CClinicalTrials.gg
Sign In
CompletedNCT01469065Updated Oct 30, 2013Results posted

A 2-week Trial Of PF-04991532 In Patients With Type 2 Diabetes

A Phase 1 interventional study of PF-04991532 and PF-04991532 in Diabetes Mellitus, Type 2, sponsored by Pfizer. Completed at 3 sites in 2 countries. Open to participants aged 18 Years to 70 Years. Per ClinicalTrials.gov, last updated 2013-10-30.

Sponsored by Pfizer · Phase 1, Interventional, and Basic science

Phase
Phase 1
Study type
Interventional
Enrollment
82
Allocation
Randomized
Ages
18 Years to 70 Years
Sex
All
01

Study summary

This will be a 2-week oral dose study of PF 04991532, performed in patients with type 2 diabetes. Safety, pharmacokinetics (how the drug is distributed in the body), and pharmacodynamics (how the drug works in the body) will be studied. Patients may be asked to wash off their diabetes medication for 4-6 prior to study drug administration, and they will remain in the clinical research unit for a total of 20 days for baseline tests, 2 weeks of dosing, and some follow up tests.

02

Conditions studied

  • Diabetes Mellitus, Type 2

Keywords

  • inpatient
  • diabetes
  • phase 1
03

In context

Diabetes Mellitus

10,923 studies on the registry are indexed under Diabetes Mellitus; 1,318 are open to participants now.

This study's enrollment of 82 is close to the median of 80 across 8,367 interventional studies indexed under Diabetes Mellitus.

Browse Diabetes Mellitus studies →

Lead sponsor

Pfizer is the lead sponsor of 3,244 studies on the registry; 139 are open to participants now.

Of its 582 completed or terminated interventional studies of FDA-regulated products, 381 (65%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 70 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Patients with type 2 diabetes mellitus who are taking either no medication for the treatment of diabetes (diet/exercise therapy only), or who are taking only a single oral anti-diabetic drug (OAD) that can be temporarily discontinued for approximately 8-10 weeks. For those taking a single OAD, treatment should be stable, where this is defined as no change in the treatment, including dose, over the past 3 months prior to Screening. OAD medications that are acceptable to be discontinued include: a sulfonylurea (SU), a meglitinide, a biguanide (eg, metformin), a dipeptidyl peptidase 4 inhibitor (DPP-4i), or an alpha glucosidase inhibitor.
  • Body Mass Index (BMI) of 18.5 to 45.0 kg/m2; and a total body weight >50 kg (110 lbs).
  • HbA1c >/=7% and \</=10% if the patient is on diet/exercise therapy only and does not require any OAD discontinuation. HbA1c >/=6.5% and \</=9% if the patient requires to be washed off an OAD.

Exclusion criteria

Exclusion Criteria:

  • Evidence or history of diabetic complications with significant end organ damage.
  • History of stroke or transient ischemic attack.
  • History of myocardial infarction.
  • History of coronary artery bypass graft or stent implantation.
  • Clinically significant peripheral vascular disease.
  • Any history or clinical evidence of congestive heart failure, NYHA Classes II IV.
  • Current history of angina/unstable angina.
  • One or more episodes of hypoglycemia within the last 3 months, or two or more episodes of hypoglycemia within the last 6 months.
  • A positive urine drug screen.
  • Use of tobacco or nicotine-containing products in excess of the equivalent of 10 cigarettes per day.
  • Blood pressure >/=160 mm Hg (systolic) or >/=100 mm Hg (diastolic), following at least 5 minutes of rest.
  • Pregnant or nursing females; females of childbearing potential.
05

Study design

Phase
Phase 1
Primary purpose
Basic science
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Investigator)
Enrollment
82 participants (actual)

Study arms

  • Experimental
    PF-04991532

    PF-04991532 experimental study medication

    Drug: PF-04991532 · Drug: PF-0499132

  • Placebo comparator
    Placebo

    PF-04991532 Matching Placebo

    Drug: Placebo

Interventions

  • DrugPF-04991532

    Oral administration of PF-04991532; 25 mg given twice a day (BID) for 14 days

  • DrugPF-04991532

    Oral administration of PF-04991532; 75 mg given twice a day (BID) for 14 days

  • DrugPF-04991532

    Oral administration of PF-04991532; 150 mg given twice a day (BID) for 14 days

  • DrugPF-0499132

    Oral administration of PF-04991532; 300 mg given twice a day (BID) for 14 days

  • DrugPlacebo

    Oral administration of PF-04991532 Matching Placebo; given twice a day (BID) for 14 days

06

What researchers measure

Primary outcomes

  1. Change From Baseline (Day -1) in Mean Daily Glucose at Day 14

    Mean daily glucose (MDG) was calculated based on the mean of 8 glucose measurements at pre-specified time points throughout the day on Day -1 and Day 14.

    Time frame: Baseline: hours -46, -44, -42, -40, -38, -36, -33, -and -30 on Day -1 (Day 1 morning dose was hour 0); Day 14: 2, 4, 6, 8, 10, 12, 15, and 18 hours after Day 14 morning dose

Secondary outcomes

  1. Area Under the Curve From Time Zero to 24 Hours Postdose (AUC24) of PF-04991532

    Area under the plasma concentration versus time curve (AUC) from time zero to 24 hours post morning dose

    Time frame: 0 (before morning dose), 0.5, 1, 2, 3, 4, 6, 10, 10.5, 11, 12, 13, 15, 18, and 24 hours after morning dose on Day 1 and Day 14

  2. Area Under the Curve From Time Zero to 10 Hours Postdose (AUC10) of PF-04991532

    Area under the plasma concentration versus time curve (AUC) from time zero to 10 hours post morning dose.

