Diabetes Mellitus, Type 2
Conditions
Keywords
Type 2 Diabetes Mellitus, Pharmacodynamics, Safety & Tolerability
Brief summary
This study is designed to assess the safety, tolerability and pharmacodynamics of 6 weeks of oral doses of PF-05175157 provided as monotherapy in subjects with type 2 diabetes mellitus.
Interventions
DRUGPF-05175157
PF-05175157 will be administered at 200 mg twice a day for 43 days.
DRUGPlacebo
Placebo tablets matched to PF-05175157 will be administered twice a day for 43 days.
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Subjects who have been diagnosed with type 2 diabetes mellitus by a medical professional according to the American Diabetes Association guidelines. * Hemoglobin A1c of ≥7 and ≤10.0% in subjects who are metformin-naive or have not taken metformin for 2 months or Hemoglobin A1c of ≥6.5 and ≤9.5% in subjects who are metformin-naïve and are taking SU or DPP-IVi which is washed off or taking metformin and are willing to discontinue metformin in a 8-week washout period.
Exclusion criteria
* Evidence or history of clinically significant hematological, renal, endocrine (other than T2DM and hypothyroidism), gastrointestinal, cardiovascular, pulmonary, hepatic, psychiatric or neurologic disease. * A waist circumference which makes fitting imto the bore of the MR scanner impossible. Subjects with history of dry eye, known ocular or systemic disease that affect the sclera or cornea.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Change From Baseline and Absolute Values in Electrocardiogram (ECG) Meeting Categorical Summarisation Criteria in Part B | Screening up to follow-up (up to approximately 10 to 14 days after the last study drug administration) | Criteria for PCI changes in ECG (12-lead) were defined as: 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 (PR interval) \>=300 milliseconds (msec) and increase of \>=25% from baseline when baseline \>200 msec or increase of \>=50% when baseline less than or equal to (\<=) 200 msec; the time from the beginning of the electrocardiogram Q wave to the end of the S wave corresponding to ventricular depolarization (QRS interval) \>=140 msec and increase of \>=50% from baseline; the time corresponding to the beginning of depolarization to repolarization of the ventricles (QT), corrected for heart rate (QTc) using the Fridericia formula (QTcF) of 450 to \< 480 msec and \>=480 msec, or an increase from baseline of 30 to \<60 msec or \>=60 msec. |
| Whole-body Glucose Uptake in Part A | 1 day | Whole-body glucose uptake (Rate of glucose disappearance, Rd) during the Step 2 Clamp |
| Whole-body Glucose Uptake in Part B in Placebo Group | 6 weeks | Whole-body glucose uptake (Rate of glucose disappearance, Rd) during the Step 2 Clamp |
| Whole-body Glucose Uptake in Part B in PF-05175157 200 mg BID Group | 6 weeks | Whole-body glucose uptake (Rate of glucose disappearance, Rd) during the Step 2 Clamp |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Serious Adverse Events (SAEs), or Discontinuation Due to Adverse Events (AEs) in Part B | Baseline to follow-up (up to approximately 10 to 14 days after the last study drug administration) | An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. |
| Number of Participants With Laboratory Test Abnormalities in Part B | Screening up to follow-up (up to approximately 10 to 14 days after the last study drug administration) | Number of participants with laboratory test abnormalities without regard to baseline abnormality. The following laboratory parameters were analyzed: hematology (hemoglobin, hematocrit, red blood cell \[RBC\] count, platelet count, white blood cell \[WBC\] count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes); blood chemistry (blood urea nitrogen \[BUN\], creatinine, glucose, calcium, sodium, potassium, chloride, total bicarbonate, aspartate aminotransferase \[AST\], alanine aminotransferase \[ALT\], total bilirubin, alkaline phosphatase, uric acid, albumin, total protein, and creatine phosphokinase); urinalysis (pH, glucose, protein, blood, ketones, nitrites, leukocyte esterase, and microscopy); others (follicle stimulating hormone \[FSH\], urine drug screen, lipid profile and very-low-density lipoproteins \[VLDL\], hemoglobin A1c \[HbA1c\], C-peptide, thyroid-stimulating hormone \[TSH\], Hepatitis B and C, human immunodeficiency virus \[HIV\], triglycerides, urine creatinine). |
| Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Categorical Summarization Criteria in Part B | Screening up to follow-up (up to approximately 10 to 14 days after the last study drug administration) | Criteria for potentially clinical important (PCI) change in vital signs included: sitting systolic blood pressure (SBP) of less than (\<) 90 millimeters of mercury (mm Hg) or change in sitting SBP of greater or equal to (\>=)30 mm Hg, sitting diastolic blood pressure (DBP) of \<50 mm Hg or change in sitting DBP of \>=20 mm Hg, sitting pulse rate of \<40 or greater than (\>) 120 beats per minute (bpm). |
| Glucose Infusion Rates (GIR) in Part A | 1 day | GIR obtained averaging respectively the last 30 minutes of glucose infusion at steady state on Step 1 (ie 150 to 180 min) and Step 2 (ie 330 to 360 min) insulin infusion. Whole-body insulin sensitivity was assessed with the euglycemic hyperinsulinemic clamp procedure; the use of 2 stepped insulin infusions and labeled glucose allowed the differentiation between hepatic and peripheral insulin sensitivity. Assessment of whole body insulin sensitivity was performed during the steady states of the low insulin infusion rate (ie, Step 1) and during the steady state of the high insulin infusion rate (ie, Step 2). These indices were called GIR1 and GIR2, respectively. |
