A Study of PF-05175157 in Healthy Volunteers and Type 2 Diabetic Patients

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)

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.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: PF-05175157 or Placebo; Drug: PF-05175157 or Placebo; Drug: PF-05175157 or Placebo

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • South Miami, Florida, United States, 33143
      • Miami Research Associates
    • South Miami, Florida, United States, 33143
      • MRA Clinical Research
    • South Miami, Florida, United States, 33143
      • Pulmonary Physicians of South Florida

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 30 mg PF-05175157 or Placebo QD	Drug: PF-05175157 or Placebo; One oral dose of PF-05175157 or placebo is administered as a powder-in-capsule once daily for 14 days immediately before breakfast, in healthy volunteers.; Drug: PF-05175157 or Placebo; One oral dose of PF-05175157 or placebo is administered as a powder-in-capsule twice daily for 14 days, immediately before breakfast and dinner, in healthy volunteers.; Drug: PF-05175157 or Placebo; One oral dose of PF-05175157 or placebo is administered as a powder-in-capsule once (or twice) daily for 14 days, immediately before breakfast (and dinner), in patients with type 2 diabetes.
Experimental: 100 mg PF-05175157 or Placebo QD; Planned dose might be modified based on emerging safety and PK data.	Drug: PF-05175157 or Placebo; One oral dose of PF-05175157 or placebo is administered as a powder-in-capsule once daily for 14 days immediately before breakfast, in healthy volunteers.; Drug: PF-05175157 or Placebo; One oral dose of PF-05175157 or placebo is administered as a powder-in-capsule twice daily for 14 days, immediately before breakfast and dinner, in healthy volunteers.; Drug: PF-05175157 or Placebo; One oral dose of PF-05175157 or placebo is administered as a powder-in-capsule once (or twice) daily for 14 days, immediately before breakfast (and dinner), in patients with type 2 diabetes.
Experimental: 200 mg PF-05175157 or Placebo QD; Planned dose might be modified based on emerging safety and PK data.	Drug: PF-05175157 or Placebo; One oral dose of PF-05175157 or placebo is administered as a powder-in-capsule once daily for 14 days immediately before breakfast, in healthy volunteers.; Drug: PF-05175157 or Placebo; One oral dose of PF-05175157 or placebo is administered as a powder-in-capsule twice daily for 14 days, immediately before breakfast and dinner, in healthy volunteers.; Drug: PF-05175157 or Placebo; One oral dose of PF-05175157 or placebo is administered as a powder-in-capsule once (or twice) daily for 14 days, immediately before breakfast (and dinner), in patients with type 2 diabetes.
Experimental: 100 mg PF-05175157 or Placebo BID; Planned dose might be modified based on emerging safety and PK data.	Drug: PF-05175157 or Placebo; One oral dose of PF-05175157 or placebo is administered as a powder-in-capsule once daily for 14 days immediately before breakfast, in healthy volunteers.; Drug: PF-05175157 or Placebo; One oral dose of PF-05175157 or placebo is administered as a powder-in-capsule twice daily for 14 days, immediately before breakfast and dinner, in healthy volunteers.; Drug: PF-05175157 or Placebo; One oral dose of PF-05175157 or placebo is administered as a powder-in-capsule once (or twice) daily for 14 days, immediately before breakfast (and dinner), in patients with type 2 diabetes.
Experimental: xxx mg PF-05175157; Dose will be determined based on results obtained from Arms 1 to 4.	Drug: PF-05175157 or Placebo; One oral dose of PF-05175157 or placebo is administered as a powder-in-capsule once daily for 14 days immediately before breakfast, in healthy volunteers.; Drug: PF-05175157 or Placebo; One oral dose of PF-05175157 or placebo is administered as a powder-in-capsule twice daily for 14 days, immediately before breakfast and dinner, in healthy volunteers.; Drug: PF-05175157 or Placebo; One oral dose of PF-05175157 or placebo is administered as a powder-in-capsule once (or twice) daily for 14 days, immediately before breakfast (and dinner), in patients with type 2 diabetes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	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.	2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	Rˇac for the AUC is defined as AUC (τ, single dose [ss]) / AUC (τ, multiple dose [sd]).	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
Renal Clearance (CLr)	CLr is the amount of unchanged drug excreted in the participants urine from time zero to end of dosing interval.	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 (t1/2)	Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.	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
Urinary Recovery	Percentage of PF-05175157 excreted unchanged in urine over the dosing interval.	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

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: July 1, 2011
• Primary Completion (Actual): February 1, 2012
• Study Completion (Actual): February 1, 2012

Study Registration Dates

• First Submitted: June 20, 2011
• First Submitted That Met QC Criteria: July 14, 2011
• First Posted (Estimate): July 18, 2011

Study Record Updates

• Last Update Posted (Estimate): November 6, 2016
• Last Update Submitted That Met QC Criteria: September 19, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Keywords: Safety; Pharmacokinetics; Healthy Volunteers; Phase 1; Pharmacodynamics; Multiple Doses; Type 2 Diabetic Patients
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: B1731007