    Time frame: 0 (before morning dose), 0.5, 1, 2, 3, 4, 6, and 10 hours after morning dose on Day 1 and Day 14

  3. Maximum Observed Plasma Concentration of PF-04991532 After Morning Dose Administration (Cmax(AM))

    Time frame: 0 (before morning dose), 0.5, 1, 2, 3, 4, 6, and 10 hours after morning

  4. Maximum Observed Plasma Concentration of PF-04991532 After Evening Dose Administration (Cmax(PM))

    Time frame: 10 (before evening dose), 10.5, 11, 12, 13, 15, 18, and 24 hours after morning dose on Day 1 and Day 14

  5. Minimum Observed Plasma Trough Concentration (Cmin) of PF-04991532

    Time frame: Day 14

  6. Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04991532 After Morning Dose Administration (Tmax(AM))

    Time frame: 0 (predose), 0.5, 1, 2, 3, 4, 6, and 10 hours after morning dose on Day 1 and Day 14

  7. Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04991532 After Evening Dose Administration (Tmax(PM))

    Time was computed as post morning dose.

    Time frame: 10 (before evening dose), 10.5, 11, 12, 13, 15, 18, and 24 hours after morning dose on Day 1 and Day 14

  8. Apparent Oral Clearance (CL/F) of PF-04991532

    Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.

    Time frame: Day 1 and Day 14: 0 (before morning dose), 0.5, 1, 2, 3, 4, 6, 10 (before evening dose), 10.5, 11, 12, 13, 15, 18 and 24 hours after morning dose

  9. Observed Accumulation Ratio of Area Under the Curve From Time Zero to 10 Hours Postdose of PF-04991532 (Rac)

    Area under the curve from time zero to 10 hours postdose of PF-04991532 (AUC10) of Day 14 divided by AUC10 of Day 1

    Time frame: 0 (before morning dose), 0.5, 1, 2, 3, 4, 6, and 10 hours after morning dose on Day 1 and Day 14

  10. Observed Accumulation Ratio of Maximum Observed Plasma Concentration of PF-04991532 After Morning Dose Administration (Rac, Cmax(AM))

    Maximum observed plasma concentration of PF-04991532 after morning dose administration (Cmax(AM)) of Day 14 divided by Cmax(AM) of Day 1

    Time frame: 0 (before morning dose), 0.5, 1, 2, 3, 4, 6, and 10 hours after morning dose on Day 1 and Day 14

  11. Dose Normalized Area Under the Curve From Time Zero to 24 Hours Postdose (AUC24(dn)) of PF-04991532

    Area under the curve from time zero to 24 Hours Postdose (AUC24) divided by total daily dose

    Time frame: 0 (before morning dose), 0.5, 1, 2, 3, 4, 6, 10, 10.5, 11, 12, 13, 15, 18, and 24 hours after morning dose on Day 1 and Day 14

  12. Dose Normalized Maximum Plasma Concentration After Morning Dose Administration (Cmax(AM)(dn)) of PF-04991532

    Maximum Observed Plasma Concentration of PF-04991532 after Morning Dose Administration (Cmax(AM)) divided by dose

    Time frame: 0 (before morning dose), 0.5, 1, 2, 3, 4, 6, and 10 hours after morning dose on Day 1 and Day 14

  13. Change From Baseline (Day -2) in Mean Daily Glucose at Day 13

    Mean daily glucose (MDG) was calculated based on the mean of 8 glucose measurements at pre-specified time points throughout the day.

    Time frame: Baseline: hours -72, -70, -68, -66, -62, -60, -57, and -54 on Day -2 (Day 1 morning dose was hour 0); Day 13: 0 (before morning dose), 2, 4, 6, 10, 12, 15 and 18 hours after Day 13 morning dose

  14. Change From Baseline in Area Under the Curve of Glucose From Time 2 to 6 Hours Post Morning Dose (Glucose AUC(2-6)) Following Mixed Meal Tolerance Test (MMTT) at Day 14

    Area under the curve of glucose from time 2 to 6 hours post morning dose (Glucose AUC(2-6)) was calculated based on 8 glucose measurements at prespecified time points using the linear trapezoidal method. Nominal times were used in the calculation. Liquid meal was administered 2 hours post morning dose of PF-04991532 for mixed meal tolerance test (MMTT).

    Time frame: Baseline: hours -46, -45.75, -45.5, -45, -44.5, -44, -43, -and -42 on Day -1 (Day 1 morning dose was hour 0); Day 14: 2, 2.25, 2.5, 3, 3.5, 4, 5, and 6 hours after Day 14 morning dose

  15. Change From Baseline in Fasting Plasma Glucose (FPG)

    The average of the Day -1 (hour -48), Day 0 (hour -24) and Day 1 pre-dose (hour 0) measurements was the baseline for fasting plasma glucose (FPG) analyses.

    Time frame: Baseline: hour -48 on Day -1, hour -24 on Day 0, and hour 0 (before morning dose) on Day 1; hour 0 (before morning dose of each day) on Days 1, 2, 3, 6, and 10; and 24 hours after Day 14 morning dose on Day 15

  16. Change From Baseline in Area Under the Curve of Insulin From Time 2 to 6 Hours Post Morning Dose (Insulin AUC(2-6)) Following Mixed Meal Tolerance Test (MMTT) at Day 14

    Area Under the Curve of Insulin from Time 2 to 6 Hours Post Morning Dose (Insulin AUC(2-6)) was calculated based on 8 insulin measurements at prespecified time points using the linear trapezoidal method. Nominal times were used in the calculation. Liquid meal was administered 2 hours post morning dose of PF-04991532 for mixed meal tolerance test (MMTT).

    Time frame: Baseline: hours -46, -45.75, -45.5, -45, -44.5, -44, -43, -and -42 on Day -1 (Day 1 morning dose was hour 0); Day 14: 2, 2.25, 2.5, 3, 3.5, 4, 5, and 6 hours after Day 14 morning dose

  17. Change From Baseline in Area Under the Curve of C-peptide From Time 2 to 6 Hours Post Morning Dose (C-peptide AUC(2-6)) Following Mixed Meal Tolerance Test (MMTT) at Day 14

    Area Under the Curve of C-peptide from Time 2 to 6 Hours Post Morning Dose (C-peptide AUC(2-6)) was calculated based on 8 C-peptide measurements at prespecified timepoints using the linear trapezoidal method. Nominal times were used in the calculation. Liquid meal was administered 2 hours post morning dose of PF-04991532 for mixed meal tolerance test (MMTT).

    Time frame: Baseline: hours -46, -45.75, -45.5, -45, -44.5, -44, -43, -and -42 on Day -1 (Day 1 morning dose was hour 0); Day 14: 2, 2.25, 2.5, 3, 3.5, 4, 5, and 6 hours after Day 14 morning dose

  18. Change From Baseline in Fasting Lipid Parameters at Day 14 and 16

    Baseline for fasting triglycerides (TG) was defined as the average of the Day -1 (hour -48), Day 0 (hour -24), and Day 1 pre-dose (hour 0) measurements. Baseline for fasting total cholesterol (TC), cholesterol (high-density lipoprotein (HDL)), and cholesterol (low-density lipoprotein (LDL)) was defined as the Day 1 pre-dose (hour 0) measurement.

    Time frame: Baseline: hour -48 on Day -1, hour -24 on Day 0, and hour 0 on Day 1 for TG and Hour 0 (before morning dose) on Day 1 for TC, HDL, and LDL; 48 hours after morning dose on Day 16 for TG and Hour 0 (before morning dose) on Day14 for TC, HDL, and LDL

07

Results

Posted Aug 29, 2013

Participant flow

Participant flow — Overall Study
MilestonePlaceboPF-04991532 25 mgPF-04991532 75 mgPF-04991532 150 mgPF-04991532 300 mg
Started1617161617
Completed1616161616
Not completed01001
Withdrew: Lack of efficacy00001
Withdrew: Other01000

Outcome measures

PrimaryChange From Baseline (Day -1) in Mean Daily Glucose at Day 14

Mean daily glucose (MDG) was calculated based on the mean of 8 glucose measurements at pre-specified time points throughout the day on Day -1 and Day 14.

Time frame:
Baseline: hours -46, -44, -42, -40, -38, -36, -33, -and -30 on Day -1 (Day 1 morning dose was hour 0); Day 14: 2, 4, 6, 8, 10, 12, 15, and 18 hours after Day 14 morning dose
Reported as:
Mean · milligram/deciliter (mg/dL)
Change From Baseline (Day -1) in Mean Daily Glucose at Day 14
milligram/deciliter (mg/dL)PlaceboPF-04991532 25 mgPF-04991532 75 mgPF-04991532 150 mgPF-04991532 300 mg
Baseline (Day -1)228.67 ± 36.26233.20 ± 41.01219.13 ± 38.16229.92 ± 52.93218.20 ± 53.01
Change from Baseline (Day 14)24.98 ± 40.48-17.55 ± 25.40-3.67 ± 33.79-9.73 ± 21.52-29.23 ± 32.80
Statistical analysis
  • Placebo vs PF-04991532 25 mg · Test-to-reference ratio (%): 84.87 · 90% CI 78.16 to 92.15
  • Placebo vs PF-04991532 75 mg · Test-to-reference ratio (%): 89.80 · 90% CI 82.69 to 97.53
  • Placebo vs PF-04991532 150 mg · Test-to-reference ratio (%): 87.15 · 90% CI 80.27 to 94.63
  • Placebo vs PF-04991532 300 mg · Test-to-reference ratio (%): 78.28 · 90% CI 72.06 to 85.03
SecondaryArea Under the Curve From Time Zero to 24 Hours Postdose (AUC24) of PF-04991532

Area under the plasma concentration versus time curve (AUC) from time zero to 24 hours post morning dose

Time frame:
0 (before morning dose), 0.5, 1, 2, 3, 4, 6, 10, 10.5, 11, 12, 13, 15, 18, and 24 hours after morning dose on Day 1 and Day 14
Reported as:
Geometric mean · nanogram*hour/milliliter (ng*hr/mL)
Area Under the Curve From Time Zero to 24 Hours Postdose (AUC24) of PF-04991532
nanogram*hour/milliliter (ng*hr/mL)PF-04991532 25 mgPF-04991532 75 mgPF-04991532 150 mgPF-04991532 300 mg
Day 1 (n=16, 16, 16, 17)441.6 ± 172.31745 ± 757.13899 ± 15496943 ± 3053
Day 14 (n=16, 16, 16, 16)487.4 ± 227.11892 ± 930.13870 ± 13697531 ± 3084
SecondaryArea Under the Curve From Time Zero to 10 Hours Postdose (AUC10) of PF-04991532

Area under the plasma concentration versus time curve (AUC) from time zero to 10 hours post morning dose.

