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The purpose of this study is to characterize the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of PF-04937319 following multiple (14 days) escalating oral doses in patients with type 2 diabetes.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| PF-04937319 | Experimental |
| |
| Placebo | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| PF-04937319 | Drug | Subjects will be dosed with PF-04937319 for 14 days. The doses planned are 10, 30, 100 and 300 mg QD. All doses will be administered as tablets (10 and 100 mg strengths). In each Cohort, 9 patients will receive PF 04937319 and 3 will receive placebo. An additional cohort of 12 patients (9 active, 3 placebo) may be performed to explore a QD or BID dose. The dose for this additional cohort could be a dose already studied or a new dose that is within the exposure stopping criteria. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. 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. Treatment-emergent are events between first dose of study drug and up to 14 days after last dose that were absent before treatment or that worsened relative to pre-treatment state. | Baseline (Day 1) up to 14 days after last dose of study treatment (up to 28 days) |
| Maximum Observed Plasma Concentration (Cmax) On Day 1 | 0 (pre-dose), 0.5, 1.5, 3, 5, 8, 12, 16, 24 hours (hrs) post morning dose on Day 1 (fasted condition) | |
| Maximum Observed Plasma Concentration (Cmax) On Day 6 | 0 (pre-dose), 0.5, 1.5, 3, 5, 8 hours post-dose on Day 6 (fed condition) | |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 1 | 0 (pre-dose), 0.5, 1.5, 3, 5, 8, 12, 16, 24 hours post morning dose on Day 1 (fasted condition) | |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 6 | 0 (pre-dose), 0.5, 1.5, 3, 5, 8 hours post-dose on Day 6 (fed condition) | |
| Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) on Day 1 | AUCtau is the area under the plasma concentration versus time curve from time zero (pre-dose) to the end of the dosing interval (tau), here dosing interval is 24 hours. | 0 (pre-dose), 0.5, 1.5, 3, 5, 8, 12, 16, 24 hours post morning dose on Day 1 (fasted condition) |
| Measure | Description | Time Frame |
|---|---|---|
| Percent Change From Baseline in Insulin Area Under the Curve From Time 2 to 6 Hours (AUC [2-6]) After a Mixed Meal Tolerance Test (MMTT) at Day 1 and 14 | Percent change from baseline in area under the plasma insulin concentration-time curve as determined by standardized MMTT. Linear trapezoidal method was used to compute AUC. Baseline value was the AUC (2-6) calculated on Day -1. | -46, -45.75, -45.5, -45, -44.5, -44, -43, -42 hrs pre-dose on Day -1; 2, 2.25, 2.5, 3, 3.5, 4, 5, 6 hrs post-dose on Day 1 and 14 (fasted condition) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Pfizer CT.gov Call Center | Pfizer | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Elite Research Institute | Miami | Florida | 33169 | United States | ||
| Miami Research Associates |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25142735 | Derived | Sharma R, Litchfield J, Atkinson K, Eng H, Amin NB, Denney WS, Pettersen JC, Goosen TC, Di L, Lee E, Pfefferkorn JA, Dalvie DK, Kalgutkar AS. Metabolites in safety testing assessment in early clinical development: a case study with a glucokinase activator. Drug Metab Dispos. 2014 Nov;42(11):1926-39. doi: 10.1124/dmd.114.060087. Epub 2014 Aug 20. |
| Label | URL |
|---|---|
| To obtain contact information for a study center near you, click here. | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | PF-04937319 10 mg | Participants received PF-04937319 10 milligram (mg) tablet orally once daily for 14 days. |
| FG001 | PF-04937319 30 mg | Participants received PF-04937319 30 mg (3 tablets of 10 mg) orally once daily for 14 days. |
| FG002 | PF-04937319 50 mg | Participants received PF-04937319 50 mg (5 tablets of 10 mg) orally once daily for 14 days. |
| FG003 | PF-04937319 100 mg | Participants received PF-04937319 100 mg tablet orally once daily for 14 days. |
| FG004 | PF-04937319 300 mg | Participants received PF-04937319 300 mg (3 tablets of 100 mg) orally once daily for 14 days. |
| FG005 | Placebo | Participants received placebo matched to PF-04937319 tablet orally once daily for 14 days. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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Safety analysis set included all participants who received at least 1 dose of study medication.