| Endogenous Gucose Production (EGP) in Part A | 1 day | EGP measured by means of euglycemic hyperinsulinemic clamp preceding insulin infusion (EGP0), on Step 1 insulin infusion (EGP1) and on Step 2 insulin infusion (EGP2). Whole-body insulin sensitivity was assessed with the euglycemic hyperinsulinemic clamp procedure; the use of 2 stepped insulin infusions and labeled glucose allowed the differentiation between hepatic and peripheral insulin sensitivity. EGP was measured under basal conditions; then during the low dose insulin infusion EGP was partially suppressed (hepatic insulin sensitivity), while during the high dose insulin infusion, EGP was almost completely suppressed and peripheral glucose uptake was maximally stimulated (peripheral insulin sensitivity). |
| [6,6-2H2] Plasma Glucose Enrichment (PGE) in Part A | 1 day | \[6,6-2H2\] PGE was the molar fraction of labeled glucose measured in plasma. Whole-body insulin sensitivity was assessed with the euglycemic hyperinsulinemic clamp procedure; the use of 2 stepped insulin infusions and labeled glucose allowed the differentiation between hepatic and peripheral insulin sensitivity. |
| Rate of Appearance of Glucose (Ra) in Part A | 1 day | Rate of appearance of glucose (Ra) in fasting state and during insulin infusions (Step 1 and Step 2). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| GIR in Part B in PF-05175157 200 mg BID Group | 6 weeks | Glucose Infusion Rate rates obtained averaging respectively the last 30 minutes of glucose infusion at steady state on Step 1 (ie 150 to 180 min) and Step 2 (ie 330 to 360 min) insulin infusion. |
| EGP in Part B in Placebo Group | 6 weeks | EGP measured by means of euglycemic hyperinsulinemic clamp preceding insulin infusion (EGP0), on Step 1 insulin infusion (EGP1) and on Step 2 insulin infusion (EGP2) |
| EGP in Part B in PF-05175157 200 mg BID Group | 6 weeks | EGP measured by means of euglycemic hyperinsulinemic clamp preceding insulin infusion (EGP0), on Step 1 insulin infusion (EGP1) and on Step 2 insulin infusion (EGP2) |
| Ra in Part B in Placebo Group | 6 weeks | Ra in fasting state and during insulin infusions (Step 1 and Step 2). |
| Ra in Part B in PF-05175157 200 mg BID Group | 6 weeks | Ra in fasting state and during insulin infusions (Step 1 and Step 2). |
| GIR in Part B in Placebo Group | 6 weeks | Glucose Infusion Rate rates obtained averaging respectively the last 30 minutes of glucose infusion at steady state on Step 1 (ie 150 to 180 min) and Step 2 (ie 330 to 360 min) insulin infusion. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Participants in Part A Participants underwent 2 step euglycemic hyperinsulinemic clamp procedure and were infused with insulin according to a specified algorithm to reduce plasma glucose levels to approximately 100 milligram (mg)/deciliter (dL). In Step 1 of the clamp, each individual's insulin infusion rate during the last 2 hours of the overnight infusion was increased by 10 mU/square meter (m\^2)/minute (min). During Step 2, all participants received an insulin infusion, at a rate of 120 mU/m\^2/min. | 6 |
| Placebo - Part B Participants received placebo twice a day at approximately 08:00 immediately before the morning meal, and at approximately 18:00 before the dinner meal. The treatment period was 6 weeks. | 6 |
| PF-05175157 200 mg Twice a Day - Part B Participants received PF-05175157 200 mg twice a day at approximately 08:00 immediately before the morning meal, and at approximately 18:00 before the dinner meal. The treatment period was 6 weeks. | 7 |
| Total | 19 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Part B | Adverse Event | 0 | 0 | 1 |
| Part B | Study terminated | 0 | 4 | 3 |
Baseline characteristics
| Characteristic | All Participants in Part A | Placebo - Part B | PF-05175157 200 mg Twice a Day - Part B | Total |
|---|---|---|---|---|
| Age, Continuous | 50.7 Years STANDARD_DEVIATION 9.5 | 49.3 Years STANDARD_DEVIATION 9.2 | 55.1 Years STANDARD_DEVIATION 4.6 | 51.9 Years STANDARD_DEVIATION 7.9 |
| Sex/Gender, Customized Female | 1 Participants | 1 Participants | 2 Participants | 4 Participants |
| Sex/Gender, Customized Male | 5 Participants | 5 Participants | 5 Participants | 15 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 | 0 / 6 | 5 / 7 | 1 / 6 |
| serious Total, serious adverse events | 0 / 6 | 1 / 7 | 0 / 6 |
Outcome results
Primary
[6,6-2H2] Plasma Glucose Enrichment (PGE) in Part A
\[6,6-2H2\] PGE was the molar fraction of labeled glucose measured in plasma. Whole-body insulin sensitivity was assessed with the euglycemic hyperinsulinemic clamp procedure; the use of 2 stepped insulin infusions and labeled glucose allowed the differentiation between hepatic and peripheral insulin sensitivity.
Time frame: 1 day
Population: All participants randomized and who had at least one euglycemic hyperinsulinemic clamp
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| All Participants in Part A | [6,6-2H2] Plasma Glucose Enrichment (PGE) in Part A | Clamp 1 | 2.96 percentage enrichment of plasma glucose |
| All Participants in Part A | [6,6-2H2] Plasma Glucose Enrichment (PGE) in Part A | Clamp 2 | 2.97 percentage enrichment of plasma glucose |
Primary
Endogenous Gucose Production (EGP) in Part A
EGP measured by means of euglycemic hyperinsulinemic clamp preceding insulin infusion (EGP0), on Step 1 insulin infusion (EGP1) and on Step 2 insulin infusion (EGP2). Whole-body insulin sensitivity was assessed with the euglycemic hyperinsulinemic clamp procedure; the use of 2 stepped insulin infusions and labeled glucose allowed the differentiation between hepatic and peripheral insulin sensitivity. EGP was measured under basal conditions; then during the low dose insulin infusion EGP was partially suppressed (hepatic insulin sensitivity), while during the high dose insulin infusion, EGP was almost completely suppressed and peripheral glucose uptake was maximally stimulated (peripheral insulin sensitivity).
