Type 2 Diabetes Patients
Conditions
Keywords
multiple dose study in type 2 diabetes patients
Brief summary
PF-04620110 is a novel compound proposed for the treatment of Type 2 diabetes mellitus. The primary purpose of this trial is to evaluate the safety and tolerability, and pharmacodynamics, of multiple oral doses of PF-04620110 in T2DM patients.
Interventions
DRUGPF-04620110
5 mg of PF-04620110 given once daily
DRUGPlacebo
Matching placebo giving for 4 weeks
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
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;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 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 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. |
| Change From Baseline in Fasting Insulin at Day 28 | 0 hour (pre-dose) on Day -1, Day 28 | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PF-04620110 2.5 mg QD, Then PF-04620110 2.5 mg BID PF-04620110 2.5 milligram (mg) orally once daily (QD) in the morning and matching placebo orally once daily (QD) in the evening for Week 1 and 2, followed by PF-04620110 2.5 mg orally twice daily (BID) for Week 3 and 4. | 16 |
| PF-04620110 5 mg QD PF-04620110 5 mg orally once daily (QD) in the morning and matching placebo orally once daily (QD) in the evening for 4 weeks. | 16 |
| Placebo Matching placebo orally twice daily (BID) for 4 weeks. | 16 |
| Total | 48 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | PF-04620110 2.5 mg QD, Then PF-04620110 2.5 mg BID | PF-04620110 5 mg QD | Placebo | Total |
|---|---|---|---|---|
| Age Continuous | 51.1 years STANDARD_DEVIATION 5.8 | 53.4 years STANDARD_DEVIATION 4.2 | 52.6 years STANDARD_DEVIATION 6.3 | 52.4 years STANDARD_DEVIATION 5.5 |
| Body Mass Index | 31.9 kg/m^2 STANDARD_DEVIATION 3.8 | 30.3 kg/m^2 STANDARD_DEVIATION 3.3 | 32.6 kg/m^2 STANDARD_DEVIATION 3.7 | 31.6 kg/m^2 STANDARD_DEVIATION 3.7 |
| Sex: Female, Male Female | 5 Participants | 4 Participants | 4 Participants | 13 Participants |
| Sex: Female, Male Male | 11 Participants | 12 Participants | 12 Participants | 35 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 12 / 16 | 15 / 16 | 10 / 16 |
| serious Total, serious adverse events | 0 / 16 | 0 / 16 | 0 / 16 |
Outcome results
Primary
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
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.
Time frame: Baseline (Day -1); 2 to 6 hours post-dose on Day 28
Population: Analysis population included all enrolled participants who received at least 1 dose of study medication and had at least 1 post-MMTT glucose area under the curve (AUC) value. Here, 'n' is participants evaluable at specified time points for each group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PF-04620110 2.5 mg QD, Then PF-04620110 2.5 mg BID | 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 (n=16, 16, 16) | 1052.7 mg*hr/dL | Standard Deviation 258.2 |
| PF-04620110 2.5 mg QD, Then PF-04620110 2.5 mg BID | 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 | Change at Day 28 (n=15, 16, 15) | -118.3 mg*hr/dL | Standard Deviation 269 |
| PF-04620110 5 mg QD | 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 (n=16, 16, 16) | 954.7 mg*hr/dL | Standard Deviation 249.2 |
| PF-04620110 5 mg QD | 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 | Change at Day 28 (n=15, 16, 15) | -143.0 mg*hr/dL | Standard Deviation 235.8 |
| Placebo | 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 (n=16, 16, 16) | 1005.4 mg*hr/dL | Standard Deviation 190 |
| Placebo | 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 | Change at Day 28 (n=15, 16, 15) | -117.7 mg*hr/dL | Standard Deviation 157.4 |
Secondary
Area Under the Concentration-Time Curve AUC (0-24) of PF-04620110
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.
Time frame: 24 hours post-morning dose on Day 28
Population: Analysis population included all enrolled participants who received at least 1 dose of study medication and had at least 1 AUC(0-24) value.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-04620110 2.5 mg QD, Then PF-04620110 2.5 mg BID | Area Under the Concentration-Time Curve AUC (0-24) of PF-04620110 | 1055 ng*hr/mL | Standard Deviation 397.7 |
| PF-04620110 5 mg QD | Area Under the Concentration-Time Curve AUC (0-24) of PF-04620110 | 1027 ng*hr/mL | Standard Deviation 441.6 |
Secondary
Change From Baseline in 24-Hour Average Plasma Glucose (APG) Post-Dose at Day 28
APG= AUC (0-24)/24. AUC (0-24) was computed using Linear trapezoidal method.
Time frame: Baseline (Day -1); 24 hours post-dose on Day 28
Population: Analysis population included all enrolled participants who received at least 1 dose of study medication and had at least 1 APG value. Here, 'n' is participants evaluable at specified time points for each group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PF-04620110 2.5 mg QD, Then PF-04620110 2.5 mg BID | Change From Baseline in 24-Hour Average Plasma Glucose (APG) Post-Dose at Day 28 | Baseline (n=16, 16, 16) | 204.9 mg/dL | Standard Deviation 52.2 |
| PF-04620110 2.5 mg QD, Then PF-04620110 2.5 mg BID | Change From Baseline in 24-Hour Average Plasma Glucose (APG) Post-Dose at Day 28 | Change at Day 28 (n=15, 16, 15) | -25.4 mg/dL | Standard Deviation 60.9 |
| PF-04620110 5 mg QD | Change From Baseline in 24-Hour Average Plasma Glucose (APG) Post-Dose at Day 28 | Change at Day 28 (n=15, 16, 15) | -23.4 mg/dL | Standard Deviation 42.5 |
| PF-04620110 5 mg QD | Change From Baseline in 24-Hour Average Plasma Glucose (APG) Post-Dose at Day 28 | Baseline (n=16, 16, 16) | 188.0 mg/dL | Standard Deviation 53.2 |
| Placebo | Change From Baseline in 24-Hour Average Plasma Glucose (APG) Post-Dose at Day 28 | Change at Day 28 (n=15, 16, 15) | -18.3 mg/dL | Standard Deviation 29.6 |
| Placebo | Change From Baseline in 24-Hour Average Plasma Glucose (APG) Post-Dose at Day 28 | Baseline (n=16, 16, 16) | 187.2 mg/dL | Standard Deviation 36.5 |
Secondary
Change From Baseline in Fasting Glucose at Day 28
Time frame: 0 hour (pre-dose) on Day -1, Day 28
Population: Analysis population included all enrolled participants who received at least 1 dose of study medication and had at least 1 fasting glucose value. Here, 'n' is participants evaluable at specified time points for each group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PF-04620110 2.5 mg QD, Then PF-04620110 2.5 mg BID | Change From Baseline in Fasting Glucose at Day 28 | Baseline (n=16, 16, 16) | 197.2 mg/dL | Standard Deviation 54.6 |
| PF-04620110 2.5 mg QD, Then PF-04620110 2.5 mg BID | Change From Baseline in Fasting Glucose at Day 28 | Change at Day 28 (16, 16, 15) | -46.9 mg/dL | Standard Deviation 49.5 |
| PF-04620110 5 mg QD | Change From Baseline in Fasting Glucose at Day 28 | Baseline (n=16, 16, 16) | 180.9 mg/dL | Standard Deviation 54.7 |
| PF-04620110 5 mg QD | Change From Baseline in Fasting Glucose at Day 28 | Change at Day 28 (16, 16, 15) | -27.1 mg/dL | Standard Deviation 34.9 |
| Placebo | Change From Baseline in Fasting Glucose at Day 28 | Baseline (n=16, 16, 16) | 194.4 mg/dL | Standard Deviation 37.4 |
| Placebo | Change From Baseline in Fasting Glucose at Day 28 | Change at Day 28 (16, 16, 15) | -25.2 mg/dL | Standard Deviation 32.1 |
Secondary
Change From Baseline in Fasting Insulin at Day 28
Time frame: 0 hour (pre-dose) on Day -1, Day 28
Population: Analysis population included all enrolled participants who received at least 1 dose of study medication and had at least 1 fasting insulin value. Here, 'n' is participants evaluable at specified time points for each group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PF-04620110 2.5 mg QD, Then PF-04620110 2.5 mg BID | Change From Baseline in Fasting Insulin at Day 28 | Baseline (n=9, 10, 8) | 10.2 micro-IU/mL | Standard Deviation 6.9 |
