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Trial registered on ANZCTR


Registration number
ACTRN12618001692224
Ethics application status
Approved
Date submitted
2/07/2018
Date registered
12/10/2018
Date last updated
12/10/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
The Efficacy, Safety and Tolerability of Oral NP202 in Adults who have Paroxysmal Atrial Fibrillation and a Cardiac Device
Scientific title
A Phase II Randomised, Double-Blind, Placebo-Controlled Study of the Efficacy, Safety and Tolerability of Oral NP202 in Adults who have Paroxysmal Atrial Fibrillation and a Cardiac Device
Secondary ID [1] 295358 0
AU/1/5B61312
Universal Trial Number (UTN)
Trial acronym
NP202-AF
Linked study record

Health condition
Health condition(s) or problem(s) studied:
atrial fibrillation
 308578 0
implantable cardiac devices 308579 0
Condition category
Condition code
Cardiovascular 307535 307535 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Randomised trial of NP202 versus placebo. NP202 is a synthetic flavonol. The mechanism of action is thought to be inhibition of pro-apoptotic kinases of the death-associated protein kinase family. NP202 has been shown to reduce rhythm disturbances in heart muscle in the ventricles, and it is compelling to discover if it similarly reduces rhythm disturbances in heart muscle in the atria. As AF is the most common rhythm disturbance in the atria, it is the most suitable target to investigate a benefit. NP202 is a tablet and dose administered is 100mg daily for 4 weeks. Adherence was monitored by drug returned at 4 weeks.
Intervention code [1] 301682 0
Treatment: Drugs
Comparator / control treatment
Placebo in form of glucose capsule. Crossover design so that participants act as their own control. Washout period was 4 weeks.
Control group
Placebo

Outcomes
Primary outcome [1] 306515 0
Efficacy endpoint: Change in the burden of atrial fibrillation expressed as a percentage identified by cardiac device interrogation.
Timepoint [1] 306515 0
Enrollment of 20-50 patients. Expected end of enrolment Jan 2020. Timepoints for outcome will be taken at baseline, at 4 weeks (after drug 1), at 8 weeks (after washout), at 12 weeks (after drug 2; primary endpoint), and at 16 weeks (after washout).
Secondary outcome [1] 348802 0
Safety endpoint: safety of NP202.
This includes MACCE is defined as the occurrence of any one of the following individual events: non-fatal MI, non-fatal stroke, cardiac hospitalisation due to heart failure, and CV death. Also includes changes in full blood count, kidney function tests and urinalysis.
Data will be coleected from patient reports as well as medical records.
Timepoint [1] 348802 0
6 months follow up after enrolment.
Secondary outcome [2] 352723 0
Tolerability of NP202
Timepoint [2] 352723 0
Tolerability will be symptom-based using patient reports and medical records. Timepoints for tolerability will be taken at baseline, at 4 weeks (after drug 1), at 8 weeks (after washout), at 12 weeks (after drug 2), and at 16 weeks (after washout).

Eligibility
Key inclusion criteria
Participants who:
• Age between 18-80 years.
• Paroxysmal (not lasting more than 7 days) atrial fibrillation.
• An implanted device (loop recorder, pacemaker or defibrillator).
• An AF burden between 0.1-90% over the past 6 months.
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Participants with:
• Pregnant or breastfeeding females.
• Estimated glomerular filtration rate (eGFR) <30ml/min.
• Liver function tests 3 x ULN due to non-cardiac disease.
• Have received any investigational research agent within 30 days or 5 half-lives (whichever is longer) prior to the first dose of IP.

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)
Allocation was concealed to PIs by pharmacist's randomisation code. Numbered containers were used for allocation concealment.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software.
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
Crossover
Other design features
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
A sample size of 20-50 subjects provides 46-80% power to detect a treatment difference of at least 50% reduction in the primary efficacy endpoint. Power was calculated for a two-sided t-test with a 5% Type I error rate.

Analysis sets:
• Full analysis set (FAS): All subjects randomised into the study. Subjects will be analysed according to the treatment to which they were randomised. Efficacy analyses performed in the FAS are considered supportive of analyses performed in the mITT set.
• Safety set: All randomised subjects who received at least one dose of study medication. Subjects will be analysed according to the treatment received. All safety analyses will be conducted in the Safety set.
• Modified Intention-to-treat (mITT) set: All randomised subjects who received at least one dose of study medication. Subjects will be analysed according to the treatment to which they were randomised. The primary efficacy analysis will be performed in the mITT set.
• Per-protocol (PP) set: All subjects from the mITT population who completed the study in compliance with the protocol and who reported no major violation of the study protocol. Subjects will be analysed according to the treatment to which they were randomised. The final decision to exclude a subject from the PP set will be taken during a blinded data review meeting before database lock. Efficacy analyses performed in the PP set are considered supportive of analyses performed in the mITT set.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
21/06/2018
Date of last participant enrolment
Anticipated
31/01/2020
Actual
Date of last data collection
Anticipated
31/07/2020
Actual
Sample size
Target
50
Accrual to date
4
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 11282 0
John Hunter Hospital - New Lambton
Recruitment postcode(s) [1] 23171 0
2305 - New Lambton

Funding & Sponsors
Funding source category [1] 299953 0
Hospital
Name [1] 299953 0
John Hunter Hospital
Country [1] 299953 0
Australia
Funding source category [2] 300891 0
Commercial sector/Industry
Name [2] 300891 0
Armaron Bio Pty Ltd
Country [2] 300891 0
Australia
Primary sponsor type
Hospital
Name
John Hunter Hospital
Address
Department of Cardiology
John Hunter Hospital
Lookout Rd
New Lambton Heights NSW 2035
Country
Australia
Secondary sponsor category [1] 299349 0
Commercial sector/Industry
Name [1] 299349 0
Armaron Bio Pty Ltd
Address [1] 299349 0
Level 1/120 Jolimont Road
East Melbourne 3002 VIC Australia
Country [1] 299349 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300817 0
Hunter New England Research Ethics Committee
Ethics committee address [1] 300817 0
Hunter New England Research Ethics & Governance Office
Locked Bag No 1
New Lambton NSW 2305
Ethics committee country [1] 300817 0
Australia
Date submitted for ethics approval [1] 300817 0
17/11/2017
Approval date [1] 300817 0
27/03/2018
Ethics approval number [1] 300817 0
HNEHREC Reference No: 17/11/15/3.01

Summary
Brief summary
NP202 has been shown to reduce rhythm disturbances in heart muscle in the ventricles, and it is compelling to discover if it similarly reduces rhythm disturbances in heart muscle in the atria. As AF is the most common rhythm disturbance in the atria, it is the most suitable target to investigate a benefit.

This is a single-centre, randomised, double blind, placebo controlled study to assess the efficacy, safety and tolerability of NP202.

Subjects will be screened during routine interrogation of their cardiac device. Eligible subjects will have a high burden of paroxysmal atrial fibrillation. They will be randomised and administered their first dose of investigational product (IP) on Study Day 1.

Subjects will take their IP dose once a day for 1 month (30 days). During this treatment period they will return to the site for study visits at Week 2, and Months 1, 2, and 3. Month 3 is the end of the Treatment Period. Subject will return for follow up and the final study visit at Month 4.

A Data Monitoring Committee (DMC) will review safety data at agreed recruitment and progression milestones to provide independent oversight of subject safety.

Armaron Bio Pty Ltd has provided the study drug at no cost. They have not have provided any funding and the study investigators have full intellectual property and rights over the study data.
Trial website
None.
Trial related presentations / publications
None.
Public notes
None.
Attachments [1] 2849 2849 0 0
/AnzctrAttachments/375463-1711153.01 HNE Governance Authorisation Letter.pdf (Ethics approval)
Attachments [2] 2850 2850 0 0
/AnzctrAttachments/375463-NP202-AF protocol final 24Jan2018 V3.0.docx (Protocol)
Attachments [3] 2851 2851 0 0
/AnzctrAttachments/375463-18. NP202-AF master PICF V3.0 29Jan2018.docx (Participant information/consent)

Contacts
Principal investigator
Name 84910 0
Dr Bradley Wilsmore
Address 84910 0
Department of Cardiology
John Hunter Hospital
Lookout Rd
New Lambton Heights NSW 2035
Country 84910 0
Australia
Phone 84910 0
+61249214200
Fax 84910 0
+61249214210
Email 84910 0
[email protected]
Contact person for public queries
Name 84911 0
Austin May
Address 84911 0
Department of Cardiology
John Hunter Hospital
Lookout Rd
New Lambton Heights NSW 2035
Country 84911 0
Australia
Phone 84911 0
+61249214200
Fax 84911 0
+61249214210
Email 84911 0
[email protected]
Contact person for scientific queries
Name 84912 0
Austin May
Address 84912 0
Department of Cardiology
John Hunter Hospital
Lookout Rd
New Lambton Heights NSW 2035
Country 84912 0
Australia
Phone 84912 0
+61249214200
Fax 84912 0
+61249214210
Email 84912 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.