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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Healthy

Intervention / Treatment
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* Drug: [11C]PF-06427878
* Drug: PF-06427878 10 mg
* Drug: PF-06427878 600 mg


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: [11C]PF-06427878<br>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<br>* Single administration via intravenous infusion of 20 ug [11C]PF-06427878 on Day 1 of all 3 Periods<br>|
| Experimental: PF-06427878 10 mg<br>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<br>* 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<br>|
| Experimental: PF-06427878 600 mg<br>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<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hyperlipidemia, positron emission tomography