Diabetes Mellitus, Type 2Phase 1NCT01272804

Multiple Dose Study Of PF-04937319 In Patients With Type 2 Diabetes

A Phase 1 study testing PF-04937319 in people with Diabetes Mellitus, Type 2 and NIDDM, run by Pfizer at 4 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

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. Read more about this study

Who is it for?: Ages 18 to 70 years
Conditions the study is for: Diabetes Mellitus, Type 2, NIDDM
What is being tested?: PF-04937319
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 61 participants
Where: 4 sitesUnited States
Study dates: Feb 2011to Jul 2011
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 70 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Patients with type 2 diabetes mellitus who are taking metformin only.
Treatment should be stable, where this is defined as no change in the treatment, including dose, over the past 2 months. Regimens may include once daily and twice daily dosing only.
Male and/or female patients (females will be women of non childbearing potential)
Body Mass Index (BMI) of 18.5 to 45.0 kg/m2; and a total body weight >50 kg (110 lbs).
HbA1c between 7.0% and 10.0%.

Who cannot join

Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing). Patients who have chronic conditions other than T2DM (for example, hypercholesterolemia or hypertension) but are controlled by either diet or stable (for the last 2 months) doses of medications may be included as well (for example, a subject with hypercholesterolemia on appropriate treatment is eligible).
Evidence or history of diabetic complications with significant end organ damage, eg, proliferative retinopathy and/or macular edema, creatinine clearance less than 60 mL/min
Any condition possibly affecting drug absorption (eg, gastrectomy)
History of stroke or transient ischemic attack or myocardial infarction within the past 6 months
History of coronary artery bypass graft or stent implantation.
Clinically significant peripheral vascular disease (eg, manifested by claudication).

Show all 10Show fewer

Any history or clinical evidence of congestive heart failure, NYHA Classes II to IV.
One or more self reported significant/severe/requiring treatment episodes of hypoglycemia within the last 3 months, or two or more self reported significant/severe/requiring treatment episodes of hypoglycaemia within the last 6 months.
Current history of angina/unstable angina.
Milk or soy allergy

Trial locations and contacts

4 sites in 1 country.

United States4 sites

Medpace Clinical Pharmacology Unit
Cincinnati, Ohio, 45212
Elite Research Institute
Miami, Florida, 33169
Miami Research Associates
South Miami, Florida, 33143
MRA Clinical Research
South Miami, Florida, 33143

Other trials in United States

About this study

Official title: A Phase 1 Placebo-controlled Trial To Assess The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Of Multiple Escalating Oral Doses Of Pf-04937319 In Adult Patients With Type 2 Diabetes Mellitus (t2dm)

Conditions: Diabetes Mellitus, Type 2, NIDDM
Being tested: PF-04937319, Placebo
Keywords: Pharmacokinetics PK Pharmacodynamics PD T2DM Phase 1 Type 2 diabetes mellitus safety and tolerability
Medical subject headings: Diabetes Mellitus, Type 2

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

PF-04937319Drug
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.
PlaceboDrug
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.

Study groups in NCT01272804
Study group	Role	What they receive
PF-04937319	Experimental	Not described Receives: Drug: PF-04937319
Placebo	Placebo comparator	Not described Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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.
Measured: 0 (pre-dose), 0.5, 1.5, 3, 5, 8, 12, 16, 24 hours post morning dose on Day 1 (fasted condition)
Maximum Observed Plasma Concentration at Steady State (Cmax, ss) On Day 14
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: -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.
Measured: -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)

Secondary outcomes (9)

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.
Measured: -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)
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.
Measured: -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.
Measured: -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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline (Day 1), Day 6 and 14

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Feb 2011Jul 2011

First posted10 Jan 2011 (estimated)
Study startFeb 2011
Primary completionJul 2011
Study completionJul 2011

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Diabetes Mellitus, Type 2Studies of the same condition, open and under way.
More trials run by PfizerThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 61 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01272804
Sponsor's protocol ID: B1621003
Status last verified: Oct 2016
First submitted: 6 Jan 2011
Last updated: 1 Feb 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