| PF-04620110 2.5 mg QD, Then PF-04620110 2.5 mg BID | Change From Baseline in Fasting Insulin at Day 28 | Change at Day 28 (n=8, 9, 8) | -0.8 micro-IU/mL | Standard Deviation 4 |
| PF-04620110 5 mg QD | Change From Baseline in Fasting Insulin at Day 28 | Baseline (n=9, 10, 8) | 19.8 micro-IU/mL | Standard Deviation 27.2 |
| PF-04620110 5 mg QD | Change From Baseline in Fasting Insulin at Day 28 | Change at Day 28 (n=8, 9, 8) | -8.0 micro-IU/mL | Standard Deviation 12.8 |
| Placebo | Change From Baseline in Fasting Insulin at Day 28 | Baseline (n=9, 10, 8) | 9.2 micro-IU/mL | Standard Deviation 4.2 |
| Placebo | Change From Baseline in Fasting Insulin at Day 28 | Change at Day 28 (n=8, 9, 8) | 0.2 micro-IU/mL | Standard Deviation 2.7 |
Secondary
Change From Baseline in Fasting Net Triglycerides at Day 28
Time frame: 0 hour (pre-dose) on Day -1, Day 28
Population: Analysis population included all enrolled participants who received at least 1 dose of study medication and had at least 1 fasting net triglycerides value. Here, 'n' is participants evaluable at specified time points for each group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PF-04620110 2.5 mg QD, Then PF-04620110 2.5 mg BID | Change From Baseline in Fasting Net Triglycerides at Day 28 | Baseline (n=16, 16, 16) | 189.1 mg/dL | Standard Deviation 111.7 |
| PF-04620110 2.5 mg QD, Then PF-04620110 2.5 mg BID | Change From Baseline in Fasting Net Triglycerides at Day 28 | Change at Day 28 (16, 16, 15) | -31.2 mg/dL | Standard Deviation 103.6 |
| PF-04620110 5 mg QD | Change From Baseline in Fasting Net Triglycerides at Day 28 | Change at Day 28 (16, 16, 15) | -18.4 mg/dL | Standard Deviation 52.1 |
| PF-04620110 5 mg QD | Change From Baseline in Fasting Net Triglycerides at Day 28 | Baseline (n=16, 16, 16) | 234.8 mg/dL | Standard Deviation 116.7 |
| Placebo | Change From Baseline in Fasting Net Triglycerides at Day 28 | Baseline (n=16, 16, 16) | 187.4 mg/dL | Standard Deviation 81.6 |
| Placebo | Change From Baseline in Fasting Net Triglycerides at Day 28 | Change at Day 28 (16, 16, 15) | -19.2 mg/dL | Standard Deviation 56.7 |
Secondary
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
Change from baseline in GIP area under the plasma concentration time curve was computed by Linear trapezoidal method.
Time frame: Baseline (Day -1); 2 to 6 hours post-dose on Day 28
Population: Analysis population included all enrolled participants who received at least 1 dose of study medication and had at least 1 GIP area under the curve (AUC) value. Here, 'n' is participants evaluable at specified time points for each group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PF-04620110 2.5 mg QD, Then PF-04620110 2.5 mg BID | 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 (n=15, 16, 16) | 1372.8 pg*hr/mL | Standard Deviation 617.2 |
| PF-04620110 2.5 mg QD, Then PF-04620110 2.5 mg BID | 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 | Change at Day 28 (n=14, 16, 15) | -141.6 pg*hr/mL | Standard Deviation 726.1 |
| PF-04620110 5 mg QD | 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 (n=15, 16, 16) | 1181.0 pg*hr/mL | Standard Deviation 614.6 |
| PF-04620110 5 mg QD | 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 | Change at Day 28 (n=14, 16, 15) | -277.1 pg*hr/mL | Standard Deviation 541.4 |
| Placebo | 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 (n=15, 16, 16) | 1619.2 pg*hr/mL | Standard Deviation 627.7 |
| Placebo | 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 | Change at Day 28 (n=14, 16, 15) | 46.8 pg*hr/mL | Standard Deviation 473.1 |
Secondary
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
Change from baseline in PYY area under the plasma concentration time curve was computed by Linear trapezoidal method.
