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Clinical Trial Results:
A 16-Week, Phase 2b, Randomized, Double-Blind, Placebo Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of Twice Daily PF-06882961 Administration in Adults With Type 2 Diabetes Mellitus Inadequately Controlled on Metformin or Diet and Exercise

Summary
EudraCT number	2019-000218-12
Trial protocol	SK HU PL BG
Global end of trial date	07 Jul 2021

Results information
Results version number	v1(current)
This version publication date	18 Jun 2022
First version publication date	18 Jun 2022
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

C3421005

ISRCTN number

US NCT number

NCT03985293

WHO universal trial number (UTN)

Sponsor organisation name

Pfizer Inc.

Sponsor organisation address

235 E 42nd Street, New York, United States, NY 10017

Public contact

Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., +1 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com

Scientific contact

Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., +1 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

07 Jul 2021

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

07 Jul 2021

Was the trial ended prematurely?

Main objective of the trial

To compare the effect of multiple dose levels of danuglipron (PF-06882961) versus placebo on glycated hemoglobin (HbA1c) in subjects with type 2 diabetes mellitus (T2DM) on stable doses of metformin and/or diet and exercise.

Protection of trial subjects

The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Conference for Harmonisation (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trials subjects were followed.

Background therapy

Evidence for comparator

Actual start date of recruitment

07 Jul 2020

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Bulgaria: 6

Country: Number of subjects enrolled

Canada: 29

Country: Number of subjects enrolled

Hungary: 72

Country: Number of subjects enrolled

Korea, Democratic People's Republic of: 10

Country: Number of subjects enrolled

Poland: 36

Country: Number of subjects enrolled

Slovakia: 36

Country: Number of subjects enrolled

Taiwan: 14

Country: Number of subjects enrolled

United States: 208

Worldwide total number of subjects

411

EEA total number of subjects

150

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

291

From 65 to 84 years

120

85 years and over

Subject disposition

Top of page

Recruitment details

Screening details

A total of 859 subjects were screened in the study, of which, 412 subjects were randomized, and 411 subjects were treated with PF-06882961 (Danuglipron)/placebo; 1 subject randomized to the PF-06882961 120 mg BID group was not treated.

Period 1 title

DOUBLE-BLIND TREATMENT

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

Placebo

Arm description

Placebo matched to PF-06882961 was administered orally twice daily (BID) with food for a total of 16 weeks, followed by an approximate 4-week follow-up.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Placebo matched to PF-06882961 was administered orally twice daily (BID) with food for a total of 16 weeks.

PF-06882961 2.5mg BID

Arm description

PF-06882961 2.5 mg was administered orally twice daily (BID) with food for a total of 16 weeks, followed by an approximate 4-week follow-up.

Arm type

Experimental

Investigational medicinal product name

danuglipron

Investigational medicinal product code

PF-06882961

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

PF-06882961 2.5 mg was administered orally twice daily (BID) with food for a total of 16 weeks.

PF-06882961 10mg BID

Arm description

PF-06882961 10 mg was administered orally twice daily (BID) with food for a total of 16 weeks, followed by an approximate 4-week follow-up.

Arm type

Experimental

Investigational medicinal product name

danuglipron

Investigational medicinal product code

PF-06882961

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

PF-06882961 10 mg was administered orally twice daily (BID) with food for a total of 16 weeks.

PF-06882961 40mg BID

Arm description

PF-06882961 40 mg was administered orally twice daily (BID) with food for a total of 16 weeks, followed by an approximate 4-week follow-up. Titration was implemented.

Arm type

Experimental

Investigational medicinal product name

danuglipron

Investigational medicinal product code

PF-06882961

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

PF-06882961 40 mg was administered orally twice daily (BID) with food for a total of 16 weeks. Titration was implemented.

PF-06882961 80mg BID

Arm description

PF-06882961 80 mg was administered orally twice daily (BID) with food for a total of 16 weeks, followed by an approximate 4-week follow-up. Titration was implemented.

Arm type

Experimental

Investigational medicinal product name

danuglipron

Investigational medicinal product code

PF-06882961

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

PF-06882961 80 mg was administered orally twice daily (BID) with food for a total of 16 weeks. Titration was implemented.

PF-06882961 120mg BID

Arm description

PF-06882961 120 mg was administered orally twice daily (BID) with food for a total of 16 weeks, followed by an approximate 4-week follow-up. Titration was implemented.

Arm type

Experimental

Investigational medicinal product name

danuglipron

Investigational medicinal product code

PF-06882961

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

PF-06882961 120 mg was administered orally twice daily (BID) with food for a total of 16 weeks. Titration was implemented.

Number of subjects in period 1	Placebo	PF-06882961 2.5mg BID	PF-06882961 10mg BID	PF-06882961 40mg BID	PF-06882961 80mg BID	PF-06882961 120mg BID
Started	66	68	68	71	67	71
Completed	57	54	63	57	47	38
Not completed	9	14	5	14	20	33
Consent withdrawn by subject	-	4	2	-	1	7
Adverse event, non-fatal	5	2	3	8	15	24
Unspecified	1	2	-	2	1	-
Lost to follow-up	1	3	-	3	3	1
No Longer Meets Eligibility Criteria	1	1	-	1	-	-
Protocol deviation	1	2	-	-	-	1

Period 2 title

FOLLOW-UP

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

Placebo

Arm description

Placebo matched to PF-06882961 was administered orally twice daily (BID) with food for a total of 16 weeks.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Placebo matched to PF-06882961 was administered orally twice daily (BID) with food for a total of 16 weeks.

PF-06882961 2.5mg BID

Arm description

PF-06882961 2.5 mg was administered orally twice daily (BID) with food for a total of 16 weeks.

Arm type

Experimental

Investigational medicinal product name

danuglipron

Investigational medicinal product code

PF-06882961

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

PF-06882961 2.5 mg was administered orally twice daily (BID) with food for a total of 16 weeks.

PF-06882961 10mg BID

Arm description

PF-06882961 10 mg was administered orally twice daily (BID) with food for a total of 16 weeks.

Arm type

Experimental

Investigational medicinal product name

danuglipron

Investigational medicinal product code

PF-06882961

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

PF-06882961 10 mg was administered orally twice daily (BID) with food for a total of 16 weeks.

PF-06882961 40mg BID

Arm description

PF-06882961 40 mg was administered orally twice daily (BID) with food for a total of 16 weeks. Titration was implemented.

Arm type

Experimental

Investigational medicinal product name

danuglipron

Investigational medicinal product code

PF-06882961

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

PF-06882961 40 mg was administered orally twice daily (BID) with food for a total of 16 weeks. Titration was implemented.

PF-06882961 80mg BID

Arm description

PF-06882961 80 mg was administered orally twice daily (BID) with food for a total of 16 weeks. Titration was implemented.

Arm type

Experimental

Investigational medicinal product name

danuglipron

Investigational medicinal product code

PF-06882961

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

PF-06882961 80 mg was administered orally twice daily (BID) with food for a total of 16 weeks. Titration was implemented.

PF-06882961 120mg BID

Arm description

PF-06882961 120 mg was administered orally twice daily (BID) with food for a total of 16 weeks. Titration was implemented.

Arm type

Experimental

Investigational medicinal product name

danuglipron

Investigational medicinal product code

PF-06882961

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

PF-06882961 120 mg was administered orally twice daily (BID) with food for a total of 16 weeks. Titration was implemented.

Number of subjects in period 2	Placebo	PF-06882961 2.5mg BID	PF-06882961 10mg BID	PF-06882961 40mg BID	PF-06882961 80mg BID	PF-06882961 120mg BID
Started	57	54	63	57	47	38
Completed	57	54	62	57	47	38
Not completed	0	0	1	0	0	0
Lost to follow-up	-	-	1	-	-	-

Baseline characteristics

Top of page

Reporting group title

Placebo

Reporting group description

Placebo matched to PF-06882961 was administered orally twice daily (BID) with food for a total of 16 weeks, followed by an approximate 4-week follow-up.

Reporting group title

PF-06882961 2.5mg BID

Reporting group description

PF-06882961 2.5 mg was administered orally twice daily (BID) with food for a total of 16 weeks, followed by an approximate 4-week follow-up.

Reporting group title

PF-06882961 10mg BID

Reporting group description

PF-06882961 10 mg was administered orally twice daily (BID) with food for a total of 16 weeks, followed by an approximate 4-week follow-up.

