B521MAD: 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

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01707082
• Collaborator: (none)
• Enrollment: 69
• Location: 1
• Arms: 7
• Duration (Months): 7
• Patients Per Site Per Month: 9.9

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: PF-06282999; Drug: Placebo; Drug: PF-06282999; Drug: Placebo; Drug: PF-06282999; Drug: Placebo; Drug: PF-06282999; Drug: Placebo; Drug: PF-06282999; Drug: Placebo; Drug: midazolam; Drug: PF-06282999; Drug: midazolam; Drug: PF-06282999	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 69 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Basic Science
• 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 Start Date: Oct 1, 2012
• Actual Primary Completion Date: May 1, 2013
• Actual Study Completion Date: May 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part A Cohort 1	Drug: PF-06282999; Tablet, 10 mg, every 8 hours, 14 days; Drug: Placebo; Tablet, 0 mg, every 8 hours, 14 days
Experimental: Part A Cohort 2	Drug: PF-06282999; Tablet, 30 mg, every 8 hours, 14 days; Drug: Placebo; Tablet, 0 mg, every 8 hours, 14 days
Experimental: Part A Cohort 3	Drug: PF-06282999; Tablet, 100 mg, every 8 hours, 14 days; Drug: Placebo; Tablet, 0 mg, every 8 hours, 14 days
Experimental: Part A Cohort 4	Drug: PF-06282999; Tablet, 250 mg, every 8 hours, 14 days; Drug: Placebo; Tablet, 0 mg, every 8 hours, 14 days
Experimental: Part A Cohort 5	Drug: PF-06282999; Tablet, 350 mg every 8 hours or 500 mg every 12 hours, 14 days; Drug: Placebo; Tablet, 0 mg, every 8 or 12 hours, 14 days
Experimental: Part B Cohort 1	Drug: midazolam; Tablet, 7.5 mg, single dose on Period 1 Day 1 and Period 2 Day 14; Drug: PF-06282999; Tablet, dose to be determined (determined in Part A), every 8 or 12 hours, 14 days
Experimental: Part B Cohort 2	Drug: midazolam; Tablet, 7.5 mg, single dose on Period 1 Day 1 and Period 2 Day 14; Drug: PF-06282999; Tablet, dose to be determined (determined in Part A), every 8 or 12 hours, 14 days

Outcome Measures

Primary Outcome Measures

1. 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]

2. 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]

3. 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]

4. 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]

5. 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]

6. 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]

7. 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]

8. 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]

9. 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]

10. 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]

11. 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

12. 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

13. 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

14. 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

15. 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]

16. Maximum Observed Plasma Concentration (Cmax) [-2,-1.5,-1,Pre-dose,1,2,4,6,8,10,14 Day 14 Period 2 Part B]

17. 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]

18. 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

1. 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

2. Diastolic Blood Pressure [Day 13 Pre-dose,1,2,4,8,12 and 16 hrs post dose Part A]

   Mean 24-hour average diastolic blood pressure

3. 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

4. Systolic Blood Pressure [Day 13 Pre-dose,1,2,4,8,12 and 16 hrs post dose Part A]

   Mean 24-hour average systolic blood pressure

5. interleukin-6 [Days 1 and 14 pre-dose Part A]

6. high-sensitivity C-reactive protein [Days 1 and 14 pre-dose Part A]

7. total cholesterol, HDL-C, triglycerides and calculated LDL-C [Days 1 and 14 pre-dose Part A]

8. ApoBTotal,ApoB48, ApoB100, ApoA-1 [Days 1 and 14 pre-dose Part A]

9. Diastolic Blood Pressure [Day 1 Pre-dose,1,2,4,8,12 and 16 hrs post dose Part B]

   Mean 24-hour average diastolic blood pressure

10. 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

11. Systolic Blood Pressure [Day 1 Pre-dose,1,2,4,8,12 and 16 hrs post dose Part B]

    Mean 24-hour average systolic blood pressure

12. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pfizer Investigational Site	Brussels		Belgium	B-1070

Sponsors and Collaborators

• Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT01707082
• Other Study ID Numbers: B5211002
• First Posted: Oct 15, 2012
• Last Update Posted: Jul 31, 2013
• Last Verified: Jul 1, 2013

• Additional relevant MeSH terms: Overweight; Midazolam

Study Results

No Results Posted as of Jul 31, 2013