Time frame: Baseline (Day -1); 2 to 6 hours post-dose on Day 28
Population: Analysis population included all enrolled participants who received at least 1 dose of study medication and had at least 1 PYY area under the curve (AUC) value. Here, 'n' is participants evaluable at specified time points for each group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PF-04620110 2.5 mg QD, Then PF-04620110 2.5 mg BID | 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 (n=15, 16, 16) | 409.0 pg*hr/mL | Standard Deviation 192.4 |
| PF-04620110 2.5 mg QD, Then PF-04620110 2.5 mg BID | 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 | Change at Day 28 (n=14, 16, 14) | 196.6 pg*hr/mL | Standard Deviation 242.8 |
| PF-04620110 5 mg QD | 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 | Change at Day 28 (n=14, 16, 14) | 96.7 pg*hr/mL | Standard Deviation 194.2 |
| PF-04620110 5 mg QD | 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 (n=15, 16, 16) | 540.7 pg*hr/mL | Standard Deviation 273.8 |
| Placebo | 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 (n=15, 16, 16) | 395.0 pg*hr/mL | Standard Deviation 114.6 |
| Placebo | 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 | Change at Day 28 (n=14, 16, 14) | 24.4 pg*hr/mL | Standard Deviation 126.9 |
Secondary
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
Change from baseline in post-dinner glucose excursion under the plasma concentration time curve was computed by Linear trapezoidal method.
Time frame: Baseline (Day -1); 12 to 16 hours post-dose on Day 28
Population: Analysis population included all enrolled participants who received at least 1 dose of study medication and had at least 1 post-dinner glucose excursion area under the curve (AUC) value. Here, 'n' is participants evaluable at specified time points for each group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PF-04620110 2.5 mg QD, Then PF-04620110 2.5 mg BID | 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 | Change at Day 28 (n=15, 16, 15) | -132.8 mg*hr/dL | Standard Deviation 267.5 |
| PF-04620110 2.5 mg QD, Then PF-04620110 2.5 mg BID | 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 (n=16, 16, 16) | 851.2 mg*hr/dL | Standard Deviation 217.2 |
| PF-04620110 5 mg QD | 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 (n=16, 16, 16) | 763.9 mg*hr/dL | Standard Deviation 215.8 |
| PF-04620110 5 mg QD | 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 | Change at Day 28 (n=15, 16, 15) | -104.8 mg*hr/dL | Standard Deviation 210.8 |
| Placebo | 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 (n=16, 16, 16) | 759.4 mg*hr/dL | Standard Deviation 180 |
| Placebo | 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 | Change at Day 28 (n=15, 16, 15) | -41.4 mg*hr/dL | Standard Deviation 124 |
Secondary
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
Change from baseline in post-lunch glucose excursion under the plasma concentration time curve was computed by Linear trapezoidal method.
Time frame: Baseline (Day -1); 6 to 10 hours post-dose on Day 28
Population: Analysis population included all enrolled participants who received at least 1 dose of study medication and had at least 1 post-lunch glucose excursion area under the curve (AUC) value. Here, 'n' is participants evaluable at specified time points for each group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PF-04620110 2.5 mg QD, Then PF-04620110 2.5 mg BID | 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 | Change at Day 28 (n=15, 16, 15) | -34.9 mg*hr/dL | Standard Deviation 377.2 |
| PF-04620110 2.5 mg QD, Then PF-04620110 2.5 mg BID | 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 (n=16, 16, 16) | 853.4 mg*hr/dL | Standard Deviation 293.4 |
| PF-04620110 5 mg QD | 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 | Change at Day 28 (n=15, 16, 15) | -41.4 mg*hr/dL | Standard Deviation 202.9 |
| PF-04620110 5 mg QD | 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 (n=16, 16, 16) | 772.3 mg*hr/dL | Standard Deviation 259.3 |
| Placebo | 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 (n=16, 16, 16) | 730.2 mg*hr/dL | Standard Deviation 174.9 |
| Placebo | 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 | Change at Day 28 (n=15, 16, 15) | -90.4 mg*hr/dL | Standard Deviation 157.3 |
Secondary
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
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.