Reporting group title

PF-06882961 40mg BID

Reporting group description

PF-06882961 40 mg was administered orally twice daily (BID) with food for a total of 16 weeks, followed by an approximate 4-week follow-up. Titration was implemented.

Reporting group title

PF-06882961 80mg BID

Reporting group description

PF-06882961 80 mg was administered orally twice daily (BID) with food for a total of 16 weeks, followed by an approximate 4-week follow-up. Titration was implemented.

Reporting group title

PF-06882961 120mg BID

Reporting group description

PF-06882961 120 mg was administered orally twice daily (BID) with food for a total of 16 weeks, followed by an approximate 4-week follow-up. Titration was implemented.

Reporting group values	Placebo	PF-06882961 2.5mg BID	PF-06882961 10mg BID	PF-06882961 40mg BID	PF-06882961 80mg BID	PF-06882961 120mg BID	Total
Number of subjects	66	68	68	71	67	71	411
Age Categorical
Units: Subjects
Adults (18-64 years)	50	47	48	47	47	52	291
Adults (65-84 years)	16	21	20	24	20	19	120
Age Continuous
Units: Years
arithmetic mean (standard deviation)	57.9 ± 10.27	58.9 ± 9.30	58.1 ± 9.43	59.6 ± 8.58	58.4 ± 9.18	58.8 ± 9.43	-
Sex: Female, Male
Units: Subjects
Male	33	38	35	34	35	34	209
Female	33	30	33	37	32	37	202
Race/Ethnicity, Customized
Units: Subjects
White	57	57	53	58	59	59	343
Black or African American	2	4	10	6	1	4	27
Asian	5	7	4	6	6	7	35
Native Hawaiian or Other Pacific Islander	1	0	0	0	0	1	2
Not reported	1	0	1	1	1	0	4
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	24	22	17	24	23	18	128
Not Hispanic or Latino	42	46	50	47	44	52	281
Unknown or Not Reported	0	0	1	0	0	1	2

End points

Top of page

Reporting group title

Placebo

Reporting group description

Placebo matched to PF-06882961 was administered orally twice daily (BID) with food for a total of 16 weeks, followed by an approximate 4-week follow-up.

Reporting group title

PF-06882961 2.5mg BID

Reporting group description

PF-06882961 2.5 mg was administered orally twice daily (BID) with food for a total of 16 weeks, followed by an approximate 4-week follow-up.

Reporting group title

PF-06882961 10mg BID

Reporting group description

PF-06882961 10 mg was administered orally twice daily (BID) with food for a total of 16 weeks, followed by an approximate 4-week follow-up.

Reporting group title

PF-06882961 40mg BID

Reporting group description

PF-06882961 40 mg was administered orally twice daily (BID) with food for a total of 16 weeks, followed by an approximate 4-week follow-up. Titration was implemented.

Reporting group title

PF-06882961 80mg BID

Reporting group description

PF-06882961 80 mg was administered orally twice daily (BID) with food for a total of 16 weeks, followed by an approximate 4-week follow-up. Titration was implemented.

Reporting group title

PF-06882961 120mg BID

Reporting group description

PF-06882961 120 mg was administered orally twice daily (BID) with food for a total of 16 weeks, followed by an approximate 4-week follow-up. Titration was implemented.

Reporting group title

Placebo

Reporting group description

Placebo matched to PF-06882961 was administered orally twice daily (BID) with food for a total of 16 weeks.

Reporting group title

PF-06882961 2.5mg BID

Reporting group description

PF-06882961 2.5 mg was administered orally twice daily (BID) with food for a total of 16 weeks.

Reporting group title

PF-06882961 10mg BID

Reporting group description

PF-06882961 10 mg was administered orally twice daily (BID) with food for a total of 16 weeks.

Reporting group title

PF-06882961 40mg BID

Reporting group description

PF-06882961 40 mg was administered orally twice daily (BID) with food for a total of 16 weeks. Titration was implemented.

Reporting group title

PF-06882961 80mg BID

Reporting group description

PF-06882961 80 mg was administered orally twice daily (BID) with food for a total of 16 weeks. Titration was implemented.

Reporting group title

PF-06882961 120mg BID

Reporting group description

PF-06882961 120 mg was administered orally twice daily (BID) with food for a total of 16 weeks. Titration was implemented.

Primary: Change From Baseline in Glycated Hemoglobin (HbA1c) at Week 16

Top of page

End point title

Change From Baseline in Glycated Hemoglobin (HbA1c) at Week 16

End point description

HbA1c can be used as a diagnostic test for diabetes. The target HbA1c level for people with diabetes is usually less than 7%. Overall number of subjects analyzed included all subjects randomly assigned to study treatment and who took at least 1 dose of study treatment.

End point type

Primary

End point timeframe

Baseline, Week 16

End point values	Placebo	PF-06882961 2.5mg BID	PF-06882961 10mg BID	PF-06882961 40mg BID	PF-06882961 80mg BID	PF-06882961 120mg BID
Number of subjects analysed	52	52	61	55	46	38
Units: Percent
least squares mean (confidence interval 90%)	-0.02 (-0.22 to 0.19)	-0.49 (-0.70 to -0.28)	-0.91 (-1.11 to -0.72)	-1.03 (-1.23 to -0.83)	-0.96 (-1.18 to -0.74)	-1.18 (-1.41 to -0.95)

PF-06882961 2.5mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 2.5mg BID

Number of subjects included in analysis

104

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0071

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-0.47

Confidence interval

level

90%

sides

2-sided

lower limit

-0.76

upper limit

-0.18

PF-06882961 10mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 10mg BID

Number of subjects included in analysis

113

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-0.9

Confidence interval

level

90%

sides

2-sided

lower limit

-1.18

upper limit

-0.62

PF-06882961 40mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 40mg BID

Number of subjects included in analysis

107

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-1.01

Confidence interval

level

90%

sides

2-sided

lower limit

-1.3

upper limit

-0.73

PF-06882961 80mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 80mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-0.94

Confidence interval

level

90%

sides

2-sided

lower limit

-1.24

upper limit

-0.65

PF-06882961 120mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 120mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-1.16

Confidence interval

level

90%

sides

2-sided

lower limit

-1.47

upper limit

-0.86

Secondary: Percentage of Subjects Achieving Less Than (<) 7% Glycated Hemoglobin (HbA1c) Levels

Top of page

End point title

Percentage of Subjects Achieving Less Than (<) 7% Glycated Hemoglobin (HbA1c) Levels

End point description

End point type

Secondary

End point timeframe

Baseline, Week 16

End point values	Placebo	PF-06882961 2.5mg BID	PF-06882961 10mg BID	PF-06882961 40mg BID	PF-06882961 80mg BID	PF-06882961 120mg BID
Number of subjects analysed	52	52	61	55	46	38
Units: Percentage of Subjects
number (not applicable)	7.7	30.8	54.1	58.2	65.2	60.5

PF-06882961 2.5mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 2.5mg BID

Number of subjects included in analysis

104

Analysis specification

Pre-specified

Analysis type

superiority

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

5.11

Confidence interval

level

90%

sides

2-sided

lower limit

1.84

upper limit

14.18

PF-06882961 10mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 10mg BID

Number of subjects included in analysis

113

Analysis specification

Pre-specified

Analysis type

superiority

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

16.85

Confidence interval

level

90%

sides

2-sided

lower limit

6.18

upper limit

45.93

PF-06882961 40mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 40mg BID

Number of subjects included in analysis

107

Analysis specification

Pre-specified

Analysis type

superiority

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

18.79

Confidence interval

level

90%

sides

2-sided

lower limit

7.03

upper limit

50.21

PF-06882961 80mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 80mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

23.97

Confidence interval

level

90%

sides

2-sided

lower limit

8.66

upper limit

66.39

PF-06882961 120mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 120mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

24.46

Confidence interval

level

90%

sides

2-sided

lower limit

8.72

upper limit

68.57

Secondary: Change From Baseline in Glycated Hemoglobin (HbA1c) at Week 2

Top of page

End point title

Change From Baseline in Glycated Hemoglobin (HbA1c) at Week 2

End point description

End point type

Secondary

End point timeframe

Baseline, Week 2

End point values	Placebo	PF-06882961 2.5mg BID	PF-06882961 10mg BID	PF-06882961 40mg BID	PF-06882961 80mg BID	PF-06882961 120mg BID
Number of subjects analysed	65	64	67	67	63	69
Units: Percent
least squares mean (confidence interval 90%)	-0.09 (-0.17 to -0.01)	-0.18 (-0.26 to -0.09)	-0.31 (-0.39 to -0.23)	-0.29 (-0.37 to -0.21)	-0.33 (-0.41 to -0.24)	-0.35 (-0.43 to -0.28)

