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Study To Compare Single Dose Of Three Modified Release Formulations Of PF-04937319 With Immediate Release Material-Sparing-Tablet (IR MST) Formulation Previously Studied In Adults With Type 2 Diabetes Mellitus.

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ClinicalTrials.gov Identifier: NCT02206607
Recruitment Status : Completed
First Posted : August 1, 2014
Results First Posted : March 4, 2016
Last Update Posted : March 4, 2016
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: None (Open Label);   Primary Purpose: Basic Science
Condition Type 2 Diabetes Mellitus
Interventions Drug: PF-04937319 IR MST
Drug: PF-04937319 MR 1
Drug: PF-04937319 MR 2
Drug: PF-04937319 MR 3
Enrollment 39
Recruitment Details  
Pre-assignment Details Prior to being enrolled in the 4 period crossover, participants were required to complete an open-label, sponsor-provided metformin period. 42 participants started the metformin period and of those 42 participants, 39 were enrolled in the 4 period crossover and received at least 1 dose PF-04937319.
Arm/Group Title Metformin Run-In Sequence ADBC: PF-04937319 150+100 mg IR First Sequence BACD: PF-04937319 250 mg MR1 First Sequence CBDA: PF-04937319 300 mg MR2 First Sequence DCAB: PF-04937319 330 mg MR3 First
Hide Arm/Group Description 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 sequences. Participants received immediate-release material sparing tablet (IR MST) administered orally at 150 mg with morning meal and 100 mg with lunch, followed by PF-04937319 modified-release formulation #3 (MR3) 330 mg, followed by PF-04937319 modified-release formulation #1 (MR1) 250 mg, followed by PF-04937319 modified-release formulation #2 (MR2) 300 mg. There was a 5 to 10-day washout between dosing across the 4 regimens. Participants received PF-04937319 MR1 250 mg, followed by PF-04937319 150+100 mg IR, followed by PF-04937319 300 mg MR2, followed by PF-04937319 330 mg MR3. There was a 5 to 10-day washout between dosing across the 4 regimens. Participants received PF-04937319 300 mg MR2, followed by PF-04937319 250 mg MR1, followed by PF-04937319 330 mg MR3, followed by PF-04937319 150+100 mg IR. There was a 5 to 10-day washout between dosing across the 4 regimens. Participants received PF-04937319 330 mg MR3, followed by PF-04937319 300 mg MR2, followed by PF-04937319 150+100 mg IR, followed by PF-04937319 250 mg MR1. There was a 5 to 10-day washout between dosing across the 4 regimens.
Period Title: Open-Label Run-In
Started 42 0 0 0 0
Completed 39 0 0 0 0
Not Completed 3 0 0 0 0
Reason Not Completed
Withdrawal by Subject             3             0             0             0             0
Period Title: First Intervention Period
Started 0 9 9 11 10
Completed 0 9 9 11 10
Not Completed 0 0 0 0 0
Period Title: First Washout Period 5 to 10 Days
Started 0 9 9 11 10
Completed 0 9 9 11 10
Not Completed 0 0 0 0 0
Period Title: Second Intervention Period
Started 0 9 9 11 10
Completed 0 9 9 10 10
Not Completed 0 0 0 1 0
Reason Not Completed
Insufficient Clinical Response             0             0             0             1             0
Period Title: Second Washout Period 5 to 10 Days
Started 0 9 9 10 10
Completed 0 9 9 10 10
Not Completed 0 0 0 0 0
Period Title: Third Intervention Period
Started 0 9 9 10 10
Completed 0 9 9 10 10
Not Completed 0 0 0 0 0
Period Title: Third Washout Period 5 to 10 Days
Started 0 9 9 10 10
Completed 0 9 9 10 10
Not Completed 0 0 0 0 0
Period Title: Fourth Intervention Period
Started 0 9 9 10 10
Completed 0 9 9 10 10
Not Completed 0 0 0 0 0
Arm/Group Title All Participants
Hide Arm/Group Description Participants received at least 1 dose of PF-04937319.
Overall Number of Baseline Participants 39
Hide Baseline Analysis Population Description
The baseline analysis population included all participants who received at least 1 dose of study treatment (PF-04937319).
