Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12619001444178
Ethics application status
Approved
Date submitted
1/10/2019
Date registered
17/10/2019
Date last updated
14/02/2020
Date data sharing statement initially provided
17/10/2019
Date results information initially provided
6/12/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
A randomised, open-label, two-way crossover study comparing the pharmacokinetics
of a solid dosage form and a solution of PN-943 in healthy volunteers
Scientific title
A randomised, open-label, two-way crossover study comparing the pharmacokinetics
of a solid dosage form and a solution of PN-943 in healthy volunteers
Secondary ID [1] 299357 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Ulcerative Colitis 314513 0
Condition category
Condition code
Oral and Gastrointestinal 312860 312860 0 0
Inflammatory bowel disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Intervention: PN-943
Cross over between oral liquid formulation and tablets
Dose 450mg

Subjects will receive the following 2 treatments:
• Treatment A: 450 mg PN-943 twice daily (BID) for 5 days as one 300 mg and one 150 mg
dosage strength IR tablet administered every 12 hours
• Treatment B: 450 mg PN-943 BID for 5 days as an oral solution administered every 12 hours

Ten subjects will be randomised to receive either Treatment A followed by Treatment B, or Treatment B followed by Treatment A. There will be a minimum washout period of 7
days between treatments. During the treatment period, the participants will receive standard meals as advised by the clinic and the principal investigator (Examples: Pea and Mint Risotto, Yoghurt, Fruit, Pad Thai, chicken/Tofu, Apricot Bites, Roast Pumpkin Spinach Wrap, Veg Bruger on Roast Beef/Roast Vegetables, Gozleme, Buddha bowl, Potato Salad, Couscous Salad). Participants will be in the clinic and intervention will be monitored directly by the study staff.
Intervention code [1] 315624 0
Treatment: Drugs
Comparator / control treatment
2 treatments are being compared
Control group
Active

Outcomes
Primary outcome [1] 321463 0
assess the multiple dose pharmacokinetics (PK) of an immediate release (IR) oral
tablet of PN-943 compared with an oral solution in healthy volunteers. The follow PK parameters will be assessed: Cmax, Tmax, AUC 0-t, AUC tau, Kel, AUC 0-inf, t1/2, CL/F, CL/Fss, Vz/F, Cssave and AI
Timepoint [1] 321463 0
PK plasma will be collected during the below timepoints:
Day1 and Day5: 0, 0.5, 1,2,4,8,12,12.5, 13,14,16 and 20 hour
Day 2, 3 and 4: 0 and 12 hours
Day 6

Additionally, PK faecal samples will be collected for 24 hours during the oral solution treatment only beginning from predose on Day 3 to predose on Day 4 as individual voids.
Primary outcome [2] 321464 0
evaluate the pharmacodynamics (PD) of PN-943 i.e. receptor occupancy after multiple dose
administration of an IR tablet and an oral solution in healthy volunteers by Plasma assay using Flow Cytometry
Timepoint [2] 321464 0
PD samples will be collected during the below timepoints:
Day1 and Day5: 0, 1,4,8,12, 13,16 and 20 hour
Day 2, 3 and 4: 0 and 12 hours
Day 6
Primary outcome [3] 321648 0
evaluate the pharmacodynamics (PD) of PN-943 i.e. a4ß7 expression after multiple dose
administration of an IR tablet and an oral solution in healthy volunteers by Plasma assay using Flow Cytometry
Timepoint [3] 321648 0
PD samples will be collected during the below timepoints:
Day1 and Day5: 0, 1,4,8,12, 13,16 and 20 hour
Day 2, 3 and 4: 0 and 12 hours
Day 6
Secondary outcome [1] 375057 0
evaluate the pharmacodynamics (PD) of PN-943 i.e. circulating a4ß7+ cell numbers in peripheral blood after multiple dose administration of an IR tablet and an oral solution in healthy volunteers.
This is a primary outcome.
Timepoint [1] 375057 0
PD samples will be collected during the below timepoints:
Day1 and Day5: 0, 1,4,8,12, 13,16 and 20 hour
Day 2, 3 and 4: 0 and 12 hours
Day 6