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| ID | Title | Description |
|---|---|---|
| BG000 | PF-04937319 10 mg | Participants received PF-04937319 10 milligram (mg) tablet orally once daily for 14 days. |
| BG001 | PF-04937319 30 mg | Participants received PF-04937319 30 mg (3 tablets of 10 mg) orally once daily for 14 days. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. 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. Treatment-emergent are events between first dose of study drug and up to 14 days after last dose that were absent before treatment or that worsened relative to pre-treatment state. | Safety analysis set included all participants who received at least 1 dose of study medication. | Posted | Number | participants | Baseline (Day 1) up to 14 days after last dose of study treatment (up to 28 days) |
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | PF-04937319 10 mg | Participants received PF-04937319 10 milligram (mg) tablet orally once daily for 14 days. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 14.0 | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Pfizer ClinicalTrials.gov Call Center | Pfizer, Inc. | 1-800-718-1021 | ClinicalTrials.gov_Inquiries@pfizer.com |
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| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| C000598526 | N,N-dimethyl-5-((2-methyl-6-((5-methylpyrazin-2-yl)carbamoyl)benzofuran-4-yl)oxy)pyrimidine-2-carboxamide |
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|
| Placebo | Drug | Placebo to match PF-04937319 will be provided. Subjects will be dosed for 14 days. In each cohort 9 subjects will receive PF-04937319 and 3 will receive placebo. |
|
| Maximum Observed Plasma Concentration at Steady State (Cmax, ss) On Day 14 | 0 (pre-dose), 0.5, 1.5, 3, 5, 8, 12, 16, 24 hours post morning dose on Day 14 (fasted condition) |
| Time to Reach Maximum Observed Plasma Concentration at Steady State (Tmax, ss) on Day 14 | 0 (pre-dose), 0.5, 1.5, 3, 5, 8, 12, 16, 24 hours post morning dose on Day 14 (fasted condition) |
| Area Under the Curve From Time Zero to End of Dosing Interval at Steady State (AUCtau, ss) on Day 14 | AUCtau, ss = Area under the plasma concentration versus time curve from time zero (pre-dose) to the end of the dosing interval (tau) at steady state, here dosing interval is 24 hours. | 0 (pre-dose), 0.5, 1.5, 3, 5, 8, 12, 16, 24 hours post morning dose on Day 14 (fasted condition) |
| Plasma Decay Half-Life (t1/2) on Day 14 | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. | 0 (pre-dose), 0.5, 1.5, 3, 5, 8, 12, 16, 24, 36, 48 hours post morning dose on Day 14 (fasted condition) |
| Minimum Observed Plasma Trough Concentration at Steady State (Cmin, ss) on Day 14 | 0 (pre-dose), 0.5, 1.5, 3, 5, 8, 12, 16 hours post morning dose on Day 14 (fasted condition) |
| Percentage of Unchanged Drug Excreted in the Urine Over Dosing Interval (Ae[%]) on Day 14 | Percentage of drug excreted unchanged in urine calculated as overall amount of unchanged drug excreted in the urine over the dosing interval (24 hours) divided by total daily dose multiplied by 100. | 0 hour (pre-dose) through 24 hours post-dose on Day 14 |
| Apparent Oral Clearance (CL/F) on Day 14 | Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. | 0 (pre-dose), 0.5, 1.5, 3, 5, 8, 12, 16, 24 hours post morning dose on Day 14 (fasted condition) |
| Apparent Volume of Distribution (Vz/F) on Day 14 | Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. | 0 (pre-dose), 0.5, 1.5, 3, 5, 8, 12, 16, 24 hours post morning dose on Day 14 (fasted condition) |
| Observed Accumulation Ratio for AUCtau (Rac) | Accumulation ratio for AUCtau (Rac) was calculated as area under the curve from time zero to end of dosing interval (AUCtau) on Day 14 divided by area under the curve from time zero to end of dosing interval (AUCtau) on Day 1. Dosing interval = 24 hours. | 0 (pre-dose), 0.5, 1.5, 3, 5, 8, 12, 16, 24 hours post morning dose on Day 1 and Day 14 (fasted condition) |
| Observed Accumulation Ratio for Cmax (Rac, Cmax) | Accumulation ratio for Cmax (Rac, Cmax) was calculated as maximum observed plasma concentration (Cmax) on Day 14 divided by maximum observed plasma concentration (Cmax) on Day 1. | 0 (pre-dose), 0.5, 1.5, 3, 5, 8, 12, 16, 24 hours post morning dose on Day 1 and Day 14 (fasted condition) |
| Percent Change From Baseline in Glucose Area Under the Curve From Time 2 to 6 Hours (AUC [2-6]) After a Mixed Meal Tolerance Test (MMTT) at Day 1 | Percent change from baseline in area under the plasma glucose concentration-time curve as determined by standardized MMTT. Linear trapezoidal method was used to compute AUC. Baseline value was the AUC (2-6) calculated on Day -1. | -46, -45.75, -45.5, -45, -44.5, -44, -43, -42 hrs pre-dose on Day -1; 2, 2.25, 2.5, 3, 3.5, 4, 5, 6 hrs post-dose on Day 1 (fasted condition) |