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 39 participants
57.7  (7.1)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 39 participants
Female
19
  48.7%
Male
20
  51.3%
1.Primary Outcome
Title Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUCinf]
Hide Description AUCinf is the area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time.
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title PF-04937319 150+100 mg IR PF-04937319 250 mg MR1 PF-04937319 300 mg MR2 PF-04937319 330 mg MR3
Hide Arm/Group Description:
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.
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.
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.
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.
Overall Number of Participants Analyzed 38 31 37 36
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nanogram*hour/milliliter (ng*hr/mL)
10690
(26%)
3187
(59%)
2725
(35%)
3430
(37%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection PF-04937319 150+100 mg IR, PF-04937319 250 mg MR1
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Geometric Mean Ratio MR1/IR
Estimated Value 31.27
Confidence Interval (2-Sided) 90%
28.09 to 34.80
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection PF-04937319 150+100 mg IR, PF-04937319 300 mg MR2
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Geometric Mean Ratio MR2/IR
Estimated Value 25.56
Confidence Interval (2-Sided) 90%
23.11 to 28.27
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection PF-04937319 150+100 mg IR, PF-04937319 330 mg MR3
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Geometric Mean Ratio MR3/IR
Estimated Value 32.04
Confidence Interval (2-Sided) 90%
28.93 to 35.49
Estimation Comments [Not Specified]
2.Primary Outcome
Title Change From Reference in Weighted-Mean-Daily-Glucose (WMDG) on Day 1
Hide Description MWG was calculated as the area under the curve (AUC) for the full 24 hours expressed.
Time Frame 0 (pre-dose) and 1, 2, 3, 4, 5, 6, 7, 8, 11, 12.5, 14, 16, 20, and 24 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title PF-04937319 150+100 mg IR PF-04937319 250 mg MR1 PF-04937319 300 mg MR2 PF-04937319 330 mg MR3
Hide Arm/Group Description:
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.
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.
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.
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.
Overall Number of Participants Analyzed 36 36 36 36
Mean (Standard Deviation)
Unit of Measure: milligrams per deciliter (mg/dL)
Observed (n=36,33,32,35) 159.47  (42.949) 176.24  (42.648) 170.85  (38.928) 180.47  (50.099)
Change From Reference (36,33,32,35) NA [1]   (NA) 15.55  (19.358) 15.96  (17.122) 20.15  (20.005)
[1]
No measure type or method of dispersion was calculated, as the 'PF-04937319 150+100 mg IR' arm is the Reference.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection PF-04937319 150+100 mg IR, PF-04937319 250 mg MR1
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.0000
Comments 1-sided p-value
Method Mixed Models Analysis
Comments Treatment, period, sequence as fixed effects and subjects-within-sequence as random effects.
Method of Estimation Estimation Parameter Least Square Mean
Estimated Value 15.72
Confidence Interval (2-Sided) 80%
11.39 to 20.06
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.357
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection PF-04937319 150+100 mg IR, PF-04937319 300 mg MR2
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.000
Comments 1-sided p-value
Method Mixed Models Analysis
Comments Treatment, period, sequence as fixed effects and subjects-within-sequence as random effects.
Method of Estimation Estimation Parameter Least Square Mean
Estimated Value 16.31
Confidence Interval (2-Sided) 80%
11.93 to 20.70
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.399
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection PF-04937319 150+100 mg IR, PF-04937319 330 mg MR3
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.0000
Comments 1-sided p-value
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean
Estimated Value 20.38
Confidence Interval (2-Sided) 80%
16.13 to 24.62
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.291
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Maximum Observed PF-04937319 Plasma Concentration (Cmax)
Hide Description [Not Specified]
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title PF-04937319 150+100 mg IR PF-04937319 250 mg MR1 PF-04937319 300 mg MR2 PF-04937319 330 mg MR3
Hide Arm/Group Description:
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.
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.
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.
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.
