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Trial registered on ANZCTR


Registration number
ACTRN12617001457336
Ethics application status
Approved
Date submitted
7/10/2017
Date registered
16/10/2017
Date last updated
8/06/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase I, Randomized, Double-Blind, Placebo-Controlled, Ascending Dose Study to Assess the Safety, Tolerability and Pharmacokinetics of Orally Administered PRN2246 in Healthy Volunteers
Scientific title
A Phase I, Randomized, Double-Blind, Placebo-Controlled, Ascending Dose Study to Assess the Safety, Tolerability and Pharmacokinetics of Orally Administered PRN2246 in Healthy Volunteers
Secondary ID [1] 293077 0
Nil known
Universal Trial Number (UTN)
U1111-1203-3503
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Immune-mediated neurologic disorders 305008 0
Condition category
Condition code
Neurological 304382 304382 0 0
Multiple sclerosis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Placebo-controlled, First-In-Human study assessing the safety, tolerability, and pharmacokinetics of PRN2246.

Part A
Up to 48 participants in 5 cohorts will take part in Part A of the study. Participants in Part A will receive a single dose of PRN2246 liquid formulation. Planned doses in Part A are Cohort A1 7.5mg, Cohort A2 15mg, Cohort A3 30mg, Cohort A4 60mg, and Cohort A5 120mg.. Participants in Part A will receive the liquid formulation whilst fasting with the exception of 1 cross over cohort that will receive the liquid formulation administered with and without food (with up to a 7 day washout between doses).

Part B
Up to 50 participants in up to 5 cohorts will take part in Part B of the study. Participants in Part B of the study will receive one dose of PRN2246 liquid formulation per day for 10 days (doses to be assigned based on data from Part A). Planned doses in Part B are Cohort B1 7.5mg, Cohort B2 15mg, Cohort B3 30mg, Cohort B4 60mg, Cohort B5 120mg.

Part C
Up to 8 participants (two groups of 4 participants each) will take part in Part C of the study. Part C will be open label and participants will receive one single 120mg dose of PRN2246 liquid formulation.

Dose escalation to subsequent cohorts in Part A and B will occur following review of the safety, tolerability, and available PK/PD information from the previous dose level. Dose levels may be adjusted based on emerging safety, tolerability, and PK data.

Study subjects will be domiciled during the study and adherence to the dosing regimen will be monitored by study staff observations, notes. Accurate dose and accountability will be checked before and after dosing.



Intervention code [1] 299320 0
Treatment: Drugs
Comparator / control treatment
The Placebo oral dose solution is an aqueous solution of 15% Hydroxypropyl Betadex, 1.0% sucralose and sterile water. Placebo for PRN2246 will be administered to subjects assigned to placebo treatment in Part A and Part B in the same volume at each dose level as active PRN2246. Subjects will be randomized to Active or Placebo in a 3-to-1 ratio.
Control group
Placebo

