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

October 3, 2012
July 29, 2013
October 2012
May 2013   (final data collection date for primary outcome measure)
  • 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 ]
Same as current
Complete list of historical versions of study NCT01707082 on ClinicalTrials.gov Archive Site
  • 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
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
Not Provided
Not Provided
 
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
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

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.

Not Provided
Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Basic Science
Healthy
  • 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: PF-06282999
    Tablet, 100 mg, every 8 hours, 14 days
  • Drug: PF-06282999
    Tablet, 250 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
  • Experimental: Part A Cohort 1
    Interventions:
    • Drug: PF-06282999
    • Drug: Placebo
  • Experimental: Part A Cohort 2
    Interventions:
    • Drug: PF-06282999
    • Drug: Placebo
  • Experimental: Part A Cohort 3
    Interventions:
    • Drug: PF-06282999
    • Drug: Placebo
  • Experimental: Part A Cohort 4
    Interventions:
    • Drug: PF-06282999
    • Drug: Placebo
  • Experimental: Part A Cohort 5
    Interventions:
    • Drug: PF-06282999
    • Drug: Placebo
  • Experimental: Part B Cohort 1
    Interventions:
    • Drug: midazolam
    • Drug: PF-06282999
  • Experimental: Part B Cohort 2
    Interventions:
    • Drug: midazolam
    • Drug: PF-06282999
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
69
May 2013
May 2013   (final data collection date for primary outcome measure)

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.
Both
18 Years to 55 Years
Yes
Contact information is only displayed when the study is recruiting subjects
Belgium
 
NCT01707082
B5211002
No
Pfizer
Pfizer
Not Provided
Study Director: Pfizer CT.gov Call Center Pfizer
Pfizer
July 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP