A Study Testing A Radioactive Compound Given Through A Vein With And Without The Non-Radioactive Compound, Given By Mouth, To Characterize Tissue Distribution Using Positron Emission Tomography Scanning

A Phase 1, Open-label, 3-period, Randomized, Partially Fixed Sequence, 2-way Crossover Study With A Microdose Of [11c]Pf-06427878 Administered With And Without Two Non-radioactive Doses Of Pf-06427878 To Characterize Tissue Distribution Using Positron Emission Tomography In Healthy Adult Male Subjects

In this study, radioactive PF-06427878 will be administered, through a vein, alone and with 2 different oral doses of non-radioactive PF-06427878 to healthy, adult, male subjects. Positron emission tomography will be used to characterize tissue distribution. The study will also characterize how the study drug behaves in the body, its safety, and how the body tolerates it.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: [11C]PF-06427878; Drug: PF-06427878 10 mg; Drug: PF-06427878 600 mg

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • New Haven Clinical Research Unit
    • New Haven, Connecticut, United States, 06520
      • Yale University School Of Medicine
    • New Haven, Connecticut, United States, 06519
      • Anylan Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• healthy males
• body mass index 17.5-30.5 kg/m2 ; body weight >50 kg
• signed and dated informed consent document
• willing and able to comply with study requirements

Exclusion Criteria:

• tobacco/nicotine containing products > equivalent of 5 cigarettes per day
• history of cumulative ionizing radiation exposure in the past year, including anticipated exposure in this study, and subjects with current, past or anticipated exposure to radiation in the workplace
• severe claustrophobia
• unable to lie still for the required period to acquire images

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: [11C]PF-06427878; Single intravenous infusion of [11C]PF-06427878 in Periods 1, 2 and 3 to investigate the liver and plasma radioactivity, radioactivity in organs relative to plasma, pharmacokinetics, and safety and tolerability	Drug: [11C]PF-06427878; Single administration via intravenous infusion of 20 ug [11C]PF-06427878 on Day 1 of all 3 Periods
Experimental: PF-06427878 10 mg; Single oral dose of 10 mg PF-06427878 in Period 2 or 3 to investigate the liver and plasma radioactivity, radioactivity in organs relative to plasma, pharmacokinetics, and safety and tolerability	Drug: PF-06427878 10 mg; Single oral administration of 10 mg PF-06427878 on Day 1 of Period 2 or 3, at approximately 2.5 hours prior to [11C]PF-06427878 administration
Experimental: PF-06427878 600 mg; Single oral dose of 600 mg PF-06427878 in Period 2 or 3 to investigate the liver and plasma radioactivity, radioactivity in organs relative to plasma, pharmacokinetics, and safety and tolerability	Drug: PF-06427878 600 mg; Single oral administration of 600 mg PF-06427878 on Day 1 of Period 2 or 3, at approximately 2.5 hours prior to [11C]PF-06427878 administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percent injected radioactivity (per gram) over time in the liver	All Periods;Day 1;0-120min
Percent injected radioactivity (per gram) over time in the plasma	All Periods;Day 1;0hr,1,2,3,4,5,5.5,6,6.5,7,8,9,10,12,15,20,25,30,40,50,60,75,90,105,120min

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relative radioactivity in liver versus plasma	Ratio of AUC of percent injected radioactivity (per gram) over time in liver to AUC of percent injected radioactivity (per gram) over time in plasma	All Periods;Day 1;0hr,1,2,3,4,5,5.5,6,6.5,7,8,9,10,12,15,20,25,30,40,50,60,75,90,105,120min
Time-course of total radioactivity as percentage of injected radioactivity (per gram) in the gall bladder, if this region is identifiable		All Periods;Day 1;0-2hr
% of parent in plasma over time	Parent is study drug PF-06427878	All Periods;Day 1;0hr,1,2,3,4,5,5.5,6,6.5,7,8,9,10,12,15,20,25,30,40,50,60,75,90,105,120min
Plasma PK of PF-06427878: AUClast, as data permit		Period 1;Day 1;0,3,5,15,30,60,90,120,135min
Plasma PK of PF-06427878: AUClast, as data permit.		Periods 2 & 3;Day 1;prebreakfast,-90,-60,0,120min
Time-course of total radioactivity as percentage of injected radioactivity (per gram) in the biliary tree, if this region is identifiable		All Periods;Day 1;0-2hr
Time-course of total radioactivity as percentage of injected radioactivity (per gram) in the abdominal fat, if this region is identifiable		All Periods;Day 1;0-2hr
Time-course of total radioactivity as percentage of injected radioactivity (per gram) in the kidney, if this region is identifiable		All Periods;Day 1;0-2hr
Time-course of total radioactivity as percentage of injected radioactivity (per gram) in the urinary bladder, if this region is identifiable		All Periods;Day 1;0-2hr
Time-course of total radioactivity as percentage of injected radioactivity (per gram) in the thigh muscle, if this region is identifiable		All Periods;Day 1;0-2hr
Plasma PK of PF-06427878: AUCinf, as data permit		Period 1;Day 1;0,3,5,15,30,60,90,120,135min
Plasma PK of PF-06427878: Cmax, as data permit		Period 1;Day 1;0,3,5,15,30,60,90,120,135min
Plasma PK of PF-06427878: Tmax, as data permit		Period 1;Day 1;0,3,5,15,30,60,90,120,135min
Plasma PK of PF-06427878: t½, as data permit		Period 1;Day 1;0,3,5,15,30,60,90,120,135min
Plasma PK of PF-06427878: CL, as data permit		Period 1;Day 1;0,3,5,15,30,60,90,120,135min
Plasma PK of PF-06427878: Vss, as data permit		Period 1;Day 1;0,3,5,15,30,60,90,120,135min
Plasma PK of PF-06427878: Vss, as data permit.		Periods 2 & 3;Day 1;prebreakfast,-90,-60,0,120min
Plasma PK of PF-06427878: AUCinf, as data permit.		Periods 2 & 3;Day 1;prebreakfast,-90,-60,0,120min
Plasma PK of PF-06427878: Cmax, as data permit.		Periods 2 & 3;Day 1;prebreakfast,-90,-60,0,120min
Plasma PK of PF-06427878: Tmax, as data permit.		Periods 2 & 3;Day 1;prebreakfast,-90,-60,0,120min
Plasma PK of PF-06427878: t½, as data permit.		Periods 2 & 3;Day 1;prebreakfast,-90,-60,0,120min
Plasma PK of PF-06427878: CL/F, as data permit.		Periods 2 & 3;Day 1;prebreakfast,-90,-60,0,120min

Collaborators and Investigators

• Sponsor: Pfizer

Study record dates

Study Major Dates

• Study Start: May 1, 2015
• Primary Completion (Actual): September 1, 2015
• Study Completion (Actual): September 1, 2015

Study Registration Dates

• First Submitted: April 2, 2015
• First Submitted That Met QC Criteria: April 2, 2015
• First Posted (Estimate): April 7, 2015

Study Record Updates

• Last Update Posted (Estimate): October 29, 2015
• Last Update Submitted That Met QC Criteria: October 27, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: positron emission tomography; hyperlipidemia
• Other Study ID Numbers: B7871003