A Study of PF-05175157 in Healthy Volunteers and Type 2 Diabetic Patients
- Registration Number
- NCT01396161
- Lead Sponsor
- Pfizer
- Brief Summary
The primary purpose of this study is to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of multiple ascending doses of PF-05175157 in healthy volunteers and patients with type 2 diabetes mellitus.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 64
- Healthy male and/or female subjects between the ages of 18 and 55 years, inclusive. Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure and pulse rate measurement, 12 lead ECG and clinical laboratory tests.
- In addition, subjects must have normal pulmonary function tests and normal ocular examination.
- Body Mass Index (BMI) of 25.5 - 35.5 kg/m2; and a total body weight >50 kg (110 lbs).
- Women must be of non-childbearing potential.
- Subjects with type 2 diabetes: HbA1c ≥7.0% and ≤10.0% if on metformin only, and ≥6.5% and ≤9.0% if patient requires to be washed-off an SU or DPP-4i.
- For subjects with type 2 diabetes, due to possible effects on disposition, CYP P450 3A4/5 and 2D6 substrates should not be co-administered with study medications.
- Evidence or history of clinically significant hematological, renal, endocrine, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic seasonal allergies at time of dosing).
- Evidence or history of any chronic ongoing or current pulmonary disease.
- History of smoking in the past 5 years and a history of smoking more than 10 pack years, or history or evidence of habitual use of other (non smoked) tobacco or nicotine containing products within 3 months of Screening, or positive cotinine test at Screening or Day -3.
- Active ocular disease including infection, glaucoma, seasonal allergies, dry eye symptoms or retinal/optic nerve disease.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description 30 mg PF-05175157 or Placebo QD PF-05175157 or Placebo - 100 mg PF-05175157 or Placebo BID PF-05175157 or Placebo Planned dose might be modified based on emerging safety and PK data. 200 mg PF-05175157 or Placebo QD PF-05175157 or Placebo Planned dose might be modified based on emerging safety and PK data. 100 mg PF-05175157 or Placebo QD PF-05175157 or Placebo Planned dose might be modified based on emerging safety and PK data. xxx mg PF-05175157 PF-05175157 or Placebo Dose will be determined based on results obtained from Arms 1 to 4.
- Primary Outcome Measures
Name Time Method Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) 2 weeks Counts of participants who had treatment-emergent adverse events (TEAEs), defined as newly occurring or worsening after first dose. Relatedness to PF-05175157 was assessed by the investigator (Yes/No). Participants with multiple occurrences of an AE within a category were counted once within the category.
- Secondary Outcome Measures
Name Time Method Maximum Observed Plasma Concentration (Cmax) Hour 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 1 and 14; at Hour 0 (pre-dose), 3.5, 12 hours post-dose for Day 4, 7 and 11 Time to Reach Maximum Observed Plasma Concentration (Tmax) Hour 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 1 and 14; at Hour 0 (pre-dose), 3.5, 12 hours post-dose for Day 4, 7 and 11 Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) Hour 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 1 and 14; at Hour 0 (pre-dose), 3.5, 12 hours post-dose for Day 4, 7 and 11 Accumulation Ratio for Area Under the Concentration-Time Curve (Rˇac, AUC) Hour 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 1 and 14; at Hour 0 (pre-dose), 3.5, 12 hours post-dose for Day 4, 7 and 11 Rˇac for the AUC is defined as AUC (τ, single dose \[ss\]) / AUC (τ, multiple dose \[sd\]).
Renal Clearance (CLr) Hour 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 1 and 14; at Hour 0 (pre-dose), 3.5, 12 hours post-dose for Day 4, 7 and 11 CLr is the amount of unchanged drug excreted in the participants urine from time zero to end of dosing interval.
Plasma Decay Half-Life (t1/2) Hour 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 1 and 14; at Hour 0 (pre-dose), 3.5, 12 hours post-dose for Day 4, 7 and 11 Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Urinary Recovery Hour 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 1 and 14; at Hour 0 (pre-dose), 3.5, 12 hours post-dose for Day 4, 7 and 11 Percentage of PF-05175157 excreted unchanged in urine over the dosing interval.
Trial Locations
- Locations (3)
MRA Clinical Research
🇺🇸South Miami, Florida, United States
Miami Research Associates
🇺🇸South Miami, Florida, United States
Pulmonary Physicians of South Florida
🇺🇸South Miami, Florida, United States