Time frame:
0 (before morning dose), 0.5, 1, 2, 3, 4, 6, and 10 hours after morning dose on Day 1 and Day 14
Reported as:
Geometric mean · ng*hr/mL
Area Under the Curve From Time Zero to 10 Hours Postdose (AUC10) of PF-04991532
ng*hr/mLPF-04991532 25 mgPF-04991532 75 mgPF-04991532 150 mgPF-04991532 300 mg
Day 1 (n=16, 16, 16, 17)372.1 ± 146.71447 ± 749.33329 ± 11535661 ± 2595
Day 14 (n=16, 16, 16, 16)384.7 ± 181.91508 ± 920.72882 ± 11285551 ± 2633
SecondaryMaximum Observed Plasma Concentration of PF-04991532 After Morning Dose Administration (Cmax(AM))
Time frame:
0 (before morning dose), 0.5, 1, 2, 3, 4, 6, and 10 hours after morning
Reported as:
Geometric mean · ng/mL
Maximum Observed Plasma Concentration of PF-04991532 After Morning Dose Administration (Cmax(AM))
ng/mLPF-04991532 25 mgPF-04991532 75 mgPF-04991532 150 mgPF-04991532 300 mg
Day 1 (n=17, 16, 16, 17)137.7 ± 57.36486.6 ± 363.71285 ± 585.81951 ± 1106
Day 14 (n=16, 16, 16, 16)148.2 ± 74.23469.8 ± 495.3902.4 ± 489.11639 ± 917.8
SecondaryMaximum Observed Plasma Concentration of PF-04991532 After Evening Dose Administration (Cmax(PM))
Time frame:
10 (before evening dose), 10.5, 11, 12, 13, 15, 18, and 24 hours after morning dose on Day 1 and Day 14
Reported as:
Geometric mean · ng/mL
Maximum Observed Plasma Concentration of PF-04991532 After Evening Dose Administration (Cmax(PM))
ng/mLPF-04991532 25 mgPF-04991532 75 mgPF-04991532 150 mgPF-04991532 300 mg
Day 1 (n=16, 16, 16, 17)97.10 ± 67.45336.0 ± 219.7932.0 ± 387.71645 ± 1132
Day 14 (n=16, 16,16, 16)89.99 ± 46.05360.7 ± 288.8772.4 ± 310.81687 ± 914.9
SecondaryMinimum Observed Plasma Trough Concentration (Cmin) of PF-04991532
Time frame:
Day 14
Reported as:
Geometric mean · ng/mL
Minimum Observed Plasma Trough Concentration (Cmin) of PF-04991532
ng/mLPF-04991532 25 mgPF-04991532 75 mgPF-04991532 150 mgPF-04991532 300 mg
Minimum Observed Plasma Trough Concentration (Cmin) of PF-049915320.1691 ± 1.3735.249 ± 3.11211.32 ± 8.12621.15 ± 12.73
SecondaryTime to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04991532 After Morning Dose Administration (Tmax(AM))
Time frame:
0 (predose), 0.5, 1, 2, 3, 4, 6, and 10 hours after morning dose on Day 1 and Day 14
Reported as:
Median · hour
Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04991532 After Morning Dose Administration (Tmax(AM))
hourPF-04991532 25 mgPF-04991532 75 mgPF-04991532 150 mgPF-04991532 300 mg
Day 1 (n=17, 16, 16, 17)1.00 (0.500 to 1.95)1.00 (0.500 to 6.00)1.83 (1.00 to 1.95)1.00 (0.500 to 3.00)
Day 14 (n=16, 16, 16, 16)1.00 (0.500 to 1.95)1.00 (0.500 to 6.00)1.83 (0.500 to 6.00)1.45 (1.00 to 6.00)
SecondaryTime to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04991532 After Evening Dose Administration (Tmax(PM))

Time was computed as post morning dose.

Time frame:
10 (before evening dose), 10.5, 11, 12, 13, 15, 18, and 24 hours after morning dose on Day 1 and Day 14
Reported as:
Median · hour
Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04991532 After Evening Dose Administration (Tmax(PM))
hourPF-04991532 25 mgPF-04991532 75 mgPF-04991532 150 mgPF-04991532 300 mg
Day 1 (n=16, 16, 16, 17)11.0 (11 to 15)11.0 (11 to 15)11.0 (11 to 12)11.0 (11 to 13)
Day 14 (n=16, 16, 16, 16)11.0 (11 to 15)11.0 (11 to 15)11.0 (11 to 18)11.0 (11 to 18)
SecondaryApparent Oral Clearance (CL/F) of PF-04991532

Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.

Time frame:
Day 1 and Day 14: 0 (before morning dose), 0.5, 1, 2, 3, 4, 6, 10 (before evening dose), 10.5, 11, 12, 13, 15, 18 and 24 hours after morning dose
Reported as:
Geometric mean · milliliter/minute (mL/min)
Apparent Oral Clearance (CL/F) of PF-04991532
milliliter/minute (mL/min)PF-04991532 25 mgPF-04991532 75 mgPF-04991532 150 mgPF-04991532 300 mg
Day 1 (n=16, 16, 16, 17)1886 ± 11121434 ± 844.71282 ± 431.51440 ± 607.7
D14 (n=16, 16, 16, 16)1710 ± 12001322 ± 937.91292 ± 624.51327 ± 537.1
SecondaryObserved Accumulation Ratio of Area Under the Curve From Time Zero to 10 Hours Postdose of PF-04991532 (Rac)

Area under the curve from time zero to 10 hours postdose of PF-04991532 (AUC10) of Day 14 divided by AUC10 of Day 1

Time frame:
0 (before morning dose), 0.5, 1, 2, 3, 4, 6, and 10 hours after morning dose on Day 1 and Day 14
Reported as:
Geometric mean · ratio
Observed Accumulation Ratio of Area Under the Curve From Time Zero to 10 Hours Postdose of PF-04991532 (Rac)
ratioPF-04991532 25 mgPF-04991532 75 mgPF-04991532 150 mgPF-04991532 300 mg
Observed Accumulation Ratio of Area Under the Curve From Time Zero to 10 Hours Postdose of PF-04991532 (Rac)1.095 ± 0.35201.049 ± 0.29950.9004 ± 0.33531.017 ± 0.2946
SecondaryObserved Accumulation Ratio of Maximum Observed Plasma Concentration of PF-04991532 After Morning Dose Administration (Rac, Cmax(AM))

Maximum observed plasma concentration of PF-04991532 after morning dose administration (Cmax(AM)) of Day 14 divided by Cmax(AM) of Day 1

Time frame:
0 (before morning dose), 0.5, 1, 2, 3, 4, 6, and 10 hours after morning dose on Day 1 and Day 14
Reported as:
Geometric mean · ratio
Observed Accumulation Ratio of Maximum Observed Plasma Concentration of PF-04991532 After Morning Dose Administration (Rac, Cmax(AM))
ratioPF-04991532 25 mgPF-04991532 75 mgPF-04991532 150 mgPF-04991532 300 mg
Observed Accumulation Ratio of Maximum Observed Plasma Concentration of PF-04991532 After Morning Dose Administration (Rac, Cmax(AM))1.057 ± 0.62670.9655 ± 0.59130.7022 ± 0.47440.8663 ± 0.3648
SecondaryDose Normalized Area Under the Curve From Time Zero to 24 Hours Postdose (AUC24(dn)) of PF-04991532

Area under the curve from time zero to 24 Hours Postdose (AUC24) divided by total daily dose

Time frame:
0 (before morning dose), 0.5, 1, 2, 3, 4, 6, 10, 10.5, 11, 12, 13, 15, 18, and 24 hours after morning dose on Day 1 and Day 14
Reported as:
Geometric mean · ng*hr/mL/mg
Dose Normalized Area Under the Curve From Time Zero to 24 Hours Postdose (AUC24(dn)) of PF-04991532
ng*hr/mL/mgPF-04991532 25 mgPF-04991532 75 mgPF-04991532 150 mgPF-04991532 300 mg
Day 1 (n=16, 16, 16, 17)4.416 ± 1.7235.810 ± 2.5206.497 ± 2.5785.787 ± 2.540
Day 14 (n=16, 16, 16, 16)4.874 ± 2.2716.307 ± 3.1076.449 ± 2.2796.275 ± 2.558
SecondaryDose Normalized Maximum Plasma Concentration After Morning Dose Administration (Cmax(AM)(dn)) of PF-04991532

Maximum Observed Plasma Concentration of PF-04991532 after Morning Dose Administration (Cmax(AM)) divided by dose

Time frame:
0 (before morning dose), 0.5, 1, 2, 3, 4, 6, and 10 hours after morning dose on Day 1 and Day 14
Reported as:
Geometric mean · ng/mL/mg
Dose Normalized Maximum Plasma Concentration After Morning Dose Administration (Cmax(AM)(dn)) of PF-04991532
ng/mL/mgPF-04991532 25 mgPF-04991532 75 mgPF-04991532 150 mgPF-04991532 300 mg
Day 1 (n=17, 16, 16, 17)2.754 ± 1.1473.245 ± 2.4314.283 ± 1.9473.252 ± 1.842
Day 14 (n=16, 16, 16, 16)2.964 ± 1.4843.132 ± 3.2963.009 ± 1.6312.732 ± 1.530
SecondaryChange From Baseline (Day -2) in Mean Daily Glucose at Day 13

Mean daily glucose (MDG) was calculated based on the mean of 8 glucose measurements at pre-specified time points throughout the day.

Time frame:
Baseline: hours -72, -70, -68, -66, -62, -60, -57, and -54 on Day -2 (Day 1 morning dose was hour 0); Day 13: 0 (before morning dose), 2, 4, 6, 10, 12, 15 and 18 hours after Day 13 morning dose
Reported as:
Mean · mg/dL
Change From Baseline (Day -2) in Mean Daily Glucose at Day 13
mg/dLPlaceboPF-04991532 25 mgPF-04991532 75 mgPF-04991532 150 mgPF-04991532 300 mg
Baseline (Day -2)214.31 ± 42.39230.70 ± 37.88207.98 ± 35.10219.59 ± 43.78204.68 ± 45.07
Change from Baseline (Day 13)18.78 ± 39.66-27.22 ± 25.34-15.78 ± 31.99-17.29 ± 17.75-33.58 ± 37.06
Statistical analysis
  • Placebo vs PF-04991532 25 mg · Test-to-reference ratio (%): 82.69 · 90% CI 76.06 to 89.90
  • Placebo vs PF-04991532 75 mg · Test-to-reference ratio (%): 85.39 · 90% CI 78.60 to 92.77
  • Placebo vs PF-04991532 150 mg · Test-to-reference ratio (%): 85.37 · 90% CI 78.59 to 92.76
  • Placebo vs PF-04991532 300 mg · Test-to-reference ratio (%): 75.82 · 90% CI 69.78 to 82.39
  • Placebo vs PF-04991532 75 mg · Difference between test and reference: -35.84 · 90% CI -52.89 to -18.78
SecondaryChange From Baseline in Area Under the Curve of Glucose From Time 2 to 6 Hours Post Morning Dose (Glucose AUC(2-6)) Following Mixed Meal Tolerance Test (MMTT) at Day 14

Area under the curve of glucose from time 2 to 6 hours post morning dose (Glucose AUC(2-6)) was calculated based on 8 glucose measurements at prespecified time points using the linear trapezoidal method. Nominal times were used in the calculation. Liquid meal was administered 2 hours post morning dose of PF-04991532 for mixed meal tolerance test (MMTT).

Time frame:
Baseline: hours -46, -45.75, -45.5, -45, -44.5, -44, -43, -and -42 on Day -1 (Day 1 morning dose was hour 0); Day 14: 2, 2.25, 2.5, 3, 3.5, 4, 5, and 6 hours after Day 14 morning dose
Reported as:
Mean · mg*hr/dL
Change From Baseline in Area Under the Curve of Glucose From Time 2 to 6 Hours Post Morning Dose (Glucose AUC(2-6)) Following Mixed Meal Tolerance Test (MMTT) at Day 14
mg*hr/dLPlaceboPF-04991532 25 mgPF-04991532 75 mgPF-04991532 150 mgPF-04991532 300 mg
Baseline (Day -1)1091.23 ± 163.301126.34 ± 119.261029.76 ± 154.841085.84 ± 245.641050.69 ± 241.70
Change from Baseline (Day 14)86.05 ± 148.94-84.44 ± 99.91-12.65 ± 114.19-60.55 ± 89.36-158.93 ± 152.09
Statistical analysis
  • Placebo vs PF-04991532 25 mg · Test-to-reference ratio (%): 86.72 · 90% CI 81.13 to 92.70
  • Placebo vs PF-04991532 75 mg · Test-to-reference ratio (%): 91.13 · 90% CI 85.24 to 97.44
  • Placebo vs PF-04991532 150 mg · Test-to-reference ratio (%): 87.05 · 90% CI 81.44 to 93.04
  • Placebo vs PF-04991532 300 mg · Test-to-reference ratio (%): 77.95 · 90% CI 72.91 to 83.34
SecondaryChange From Baseline in Fasting Plasma Glucose (FPG)

The average of the Day -1 (hour -48), Day 0 (hour -24) and Day 1 pre-dose (hour 0) measurements was the baseline for fasting plasma glucose (FPG) analyses.

Time frame:
Baseline: hour -48 on Day -1, hour -24 on Day 0, and hour 0 (before morning dose) on Day 1; hour 0 (before morning dose of each day) on Days 1, 2, 3, 6, and 10; and 24 hours after Day 14 morning dose on Day 15
Reported as:
Mean · mg/dL
Change From Baseline in Fasting Plasma Glucose (FPG)
mg/dLPlaceboPF-04991532 25 mgPF-04991532 75 mgPF-04991532 150 mgPF-04991532 300 mg
Day 2 (n=16, 17, 16, 16, 17)-4.19 ± 17.77-5.04 ± 10.43-4.33 ± 18.150.29 ± 14.93-5.55 ± 36.08
Day 3 (n=16, 17, 16, 16, 17)-0.63 ± 15.76-8.92 ± 11.86-2.15 ± 15.250.23 ± 14.06-7.78 ± 16.40
Day 6 (n=16, 16, 16, 16, 16)3.44 ± 26.69-9.40 ± 16.68-9.90 ± 18.13-6.33 ± 12.24-16.90 ± 23.67
Day 10 (n=16, 16, 16, 16, 16)-10.88 ± 43.97-17.21 ± 24.08-16.96 ± 26.78-10.33 ± 15.75-17.40 ± 30.99
Day 14 (n=16, 16, 16, 16, 16)9.00 ± 26.90-17.83 ± 25.71-14.52 ± 23.08-7.27 ± 8.78-11.40 ± 19.12
Day 15 (n=16, 16, 16, 16, 15)12.63 ± 44.47-9.71 ± 25.96-8.15 ± 22.81-0.58 ± 16.71-4.22 ± 37.34
Statistical analysis
  • Placebo vs PF-04991532 25 mg · Test-to-reference ratio (%) at day 2: 100.04 · 90% CI 92.70 to 107.96
  • Placebo vs PF-04991532 75 mg · Test-to-reference ratio (%) at day 2: 99.44 · 90% CI 92.04 to 107.43
  • Placebo vs PF-04991532 150 mg · Test-to-reference ratio (%) at day 2: 101.67 · 90% CI 94.10 to 109.84
  • Placebo vs PF-04991532 300 mg · Test-to-reference ratio (%) at day 2: 96.82 · 90% CI 89.69 to 104.52
  • Placebo vs PF-04991532 25 mg · Test-to-reference ratio (%) at day 3: 95.85 · 90% CI 88.82 to 103.44
  • Placebo vs PF-04991532 75 mg · Test-to-reference ratio (%) at day 3: 98.71 · 90% CI 91.37 to 106.64
  • Placebo vs PF-04991532 150 mg · Test-to-reference ratio (%) at day 3: 99.72 · 90% CI 92.30 to 107.73
  • Placebo vs PF-04991532 300 mg · Test-to-reference ratio (%) at day 3: 94.49 · 90% CI 87.53 to 102.10
  • Placebo vs PF-04991532 25 mg · Test-to-reference ratio (%) at day 6: 93.43 · 90% CI 86.50 to 100.91
  • Placebo vs PF-04991532 75 mg · Test-to-reference ratio (%) at day 6: 92.71 · 90% CI 85.81 to 100.15
  • Placebo vs PF-04991532 150 mg · Test-to-reference ratio (%) at day 6: 94.08 · 90% CI 87.08 to 101.64
  • Placebo vs PF-04991532 300 mg · Test-to-reference ratio (%) at day 6: 87.74 · 90% CI 81.20 to 94.81
  • Placebo vs PF-04991532 25 mg · Test-to-reference ratio (%) at day 10: 96.91 · 90% CI 89.72 to 104.67
  • Placebo vs PF-04991532 75 mg · Test-to-reference ratio (%) at day 10: 96.05 · 90% CI 88.90 to 103.76
  • Placebo vs PF-04991532 150 mg · Test-to-reference ratio (%) at day 10: 99.63 · 90% CI 92.21 to 107.64
  • Placebo vs PF-04991532 300 mg · Test-to-reference ratio (%) at day 10: 94.50 · 90% CI 87.46 to 102.11
  • Placebo vs PF-04991532 25 mg · Test-to-reference ratio (%) at day 14: 86.75 · 90% CI 80.32 to 93.69
  • Placebo vs PF-04991532 75 mg · Test-to-reference ratio (%) at day 14: 87.87 · 90% CI 81.34 to 94.93
  • Placebo vs PF-04991532 150 mg · Test-to-reference ratio (%) at day 14: 91.35 · 90% CI 84.55 to 98.70
  • Placebo vs PF-04991532 300 mg · Test-to-reference ratio (%) at day 14: 88.60 · 90% CI 82.00 to 95.74
  • Placebo vs PF-04991532 25 mg · Test-to-reference ratio (%) at day 15: 90.45 · 90% CI 83.75 to 97.69
  • Placebo vs PF-04991532 75 mg · Test-to-reference ratio (%) at day 15: 90.45 · 90% CI 84.03 to 98.08
  • Placebo vs PF-04991532 150 mg · Test-to-reference ratio (%) at day 15: 94.75 · 90% CI 87.69 to 102.34
  • Placebo vs PF-04991532 300 mg · Test-to-reference ratio (%) at day 15: 93.18 · 90% CI 86.17 to 100.77
SecondaryChange From Baseline in Area Under the Curve of Insulin From Time 2 to 6 Hours Post Morning Dose (Insulin AUC(2-6)) Following Mixed Meal Tolerance Test (MMTT) at Day 14

