Multiple Dose Safety Tolerability, Pharmacokinetics And Midazolam Interaction In Healthy Overweight And Obese Subjects

A Phase 1 Placebo-Controlled Study To Assess Safety, Tolerability, Pharmacokinetics And Effect On Midazolam Pharmacokinetics Of Multiple Oral Doses Of PF-05175157 Administered In A Tablet Formulation In Otherwise Healthy Overweight And Obese Subjects

This study is designed to assess the safety, tolerability and pharmacokinetics of multiple oral 200-mg doses of PF-05175157 administered twice daily for 14 days in healthy overweight and obese subjects.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Chula Vista, California, United States, 91911
      • Pfizer Investigational Site

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:

Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study:

• 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).
• Women must be of non childbearing potential.
• Body Mass Index (BMI) of 25 to 35 kg/m2 inclusive; and a total body weight >50 kg (110 lbs).
• An informed consent document signed and dated by the subject.
• Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

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).
• 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. 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
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PF-05175157, Midazolam; Day 0: Midazolam 2 mg administered alone Days 1-14: 200 mg PF-05175157 administered BID Day 11: Midazolam and PF-05175157	Drug: PF-05175157; 200 mg tablet administered twice per day for 14 days; Drug: Midazolam; 2mg administered as single doses on Days 0 and 11
Experimental: Placebo, Midazolam; Day 0: Midazolam 2 mg administered alone Days 1-14: Placebo administered BID Day 11: Midazolam and Placebo	Drug: Midazolam; 2mg administered as single doses on Days 0 and 11; Other: Placebo; Placebo administered twice per day for 14 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Plasma PF-05175157 Concentration (Cmax)	Single Dose	0 - 10 hrs postdose
Area Under the Curve from Time Zero to end of dosing interval for PF-05175157 (AUCtau)	Single Dose	0 - 10 hrs postdose
Time to Reach Maximum Observed Plasma PF-05175157 Concentration (Tmax)	Single Dose	0 - 10 hrs postdose
Maximum Observed Plasma PF-05175157 Concentration (Cmax)	Steady State	0 - 48 hours postdose
Area Under the Curve from Time Zero to end of dosing interval (AUCtau) for PF-05175157	Steady State	0 - 48 hours postdose
Time to Reach Maximum Observed Plasma PF-05175157 Concentration (Tmax)	Steady State	0 - 48 hours postdose
Apparent Oral Clearance of PF-05175157 (CL/F)		0 - 48 hours postdose
Accumulation Ratio of PF-05175157 (Rac)		0 - 10 hours postdose
Plasma Decay Half-Life of PF-05175157 (t1/2)		0 - 48 hours postdose
Apparent Volume of Distribution of PF-05175157 (Vz/F)		0 - 48 hours postdose
Urinary Recovery for PF-05175157 (AE24)	Amount of PF-05175157 recovered in urine over 24 hours	0 - 24 hours postdose
Renal Clearance for PF-05175157 (CLr)		0 - 24 hours post dose
Area Under the Curve From Time Zero to Last Quantifiable Concentration for midazolam [AUC (0-t)]		0 - 48 hours postdose
Area Under the Curve From Time Zero to Extrapolated Infinite Time for midazolam [AUC (0 - inf)]		0 - 48 hours postdose
Maximum Observed Plasma Concentration for midazolam (Cmax)		0 - 48 hours postdose
Time to Reach Maximum Observed Plasma midazolam Concentration (Tmax)		0 - 48 hours post dose
Plasma Decay Half-Life of midazolam (t1/2)		0 - 48 hours postdose
Fasting triglycerides		14 days
Total cholesterol		14 days
LDL cholesterol		14 days
HDL cholesterol		14 days

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: April 1, 2013
• Primary Completion (Actual): August 1, 2013
• Study Completion (Actual): August 1, 2013

Study Registration Dates

• First Submitted: March 6, 2013
• First Submitted That Met QC Criteria: March 6, 2013
• First Posted (Estimate): March 8, 2013

Study Record Updates

• Last Update Posted (Estimate): September 17, 2013
• Last Update Submitted That Met QC Criteria: September 16, 2013
• Last Verified: September 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Body Weight; Diabetes Mellitus, Type 2; Overweight; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Midazolam
• Other Study ID Numbers: B1731021