PF-06882961 2.5mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 2.5mg BID

Number of subjects included in analysis

129

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1578

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-0.09

Confidence interval

level

90%

sides

2-sided

lower limit

-0.19

upper limit

0.01

PF-06882961 10mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 10mg BID

Number of subjects included in analysis

132

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0003

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-0.22

Confidence interval

level

90%

sides

2-sided

lower limit

-0.32

upper limit

-0.12

PF-06882961 40mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 40mg BID

Number of subjects included in analysis

132

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0013

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-0.2

Confidence interval

level

90%

sides

2-sided

lower limit

-0.3

upper limit

-0.1

PF-06882961 80mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 80mg BID

Number of subjects included in analysis

128

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-0.24

Confidence interval

level

90%

sides

2-sided

lower limit

-0.34

upper limit

-0.14

PF-06882961 120mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 120mg BID

Number of subjects included in analysis

134

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-0.26

Confidence interval

level

90%

sides

2-sided

lower limit

-0.36

upper limit

-0.16

Secondary: Change From Baseline in Glycated Hemoglobin (HbA1c) at Week 4

Top of page

End point title

Change From Baseline in Glycated Hemoglobin (HbA1c) at Week 4

End point description

End point type

Secondary

End point timeframe

Baseline, Week 4

End point values	Placebo	PF-06882961 2.5mg BID	PF-06882961 10mg BID	PF-06882961 40mg BID	PF-06882961 80mg BID	PF-06882961 120mg BID
Number of subjects analysed	60	58	68	63	54	60
Units: Percent
least squares mean (confidence interval 90%)	-0.08 (-0.19 to 0.04)	-0.38 (-0.50 to -0.26)	-0.51 (-0.62 to -0.39)	-0.63 (-0.74 to -0.52)	-0.58 (-0.70 to -0.46)	-0.64 (-0.75 to -0.53)

PF-06882961 2.5mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 2.5mg BID

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0013

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-0.3

Confidence interval

level

90%

sides

2-sided

lower limit

-0.46

upper limit

-0.15

PF-06882961 10mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 10mg BID

Number of subjects included in analysis

128

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-0.43

Confidence interval

level

90%

sides

2-sided

lower limit

-0.58

upper limit

-0.28

PF-06882961 40mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 40mg BID

Number of subjects included in analysis

123

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-0.55

Confidence interval

level

90%

sides

2-sided

lower limit

-0.7

upper limit

-0.4

PF-06882961 80mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 80mg BID

Number of subjects included in analysis

114

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-0.5

Confidence interval

level

90%

sides

2-sided

lower limit

-0.66

upper limit

-0.35

PF-06882961 120mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 120mg BID

Number of subjects included in analysis

120

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-0.56

Confidence interval

level

90%

sides

2-sided

lower limit

-0.71

upper limit

-0.41

Secondary: Change From Baseline in Glycated Hemoglobin (HbA1c) at Week 6

Top of page

End point title

Change From Baseline in Glycated Hemoglobin (HbA1c) at Week 6

End point description

End point type

Secondary

End point timeframe

Baseline, Week 6

End point values	Placebo	PF-06882961 2.5mg BID	PF-06882961 10mg BID	PF-06882961 40mg BID	PF-06882961 80mg BID	PF-06882961 120mg BID
Number of subjects analysed	60	55	66	59	51	52
Units: Percent
least squares mean (confidence interval 90%)	-0.07 (-0.21 to 0.07)	-0.47 (-0.61 to -0.34)	-0.71 (-0.84 to -0.57)	-0.84 (-0.97 to -0.71)	-0.79 (-0.93 to -0.65)	-0.84 (-0.98 to -0.71)

PF-06882961 2.5mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 2.5mg BID

Number of subjects included in analysis

115

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0004

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-0.4

Confidence interval

level

90%

sides

2-sided

lower limit

-0.59

upper limit

-0.22

PF-06882961 10mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 10mg BID

Number of subjects included in analysis

126

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-0.64

Confidence interval

level

90%

sides

2-sided

lower limit

-0.81

upper limit

-0.46

PF-06882961 40mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 40mg BID

Number of subjects included in analysis

119

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-0.77

Confidence interval

level

90%

sides

2-sided

lower limit

-0.95

upper limit

-0.59

PF-06882961 80mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 80mg BID

Number of subjects included in analysis

111

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-0.72

Confidence interval

level

90%

sides

2-sided

lower limit

-0.91

upper limit

-0.53

PF-06882961 120mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 120mg BID

Number of subjects included in analysis

112

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-0.77

Confidence interval

level

90%

sides

2-sided

lower limit

-0.95

upper limit

-0.59

Secondary: Change From Baseline in Glycated Hemoglobin (HbA1c) at Week 8

Top of page

End point title

Change From Baseline in Glycated Hemoglobin (HbA1c) at Week 8

End point description

End point type

Secondary

End point timeframe

Baseline, Week 8

End point values	Placebo	PF-06882961 2.5mg BID	PF-06882961 10mg BID	PF-06882961 40mg BID	PF-06882961 80mg BID	PF-06882961 120mg BID
Number of subjects analysed	56	51	66	58	45	42
Units: Percent
least squares mean (confidence interval 90%)	-0.13 (-0.29 to 0.03)	-0.50 (-0.66 to -0.34)	-0.78 (-0.93 to -0.62)	-0.97 (-1.13 to -0.82)	-0.92 (-1.09 to -0.76)	-1.02 (-1.18 to -0.86)

PF-06882961 2.5mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 2.5mg BID

Number of subjects included in analysis

107

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0054

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-0.37

Confidence interval

level

90%

sides

2-sided

lower limit

-0.59

upper limit

-0.15

PF-06882961 10mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 10mg BID

Number of subjects included in analysis

122

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-0.65

Confidence interval

level

90%

sides

2-sided

lower limit

-0.86

upper limit

-0.44

PF-06882961 40mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 40mg BID

Number of subjects included in analysis

114

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-0.84

Confidence interval

level

90%

sides

2-sided

lower limit

-1.06

upper limit

-0.63

PF-06882961 80mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 80mg BID

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-0.8

Confidence interval

level

90%

sides

2-sided

lower limit

-1.02

upper limit

-0.57

PF-06882961 120mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 120mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-0.89

Confidence interval

level

90%

sides

2-sided

lower limit

-1.11

upper limit

-0.67

Secondary: Change From Baseline in Glycated Hemoglobin (HbA1c) at Week 12

Top of page

End point title

Change From Baseline in Glycated Hemoglobin (HbA1c) at Week 12

End point description

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	Placebo	PF-06882961 2.5mg BID	PF-06882961 10mg BID	PF-06882961 40mg BID	PF-06882961 80mg BID	PF-06882961 120mg BID
Number of subjects analysed	55	53	63	58	46	38
Units: Percent
least squares mean (confidence interval 90%)	-0.09 (-0.28 to 0.10)	-0.53 (-0.72 to -0.34)	-0.88 (-1.06 to -0.70)	-1.06 (-1.25 to -0.88)	-0.91 (-1.12 to -0.71)	-1.11 (-1.32 to -0.91)

PF-06882961 10mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 10mg BID

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-0.79

Confidence interval

level

90%

sides

2-sided

lower limit

-1.05

upper limit

-0.54

PF-06882961 2.5mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 2.5mg BID

Number of subjects included in analysis

108

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0061

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-0.44

Confidence interval

level

90%

sides

2-sided

lower limit

-0.71

upper limit

-0.18

PF-06882961 80mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 80mg BID

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-0.83

Confidence interval

level

90%

sides

2-sided

lower limit

-1.1

upper limit

-0.56

PF-06882961 40mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 40mg BID

Number of subjects included in analysis

113

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-0.98

Confidence interval

level

90%

sides

2-sided

lower limit

-1.24

upper limit

-0.72

PF-06882961 120mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 120mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-1.03

Confidence interval

level

90%

sides

2-sided

lower limit

-1.3

upper limit

-0.75

Secondary: Change From Baseline in Fasting Plasma Glucose at Week 2

Top of page

End point title

Change From Baseline in Fasting Plasma Glucose at Week 2

End point description

The fasting plasma glucose test measures the levels of glucose (sugar) in the blood, with a normal range of 70 milligram per deciliter (mg/dL) to 99 mg/dL. Overall number of subjects analyzed included all subjects randomly assigned to study treatment and who took at least 1 dose of study treatment.