Area Under the Curve of Insulin from Time 2 to 6 Hours Post Morning Dose (Insulin AUC(2-6)) was calculated based on 8 insulin measurements at prespecified time points using the linear trapezoidal method. Nominal times were used in the calculation. Liquid meal was administered 2 hours post morning dose of PF-04991532 for mixed meal tolerance test (MMTT).

Time frame:
Baseline: hours -46, -45.75, -45.5, -45, -44.5, -44, -43, -and -42 on Day -1 (Day 1 morning dose was hour 0); Day 14: 2, 2.25, 2.5, 3, 3.5, 4, 5, and 6 hours after Day 14 morning dose
Reported as:
Mean · milliUnit*hour/liter (mU*hr/L)
Change From Baseline in Area Under the Curve of Insulin From Time 2 to 6 Hours Post Morning Dose (Insulin AUC(2-6)) Following Mixed Meal Tolerance Test (MMTT) at Day 14
milliUnit*hour/liter (mU*hr/L)PlaceboPF-04991532 25 mgPF-04991532 75 mgPF-04991532 150 mgPF-04991532 300 mg
Baseline (Day -1)149.12 ± 117.08139.40 ± 77.81166.87 ± 132.39111.13 ± 69.16276.61 ± 313.03
Change from Baseline (Day 14)-3.96 ± 18.0915.87 ± 27.16-3.06 ± 32.7911.82 ± 24.87-38.06 ± 73.89
Statistical analysis
  • Placebo vs PF-04991532 25 mg · Test-to-reference ratio (%): 112.83 · 90% CI 99.84 to 127.50
  • Placebo vs PF-04991532 75 mg · Test-to-reference ratio (%): 102.11 · 90% CI 90.78 to 114.85
  • Placebo vs PF-04991532 150 mg · Test-to-reference ratio (%): 111.04 · 90% CI 98.50 to 125.18
  • Placebo vs PF-04991532 300 mg · Test-to-reference ratio (%): 96.73 · 90% CI 85.46 to 109.48
SecondaryChange From Baseline in Area Under the Curve of C-peptide From Time 2 to 6 Hours Post Morning Dose (C-peptide AUC(2-6)) Following Mixed Meal Tolerance Test (MMTT) at Day 14

Area Under the Curve of C-peptide from Time 2 to 6 Hours Post Morning Dose (C-peptide AUC(2-6)) was calculated based on 8 C-peptide measurements at prespecified timepoints using the linear trapezoidal method. Nominal times were used in the calculation. Liquid meal was administered 2 hours post morning dose of PF-04991532 for mixed meal tolerance test (MMTT).

