Trial Outcomes & Findings for A 6-Week Study Of PF-05175157 In Type 2 Diabetes Mellitus (NCT NCT01792635)
NCT ID: NCT01792635
Last Updated: 2017-02-16
Results Overview
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.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
19 participants
Primary outcome timeframe
1 day
Results posted on
2017-02-16
Participant Flow
Participant milestones
| Measure |
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.
|
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.
|
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.
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Part A
STARTED
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6
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Part A
COMPLETED
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6
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Part A
NOT COMPLETED
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0
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0
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0
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Part B
STARTED
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0
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6
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7
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Part B
COMPLETED
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0
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2
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3
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Part B
NOT COMPLETED
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0
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4
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4
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Reasons for withdrawal
| Measure |
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.
|
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.
|
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.
|
|---|---|---|---|
|
Part B
Adverse Event
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0
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0
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1
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Part B
Study terminated
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0
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4
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3
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Baseline Characteristics
A 6-Week Study Of PF-05175157 In Type 2 Diabetes Mellitus
Baseline characteristics by cohort
| Measure |
All Participants in Part A
n=6 Participants
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.
|
Placebo - Part B
n=6 Participants
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.
|
PF-05175157 200 mg Twice a Day - Part B
n=7 Participants
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.
|
Total
n=19 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
50.7 Years
STANDARD_DEVIATION 9.5 • n=5 Participants
|
49.3 Years
STANDARD_DEVIATION 9.2 • n=7 Participants
|
55.1 Years
STANDARD_DEVIATION 4.6 • n=5 Participants
|
51.9 Years
STANDARD_DEVIATION 7.9 • n=4 Participants
|
|
Sex/Gender, Customized
Male
|
5 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
15 Participants
n=4 Participants
|
|
Sex/Gender, Customized
Female
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: 1 dayPopulation: All participants randomized and who had at least one euglycemic hyperinsulinemic clamp
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.
Outcome measures
| Measure |
All Participants in Part A
n=6 Participants
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.
|
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.
|
|---|---|---|
|
Glucose Infusion Rates (GIR) in Part A
Clamp 1 GIR1
|
191 mg/min
Interval 153.0 to 229.0
|
—
|
|
Glucose Infusion Rates (GIR) in Part A
Clamp 1 GIR2
|
780 mg/min
Interval 580.0 to 980.0
|
—
|
|
Glucose Infusion Rates (GIR) in Part A
Clamp 2 GIR1
|
152 mg/min
Interval 132.0 to 172.0
|
—
|
PRIMARY outcome
Timeframe: 1 dayPopulation: All participants randomized and who had at least one euglycemic hyperinsulinemic clamp
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).
Outcome measures
| Measure |
All Participants in Part A
n=6 Participants
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.
|
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.
|
|---|---|---|
|
Endogenous Gucose Production (EGP) in Part A
Clamp 1 EGP0
|
1.79 mg/kilogram (kg) body weight (BW)/min
Interval 1.48 to 1.99
|
—
|
|
Endogenous Gucose Production (EGP) in Part A
Clamp 1 EGP1
|
0.85 mg/kilogram (kg) body weight (BW)/min
Interval 0.51 to 0.98
|
—
|
|
Endogenous Gucose Production (EGP) in Part A
Clamp 1 EGP2
|
0.07 mg/kilogram (kg) body weight (BW)/min
Interval -0.02 to 0.36
|
—
|
|
Endogenous Gucose Production (EGP) in Part A
Clamp 2 EGP0
|
1.68 mg/kilogram (kg) body weight (BW)/min
Interval 1.59 to 1.89
|
—
|
|
Endogenous Gucose Production (EGP) in Part A
Clamp 2 EGP1
|
0.81 mg/kilogram (kg) body weight (BW)/min
Interval 0.71 to 0.98
|
—
|
PRIMARY outcome
Timeframe: 1 dayPopulation: All participants randomized and who had at least one euglycemic hyperinsulinemic clamp
\[6,6-2H2\] 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.
Outcome measures
| Measure |
All Participants in Part A
n=6 Participants
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.
|
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.
|
|---|---|---|
|
[6,6-2H2] Plasma Glucose Enrichment (PGE) in Part A
Clamp 1
|
2.96 percentage enrichment of plasma glucose
Interval 2.94 to 2.98
|
—
|
|
[6,6-2H2] Plasma Glucose Enrichment (PGE) in Part A
Clamp 2
|
2.97 percentage enrichment of plasma glucose
Interval 2.88 to 3.06
|
—
|
PRIMARY outcome
Timeframe: 1 dayPopulation: All participants randomized and who had at least one euglycemic hyperinsulinemic clamp.