End point type

Secondary

End point timeframe

Baseline, Week 2

End point values	Placebo	PF-06882961 2.5mg BID	PF-06882961 10mg BID	PF-06882961 40mg BID	PF-06882961 80mg BID	PF-06882961 120mg BID
Number of subjects analysed	65	64	67	68	63	68
Units: mg/dL
least squares mean (confidence interval 90%)	-5.58 (-12.66 to 1.49)	-22.72 (-29.78 to -15.65)	-21.96 (-28.91 to -15.01)	-27.79 (-34.60 to -20.98)	-24.18 (-31.28 to -17.08)	-30.92 (-37.66 to -24.17)

PF-06882961 2.5mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 2.5mg BID

Number of subjects included in analysis

129

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0014

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-17.13

Confidence interval

level

90%

sides

2-sided

lower limit

-25.94

upper limit

-8.33

PF-06882961 10mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 10mg BID

Number of subjects included in analysis

132

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0021

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-16.38

Confidence interval

level

90%

sides

2-sided

lower limit

-25.08

upper limit

-7.67

PF-06882961 40mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 40mg BID

Number of subjects included in analysis

133

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-22.2

Confidence interval

level

90%

sides

2-sided

lower limit

-30.88

upper limit

-13.53

PF-06882961 80mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 80mg BID

Number of subjects included in analysis

128

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0006

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-18.59

Confidence interval

level

90%

sides

2-sided

lower limit

-27.43

upper limit

-9.76

PF-06882961 120mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 120mg BID

Number of subjects included in analysis

133

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-25.33

Confidence interval

level

90%

sides

2-sided

lower limit

-34

upper limit

-16.67

Secondary: Change From Baseline in Fasting Plasma Glucose at Week 4

Top of page

End point title

Change From Baseline in Fasting Plasma Glucose at Week 4

End point description

The fasting plasma glucose test measures the levels of glucose (sugar) in the blood, with a normal range of 70 mg/dL to 99 mg/dL. Overall number of subjects analyzed included all subjects randomly assigned to study treatment and who took at least 1 dose of study treatment.

End point type

Secondary

End point timeframe

Baseline, Week 4

End point values	Placebo	PF-06882961 2.5mg BID	PF-06882961 10mg BID	PF-06882961 40mg BID	PF-06882961 80mg BID	PF-06882961 120mg BID
Number of subjects analysed	60	58	68	62	55	60
Units: mg/dL
least squares mean (confidence interval 90%)	-5.98 (-13.62 to 1.66)	-17.77 (-25.46 to -10.09)	-24.66 (-31.98 to -17.35)	-33.42 (-40.83 to -26.00)	-33.34 (-41.25 to -25.44)	-34.06 (-41.52 to -26.00)

PF-06882961 80mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 2.5mg BID

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0468

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-11.79

Confidence interval

level

90%

sides

2-sided

lower limit

-21.55

upper limit

-2.04

PF-06882961 10mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 10mg BID

Number of subjects included in analysis

128

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0012

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-18.68

Confidence interval

level

90%

sides

2-sided

lower limit

-28.12

upper limit

-9.25

PF-06882961 40mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 40mg BID

Number of subjects included in analysis

122

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-27.44

Confidence interval

level

90%

sides

2-sided

lower limit

-37.03

upper limit

-17.85

PF-06882961 80mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 80mg BID

Number of subjects included in analysis

115

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-27.36

Confidence interval

level

90%

sides

2-sided

lower limit

-37.22

upper limit

-17.51

PF-06882961 120mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 120mg BID

Number of subjects included in analysis

120

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-28.09

Confidence interval

level

90%

sides

2-sided

lower limit

-37.72

upper limit

-18.45

Secondary: Change From Baseline in Fasting Plasma Glucose at Week 6

Top of page

End point title

Change From Baseline in Fasting Plasma Glucose at Week 6

End point description

End point type

Secondary

End point timeframe

Baseline, Week 6

End point values	Placebo	PF-06882961 2.5mg BID	PF-06882961 10mg BID	PF-06882961 40mg BID	PF-06882961 80mg BID	PF-06882961 120mg BID
Number of subjects analysed	60	55	66	60	51	53
Units: mg/dL
least squares mean (confidence interval 90%)	-0.88 (-8.62 to 6.86)	-16.78 (-24.67 to -8.89)	-26.41 (-33.88 to -18.94)	-30.89 (-38.47 to -23.30)	-28.36 (-36.51 to -20.21)	-32.65 (-40.44 to -24.87)

PF-06882961 2.5mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 2.5mg BID

Number of subjects included in analysis

115

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0091

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-15.9

Confidence interval

level

90%

sides

2-sided

lower limit

-25.9

upper limit

-5.9

PF-06882961 10mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 10mg BID

Number of subjects included in analysis

126

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-25.53

Confidence interval

level

90%

sides

2-sided

lower limit

-35.18

upper limit

-15.89

PF-06882961 40mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 40mg BID

Number of subjects included in analysis

120

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-30.01

Confidence interval

level

90%

sides

2-sided

lower limit

-39.8

upper limit

-20.21

PF-06882961 80mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 80mg BID

Number of subjects included in analysis

111

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-27.48

Confidence interval

level

90%

sides

2-sided

lower limit

-37.63

upper limit

-17.33

PF-06882961 120mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 120mg BID

Number of subjects included in analysis

113

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-31.77

Confidence interval

level

90%

sides

2-sided

lower limit

-41.77

upper limit

-21.78

Secondary: Change From Baseline in Fasting Plasma Glucose at Week 8

Top of page

End point title

Change From Baseline in Fasting Plasma Glucose at Week 8

End point description

End point type

Secondary

End point timeframe

Baseline, Week 8

End point values	Placebo	PF-06882961 2.5mg BID	PF-06882961 10mg BID	PF-06882961 40mg BID	PF-06882961 80mg BID	PF-06882961 120mg BID
Number of subjects analysed	57	53	64	58	48	42
Units: mg/dL
least squares mean (confidence interval 90%)	-9.10 (-16.80 to -1.41)	-12.73 (-20.53 to -4.93)	-26.23 (-33.57 to -18.89)	-29.74 (-37.26 to -22.23)	-33.22 (-41.36 to -25.09)	-34.31 (-42.46 to -26.16)

PF-06882961 2.5mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 2.5mg BID

Number of subjects included in analysis

110

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5449

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-3.63

Confidence interval

level

90%

sides

2-sided

lower limit

-13.51

upper limit

6.25

PF-06882961 10mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 10mg BID

Number of subjects included in analysis

121

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0031

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-17.12

Confidence interval

level

90%

sides

2-sided

lower limit

-26.62

upper limit

-7.63

PF-06882961 40mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 40mg BID

Number of subjects included in analysis

115

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0005

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-20.64

Confidence interval

level

90%

sides

2-sided

lower limit

-30.31

upper limit

-10.96

PF-06882961 80mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 80mg BID

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-24.12

Confidence interval

level

90%

sides

2-sided

lower limit

-34.2

upper limit

-14.04

PF-06882961 120mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 120mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-25.21

Confidence interval

level

90%

sides

2-sided

lower limit

-35.44

upper limit

-14.97

Secondary: Change From Baseline in Fasting Plasma Glucose at Week 12

Top of page

End point title

Change From Baseline in Fasting Plasma Glucose at Week 12

End point description

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	Placebo	PF-06882961 2.5mg BID	PF-06882961 10mg BID	PF-06882961 40mg BID	PF-06882961 80mg BID	PF-06882961 120mg BID
Number of subjects analysed	55	53	63	58	46	37
Units: mg/dL
least squares mean (confidence interval 90%)	1.21 (-7.93 to 10.35)	-6.49 (-15.70 to 2.73)	-22.56 (-31.17 to -13.95)	-32.01 (-40.89 to -23.14)	-30.45 (-40.26 to -20.64)	-32.38 (-42.83 to -21.94)