| Percent Change From Baseline in Glucose Area Under the Curve From Time 2 to 6 Hours (AUC [2-6]) After a Mixed Meal Tolerance Test (MMTT) at Day 14 | Percent change from baseline in area under the plasma glucose concentration-time curve as determined by standardized MMTT. Linear trapezoidal method was used to compute AUC. Baseline value was the AUC (2-6) calculated on Day -1. | -46, -45.75, -45.5, -45, -44.5, -44, -43, -42 hrs pre-dose on Day -1; 2, 2.25, 2.5, 3, 3.5, 4, 5, 6 hrs post-dose on Day 14 (fasted condition) |
| Percent Change From Baseline in C-peptide Area Under the Curve From Time 2 to 6 Hours (AUC [2-6]) After a Mixed Meal Tolerance Test (MMTT) at Day 1 and 14 | Percent change from baseline in area under the plasma C-peptide concentration-time curve as determined by standardized MMTT. Linear trapezoidal method was used to compute AUC. Baseline value was the AUC (2-6) calculated on Day -1. | -46, -45.75, -45.5, -45, -44.5, -44, -43, -42 hrs pre-dose on Day -1; 2, 2.25, 2.5, 3, 3.5, 4, 5, 6 hrs post-dose on Day 1 and 14 (fasted condition) |
| Change From Baseline in Average Plasma Glucose at Day 1, 6, 14 | Glucometer testing performed by finger-stick at 8 time points per day to measure glucose levels. Average plasma glucose was calculated as area under the plasma glucose concentration-time curve from 0 to 24 hours (AUC [0-24]) divided by 24. | -46, -44, -42, -40, -38, -36, -30, -27 hrs pre-dose on Day -1; 2, 6, 8, 10, 12,18,21 hrs post-dose on Day 1, 6 and 14; additional 0 hr (pre-dose) on Day 6 and 4 hr post-dose on Day 1 and 14 |
| Change From Baseline in Fasting Plasma Glucose at Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15 | Baseline (Pre-dose on Day 1), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 |
| Change From Baseline in Triglyceride (TG) Level at Day 3, 6, 10, 14, 16 and Follow-up | Blood sample for lipid biomarker was taken following 12-hours fasting. Baseline value was collected on Day -2 for lipids. | Baseline (Day -2), Day 3, 6, 10, 14, 16 and Follow-up (7 to 14 days after last dose of study medication) |
| Change From Baseline in Total Cholesterol (TC) Level at Day 3, 6, 10, 14, 16 and Follow-up | Blood sample for lipid biomarker was taken following 12-hours fasting. Baseline value was collected on Day -2 for lipids. | Baseline (Day -2), Day 3, 6, 10, 14, 16 and Follow-up (7 to 14 days after last dose of study medication) |
| Change From Baseline in Low Density Lipoprotein-Cholesterol (LDL-C) Level at Day 3, 6, 10, 14, 16 and Follow-up | Blood sample for lipid biomarker was taken following 12-hours fasting. Baseline value was collected on Day -2 for lipids. | Baseline (Day -2), Day 3, 6, 10, 14, 16 and Follow-up (7 to 14 days after last dose of study medication) |
| Change From Baseline in High Density Lipoprotein-Cholesterol (HDL-C) Level at Day 3, 6, 10, 14, 16 and Follow-up | Blood sample for lipid biomarker was taken following 12-hours fasting. Baseline value was collected on Day -2 for lipids. | Baseline (Day -2), Day 3, 6, 10, 14, 16 and Follow-up (7 to 14 days after last dose of study medication) |
| Change From Baseline in Lactate Level at Day 6 and 14 | Baseline value was collected at 0 hour on Day 1 for lactate. | Baseline (Day 1), Day 6 and 14 |
| South Miami |
| Florida |
| 33143 |
| United States |
| MRA Clinical Research | South Miami | Florida | 33143 | United States |
| Medpace Clinical Pharmacology Unit | Cincinnati | Ohio | 45212 | United States |
| BG002 | PF-04937319 50 mg | Participants received PF-04937319 50 mg (5 tablets of 10 mg) orally once daily for 14 days. |
| BG003 | PF-04937319 100 mg | Participants received PF-04937319 100 mg tablet orally once daily for 14 days. |
| BG004 | PF-04937319 300 mg | Participants received PF-04937319 300 mg (3 tablets of 100 mg) orally once daily for 14 days. |
| BG005 | Placebo | Participants received placebo matched to PF-04937319 tablet orally once daily for 14 days. |
| BG006 | Total | Total of all reporting groups |
| years |
|
| Gender | Count of Participants | Participants |
|
Participants received PF-04937319 10 milligram (mg) tablet orally once daily for 14 days. |
| OG001 | PF-04937319 30 mg | Participants received PF-04937319 30 mg (3 tablets of 10 mg) orally once daily for 14 days. |
| OG002 | PF-04937319 50 mg | Participants received PF-04937319 50 mg (5 tablets of 10 mg) orally once daily for 14 days. |
| OG003 | PF-04937319 100 mg | Participants received PF-04937319 100 mg tablet orally once daily for 14 days. |
| OG004 | PF-04937319 300 mg | Participants received PF-04937319 300 mg (3 tablets of 100 mg) orally once daily for 14 days. |
| OG005 | Placebo | Participants received placebo matched to PF-04937319 tablet orally once daily for 14 days. |
|
|
