A Multiple Dose Study Of PF-04620110 In Type 2 Diabetes Patients

• PF-04620110 (Drug): 5 mg of PF-04620110 given once daily
• PF-04620110 (Drug): 2.5 mg of PF-04620110 given twice daily
• Placebo (Drug): Matching placebo giving for 4 weeks

Primary outcomes

• Change From Baseline in Post-Prandial Glucose Area Under the Concentration-Time Curve From Time 2 to 6 Hours (AUC 2-6) After a Mixed Meal Tolerance Test (MMTT) at Day 28 [Baseline (Day -1); 2 to 6 hours post-dose on Day 28]: Change from baseline in post-prandial area under the plasma glucose concentration time curve as determined by standardized MMTT. Linear trapezoidal method was used to compute AUC.

Secondary outcomes

• Change From Baseline in 24-Hour Average Plasma Glucose (APG) Post-Dose at Day 28 [Baseline (Day -1); 24 hours post-dose on Day 28]: APG= AUC (0-24)/24. AUC (0-24) was computed using Linear trapezoidal method.
• Change From Baseline in Post-Prandial Insulin Area Under the Concentration-Time Curve From Time 2 to 6 Hours (AUC 2-6) After a Mixed Meal Tolerance Test (MMTT) at Day 28 [Baseline (Day -1); 2 to 6 hours post-dose on Day 28]: Change from baseline in post-prandial plasma insulin AUC under the plasma insulin concentration versus time curve as determined by standardized MMTT. Linear trapezoidal method was used to compute AUC.
• Change From Baseline in Post-Prandial C-Peptide Area Under the Concentration-Time Curve From Time 2 to 6 Hours (AUC 2-6) After a Mixed Meal Tolerance Test (MMTT) at Day 28 [Baseline (Day -1); 2 to 6 hours post-dose on Day 28]: Change from baseline in post-prandial area under the plasma C-peptide concentration time curve as determined by standardized MMTT. Linear trapezoidal method was used to compute AUC.
• Change From Baseline in Post-Prandial Net Triglyceride Area Under the Concentration-Time Curve From Time 2 to 6 Hours (AUC 2-6) After a Mixed Meal Tolerance Test (MMTT) at Day 28 [Baseline (Day -1); 2 to 6 hours post-dose on Day 28]: Change from baseline in post-prandial area under the plasma net triglyceride concentration time curve as determined by standardized MMTT. Linear trapezoidal method was used to compute AUC.
• Change From Baseline in Total Amide Glucagon Like Peptide-1 (GLP-1) and Active Glucagon Like Peptide-1 (GLP-1) Area Under the Concentration-Time Curve From Time 2 to 6 Hours (AUC 2-6) at Day 28 [Baseline (Day -1); 2 to 6 hours post-dose on Day 28]: Change from baseline in total amide GLP-1 and active GLP-1 area under the plasma concentration time curve was computed by Linear trapezoidal method.
• Change From Baseline in Gastric Inhibitory Peptide (GIP) Area Under the Concentration-Time Curve From Time 2 to 6 Hours (AUC 2-6) at Day 28 [Baseline (Day -1); 2 to 6 hours post-dose on Day 28]: Change from baseline in GIP area under the plasma concentration time curve was computed by Linear trapezoidal method.
• Change From Baseline in Peptide YY (PYY) Area Under the Concentration-Time Curve From Time 2 to 6 Hours (AUC 2-6) at Day 28 [Baseline (Day -1); 2 to 6 hours post-dose on Day 28]: Change from baseline in PYY area under the plasma concentration time curve was computed by Linear trapezoidal method.
• Change From Baseline in Fasting Glucose at Day 28 [0 hour (pre-dose) on Day -1, Day 28]
• Change From Baseline in Fasting Insulin at Day 28 [0 hour (pre-dose) on Day -1, Day 28]
• Change From Baseline in Fasting Net Triglycerides at Day 28 [0 hour (pre-dose) on Day -1, Day 28]
• Change From Baseline in Post-Lunch Glucose Excursions Area Under the Concentration-Time Curve From Time 6 to 10 Hours (AUC 6-10) Post-dose at Day 28 [Baseline (Day -1); 6 to 10 hours post-dose on Day 28]: Change from baseline in post-lunch glucose excursion under the plasma concentration time curve was computed by Linear trapezoidal method.
• Change From Baseline in Post-Dinner Glucose Excursions Area Under the Concentration-Time Curve From Time 12 to 16 Hours (AUC 12-16) Post-dose at Day 28 [Baseline (Day -1); 12 to 16 hours post-dose on Day 28]: Change from baseline in post-dinner glucose excursion under the plasma concentration time curve was computed by Linear trapezoidal method.
• Maximum Observed Plasma Concentration (Cmax) of PF-04620110 [24 hours post-morning dose on Day 28]
• Minimum Observed Plasma Trough Concentration (Cmin) of PF-04620110 [24 hours post-morning dose on Day 28]
• Time to Cmax (Tmax) of PF-04620110 [24 hours post-morning dose on Day 28]
• Area Under the Concentration-Time Curve AUC (0-24) of PF-04620110 [24 hours post-morning dose on Day 28]: Area under the plasma concentration-time curve from time 0 (pre-dose) to 24 hours. AUC (0-24) was computed using the linear trapezoidal method.

Sex: All, ages: 18 Years to 60 Years

Inclusion Criteria:

* Male and/or female subjects between the ages of 18 and 60 years;
* Body Mass Index (BMI) of >25.0 kg/m2 and <40 kg/m2;
* Subjects must have a historical diagnosis of T2DM in accordance with the ADA guidelines;
* Subjects who have been on well-tolerated and stable doses of metformin

Exclusion Criteria:

* Recent evidence (6 months prior to screening) or history of unstable major organ disease;
* Diagnosis of Type 1 diabetes mellitus;
* Current medical history of myocardial infarction, unstable angina, or history of stroke (including TIA) within 6 months prior to Screening;
* Treatment with thiazolidinediones (TZDs), or subcutaneously administered antidiabetic agents;

Participant flow

Outcome results

• Change From Baseline in Post-Prandial Glucose Area Under the Concentration-Time Curve From Time 2 to 6 Hours (AUC 2-6) After a Mixed Meal Tolerance Test (MMTT) at Day 28 (Primary), Mean, mg*hr/dL: PF-04620110 2.5 mg QD, Then PF-04620110 2.5 mg BID 1052.7 +/- 258.2; PF-04620110 5 mg QD 954.7 +/- 249.2; Placebo 1005.4 +/- 190.0
• Change From Baseline in 24-Hour Average Plasma Glucose (APG) Post-Dose at Day 28 (Secondary), Mean, mg/dL: PF-04620110 2.5 mg QD, Then PF-04620110 2.5 mg BID 204.9 +/- 52.2; PF-04620110 5 mg QD 188.0 +/- 53.2; Placebo 187.2 +/- 36.5
• Change From Baseline in Post-Prandial Insulin Area Under the Concentration-Time Curve From Time 2 to 6 Hours (AUC 2-6) After a Mixed Meal Tolerance Test (MMTT) at Day 28 (Secondary), Mean, micro-IU*hr/mL: PF-04620110 2.5 mg QD, Then PF-04620110 2.5 mg BID 122.9 +/- 82.9; PF-04620110 5 mg QD 220.2 +/- 282.9; Placebo 156.7 +/- 63.3
• Change From Baseline in Post-Prandial C-Peptide Area Under the Concentration-Time Curve From Time 2 to 6 Hours (AUC 2-6) After a Mixed Meal Tolerance Test (MMTT) at Day 28 (Secondary), Mean, ng*hr/mL: PF-04620110 2.5 mg QD, Then PF-04620110 2.5 mg BID 17.8 +/- 6.2; PF-04620110 5 mg QD 21.6 +/- 10.1; Placebo 20.3 +/- 5.4
• Change From Baseline in Post-Prandial Net Triglyceride Area Under the Concentration-Time Curve From Time 2 to 6 Hours (AUC 2-6) After a Mixed Meal Tolerance Test (MMTT) at Day 28 (Secondary), Mean, mg*hr/dL: PF-04620110 2.5 mg QD, Then PF-04620110 2.5 mg BID 860.6 +/- 456.9; PF-04620110 5 mg QD 1014.4 +/- 403.5; Placebo 961.2 +/- 380.7
• Change From Baseline in Total Amide Glucagon Like Peptide-1 (GLP-1) and Active Glucagon Like Peptide-1 (GLP-1) Area Under the Concentration-Time Curve From Time 2 to 6 Hours (AUC 2-6) at Day 28 (Secondary), Mean, pmol*hr/L: PF-04620110 2.5 mg QD, Then PF-04620110 2.5 mg BID 54.4 +/- 26.8; PF-04620110 5 mg QD 63.2 +/- 36.4; Placebo 70.2 +/- 88.1
