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

A Phase 1 Placebo-Controlled Study To Assess The Safety, Tolerability, Pharmacokinetics And Effect On Midazolam Pharmacokinetics Of Multiple Oral Doses Of PF-05175157 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: Glucose Metabolism Disorders; Diabetes Mellitus, Type 2; Diabetes Mellitus
• Intervention / Treatment: Drug: Pf-05175157; Drug: placebo; Drug: midazolam

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • South Miami, Florida, United States, 33143
      • 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:

• 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).
• Body Mass Index (BMI) of 25 to 35 kg/m2 inclusive; and a total body weight >50 kg (110 lbs).
• 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: N/A
• Interventional Model: Single Group Assignment
• Masking: Single

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm Label Pf-05175157, placebo, midazolam	Drug: Pf-05175157; 200-mg administered twice daily for 14 days; Drug: placebo; placebo administered twice daily for 14 days; Drug: midazolam; midazolam 3-mg admistered as single doses on Day 0 and Day 11.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum Observed Plasma Concentration (Cmax)	0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hrs postdose
Area Under the Curve from Time Zero to end of dosing interval (AUCtau)	0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hrs postdose
Time to Reach Maximum Observed Plasma Concentration (Tmax)	0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hrs postdose
Maximum Observed Plasma Concentration (Cmax)	0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 hours postdose
Time to Reach Maximum Observed Plasma Concentration (Tmax)	0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 hours postdose
Area Under the Curve from Time Zero to end of dosing interval (AUCtau)	0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 hours postdose
Plasma Decay Half-Life (t1/2)	0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 hours postdose
Apparent Volume of Distribution (Vz/F)	0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 hours postdose
Apparent Oral Clearance (CL/F)	0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 hours postdose
Accumulation Ratio (Rac)	0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours postdose
Ae,tau	0-12 hr
Ae%	0-12 hr
Clr	0-12 hr
Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)]	0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours
Maximum Observed Plasma Concentration (Cmax)	0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours
Time to Reach Maximum Observed Plasma Concentration (Tmax)	0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours
Plasma Decay Half-Life (t1/2)	0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - 8)]	0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours
fasting triglycerides	14 days
fasting LDL-cholesterol	14 days
fasting total cholesterol	14 days
fasting 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: October 1, 2012
• Primary Completion (Actual): November 1, 2012
• Study Completion (Actual): November 1, 2012

Study Registration Dates

• First Submitted: October 23, 2012
• First Submitted That Met QC Criteria: December 21, 2012
• First Posted (Estimate): December 31, 2012

Study Record Updates

• Last Update Posted (Estimate): December 31, 2012
• Last Update Submitted That Met QC Criteria: December 21, 2012
• Last Verified: December 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Body Weight; Diabetes Mellitus; Diabetes Mellitus, Type 2; Overweight; Metabolic Diseases; Glucose Metabolism Disorders; 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: B1731017