PF-06882961 2.5mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 2.5mg BID

Number of subjects included in analysis

108

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.294

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-7.7

Confidence interval

level

90%

sides

2-sided

lower limit

-19.78

upper limit

4.38

PF-06882961 10mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 10mg BID

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0008

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-23.77

Confidence interval

level

90%

sides

2-sided

lower limit

-35.37

upper limit

-12.17

PF-06882961 40mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 40mg BID

Number of subjects included in analysis

113

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-33.23

Confidence interval

level

90%

sides

2-sided

lower limit

-45.05

upper limit

-21.4

PF-06882961 80mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 80mg BID

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-31.66

Confidence interval

level

90%

sides

2-sided

lower limit

-44.14

upper limit

-19.19

PF-06882961 120mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 120mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-33.59

Confidence interval

level

90%

sides

2-sided

lower limit

-46.67

upper limit

-20.51

Secondary: Change From Baseline in Fasting Plasma Glucose at Week 16

Top of page

End point title

Change From Baseline in Fasting Plasma Glucose at Week 16

End point description

End point type

Secondary

End point timeframe

Baseline, Week 16

End point values	Placebo	PF-06882961 2.5mg BID	PF-06882961 10mg BID	PF-06882961 40mg BID	PF-06882961 80mg BID	PF-06882961 120mg BID
Number of subjects analysed	52	52	61	56	45	38
Units: mg/dL
least squares mean (confidence interval 90%)	1.31 (-7.58 to 10.20)	-12.81 (-21.71 to -3.91)	-24.53 (-32.88 to -16.18)	-30.47 (-39.06 to -21.87)	-25.71 (-35.15 to -16.26)	-31.93 (-41.73 to -22.13)

PF-06882961 2.5mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 2.5mg BID

Number of subjects included in analysis

104

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0464

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-14.12

Confidence interval

level

90%

sides

2-sided

lower limit

-25.77

upper limit

-2.47

PF-06882961 10mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 10mg BID

Number of subjects included in analysis

113

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0002

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-25.84

Confidence interval

level

90%

sides

2-sided

lower limit

-37.05

upper limit

-14.62

PF-06882961 40mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 40mg BID

Number of subjects included in analysis

108

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-31.78

Confidence interval

level

90%

sides

2-sided

lower limit

-43.2

upper limit

-20.35

PF-06882961 80mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 80mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0002

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-27.02

Confidence interval

level

90%

sides

2-sided

lower limit

-39.03

upper limit

-15.01

PF-06882961 120mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 120mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-33.24

Confidence interval

level

90%

sides

2-sided

lower limit

-45.63

upper limit

-20.84

Secondary: Change From Baseline in Body Weight at Week 2

Top of page

End point title

Change From Baseline in Body Weight at Week 2

End point description

Weight was recorded using a calibrated scale (with the same scale used if possible for the duration of the study) reporting weight in kilograms (kg), and accuracy to the nearest 0.1 kg. Overall number of subjects analyzed included all subjects randomly assigned to study treatment and who took at least 1 dose of study treatment.

End point type

Secondary

End point timeframe

Baseline, Week 2

End point values	Placebo	PF-06882961 2.5mg BID	PF-06882961 10mg BID	PF-06882961 40mg BID	PF-06882961 80mg BID	PF-06882961 120mg BID
Number of subjects analysed	65	64	68	68	63	69
Units: Kilogram
least squares mean (confidence interval 90%)	-0.15 (-0.47 to 0.17)	-0.09 (-0.41 to 0.23)	-0.12 (-0.44 to 0.19)	-0.23 (-0.54 to 0.08)	-0.57 (-0.89 to -0.24)	-0.54 (-0.85 to -0.24)

PF-06882961 2.5mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 2.5mg BID

Number of subjects included in analysis

129

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.8011

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

0.06

Confidence interval

level

90%

sides

2-sided

lower limit

-0.33

upper limit

0.44

PF-06882961 10mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 10mg BID

Number of subjects included in analysis

133

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9149

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

0.02

Confidence interval

level

90%

sides

2-sided

lower limit

-0.35

upper limit

0.4

PF-06882961 40mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 40mg BID

Number of subjects included in analysis

133

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7216

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-0.08

Confidence interval

level

90%

sides

2-sided

lower limit

-0.46

upper limit

0.3

PF-06882961 80mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 80mg BID

Number of subjects included in analysis

128

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0758

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-0.42

Confidence interval

level

90%

sides

2-sided

lower limit

-0.8

upper limit

-0.03

PF-06882961 120mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 120mg BID

Number of subjects included in analysis

134

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.086

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-0.4

Confidence interval

level

90%

sides

2-sided

lower limit

-0.77

upper limit

-0.02

Secondary: Change From Baseline in Body Weight at Week 4

Top of page

End point title

Change From Baseline in Body Weight at Week 4

End point description

End point type

Secondary

End point timeframe

Baseline, Week 4

End point values	Placebo	PF-06882961 2.5mg BID	PF-06882961 10mg BID	PF-06882961 40mg BID	PF-06882961 80mg BID	PF-06882961 120mg BID
Number of subjects analysed	61	58	68	63	55	61
Units: Kilogram
least squares mean (confidence interval 90%)	-0.25 (-0.64 to 0.15)	-0.33 (-0.72 to 0.07)	-0.08 (-0.46 to 0.30)	-0.77 (-1.15 to -0.39)	-1.05 (-1.45 to -0.64)	-1.33 (-1.71 to -0.95)

PF-06882961 2.5mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 2.5mg BID

Number of subjects included in analysis

119

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7898

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-0.08

Confidence interval

level

90%

sides

2-sided

lower limit

-0.59

upper limit

0.42

PF-06882961 10mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 10mg BID

Number of subjects included in analysis

129

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5829

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

0.16

Confidence interval

level

90%

sides

2-sided

lower limit

-0.33

upper limit

0.66

PF-06882961 40mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 40mg BID

Number of subjects included in analysis

124

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0827

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-0.52

Confidence interval

level

90%

sides

2-sided

lower limit

-1.02

upper limit

-0.03

PF-06882961 80mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 80mg BID

Number of subjects included in analysis

116

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0101

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-0.8

Confidence interval

level

90%

sides

2-sided

lower limit

-1.31

upper limit

-0.29

PF-06882961 120mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 120mg BID

Number of subjects included in analysis

122

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0004

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-1.09

Confidence interval

level

90%

sides

2-sided

lower limit

-1.59

upper limit

-0.59

Secondary: Change From Baseline in Body Weight at Week 6

Top of page

End point title

Change From Baseline in Body Weight at Week 6

End point description

End point type

Secondary

End point timeframe

Baseline, Week 6

End point values	Placebo	PF-06882961 2.5mg BID	PF-06882961 10mg BID	PF-06882961 40mg BID	PF-06882961 80mg BID	PF-06882961 120mg BID
Number of subjects analysed	60	55	66	60	51	53
Units: Kilogram
least squares mean (confidence interval 90%)	-0.09 (-0.57 to 0.40)	-0.19 (-0.68 to 0.31)	-0.32 (-0.78 to 0.15)	-0.83 (-1.31 to -0.36)	-1.69 (-2.20 to -1.19)	-2.34 (-2.83 to -1.85)

PF-06882961 2.5mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 2.5mg BID

Number of subjects included in analysis

115

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7985

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-0.1

Confidence interval

level

90%

sides

2-sided

lower limit

-0.75

upper limit

0.55

PF-06882961 10mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 10mg BID

Number of subjects included in analysis

126

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5484

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-0.23

Confidence interval

level

90%

sides

2-sided

lower limit

-0.86

upper limit

0.4

PF-06882961 40mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 40mg BID

Number of subjects included in analysis

120

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0541

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-0.75

Confidence interval

level

90%

sides

2-sided

lower limit

-1.38

upper limit

-0.11

PF-06882961 80mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 80mg BID

Number of subjects included in analysis

111

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-1.6

Confidence interval

level

90%

sides

2-sided

lower limit

-2.26

upper limit

-0.95

PF-06882961 120mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 120mg BID

Number of subjects included in analysis

113

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-2.25

Confidence interval

level

90%

sides

2-sided

lower limit

-2.9

upper limit

-1.6

Secondary: Change From Baseline in Body Weight at Week 8

Top of page

End point title

Change From Baseline in Body Weight at Week 8

End point description

End point type

Secondary

End point timeframe

Baseline, Week 8

End point values	Placebo	PF-06882961 2.5mg BID	PF-06882961 10mg BID	PF-06882961 40mg BID	PF-06882961 80mg BID	PF-06882961 120mg BID
Number of subjects analysed	57	54	66	58	48	42
Units: Kilogram
least squares mean (confidence interval 90%)	-0.36 (-0.89 to 0.16)	-0.05 (-0.59 to 0.49)	-0.27 (-0.78 to 0.23)	-1.09 (-1.60 to -0.57)	-1.97 (-2.52 to -1.42)	-3.31 (-3.85 to -2.77)

PF-06882961 2.5mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 2.5mg BID

Number of subjects included in analysis

111

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4692

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

0.31

Confidence interval

level

90%

sides

2-sided

lower limit

-0.4

upper limit

1.03

PF-06882961 10mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 10mg BID

Number of subjects included in analysis

123

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.8274

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

0.09

Confidence interval

level

90%

sides

2-sided

lower limit

-0.6

upper limit

0.78

PF-06882961 40mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 40mg BID

Number of subjects included in analysis

115

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0887

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-0.72

Confidence interval

level

90%

sides

2-sided

lower limit

-1.42

upper limit

-0.02

PF-06882961 80mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 80mg BID

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0003

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-1.61

Confidence interval

level

90%

sides

2-sided

lower limit

-2.33

upper limit

-0.88

PF-06882961 120mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 120mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-2.95

Confidence interval

level

90%

sides

2-sided

lower limit

-3.67

upper limit

-2.22

Secondary: Change From Baseline in Body Weight at Week 12

Top of page

End point title

Change From Baseline in Body Weight at Week 12

End point description

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	Placebo	PF-06882961 2.5mg BID	PF-06882961 10mg BID	PF-06882961 40mg BID	PF-06882961 80mg BID	PF-06882961 120mg BID
Number of subjects analysed	55	53	63	58	46	38
Units: Kilogram
least squares mean (confidence interval 90%)	-0.24 (-0.85 to 0.38)	-0.09 (-0.72 to 0.53)	-0.00 (-0.59 to 0.58)	-1.05 (-1.65 to -0.44)	-2.52 (-3.17 to -1.87)	-3.81 (-4.46 to -3.16)

PF-06882961 2.5mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 2.5mg BID

Number of subjects included in analysis

108

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7758

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

0.15

Confidence interval

level

90%

sides

2-sided

lower limit

-0.7

upper limit

0.99

PF-06882961 10mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 10mg BID

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.6367

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

0.23

Confidence interval

level

90%

sides

2-sided

lower limit

-0.58

upper limit

1.05

PF-06882961 40mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 40mg BID

Number of subjects included in analysis

113

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1082

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-0.81

Confidence interval

level

90%

sides

2-sided

lower limit

-1.63

upper limit

0.02

PF-06882961 80mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 80mg BID

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-2.28

Confidence interval

level

90%

sides

2-sided

lower limit

-3.14

upper limit

-1.42

PF-06882961 120mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 120mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-3.57

Confidence interval

level

90%

sides

2-sided

lower limit

-4.44

upper limit

-2.7

Secondary: Change From Baseline in Body Weight at Week 16

Top of page

End point title

Change From Baseline in Body Weight at Week 16

End point description

End point type

Secondary

End point timeframe

Baseline, Week 16

End point values	Placebo	PF-06882961 2.5mg BID	PF-06882961 10mg BID	PF-06882961 40mg BID	PF-06882961 80mg BID	PF-06882961 120mg BID
Number of subjects analysed	52	53	62	57	46	38
Units: Kilogram
least squares mean (confidence interval 90%)	-0.43 (-1.12 to 0.25)	0.02 (-0.68 to 0.72)	-0.06 (-0.71 to 0.60)	-1.16 (-1.84 to -0.49)	-2.48 (-3.20 to -1.75)	-4.60 (-5.34 to -3.86)

PF-06882961 2.5mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 2.5mg BID

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4325

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

0.45

Confidence interval

level

90%

sides

2-sided

lower limit

-0.5

upper limit

1.41

PF-06882961 10mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 10mg BID

Number of subjects included in analysis

114

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4978

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

0.38

Confidence interval

level

90%

sides

2-sided

lower limit

-0.54

upper limit

1.3

PF-06882961 40mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 40mg BID

Number of subjects included in analysis

109

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.197

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-0.73

Confidence interval

level

90%

sides

2-sided

lower limit

-1.66

upper limit

0.2

PF-06882961 80mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 80mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0006

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-2.04

Confidence interval

level

90%

sides

2-sided

lower limit

-3.01

upper limit

-1.07

PF-06882961 120mg BID versus Placebo

Comparison groups

Placebo v PF-06882961 120mg BID

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS Mean

Point estimate

-4.17

Confidence interval

level

90%

sides

2-sided

lower limit

-5.15

upper limit

-3.18

Secondary: Number of Subjects With Treatment Emergent Adverse Events (Adverse Events [AEs] and Serious Adverse Events [SAEs])

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End point title

Number of Subjects With Treatment Emergent Adverse Events (Adverse Events [AEs] and Serious Adverse Events [SAEs])

End point description

An adverse event (AE) was any untoward medical occurrence in a patient or clinical study subject, temporally associated with the use of study treatment, whether or not considered related to the study treatment. A serious AE (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening; initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect. Any such events with initial onset or increasing in severity after the first dose of study treatment were counted as treatment-emergent. Safety analysis set included all subjects randomly assigned to study treatment and who took at least 1 dose of study treatment.

End point type

Secondary

End point timeframe

Baseline up to Week 21

End point values	Placebo	PF-06882961 2.5mg BID	PF-06882961 10mg BID	PF-06882961 40mg BID	PF-06882961 80mg BID	PF-06882961 120mg BID
Number of subjects analysed	66	68	68	71	67	71
Units: Subjects
Number of Subjects With Treatment Emergent AEs	32	32	31	42	43	44
Number of Subjects With Treatment Emergent SAEs	1	1	2	6	2	1

No statistical analyses for this end point

Secondary: Number of Subjects With Treatment Emergent Clinical Laboratory Abnormalities Without Regard to Baseline Abnormality

Top of page

End point title

Number of Subjects With Treatment Emergent Clinical Laboratory Abnormalities Without Regard to Baseline Abnormality

End point description

Following laboratory parameters were assessed against pre-defined abnormality criteria: hematology (hemoglobin, hematocrit, erythrocytes, reticulocytes, platelets, leukocytes, lymphocytes, neutrophils, basophils, eosinophils, monocytes, activated partial thromboplastin time, prothrombin time, PT/INR, reticulocytes); chemistry (indirect bilirubin, direct bilirubin, protein, albumin, blood urea nitrogen, creatinine, creatine kinase, urate, calcium, sodium, potassium, chloride, bicarbonate, urine urobilinogen); urinalysis (pH, urine glucose, urine ketones, urine protein, urine hemoglobin, nitrites, leukocyte esterase, urine erythrocytes, urine leukocytes, urine hyaline casts, urine bilirubin); lipid panel (low density lipoprotein cholesterol, high density lipoprotein cholesterol). Overall number of subjects analyzed included all subjects randomly assigned to study treatment and who took at least 1 dose of study treatment and had at least 1 measurement available.

End point type

Secondary

End point timeframe

Baseline Through Week 21

End point values	Placebo	PF-06882961 2.5mg BID	PF-06882961 10mg BID	PF-06882961 40mg BID	PF-06882961 80mg BID	PF-06882961 120mg BID
Number of subjects analysed	65	68	68	71	67	71
Units: Subjects
Number of Subjects With Laboratory Abnormalities	60	57	57	57	60	64

No statistical analyses for this end point

Secondary: Number of Subjects With Treatment Emergent Vital Signs Abnormalities

Top of page

End point title

Number of Subjects With Treatment Emergent Vital Signs Abnormalities

End point description

Vital signs abnormality criteria: 1) supine systolic blood pressure (SBP) <90 millimeters of mercury (mmHg); 2) supine diastolic blood pressure (DBP) <50 mmHg; 3) supine pulse rate <40 or >120 beats per minute (bpm); 4) change from baseline (increase or decrease) in supine SBP greater than or equal to (>=) 30 mmHg; 5) change from baseline (increase or decrease) in supine DBP >= 20 mmHg. Overall number of subjects analyzed included all subjects randomly assigned to study treatment, took at least 1 dose of study treatment and had at least 1 measurement available.