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.
PubMed 25142735

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 1 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 1 Placebo-controlled Trial To Assess The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Of Multiple Escalating Oral Doses Of Pf-04937319 In Adult Patients With Type 2 Diabetes Mellitus (t2dm)
ClinicalTrials.gov ID: NCT01272804
Acronym / sponsor ID: B1621003
Conditions: Diabetes Mellitus, Type 2, NIDDM
Keywords: Pharmacokinetics PK Pharmacodynamics PD T2DM Phase 1 Type 2 diabetes mellitus safety and tolerability
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 61 participants (actual)
Lead sponsor: PfizerIndustry (pharma, biotech, devices)
Study start: Feb 2011
Primary completion: Jul 2011 (actual)
Study completion: Jul 2011 (actual)
First posted: 10 Jan 2011 (estimated)
Results: Posted 1 Feb 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 2

Arm	Type	Receives
PF-04937319	Experimental	Drug: PF-04937319
Placebo	Placebo comparator	Drug: Placebo

Who may qualify

Ages: 18 to 70 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

Patients with type 2 diabetes mellitus who are taking metformin only.
Treatment should be stable, where this is defined as no change in the treatment, including dose, over the past 2 months. Regimens may include once daily and twice daily dosing only.
Male and/or female patients (females will be women of non childbearing potential)
Body Mass Index (BMI) of 18.5 to 45.0 kg/m2; and a total body weight >50 kg (110 lbs).
HbA1c between 7.0% and 10.0%.

Key exclusion criteria (10 listed)

Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing). Patients who have chronic conditions other than T2DM (for example, hypercholesterolemia or hypertension) but are controlled by either diet or stable (for the last 2 months) doses of medications may be included as well (for example, a subject with hypercholesterolemia on appropriate treatment is eligible).
Evidence or history of diabetic complications with significant end organ damage, eg, proliferative retinopathy and/or macular edema, creatinine clearance less than 60 mL/min
Any condition possibly affecting drug absorption (eg, gastrectomy)
History of stroke or transient ischemic attack or myocardial infarction within the past 6 months
History of coronary artery bypass graft or stent implantation.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
PF-04937319Subjects 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.	Drug	PF-04937319
PlaceboPlacebo 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.	Drug	Placebo

Primary outcome

Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: Baseline (Day 1) up to 14 days after last dose of study treatment (up to 28 days)
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.
Maximum Observed Plasma Concentration (Cmax) On Day 1
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 0 (pre-dose), 0.5, 1.5, 3, 5, 8, 12, 16, 24 hours post morning dose on Day 1 (fasted condition)
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.
Maximum Observed Plasma Concentration at Steady State (Cmax, ss) On Day 14
Time frame: 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
Time frame: 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
Time frame: 0 (pre-dose), 0.5, 1.5, 3, 5, 8, 12, 16, 24 hours post morning dose on Day 14 (fasted condition)
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.
Plasma Decay Half-Life (t1/2) on Day 14
Time frame: 0 (pre-dose), 0.5, 1.5, 3, 5, 8, 12, 16, 24, 36, 48 hours post morning dose on Day 14 (fasted condition)
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Minimum Observed Plasma Trough Concentration at Steady State (Cmin, ss) on Day 14
Time frame: 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
Time frame: 0 hour (pre-dose) through 24 hours post-dose 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.
Apparent Oral Clearance (CL/F) on Day 14
Time frame: 0 (pre-dose), 0.5, 1.5, 3, 5, 8, 12, 16, 24 hours post morning dose on Day 14 (fasted condition)
Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Apparent Volume of Distribution (Vz/F) on Day 14
Time frame: 0 (pre-dose), 0.5, 1.5, 3, 5, 8, 12, 16, 24 hours post morning dose on Day 14 (fasted condition)
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.
Observed Accumulation Ratio for AUCtau (Rac)
Time frame: 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)
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.
Observed Accumulation Ratio for Cmax (Rac, Cmax)
Time frame: 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)
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.
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
Time frame: -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 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.
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
Time frame: -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 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.

9 secondary outcomes

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
Time frame: -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)
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
Time frame: -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
Time frame: -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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Baseline (Day 1), Day 6 and 14

Results and safety

Results posted to the registry on 1 Feb 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
PF-04937319 10 mg	9	8
PF-04937319 30 mg	9	9
PF-04937319 50 mg	9	9
PF-04937319 100 mg	9	9
PF-04937319 300 mg	9	7
Placebo	16	15

Primary outcome: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

Time frame: Baseline (Day 1) up to 14 days after last dose of study treatment (up to 28 days). Number. Unit: participants

Measure	PF-04937319 10 mg n = 9	PF-04937319 30 mg n = 9	PF-04937319 50 mg n = 9	PF-04937319 100 mg n = 9	PF-04937319 300 mg n = 9	Placebo n = 16
AEs	6	5	0	3	8	5
SAEs	0	0	0	0	0	0

Population analysed: Safety analysis set included all participants who received at least 1 dose of study medication.

Primary outcome: Maximum Observed Plasma Concentration (Cmax) On Day 1

Time frame: 0 (pre-dose), 0.5, 1.5, 3, 5, 8, 12, 16, 24 hours (hrs) post morning dose on Day 1 (fasted condition). Geometric mean (Geometric Coefficient of Variation). Unit: nanogram per milliliter (ng/mL)

Measure	PF-04937319 10 mg n = 9	PF-04937319 30 mg n = 9	PF-04937319 50 mg n = 9	PF-04937319 100 mg n = 9	PF-04937319 300 mg n = 9
Value	38.22 (25)	69.49 (32)	119.4 (38)	245.4 (42)	449.3 (39)

Population analysed: Pharmacokinetic (PK) parameter analysis population included all enrolled participants treated with PF-04937319 who had at least 1 of the PK parameters of interest.

Primary outcome: Maximum Observed Plasma Concentration (Cmax) On Day 6

Time frame: 0 (pre-dose), 0.5, 1.5, 3, 5, 8 hours post-dose on Day 6 (fed condition). Geometric mean (Geometric Coefficient of Variation). Unit: ng/mL

Measure	PF-04937319 10 mg n = 9	PF-04937319 30 mg n = 9	PF-04937319 50 mg n = 9	PF-04937319 100 mg n = 9	PF-04937319 300 mg n = 7
Value	57.73 (17)	122.3 (17)	234.1 (24)	421.5 (31)	970.6 (35)

Population analysed: 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.

Primary outcome: Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 1

Time frame: 0 (pre-dose), 0.5, 1.5, 3, 5, 8, 12, 16, 24 hours post morning dose on Day 1 (fasted condition). Median (Full Range). Unit: hour

Measure	PF-04937319 10 mg n = 9	PF-04937319 30 mg n = 9	PF-04937319 50 mg n = 9	PF-04937319 100 mg n = 9	PF-04937319 300 mg n = 9
Value	3.00 (1.50 to 8.00)	3.00 (1.50 to 8.00)	3.00 (2.95 to 5.00)	3.00 (3.00 to 5.00)	3.00 (1.50 to 8.00)

Population analysed: PK parameter analysis population included all enrolled participants treated with PF-04937319 who had at least 1 of the PK parameters of interest.

9 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
PF-04937319 10 mg	0 of 9 (0%)	6 of 9 (66.7%)	Not reported
PF-04937319 30 mg	0 of 9 (0%)	5 of 9 (55.6%)	Not reported
PF-04937319 50 mg	0 of 9 (0%)	0 of 9 (0%)	Not reported
PF-04937319 100 mg	0 of 9 (0%)	3 of 9 (33.3%)	Not reported
PF-04937319 300 mg	0 of 9 (0%)	8 of 9 (88.9%)	Not reported
Placebo	0 of 16 (0%)	5 of 16 (31.3%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 1 Feb 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 25142735Sharma 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.
To obtain contact information for a study center near you, click here.Link provided by the sponsor.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Pfizer CT.gov Call Center study director

Pfizer

4 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing PF-04937319 in people with Diabetes Mellitus, Type 2 and NIDDM, run by Pfizer at 4 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Feb 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 1 Feb 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) (time frame: Baseline (Day 1) up to 14 days after last dose of study treatment (up to 28 days)). The study lists 18 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01272804, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Feb 2017.