Eligibility
Key inclusion criteria
Normal healthy volunteers 18-55 years
Good general health,
BMI 18-30kg/m2
Non-smokers
Lab values within normal range. Willing to consume standard meal provided (Standard meal will be as advised by the clinic and principal investigator).
Ability and willingness to attend visits to the site and provide written informed consent prior to entry into the study.
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
History of significant abnormalities or diseases
Clinical significant lab or ECG abnormalities
History of clinically significant endocrine, neurological, gastrointestinal, cardiovascular,
haematological, hepatic, immunological, renal, respiratory, or genitourinary abnormalities or diseases.
History of neoplastic disease
Mentally or legally incapacitated
History of severe allergic or anaphylactic reactions
History of substance abuse, severe allergic or anaphylactic reactions. Regular Alcohol consumption (>21units per week).
Clinically significant lab abnormality or ECG
Inability to comply with the requirements of the study protocol

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)
A randomisation list will be generated by the unblinded statistician and be transferred electronically to the pharmacist on site
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation provided by the biostatistician
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 1
Type of endpoint/s
Pharmacokinetics / pharmacodynamics
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/11/2019
Actual
7/11/2019
Date of last participant enrolment
Anticipated
7/11/2019
Actual
19/11/2019
Date of last data collection
Anticipated
14/12/2019
Actual
14/12/2019
Sample size
Target
10
Accrual to date
Final
10
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 14836 0
Nucleus Network - Melbourne
Recruitment postcode(s) [1] 28089 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 303871 0
Commercial sector/Industry
Name [1] 303871 0
Protagonist Pty Ltd.
Country [1] 303871 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Protagonist Pty Ltd.
Address
306 Carmody Road,
St Lucia, Brisbane, QLD 4067 Australia
Country
Australia
Secondary sponsor category [1] 304014 0
None
Name [1] 304014 0
Address [1] 304014 0
Country [1] 304014 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 304378 0
Bellberry Human Research Ethics Committee
Ethics committee address [1] 304378 0
129 Glen Osmond Road, Eastwood, South Australia 5063
Ethics committee country [1] 304378 0
Australia
Date submitted for ethics approval [1] 304378 0
21/08/2019
Approval date [1] 304378 0
09/10/2019
Ethics approval number [1] 304378 0

Summary
Brief summary
Protagonist Therapeutics, Inc. is developing PN-943 as a potential oral therapy for patients with ulcerative colitis (UC).
This study will be conducted in 10 normal healthy volunteers who meet all of the inclusion criteria and none of the exclusion criteria.
The study is to assess the multiple dose pharmacokinetics (PK) and pharmacodynamics (PD) of an oral immediate release (IR) tablet of PN-943 compared with an oral solution in
healthy volunteers.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 96750 0
Dr Ben Snyder
Address 96750 0
Nucleus Network Pty Ltd
5th Floor, Burnet Tower, AMREP Precinct
89 Commercial Road, Melbourne
VIC, 3004
Country 96750 0
Australia
Phone 96750 0
+61 390768960
Fax 96750 0
Email 96750 0
[email protected]
Contact person for public queries
Name 96751 0
Ms Virginia Papandreou
Address 96751 0
Nucleus Network Pty Ltd
5th Floor, Burnet Tower, AMREP Precinct
89 Commercial Road, Melbourne
VIC, 3004
Country 96751 0
Australia
Phone 96751 0
+61 401 675 082
Fax 96751 0
Email 96751 0
[email protected]
Contact person for scientific queries
Name 96752 0
Dr Nishit B. Modi
Address 96752 0
Protagonist Therapeutics, Inc.
7707 Gateway Blvd. Suite 140
Newark, CA
Zip code: 94560-1160
Country 96752 0
United States of America
Phone 96752 0
+1 510 474 0988
Fax 96752 0
Email 96752 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
It’s a healthy volunteer study and the individual participant results are not useful to the participants or to others outside of the sponsor


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.