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Trial registered on ANZCTR


Registration number
ACTRN12618000541202
Ethics application status
Approved
Date submitted
21/03/2018
Date registered
11/04/2018
Date last updated
20/02/2019
Date data sharing statement initially provided
18/01/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase 1 clinical trial to assess the safety, tolerability and pharmacokinetics of PBT434 in healthy volunteers.
Scientific title
A randomised, Phase 1, double-blind, placebo-controlled single and multiple ascending dose study to assess the safety, tolerability and pharmockinetics of PBT434 in healthy volunteers.
Secondary ID [1] 294359 0
None
Universal Trial Number (UTN)
U1111-1211-0052
Trial acronym
PBT434-101
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Atypical Parkinsonism
307081 0
Idiopathic Parkinson's Disease 307082 0
Condition category
Condition code
Neurological 306190 306190 0 0
Parkinson's disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
PBT434 is supplied as 50mg and 200 mg immediate release oral capsules. The doses in the SAD phase are: 50 mg, 100 mg, 300 mg, and 600 mg, given as a single dose. Up to two additional dose levels may be evaluated if supported by available toxicology data and approved by the SRT.

Up to four dosage regimens of PBT434 will be evaluated in the MAD portion of the study; 100 mg twice a day (200 mg Total Daily Dose (TDD), 300 mg twice a day (600 mg TDD). Up to two additional dose regimens may be evaluated based on available PK, safety, and toxicological data. The dose in the multiple ascending dose (MAD) phase is given twice daily for Days 1-7, and once daily on Day 8.

Participants do not take part in both the SAD and MAD phases. The phases are independently randomised.

In both the SAD and MAD phases, hand and mouth checks will be performed after each dose to assure that IP has been swallowed by the subject.
Intervention code [1] 300661 0
Treatment: Drugs
Comparator / control treatment
Placebo is supplied as an identical looking, immediate release capsule. The single ascending dose and multiple ascending dose phases of the study are both placebo-controlled. The composition of the placebo is microcrystalline cellulose in hard gelatin capsule
Control group
Placebo

Outcomes
Primary outcome [1] 305201 0
To evaluate the safety and tolerability of PBT434 after single and multiple oral dose administration by measuring adverse events (AEs), Physical examination, Vital signs, Safety 12-lead Electrocardiograms (ECGs) and Clinical laboratory values
Timepoint [1] 305201 0
Single Ascending Dose Phase: Days 1, 2,3, 4, 6 post administration of dose on Day 1
Multiple Ascending Dose Phase, Days 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 post administration of first dose on Day 1
Secondary outcome [1] 344483 0
To determine the pharmacokinetics (PK) of PBT434 (and potential metabolites) after single and multiple dose administration; by measuring plasma the following PK parameters:

• AUC(0-t)
• AUC(inf)
• %AUCextrap
• Cmax
• tmax
• t½
• Vz/F
• CL/F (parent only)
• Apparent terminal elimination rate constant

Timepoint [1] 344483 0
Single Ascending Dose Phase: Plasma samples are collected on days 1, 2,3, 4, and 6 post administration of dose on Day 1. The specific plasma collection time-points are pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 16, 24, 30, 36, 48, 72, and 120h post administration of the dose on Day 1, Multiple Ascending Dose Phase: Plasma samples are collected on Days 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 post administration of first dose on Day 1. The specific plasma collection time-points are: Day 1: pre-dose, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 4, 6, 8 and 12 hour post administration of the dose on Day 1. Day 6: pre-dose following dose administration on Day 6 Day 7: pre-dose following dose administration on Day 7 Days 8, 9, 10 & 12: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 12, 16, 24, 30, 36, 48 and 96 hour post administration of the dose on Day 8.
Secondary outcome [2] 344484 0
To evaluate the pharmacokinetics of PBT434 (and potential metabolites) after multiple oral dose administration in healthy elderly subjects by measurement of the following plasma PK parameters:

• AUC
• Cmax
• Cmin
• Cavg
• Tmax
• t½
• PTF% (Percent Fluctuation)
• Accumulation index (Cmax SS/Cmax FD)
• Accumulation index (AUCSS/AUCFD)

Timepoint [2] 344484 0
Multiple Ascending Dose Phase: Plasma samples are collected on Days 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 post administration of first dose on Day 1. The specific plasma collection time-points are: Day 1: pre-dose, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 4, 6, 8 and 12 hour post administration of the dose on Day 1. Day 6: pre-dose following dose administration on Day 6 Day 7: pre-dose following dose administration on Day 7 Days 8, 9, 10 & 12: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 12, 16, 24, 30, 36, 48 and 96 hour post administration of the dose on Day 8.
Secondary outcome [3] 344485 0
To evaluate the preliminary effect of food on the pharmacokinetics of PBT434 (and potential metabolites) after single dose administration by measuring the following plasma PK parameters:

• AUC(0-t)
• AUC(inf)
• %AUCextrap
• Cmax
• tmax
• t½
• Vz/F
• CL/F (parent only)
• Apparent terminal elimination rate constant
Timepoint [3] 344485 0
Single Ascending Dose Phase: Plasma samples are collected on days 1, 2,3, 4, and 6 post administration of dose on Day 1. The specific plasma collection time-points are pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 16, 24, 30, 36, 48, 72, and 120h post administration of the dose on Day 1,
Secondary outcome [4] 367159 0
To evaluate the preliminary effect of smoking on the pharmacokinetics of PBT434 (and potential metabolites) after single dose administration by measuring the following plasma PK parameters: • AUC(0-t) • AUC(inf) • Cmax (smoker versus non smoker).
Timepoint [4] 367159 0
Single Ascending Dose Phase: Plasma samples are collected on days 1, 2,3, 4, and 6 post administration of dose on Day 1. The specific plasma collection time-points are pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 16, 24, 30, 36, 48, 72, and 120h post administration of the dose on Day 1,

Eligibility
Key inclusion criteria
SAD and MAD phases require healthy male and female adult volunteers aged between 18 and 55 (n=106 total in this age group).

One cohort of the MAD phase will be conducted in healthy elderly participants. The elderly cohort in MAD will be comprised of healthy male and female (not of childbearing potential) volunteers aged greater than or equal to 65 years (n=10 participants in this age group).
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
History or presence of malignancy, clinically relevent medical illness, including cardiovascular, GI, hepatic, renal endocrine, neurologic and psychiatric, systemic allergic disease.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Central randomisation
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
Intervention assignment
Other
Other design features
Single Ascending Dose Phase:
This phase will contain up to 6 dose escalation cohorts, each comprising 8 subjects per cohort randomized in a ratio of 6:2 (PBT434:placebo). Each dose cohort will use a sentinel group of 2 subjects randomized in a ratio of 1:1 (PBT434:placebo). The sentinel group will be dosed 1 day prior to the remaining subjects in each cohort. The preliminary effects of food on the PK of PBT434 will also be evaluated in one of the cohorts (dose level up to 900 mg to be selected by the Safety Review Team), as a fixed-sequence crossover. The preliminary effects of smoking on the PK of PBT434 will also be evaluated in one of the cohorts (dose to be selected by the Safety Review Team),

Multiple Ascending Dose:
There will be up to 4 dose regimens, each comprising 10 subjects per cohort randomized in a ratio of 8:2 (PBT434:placebo). The MAD phase will contain 1 cohort of elderly subjects, comprising 10 subjects randomised in a ratio of 8:2 (PBT434:placebo).
Phase
Phase 1
Type of endpoint(s)
Safety
Statistical methods / analysis
Approximately 106 volunteers (96 healthy young adults, 10 healthy elderly adults) who meet all eligibility criteria will be dosed. The sample size is not based on statistical considerations . The sample sizes chosen are based on clinical and regulatory considerations and precedence for first-in-human studies. The number of subjects proposed is considered sufficient to investigate the initial safety, tolerability and PK profile of PBT434.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 10400 0
Nucleus Network - Melbourne
Recruitment postcode(s) [1] 22080 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 299001 0
Commercial sector/Industry
Name [1] 299001 0
Prana Biotechnology Limited
Address [1] 299001 0
Level 3, 460 Bourke St, Melbourne, Victoria, 3000
Country [1] 299001 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Prana Biotechnology Limited
Address
Level 3, 460 Bourke St, Melbourne, Victoria, 3000
Country
Australia
Secondary sponsor category [1] 298225 0
None
Name [1] 298225 0
Address [1] 298225 0
Country [1] 298225 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299930 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 299930 0
55 Commercial Rd, Melbourne VIC 3004
Ethics committee country [1] 299930 0
Australia
Date submitted for ethics approval [1] 299930 0
28/03/2018
Approval date [1] 299930 0
01/05/2018
Ethics approval number [1] 299930 0

Summary
Brief summary
This is a Phase 1 Single and Multiple Ascending Dose Study of PBT434 in Healthy Volunteers. The first in human study consists of two parts, both of which are randomised, double-blind, and placebo-controlled: The single ascending dose (SAD) and the multiple ascending dose (MAD) parts of the study will be conducted in sequential stages. Key safety and PK data from the SAD portion will be reviewed before progressing to the MAD part of the study.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 82022 0
Dr Jason Lickliter
Address 82022 0
Nucleus Network
Level 5 Burnet Building AMREP Precinct
89 Commercial Rd
Melbourne, Vic, 3004
Country 82022 0
Australia
Phone 82022 0
+61390768960
Fax 82022 0
Email 82022 0
j.lickliter@nucleusnetwork.com.au
Contact person for public queries
Name 82023 0
Ms Cynthia Wong
Address 82023 0
Prana Biotechnology
39899 Balentine Drive, Suite 360, Newark, CA 94560,
Country 82023 0
United States of America
Phone 82023 0
+16503002141
Fax 82023 0
Email 82023 0
cwong@pranabio.com
Contact person for scientific queries
Name 82024 0
Dr David Stamler
Address 82024 0
Prana Biotechnology,
39899 Balentine Drive, Suite 360, Newark, CA 94560
Country 82024 0
United States of America
Phone 82024 0
+16503002141
Fax 82024 0
Email 82024 0
dstamler@pranabio.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
No other documents available
Summary results
No Results