Absorption, Metabolism and Excretion Study of [14C]PBT2 and Absolute Bioavailability of PBT2

Study Overview
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Brief Summary
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The purpose of the study is to investigate how the test drug, PBT2, is taken up, broken down and removed from the body when given as an oral capsule, a radiolabelled oral suspension and a radiolabelled intravenous injection.

Official Title
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A Phase I , Open-Label Study to Evaluate the Absorption, Metabolism and Excretion of [14C]-PBT2 and to Estimate the Absolute Bioavailability of PBT2 in Healthy Male Subjects

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: IV PBT2 microtracer and oral PBT2 single dose
* Drug: oral 14C-PBT2


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy males Body mass index of 18.0 to 35.0 kg/m2 Exclusion Criteria: History of any drug or alcohol abuse in the past 2 years Regular alcohol consumption >21 units per week (1 unit = ½ pint beer, 25 mL of 40% spirit or a 125 mL glass of wine) Current smokers and those who have smoked within the last 12 months Radiation exposure, including that from the present study, excluding background radiation but including diagnostic x-rays and other medical exposures, exceeding 5 mSv in the last 12 months or 10 mSv in the last 5 years. Clinically significant abnormal biochemistry, haematology or urinalysis as judged by the investigator Positive drugs of abuse test result Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) results History of cardiovascular, renal, hepatic, chronic respiratory or GI disease as judged by the investigator

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 65 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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Absolute Bioavailability<br>IV PBT2 microtracer and oral PBT2 single dose | Drug: IV PBT2 microtracer and oral PBT2 single dose<br> <br> |
| Experimental: Radiolabelled AME<br>oral 14C PBT2 | Drug: oral 14C-PBT2<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute Bioavailability of PBT2 (F%) | Absolute bioavailability is the amount of drug from a formulation that reaches the systemic circulation relative to an IV dose, computed as AUC(oral)/AUC(IV), with range from 0% (no drug) to 100% (all of the administered drug). | 0 to 72 hours post oral dose | 
| Mass Balance | Amount excreted as a percentage of the administered dose (%Ae) | 168 h (7 days) post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| IV PK Profile of [14C]-PBT2 and Total Radioactivity as Assessed by AUC(0 Last) | Area under the plasma concentration vs time curve from time 0h to the last time point of IV [14C]-PBT2 . | 0 to 72 h post oral dose | 
| Oral PK Profile of PBT2 as Assessed by AUC(0-last) | Area under the plasma concentration vs time curve from time 0h to the last time point of oral PBT2 . | 72 h post oral dose | 
| Safety and Tolerability of PBT2 | As assessed by the number of participants with adverse events | 72 h post oral dose | 
| Ratio of Whole Blood, Plasma [14C] PBT2 at 24 Hours | Ratio of whole blood, plasma [14C] PBT2 at 24 hours | 0 to 24 hours | 
| Oral PK Profile of [14C]-PBT2 as Assessed by AUC(0-last) | area under the plasma concentration vs time curve to the last timepoint | 0 to 72 hours |