Time frame: 1 day
Population: All participants randomized and who had at least one euglycemic hyperinsulinemic clamp
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| All Participants in Part A | Endogenous Gucose Production (EGP) in Part A | Clamp 1 EGP0 | 1.79 mg/kilogram (kg) body weight (BW)/min |
| All Participants in Part A | Endogenous Gucose Production (EGP) in Part A | Clamp 1 EGP1 | 0.85 mg/kilogram (kg) body weight (BW)/min |
| All Participants in Part A | Endogenous Gucose Production (EGP) in Part A | Clamp 1 EGP2 | 0.07 mg/kilogram (kg) body weight (BW)/min |
| All Participants in Part A | Endogenous Gucose Production (EGP) in Part A | Clamp 2 EGP0 | 1.68 mg/kilogram (kg) body weight (BW)/min |
| All Participants in Part A | Endogenous Gucose Production (EGP) in Part A | Clamp 2 EGP1 | 0.81 mg/kilogram (kg) body weight (BW)/min |
Primary
Glucose Infusion Rates (GIR) in Part A
GIR obtained averaging respectively the last 30 minutes of glucose infusion at steady state on Step 1 (ie 150 to 180 min) and Step 2 (ie 330 to 360 min) insulin infusion. Whole-body insulin sensitivity was assessed with the euglycemic hyperinsulinemic clamp procedure; the use of 2 stepped insulin infusions and labeled glucose allowed the differentiation between hepatic and peripheral insulin sensitivity. Assessment of whole body insulin sensitivity was performed during the steady states of the low insulin infusion rate (ie, Step 1) and during the steady state of the high insulin infusion rate (ie, Step 2). These indices were called GIR1 and GIR2, respectively.
Time frame: 1 day
Population: All participants randomized and who had at least one euglycemic hyperinsulinemic clamp
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| All Participants in Part A | Glucose Infusion Rates (GIR) in Part A | Clamp 1 GIR1 | 191 mg/min |
| All Participants in Part A | Glucose Infusion Rates (GIR) in Part A | Clamp 1 GIR2 | 780 mg/min |
| All Participants in Part A | Glucose Infusion Rates (GIR) in Part A | Clamp 2 GIR1 | 152 mg/min |
Primary
Number of Participants With Change From Baseline and Absolute Values in Electrocardiogram (ECG) Meeting Categorical Summarisation Criteria in Part B
Criteria for PCI changes in ECG (12-lead) were defined as: 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 (PR interval) \>=300 milliseconds (msec) and increase of \>=25% from baseline when baseline \>200 msec or increase of \>=50% when baseline less than or equal to (\<=) 200 msec; the time from the beginning of the electrocardiogram Q wave to the end of the S wave corresponding to ventricular depolarization (QRS interval) \>=140 msec and increase of \>=50% from baseline; the time corresponding to the beginning of depolarization to repolarization of the ventricles (QT), corrected for heart rate (QTc) using the Fridericia formula (QTcF) of 450 to \< 480 msec and \>=480 msec, or an increase from baseline of 30 to \<60 msec or \>=60 msec.
Time frame: Screening up to follow-up (up to approximately 10 to 14 days after the last study drug administration)
Population: All participants who were admitted to the CRU on Day -5.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| All Participants in Part A | Number of Participants With Change From Baseline and Absolute Values in Electrocardiogram (ECG) Meeting Categorical Summarisation Criteria in Part B | QTc increase from Baseline of >=60 msec | 0 Participants |
| All Participants in Part A | Number of Participants With Change From Baseline and Absolute Values in Electrocardiogram (ECG) Meeting Categorical Summarisation Criteria in Part B | QTcF increase from Baseline of >=60 msec | 0 Participants |
| PF-05175157 200 mg Twice a Day - Part B | Number of Participants With Change From Baseline and Absolute Values in Electrocardiogram (ECG) Meeting Categorical Summarisation Criteria in Part B | QTc increase from Baseline of >=60 msec | 1 Participants |
| PF-05175157 200 mg Twice a Day - Part B | Number of Participants With Change From Baseline and Absolute Values in Electrocardiogram (ECG) Meeting Categorical Summarisation Criteria in Part B | QTcF increase from Baseline of >=60 msec | 1 Participants |
Primary
Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Categorical Summarization Criteria in Part B
Criteria for potentially clinical important (PCI) change in vital signs included: sitting systolic blood pressure (SBP) of less than (\<) 90 millimeters of mercury (mm Hg) or change in sitting SBP of greater or equal to (\>=)30 mm Hg, sitting diastolic blood pressure (DBP) of \<50 mm Hg or change in sitting DBP of \>=20 mm Hg, sitting pulse rate of \<40 or greater than (\>) 120 beats per minute (bpm).
Time frame: Screening up to follow-up (up to approximately 10 to 14 days after the last study drug administration)
Population: All participants who were admitted to the CRU on Day -5
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| All Participants in Part A | Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Categorical Summarization Criteria in Part B | SBP <90 mm Hg | 0 Participants |
| All Participants in Part A | Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Categorical Summarization Criteria in Part B | DBP <50 mm Hg | 0 Participants |
| All Participants in Part A | Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Categorical Summarization Criteria in Part B | Pulse Rate <40 bpm | 0 Participants |
| All Participants in Part A | Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Categorical Summarization Criteria in Part B | Pulse Rate >120 bpm | 0 Participants |
| All Participants in Part A | Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Categorical Summarization Criteria in Part B | SBP maximum increase from baseline >=30 mm Hg | 0 Participants |
| All Participants in Part A | Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Categorical Summarization Criteria in Part B | DBP maximum increase from baseline >=20 mm Hg | 0 Participants |
| All Participants in Part A | Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Categorical Summarization Criteria in Part B | SBP maximum decrease from baseline >=30 mm Hg | 0 Participants |
| All Participants in Part A | Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Categorical Summarization Criteria in Part B | DBP maximum decrease from baseline >=20 mm Hg | 0 Participants |
| PF-05175157 200 mg Twice a Day - Part B | Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Categorical Summarization Criteria in Part B | DBP maximum decrease from baseline >=20 mm Hg | 0 Participants |
| PF-05175157 200 mg Twice a Day - Part B | Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Categorical Summarization Criteria in Part B | SBP <90 mm Hg | 0 Participants |
| PF-05175157 200 mg Twice a Day - Part B | Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Categorical Summarization Criteria in Part B | SBP maximum increase from baseline >=30 mm Hg | 0 Participants |
| PF-05175157 200 mg Twice a Day - Part B | Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Categorical Summarization Criteria in Part B | DBP <50 mm Hg | 0 Participants |
| PF-05175157 200 mg Twice a Day - Part B | Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Categorical Summarization Criteria in Part B | SBP maximum decrease from baseline >=30 mm Hg | 1 Participants |
| PF-05175157 200 mg Twice a Day - Part B | Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Categorical Summarization Criteria in Part B | Pulse Rate <40 bpm | 0 Participants |
| PF-05175157 200 mg Twice a Day - Part B | Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Categorical Summarization Criteria in Part B | DBP maximum increase from baseline >=20 mm Hg | 0 Participants |
| PF-05175157 200 mg Twice a Day - Part B | Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Categorical Summarization Criteria in Part B | Pulse Rate >120 bpm | 0 Participants |
Primary
Number of Participants With Laboratory Test Abnormalities in Part B
Number of participants with laboratory test abnormalities without regard to baseline abnormality. The following laboratory parameters were analyzed: hematology (hemoglobin, hematocrit, red blood cell \[RBC\] count, platelet count, white blood cell \[WBC\] count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes); blood chemistry (blood urea nitrogen \[BUN\], creatinine, glucose, calcium, sodium, potassium, chloride, total bicarbonate, aspartate aminotransferase \[AST\], alanine aminotransferase \[ALT\], total bilirubin, alkaline phosphatase, uric acid, albumin, total protein, and creatine phosphokinase); urinalysis (pH, glucose, protein, blood, ketones, nitrites, leukocyte esterase, and microscopy); others (follicle stimulating hormone \[FSH\], urine drug screen, lipid profile and very-low-density lipoproteins \[VLDL\], hemoglobin A1c \[HbA1c\], C-peptide, thyroid-stimulating hormone \[TSH\], Hepatitis B and C, human immunodeficiency virus \[HIV\], triglycerides, urine creatinine).
Time frame: Screening up to follow-up (up to approximately 10 to 14 days after the last study drug administration)
Population: All participants who were admitted to the Clinical Research Unit (CRU) on Day -5
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Participants in Part A | Number of Participants With Laboratory Test Abnormalities in Part B | 6 Participants |
| PF-05175157 200 mg Twice a Day - Part B | Number of Participants With Laboratory Test Abnormalities in Part B | 7 Participants |
Primary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Serious Adverse Events (SAEs), or Discontinuation Due to Adverse Events (AEs) in Part B
An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Time frame: Baseline to follow-up (up to approximately 10 to 14 days after the last study drug administration)
Population: All participants who were admitted to the clinical research unit (CRU) on Day -5
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| All Participants in Part A | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Serious Adverse Events (SAEs), or Discontinuation Due to Adverse Events (AEs) in Part B | Participants w ith AEs | 1 Participants |
| All Participants in Part A | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Serious Adverse Events (SAEs), or Discontinuation Due to Adverse Events (AEs) in Part B | Participants w ith SAEs | 0 Participants |
| All Participants in Part A | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Serious Adverse Events (SAEs), or Discontinuation Due to Adverse Events (AEs) in Part B | Participants discontinued due to AEs | 0 Participants |
| PF-05175157 200 mg Twice a Day - Part B | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Serious Adverse Events (SAEs), or Discontinuation Due to Adverse Events (AEs) in Part B | Participants w ith AEs | 5 Participants |
| PF-05175157 200 mg Twice a Day - Part B | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Serious Adverse Events (SAEs), or Discontinuation Due to Adverse Events (AEs) in Part B | Participants w ith SAEs | 1 Participants |
| PF-05175157 200 mg Twice a Day - Part B | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Serious Adverse Events (SAEs), or Discontinuation Due to Adverse Events (AEs) in Part B | Participants discontinued due to AEs | 1 Participants |
Primary
Rate of Appearance of Glucose (Ra) in Part A
Rate of appearance of glucose (Ra) in fasting state and during insulin infusions (Step 1 and Step 2).