Time frame: Baseline (Day -1); 2 to 6 hours post-dose on Day 28
Population: Analysis population included all enrolled participants who received at least 1 dose of study medication and had at least 1 post-MMTT C-peptide area under the curve (AUC) value. Here, 'n' is participants evaluable at specified time points for each group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PF-04620110 2.5 mg QD, Then PF-04620110 2.5 mg BID | 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 (n=16, 16, 16) | 17.8 ng*hr/mL | Standard Deviation 6.2 |
| PF-04620110 2.5 mg QD, Then PF-04620110 2.5 mg BID | 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 | Change at Day 28 (15, 16, 15) | -0.2 ng*hr/mL | Standard Deviation 6 |
| PF-04620110 5 mg QD | 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 (n=16, 16, 16) | 21.6 ng*hr/mL | Standard Deviation 10.1 |
| PF-04620110 5 mg QD | 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 | Change at Day 28 (15, 16, 15) | -4.0 ng*hr/mL | Standard Deviation 6.2 |
| Placebo | 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 (n=16, 16, 16) | 20.3 ng*hr/mL | Standard Deviation 5.4 |
| Placebo | 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 | Change at Day 28 (15, 16, 15) | -0.2 ng*hr/mL | Standard Deviation 5.2 |
Secondary
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
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.
Time frame: Baseline (Day -1); 2 to 6 hours post-dose on Day 28
Population: Analysis population included all enrolled participants who received at least 1 dose of study medication and had at least 1 post-MMTT insulin area under the curve (AUC) value. Here, 'n' is participants evaluable at specified time points for each group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PF-04620110 2.5 mg QD, Then PF-04620110 2.5 mg BID | 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 (n=16, 16, 16) | 122.9 micro-IU*hr/mL | Standard Deviation 82.9 |
| PF-04620110 2.5 mg QD, Then PF-04620110 2.5 mg BID | 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 | Change at Day 28 (n=15, 16, 15) | 12.4 micro-IU*hr/mL | Standard Deviation 63.9 |
| PF-04620110 5 mg QD | 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 (n=16, 16, 16) | 220.2 micro-IU*hr/mL | Standard Deviation 282.9 |
| PF-04620110 5 mg QD | 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 | Change at Day 28 (n=15, 16, 15) | 0.6 micro-IU*hr/mL | Standard Deviation 159.3 |
| Placebo | 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 (n=16, 16, 16) | 156.7 micro-IU*hr/mL | Standard Deviation 63.3 |
| Placebo | 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 | Change at Day 28 (n=15, 16, 15) | 41.0 micro-IU*hr/mL | Standard Deviation 46 |
Secondary
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
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.
Time frame: Baseline (Day -1); 2 to 6 hours post-dose on Day 28
Population: Analysis population included all enrolled participants who received at least 1 dose of study medication and had at least 1 post-MMTT net triglyceride area under the curve (AUC) value. Here, 'n' is participants evaluable at specified time points for each group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PF-04620110 2.5 mg QD, Then PF-04620110 2.5 mg BID | 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 (n=16, 16, 16) | 860.6 mg*hr/dL | Standard Deviation 456.9 |
| PF-04620110 2.5 mg QD, Then PF-04620110 2.5 mg BID | 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 | Change at Day 28 (n=13, 16, 15) | -185.0 mg*hr/dL | Standard Deviation 436.7 |
| PF-04620110 5 mg QD | 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 (n=16, 16, 16) | 1014.4 mg*hr/dL | Standard Deviation 403.5 |
| PF-04620110 5 mg QD | 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 | Change at Day 28 (n=13, 16, 15) | -100.5 mg*hr/dL | Standard Deviation 268.4 |
| Placebo | 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 (n=16, 16, 16) | 961.2 mg*hr/dL | Standard Deviation 380.7 |
| Placebo | 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 | Change at Day 28 (n=13, 16, 15) | -110.3 mg*hr/dL | Standard Deviation 245.3 |
Secondary
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
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.
