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

Overview

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.

Full Title of Study: “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”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Basic Science
    • Masking: Double (Participant, Investigator)
  • Study Primary Completion Date: May 2013

Interventions

  • Drug: PF-06282999
    • Tablet, 10 mg, every 8 hours, 14 days
  • Drug: Placebo
    • Tablet, 0 mg, every 8 hours, 14 days
  • Drug: PF-06282999
    • Tablet, 30 mg, every 8 hours, 14 days
  • Drug: Placebo
    • Tablet, 0 mg, every 8 hours, 14 days
  • Drug: PF-06282999
    • Tablet, 100 mg, every 8 hours, 14 days
  • Drug: Placebo
    • Tablet, 0 mg, every 8 hours, 14 days
  • Drug: PF-06282999
    • Tablet, 250 mg, every 8 hours, 14 days
  • Drug: Placebo
    • Tablet, 0 mg, every 8 hours, 14 days
  • 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
  • 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
  • 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

Arms, Groups and Cohorts

  • Experimental: Part A Cohort 1
  • Experimental: Part A Cohort 2
  • Experimental: Part A Cohort 3
  • Experimental: Part A Cohort 4
  • Experimental: Part A Cohort 5
  • Experimental: Part B Cohort 1
  • Experimental: Part B Cohort 2

Clinical Trial Outcome Measures

Primary 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
    • 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
    • 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
    • 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
    • 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
  • 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
  • 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
  • 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

Secondary Measures

  • Diastolic Blood Pressure
    • Time Frame: Day 1 Pre-dose,1,2,4,8,12 and 16 hrs post dose Part A
    • 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
    • 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
    • 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
    • Mean 24-hour average systolic blood pressure
  • interleukin-6
    • Time Frame: Days 1 and 14 pre-dose Part A
  • high-sensitivity C-reactive protein
    • Time Frame: Days 1 and 14 pre-dose Part A
  • total cholesterol, HDL-C, triglycerides and calculated LDL-C
    • Time Frame: Days 1 and 14 pre-dose Part A
  • ApoBTotal,ApoB48, ApoB100, ApoA-1
    • Time Frame: Days 1 and 14 pre-dose Part A
  • Diastolic Blood Pressure
    • Time Frame: Day 1 Pre-dose,1,2,4,8,12 and 16 hrs post dose Part B
    • 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
    • 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
    • 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
    • Mean 24-hour average systolic blood pressure

Participating in This Clinical Trial

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.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 55 Years

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • Pfizer
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Pfizer CT.gov Call Center, Study Director, Pfizer

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