Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12618001523291
Ethics application status
Approved
Date submitted
6/09/2018
Date registered
11/09/2018
Date last updated
23/01/2019
Date data sharing statement initially provided
23/01/2019
Date results information initially provided
23/01/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase 1, Randomized, Open-Label Study of the Relative Bioavailability and Effect of Food on the Pharmacokinetics of a Novel Formulation of PRN2246 Compared to a Reference Formulation in Healthy Adult Participants
Scientific title
A Phase 1, Randomized, Open-Label Study of the Relative Bioavailability and Effect of Food on the Pharmacokinetics of a Novel Formulation of PRN2246 Compared to a Reference Formulation in Healthy Adult Participants
Secondary ID [1] 295766 0
Nil
Universal Trial Number (UTN)
U1111-1218-9015
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Immune-mediated neurologic disorders 309166 0
Condition category
Condition code
Neurological 308044 308044 0 0
Multiple sclerosis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
PRN2246-002 is a single-center, three-period, open-label, randomized, complete-crossover study in healthy adult participants.

All participants will complete all three periods of the study. Beginning Day 1, participants will be randomized to the order of treatment (1, 2, and 3), with blood sampling for plasma PK over 24 hours after each dose of study drug. PRN2246 doses will be administered 48 hours apart. Treatments are as listed below:
Treatment 1: Following an overnight fast, participants will receive a single 60mg oral dose of the liquid PRN2246 formulation (reference).
Treatment 2: Following an overnight fast, participants will receive a single 60mg oral dose of tablet PRN2246 formulation (test).
Treatment 3: Participants will receive a single 60mg oral dose of the tablet (4x15mg) formulation of PRN2246 (test) within 30 minutes of a standardized high-fat breakfast.

Following discharge from the study unit in the morning of Day 6, participants will return for a follow-up (FU) assessment on Day 10 (plus or minus 1 day).
Intervention code [1] 312092 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Active

Outcomes
Primary outcome [1] 307034 0
Relative oral bioavailability (area under the curve from time 0 to the last quantifiable concentration (AUClast), area under the curve from time 0 to infinity (AUC0-inf), and the maximum observed concentration (Cmax) of PRN2246 when administered as a reference liquid formulation compared to the test tablet formulation under fasting conditions.
Timepoint [1] 307034 0
Blood samples for PRN2246 PK will be collected predose (prior to dosing) and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours after PRN2246 dosing on Days 1, 3, and 5.
Primary outcome [2] 307035 0
Impact of food on PRN2246 AUClast, AUC0-inf, and Cmax when administered as a tablet (test formulation) under fasting and fed conditions
Timepoint [2] 307035 0
Blood samples for PRN2246 PK will be collected predose (prior to dosing) and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours after PRN2246 dosing on Days 1, 3, and 5.
Secondary outcome [1] 350454 0
Single-dose PK of PRN2246 including plasma Cmax, time to maximum observed concentration (tmax), AUClast, AUC0-inf, and plasma terminal half-life
Timepoint [1] 350454 0
Blood samples for PRN2246 PK will be collected predose (prior to dosing) and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours after PRN2246 dosing on Days 1, 3, and 5.
Secondary outcome [2] 350455 0
Safety and tolerability including the assessment of physical examinations, electrocardiograms, vital signs, clinical laboratory results, and adverse events
Timepoint [2] 350455 0
Vital signs will be taken at screening; following admission on Day -1; and in the mornings of Days 2, 4, and 6, and at FU. In addition, vital signs will be taken within 3 hours prior to and 1 hour after each PRN2246 dose on Days 1, 3, and 5.
ECGs will be obtained at screening, following admission on Day -1, and at FU. In addition, triplicate ECGs will be obtained within 3 hours prior to and 1hour post PRN2246 dosing on Days 1, 3, and 5.
Blood and urine will be collected for hematology, coagulation, serum chemistry, and urinalysis at screening; on admission on Days -1, 3 and 6; and at follow-up.
Serum pregnancy test will be performed in all females at screening and a urine pregnancy test will be performed at Day -1.
Complete physical exam will be performed at screening and follow-up. An abbreviated exam will be performed at day -1 and then every day until discharge on day 6.

