Healthy
Conditions
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.
Interventions
DRUGPF-06282999
Tablet, 10 mg, every 8 hours, 14 days
DRUGPlacebo
Tablet, 0 mg, every 8 hours, 14 days
DRUGmidazolam
Tablet, 7.5 mg, single dose on Period 1 Day 1 and Period 2 Day 14
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| 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 | — |
| 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) | 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 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)] | Pre-dose,0.5,1,2,3,4,5,6,8,10,12 and 16 hrs post dose Day 1 Period 1 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 | — |
| 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 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Systolic Blood Pressure | Day 1 Pre-dose,1,2,4,8,12 and 16 hrs post dose Part A | 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 | — |
| ApoBTotal,ApoB48, ApoB100, ApoA-1 | Days 1 and 14 pre-dose Part A | — |
| Diastolic Blood Pressure | Day 1 Pre-dose,1,2,4,8,12 and 16 hrs post dose Part A | Mean 24-hour average diastolic blood pressure |
Countries
Belgium
Outcome results
None listed