Clinical trial NCT01396161: A Study of PF-05175157 in Healthy Volunteers and Type 2 Diabetic Patients
Official title: A Phase 1 Placebo-controlled Study To Assess The Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Of Multiple Ascending Oral Doses Of Pf-05175157 In Healthy Volunteers And In Patients With Type 2 Diabetes Mellitus (t2dm)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Diabetes Mellitus, Type 2
Keywords: Phase 1
Multiple Doses
Safety
Pharmacokinetics
Pharmacodynamics
Healthy Volunteers
Type 2 Diabetic Patients
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2011-07-18
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: 2 weeks
Secondary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax)
timeFrame: 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
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax)
timeFrame: 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
measure: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau)
timeFrame: 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
measure: Accumulation Ratio for Area Under the Concentration-Time Curve (Rˇac, AUC)
timeFrame: 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
measure: Renal Clearance (CLr)
timeFrame: 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
measure: Plasma Decay Half-Life (t1/2)
timeFrame: 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
measure: Urinary Recovery
timeFrame: 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
Other outcomes:
Locations:
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: South Miami
country: United States
facility: Pulmonary Physicians of South Florida
state: Florida
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: