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Trial registered on ANZCTR


Registration number
ACTRN12615000614594
Ethics application status
Approved
Date submitted
28/05/2015
Date registered
12/06/2015
Date last updated
30/07/2015
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase 1, Single-Center, Open-label Study to Evaluate the Pharmacokinetics of PRN1008 in Healthy Male and Female Volunteers
Scientific title
A Phase 1, Single-Center, Open-label Study to Evaluate the Pharmacokinetics of PRN1008 in Healthy Male and Female Volunteers
Secondary ID [1] 286772 0
NIL
Universal Trial Number (UTN)
NIL
Trial acronym
NIL
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Rheumatoid Arthritis 295149 0
Inflammatory Bowel Disease 295313 0
Systemic Lupus Erythematosus 295314 0
Condition category
Condition code
Inflammatory and Immune System 295389 295389 0 0
Autoimmune diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This will be a single-center, two-period, open-label study to investigate the single dose pharmacokinetics of PRN1008 when administered as a liquid formulation (at 300mg) compared to a capsule formulation under fasted conditions (also at a dosage of 300mg).

Participants will be screened for participation in this study within 28 days before dosing. Participants will be admitted to the study unit the day before dosing (Day -1), then dosed in the mornings of Days 1 and 3, and will remain in the clinic up to Day 4, after collection of the final PK sample.

Participants will be randomized to one of the two possible orders in which the following treatments will be completed. Doses will be approximately 48 hours apart:

*Treatment 1:
Immediately prior to and following a single oral 300 mg dose of PRN1008 liquid formulation, blood samples will be obtained over a period of 24 hours for determination of the PRN1008 PK profile.

*Treatment 2:
Immediately prior to and following a single oral 300 mg dose of PRN1008 capsule formulation, blood samples will be obtained over a period of 24 hours for determination of the PRN1008 PK profile.

Following discharge from the study unit, subjects will return for a follow-up assessment 7 plus or minus 2 days after final study drug administration.
Intervention code [1] 291929 0
Treatment: Drugs
Comparator / control treatment
Liquid formulation of PRN1008 for oral administration compared with capsule formulation of PRN1008 for oral administration both at 300mg dose level.
Control group
Active

Outcomes
Primary outcome [1] 295132 0
To evaluate the relative bioavailability of a single oral dose of PRN1008 when administered as a liquid formulation and a capsule formulation in the fasted state.

This will be assessed via administering PRN1008 as a capsule compared with the PRN1008 as liquid formulation and then taking pharmacokinetic blood samples from subjects at the specified times note din primary time points for analyses.
Timepoint [1] 295132 0
Pre-dose (time 0 minutes ) and at 30min, 1hr, 1.5hr, 2hr, 2.5hr, 3hr, 4hr, 6hr, 8hr, 10hr, 12hr and 24 hrs after PRN1008 dosing (both capsule and oral formulation)
Secondary outcome [1] 314824 0
To evaluated the safety and tolerability of PRN1008 (capsule and liquid formulations) tolerability, including the assessment of physical examinations, ECGs, vital signs, clinical laboratory results and adverse events. This a composite secondary outcome.
Timepoint [1] 314824 0
*Physical examination: at screening, Day -1, Day 1, Day 2, Day 3, Day 4 and follow up visits.
*ECG: at screening and Day -1. Then at various time points on Day 1 and Day 3.
*Vitals: at screening and Day-1 then various time points on Day 1, Day 2, Day 3, Day 4 and the follow up visit.
*Clinical Laboratory Tests: at screening and Day-1, then Day 4 and follow up visit.
*Adverse Events: all visits from screening through to the follow up visit.

Eligibility
Key inclusion criteria
*Healthy adult male or non-pregnant non-lactating females, 40 to 75 years of age (inclusive) at the time of screening.
*Body mass index (BMI) equal to or greater than 18 and equal to or less than 35 (kg/m2) (inclusive) and a minimum body weight of 45 kg.
*Able to participate and comply with all study procedures and restrictions, and willing to provide written informed consent to participate in the study.
*Negative urine drug/alcohol testing at screening and check-in (Day -1).
Minimum age
40 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
*Positive testing for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C antibodies (HCV).
*History or presence of alcoholism or drug abuse within the 2 years prior to the first study drug administration.
*History of any significant (as determined by the Investigator) drug-related allergic reactions such as, anaphylaxis, Stevens-Johnson syndrome, urticaria or multiple drug allergies.
*Blood donation or significant blood loss within 30 days prior to screening.
*Plasma donation within 14 days prior to the first study drug administration.
*Participation in another clinical trial of a drug or device whereby the last investigational drug/device administration is within 30 days prior to the first study drug administration or 5 half-lives, whichever is longer.
*Surgery within the past three months prior to the first study drug administration determined by the PI to be clinically relevant.
*Personal or family history of prolonged QT syndrome or family history of sudden death.
*QTcF greater than 450 msec (males) or greater than 470 msec (females) or less than 300 msec at screening or baseline visit, unless deemed clinically insignificant by the Investigator.
*Seated resting systolic blood pressure (SBP) greater than 150 or less than 90 mm Hg, or diastolic blood pressure greater than 95 or less than 50 mm Hg.
*History or presence of any other medical condition that makes the participant unsuitable for the study in the opinion of the Investigator.

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 cannot commence enrolment procedures until all entry criteria have been fulfilled.Where the clinical significance of an abnormal screening test result (lab or any other tests) is considered uncertain, the test may be repeated.

Participants will be recruited from the study site's internal database. Eligible subjects will be allocated to a treatment by a treatment schedule randomly generated by a biostatistician.

Whilst the treatment allocation is not concealed, participants will be randomly assigned to either treatment 1 or treatment 2 at day 1 and will then have the opposing treatment at Day 3.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Participants will be numbered sequentially in the following format: ARnn (where A is the study reference number, R is the replacement number should the participant be a replacement, nn being the sequential number into the study starting a 01).

Subjects will be randomised to a treatment via a simple a randomisation table created by computer software (i.e. computerised sequence generation) which will be provided to the site by the biostatistician.

The Investigator or designee will enter data for each enrolled participant in the study CRF and enter the corresponding number for enrolment to the treatment groups in the appropriate place in each participant’s CRF. A participant Enrolment and Identification Code List must be maintained by the Investigator or Pharmacist, or designee.

Under no circumstances will participants who enrol in this study and complete treatment as specified be permitted to re-enrol in the study.

Approximately 4 alternative participants may be included in the case that participants become ineligible or drop out of the study prior to Day 1 dosing.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
NIL
Phase
Phase 1
Type of endpoint/s
Bio-availability
Statistical methods / analysis
Plasma concentrations and the computed PK parameters will be listed for PRN1008 by formulation. Individual and mean concentration versus time data will be plotted on linear and semi-logarithmic scales. Summary statistics of PK parameters (primary and secondary) will be presented for each treatment period including means, geometric means, standard deviations, coefficient of variation (CV), medians and ranges, as appropriate.

Geometric mean ratios and 90 percent confidence limits of AUC and Cmax by formulation will be computed. Analysis of variance (ANOVA) will be applied to the log-transformed primary PK parameters. Additional summaries or analyses may be applied to the data as appropriate.

Participants will be allocated to one of two orders of completing Treatment 1 and Treatment 2, using a 1:1 randomized block approach.

No formal sample size calculations were performed. The sample size was determined by practical considerations, and is typical for a study of this type. Based on past experience with PRN1008, 12 subjects are sufficient to characterize the PK of a single dose administration considering observed PK variability.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
22/06/2015
Actual
22/06/2015
Date of last participant enrolment
Anticipated
22/06/2015
Actual
22/06/2015
Date of last data collection
Anticipated
Actual
Sample size
Target
12
Accrual to date
Final
12
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 3916 0
Linear Clinical Research - Nedlands
Recruitment postcode(s) [1] 9704 0
6009 - Nedlands

Funding & Sponsors
Funding source category [1] 291321 0
Commercial sector/Industry
Name [1] 291321 0
Principia Biopharma Australia Pty Ltd
Country [1] 291321 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Clinical Network Services (CNS) Pty Ltd
Address
Level 4, 88 Jephson Street, Toowong, QLD, 4066
Country
Australia
Secondary sponsor category [1] 290006 0
None
Name [1] 290006 0
N/A
Address [1] 290006 0
N/A
Country [1] 290006 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292885 0
Bellberry Limited
Ethics committee address [1] 292885 0
129 Glen Osmond Road
Eastwood
SA 5063
Ethics committee country [1] 292885 0
Australia
Date submitted for ethics approval [1] 292885 0
29/04/2015
Approval date [1] 292885 0
25/05/2015
Ethics approval number [1] 292885 0
2015-04-296

Summary
Brief summary
This will be a single-center, two-period, open-label study to investigate the single-dose pharmacokinetics of PRN1008 when administered as a liquid formulation compared to a capsule formulation under fasted conditions.
Participants will be screened for participation in this study within 28 days before dosing. Participants will be admitted to the study unit the day before dosing (Day -1), then dosed in the mornings of Days 1 and 3, and will remain in the clinic up to Day 4, after collection of the final PK sample.
Participants enrolled will be randomized to one of the two possible orders in which the following treatments will be completed. Doses will be approximately 48 hours apart.
Trial website
N/A
Trial related presentations / publications
N/A
Public notes
N/A

Contacts
Principal investigator
Name 57490 0
Dr Janakan Krishnarajah
Address 57490 0
Linear Clinical Research Ltd
1st Floor B Block
Hospital Avenue
Nedlands WA 6009
Country 57490 0
Australia
Phone 57490 0
+61 8 63825100
Fax 57490 0
Email 57490 0
[email protected]
Contact person for public queries
Name 57491 0
Mr Simon Scott
Address 57491 0
Linear Clinical Research Ltd
1st Floor B Block
Hospital Avenue
Nedlands WA 6009
Country 57491 0
Australia
Phone 57491 0
+61 8 63825100
Fax 57491 0
Email 57491 0
[email protected]
Contact person for scientific queries
Name 57492 0
Dr Janakan Krishnarajah
Address 57492 0
Linear Clinical Research Ltd
1st Floor B Block
Hospital Avenue
Nedlands WA 6009
Country 57492 0
Australia
Phone 57492 0
+61 8 63825100
Fax 57492 0
Email 57492 0
[email protected]

No information has been provided regarding IPD availability


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.