Outcomes
Primary outcome [1] 303602 0
Safety and tolerability, including the assessment of physical examinations, ECGs, vital signs, clinical laboratory results, and adverse events
Timepoint [1] 303602 0
Part A - Single dose administration Safety and tolerability of PRN2246 will be assessed by monitoring vital signs, laboratory tests, ECGs and AEs at regular intervals for 7 days following administration of a single dose of PRN2246 Adverse Events will be assessed pre-dose Day 1, immediately following dosing and at 15 and 30 minutes, and 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24 (Day 2), 36, and 48 (Day 3) hours post-dose, and Day 7. Vital Signs will be assessed pre-dose Day 1, 30 minutes, and 1, 2, 4, 8, 12, 24 (Day 2), and 48 (Day 3) hours post-dose, and Day 7. ECGs will be assessed pre-dose Day 1, 15 and 30 minutes, and 2, 4, 8, 12, 24 (Day 2), and 48 (Day 3) hours post-dose, and Day 7. Clinical Laboratory Test Results will be assessed pre-dose (Day 1), and at 24 and 48 (Day 3) hours post-dose, and Day 7. Part B - Repeat dose administration Safety and tolerability of PRN2246 will be assessed by monitoring vital signs, laboratory tests, ECGs and AEs at regular intervals for 7 days following administration of a single dose of PRN2246 daily for 10 days. Adverse Events will be assessed pre-dose Day 1, immediately following dosing and at 15 and 30 minutes, and 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24 (Day 2), 36, and 48 (Day 3) hours post-dose, and throughout dosing on Day 4 through Day 10, and on Days 11, 12 and Day 17. Vital Signs will be assessed pre-dose Day 1, 30 minutes, and 1, 2, 4, 8, 12, 24 (Day 2) hours post-dose, and on Days 3 through 12 and Day 17. ECGs will be assessed pre-dose Day 1, 15 and 30 minutes, and 2, 4, 8, 12, 24 (Day 2), and 48 (Day 3) hours post-dose, and on Day 10 at 2, 4, 8, 12, 24 (Day 11), and 48 (Day 12) hours post-dose and Day 17. Clinical Laboratory results will be assessed pre-dose (Day 1), and at 24 and 48 (Day 3) hours post-dose, and Days 4, 7, 10, 12, and Day 17. Part C - Single dose administration Safety and tolerability of PRN2246 will be assessed by monitoring vital signs, laboratory tests, ECGs and AEs at regular intervals for 7 days following administration of a single dose of PRN2246 Adverse Events will be assessed pre-dose Day 1, immediately following dosing and at 15 and 30 minutes, and 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24 (Day 2), 36, and 48 (Day 3) hours post-dose, and Day 7. Vital Signs will be assessed pre-dose Day 1, 30 minutes, and 1, 2, 4, 8, 12, 24 (Day 2), and 48 (Day 3) hours post-dose, and Day 7. ECGs will be assessed pre-dose Day 1, 15 and 30 minutes, and 2, 4, 8, 12, 24 (Day 2), and 48 (Day 3) hours post-dose, and Day 7. Clinical Laboratory Test Results will be assessed pre-dose (Day 1), and at 24 and 48 (Day 3) hours post-dose, and Day 7.
Secondary outcome [1] 339546 0
Nil
Timepoint [1] 339546 0
Nil

Eligibility
Key inclusion criteria
1. Healthy adult male and/or female volunteers, 18 to 55 years of age (inclusive) at the time of screening
2. Body mass index (BMI) greater than or equal to 18 (kg/m2) and less than or equal to 30.5 (kg/m2), and a minimum body weight of 45kg at screening
3. Able to participate and comply with all study procedures and restrictions, and willing to provide written informed consent to participate in the study
4. Male volunteers with female partners of child-bearing potential must be willing to practice true abstinence or use two highly effective methods of contraception (including one barrier method) from Day 1 until 90 days after their last dose of study treatment
5. Female volunteers must be surgically sterile or post-menopausal
6. Negative urine drug and alcohol breath testing at screening and check-in (Day 1)
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Pregnant or lactating women, and male partners of women who are pregnant or lactating
2. Women of child-bearing potential
3. Positive testing for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C antibodies (HCV)
4. Any active acute or chronic disease or infection judged to be clinically significant by the Investigator
5. Use of more than 1-2 tobacco/nicotine-containing or cannabis products per month within 6 months prior to the first study drug administration
6. Participant is febrile, temperature > 37.5 °C. at screening, clinic check-in/ Day -1, or pre dose
7. History or presence of alcoholism or drug abuse within the 2 years prior to the first study drug administration
8. History of any significant (as determined by the Investigator) drug-related allergic reactions such as, anaphylaxis, Stevens-Johnson syndrome, urticaria or multiple drug allergies
9. Use of any over-the-counter (OTC) medication, including herbal products, within the 7 days prior to Day 1, other than limited paracetamol use (less than or equal to 2g/day). Use of any prescription medication within the 14 days prior to the first study drug administration or 5 half-lives, whichever is longer
10. Blood donation or significant blood loss within 60 days prior to screening
11. Plasma donation within 14 days prior to the first study drug administration
12. Participation in another clinical trial of a drug or device whereby the last investigational drug/device administration is within 60 days prior to the first study drug administration or 5 half-lives, whichever is longer
13. Surgery within the past three months prior to the first study drug administration determined by the Investigator to be clinically relevant
14. Personal or family history of prolonged QT syndrome or family history of sudden cardiac death
15. QTcF > 450 msec (males) or > 470 msec (females) or < 300 msec at screening or baseline visit, or deemed clinically significant by the Investigator
16. Screening ECG with QRS and/or T-wave judged to be unfavorable for a consistently accurate QT measurement as judged by the Investigator
17. History of active treatment for tuberculosis within the past 5 years
18. Receipt of a live vaccine within 60 days prior to Day 1 thru to the study follow-up visit
19. Evidence of atrial fibrillation, atrial flutter, complete bundle branch block, Wolff-Parkinson-White Syndrome, or cardiac pacemaker at screening or baseline visit
20. Resting systolic blood pressure (SBP) greater than 140 or less than 90 mm Hg, or diastolic blood pressure greater than 90 or less than 50 mm Hg
21. Resting HR < 45 pm or > 90 bpm at screening or baseline visit
22. Hypersensitivity or history of idiosyncratic reaction to any components or excipients of the investigational or placebo formulation
23. Regular alcohol consumption > 14 units per week (1 unit equals ½ pint beer, 25 mL of 40% spirit or a 125 mL glass of wine)
24. Failure to satisfy the Investigator of fitness to participate for any other reason
25. History or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, neurological, or psychiatric disease
26. Any significant acute illness within 30 days prior to Day 1