| Primary | Maximum Observed Plasma Concentration (Cmax) On Day 1 | Pharmacokinetic (PK) parameter analysis population included all enrolled participants treated with PF-04937319 who had at least 1 of the PK parameters of interest. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram per milliliter (ng/mL) | 0 (pre-dose), 0.5, 1.5, 3, 5, 8, 12, 16, 24 hours (hrs) post morning dose on Day 1 (fasted condition) |
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| Primary | Maximum Observed Plasma Concentration (Cmax) On Day 6 | PK parameter analysis population included all enrolled participants treated with PF-04937319 who had at least 1 of the PK parameters of interest. Here 'N' (number of participants analyzed) signifies participants evaluable for this measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 0 (pre-dose), 0.5, 1.5, 3, 5, 8 hours post-dose on Day 6 (fed condition) |
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| Primary | Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 1 | PK parameter analysis population included all enrolled participants treated with PF-04937319 who had at least 1 of the PK parameters of interest. | Posted | Median | Full Range | hour | 0 (pre-dose), 0.5, 1.5, 3, 5, 8, 12, 16, 24 hours post morning dose on Day 1 (fasted condition) |
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| Primary | Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 6 | PK parameter analysis population included all enrolled participants treated with PF-04937319 who had at least 1 of the PK parameters of interest. Here 'N' (number of participants analyzed) signifies participants evaluable for this measure. | Posted | Median | Full Range | hour | 0 (pre-dose), 0.5, 1.5, 3, 5, 8 hours post-dose on Day 6 (fed condition) |
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| Primary | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) on Day 1 | AUCtau is the area under the plasma concentration versus time curve from time zero (pre-dose) to the end of the dosing interval (tau), here dosing interval is 24 hours. | PK parameter analysis population included all enrolled participants treated with PF-04937319 who had at least 1 of the PK parameters of interest. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram*hour per milliliter | 0 (pre-dose), 0.5, 1.5, 3, 5, 8, 12, 16, 24 hours post morning dose on Day 1 (fasted condition) |
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| Primary | Maximum Observed Plasma Concentration at Steady State (Cmax, ss) On Day 14 | PK parameter analysis population included all enrolled participants treated with PF-04937319 who had at least 1 of the PK parameters of interest. Here 'N' (number of participants analyzed) signifies participants evaluable for this measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 0 (pre-dose), 0.5, 1.5, 3, 5, 8, 12, 16, 24 hours post morning dose on Day 14 (fasted condition) |
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| Primary | Time to Reach Maximum Observed Plasma Concentration at Steady State (Tmax, ss) on Day 14 | PK parameter analysis population included all enrolled participants treated with PF-04937319 who had at least 1 of the PK parameters of interest. Here 'N' (number of participants analyzed) signifies participants evaluable for this measure. | Posted | Median | Full Range | hour | 0 (pre-dose), 0.5, 1.5, 3, 5, 8, 12, 16, 24 hours post morning dose on Day 14 (fasted condition) |
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| Primary | Area Under the Curve From Time Zero to End of Dosing Interval at Steady State (AUCtau, ss) on Day 14 | AUCtau, ss = Area under the plasma concentration versus time curve from time zero (pre-dose) to the end of the dosing interval (tau) at steady state, here dosing interval is 24 hours. | PK parameter analysis population included all enrolled participants treated with PF-04937319 who had at least 1 of the PK parameters of interest. Here 'N' (number of participants analyzed) signifies participants evaluable for this measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram*hour per milliliter | 0 (pre-dose), 0.5, 1.5, 3, 5, 8, 12, 16, 24 hours post morning dose on Day 14 (fasted condition) |
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| Primary | Plasma Decay Half-Life (t1/2) on Day 14 | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. | PK parameter analysis population included all enrolled participants treated with PF-04937319 who had at least 1 of the PK parameters of interest. Here 'N' (number of participants analyzed) signifies participants evaluable for this measure. | Posted | Mean | Standard Deviation | hour | 0 (pre-dose), 0.5, 1.5, 3, 5, 8, 12, 16, 24, 36, 48 hours post morning dose on Day 14 (fasted condition) |
