 days in either second or third intervention period.
|
Placebo
n=12 participants at risk
All participants who received placebo matched to PF-04937319 administered orally with morning meal and with afternoon meal for 7 days in either first, second or third intervention period.
|
|---|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/12
|
0.00%
0/12
|
8.3%
1/12
|
|
Investigations
Blood uric acid increased
|
0.00%
0/12
|
8.3%
1/12
|
0.00%
0/12
|
|
Investigations
Haemoglobin decreased
|
0.00%
0/12
|
8.3%
1/12
|
0.00%
0/12
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
8.3%
1/12
|
33.3%
4/12
|
0.00%
0/12
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
- Publication restrictions are in place
Restriction type: OTHER