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)
Participants will be recruited from the study site's internal database. Eligible subjects will be allocated to a treatment by contacting the holder of the study allocation schedule. The treatment allocation will be concealed form the participant and the investigator.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Static randomization list
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
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis
As appropriate, listings, summary tables, and graphs (individual plots and mean plots) by treatment group within cohort will be provided for safety and tolerability assessment.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
18/10/2017
Actual
17/10/2017
Date of last participant enrolment
Anticipated
12/07/2018
Actual
Date of last data collection
Anticipated
15/08/2018
Actual
Sample size
Target
98
Accrual to date
80
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 9172 0
Linear Clinical Research - Nedlands
Recruitment postcode(s) [1] 17685 0
6009 - Nedlands

Funding & Sponsors
Funding source category [1] 297699 0
Commercial sector/Industry
Name [1] 297699 0
Principia Biopharma Australia Pty Ltd
Country [1] 297699 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Clinical Network Services
Address
Level 4, 88 Jephson Street, Toowong, Queensland 4066
Country
Australia
Secondary sponsor category [1] 296730 0
None
Name [1] 296730 0
Address [1] 296730 0
Country [1] 296730 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298770 0
Bellberry Limited
Ethics committee address [1] 298770 0
129 Glen Osmond Rd
Eastwood SA 5063
Ethics committee country [1] 298770 0
Australia
Date submitted for ethics approval [1] 298770 0
08/08/2017
Approval date [1] 298770 0
06/10/2017
Ethics approval number [1] 298770 0
2017-08-607-A-1

Summary
Brief summary
Placebo-controlled, First-In-Human study assessing the safety and tolerability of PRN2246 in healthy volunteers. Participants in Part A of the study will receive a single dose of PRN2246. Participants in Part B of the study will receive one dose of PRN2246 per day for up to 10 days
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 78178 0
Dr Andrew Redfern
Address 78178 0
Linear Clinical Research
Level 1, B Block, QEII Medical Cntr, Hospital A
Nedlands, WA 6009
Country 78178 0
Australia
Phone 78178 0
+61863825100
Fax 78178 0
Email 78178 0
[email protected]
Contact person for public queries
Name 78179 0
Simon Smith
Address 78179 0
Linear Clinical Research
Level 1, B Block, QEII Medical Cntr, Hospital A
Nedlands, WA 6009
Country 78179 0
Australia
Phone 78179 0
+61863825100
Fax 78179 0
Email 78179 0
[email protected]
Contact person for scientific queries
Name 78180 0
Andrew Redfern
Address 78180 0
Linear Clinical Research
Level 1, B Block, QEII Medical Cntr, Hospital A
Nedlands, WA 6009
Country 78180 0
Australia
Phone 78180 0
+61863825100
Fax 78180 0
Email 78180 0
[email protected]

No information has been provided regarding IPD availability


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No Supporting Document Provided



Results publications and other study-related documents

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