A Study To Test The Safety, Amount And Effects Of PF-06282999 In Healthy Overweight Adults And A Study To Test The Effects Of PF-06282999 On The Amount Of The Approved Drug, Midazolam, In Healthy Adults (B521MAD)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01707082
First received: October 3, 2012
Last updated: July 29, 2013
Last verified: July 2013
  Purpose

Part A of the study will test the safety, the amount of drug in the body, and effects of the drug in the body after multiple doses. This will be conducted in healthy overweight adults. Part B of the study will test the effects of multiple doses of the investigational drug on the amount of midazolam, an approved drug, in healthy adults.


Condition Intervention Phase
Healthy
Drug: PF-06282999
Drug: Placebo
Drug: midazolam
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Basic Science
Official Title: A Phase 1, Randomized, Placebo-Controlled, Multiple Dose Study To Evaluate The Safety, Pharmacokinetics And Pharmacodynamics Of PF-06282999 In Healthy Overweight Subjects And A Fixed-Sequence Study To Assess The Effect Of PF-06282999 On The Pharmacokinetics Of Midazolam In Healthy Subjects

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Maximum Observed Plasma Concentration (Cmax) [ Time Frame: Pre-dose,0.5,1,2,3,4,5,6,7,8 and 16 hrs post morning dose Day 1 Part A ] [ Designated as safety issue: No ]
  • Time to Reach Maximum Observed Plasma Concentration (Tmax) [ Time Frame: Pre-dose,0.5,1,2,3,4,5,6,7,8 and 16 hrs post morning dose Day 1 Part A ] [ Designated as safety issue: No ]
  • Area Under the Curve from Time Zero to end of dosing interval (AUCtau) [ Time Frame: Pre-dose,0.5,1,2,3,4,5,6,7,8 and 16 hrs post morning dose Day 1 Part A ] [ Designated as safety issue: No ]
  • Apparent Oral Clearance (CL/F) [ Time Frame: Pre-dose,0.5,1,2,3,4,5,6,7,8 and 16 hrs post morning dose Day 1 Part A ] [ Designated as safety issue: No ]
  • Maximum Observed Plasma Concentration (Cmax) [ Time Frame: Pre-dose,0.5,1,2,3,4,5,6,7,8,10,12,16,24,36, and 48 hrs post morning dose Day 14 Part A ] [ Designated as safety issue: No ]
  • Time to Reach Maximum Observed Plasma Concentration (Tmax) [ Time Frame: Pre-dose,0.5,1,2,3,4,5,6,7,8,10,12,16,24,36, and 48 hrs post morning dose Day 14 Part A ] [ Designated as safety issue: No ]
  • Area Under the Curve from Time Zero to end of dosing interval (AUCtau) [ Time Frame: Pre-dose,0.5,1,2,3,4,5,6,7,8,10,12,16,24,36, and 48 hrs post morning dose Day 14 Part A ] [ Designated as safety issue: No ]
  • Minimum Observed Plasma Trough Concentration (Cmin) [ Time Frame: Pre-dose,0.5,1,2,3,4,5,6,7,8,10,12,16,24,36, and 48 hrs post morning dose Day 14 Part A ] [ Designated as safety issue: No ]
  • Apparent Oral Clearance (CL/F) [ Time Frame: Pre-dose,0.5,1,2,3,4,5,6,7,8,10,12,16,24,36, and 48 hrs post morning dose Day 14 Part A ] [ Designated as safety issue: No ]
  • Plasma Decay Half-Life (t1/2) [ Time Frame: Pre-dose,0.5,1,2,3,4,5,6,7,8,10,12,16,24,36, and 48 hrs post morning dose Day 14 Part A ] [ Designated as safety issue: No ]
  • Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) [ Time Frame: Pre-dose,0.5,1,2,3,4,5,6,8,10,12 and 16 hrs post dose Day 1 Period 1 Part B ] [ Designated as safety issue: No ]
    Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) Midazolam

  • Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) [ Time Frame: -2,-1.5,-1,Pre-dose,1,2,4,6,8,10,14 Day 14 Period 2 Part B ] [ Designated as safety issue: No ]
    Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) Midazolam

  • Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - 8)] [ Time Frame: Pre-dose,0.5,1,2,3,4,5,6,8,10,12 and 16 hrs post dose Day 1 Period 1 Part B ] [ Designated as safety issue: No ]
    AUC (0 - 8)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - 8). It is obtained from AUC (0 - t) plus AUC (t - 8). Midazolam

  • Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - 8)] [ Time Frame: -2,-1.5,-1,Pre-dose,1,2,4,6,8,10,14 Day 14 Period 2 Part B ] [ Designated as safety issue: No ]
    AUC (0 - 8)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - 8). It is obtained from AUC (0 - t) plus AUC (t - 8). Midazolam

  • Maximum Observed Plasma Concentration (Cmax) [ Time Frame: Pre-dose,0.5,1,2,3,4,5,6,8,10,12 and 16 hrs post dose Day 1 Period 1 Part B ] [ Designated as safety issue: No ]
  • Maximum Observed Plasma Concentration (Cmax) [ Time Frame: -2,-1.5,-1,Pre-dose,1,2,4,6,8,10,14 Day 14 Period 2 Part B ] [ Designated as safety issue: No ]
  • Average Concentration (Cav) [ Time Frame: Pre-dose,0.5,1,2,3,4,5,6,7,8,10,12,16,24,36, and 48 hrs post morning dose Day 14 Part A ] [ Designated as safety issue: No ]
  • Accumulation Ratio [ Time Frame: Pre-dose,0.5,1,2,3,4,5,6,7,8,10,12,16,24,36, and 48 hrs post morning dose Day 14 Part A ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Diastolic Blood Pressure [ Time Frame: Day 1 Pre-dose,1,2,4,8,12 and 16 hrs post dose Part A ] [ Designated as safety issue: No ]
    Mean 24-hour average diastolic blood pressure

  • Diastolic Blood Pressure [ Time Frame: Day 13 Pre-dose,1,2,4,8,12 and 16 hrs post dose Part A ] [ Designated as safety issue: No ]
    Mean 24-hour average diastolic blood pressure

  • Systolic Blood Pressure [ Time Frame: Day 1 Pre-dose,1,2,4,8,12 and 16 hrs post dose Part A ] [ Designated as safety issue: No ]
    Mean 24-hour average systolic blood pressure

  • Systolic Blood Pressure [ Time Frame: Day 13 Pre-dose,1,2,4,8,12 and 16 hrs post dose Part A ] [ Designated as safety issue: No ]
    Mean 24-hour average systolic blood pressure

  • interleukin-6 [ Time Frame: Days 1 and 14 pre-dose Part A ] [ Designated as safety issue: No ]
  • high-sensitivity C-reactive protein [ Time Frame: Days 1 and 14 pre-dose Part A ] [ Designated as safety issue: No ]
  • total cholesterol, HDL-C, triglycerides and calculated LDL-C [ Time Frame: Days 1 and 14 pre-dose Part A ] [ Designated as safety issue: No ]
  • ApoBTotal,ApoB48, ApoB100, ApoA-1 [ Time Frame: Days 1 and 14 pre-dose Part A ] [ Designated as safety issue: No ]
  • Diastolic Blood Pressure [ Time Frame: Day 1 Pre-dose,1,2,4,8,12 and 16 hrs post dose Part B ] [ Designated as safety issue: No ]
    Mean 24-hour average diastolic blood pressure

  • Diastolic Blood Pressure [ Time Frame: Day 13 Pre-dose,1,2,4,8,12 and 16 hrs post dose Part B ] [ Designated as safety issue: No ]
    Mean 24-hour average diastolic blood pressure

  • Systolic Blood Pressure [ Time Frame: Day 1 Pre-dose,1,2,4,8,12 and 16 hrs post dose Part B ] [ Designated as safety issue: No ]
    Mean 24-hour average systolic blood pressure

  • Systolic Blood Pressure [ Time Frame: Day 13 Pre-dose,1,2,4,8,12 and 16 hrs post dose Part B ] [ Designated as safety issue: No ]
    Mean 24-hour average systolic blood pressure


Enrollment: 69
Study Start Date: October 2012
Study Completion Date: May 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part A Cohort 1 Drug: PF-06282999
Tablet, 10 mg, every 8 hours, 14 days
Drug: Placebo
Tablet, 0 mg, every 8 hours, 14 days
Experimental: Part A Cohort 2 Drug: PF-06282999
Tablet, 30 mg, every 8 hours, 14 days
Drug: Placebo
Tablet, 0 mg, every 8 hours, 14 days
Experimental: Part A Cohort 3 Drug: PF-06282999
Tablet, 100 mg, every 8 hours, 14 days
Drug: Placebo
Tablet, 0 mg, every 8 hours, 14 days
Experimental: Part A Cohort 4 Drug: PF-06282999
Tablet, 250 mg, every 8 hours, 14 days
Drug: Placebo
Tablet, 0 mg, every 8 hours, 14 days
Experimental: Part A Cohort 5 Drug: PF-06282999
Tablet, 350 mg every 8 hours or 500 mg every 12 hours, 14 days
Drug: Placebo
Tablet, 0 mg, every 8 or 12 hours, 14 days
Experimental: Part B Cohort 1 Drug: midazolam
Tablet, 7.5 mg, single dose on Period 1 Day 1 and Period 2 Day 14
Drug: PF-06282999
Tablet, dose to be determined (determined in Part A), every 8 or 12 hours, 14 days
Experimental: Part B Cohort 2 Drug: midazolam
Tablet, 7.5 mg, single dose on Period 1 Day 1 and Period 2 Day 14
Drug: PF-06282999
Tablet, dose to be determined (determined in Part A), every 8 or 12 hours, 14 days

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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). Women must be of non childbearing potential.
  • Body Mass Index (BMI) of 27.0 to 35.0 kg/m2 (Part A) or 17.5 to 30.5 kg/m2 (Part B); and a total body weight >50 kg (110 lbs).

Exclusion Criteria:

  • Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including clinically significant drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing).
  • Subject with any contraindication to midazolam according to the country specific labeling or subject with previous intolerance or allergy to benzodiazepines (applicable to Part B of study only).
  • Subjects who were enrolled in Part A are excluded from participation in Part B of this study.
  • Subjects who have previously participated in a study with PF-06282999.
  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: NCT01707082

Locations
Belgium
Pfizer Investigational Site
Brussels, Belgium, B-1070
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: NCT01707082     History of Changes
Other Study ID Numbers: B5211002
Study First Received: October 3, 2012
Last Updated: July 29, 2013
Health Authority: European Union: European Medicines Agency

Additional relevant MeSH terms:
Overweight
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 August 01, 2014