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| Primary | Minimum Observed Plasma Trough Concentration at Steady State (Cmin, ss) on Day 14 | PK parameter analysis population included all enrolled participants treated with PF-04937319 who had at least 1 of the PK parameters of interest. Here 'N' (number of participants analyzed) signifies participants evaluable for this measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 0 (pre-dose), 0.5, 1.5, 3, 5, 8, 12, 16 hours post morning dose on Day 14 (fasted condition) |
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| Primary | Percentage of Unchanged Drug Excreted in the Urine Over Dosing Interval (Ae[%]) on Day 14 | Percentage of drug excreted unchanged in urine calculated as overall amount of unchanged drug excreted in the urine over the dosing interval (24 hours) divided by total daily dose multiplied by 100. | PK parameter analysis population included all enrolled participants treated with PF-04937319 who had at least 1 of the PK parameters of interest. Here 'N' (number of participants analyzed) signifies participants evaluable for this measure. | Posted | Mean | Standard Deviation | percentage of dose | 0 hour (pre-dose) through 24 hours post-dose on Day 14 |
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| Primary | Apparent Oral Clearance (CL/F) on Day 14 | Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. | PK parameter analysis population included all enrolled participants treated with PF-04937319 who had at least 1 of the PK parameters of interest. Here 'N' (number of participants analyzed) signifies participants evaluable for this measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | liter per hour | 0 (pre-dose), 0.5, 1.5, 3, 5, 8, 12, 16, 24 hours post morning dose on Day 14 (fasted condition) |
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| Primary | Apparent Volume of Distribution (Vz/F) on Day 14 | Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. | PK parameter analysis population included all enrolled participants treated with PF-04937319 who had at least 1 of the PK parameters of interest. Here 'N' (number of participants analyzed) signifies participants evaluable for this measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | liter | 0 (pre-dose), 0.5, 1.5, 3, 5, 8, 12, 16, 24 hours post morning dose on Day 14 (fasted condition) |
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| Primary | Observed Accumulation Ratio for AUCtau (Rac) | Accumulation ratio for AUCtau (Rac) was calculated as area under the curve from time zero to end of dosing interval (AUCtau) on Day 14 divided by area under the curve from time zero to end of dosing interval (AUCtau) on Day 1. Dosing interval = 24 hours. | PK parameter analysis population included all enrolled participants treated with PF-04937319 who had at least 1 of the PK parameters of interest. Here 'N' (number of participants analyzed) signifies participants evaluable for this measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | ratio | 0 (pre-dose), 0.5, 1.5, 3, 5, 8, 12, 16, 24 hours post morning dose on Day 1 and Day 14 (fasted condition) |
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| Primary | Observed Accumulation Ratio for Cmax (Rac, Cmax) | Accumulation ratio for Cmax (Rac, Cmax) was calculated as maximum observed plasma concentration (Cmax) on Day 14 divided by maximum observed plasma concentration (Cmax) on Day 1. | PK parameter analysis population included all enrolled participants treated with PF-04937319 who had at least 1 of the PK parameters of interest. Here 'N' (number of participants analyzed) signifies participants evaluable for this measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | ratio | 0 (pre-dose), 0.5, 1.5, 3, 5, 8, 12, 16, 24 hours post morning dose on Day 1 and Day 14 (fasted condition) |
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| Primary | Percent Change From Baseline in Glucose Area Under the Curve From Time 2 to 6 Hours (AUC [2-6]) After a Mixed Meal Tolerance Test (MMTT) at Day 1 | Percent change from baseline in area under the plasma glucose concentration-time curve as determined by standardized MMTT. Linear trapezoidal method was used to compute AUC. Baseline value was the AUC (2-6) calculated on Day -1. | Pharmacodynamic (PD) analysis population included all enrolled participants who received at least 1 dose of study medication and had at least 1 PD parameter. | Posted | Mean | Standard Deviation | percent change | -46, -45.75, -45.5, -45, -44.5, -44, -43, -42 hrs pre-dose on Day -1; 2, 2.25, 2.5, 3, 3.5, 4, 5, 6 hrs post-dose on Day 1 (fasted condition) |
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| Primary | Percent Change From Baseline in Glucose Area Under the Curve From Time 2 to 6 Hours (AUC [2-6]) After a Mixed Meal Tolerance Test (MMTT) at Day 14 | Percent change from baseline in area under the plasma glucose concentration-time curve as determined by standardized MMTT. Linear trapezoidal method was used to compute AUC. Baseline value was the AUC (2-6) calculated on Day -1. | PD analysis population included all enrolled participants who received at least 1 dose of study medication and had at least 1 PD parameter. Here 'N' (number of participants analyzed) signifies participants evaluable for this measure. | Posted | Mean | Standard Deviation | percent change | -46, -45.75, -45.5, -45, -44.5, -44, -43, -42 hrs pre-dose on Day -1; 2, 2.25, 2.5, 3, 3.5, 4, 5, 6 hrs post-dose on Day 14 (fasted condition) |
