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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: IV PBT2 microtracer and oral PBT2 single dose; Drug: oral 14C-PBT2

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Nottinghamshire
    • Nottingham, Nottinghamshire, United Kingdom, NG11 6JS
      • Quotient Clinical

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Prana Biotechnology Limited
• Investigators: Study Director: Caroline Herd, PhD, Prana Biotechnology Ltd

Study record dates

Study Major Dates

• Study Start: June 1, 2014
• Primary Completion (Actual): July 1, 2014
• Study Completion (Actual): July 1, 2014

Study Registration Dates

• First Submitted: July 30, 2014
• First Submitted That Met QC Criteria: September 25, 2014
• First Posted (Estimate): September 26, 2014

Study Record Updates

• Last Update Posted (Estimate): March 30, 2016
• Last Update Submitted That Met QC Criteria: February 28, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Other Study ID Numbers: PBT2-102; 2014-000389-24 (EudraCT Number)