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

Pfizer69 enrolled

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

DOUBLE

Enrollment

Conditions

Healthy

Interventions

PF-06282999DRUG

Tablet, 10 mg, every 8 hours, 14 days

PlaceboDRUG

Tablet, 0 mg, every 8 hours, 14 days

PF-06282999DRUG

Tablet, 30 mg, every 8 hours, 14 days

Placebo

Eligibility

Sex: ALLMin age: 18 YearsMax age: 55 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Locations (1)

Pfizer Investigational Site

Brussels, Belgium

Outcomes

Primary Outcomes

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)

Data from ClinicalTrials.gov

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Tablet, 0 mg, every 8 hours, 14 days

PF-06282999DRUG

Tablet, 100 mg, every 8 hours, 14 days

PlaceboDRUG

Tablet, 0 mg, every 8 hours, 14 days

PF-06282999DRUG

Tablet, 250 mg, every 8 hours, 14 days

PlaceboDRUG

Tablet, 0 mg, every 8 hours, 14 days

PF-06282999DRUG

Tablet, 350 mg every 8 hours or 500 mg every 12 hours, 14 days

PlaceboDRUG

Tablet, 0 mg, every 8 or 12 hours, 14 days

midazolamDRUG

Tablet, 7.5 mg, single dose on Period 1 Day 1 and Period 2 Day 14

PF-06282999DRUG

Tablet, dose to be determined (determined in Part A), every 8 or 12 hours, 14 days

midazolamDRUG

Tablet, 7.5 mg, single dose on Period 1 Day 1 and Period 2 Day 14

PF-06282999DRUG

Tablet, dose to be determined (determined in Part A), every 8 or 12 hours, 14 days

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)

Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) Midazolam

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 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

Time frame: -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

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 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

Time frame: -2,-1.5,-1,Pre-dose,1,2,4,6,8,10,14 Day 14 Period 2 Part B

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 Outcomes

Diastolic Blood Pressure

Mean 24-hour average diastolic blood pressure

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: Day 13 Pre-dose,1,2,4,8,12 and 16 hrs post dose Part A

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

Mean 24-hour average diastolic blood pressure

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: Day 13 Pre-dose,1,2,4,8,12 and 16 hrs post dose Part B