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
- Registration Number
- NCT01707082
- Lead Sponsor
- Pfizer
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 69
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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part A Cohort 1 Placebo - Part A Cohort 2 Placebo - Part A Cohort 3 Placebo - Part A Cohort 4 Placebo - Part A Cohort 5 Placebo - Part A Cohort 5 PF-06282999 - Part A Cohort 4 PF-06282999 - Part B Cohort 2 midazolam - Part A Cohort 1 PF-06282999 - Part A Cohort 2 PF-06282999 - Part B Cohort 1 midazolam - Part B Cohort 1 PF-06282999 - Part B Cohort 2 PF-06282999 - Part A Cohort 3 PF-06282999 -
- Primary Outcome Measures
Name Time Method Maximum Observed Plasma Concentration (Cmax) -2,-1.5,-1,Pre-dose,1,2,4,6,8,10,14 Day 14 Period 2 Part B 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 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 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 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) -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)] -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
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
Name Time Method ApoBTotal,ApoB48, ApoB100, ApoA-1 Days 1 and 14 pre-dose Part A Diastolic Blood Pressure 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 Day 13 Pre-dose,1,2,4,8,12 and 16 hrs post dose Part B Mean 24-hour average systolic blood pressure
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
Trial Locations
- Locations (1)
Pfizer Investigational Site
🇧🇪Brussels, Belgium