End point type

Secondary

End point timeframe

Baseline through Week 21

End point values	Placebo	PF-06882961 2.5mg BID	PF-06882961 10mg BID	PF-06882961 40mg BID	PF-06882961 80mg BID	PF-06882961 120mg BID
Number of subjects analysed	65	68	68	71	67	71
Units: Subjects
Supine SBP <90 mmHg	0	0	0	0	0	0
Supine SBP increase >=30 mmHg	3	4	3	3	0	5
Supine SBP decrease >=30 mmHg	4	4	3	5	5	0
Supine DBP <50 mmHg	1	0	0	1	0	1
Supine DBP increase >=20 mmHg	1	1	2	3	3	3
Supine DBP decrease >=20 mmHg	3	4	1	3	2	1
Supine pulse rate <40 bpm	0	0	0	0	0	0
Supine pulse rate >120 bpm	0	0	0	0	0	0

No statistical analyses for this end point

Secondary: Number of Subjects With Treatment Emergent ECG Abnormalities

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End point title

Number of Subjects With Treatment Emergent ECG Abnormalities

End point description

ECG categorical abnormality criteria: 1. PR interval (the interval between the start of the P wave and the start of the QRS complex, corresponding to the time between the onset of the atrial depolarization and onset of ventricular depolarization): a) greater than or equal to (>=) 300 millisecond (msec), b) >=25% increase when baseline is > 200 msec or >=50% increase when baseline is less than or equal to (<=) 200 msec. 2. QRS interval (time from ECG Q wave to the end of the S wave corresponding to ventricle depolarization): a) >=140 msec, b) >=50% increase from baseline. 3. QTcF interval (QT corrected using the Fridericia formula): a) >450 msec and <=480 msec, b) >480 msec and <=500 msec, c) >500 msec, d) >30 msec and <=60 msec increase from baseline, e) >60 msec increase from baseline. Overall number of subjects analyzed included all subjects randomly assigned to study treatment, took at least 1 dose of study treatment and had at least 1 measurement available.

End point type

Secondary

End point timeframe

Baseline Through Week 21

End point values	Placebo	PF-06882961 2.5mg BID	PF-06882961 10mg BID	PF-06882961 40mg BID	PF-06882961 80mg BID	PF-06882961 120mg BID
Number of subjects analysed	65	68	68	71	67	71
Units: Subjects
PR interval ≥300 msec	0	0	0	0	0	1
%Change in PR interval ≥25/50%	3	0	0	0	1	0
QRS interval ≥140 msec	1	1	0	0	0	0
%Change in QRS interval ≥50%	1	1	0	0	0	0
QTcF interval >450 and ≤480 msec	2	3	2	1	3	4
QTcF interval >480 and ≤500 msec	0	0	0	0	0	1
QTcF interval >500 msec	0	0	0	0	0	0
Change in QTcF interval >30 and ≤60 msec	2	3	2	6	3	6
Change in QTcF interval >60 msec	0	0	1	1	0	3

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Baseline up to Week 21

Adverse event reporting additional description

For the number of adverse events, if the same subject in a given treatment had more than 1 occurrence in the same preferred term event category, the preferred term event for the subject was counted once, and only the most severe occurrence was counted.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

24.0

Reporting group title

Placebo

Reporting group description

Placebo matched to PF-06882961 was administered orally twice daily (BID) with food for a total of 16 weeks.

Reporting group title

PF-06882961 2.5mg BID

Reporting group description

PF-06882961 2.5 mg was administered orally twice daily (BID) with food for a total of 16 weeks.

Reporting group title

PF-06882961 10mg BID

Reporting group description

PF-06882961 10 mg was administered orally twice daily (BID) with food for a total of 16 weeks.

Reporting group title

PF-06882961 40mg BID

Reporting group description

PF-06882961 40 mg was administered orally twice daily (BID) with food for a total of 16 weeks. Titration was implemented.

Reporting group title

PF-06882961 80mg BID

Reporting group description

PF-06882961 80 mg was administered orally twice daily (BID) with food for a total of 16 weeks. Titration was implemented.

Reporting group title

PF-06882961 120mg BID

Reporting group description

PF-06882961 120 mg was administered orally twice daily (BID) with food for a total of 16 weeks. Titration was implemented.

Serious adverse events	Placebo	PF-06882961 2.5mg BID	PF-06882961 10mg BID	PF-06882961 40mg BID	PF-06882961 80mg BID	PF-06882961 120mg BID
Total subjects affected by serious adverse events
subjects affected / exposed	1 / 66 (1.52%)	1 / 68 (1.47%)	2 / 68 (2.94%)	6 / 71 (8.45%)	2 / 67 (2.99%)	1 / 71 (1.41%)
number of deaths (all causes)	0	1	0	2	0	0
number of deaths resulting from adverse events	0	1	0	2	0	0
Investigations
Gamma-glutamyltransferase increased
subjects affected / exposed	0 / 66 (0.00%)	0 / 68 (0.00%)	0 / 68 (0.00%)	1 / 71 (1.41%)	0 / 67 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
SARS-CoV-2 test positive
subjects affected / exposed	0 / 66 (0.00%)	0 / 68 (0.00%)	0 / 68 (0.00%)	1 / 71 (1.41%)	0 / 67 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma
subjects affected / exposed	0 / 66 (0.00%)	0 / 68 (0.00%)	0 / 68 (0.00%)	0 / 71 (0.00%)	0 / 67 (0.00%)	1 / 71 (1.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Ankle fracture
subjects affected / exposed	1 / 66 (1.52%)	0 / 68 (0.00%)	0 / 68 (0.00%)	0 / 71 (0.00%)	0 / 67 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Seroma
subjects affected / exposed	0 / 66 (0.00%)	0 / 68 (0.00%)	0 / 68 (0.00%)	1 / 71 (1.41%)	0 / 67 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
Hypertension
subjects affected / exposed	0 / 66 (0.00%)	0 / 68 (0.00%)	0 / 68 (0.00%)	0 / 71 (0.00%)	1 / 67 (1.49%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Acute myocardial infarction
subjects affected / exposed	0 / 66 (0.00%)	1 / 68 (1.47%)	0 / 68 (0.00%)	0 / 71 (0.00%)	0 / 67 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Palpitations
subjects affected / exposed	0 / 66 (0.00%)	0 / 68 (0.00%)	0 / 68 (0.00%)	1 / 71 (1.41%)	0 / 67 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Multiple sclerosis
subjects affected / exposed	0 / 66 (0.00%)	0 / 68 (0.00%)	1 / 68 (1.47%)	0 / 71 (0.00%)	0 / 67 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Paraesthesia
subjects affected / exposed	0 / 66 (0.00%)	0 / 68 (0.00%)	0 / 68 (0.00%)	1 / 71 (1.41%)	0 / 67 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	0 / 66 (0.00%)	0 / 68 (0.00%)	1 / 68 (1.47%)	0 / 71 (0.00%)	0 / 67 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Cholecystitis acute
subjects affected / exposed	0 / 66 (0.00%)	0 / 68 (0.00%)	0 / 68 (0.00%)	0 / 71 (0.00%)	1 / 67 (1.49%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Drug-induced liver injury
subjects affected / exposed	0 / 66 (0.00%)	0 / 68 (0.00%)	0 / 68 (0.00%)	1 / 71 (1.41%)	0 / 67 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
COVID-19 pneumonia
subjects affected / exposed	0 / 66 (0.00%)	1 / 68 (1.47%)	0 / 68 (0.00%)	1 / 71 (1.41%)	0 / 67 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	0 / 66 (0.00%)	0 / 68 (0.00%)	0 / 68 (0.00%)	1 / 71 (1.41%)	0 / 67 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Placebo	PF-06882961 2.5mg BID	PF-06882961 10mg BID	PF-06882961 40mg BID	PF-06882961 80mg BID	PF-06882961 120mg BID
Total subjects affected by non serious adverse events
subjects affected / exposed	15 / 66 (22.73%)	21 / 68 (30.88%)	17 / 68 (25.00%)	33 / 71 (46.48%)	40 / 67 (59.70%)	35 / 71 (49.30%)
Investigations
SARS-CoV-2 test positive
subjects affected / exposed	2 / 66 (3.03%)	4 / 68 (5.88%)	3 / 68 (4.41%)	2 / 71 (2.82%)	1 / 67 (1.49%)	1 / 71 (1.41%)
occurrences all number	2	4	3	2	1	1
Vascular disorders
Hypertension
subjects affected / exposed	0 / 66 (0.00%)	1 / 68 (1.47%)	3 / 68 (4.41%)	1 / 71 (1.41%)	4 / 67 (5.97%)	1 / 71 (1.41%)
occurrences all number	0	1	3	1	4	1
Nervous system disorders
Dizziness
subjects affected / exposed	1 / 66 (1.52%)	1 / 68 (1.47%)	4 / 68 (5.88%)	3 / 71 (4.23%)	1 / 67 (1.49%)	5 / 71 (7.04%)
occurrences all number	1	2	4	3	3	7
Headache
subjects affected / exposed	4 / 66 (6.06%)	4 / 68 (5.88%)	1 / 68 (1.47%)	5 / 71 (7.04%)	2 / 67 (2.99%)	7 / 71 (9.86%)
occurrences all number	4	4	1	5	3	9
Gastrointestinal disorders
Abdominal distension
subjects affected / exposed	1 / 66 (1.52%)	0 / 68 (0.00%)	1 / 68 (1.47%)	4 / 71 (5.63%)	3 / 67 (4.48%)	2 / 71 (2.82%)
occurrences all number	1	0	1	5	3	3
Diarrhoea
subjects affected / exposed	2 / 66 (3.03%)	3 / 68 (4.41%)	4 / 68 (5.88%)	8 / 71 (11.27%)	12 / 67 (17.91%)	7 / 71 (9.86%)
occurrences all number	2	3	6	10	14	7
Dyspepsia
subjects affected / exposed	0 / 66 (0.00%)	4 / 68 (5.88%)	3 / 68 (4.41%)	2 / 71 (2.82%)	9 / 67 (13.43%)	2 / 71 (2.82%)
occurrences all number	0	4	3	2	10	2
Gastrooesophageal reflux disease
subjects affected / exposed	0 / 66 (0.00%)	1 / 68 (1.47%)	2 / 68 (2.94%)	2 / 71 (2.82%)	4 / 67 (5.97%)	5 / 71 (7.04%)
occurrences all number	0	1	2	2	4	5
Nausea
subjects affected / exposed	2 / 66 (3.03%)	5 / 68 (7.35%)	5 / 68 (7.35%)	11 / 71 (15.49%)	22 / 67 (32.84%)	23 / 71 (32.39%)
occurrences all number	2	5	7	13	27	32
Vomiting
subjects affected / exposed	0 / 66 (0.00%)	0 / 68 (0.00%)	1 / 68 (1.47%)	5 / 71 (7.04%)	11 / 67 (16.42%)	18 / 71 (25.35%)
occurrences all number	0	0	1	6	17	37
Infections and infestations
Urinary tract infection
subjects affected / exposed	0 / 66 (0.00%)	1 / 68 (1.47%)	0 / 68 (0.00%)	5 / 71 (7.04%)	3 / 67 (4.48%)	1 / 71 (1.41%)
occurrences all number	0	1	0	5	4	1
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	0 / 66 (0.00%)	2 / 68 (2.94%)	0 / 68 (0.00%)	2 / 71 (2.82%)	1 / 67 (1.49%)	5 / 71 (7.04%)
occurrences all number	0	3	0	2	1	5
Hyperglycaemia
subjects affected / exposed	6 / 66 (9.09%)	2 / 68 (2.94%)	1 / 68 (1.47%)	0 / 71 (0.00%)	4 / 67 (5.97%)	0 / 71 (0.00%)
occurrences all number	6	4	1	0	4	0
Hypoglycaemia
subjects affected / exposed	0 / 66 (0.00%)	1 / 68 (1.47%)	1 / 68 (1.47%)	4 / 71 (5.63%)	6 / 67 (8.96%)	3 / 71 (4.23%)
occurrences all number	0	1	1	6	8	3