Time frame: 1 day
Population: All participants randomized and who had at least one euglycemic hyperinsulinemic clamp.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| All Participants in Part A | Rate of Appearance of Glucose (Ra) in Part A | Clamp 1 Step 1 | 3.575 mg/kg BW/min |
| All Participants in Part A | Rate of Appearance of Glucose (Ra) in Part A | Clamp 1 Step 2 | 14.829 mg/kg BW/min |
| All Participants in Part A | Rate of Appearance of Glucose (Ra) in Part A | Clamp 2 Step 1 | 2.859 mg/kg BW/min |
Primary
Whole-body Glucose Uptake in Part A
Whole-body glucose uptake (Rate of glucose disappearance, Rd) during the Step 2 Clamp
Time frame: 1 day
Population: All participants randomized and who had at least one euglycemic hyperinsulinemic clamp.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| All Participants in Part A | Whole-body Glucose Uptake in Part A | 14.829 mg/kg BW/min |
Primary
Whole-body Glucose Uptake in Part B in PF-05175157 200 mg BID Group
Whole-body glucose uptake (Rate of glucose disappearance, Rd) during the Step 2 Clamp
Time frame: 6 weeks
Population: Part B of the study was terminated due to the safety issue. Due to the limited participant number who completed study there no summary statistics were done by dosing regimen for Part B.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| All Participants in Part A | Whole-body Glucose Uptake in Part B in PF-05175157 200 mg BID Group | Step 2 Value 1 | 3.775 mg/kg BW/min |
| All Participants in Part A | Whole-body Glucose Uptake in Part B in PF-05175157 200 mg BID Group | Step 2 Value 2 | 9.033 mg/kg BW/min |
| All Participants in Part A | Whole-body Glucose Uptake in Part B in PF-05175157 200 mg BID Group | Step 2 Value 3 | 8.903 mg/kg BW/min |
| All Participants in Part A | Whole-body Glucose Uptake in Part B in PF-05175157 200 mg BID Group | Step 2 Value 4 | 11.310 mg/kg BW/min |
| All Participants in Part A | Whole-body Glucose Uptake in Part B in PF-05175157 200 mg BID Group | Step 2 Value 5 | 4.133 mg/kg BW/min |
| All Participants in Part A | Whole-body Glucose Uptake in Part B in PF-05175157 200 mg BID Group | Step 2 Value 6 | 6.763 mg/kg BW/min |
| All Participants in Part A | Whole-body Glucose Uptake in Part B in PF-05175157 200 mg BID Group | Step 2 Value 7 | 8.243 mg/kg BW/min |
| All Participants in Part A | Whole-body Glucose Uptake in Part B in PF-05175157 200 mg BID Group | Step 2 Value 8 | 7.180 mg/kg BW/min |
| All Participants in Part A | Whole-body Glucose Uptake in Part B in PF-05175157 200 mg BID Group | Step 2 Value 9 | 10.113 mg/kg BW/min |
| All Participants in Part A | Whole-body Glucose Uptake in Part B in PF-05175157 200 mg BID Group | Step 2 Value 10 | 6.205 mg/kg BW/min |
Primary
Whole-body Glucose Uptake in Part B in Placebo Group
Whole-body glucose uptake (Rate of glucose disappearance, Rd) during the Step 2 Clamp
Time frame: 6 weeks
Population: Part B of the study was terminated due to the safety issue. Due to the limited participant number who completed study there no summary statistics were done by dosing regimen for Part B.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| All Participants in Part A | Whole-body Glucose Uptake in Part B in Placebo Group | Step 2 Value 6 | 3.940 mg/kg BW/min |
| All Participants in Part A | Whole-body Glucose Uptake in Part B in Placebo Group | Step 2 Value 1 | 4.245 mg/kg BW/min |
| All Participants in Part A | Whole-body Glucose Uptake in Part B in Placebo Group | Step 2 Value 2 | 6.325 mg/kg BW/min |
| All Participants in Part A | Whole-body Glucose Uptake in Part B in Placebo Group | Step 2 Value 3 | 2.793 mg/kg BW/min |
| All Participants in Part A | Whole-body Glucose Uptake in Part B in Placebo Group | Step 2 Value 4 | 6.835 mg/kg BW/min |
| All Participants in Part A | Whole-body Glucose Uptake in Part B in Placebo Group | Step 2 Value 5 | 4.400 mg/kg BW/min |
| All Participants in Part A | Whole-body Glucose Uptake in Part B in Placebo Group | Step 2 Value 7 | 4.553 mg/kg BW/min |
| All Participants in Part A | Whole-body Glucose Uptake in Part B in Placebo Group | Step 2 Value 8 | 4.225 mg/kg BW/min |
Secondary
EGP in Part B in PF-05175157 200 mg BID Group
EGP measured by means of euglycemic hyperinsulinemic clamp preceding insulin infusion (EGP0), on Step 1 insulin infusion (EGP1) and on Step 2 insulin infusion (EGP2)
Time frame: 6 weeks
Population: Part B of the study was terminated due to the safety issue. Due to the limited participant number who completed study there no summary statistics were done by dosing regimen for Part B.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| All Participants in Part A | EGP in Part B in PF-05175157 200 mg BID Group | EGP0 Value 1 | 1.240 mg/kg fat free mass (FFM)/min |
| All Participants in Part A | EGP in Part B in PF-05175157 200 mg BID Group | EGP0 Value 2 | 1.445 mg/kg fat free mass (FFM)/min |
