Trial Outcomes & Findings for Absorption, Metabolism and Excretion Study of [14C]PBT2 and Absolute Bioavailability of PBT2 (NCT NCT02249728)

NCT ID: NCT02249728

Last Updated: 2016-03-30

Results Overview

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).

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 6 participants
• Primary outcome timeframe: 0 to 72 hours post oral dose
• Results posted on: 2016-03-30

Participant Flow

Participants were screened and enrolled into one study site in the United Kingdom.

Participant milestones

Measure	All Study Participants In Part One (Absolute Bioavailability), a single dose of oral PBT2 250 mg capsule administered followed by IV PBT2 microtracer. Participants then proceed into Part Two. In Part Two (Radiolabelled AME), a single dose of oral PBT2 250mg 14C suspension administered
Part One (4 Days) STARTED	6
Part One (4 Days) COMPLETED	6
Part One (4 Days) NOT COMPLETED	0
Part Two (up to 6 Days) STARTED	6
Part Two (up to 6 Days) COMPLETED	6
Part Two (up to 6 Days) NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	All Study Participants n=6 Participants In Part One (Absolute Bioavailability), a single dose of oral PBT2 250 mg capsule administered followed by IV PBT2 microtracer. Following completion of Part One, participants crossed over into Part Two (Radiolabelled AME), where a single dose of oral PBT2 250 mg 14C suspension was administered.
Age, Continuous	51.8 years STANDARD_DEVIATION 5.9 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	6 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United Kingdom	6 participants n=5 Participants
BMI	27.55 kg/m^2 STANDARD_DEVIATION 4.72 • n=5 Participants

PRIMARY outcome

Timeframe: 0 to 72 hours post oral dose

Population: PK Population

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).

Outcome measures

Measure	Part One Absolute Bioavailability n=6 Participants In Part One (Absolute Bioavailability), a single dose of oral PBT2 250 mg capsule administered followed by IV PBT2 microtracer. Participants then proceed into Part Two. In Part Two (Radiolabelled AME), a single dose of oral PBT2 250mg 14C suspension administered
Absolute Bioavailability of PBT2 (F%)	15.936 percentage of absolute bioavailability Standard Deviation 28.2

PRIMARY outcome

Timeframe: 168 h (7 days) post dose

Population: PK Population

Amount excreted as a percentage of the administered dose (%Ae)

Outcome measures

Measure	Part One Absolute Bioavailability n=5 Participants In Part One (Absolute Bioavailability), a single dose of oral PBT2 250 mg capsule administered followed by IV PBT2 microtracer. Participants then proceed into Part Two. In Part Two (Radiolabelled AME), a single dose of oral PBT2 250mg 14C suspension administered
Mass Balance	98.65 percentage of administered dose Standard Deviation 1.28

SECONDARY outcome

Timeframe: 0 to 72 h post oral dose

Population: PK Population

Area under the plasma concentration vs time curve from time 0h to the last time point of IV [14C]-PBT2 .

Outcome measures

Measure	Part One Absolute Bioavailability n=6 Participants In Part One (Absolute Bioavailability), a single dose of oral PBT2 250 mg capsule administered followed by IV PBT2 microtracer. Participants then proceed into Part Two. In Part Two (Radiolabelled AME), a single dose of oral PBT2 250mg 14C suspension administered
IV PK Profile of [14C]-PBT2 and Total Radioactivity as Assessed by AUC(0 Last)	3.40 ng*hr/ml Geometric Coefficient of Variation 28.8

SECONDARY outcome

Timeframe: 72 h post oral dose

Area under the plasma concentration vs time curve from time 0h to the last time point of oral PBT2 .

Outcome measures

Measure	Part One Absolute Bioavailability n=6 Participants In Part One (Absolute Bioavailability), a single dose of oral PBT2 250 mg capsule administered followed by IV PBT2 microtracer. Participants then proceed into Part Two. In Part Two (Radiolabelled AME), a single dose of oral PBT2 250mg 14C suspension administered
Oral PK Profile of PBT2 as Assessed by AUC(0-last)	1330 ng*hr/ml Geometric Coefficient of Variation 51.2

SECONDARY outcome

Timeframe: 72 h post oral dose

Population: Safety Population

As assessed by the number of participants with adverse events

Outcome measures

Measure	Part One Absolute Bioavailability n=6 Participants In Part One (Absolute Bioavailability), a single dose of oral PBT2 250 mg capsule administered followed by IV PBT2 microtracer. Participants then proceed into Part Two. In Part Two (Radiolabelled AME), a single dose of oral PBT2 250mg 14C suspension administered
Safety and Tolerability of PBT2	1 participants

SECONDARY outcome

Timeframe: 0 to 24 hours

Population: PK population

Ratio of whole blood, plasma [14C] PBT2 at 24 hours

Outcome measures

Measure	Part One Absolute Bioavailability n=6 Participants In Part One (Absolute Bioavailability), a single dose of oral PBT2 250 mg capsule administered followed by IV PBT2 microtracer. Participants then proceed into Part Two. In Part Two (Radiolabelled AME), a single dose of oral PBT2 250mg 14C suspension administered
Ratio of Whole Blood, Plasma [14C] PBT2 at 24 Hours	0.488 ratio [14C] PBT2 Geometric Coefficient of Variation 5.1

SECONDARY outcome

Timeframe: 0 to 72 hours

Population: PK Population

area under the plasma concentration vs time curve to the last timepoint

Outcome measures

Measure	Part One Absolute Bioavailability n=6 Participants In Part One (Absolute Bioavailability), a single dose of oral PBT2 250 mg capsule administered followed by IV PBT2 microtracer. Participants then proceed into Part Two. In Part Two (Radiolabelled AME), a single dose of oral PBT2 250mg 14C suspension administered
Oral PK Profile of [14C]-PBT2 as Assessed by AUC(0-last)	1660 ng*hr/mL Geometric Coefficient of Variation 48.3

Adverse Events

All Study Participants

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	All Study Participants n=6 participants at risk In Part One (Absolute Bioavailability), a single dose of oral PBT2 250 mg capsule administered followed by IV PBT2 microtracer. Participants then proceed into Part Two. In Part Two (Radiolabelled AME), a single dose of oral PBT2 250mg 14C suspension administered
Skin and subcutaneous tissue disorders Mild Hyperhidrosis	16.7% 1/6 • Number of events 1 • Reported AEs from dosing in Part 1 to the end of the study (Day 15 to 20).

Additional Information

Dr Dianne Angus

Prana Biotechnology

Phone: +61 393494906

Email: info@pranabio.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: LTE60