Phase 1
N=61
Multiple Dose Study Of PF-04937319 In Patients With Type 2 Diabetes
Diabetes Mellitus, Type 2 · NIDDM
Bottom Line
View on ClinicalTrials.gov: NCT01272804 ↗Enrolled (actual)
61
Serious AEs
0.0%
Results posted
Feb 2017
Primary outcome: Primary: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) — 6; 5; 0; 3 participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- PF-04937319 (Drug); Placebo (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Pfizer
- Primary completion
- Jul 2011
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) |
6; 5; 0; 3; 8; 5 | — |
| PRIMARY Maximum Observed Plasma Concentration (Cmax) On Day 1 |
38.22; 69.49; 119.4; 245.4; 449.3 | — |
| PRIMARY Maximum Observed Plasma Concentration (Cmax) On Day 6 |
57.73; 122.3; 234.1; 421.5; 970.6 | — |
| PRIMARY Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 1 |
3.00; 3.00; 3.00; 3.00; 3.00 | — |
| PRIMARY Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 6 |
1.50; 1.50; 1.50; 1.50; 1.50 | — |
| PRIMARY Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) on Day 1 |
407.0; 867.7; 1456; 2749; 6034 | — |
| PRIMARY Maximum Observed Plasma Concentration at Steady State (Cmax, ss) On Day 14 |
51.09; 79.30; 171.3; 251.5; 555.9 | — |
| PRIMARY Time to Reach Maximum Observed Plasma Concentration at Steady State (Tmax, ss) on Day 14 |
3.00; 3.00; 3.00; 3.00; 3.00 | — |
| PRIMARY Area Under the Curve From Time Zero to End of Dosing Interval at Steady State (AUCtau, ss) on Day 14 |
458.0; 928.7; 1889; 3167; 7446 | — |
| PRIMARY Plasma Decay Half-Life (t1/2) on Day 14 |
6.563; 6.884; 6.348; 6.960; 8.479 | — |
| PRIMARY Minimum Observed Plasma Trough Concentration at Steady State (Cmin, ss) on Day 14 |
1.380; 10.56; 22.73; 41.68; 129.8 | — |
| PRIMARY Percentage of Unchanged Drug Excreted in the Urine Over Dosing Interval (Ae[%]) on Day 14 |
0.3904; 0.3533; 0.6463; 0.5380; 0.4294 | — |
| PRIMARY Apparent Oral Clearance (CL/F) on Day 14 |
21.86; 32.32; 26.48; 31.56; 40.29 | — |
| PRIMARY Apparent Volume of Distribution (Vz/F) on Day 14 |
205.3; 311.6; 236.7; 314.0; 475.2 | — |
| PRIMARY Observed Accumulation Ratio for AUCtau (Rac) |
1.204; 1.069; 1.296; 1.152; 1.118 | — |
| PRIMARY Observed Accumulation Ratio for Cmax (Rac, Cmax) |
1.414; 1.141; 1.437; 1.026; 1.080 | — |
| 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 |
-0.46; -2.67; 6.41; -12.11; -12.29; -3.71 | — |
| 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 |
-11.94; -4.91; -4.11; -26.83; -11.37; -2.86 | — |
| 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 |
-2.22; 13.24; 24.11; 4.41; 18.10; -2.92 | — |
| 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 |
-2.36; 8.53; 12.65; 2.37; 16.34; -1.43 | — |
| SECONDARY Change From Baseline in Average Plasma Glucose at Day 1, 6, 14 |
192.10; 188.83; 195.78; 205.38; 170.95; 189.07 | — |
| 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 |
173.78; 181.33; 190.11; 193.67; 162.33; 172.44 | — |
| SECONDARY Change From Baseline in Triglyceride (TG) Level at Day 3, 6, 10, 14, 16 and Follow-up |
178.89; 152.33; 175.56; 192.78; 123.33; 152.31 | — |
| SECONDARY Change From Baseline in Total Cholesterol (TC) Level at Day 3, 6, 10, 14, 16 and Follow-up |
200.56; 207.33; 205.00; 213.22; 170.22; 181.94 | — |
| SECONDARY Change From Baseline in Low Density Lipoprotein-Cholesterol (LDL-C) Level at Day 3, 6, 10, 14, 16 and Follow-up |
116.67; 133.56; 123.44; 130.67; 96.11; 102.44 | — |
| SECONDARY Change From Baseline in High Density Lipoprotein-Cholesterol (HDL-C) Level at Day 3, 6, 10, 14, 16 and Follow-up |
48.11; 43.33; 46.44; 43.89; 49.44; 48.94 | — |
| SECONDARY Change From Baseline in Lactate Level at Day 6 and 14 |
17.64; 10.17; 14.14; 21.66; 11.57; 14.74 | — |
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
Data sourced from ClinicalTrials.gov (NCT01272804). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.