| All Participants in Part A | EGP in Part B in PF-05175157 200 mg BID Group | EGP0 Value 3 | 2.083 mg/kg fat free mass (FFM)/min |
| All Participants in Part A | EGP in Part B in PF-05175157 200 mg BID Group | EGP0 Value 4 | 1.708 mg/kg fat free mass (FFM)/min |
| All Participants in Part A | EGP in Part B in PF-05175157 200 mg BID Group | EGP0 Value 5 | 1.695 mg/kg fat free mass (FFM)/min |
| All Participants in Part A | EGP in Part B in PF-05175157 200 mg BID Group | EGP0 Value 6 | 1.615 mg/kg fat free mass (FFM)/min |
| All Participants in Part A | EGP in Part B in PF-05175157 200 mg BID Group | EGP0 Value 7 | 1.690 mg/kg fat free mass (FFM)/min |
| All Participants in Part A | EGP in Part B in PF-05175157 200 mg BID Group | EGP0 Value 8 | 1.393 mg/kg fat free mass (FFM)/min |
| All Participants in Part A | EGP in Part B in PF-05175157 200 mg BID Group | EGP0 Value 9 | 1.448 mg/kg fat free mass (FFM)/min |
| All Participants in Part A | EGP in Part B in PF-05175157 200 mg BID Group | EGP0 Value 10 | 1.345 mg/kg fat free mass (FFM)/min |
| All Participants in Part A | EGP in Part B in PF-05175157 200 mg BID Group | EGP1 Value 1 | 0.568 mg/kg fat free mass (FFM)/min |
| All Participants in Part A | EGP in Part B in PF-05175157 200 mg BID Group | EGP1 Value 2 | 0.250 mg/kg fat free mass (FFM)/min |
| All Participants in Part A | EGP in Part B in PF-05175157 200 mg BID Group | EGP1 Value 3 | 0.788 mg/kg fat free mass (FFM)/min |
| All Participants in Part A | EGP in Part B in PF-05175157 200 mg BID Group | EGP1 Value 4 | 0.575 mg/kg fat free mass (FFM)/min |
| All Participants in Part A | EGP in Part B in PF-05175157 200 mg BID Group | EGP1 Value 5 | 1.183 mg/kg fat free mass (FFM)/min |
| All Participants in Part A | EGP in Part B in PF-05175157 200 mg BID Group | EGP1 Value 6 | 0.538 mg/kg fat free mass (FFM)/min |
| All Participants in Part A | EGP in Part B in PF-05175157 200 mg BID Group | EGP1 Value 7 | 0.765 mg/kg fat free mass (FFM)/min |
| All Participants in Part A | EGP in Part B in PF-05175157 200 mg BID Group | EGP1 Value 8 | 0.555 mg/kg fat free mass (FFM)/min |
| All Participants in Part A | EGP in Part B in PF-05175157 200 mg BID Group | EGP1 Value 9 | 0.193 mg/kg fat free mass (FFM)/min |
| All Participants in Part A | EGP in Part B in PF-05175157 200 mg BID Group | EGP1 Value 10 | 0.418 mg/kg fat free mass (FFM)/min |
| All Participants in Part A | EGP in Part B in PF-05175157 200 mg BID Group | EGP2 Value 1 | 0.253 mg/kg fat free mass (FFM)/min |
| All Participants in Part A | EGP in Part B in PF-05175157 200 mg BID Group | EGP2 Value 2 | 0.165 mg/kg fat free mass (FFM)/min |
| All Participants in Part A | EGP in Part B in PF-05175157 200 mg BID Group | EGP2 Value 3 | -0.035 mg/kg fat free mass (FFM)/min |
| All Participants in Part A | EGP in Part B in PF-05175157 200 mg BID Group | EGP2 Value 4 | 0.243 mg/kg fat free mass (FFM)/min |
| All Participants in Part A | EGP in Part B in PF-05175157 200 mg BID Group | EGP2 Value 5 | 0.543 mg/kg fat free mass (FFM)/min |
| All Participants in Part A | EGP in Part B in PF-05175157 200 mg BID Group | EGP2 Value 6 | 0.110 mg/kg fat free mass (FFM)/min |
| All Participants in Part A | EGP in Part B in PF-05175157 200 mg BID Group | EGP2 Value 7 | 0.190 mg/kg fat free mass (FFM)/min |
| All Participants in Part A | EGP in Part B in PF-05175157 200 mg BID Group | EGP2 Value 8 | -0.313 mg/kg fat free mass (FFM)/min |
| All Participants in Part A | EGP in Part B in PF-05175157 200 mg BID Group | EGP2 Value 9 | -0.253 mg/kg fat free mass (FFM)/min |
| All Participants in Part A | EGP in Part B in PF-05175157 200 mg BID Group | EGP2 Value 10 | 0.198 mg/kg fat free mass (FFM)/min |
Secondary
EGP in Part B in Placebo Group
EGP measured by means of euglycemic hyperinsulinemic clamp preceding insulin infusion (EGP0), on Step 1 insulin infusion (EGP1) and on Step 2 insulin infusion (EGP2)
Time frame: 6 weeks
Population: Part B of the study was terminated due to the safety issue. Due to the limited participant number who completed study there no summary statistics were done by dosing regimen for Part B.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| All Participants in Part A | EGP in Part B in Placebo Group | EGP0 Value 1 | 1.540 mg/kg fat free mass (FFM)/min |
| All Participants in Part A | EGP in Part B in Placebo Group | EGP0 Value 2 | 1.690 mg/kg fat free mass (FFM)/min |
| All Participants in Part A | EGP in Part B in Placebo Group | EGP0 Value 3 | 1.285 mg/kg fat free mass (FFM)/min |
| All Participants in Part A | EGP in Part B in Placebo Group | EGP0 Value 4 | 1.575 mg/kg fat free mass (FFM)/min |
| All Participants in Part A | EGP in Part B in Placebo Group | EGP0 Value 5 | 1.965 mg/kg fat free mass (FFM)/min |
| All Participants in Part A | EGP in Part B in Placebo Group | EGP0 Value 6 | 1.538 mg/kg fat free mass (FFM)/min |
| All Participants in Part A | EGP in Part B in Placebo Group | EGP0 Value 7 | 1.518 mg/kg fat free mass (FFM)/min |
| All Participants in Part A | EGP in Part B in Placebo Group | EGP0 Value 8 | 1.518 mg/kg fat free mass (FFM)/min |
| All Participants in Part A | EGP in Part B in Placebo Group | EGP1 Value 1 | 0.600 mg/kg fat free mass (FFM)/min |
| All Participants in Part A | EGP in Part B in Placebo Group | EGP1 Value 2 | 0.585 mg/kg fat free mass (FFM)/min |
| All Participants in Part A | EGP in Part B in Placebo Group | EGP1 Value 3 | 0.525 mg/kg fat free mass (FFM)/min |
| All Participants in Part A | EGP in Part B in Placebo Group | EGP1 Value 4 | 0.500 mg/kg fat free mass (FFM)/min |
| All Participants in Part A | EGP in Part B in Placebo Group | EGP1 Value 5 | 0.808 mg/kg fat free mass (FFM)/min |
| All Participants in Part A | EGP in Part B in Placebo Group | EGP1 Value 6 | 0.830 mg/kg fat free mass (FFM)/min |
| All Participants in Part A | EGP in Part B in Placebo Group | EGP1 Value 7 | 0.560 mg/kg fat free mass (FFM)/min |
| All Participants in Part A | EGP in Part B in Placebo Group | EGP1 Value 8 | 0.825 mg/kg fat free mass (FFM)/min |
| All Participants in Part A | EGP in Part B in Placebo Group | EGP2 Value 1 | 0.200 mg/kg fat free mass (FFM)/min |
| All Participants in Part A | EGP in Part B in Placebo Group | EGP2 Value 2 | -0.063 mg/kg fat free mass (FFM)/min |
| All Participants in Part A | EGP in Part B in Placebo Group | EGP2 Value 3 | -0.050 mg/kg fat free mass (FFM)/min |
| All Participants in Part A | EGP in Part B in Placebo Group | EGP2 Value 4 | 0.280 mg/kg fat free mass (FFM)/min |
| All Participants in Part A | EGP in Part B in Placebo Group | EGP2 Value 5 | 0.145 mg/kg fat free mass (FFM)/min |
| All Participants in Part A | EGP in Part B in Placebo Group | EGP2 Value 6 | 0.223 mg/kg fat free mass (FFM)/min |
| All Participants in Part A | EGP in Part B in Placebo Group | EGP2 Value 7 | 0.180 mg/kg fat free mass (FFM)/min |
| All Participants in Part A | EGP in Part B in Placebo Group | EGP2 Value 8 | 0.405 mg/kg fat free mass (FFM)/min |
Secondary
GIR in Part B in PF-05175157 200 mg BID Group
Glucose Infusion Rate rates obtained averaging respectively the last 30 minutes of glucose infusion at steady state on Step 1 (ie 150 to 180 min) and Step 2 (ie 330 to 360 min) insulin infusion.
Time frame: 6 weeks
Population: Part B of the study was terminated due to the safety issue. Due to the limited participant number who completed study there no summary statistics were done by dosing regimen for Part B.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| All Participants in Part A | GIR in Part B in PF-05175157 200 mg BID Group | GIR2 Value 1 | 359.2 mg/min |
| All Participants in Part A | GIR in Part B in PF-05175157 200 mg BID Group | GIR1 Value 1 | 170.5 mg/min |
| All Participants in Part A | GIR in Part B in PF-05175157 200 mg BID Group | GIR1 Value 2 | 425.0 mg/min |
| All Participants in Part A | GIR in Part B in PF-05175157 200 mg BID Group | GIR1 Value 3 | 334.2 mg/min |
| All Participants in Part A | GIR in Part B in PF-05175157 200 mg BID Group | GIR1 Value 4 | 409.3 mg/min |
| All Participants in Part A | GIR in Part B in PF-05175157 200 mg BID Group | GIR1 Value 5 | 50.0 mg/min |
| All Participants in Part A | GIR in Part B in PF-05175157 200 mg BID Group | GIR1 Value 6 | 160.9 mg/min |
| All Participants in Part A | GIR in Part B in PF-05175157 200 mg BID Group | GIR1 Value 7 | 113.2 mg/min |
| All Participants in Part A | GIR in Part B in PF-05175157 200 mg BID Group | GIR1 Value 8 | 157.7 mg/min |
| All Participants in Part A | GIR in Part B in PF-05175157 200 mg BID Group | GIR1 Value 9 | 215.2 mg/min |
| All Participants in Part A | GIR in Part B in PF-05175157 200 mg BID Group | GIR1 Value 10 | 159.9 mg/min |
| All Participants in Part A | GIR in Part B in PF-05175157 200 mg BID Group | GIR2 Value 2 | 896.5 mg/min |
| All Participants in Part A | GIR in Part B in PF-05175157 200 mg BID Group | GIR2 Value 3 | 896.3 mg/min |
| All Participants in Part A | GIR in Part B in PF-05175157 200 mg BID Group | GIR2 Value 4 | 1078.5 mg/min |
| All Participants in Part A | GIR in Part B in PF-05175157 200 mg BID Group | GIR2 Value 5 | 357.6 mg/min |
| All Participants in Part A | GIR in Part B in PF-05175157 200 mg BID Group | GIR2 Value 6 | 564.0 mg/min |
| All Participants in Part A | GIR in Part B in PF-05175157 200 mg BID Group | GIR2 Value 7 | 693.1 mg/min |
| All Participants in Part A | GIR in Part B in PF-05175157 200 mg BID Group | GIR2 Value 8 | 647.2 mg/min |
| All Participants in Part A | GIR in Part B in PF-05175157 200 mg BID Group | GIR2 Value 9 | 889.4 mg/min |
| All Participants in Part A | GIR in Part B in PF-05175157 200 mg BID Group | GIR2 Value 10 | 519.5 mg/min |
Secondary
GIR in Part B in Placebo Group
Glucose Infusion Rate rates obtained averaging respectively the last 30 minutes of glucose infusion at steady state on Step 1 (ie 150 to 180 min) and Step 2 (ie 330 to 360 min) insulin infusion.