Time frame:
Baseline: hours -46, -45.75, -45.5, -45, -44.5, -44, -43, -and -42 on Day -1 (Day 1 morning dose was hour 0); Day 14: 2, 2.25, 2.5, 3, 3.5, 4, 5, and 6 hours after Day 14 morning dose
Reported as:
Mean · ng*hr/mL
Change From Baseline in Area Under the Curve of C-peptide From Time 2 to 6 Hours Post Morning Dose (C-peptide AUC(2-6)) Following Mixed Meal Tolerance Test (MMTT) at Day 14
ng*hr/mLPlaceboPF-04991532 25 mgPF-04991532 75 mgPF-04991532 150 mgPF-04991532 300 mg
Baseline (Day -1)15.79 ± 6.0817.04 ± 6.7317.20 ± 5.8915.23 ± 4.5119.21 ± 7.61
Change from Baseline (Day 14)0.09 ± 2.151.34 ± 2.64-1.53 ± 2.88-0.55 ± 1.63-2.12 ± 2.97
Statistical analysis
  • Placebo vs PF-04991532 25 mg · Test-to-reference ratio (%): 107.13 · 90% CI 98.69 to 116.30
  • Placebo vs PF-04991532 75 mg · Test-to-reference ratio (%): 92.57 · 90% CI 85.26 to 100.50
  • Placebo vs PF-04991532 150 mg · Test-to-reference ratio (%): 96.07 · 90% CI 88.51 to 104.27
  • Placebo vs PF-04991532 300 mg · Test-to-reference ratio (%): 91.70 · 90% CI 84.38 to 99.65
SecondaryChange From Baseline in Fasting Lipid Parameters at Day 14 and 16

Baseline for fasting triglycerides (TG) was defined as the average of the Day -1 (hour -48), Day 0 (hour -24), and Day 1 pre-dose (hour 0) measurements. Baseline for fasting total cholesterol (TC), cholesterol (high-density lipoprotein (HDL)), and cholesterol (low-density lipoprotein (LDL)) was defined as the Day 1 pre-dose (hour 0) measurement.

Time frame:
Baseline: hour -48 on Day -1, hour -24 on Day 0, and hour 0 on Day 1 for TG and Hour 0 (before morning dose) on Day 1 for TC, HDL, and LDL; 48 hours after morning dose on Day 16 for TG and Hour 0 (before morning dose) on Day14 for TC, HDL, and LDL
Reported as:
Mean · mg/dL
Change From Baseline in Fasting Lipid Parameters at Day 14 and 16
mg/dLPlaceboPF-04991532 25 mgPF-04991532 75 mgPF-04991532 150 mgPF-04991532 300 mg
Triglycerides (Day 16) (n=16, 16, 16, 16, 16)-9.81 ± 35.8712.79 ± 45.6437.52 ± 98.1318.24 ± 36.0858.00 ± 67.31
Total Cholesterol (Day 14) (n=16, 16, 16, 15, 16)0.06 ± 16.98-11.75 ± 31.624.19 ± 20.041.80 ± 19.2911.38 ± 30.17
Cholesterol HDL (Day 14) (n=16, 16, 16, 16, 16)1.75 ± 4.48-1.88 ± 7.751.88 ± 6.040.69 ± 8.443.94 ± 7.17
Cholesterol LDL (Day 14) (n=16, 16, 15, 14, 15)2.38 ± 17.64-8.06 ± 26.984.67 ± 22.48-0.79 ± 16.401.53 ± 25.53

Adverse events

Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Placebo—0/16 (0%)4/16 (25%)
PF-04991532 25 mg—0/17 (0%)3/17 (17.6%)
PF-04991532 75 mg—0/16 (0%)7/16 (43.8%)
PF-04991532 150 mg—0/16 (0%)5/16 (31.3%)
PF-04991532 300 mg—0/17 (0%)4/17 (23.5%)
Most frequent other events
Showing 10 of 27
Most frequent other events
EventPlaceboPF-04991532 25 mgPF-04991532 75 mgPF-04991532 150 mgPF-04991532 300 mg
HeadacheNervous system disorders0/161/173/160/160/17
TachycardiaCardiac disorders0/160/172/160/160/17
HyperglycaemiaMetabolism and nutrition disorders2/160/170/161/160/17
DiarrhoeaGastrointestinal disorders0/160/170/161/160/17
GingivitisGastrointestinal disorders1/160/170/160/160/17
PainGeneral disorders0/160/171/160/160/17
CarbuncleInfections and infestations0/160/170/161/160/17
CystitisInfections and infestations0/160/171/160/160/17
LaryngitisInfections and infestations0/160/171/160/160/17
RhinitisInfections and infestations1/160/171/160/160/17

Baseline characteristics

Age Continuous
Age Continuous(years)PlaceboPF-04991532 25 mgPF-04991532 75 mgPF-04991532 150 mgPF-04991532 300 mgTotal
Mean59.2 ± 8.256.4 ± 9.057.4 ± 10.757.0 ± 9.456.1 ± 8.057.2 ± 8.9
Sex: Female, Male
Sex: Female, Male(Participants)PlaceboPF-04991532 25 mgPF-04991532 75 mgPF-04991532 150 mgPF-04991532 300 mgTotal
Female4452520
Male121311141262
08

Study locations

3 sites
  • Pfizer Investigational Site
    Chula Vista, California 91911, United States
  • Pfizer Investigational Site
    Miami, Florida 33169, United States
  • Pfizer Investigational Site
    Hachioji-shi, Tokyo, Japan
09

References and documents

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Oct 30, 2013, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT01469065
Lead sponsor
Pfizer
Responsible party
Sponsor
First posted
Nov 10, 2011
Start date
Dec 2011
Primary completion
May 2012
Completion
May 2012
Results posted
Aug 29, 2013
Last update
Oct 30, 2013

Study contacts

Pfizer CT.gov Call Center
study director · Pfizer

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Sep 2013. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies in this condition

Diabetes Mellitus→

Other studies from this sponsor

Pfizer

Start the discussion