Time frame: Baseline (Day -1); 2 to 6 hours post-dose on Day 28
Population: Analysis population included all enrolled participants who received at least 1 dose of study medication and had at least 1 total amide GLP-1 and active GLP-1 area under the curve (AUC) value. Here, 'n' is participants evaluable at specified time points for each group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PF-04620110 2.5 mg QD, Then PF-04620110 2.5 mg BID | 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 | Active GLP-1: Change at Day 28 (n=14, 14, 14) | 12.5 pmol*hr/L | Standard Deviation 15 |
| PF-04620110 2.5 mg QD, Then PF-04620110 2.5 mg BID | 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 | Total amide GLP-1: Baseline (n=16, 15, 15) | 54.4 pmol*hr/L | Standard Deviation 26.8 |
| PF-04620110 2.5 mg QD, Then PF-04620110 2.5 mg BID | 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 | Active GLP-1: Baseline (n=15, 16, 15) | 16.3 pmol*hr/L | Standard Deviation 11.5 |
| PF-04620110 2.5 mg QD, Then PF-04620110 2.5 mg BID | 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 | Total amide GLP-1: Change at Day 28 (n=15, 15, 14) | 25.3 pmol*hr/L | Standard Deviation 27.9 |
| PF-04620110 5 mg QD | 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 | Active GLP-1: Change at Day 28 (n=14, 14, 14) | -0.5 pmol*hr/L | Standard Deviation 23.6 |
| PF-04620110 5 mg QD | 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 | Total amide GLP-1: Baseline (n=16, 15, 15) | 63.2 pmol*hr/L | Standard Deviation 36.4 |
| PF-04620110 5 mg QD | 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 | Total amide GLP-1: Change at Day 28 (n=15, 15, 14) | 4.7 pmol*hr/L | Standard Deviation 29.5 |
| PF-04620110 5 mg QD | 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 | Active GLP-1: Baseline (n=15, 16, 15) | 21.0 pmol*hr/L | Standard Deviation 21.5 |
| Placebo | 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 | Active GLP-1: Change at Day 28 (n=14, 14, 14) | 2.1 pmol*hr/L | Standard Deviation 11.1 |
| Placebo | 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 | Active GLP-1: Baseline (n=15, 16, 15) | 13.9 pmol*hr/L | Standard Deviation 11.4 |
| Placebo | 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 | Total amide GLP-1: Baseline (n=16, 15, 15) | 70.2 pmol*hr/L | Standard Deviation 88.1 |
| Placebo | 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 | Total amide GLP-1: Change at Day 28 (n=15, 15, 14) | -17.5 pmol*hr/L | Standard Deviation 88.9 |
Secondary
Maximum Observed Plasma Concentration (Cmax) of PF-04620110
Time frame: 24 hours post-morning dose on Day 28
Population: Analysis population included all enrolled participants who received at least 1 dose of study medication and had at least 1 Cmax value.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-04620110 2.5 mg QD, Then PF-04620110 2.5 mg BID | Maximum Observed Plasma Concentration (Cmax) of PF-04620110 | 91.0 ng/mL | Standard Deviation 39.3 |
| PF-04620110 5 mg QD | Maximum Observed Plasma Concentration (Cmax) of PF-04620110 | 112.0 ng/mL | Standard Deviation 43.7 |
Secondary
Minimum Observed Plasma Trough Concentration (Cmin) of PF-04620110
Time frame: 24 hours post-morning dose on Day 28
Population: Analysis population included all enrolled participants who received at least 1 dose of study medication and had at least 1 Cmin value.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-04620110 2.5 mg QD, Then PF-04620110 2.5 mg BID | Minimum Observed Plasma Trough Concentration (Cmin) of PF-04620110 | 16.2 ng/mL | Standard Deviation 12.4 |
| PF-04620110 5 mg QD | Minimum Observed Plasma Trough Concentration (Cmin) of PF-04620110 | 5.2 ng/mL | Standard Deviation 9.2 |
Secondary
Time to Cmax (Tmax) of PF-04620110
Time frame: 24 hours post-morning dose on Day 28
Population: Analysis population included all enrolled participants who received at least 1 dose of study medication and had at least 1 Tmax value.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PF-04620110 2.5 mg QD, Then PF-04620110 2.5 mg BID | Time to Cmax (Tmax) of PF-04620110 | 3.0 hr |
| PF-04620110 5 mg QD | Time to Cmax (Tmax) of PF-04620110 | 3.0 hr |