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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01807377
First received: March 6, 2013
Last updated: September 16, 2013
Last verified: September 2013
  Purpose

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.


Condition Intervention Phase
Diabetes Mellitus Type 2
Drug: PF-05175157
Drug: Midazolam
Other: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Basic Science
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Maximum Observed Plasma PF-05175157 Concentration (Cmax) [ Time Frame: 0 - 10 hrs postdose ] [ Designated as safety issue: No ]
    Single Dose

  • Area Under the Curve from Time Zero to end of dosing interval for PF-05175157 (AUCtau) [ Time Frame: 0 - 10 hrs postdose ] [ Designated as safety issue: No ]
    Single Dose

  • Time to Reach Maximum Observed Plasma PF-05175157 Concentration (Tmax) [ Time Frame: 0 - 10 hrs postdose ] [ Designated as safety issue: No ]
    Single Dose

  • Maximum Observed Plasma PF-05175157 Concentration (Cmax) [ Time Frame: 0 - 48 hours postdose ] [ Designated as safety issue: No ]
    Steady State

  • Area Under the Curve from Time Zero to end of dosing interval (AUCtau) for PF-05175157 [ Time Frame: 0 - 48 hours postdose ] [ Designated as safety issue: No ]
    Steady State

  • Time to Reach Maximum Observed Plasma PF-05175157 Concentration (Tmax) [ Time Frame: 0 - 48 hours postdose ] [ Designated as safety issue: No ]
    Steady State

  • Apparent Oral Clearance of PF-05175157 (CL/F) [ Time Frame: 0 - 48 hours postdose ] [ Designated as safety issue: No ]
  • Accumulation Ratio of PF-05175157 (Rac) [ Time Frame: 0 - 10 hours postdose ] [ Designated as safety issue: No ]
  • Plasma Decay Half-Life of PF-05175157 (t1/2) [ Time Frame: 0 - 48 hours postdose ] [ Designated as safety issue: No ]
  • Apparent Volume of Distribution of PF-05175157 (Vz/F) [ Time Frame: 0 - 48 hours postdose ] [ Designated as safety issue: No ]
  • Urinary Recovery for PF-05175157 (AE24) [ Time Frame: 0 - 24 hours postdose ] [ Designated as safety issue: No ]
    Amount of PF-05175157 recovered in urine over 24 hours

  • Renal Clearance for PF-05175157 (CLr) [ Time Frame: 0 - 24 hours post dose ] [ Designated as safety issue: No ]
  • Area Under the Curve From Time Zero to Last Quantifiable Concentration for midazolam [AUC (0-t)] [ Time Frame: 0 - 48 hours postdose ] [ Designated as safety issue: No ]
  • Area Under the Curve From Time Zero to Extrapolated Infinite Time for midazolam [AUC (0 - inf)] [ Time Frame: 0 - 48 hours postdose ] [ Designated as safety issue: No ]
  • Maximum Observed Plasma Concentration for midazolam (Cmax) [ Time Frame: 0 - 48 hours postdose ] [ Designated as safety issue: No ]
  • Time to Reach Maximum Observed Plasma midazolam Concentration (Tmax) [ Time Frame: 0 - 48 hours post dose ] [ Designated as safety issue: No ]
  • Plasma Decay Half-Life of midazolam (t1/2) [ Time Frame: 0 - 48 hours postdose ] [ Designated as safety issue: No ]
  • Fasting triglycerides [ Time Frame: 14 days ] [ Designated as safety issue: No ]
  • Total cholesterol [ Time Frame: 14 days ] [ Designated as safety issue: No ]
  • LDL cholesterol [ Time Frame: 14 days ] [ Designated as safety issue: No ]
  • HDL cholesterol [ Time Frame: 14 days ] [ Designated as safety issue: No ]

Enrollment: 15
Study Start Date: April 2013
Study Completion Date: August 2013
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Other: Placebo
Placebo administered twice per day for 14 days
Drug: Midazolam
2mg administered as single doses on Days 0 and 11

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01807377

Locations
United States, California
Pfizer Investigational Site
Chula Vista, California, United States, 91911
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01807377     History of Changes
Other Study ID Numbers: B1731021
Study First Received: March 6, 2013
Last Updated: September 16, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Diabetes Mellitus
Overweight
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Body Weight
Signs and Symptoms
Midazolam
Adjuvants, Anesthesia
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
GABA Modulators
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 18, 2014