More information

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Were there any global substantial amendments to the protocol? Yes

19 May 2020

• Added exclusion of sulfasalazine (a breast cancer resistance protein [BCRP] substrate) from study as PF-06882961 has the potential to inhibit intestinal BCRP. Updated the nonclinical safety data to align with the available toxicology information (6 month toxicology study in cynomolgus monkeys). • Added the minimum time frame of monthly between safety reviews to ensure that there was ample time to prepare all data reports and ensure a timely review of safety data. The interim analysis of unblinded safety data permitted possible updates to study conduct if needed. • Lowered the cut off for blood pressure to a more conservative level to optimize blood pressure control prior to study entry.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: A 16-Week, Phase 2b, Randomized, Double-Blind, Placebo Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of Twice Daily PF-06882961 Administration in Adults With Type 2 Diabetes Mellitus Inadequately Controlled on Metformin or Diet and Exercise

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Change From Baseline in Glycated Hemoglobin (HbA1c) at Week 16

Primary: Change From Baseline in Glycated Hemoglobin (HbA1c) at Week 16

Secondary: Percentage of Subjects Achieving Less Than (<) 7% Glycated Hemoglobin (HbA1c) Levels

Secondary: Percentage of Subjects Achieving Less Than (<) 7% Glycated Hemoglobin (HbA1c) Levels

Secondary: Change From Baseline in Glycated Hemoglobin (HbA1c) at Week 2

Secondary: Change From Baseline in Glycated Hemoglobin (HbA1c) at Week 2

Secondary: Change From Baseline in Glycated Hemoglobin (HbA1c) at Week 4

Secondary: Change From Baseline in Glycated Hemoglobin (HbA1c) at Week 4

Secondary: Change From Baseline in Glycated Hemoglobin (HbA1c) at Week 6

Secondary: Change From Baseline in Glycated Hemoglobin (HbA1c) at Week 6

Secondary: Change From Baseline in Glycated Hemoglobin (HbA1c) at Week 8

Secondary: Change From Baseline in Glycated Hemoglobin (HbA1c) at Week 8

Secondary: Change From Baseline in Glycated Hemoglobin (HbA1c) at Week 12

Secondary: Change From Baseline in Glycated Hemoglobin (HbA1c) at Week 12

Secondary: Change From Baseline in Fasting Plasma Glucose at Week 2

Secondary: Change From Baseline in Fasting Plasma Glucose at Week 2

Secondary: Change From Baseline in Fasting Plasma Glucose at Week 4

Secondary: Change From Baseline in Fasting Plasma Glucose at Week 4

Secondary: Change From Baseline in Fasting Plasma Glucose at Week 6

Secondary: Change From Baseline in Fasting Plasma Glucose at Week 6

Secondary: Change From Baseline in Fasting Plasma Glucose at Week 8

Secondary: Change From Baseline in Fasting Plasma Glucose at Week 8

Secondary: Change From Baseline in Fasting Plasma Glucose at Week 12

Secondary: Change From Baseline in Fasting Plasma Glucose at Week 12

Secondary: Change From Baseline in Fasting Plasma Glucose at Week 16

Secondary: Change From Baseline in Fasting Plasma Glucose at Week 16

Secondary: Change From Baseline in Body Weight at Week 2

Secondary: Change From Baseline in Body Weight at Week 2

Secondary: Change From Baseline in Body Weight at Week 4

Secondary: Change From Baseline in Body Weight at Week 4

Secondary: Change From Baseline in Body Weight at Week 6

Secondary: Change From Baseline in Body Weight at Week 6

Secondary: Change From Baseline in Body Weight at Week 8

Secondary: Change From Baseline in Body Weight at Week 8

Secondary: Change From Baseline in Body Weight at Week 12

Secondary: Change From Baseline in Body Weight at Week 12

Secondary: Change From Baseline in Body Weight at Week 16

Secondary: Change From Baseline in Body Weight at Week 16

Secondary: Number of Subjects With Treatment Emergent Adverse Events (Adverse Events [AEs] and Serious Adverse Events [SAEs])

Secondary: Number of Subjects With Treatment Emergent Adverse Events (Adverse Events [AEs] and Serious Adverse Events [SAEs])

Secondary: Number of Subjects With Treatment Emergent Clinical Laboratory Abnormalities Without Regard to Baseline Abnormality

Secondary: Number of Subjects With Treatment Emergent Clinical Laboratory Abnormalities Without Regard to Baseline Abnormality

Secondary: Number of Subjects With Treatment Emergent Vital Signs Abnormalities

Secondary: Number of Subjects With Treatment Emergent Vital Signs Abnormalities

Secondary: Number of Subjects With Treatment Emergent ECG Abnormalities

Secondary: Number of Subjects With Treatment Emergent ECG Abnormalities

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A 16-Week, Phase 2b, Randomized, Double-Blind, Placebo Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of Twice Daily PF-06882961 Administration in Adults With Type 2 Diabetes Mellitus Inadequately Controlled on Metformin or Diet and Exercise