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)

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: PF-06282999; Drug: Placebo; Drug: PF-06282999; Drug: PF-06282999; Drug: PF-06282999; Drug: PF-06282999; Drug: Placebo; Drug: PF-06282999; Drug: midazolam

• Study Type: Interventional
• Enrollment (Actual): 69
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, B-1070
    • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• 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). 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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; 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: PF-06282999; Tablet, dose to be determined (determined in Part A), every 8 or 12 hours, 14 days
Experimental: Part A Cohort 2	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: PF-06282999; Tablet, dose to be determined (determined in Part A), every 8 or 12 hours, 14 days
Experimental: Part A Cohort 3	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: PF-06282999; Tablet, dose to be determined (determined in Part A), every 8 or 12 hours, 14 days
Experimental: Part A Cohort 4	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: PF-06282999; Tablet, dose to be determined (determined in Part A), every 8 or 12 hours, 14 days
Experimental: Part A Cohort 5	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: PF-06282999; Tablet, dose to be determined (determined in Part A), every 8 or 12 hours, 14 days
Experimental: Part B Cohort 1	Drug: PF-06282999; Tablet, 10 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: 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
Experimental: Part B Cohort 2	Drug: PF-06282999; Tablet, 10 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: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Plasma Concentration (Cmax)		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)		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)		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)		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)		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)		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)		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)		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)		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)		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)	Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) Midazolam	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 Curve From Time Zero to Last Quantifiable Concentration (AUClast)	Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) Midazolam	-2,-1.5,-1,Pre-dose,1,2,4,6,8,10,14 Day 14 Period 2 Part B
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - 8)]	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	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 Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - 8)]	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	-2,-1.5,-1,Pre-dose,1,2,4,6,8,10,14 Day 14 Period 2 Part B
Maximum Observed Plasma Concentration (Cmax)		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)		-2,-1.5,-1,Pre-dose,1,2,4,6,8,10,14 Day 14 Period 2 Part B
Average Concentration (Cav)		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		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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diastolic Blood Pressure	Mean 24-hour average diastolic blood pressure	Day 1 Pre-dose,1,2,4,8,12 and 16 hrs post dose Part A
Diastolic Blood Pressure	Mean 24-hour average diastolic blood pressure	Day 13 Pre-dose,1,2,4,8,12 and 16 hrs post dose Part A
Systolic Blood Pressure	Mean 24-hour average systolic blood pressure	Day 1 Pre-dose,1,2,4,8,12 and 16 hrs post dose Part A
Systolic Blood Pressure	Mean 24-hour average systolic blood pressure	Day 13 Pre-dose,1,2,4,8,12 and 16 hrs post dose Part A
interleukin-6		Days 1 and 14 pre-dose Part A
high-sensitivity C-reactive protein		Days 1 and 14 pre-dose Part A
total cholesterol, HDL-C, triglycerides and calculated LDL-C		Days 1 and 14 pre-dose Part A
ApoBTotal,ApoB48, ApoB100, ApoA-1		Days 1 and 14 pre-dose Part A
Diastolic Blood Pressure	Mean 24-hour average diastolic blood pressure	Day 1 Pre-dose,1,2,4,8,12 and 16 hrs post dose Part B
Diastolic Blood Pressure	Mean 24-hour average diastolic blood pressure	Day 13 Pre-dose,1,2,4,8,12 and 16 hrs post dose Part B
Systolic Blood Pressure	Mean 24-hour average systolic blood pressure	Day 1 Pre-dose,1,2,4,8,12 and 16 hrs post dose Part B
Systolic Blood Pressure	Mean 24-hour average systolic blood pressure	Day 13 Pre-dose,1,2,4,8,12 and 16 hrs post dose Part B

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): May 1, 2013
• Study Completion (Actual): May 1, 2013

Study Registration Dates

• First Submitted: October 3, 2012
• First Submitted That Met QC Criteria: October 12, 2012
• First Posted (Estimate): October 15, 2012

Study Record Updates

• Last Update Posted (Estimate): July 31, 2013
• Last Update Submitted That Met QC Criteria: July 29, 2013
• Last Verified: July 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Body Weight; Overweight; 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: B5211002