Rate of appearance of glucose (Ra) in fasting state and during insulin infusions (Step 1 and Step 2).
Outcome measures
| Measure |
All Participants in Part A
n=6 Participants
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.
|
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.
|
|---|---|---|
|
Rate of Appearance of Glucose (Ra) in Part A
Clamp 1 Step 1
|
3.575 mg/kg BW/min
Interval 2.74 to 4.41
|
—
|
|
Rate of Appearance of Glucose (Ra) in Part A
Clamp 1 Step 2
|
14.829 mg/kg BW/min
Interval 9.9 to 19.76
|
—
|
|
Rate of Appearance of Glucose (Ra) in Part A
Clamp 2 Step 1
|
2.859 mg/kg BW/min
Interval 2.24 to 3.47
|
—
|
PRIMARY outcome
Timeframe: 1 dayPopulation: All participants randomized and who had at least one euglycemic hyperinsulinemic clamp.
Whole-body glucose uptake (Rate of glucose disappearance, Rd) during the Step 2 Clamp
Outcome measures
| Measure |
All Participants in Part A
n=6 Participants
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.
|
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.
|
|---|---|---|
|
Whole-body Glucose Uptake in Part A
|
14.829 mg/kg BW/min
Interval 9.9 to 19.76
|
—
|
PRIMARY outcome
Timeframe: 6 weeksPopulation: 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.
Whole-body glucose uptake (Rate of glucose disappearance, Rd) during the Step 2 Clamp
Outcome measures
| Measure |
All Participants in Part A
n=6 Participants
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.
|
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.
|
|---|---|---|
|
Whole-body Glucose Uptake in Part B in Placebo Group
Step 2 Value 1
|
4.245 mg/kg BW/min
Interval 4.18 to 4.41
|
—
|
|
Whole-body Glucose Uptake in Part B in Placebo Group
Step 2 Value 2
|
6.325 mg/kg BW/min
Interval 6.26 to 6.45
|
—
|
|
Whole-body Glucose Uptake in Part B in Placebo Group
Step 2 Value 3
|
2.793 mg/kg BW/min
Interval 2.72 to 2.85
|
—
|
|
Whole-body Glucose Uptake in Part B in Placebo Group
Step 2 Value 4
|
6.835 mg/kg BW/min
Interval 6.56 to 7.38
|
—
|
|
Whole-body Glucose Uptake in Part B in Placebo Group
Step 2 Value 5
|
4.400 mg/kg BW/min
Interval 3.97 to 5.23
|
—
|
|
Whole-body Glucose Uptake in Part B in Placebo Group
Step 2 Value 6
|
3.940 mg/kg BW/min
Interval 3.86 to 3.98
|
—
|
|
Whole-body Glucose Uptake in Part B in Placebo Group
Step 2 Value 7
|
4.553 mg/kg BW/min
Interval 4.37 to 4.62
|
—
|
|
Whole-body Glucose Uptake in Part B in Placebo Group
Step 2 Value 8
|
4.225 mg/kg BW/min
Interval 4.16 to 4.4
|
—
|
PRIMARY outcome
Timeframe: 6 weeksPopulation: 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.
Whole-body glucose uptake (Rate of glucose disappearance, Rd) during the Step 2 Clamp
Outcome measures
| Measure |
All Participants in Part A
n=7 Participants
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.
|
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.
|
|---|---|---|
|
Whole-body Glucose Uptake in Part B in PF-05175157 200 mg BID Group
Step 2 Value 2
|
9.033 mg/kg BW/min
Interval 8.95 to 9.08
|
—
|
|
Whole-body Glucose Uptake in Part B in PF-05175157 200 mg BID Group
Step 2 Value 3
|
8.903 mg/kg BW/min
Interval 8.33 to 9.37
|
—
|
|
Whole-body Glucose Uptake in Part B in PF-05175157 200 mg BID Group
Step 2 Value 4
|
11.310 mg/kg BW/min
Interval 11.13 to 11.47
|
—
|
|
Whole-body Glucose Uptake in Part B in PF-05175157 200 mg BID Group
Step 2 Value 5
|
4.133 mg/kg BW/min
Interval 3.98 to 4.5
|
—
|
|
Whole-body Glucose Uptake in Part B in PF-05175157 200 mg BID Group
Step 2 Value 6
|
6.763 mg/kg BW/min
Interval 5.98 to 7.93
|
—
|
|
Whole-body Glucose Uptake in Part B in PF-05175157 200 mg BID Group
Step 2 Value 7
|
8.243 mg/kg BW/min
Interval 8.06 to 8.73
|
—
|
|
Whole-body Glucose Uptake in Part B in PF-05175157 200 mg BID Group
Step 2 Value 8
|
7.180 mg/kg BW/min
Interval 7.03 to 7.39
|
—
|
|
Whole-body Glucose Uptake in Part B in PF-05175157 200 mg BID Group
Step 2 Value 9
|
10.113 mg/kg BW/min
Interval 9.8 to 10.28
|
—
|
|
Whole-body Glucose Uptake in Part B in PF-05175157 200 mg BID Group
Step 2 Value 10
|
6.205 mg/kg BW/min
Interval 6.16 to 6.31
|
—
|
|
Whole-body Glucose Uptake in Part B in PF-05175157 200 mg BID Group
Step 2 Value 1
|
3.775 mg/kg BW/min
Interval 3.7 to 3.83
|
—
|
PRIMARY outcome
Timeframe: 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
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.
Outcome measures
| Measure |
All Participants in Part A
n=6 Participants
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.
|
PF-05175157 200 mg Twice a Day - Part B
n=7 Participants
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.
|
|---|---|---|
|
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
|
5 Participants
|
|
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
|
1 Participants
|
|
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
|
1 Participants
|
PRIMARY outcome
Timeframe: 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
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).
Outcome measures
| Measure |
All Participants in Part A
n=6 Participants
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.
|
PF-05175157 200 mg Twice a Day - Part B
n=7 Participants
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.
|
|---|---|---|
|
Number of Participants With Laboratory Test Abnormalities in Part B
|
6 Participants
|
7 Participants
|
PRIMARY outcome
Timeframe: 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
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).
Outcome measures
| Measure |
All Participants in Part A
n=6 Participants
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.
|
PF-05175157 200 mg Twice a Day - Part B
n=7 Participants
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.
|
|---|---|---|
|
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
|
0 Participants
|
|
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
|
0 Participants
|
|
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
|
0 Participants
|
|
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
|
0 Participants
|
|
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
|
0 Participants
|
|
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
|
0 Participants
|
|
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
|
0 Participants
|
|
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
|
1 Participants
|
PRIMARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
All Participants in Part A
n=6 Participants
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.
|
PF-05175157 200 mg Twice a Day - Part B
n=7 Participants
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.
|
|---|---|---|
|
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
|
1 Participants
|
|
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
|
1 Participants
|
SECONDARY outcome
Timeframe: 6 weeksPopulation: 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.
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.
Outcome measures
| Measure |
All Participants in Part A
n=6 Participants
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.
|
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.
|
|---|---|---|
|
GIR in Part B in Placebo Group
GIR1 Value 1
|
139.4 mg/min
Interval 0.0 to 150.0
|
—
|
|
GIR in Part B in Placebo Group
GIR1 Value 2
|
178.3 mg/min
Interval 176.0 to 246.0
|
—
|
|
GIR in Part B in Placebo Group
GIR1 Value 3
|
52.4 mg/min
Interval 0.0 to 97.0
|
—
|
|
GIR in Part B in Placebo Group
GIR1 Value 4
|
196.5 mg/min
Interval 181.0 to 197.0
|
—
|
|
GIR in Part B in Placebo Group
GIR1 Value 5
|
145.7 mg/min
Interval 92.0 to 161.0
|
—
|
|
GIR in Part B in Placebo Group
GIR1 Value 6
|
104.7 mg/min
Interval 103.0 to 140.0
|
—
|
|
GIR in Part B in Placebo Group
GIR1 Value 7
|
154.7 mg/min
Interval 143.0 to 218.0
|
—
|
|
GIR in Part B in Placebo Group
GIR1 Value 8
|
85.4 mg/min
Interval 68.0 to 86.0
|
—
|
|
GIR in Part B in Placebo Group
GIR2 Value 1
|
413.9 mg/min
Interval 411.0 to 461.0
|
—
|
|
GIR in Part B in Placebo Group
GIR2 Value 2
|
645.0 mg/min
Interval 645.0 to 645.0
|
—
|
|
GIR in Part B in Placebo Group
GIR2 Value 3
|
293.4 mg/min
Interval 217.0 to 296.0
|
—
|
|
GIR in Part B in Placebo Group
GIR2 Value 4
|
668.2 mg/min
Interval 610.0 to 711.0
|
—
|
|
GIR in Part B in Placebo Group
GIR2 Value 5
|
400.4 mg/min
Interval 368.0 to 504.0
|
—
|
|
GIR in Part B in Placebo Group
GIR2 Value 6
|
359.3 mg/min
Interval 289.0 to 363.0
|
—
|
|
GIR in Part B in Placebo Group
GIR2 Value 7
|
338.0 mg/min
Interval 338.0 to 338.0
|
—
|
|
GIR in Part B in Placebo Group
GIR2 Value 8
|
343.3 mg/min
Interval 322.0 to 344.0
|
—
|
SECONDARY outcome
Timeframe: 6 weeksPopulation: 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.
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.
Outcome measures
| Measure |
All Participants in Part A
n=7 Participants
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.
|
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.
|
|---|---|---|
|
GIR in Part B in PF-05175157 200 mg BID Group
GIR1 Value 1
|
170.5 mg/min
Interval 118.0 to 191.0
|
—
|
|
GIR in Part B in PF-05175157 200 mg BID Group
GIR1 Value 2
|
425.0 mg/min
Interval 367.0 to 427.0
|
—
|
|
GIR in Part B in PF-05175157 200 mg BID Group
GIR1 Value 3
|
334.2 mg/min
Interval 311.0 to 335.0
|
—
|
|
GIR in Part B in PF-05175157 200 mg BID Group
GIR1 Value 4
|
409.3 mg/min
Interval 277.0 to 521.0
|
—
|
|
GIR in Part B in PF-05175157 200 mg BID Group
GIR1 Value 5
|
50.0 mg/min
Interval 50.0 to 50.0
|
—
|
|
GIR in Part B in PF-05175157 200 mg BID Group
GIR1 Value 6
|
160.9 mg/min
Interval 160.0 to 188.0
|
—
|
|
GIR in Part B in PF-05175157 200 mg BID Group
GIR1 Value 7
|
113.2 mg/min
Interval 68.0 to 116.0
|
—
|
|
GIR in Part B in PF-05175157 200 mg BID Group
GIR1 Value 8
|
157.7 mg/min
Interval 113.0 to 225.0
|
—
|
|
GIR in Part B in PF-05175157 200 mg BID Group
GIR1 Value 9
|
215.2 mg/min
Interval 201.0 to 236.0
|
—
|
|
GIR in Part B in PF-05175157 200 mg BID Group
GIR1 Value 10
|
159.9 mg/min
Interval 159.0 to 178.0
|
—
|
|
GIR in Part B in PF-05175157 200 mg BID Group
GIR2 Value 1
|
359.2 mg/min
Interval 270.0 to 368.0
|
—
|
|
GIR in Part B in PF-05175157 200 mg BID Group
GIR2 Value 2
|
896.5 mg/min
Interval 871.0 to 921.0
|
—
|
|
GIR in Part B in PF-05175157 200 mg BID Group
GIR2 Value 3
|
896.3 mg/min
Interval 864.0 to 1064.0
|
—
|
|
GIR in Part B in PF-05175157 200 mg BID Group
GIR2 Value 4
|
1078.5 mg/min
Interval 1068.0 to 1079.0
|
—
|
|
GIR in Part B in PF-05175157 200 mg BID Group
GIR2 Value 5
|
357.6 mg/min
Interval 357.0 to 370.0
|
—
|
|
GIR in Part B in PF-05175157 200 mg BID Group
GIR2 Value 6
|
564.0 mg/min
Interval 520.0 to 656.0
|
—
|
|
GIR in Part B in PF-05175157 200 mg BID Group
GIR2 Value 7
|
693.1 mg/min
Interval 666.0 to 728.0
|
—
|
|
GIR in Part B in PF-05175157 200 mg BID Group
GIR2 Value 8
|
647.2 mg/min
Interval 623.0 to 681.0
|
—
|
|
GIR in Part B in PF-05175157 200 mg BID Group
GIR2 Value 9
|
889.4 mg/min
Interval 821.0 to 893.0
|
—
|
|
GIR in Part B in PF-05175157 200 mg BID Group
GIR2 Value 10
|
519.5 mg/min
Interval 512.0 to 540.0
|
—
|
SECONDARY outcome
Timeframe: 6 weeksPopulation: 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.
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)
Outcome measures
| Measure |
All Participants in Part A
n=6 Participants
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.
|
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.
|
|---|---|---|
|
EGP in Part B in Placebo Group
EGP0 Value 1
|
1.540 mg/kg fat free mass (FFM)/min
Interval 1.49 to 1.6
|
—
|
|
EGP in Part B in Placebo Group
EGP0 Value 2
|
1.690 mg/kg fat free mass (FFM)/min
Interval 1.64 to 1.75
|
—
|
|
EGP in Part B in Placebo Group
EGP0 Value 3
|
1.285 mg/kg fat free mass (FFM)/min
Interval 1.24 to 1.33
|
—
|
|
EGP in Part B in Placebo Group
EGP0 Value 4
|
1.575 mg/kg fat free mass (FFM)/min
Interval 1.55 to 1.62
|
—
|
|
EGP in Part B in Placebo Group
EGP0 Value 5
|
1.965 mg/kg fat free mass (FFM)/min
Interval 1.89 to 2.04
|
—
|
|
EGP in Part B in Placebo Group
EGP0 Value 6
|
1.538 mg/kg fat free mass (FFM)/min
Interval 1.5 to 1.58
|
—
|
|
EGP in Part B in Placebo Group
EGP0 Value 7
|
1.518 mg/kg fat free mass (FFM)/min
Interval 1.47 to 1.56
|
—
|
|
EGP in Part B in Placebo Group
EGP0 Value 8
|
1.518 mg/kg fat free mass (FFM)/min
Interval 1.49 to 1.56
|
—
|
|
EGP in Part B in Placebo Group
EGP1 Value 1
|
0.600 mg/kg fat free mass (FFM)/min
Interval 0.57 to 0.66
|
—
|
|
EGP in Part B in Placebo Group
EGP1 Value 2
|
0.585 mg/kg fat free mass (FFM)/min
Interval 0.55 to 0.61
|
—
|
|
EGP in Part B in Placebo Group
EGP1 Value 3
|
0.525 mg/kg fat free mass (FFM)/min
Interval 0.49 to 0.59
|
—
|
|
EGP in Part B in Placebo Group
EGP1 Value 4
|
0.500 mg/kg fat free mass (FFM)/min
Interval 0.49 to 0.52
|
—
|
|
EGP in Part B in Placebo Group
EGP1 Value 5
|
0.808 mg/kg fat free mass (FFM)/min
Interval 0.75 to 0.86
|
—
|
|
EGP in Part B in Placebo Group
EGP1 Value 6
|
0.830 mg/kg fat free mass (FFM)/min
Interval 0.82 to 0.84
|
—
|
|
EGP in Part B in Placebo Group
EGP1 Value 7
|
0.560 mg/kg fat free mass (FFM)/min
Interval 0.55 to 0.58
|
—
|
|
EGP in Part B in Placebo Group
EGP1 Value 8
|
0.825 mg/kg fat free mass (FFM)/min
Interval 0.78 to 0.85
|
—
|
|
EGP in Part B in Placebo Group
EGP2 Value 1
|
0.200 mg/kg fat free mass (FFM)/min
Interval 0.17 to 0.22
|
—
|
|
EGP in Part B in Placebo Group
EGP2 Value 2
|
-0.063 mg/kg fat free mass (FFM)/min
Interval -0.09 to -0.03
|
—
|
|
EGP in Part B in Placebo Group
EGP2 Value 3
|
-0.050 mg/kg fat free mass (FFM)/min
Interval -0.1 to -0.01
|
—
|
|
EGP in Part B in Placebo Group
EGP2 Value 4
|
0.280 mg/kg fat free mass (FFM)/min
Interval 0.25 to 0.31
|
—
|
|
EGP in Part B in Placebo Group
EGP2 Value 5
|
0.145 mg/kg fat free mass (FFM)/min
Interval 0.06 to 0.23
|
—
|
|
EGP in Part B in Placebo Group
EGP2 Value 6
|
0.223 mg/kg fat free mass (FFM)/min
Interval 0.2 to 0.24
|
—
|
|
EGP in Part B in Placebo Group
EGP2 Value 7
|
0.180 mg/kg fat free mass (FFM)/min
Interval 0.17 to 0.19
|
—
|
|
EGP in Part B in Placebo Group
EGP2 Value 8
|
0.405 mg/kg fat free mass (FFM)/min
Interval 0.38 to 0.46
|
—
|
SECONDARY outcome
Timeframe: 6 weeksPopulation: 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.
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)
Outcome measures
| Measure |
All Participants in Part A
n=7 Participants
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.
|
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.
|
|---|---|---|
|
EGP in Part B in PF-05175157 200 mg BID Group
EGP0 Value 5
|
1.695 mg/kg fat free mass (FFM)/min
Interval 1.67 to 1.72
|
—
|
|
EGP in Part B in PF-05175157 200 mg BID Group
EGP0 Value 6
|
1.615 mg/kg fat free mass (FFM)/min
Interval 1.59 to 1.65
|
—
|
|
EGP in Part B in PF-05175157 200 mg BID Group
EGP0 Value 7
|
1.690 mg/kg fat free mass (FFM)/min
Interval 1.64 to 1.75
|
—
|
|
EGP in Part B in PF-05175157 200 mg BID Group
EGP0 Value 8
|
1.393 mg/kg fat free mass (FFM)/min
Interval 1.25 to 1.46
|
—
|
|
EGP in Part B in PF-05175157 200 mg BID Group
EGP0 Value 9
|
1.448 mg/kg fat free mass (FFM)/min
Interval 1.43 to 1.46
|
—
|
|
EGP in Part B in PF-05175157 200 mg BID Group
EGP0 Value 10
|
1.345 mg/kg fat free mass (FFM)/min
Interval 1.33 to 1.36
|
—
|
|
EGP in Part B in PF-05175157 200 mg BID Group
EGP1 Value 1
|
0.568 mg/kg fat free mass (FFM)/min
Interval 0.54 to 0.59
|
—
|
|
EGP in Part B in PF-05175157 200 mg BID Group
EGP1 Value 2
|
0.250 mg/kg fat free mass (FFM)/min
Interval 0.22 to 0.28
|
—
|
|
EGP in Part B in PF-05175157 200 mg BID Group
EGP1 Value 3
|
0.788 mg/kg fat free mass (FFM)/min
Interval 0.69 to 0.89
|
—
|
|
EGP in Part B in PF-05175157 200 mg BID Group
EGP1 Value 4
|
0.575 mg/kg fat free mass (FFM)/min
Interval 0.54 to 0.62
|
—
|
|
EGP in Part B in PF-05175157 200 mg BID Group
EGP1 Value 5
|
1.183 mg/kg fat free mass (FFM)/min
Interval 1.12 to 1.22
|
—
|
|
EGP in Part B in PF-05175157 200 mg BID Group
EGP1 Value 6
|
0.538 mg/kg fat free mass (FFM)/min
Interval 0.52 to 0.55
|
—
|
|
EGP in Part B in PF-05175157 200 mg BID Group
EGP1 Value 7
|
0.765 mg/kg fat free mass (FFM)/min
Interval 0.74 to 0.78
|
—
|
|
EGP in Part B in PF-05175157 200 mg BID Group
EGP1 Value 8
|
0.555 mg/kg fat free mass (FFM)/min
Interval 0.53 to 0.58
|
—
|
|
EGP in Part B in PF-05175157 200 mg BID Group
EGP1 Value 9
|
0.193 mg/kg fat free mass (FFM)/min
Interval 0.11 to 0.23
|
—
|
|
EGP in Part B in PF-05175157 200 mg BID Group
EGP1 Value 10
|
0.418 mg/kg fat free mass (FFM)/min
Interval 0.35 to 0.45
|
—
|
|
EGP in Part B in PF-05175157 200 mg BID Group
EGP2 Value 1
|
0.253 mg/kg fat free mass (FFM)/min
Interval 0.23 to 0.29
|
—
|
|
EGP in Part B in PF-05175157 200 mg BID Group
EGP2 Value 2
|
0.165 mg/kg fat free mass (FFM)/min
Interval 0.09 to 0.21
|
—
|
|
EGP in Part B in PF-05175157 200 mg BID Group
EGP2 Value 3
|
-0.035 mg/kg fat free mass (FFM)/min
Interval -0.43 to 0.14
|
—
|
|
EGP in Part B in PF-05175157 200 mg BID Group
EGP2 Value 4
|
0.243 mg/kg fat free mass (FFM)/min
Interval 0.1 to 0.39
|
—
|
|
EGP in Part B in PF-05175157 200 mg BID Group
EGP2 Value 5
|
0.543 mg/kg fat free mass (FFM)/min
Interval 0.47 to 0.67
|
—
|
|
EGP in Part B in PF-05175157 200 mg BID Group
EGP2 Value 6
|
0.110 mg/kg fat free mass (FFM)/min
Interval 0.03 to 0.15
|
—
|
|
EGP in Part B in PF-05175157 200 mg BID Group
EGP2 Value 7
|
0.190 mg/kg fat free mass (FFM)/min
Interval 0.15 to 0.24
|
—
|
|
EGP in Part B in PF-05175157 200 mg BID Group
EGP2 Value 8
|
-0.313 mg/kg fat free mass (FFM)/min
Interval -0.42 to -0.23
|
—
|
|
EGP in Part B in PF-05175157 200 mg BID Group
EGP2 Value 9
|
-0.253 mg/kg fat free mass (FFM)/min
Interval -0.34 to -0.2
|
—
|
|
EGP in Part B in PF-05175157 200 mg BID Group
EGP2 Value 10
|
0.198 mg/kg fat free mass (FFM)/min
Interval 0.19 to 0.21
|
—
|
|
EGP in Part B in PF-05175157 200 mg BID Group
EGP0 Value 1
|
1.240 mg/kg fat free mass (FFM)/min
Interval 1.23 to 1.27
|
—
|
|
EGP in Part B in PF-05175157 200 mg BID Group
EGP0 Value 2
|
1.445 mg/kg fat free mass (FFM)/min
Interval 1.42 to 1.46
|
—
|
|
EGP in Part B in PF-05175157 200 mg BID Group
EGP0 Value 3
|
2.083 mg/kg fat free mass (FFM)/min
Interval 2.03 to 2.15
|
—
|
|
EGP in Part B in PF-05175157 200 mg BID Group
EGP0 Value 4
|
1.708 mg/kg fat free mass (FFM)/min
Interval 1.68 to 1.73
|
—
|
SECONDARY outcome
Timeframe: 6 weeksPopulation: 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.
Ra in fasting state and during insulin infusions (Step 1 and Step 2).
Outcome measures
| Measure |
All Participants in Part A
n=6 Participants
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.
|
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.
|
|---|---|---|
|
Ra in Part B in Placebo Group
Step 2 Value 1
|
4.245 mg/kg BW/min
Interval 4.18 to 4.41
|
—
|
|
Ra in Part B in Placebo Group
Step 2 Value 2
|
6.325 mg/kg BW/min
Interval 6.26 to 6.45
|
—
|
|
Ra in Part B in Placebo Group
Step 2 Value 3
|
2.793 mg/kg BW/min
Interval 2.72 to 2.85
|
—
|
|
Ra in Part B in Placebo Group
Step 2 Value 4
|
6.835 mg/kg BW/min
Interval 6.56 to 7.38
|
—
|
|
Ra in Part B in Placebo Group
Step 2 Value 5
|
4.400 mg/kg BW/min
Interval 3.97 to 5.23
|
—
|
|
Ra in Part B in Placebo Group
Step 2 Value 6
|
3.940 mg/kg BW/min
Interval 3.86 to 3.98
|
—
|
|
Ra in Part B in Placebo Group
Step 2 Value 7
|
4.553 mg/kg BW/min
Interval 4.37 to 4.62
|
—
|
|
Ra in Part B in Placebo Group
Step 2 Value 8
|
4.225 mg/kg BW/min
Interval 4.16 to 4.4
|
—
|
SECONDARY outcome
Timeframe: 6 weeksPopulation: 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.
Ra in fasting state and during insulin infusions (Step 1 and Step 2).
Outcome measures
| Measure |
All Participants in Part A
n=7 Participants
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.
|
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.
|
|---|---|---|
|
Ra in Part B in PF-05175157 200 mg BID Group
Step 2 Value 1
|
3.775 mg/kg BW/min
Interval 3.7 to 3.83
|
—
|
|
Ra in Part B in PF-05175157 200 mg BID Group
Step 2 Value 2
|
9.033 mg/kg BW/min
Interval 8.95 to 9.08
|
—
|
|
Ra in Part B in PF-05175157 200 mg BID Group
Step 2 Value 3
|
8.903 mg/kg BW/min
Interval 8.33 to 9.37
|
—
|
|
Ra in Part B in PF-05175157 200 mg BID Group
Step 2 Value 4
|
11.310 mg/kg BW/min
Interval 11.13 to 11.47
|
—
|
|
Ra in Part B in PF-05175157 200 mg BID Group
Step 2 Value 5
|
4.133 mg/kg BW/min
Interval 3.98 to 4.5
|
—
|
|
Ra in Part B in PF-05175157 200 mg BID Group
Step 2 Value 6
|
6.763 mg/kg BW/min
Interval 5.98 to 7.93
|
—
|
|
Ra in Part B in PF-05175157 200 mg BID Group
Step 2 Value 7
|
8.243 mg/kg BW/min
Interval 8.06 to 8.73
|
—
|
|
Ra in Part B in PF-05175157 200 mg BID Group
Step 2 Value 8
|
7.180 mg/kg BW/min
Interval 7.03 to 7.39
|
—
|
|
Ra in Part B in PF-05175157 200 mg BID Group
Step 2 Value 9
|
10.113 mg/kg BW/min
Interval 9.8 to 10.28
|
—
|
|
Ra in Part B in PF-05175157 200 mg BID Group
Step 2 Value 10
|
6.205 mg/kg BW/min
Interval 6.16 to 6.31
|
—
|
Adverse Events
All Participants in Part A
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
PF-05175157 200 mg Twice a Day - Part B
Serious events: 1 serious events
Other events: 5 other events
Deaths: 0 deaths
Placebo - Part B
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
All Participants in Part A
n=6 participants at risk
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.
|
PF-05175157 200 mg Twice a Day - Part B
n=7 participants at risk
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.
|
Placebo - Part B
n=6 participants at risk
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.