Time frame: 6 weeks
Population: Part B of the study was terminated due to the safety issue. Due to the limited participant number who completed study there no summary statistics were done by dosing regimen for Part B.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| All Participants in Part A | GIR in Part B in Placebo Group | GIR1 Value 6 | 104.7 mg/min |
| All Participants in Part A | GIR in Part B in Placebo Group | GIR1 Value 1 | 139.4 mg/min |
| All Participants in Part A | GIR in Part B in Placebo Group | GIR1 Value 2 | 178.3 mg/min |
| All Participants in Part A | GIR in Part B in Placebo Group | GIR1 Value 3 | 52.4 mg/min |
| All Participants in Part A | GIR in Part B in Placebo Group | GIR1 Value 4 | 196.5 mg/min |
| All Participants in Part A | GIR in Part B in Placebo Group | GIR1 Value 5 | 145.7 mg/min |
| All Participants in Part A | GIR in Part B in Placebo Group | GIR1 Value 7 | 154.7 mg/min |
| All Participants in Part A | GIR in Part B in Placebo Group | GIR1 Value 8 | 85.4 mg/min |
| All Participants in Part A | GIR in Part B in Placebo Group | GIR2 Value 1 | 413.9 mg/min |
| All Participants in Part A | GIR in Part B in Placebo Group | GIR2 Value 2 | 645.0 mg/min |
| All Participants in Part A | GIR in Part B in Placebo Group | GIR2 Value 3 | 293.4 mg/min |
| All Participants in Part A | GIR in Part B in Placebo Group | GIR2 Value 4 | 668.2 mg/min |
| All Participants in Part A | GIR in Part B in Placebo Group | GIR2 Value 5 | 400.4 mg/min |
| All Participants in Part A | GIR in Part B in Placebo Group | GIR2 Value 6 | 359.3 mg/min |
| All Participants in Part A | GIR in Part B in Placebo Group | GIR2 Value 7 | 338.0 mg/min |
| All Participants in Part A | GIR in Part B in Placebo Group | GIR2 Value 8 | 343.3 mg/min |
Secondary
Ra in Part B in PF-05175157 200 mg BID Group
Ra in fasting state and during insulin infusions (Step 1 and Step 2).
Time frame: 6 weeks
Population: Part B of the study was terminated due to the safety issue. Due to the limited participant number who completed study there no summary statistics were done by dosing regimen for Part B.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| All Participants in Part A | Ra in Part B in PF-05175157 200 mg BID Group | Step 2 Value 1 | 3.775 mg/kg BW/min |
| All Participants in Part A | Ra in Part B in PF-05175157 200 mg BID Group | Step 2 Value 2 | 9.033 mg/kg BW/min |
| All Participants in Part A | Ra in Part B in PF-05175157 200 mg BID Group | Step 2 Value 3 | 8.903 mg/kg BW/min |
| All Participants in Part A | Ra in Part B in PF-05175157 200 mg BID Group | Step 2 Value 4 | 11.310 mg/kg BW/min |
| All Participants in Part A | Ra in Part B in PF-05175157 200 mg BID Group | Step 2 Value 5 | 4.133 mg/kg BW/min |
| All Participants in Part A | Ra in Part B in PF-05175157 200 mg BID Group | Step 2 Value 6 | 6.763 mg/kg BW/min |
| All Participants in Part A | Ra in Part B in PF-05175157 200 mg BID Group | Step 2 Value 7 | 8.243 mg/kg BW/min |
| All Participants in Part A | Ra in Part B in PF-05175157 200 mg BID Group | Step 2 Value 8 | 7.180 mg/kg BW/min |
| All Participants in Part A | Ra in Part B in PF-05175157 200 mg BID Group | Step 2 Value 9 | 10.113 mg/kg BW/min |
| All Participants in Part A | Ra in Part B in PF-05175157 200 mg BID Group | Step 2 Value 10 | 6.205 mg/kg BW/min |
Secondary
Ra in Part B in Placebo Group
Ra in fasting state and during insulin infusions (Step 1 and Step 2).
Time frame: 6 weeks
Population: Part B of the study was terminated due to the safety issue. Due to the limited participant number who completed study there no summary statistics were done by dosing regimen for Part B.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| All Participants in Part A | Ra in Part B in Placebo Group | Step 2 Value 1 | 4.245 mg/kg BW/min |
| All Participants in Part A | Ra in Part B in Placebo Group | Step 2 Value 2 | 6.325 mg/kg BW/min |
| All Participants in Part A | Ra in Part B in Placebo Group | Step 2 Value 3 | 2.793 mg/kg BW/min |
| All Participants in Part A | Ra in Part B in Placebo Group | Step 2 Value 4 | 6.835 mg/kg BW/min |
| All Participants in Part A | Ra in Part B in Placebo Group | Step 2 Value 5 | 4.400 mg/kg BW/min |
| All Participants in Part A | Ra in Part B in Placebo Group | Step 2 Value 6 | 3.940 mg/kg BW/min |
| All Participants in Part A | Ra in Part B in Placebo Group | Step 2 Value 7 | 4.553 mg/kg BW/min |
| All Participants in Part A | Ra in Part B in Placebo Group | Step 2 Value 8 | 4.225 mg/kg BW/min |