Clinical trial NCT01707082: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2012-10-15
Enrollment: 69
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: 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.


Eligibility 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.

Primary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax)
timeFrame: Pre-dose,0.5,1,2,3,4,5,6,7,8 and 16 hrs post morning dose Day 1 Part A
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax)
timeFrame: Pre-dose,0.5,1,2,3,4,5,6,7,8 and 16 hrs post morning dose Day 1 Part A
measure: Area Under the Curve from Time Zero to end of dosing interval (AUCtau)
timeFrame: Pre-dose,0.5,1,2,3,4,5,6,7,8 and 16 hrs post morning dose Day 1 Part A
measure: Apparent Oral Clearance (CL/F)
timeFrame: Pre-dose,0.5,1,2,3,4,5,6,7,8 and 16 hrs post morning dose Day 1 Part A
measure: Maximum Observed Plasma Concentration (Cmax)
timeFrame: 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
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax)
timeFrame: 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
measure: Area Under the Curve from Time Zero to end of dosing interval (AUCtau)
timeFrame: 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
measure: Minimum Observed Plasma Trough Concentration (Cmin)
timeFrame: 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
measure: Apparent Oral Clearance (CL/F)
timeFrame: 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
measure: Plasma Decay Half-Life (t1/2)
timeFrame: 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
measure: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)
timeFrame: Pre-dose,0.5,1,2,3,4,5,6,8,10,12 and 16 hrs post dose Day 1 Period 1 Part B
measure: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)
timeFrame: -2,-1.5,-1,Pre-dose,1,2,4,6,8,10,14 Day 14 Period 2 Part B
measure: Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - 8)]
timeFrame: Pre-dose,0.5,1,2,3,4,5,6,8,10,12 and 16 hrs post dose Day 1 Period 1 Part B
measure: Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - 8)]
timeFrame: -2,-1.5,-1,Pre-dose,1,2,4,6,8,10,14 Day 14 Period 2 Part B
measure: Maximum Observed Plasma Concentration (Cmax)
timeFrame: Pre-dose,0.5,1,2,3,4,5,6,8,10,12 and 16 hrs post dose Day 1 Period 1 Part B
measure: Maximum Observed Plasma Concentration (Cmax)
timeFrame: -2,-1.5,-1,Pre-dose,1,2,4,6,8,10,14 Day 14 Period 2 Part B
measure: Average Concentration (Cav)
timeFrame: 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
measure: Accumulation Ratio
timeFrame: 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:
measure: Diastolic Blood Pressure
timeFrame: Day 1 Pre-dose,1,2,4,8,12 and 16 hrs post dose Part A
measure: Diastolic Blood Pressure
timeFrame: Day 13 Pre-dose,1,2,4,8,12 and 16 hrs post dose Part A
measure: Systolic Blood Pressure
timeFrame: Day 1 Pre-dose,1,2,4,8,12 and 16 hrs post dose Part A
measure: Systolic Blood Pressure
timeFrame: Day 13 Pre-dose,1,2,4,8,12 and 16 hrs post dose Part A
measure: interleukin-6
timeFrame: Days 1 and 14 pre-dose Part A
measure: high-sensitivity C-reactive protein
timeFrame: Days 1 and 14 pre-dose Part A
measure: total cholesterol, HDL-C, triglycerides and calculated LDL-C
timeFrame: Days 1 and 14 pre-dose Part A
measure: ApoBTotal,ApoB48, ApoB100, ApoA-1
timeFrame: Days 1 and 14 pre-dose Part A
measure: Diastolic Blood Pressure
timeFrame: Day 1 Pre-dose,1,2,4,8,12 and 16 hrs post dose Part B
measure: Diastolic Blood Pressure
timeFrame: Day 13 Pre-dose,1,2,4,8,12 and 16 hrs post dose Part B
measure: Systolic Blood Pressure
timeFrame: Day 1 Pre-dose,1,2,4,8,12 and 16 hrs post dose Part B
measure: Systolic Blood Pressure
timeFrame: Day 13 Pre-dose,1,2,4,8,12 and 16 hrs post dose Part B
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Pfizer Investigational Site
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: