Clinical trial NCT01272804: Multiple Dose Study Of PF-04937319 In Patients With Type 2 Diabetes
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Diabetes Mellitus, Type 2
NIDDM
Keywords: Pharmacokinetics PK Pharmacodynamics PD T2DM Phase 1 Type 2 diabetes mellitus safety and tolerability
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2011-01-10
Enrollment: 61
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: Inclusion Criteria:

* 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%.

Exclusion Criteria:

* 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).
* 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

Primary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline (Day 1) up to 14 days after last dose of study treatment (up to 28 days)
measure: Maximum Observed Plasma Concentration (Cmax) On Day 1
timeFrame: 0 (pre-dose), 0.5, 1.5, 3, 5, 8, 12, 16, 24 hours (hrs) post morning dose on Day 1 (fasted condition)
measure: Maximum Observed Plasma Concentration (Cmax) On Day 6
timeFrame: 0 (pre-dose), 0.5, 1.5, 3, 5, 8 hours post-dose on Day 6 (fed condition)
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 1
timeFrame: 0 (pre-dose), 0.5, 1.5, 3, 5, 8, 12, 16, 24 hours post morning dose on Day 1 (fasted condition)
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 6
timeFrame: 0 (pre-dose), 0.5, 1.5, 3, 5, 8 hours post-dose on Day 6 (fed condition)
measure: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) on Day 1
timeFrame: 0 (pre-dose), 0.5, 1.5, 3, 5, 8, 12, 16, 24 hours post morning dose on Day 1 (fasted condition)
measure: Maximum Observed Plasma Concentration at Steady State (Cmax, ss) On Day 14
timeFrame: 0 (pre-dose), 0.5, 1.5, 3, 5, 8, 12, 16, 24 hours post morning dose on Day 14 (fasted condition)
measure: Time to Reach Maximum Observed Plasma Concentration at Steady State (Tmax, ss) on Day 14
timeFrame: 0 (pre-dose), 0.5, 1.5, 3, 5, 8, 12, 16, 24 hours post morning dose on Day 14 (fasted condition)
measure: Area Under the Curve From Time Zero to End of Dosing Interval at Steady State (AUCtau, ss) on Day 14
timeFrame: 0 (pre-dose), 0.5, 1.5, 3, 5, 8, 12, 16, 24 hours post morning dose on Day 14 (fasted condition)
measure: Plasma Decay Half-Life (t1/2) on Day 14
timeFrame: 0 (pre-dose), 0.5, 1.5, 3, 5, 8, 12, 16, 24, 36, 48 hours post morning dose on Day 14 (fasted condition)
measure: Minimum Observed Plasma Trough Concentration at Steady State (Cmin, ss) on Day 14
timeFrame: 0 (pre-dose), 0.5, 1.5, 3, 5, 8, 12, 16 hours post morning dose on Day 14 (fasted condition)
measure: Percentage of Unchanged Drug Excreted in the Urine Over Dosing Interval (Ae[%]) on Day 14
timeFrame: 0 hour (pre-dose) through 24 hours post-dose on Day 14
measure: Apparent Oral Clearance (CL/F) on Day 14
timeFrame: 0 (pre-dose), 0.5, 1.5, 3, 5, 8, 12, 16, 24 hours post morning dose on Day 14 (fasted condition)
measure: Apparent Volume of Distribution (Vz/F) on Day 14
timeFrame: 0 (pre-dose), 0.5, 1.5, 3, 5, 8, 12, 16, 24 hours post morning dose on Day 14 (fasted condition)
measure: Observed Accumulation Ratio for AUCtau (Rac)
timeFrame: 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)
measure: Observed Accumulation Ratio for Cmax (Rac, Cmax)
timeFrame: 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)
measure: 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
timeFrame: -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)
measure: 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
timeFrame: -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:
measure: 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
timeFrame: -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)
measure: 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
timeFrame: -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)
measure: Change From Baseline in Average Plasma Glucose at Day 1, 6, 14
timeFrame: -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
measure: Change From Baseline in Fasting Plasma Glucose at Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15
timeFrame: Baseline (Pre-dose on Day 1), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15
measure: Change From Baseline in Triglyceride (TG) Level at Day 3, 6, 10, 14, 16 and Follow-up
timeFrame: Baseline (Day -2), Day 3, 6, 10, 14, 16 and Follow-up (7 to 14 days after last dose of study medication)
measure: Change From Baseline in Total Cholesterol (TC) Level at Day 3, 6, 10, 14, 16 and Follow-up
timeFrame: Baseline (Day -2), Day 3, 6, 10, 14, 16 and Follow-up (7 to 14 days after last dose of study medication)
measure: Change From Baseline in Low Density Lipoprotein-Cholesterol (LDL-C) Level at Day 3, 6, 10, 14, 16 and Follow-up
timeFrame: Baseline (Day -2), Day 3, 6, 10, 14, 16 and Follow-up (7 to 14 days after last dose of study medication)
measure: Change From Baseline in High Density Lipoprotein-Cholesterol (HDL-C) Level at Day 3, 6, 10, 14, 16 and Follow-up
timeFrame: Baseline (Day -2), Day 3, 6, 10, 14, 16 and Follow-up (7 to 14 days after last dose of study medication)
measure: Change From Baseline in Lactate Level at Day 6 and 14
timeFrame: Baseline (Day 1), Day 6 and 14
Other outcomes:
Locations:
city: Miami
country: United States
facility: Elite Research Institute
state: Florida
city: South Miami
country: United States
facility: Miami Research Associates
state: Florida
city: South Miami
country: United States
facility: MRA Clinical Research
state: Florida
city: Cincinnati
country: United States
facility: Medpace Clinical Pharmacology Unit
state: Ohio
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: 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.