Overall Number of Participants Analyzed 38 39 39 38
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
641.2
(22%)
161.8
(37%)
171.3
(24%)
236.2
(24%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection PF-04937319 150+100 mg IR, PF-04937319 250 mg MR1
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Geometric Mean Ratio MR1/IR
Estimated Value 25.21
Confidence Interval (2-Sided) 90%
23.28 to 27.31
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection PF-04937319 150+100 mg IR, PF-04937319 300 mg MR2
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Geometric Mean Ratio MR2/IR
Estimated Value 26.38
Confidence Interval (2-Sided) 90%
24.36 to 28.57
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection PF-04937319 150+100 mg IR, PF-04937319 330 mg MR3
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Geometric Mean Ratio MR3/IR
Estimated Value 36.94
Confidence Interval (2-Sided) 90%
34.09 to 40.02
Estimation Comments [Not Specified]
4.Secondary Outcome
Title PF-04937319 Plasma Concentration at 5 Hours After Morning Dose (C5)
Hide Description [Not Specified]
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title PF-04937319 150+100 mg IR PF-04937319 250 mg MR1 PF-04937319 300 mg MR2 PF-04937319 330 mg MR3
Hide Arm/Group Description:
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.
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.
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.
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.
Overall Number of Participants Analyzed 38 39 39 38
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
413.2
(26%)
124.3
(43%)
154.3
(29%)
202.1
(30%)
5.Secondary Outcome
Title PF-04937319 Plasma Concentration at 16 Hours After Morning Dose (C16)
Hide Description [Not Specified]
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title PF-04937319 150+100 mg IR PF-04937319 250 mg MR1 PF-04937319 300 mg MR2 PF-04937319 330 mg MR3
Hide Arm/Group Description:
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.
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.
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.
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.
Overall Number of Participants Analyzed 38 39 39 38
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
324.7
(34%)
74.49
(57%)
58.88
(37%)
77.92
(37%)
6.Secondary Outcome
Title PF-04937319 Plasma Concentration at 24 Hours After Morning Dose (C24)
Hide Description [Not Specified]
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title PF-04937319 150+100 mg IR PF-04937319 250 mg MR1 PF-04937319 300 mg MR2 PF-04937319 330 mg MR3
Hide Arm/Group Description:
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.
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.
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.
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.
Overall Number of Participants Analyzed 38 39 39 38
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/dL
171.1
(37%)
56.04
(64%)
39.38
(52%)
48.17
(47%)
7.Secondary Outcome
Title Ratio of Maximum to Approximate Trough PF-04937319 Concentration (Cmax/C24)
Hide Description 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.
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title PF-04937319 150+100 mg IR PF-04937319 250 mg MR1 PF-04937319 300 mg MR2 PF-04937319 330 mg MR3
Hide Arm/Group Description:
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.
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.
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.
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.
Overall Number of Participants Analyzed 38 39 39 38
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ratio
3.748
(33%)
2.887
(49%)
4.350
(48%)
4.903
(43%)
8.Secondary Outcome
Title Time to Reach Maximum Observed PF-04937319 Plasma Concentration (Tmax)
Hide Description [Not Specified]
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title PF-04937319 150+100 mg IR PF-04937319 250 mg MR1 PF-04937319 300 mg MR2 PF-04937319 330 mg MR3
Hide Arm/Group Description:
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.
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.
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.
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.
Overall Number of Participants Analyzed 38 39 39 38
Median (Full Range)
Unit of Measure: hours
8.00
(3.00 to 15.2)
6.00
(4.00 to 48.0)
5.00
(1.00 to 7.07)
5.00
(3.00 to 7.00)
9.Secondary Outcome
Title Area Under the Curve From Time Zero to Last Quantifiable PF-04937319 Concentration (AUClast)
Hide Description Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title PF-04937319 150+100 mg IR PF-04937319 250 mg MR1 PF-04937319 300 mg MR2 PF-04937319 330 mg MR3
Hide Arm/Group Description:
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.
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.
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.
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.
Overall Number of Participants Analyzed 38 39 39 38
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*hr/mL
10560
(26%)
3287
(55%)
2644
(34%)
3369
(34%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection PF-04937319 150+100 mg IR, PF-04937319 250 mg MR1
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Geometric Mean Ratio MR1/IR
Estimated Value 31.06
Confidence Interval (2-Sided) 90%
28.28 to 34.10
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection PF-04937319 150+100 mg IR, PF-04937319 300 mg MR2
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Geometric Mean Ratio MR2/IR
Estimated Value 24.96
Confidence Interval (2-Sided) 90%
22.73 to 27.40
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection PF-04937319 150+100 mg IR, PF-04937319 330 mg MR3
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Geometric Mean Ratio MR3/IR
Estimated Value 31.69
Confidence Interval (2-Sided) 90%
28.86 to 34.81
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Terminal Elimination Half-Life (t1/2)
Hide Description t1/2 is the time measured for the plasma concentration to decrease by one half.