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| Secondary | Percent Change From Baseline in Insulin Area Under the Curve From Time 2 to 6 Hours (AUC [2-6]) After a Mixed Meal Tolerance Test (MMTT) at Day 1 and 14 | Percent change from baseline in area under the plasma insulin concentration-time curve as determined by standardized MMTT. Linear trapezoidal method was used to compute AUC. Baseline value was the AUC (2-6) calculated on Day -1. | PD analysis population included all enrolled participants who received at least 1 dose of study medication and had at least 1 PD parameter. Here 'n' signifies participants evaluable for this measure at specified time point for each arm group, respectively. | Posted | Mean | Standard Deviation | percent change | -46, -45.75, -45.5, -45, -44.5, -44, -43, -42 hrs pre-dose on Day -1; 2, 2.25, 2.5, 3, 3.5, 4, 5, 6 hrs post-dose on Day 1 and 14 (fasted condition) |
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| Secondary | Percent Change From Baseline in C-peptide Area Under the Curve From Time 2 to 6 Hours (AUC [2-6]) After a Mixed Meal Tolerance Test (MMTT) at Day 1 and 14 | Percent change from baseline in area under the plasma C-peptide concentration-time curve as determined by standardized MMTT. Linear trapezoidal method was used to compute AUC. Baseline value was the AUC (2-6) calculated on Day -1. | PD analysis population included all enrolled participants who received at least 1 dose of study medication and had at least 1 PD parameter. Here 'n' signifies participants evaluable for this measure at specified time point for each arm group, respectively. | Posted | Mean | Standard Deviation | percent change | -46, -45.75, -45.5, -45, -44.5, -44, -43, -42 hrs pre-dose on Day -1; 2, 2.25, 2.5, 3, 3.5, 4, 5, 6 hrs post-dose on Day 1 and 14 (fasted condition) |
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| Secondary | Change From Baseline in Average Plasma Glucose at Day 1, 6, 14 | Glucometer testing performed by finger-stick at 8 time points per day to measure glucose levels. Average plasma glucose was calculated as area under the plasma glucose concentration-time curve from 0 to 24 hours (AUC [0-24]) divided by 24. | PD analysis population included all enrolled participants who received at least 1 dose of study medication and had at least 1 PD parameter. Here 'n' signifies participants evaluable for this measure at specified time point for each arm group, respectively. | Posted | Mean | Standard Deviation | mg/dL | -46, -44, -42, -40, -38, -36, -30, -27 hrs pre-dose on Day -1; 2, 6, 8, 10, 12,18,21 hrs post-dose on Day 1, 6 and 14; additional 0 hr (pre-dose) on Day 6 and 4 hr post-dose on Day 1 and 14 |
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| Secondary | Change From Baseline in Fasting Plasma Glucose at Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15 | PD analysis population included all enrolled participants who received at least 1 dose of study medication and had at least 1 PD parameter. Here 'n' signifies participants evaluable for this measure at specified time point for each arm group, respectively. | Posted | Mean | Standard Deviation | mg/dL | Baseline (Pre-dose on Day 1), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 |
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| Secondary | Change From Baseline in Triglyceride (TG) Level at Day 3, 6, 10, 14, 16 and Follow-up | Blood sample for lipid biomarker was taken following 12-hours fasting. Baseline value was collected on Day -2 for lipids. | PD analysis population included all enrolled participants who received at least 1 dose of study medication and had at least 1 PD parameter. Here 'n' signifies participants evaluable for this measure at specified time point for each arm group, respectively. | Posted | Mean | Standard Deviation | mg/dL | Baseline (Day -2), Day 3, 6, 10, 14, 16 and Follow-up (7 to 14 days after last dose of study medication) |
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| Secondary | Change From Baseline in Total Cholesterol (TC) Level at Day 3, 6, 10, 14, 16 and Follow-up | Blood sample for lipid biomarker was taken following 12-hours fasting. Baseline value was collected on Day -2 for lipids. | PD analysis population included all enrolled participants who received at least 1 dose of study medication and had at least 1 PD parameter. Here 'n' signifies participants evaluable for this measure at specified time point for each arm group, respectively. | Posted | Mean | Standard Deviation | mg/dL | Baseline (Day -2), Day 3, 6, 10, 14, 16 and Follow-up (7 to 14 days after last dose of study medication) |