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.00%
0/6 • Baseline up to follow-up (up to approximately 3 days after the last clamp procedure in Part A and up to approximately 10 to 14 days after the last study drug administration in Part B)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
14.3%
1/7 • Baseline up to follow-up (up to approximately 3 days after the last clamp procedure in Part A and up to approximately 10 to 14 days after the last study drug administration in Part B)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
0.00%
0/6 • Baseline up to follow-up (up to approximately 3 days after the last clamp procedure in Part A and up to approximately 10 to 14 days after the last study drug administration in Part B)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
Other adverse events
| Measure |
All Participants in Part A
n=6 participants at risk
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.
|
PF-05175157 200 mg Twice a Day - Part B
n=7 participants at risk
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.
|
Placebo - Part B
n=6 participants at risk
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.
|
|---|---|---|---|
|
Eye disorders
Lacrimation increased
|
0.00%
0/6 • Baseline up to follow-up (up to approximately 3 days after the last clamp procedure in Part A and up to approximately 10 to 14 days after the last study drug administration in Part B)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
14.3%
1/7 • Baseline up to follow-up (up to approximately 3 days after the last clamp procedure in Part A and up to approximately 10 to 14 days after the last study drug administration in Part B)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
0.00%
0/6 • Baseline up to follow-up (up to approximately 3 days after the last clamp procedure in Part A and up to approximately 10 to 14 days after the last study drug administration in Part B)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/6 • Baseline up to follow-up (up to approximately 3 days after the last clamp procedure in Part A and up to approximately 10 to 14 days after the last study drug administration in Part B)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
14.3%
1/7 • Baseline up to follow-up (up to approximately 3 days after the last clamp procedure in Part A and up to approximately 10 to 14 days after the last study drug administration in Part B)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
0.00%
0/6 • Baseline up to follow-up (up to approximately 3 days after the last clamp procedure in Part A and up to approximately 10 to 14 days after the last study drug administration in Part B)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/6 • Baseline up to follow-up (up to approximately 3 days after the last clamp procedure in Part A and up to approximately 10 to 14 days after the last study drug administration in Part B)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
14.3%
1/7 • Baseline up to follow-up (up to approximately 3 days after the last clamp procedure in Part A and up to approximately 10 to 14 days after the last study drug administration in Part B)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
0.00%
0/6 • Baseline up to follow-up (up to approximately 3 days after the last clamp procedure in Part A and up to approximately 10 to 14 days after the last study drug administration in Part B)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.00%
0/6 • Baseline up to follow-up (up to approximately 3 days after the last clamp procedure in Part A and up to approximately 10 to 14 days after the last study drug administration in Part B)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
14.3%
1/7 • Baseline up to follow-up (up to approximately 3 days after the last clamp procedure in Part A and up to approximately 10 to 14 days after the last study drug administration in Part B)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
0.00%
0/6 • Baseline up to follow-up (up to approximately 3 days after the last clamp procedure in Part A and up to approximately 10 to 14 days after the last study drug administration in Part B)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/6 • Baseline up to follow-up (up to approximately 3 days after the last clamp procedure in Part A and up to approximately 10 to 14 days after the last study drug administration in Part B)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
14.3%
1/7 • Baseline up to follow-up (up to approximately 3 days after the last clamp procedure in Part A and up to approximately 10 to 14 days after the last study drug administration in Part B)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
0.00%
0/6 • Baseline up to follow-up (up to approximately 3 days after the last clamp procedure in Part A and up to approximately 10 to 14 days after the last study drug administration in Part B)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Skin and subcutaneous tissue disorders
Blister
|
0.00%
0/6 • Baseline up to follow-up (up to approximately 3 days after the last clamp procedure in Part A and up to approximately 10 to 14 days after the last study drug administration in Part B)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
14.3%
1/7 • Baseline up to follow-up (up to approximately 3 days after the last clamp procedure in Part A and up to approximately 10 to 14 days after the last study drug administration in Part B)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
0.00%
0/6 • Baseline up to follow-up (up to approximately 3 days after the last clamp procedure in Part A and up to approximately 10 to 14 days after the last study drug administration in Part B)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/6 • Baseline up to follow-up (up to approximately 3 days after the last clamp procedure in Part A and up to approximately 10 to 14 days after the last study drug administration in Part B)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
14.3%
1/7 • Baseline up to follow-up (up to approximately 3 days after the last clamp procedure in Part A and up to approximately 10 to 14 days after the last study drug administration in Part B)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
16.7%
1/6 • Baseline up to follow-up (up to approximately 3 days after the last clamp procedure in Part A and up to approximately 10 to 14 days after the last study drug administration in Part B)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
- Publication restrictions are in place
Restriction type: OTHER