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

Healthy Clinical Trial

— B521MAD  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01707082
• Other study ID #: B5211002
• Status: Completed
• Phase: Phase 1
• First received: October 3, 2012
• Last updated: July 29, 2013
• Start date: October 2012
• Est. completion date: May 2013

Study information

• Verified date: July 2013
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: European Union: European Medicines Agency
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 69
• Est. completion date: May 2013
• Est. primary completion date: May 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• PF-06282999
Tablet, 10 mg, every 8 hours, 14 days
• Placebo
Tablet, 0 mg, every 8 hours, 14 days
• PF-06282999
Tablet, 30 mg, every 8 hours, 14 days
• Placebo
Tablet, 0 mg, every 8 hours, 14 days
• PF-06282999
Tablet, 100 mg, every 8 hours, 14 days
• Placebo
Tablet, 0 mg, every 8 hours, 14 days
• PF-06282999
Tablet, 250 mg, every 8 hours, 14 days
• Placebo
Tablet, 0 mg, every 8 hours, 14 days
• PF-06282999
Tablet, 350 mg every 8 hours or 500 mg every 12 hours, 14 days
• Placebo
Tablet, 0 mg, every 8 or 12 hours, 14 days
• midazolam
Tablet, 7.5 mg, single dose on Period 1 Day 1 and Period 2 Day 14
• PF-06282999
Tablet, dose to be determined (determined in Part A), every 8 or 12 hours, 14 days
• midazolam
Tablet, 7.5 mg, single dose on Period 1 Day 1 and Period 2 Day 14
• PF-06282999
Tablet, dose to be determined (determined in Part A), every 8 or 12 hours, 14 days

Locations

Country	Name	City	State
Belgium	Pfizer Investigational Site	Brussels

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	Maximum Observed Plasma Concentration (Cmax)		-2,-1.5,-1,Pre-dose,1,2,4,6,8,10,14 Day 14 Period 2 Part B	No
Primary	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	No
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	interleukin-6		Days 1 and 14 pre-dose Part A	No
Secondary	high-sensitivity C-reactive protein		Days 1 and 14 pre-dose Part A	No
Secondary	total cholesterol, HDL-C, triglycerides and calculated LDL-C		Days 1 and 14 pre-dose Part A	No
Secondary	ApoBTotal,ApoB48, ApoB100, ApoA-1		Days 1 and 14 pre-dose Part A	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No

External Links

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