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| Secondary | Change From Baseline in Low Density Lipoprotein-Cholesterol (LDL-C) Level at Day 3, 6, 10, 14, 16 and Follow-up | Blood sample for lipid biomarker was taken following 12-hours fasting. Baseline value was collected on Day -2 for lipids. | PD analysis population included all enrolled participants who received at least 1 dose of study medication and had at least 1 PD parameter. Here 'n' signifies participants evaluable for this measure at specified time point for each arm group, respectively. | Posted | Mean | Standard Deviation | mg/dL | Baseline (Day -2), Day 3, 6, 10, 14, 16 and Follow-up (7 to 14 days after last dose of study medication) |
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| Secondary | Change From Baseline in High Density Lipoprotein-Cholesterol (HDL-C) Level at Day 3, 6, 10, 14, 16 and Follow-up | Blood sample for lipid biomarker was taken following 12-hours fasting. Baseline value was collected on Day -2 for lipids. | PD analysis population included all enrolled participants who received at least 1 dose of study medication and had at least 1 PD parameter. Here 'n' signifies participants evaluable for this measure at specified time point for each arm group, respectively. | Posted | Mean | Standard Deviation | mg/dL | Baseline (Day -2), Day 3, 6, 10, 14, 16 and Follow-up (7 to 14 days after last dose of study medication) |
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| Secondary | Change From Baseline in Lactate Level at Day 6 and 14 | Baseline value was collected at 0 hour on Day 1 for lactate. | PD analysis population included all enrolled participants who received at least 1 dose of study medication and had at least 1 PD parameter. Here 'n' signifies participants evaluable for this measure at specified time point for each arm group, respectively. | Posted | Mean | Standard Deviation | mg/dL | Baseline (Day 1), Day 6 and 14 |
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| 0 |
| 9 |
| 6 |
| 9 |
| EG001 | PF-04937319 30 mg | Participants received PF-04937319 30 mg (3 tablets of 10 mg) orally once daily for 14 days. | 0 | 9 | 5 | 9 |
| EG002 | PF-04937319 50 mg | Participants received PF-04937319 50 mg (5 tablets of 10 mg) orally once daily for 14 days. | 0 | 9 | 0 | 9 |
| EG003 | PF-04937319 100 mg | Participants received PF-04937319 100 mg tablet orally once daily for 14 days. | 0 | 9 | 3 | 9 |
| EG004 | PF-04937319 300 mg | Participants received PF-04937319 300 mg (3 tablets of 100 mg) orally once daily for 14 days. | 0 | 9 | 8 | 9 |
| EG005 | Placebo | Participants received placebo matched to PF-04937319 tablet orally once daily for 14 days. | 0 | 16 | 5 | 16 |
| Vertigo | Ear and labyrinth disorders | MedDRA 14.0 | Non-systematic Assessment |
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| Conjunctivitis | Eye disorders | MedDRA 14.0 | Non-systematic Assessment |
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| Abdominal distension | Gastrointestinal disorders | MedDRA 14.0 | Non-systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 14.0 | Non-systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | MedDRA 14.0 | Non-systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 14.0 | Non-systematic Assessment |
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| Acute sinusitis | Infections and infestations | MedDRA 14.0 | Non-systematic Assessment |
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| Infected sebaceous cyst | Infections and infestations | MedDRA 14.0 | Non-systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA 14.0 | Non-systematic Assessment |
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| Viral upper respiratory tract infection | Infections and infestations | MedDRA 14.0 | Non-systematic Assessment |
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| Contusion | Injury, poisoning and procedural complications | MedDRA 14.0 | Non-systematic Assessment |
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| Blood glucose decreased | Investigations | MedDRA 14.0 | Non-systematic Assessment |
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| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 14.0 | Non-systematic Assessment |
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| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA 14.0 | Non-systematic Assessment |
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| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 14.0 | Non-systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 14.0 | Non-systematic Assessment |
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| Anxiety | Psychiatric disorders | MedDRA 14.0 | Non-systematic Assessment |
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| Micturition urgency | Renal and urinary disorders | MedDRA 14.0 | Non-systematic Assessment |
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| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Non-systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA 14.0 | Non-systematic Assessment |
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| Skin disorder | Skin and subcutaneous tissue disorders | MedDRA 14.0 | Non-systematic Assessment |
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| Skin irritation | Skin and subcutaneous tissue disorders | MedDRA 14.0 | Non-systematic Assessment |
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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.
| D004700 | Endocrine System Diseases |
| Percent Change at Day 14 (n=8,9,9,9,7,15) |
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| Percent Change at Day 14 (n=8,9,9,9,7,15) |
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| Change at Day 1 (n=9,9,9,9,9,16) |
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| Change at Day 6 (n=8,9,9,9,7,15) |
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| Change at Day 14 (n=8,9,9,9,7,15) |
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| Change at Day 2 (n=9,9,9,9,9,16) |
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| Change at Day 3 (n=9,9,9,9,9,16) |
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| Change at Day 4 (n=9,9,9,9,8,16) |
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| Change at Day 5 (n=9,9,9,9,9,16) |
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| Change at Day 6 (n=9,9,9,9,7,15) |
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| Change at Day 7 (n=8,9,9,9,7,15) |
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| Change at Day 8 (n=8,9,9,9,7,15) |
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| Change at Day 9 (n=8,9,9,9,7,15) |
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| Change at Day 10 (n=8,9,9,9,7,15) |
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| Change at Day 11 (n=8,9,9,9,7,15) |
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| Change at Day 12 (n=8,9,9,9,7,15) |
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| Change at Day 13 (n=8,9,9,9,7,15) |
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| Change at Day 14 (n=8,9,9,9,7,15) |
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| Change at Day 15 (n=8,9,9,9,7,15) |
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| Change at Day 3 (n=9,9,9,9,9,16) |
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| Change at Day 6 (n=9,9,9,9,7,15) |
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| Change at Day 10 (n=8,9,9,9,7,15) |
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| Change at Day 14 (n=8,9,9,9,7,15) |
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| Change at Day 16 (n=8,9,9,9,7,14) |
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| Change at Follow-up (n=9,9,9,9,7,16) |
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| Change at Day 3 (n=9,9,9,9,9,16) |
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| Change at Day 6 (n=9,9,9,9,7,15) |
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| Change at Day 10 (n=8,9,9,9,7,15) |
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| Change at Day 14 (n=8,9,9,9,7,15) |
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| Change at Day 16 (n=8,9,9,9,7,14) |
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| Change at Follow-up (n=9,9,9,9,7,16) |
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| Change at Day 3 (n=9,9,9,9,9,16) |
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| Change at Day 6 (n=9,9,9,9,7,15) |
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| Change at Day 10 (n=8,9,9,9,7,15) |
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| Change at Day 14 (n=8,9,9,9,7,15) |
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| Change at Day 16 (n=8,9,9,9,7,14) |
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| Change at Follow-up (n=9,8,9,9,7,16) |
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| Change at Day 3 (n=9,9,9,9,9,16) |
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| Change at Day 6 (n=9,9,9,9,7,15) |
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| Change at Day 10 (n=8,9,9,9,7,15) |
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| Change at Day 14 (n=8,9,9,9,7,15) |
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| Change at Day 16 (n=8,9,9,9,7,14) |
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| Change at Follow-up (n=9,9,9,9,7,16) |
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| Change at Day 6 (n=9,9,9,9,7,15) |
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| Change at Day 14 (n=8,9,9,9,7,15) |
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