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title PF-04937319 150+100 mg IR PF-04937319 250 mg MR1 PF-04937319 300 mg MR2 PF-04937319 330 mg MR3
Hide Arm/Group Description:
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.
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.
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.
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.
Overall Number of Participants Analyzed 38 31 37 36
Mean (Standard Deviation)
Unit of Measure: hour
8.648  (2.7801) 12.10  (5.5922) 13.52  (6.9657) 12.62  (6.1783)
11.Secondary Outcome
Title Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)
Hide Description 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.
Time Frame Baseline up to 28 days after last study drug administration in Period 4
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis population included all participants who received at least 1 dose of open-label, sponsor-provided metformin.
Arm/Group Title Metformin Run-In PF-04937319 150+100 mg IR PF-04937319 250 mg MR1 PF-04937319 300 mg MR2 PF-04937319 330 mg MR3
Hide Arm/Group Description:
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.
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.
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.
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.
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.
Overall Number of Participants Analyzed 42 38 39 39 38
Measure Type: Number
Unit of Measure: participants
AEs 2 16 11 16 10
SAEs 0 0 0 0 0
Time Frame Baseline up to 28 days after last study drug administration in Period 4
Adverse Event Reporting Description The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
 
Arm/Group Title Metformin Run-In PF-04937319 150+100 mg IR PF-04937319 250 mg MR1 PF-04937319 300 mg MR2 PF-04937319 330 mg MR3
Hide Arm/Group Description 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. 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. 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. 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. 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.
All-Cause Mortality
Metformin Run-In PF-04937319 150+100 mg IR PF-04937319 250 mg MR1 PF-04937319 300 mg MR2 PF-04937319 330 mg MR3
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Metformin Run-In PF-04937319 150+100 mg IR PF-04937319 250 mg MR1 PF-04937319 300 mg MR2 PF-04937319 330 mg MR3
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/42 (0.00%)   0/38 (0.00%)   0/39 (0.00%)   0/39 (0.00%)   0/38 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Metformin Run-In PF-04937319 150+100 mg IR PF-04937319 250 mg MR1 PF-04937319 300 mg MR2 PF-04937319 330 mg MR3
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/42 (2.38%)   11/38 (28.95%)   6/39 (15.38%)   10/39 (25.64%)   5/38 (13.16%) 
Gastrointestinal disorders           
Diarrhoea * 1  0/42 (0.00%)  0/38 (0.00%)  0/39 (0.00%)  2/39 (5.13%)  2/38 (5.26%) 
Toothache * 1  0/42 (0.00%)  2/38 (5.26%)  2/39 (5.13%)  1/39 (2.56%)  1/38 (2.63%) 
Infections and infestations           
Upper respiratory tract infection * 1  0/42 (0.00%)  0/38 (0.00%)  1/39 (2.56%)  2/39 (5.13%)  0/38 (0.00%) 
Metabolism and nutrition disorders           
Hypoglycaemia * 1  0/42 (0.00%)  4/38 (10.53%)  0/39 (0.00%)  1/39 (2.56%)  1/38 (2.63%) 
Nervous system disorders           
Headache * 1  1/42 (2.38%)  7/38 (18.42%)  2/39 (5.13%)  3/39 (7.69%)  2/38 (5.26%) 
Respiratory, thoracic and mediastinal disorders           
Sinus congestion * 1  0/42 (0.00%)  0/38 (0.00%)  1/39 (2.56%)  2/39 (5.13%)  0/38 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 17.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
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Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
Phone: 1-800-718-1021
EMail: ClinicalTrials.gov_Inquiries@pfizer.com
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT02206607     History of Changes
Other Study ID Numbers: B1621015
First Submitted: July 30, 2014
First Posted: August 1, 2014
Results First Submitted: December 14, 2015
Results First Posted: March 4, 2016
Last Update Posted: March 4, 2016