• Change From Baseline in Gastric Inhibitory Peptide (GIP) Area Under the Concentration-Time Curve From Time 2 to 6 Hours (AUC 2-6) at Day 28 (Secondary), Mean, pg*hr/mL: PF-04620110 2.5 mg QD, Then PF-04620110 2.5 mg BID 1372.8 +/- 617.2; PF-04620110 5 mg QD 1181.0 +/- 614.6; Placebo 1619.2 +/- 627.7
• Change From Baseline in Peptide YY (PYY) Area Under the Concentration-Time Curve From Time 2 to 6 Hours (AUC 2-6) at Day 28 (Secondary), Mean, pg*hr/mL: PF-04620110 2.5 mg QD, Then PF-04620110 2.5 mg BID 409.0 +/- 192.4; PF-04620110 5 mg QD 540.7 +/- 273.8; Placebo 395.0 +/- 114.6
• Change From Baseline in Fasting Glucose at Day 28 (Secondary), Mean, mg/dL: PF-04620110 2.5 mg QD, Then PF-04620110 2.5 mg BID 197.2 +/- 54.6; PF-04620110 5 mg QD 180.9 +/- 54.7; Placebo 194.4 +/- 37.4
• Change From Baseline in Fasting Insulin at Day 28 (Secondary), Mean, micro-IU/mL: PF-04620110 2.5 mg QD, Then PF-04620110 2.5 mg BID 10.2 +/- 6.9; PF-04620110 5 mg QD 19.8 +/- 27.2; Placebo 9.2 +/- 4.2
• Change From Baseline in Fasting Net Triglycerides at Day 28 (Secondary), Mean, mg/dL: PF-04620110 2.5 mg QD, Then PF-04620110 2.5 mg BID 189.1 +/- 111.7; PF-04620110 5 mg QD 234.8 +/- 116.7; Placebo 187.4 +/- 81.6
• Change From Baseline in Post-Lunch Glucose Excursions Area Under the Concentration-Time Curve From Time 6 to 10 Hours (AUC 6-10) Post-dose at Day 28 (Secondary), Mean, mg*hr/dL: PF-04620110 2.5 mg QD, Then PF-04620110 2.5 mg BID 853.4 +/- 293.4; PF-04620110 5 mg QD 772.3 +/- 259.3; Placebo 730.2 +/- 174.9
• Change From Baseline in Post-Dinner Glucose Excursions Area Under the Concentration-Time Curve From Time 12 to 16 Hours (AUC 12-16) Post-dose at Day 28 (Secondary), Mean, mg*hr/dL: PF-04620110 2.5 mg QD, Then PF-04620110 2.5 mg BID 851.2 +/- 217.2; PF-04620110 5 mg QD 763.9 +/- 215.8; Placebo 759.4 +/- 180.0
• Maximum Observed Plasma Concentration (Cmax) of PF-04620110 (Secondary), Geometric mean, ng/mL: PF-04620110 2.5 mg QD, Then PF-04620110 2.5 mg BID 91.0 +/- 39.3; PF-04620110 5 mg QD 112.0 +/- 43.7
• Minimum Observed Plasma Trough Concentration (Cmin) of PF-04620110 (Secondary), Geometric mean, ng/mL: PF-04620110 2.5 mg QD, Then PF-04620110 2.5 mg BID 16.2 +/- 12.4; PF-04620110 5 mg QD 5.2 +/- 9.2
• Time to Cmax (Tmax) of PF-04620110 (Secondary), Median, hr: PF-04620110 2.5 mg QD, Then PF-04620110 2.5 mg BID 3.0 (1.7 to 12.0); PF-04620110 5 mg QD 3.0 (1.7 to 12.0)
• Area Under the Concentration-Time Curve AUC (0-24) of PF-04620110 (Secondary), Geometric mean, ng*hr/mL: PF-04620110 2.5 mg QD, Then PF-04620110 2.5 mg BID 1055 +/- 397.7; PF-04620110 5 mg QD 1027 +/- 441.6

Adverse events

Other adverse events by term

• Pfizer CT.gov Call Center, Study director, Pfizer