Eligibility
Key inclusion criteria
1. Healthy adult male and/or female participants, 18 to 55 years of age (inclusive) at the time of screening
2. Body mass index more than or equal to 18.0 and less than or equal to 30.5 (kg per m2) (inclusive) and a minimum body weight of 45 kg at screening
3. Male participants with female partners of childbearing potential must be willing to practice true abstinence or use two highly effective methods of contraception (including one barrier method) from Day 1 until 3 months after their final dose of study drug
4. Female participants must be surgically sterile or postmenopausal (no spontaneous menstrual period for at least 1 year), confirmed by follicle-stimulating hormone (FSH) more than 40 mIU per mL. Sterilization procedure must have been completed at least 6 months prior to the first study drug administration.
5. Negative urine drug/alcohol breath testing at screening and check-in (Day -1). Screening urine drug and/or alcohol breath testing may be repeated once if deemed appropriate by the site investigator.
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. Positive testing for human immunodeficiency virus (HIV), hepatitis B surface antigen, or hepatitis C antibodies
3. Use of more than two tobacco/nicotine-containing or cannabis products per month within 6 months prior to the first study drug administration
4. History or presence of alcoholism or drug abuse within the 2 years prior to the first study drug administration
5. Use of any over-the-counter medication, including herbal products, within the 7 days prior to Day 1, other than limited paracetamol use (less than or equal to 2 g/day). Use of any prescription medication within the 14 days prior to the first study drug administration or 5 half-lives, whichever is longer
6. Blood donation or significant blood loss within 60 days prior to screening
7. 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
8. Surgery within the past 3 months prior to the first study drug administration determined by the Investigator to be clinically relevant
9. History of active treatment for tuberculosis within the past 5 years
10. Regular alcohol consumption more than 14 units per week (1 unit equals 1 pint beer, 25 mL of 40 percent spirit, or a 125-mL glass of wine)

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)
The study is open-label, but the sequence in which the subjects will receive each treatment is randomised. Allocation is not concealed.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 1
Type of endpoint/s
Bio-availability
Statistical methods / analysis
A sample size of approximately 14 participants will allow the comparison of the bioavailability of the PRN2246 tablet formulation versus the PRN2246 liquid formulation and the evaluation of the effect of food in the PK of PRN2246 when administered as oral tablet.
Assessment of relative oral bioavailability of the test compared to the reference formulation and the effect of food on PK of PRN2246 administered as tablet will be performed using analysis of variance (ANOVA) on log-transformed data.
All safety analyses will be based on the safety analysis population. As appropriate, listings,
summary tables, and graphs (individual plots and/or mean plots) by treatment will be provided for safety and tolerability assessments.
Individual and mean plasma concentrations at each sampling time point for PRN2246 will be presented by listings and descriptive summary statistics including means,
geometric means, ranges, standard deviations, and coefficients of variation. Individual and mean concentration versus time will be plotted on linear and semi-logarithmic scales.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
14/10/2018
Actual
14/10/2018
Date of last participant enrolment
Anticipated
25/10/2018
Actual
25/10/2018
Date of last data collection
Anticipated
26/10/2018
Actual
9/11/2018
Sample size
Target
14
Accrual to date
Final
14
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 11631 0
Linear Clinical Research - Nedlands
Recruitment postcode(s) [1] 23677 0
6009 - Nedlands

Funding & Sponsors
Funding source category [1] 300353 0
Commercial sector/Industry
Name [1] 300353 0
Principia Biopharma, Inc.
Country [1] 300353 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Clinical Network Services (CNS) Pty Ltd
Address
Level 4, 88 Jephson St, Toowong
Queensland, 4066, Australia
Country
Australia
Secondary sponsor category [1] 299797 0
None
Name [1] 299797 0
Address [1] 299797 0
Country [1] 299797 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 301168 0
Bellberry Bellberry Human Research Ethics Committee H (EC00459)
Ethics committee address [1] 301168 0
129 Glen Osmond Rd
Eastwood SA 5063
Ethics committee country [1] 301168 0
Australia
Date submitted for ethics approval [1] 301168 0
08/08/2018
Approval date [1] 301168 0
05/09/2018
Ethics approval number [1] 301168 0
2018-08-609

Summary
Brief summary
A Phase 1, randomized, 0pen-label study of the relative bioavailability and effect of food on the pharmacokinetics of a novel formulation of PRN2246 compared to a reference
formulation. The study will be performed at a single-centre in healthy adult participants. This is a complete-crossover study where each participant will receive all three treatments.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 86078 0
Dr Ana Liza Sun
Address 86078 0
Linear Clinical Research
QEII Medical Centre
First Floor, B Block Hospital Avenue
Nedlands WA 6009
Country 86078 0
Australia
Phone 86078 0
+61 8 6382 5100
Fax 86078 0
Email 86078 0
contactus@linear.org.au
Contact person for public queries
Name 86079 0
Dr Ana Liza Sun
Address 86079 0
Linear Clinical Research
QEII Medical Centre
First Floor, B Block Hospital Avenue
Nedlands WA 6009
Country 86079 0
Australia
Phone 86079 0
+61 8 6382 5100
Fax 86079 0
Email 86079 0
contactus@linear.org.au
Contact person for scientific queries
Name 86080 0
Ms Ann Neale
Address 86080 0
Principia Biopharma, Inc
400 East Jamie Court, Suite 302
South San Francisco, California 94080
Country 86080 0
United States of America
Phone 86080 0
+1 650-416-7784
Fax 86080 0
Email 86080 0
clinicaltrials@principiabio.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
The data sharing statement was marked 'No' because this is 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 other documents available
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
No
Results – basic reporting
Results – plain English summary