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Trial registered on ANZCTR


Registration number
ACTRN12616001455459
Ethics application status
Approved
Date submitted
17/10/2016
Date registered
18/10/2016
Date last updated
21/09/2021
Date data sharing statement initially provided
18/03/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Open-label Extension Study of ZYN002 (transdermal gel) in Patients with Partial Onset Seizures
Scientific title
Open Label Extension Study to ZYN2-CL-03 to Assess the Long Term Safety and Efficacy of ZYN002 Administered as a Transdermal Gel to Patients with Partial Onset Seizures (STAR 2)
Secondary ID [1] 290306 0
Zynerba ZYN2-CL-004
Universal Trial Number (UTN)
nil
Trial acronym
STAR2
Linked study record
ACTRN12616000510448

Health condition
Health condition(s) or problem(s) studied:
Epilepsy 300561 0
Condition category
Condition code
Neurological 300414 300414 0 0
Epilepsy

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
ZYN002 will be administered as a transdermal gel for 24 months with all patients starting at ZYN002 - CBD 195 mg every 12 hours (390 mg daily), with the option after Month 1 to either increase or reduce the dose of ZYN002 as determined by the investigator. The dose may be increased to 292.5 mg every 12 hours (585 mg daily). After one month at the 585 mg daily dose, the Investigator has the option to increase the dose to 390 mg every 12 hours (780 mg daily).
After the Month 24 visit, or the last visit if the patient terminates early from the study, patients will have either a one week or two week taper period. Patients will have their dose reduced by 50% the first week and another 50% the second week and then treatment will be discontinued.
As applicable, ZYN002 gel will be applied to the skin of both the right and left shoulder and/or upper arms and right/left thighs.
Participants will bring used and unused sachets to each visit for site to check treatment compliance.
Intervention code [1] 296114 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 299857 0
To evaluate the long term safety and tolerability of ZYN002 in partial onset (focal) seizures in adult epilepsy patients over a 24-month treatment period. Assessed by: physical exams, neurological exams, examination of skin, vital signs, ECGs, clinical laboratory tests e.g. haematology, chemistry, urinalysis, pregnancy test (when applicable), assessing suicide risk and adverse event (AE) monitoring.
Timepoint [1] 299857 0
Safety and tolerability will be assessed at every study visit from Day 1 to End of study visit (Week 2 and Months 1, 2, 3, 6, 9, 12, 15, 18, 24, Adhoc visits and End of Study)
Secondary outcome [1] 328325 0
To evaluate the long term efficacy of ZYN002 in partial onset (focal) seizures in adult epilepsy patients over a 24-month treatment period. Assessed by: monitoring seizure frequency and type in daily diary.
Timepoint [1] 328325 0
Investigator will review daily diary at each study visit (Week 2 and Months 1, 2, 3, 6, 9, 12, 15, 18, 21, 24 and Adhoc visits).

Eligibility
Key inclusion criteria
1. Must have completed 12 weeks of the ZYN2-CL-03 protocol, with greater than 95% compliance with study drug application and daily seizure and skin check diaries.
2. Patient agrees to abide by all study restrictions and comply with all study procedures.
3. Patient must be adequately informed of the nature and risks of the study and give written informed consent on Day 1.
4. In the Investigator’s opinion, the patient is reliable and is willing and able to comply with all protocol requirements and procedures.
5. Females of child-bearing potential must have a negative urine pregnancy test at Day 1 and at Months 1, 2, 3, 6, 9, 12, 15, 18, 24, Adhoc and End of Study. Females of child-bearing potential and male patients with a partner of child-bearing potential must continue to use an acceptable method of contraception until at least 3 months after the last dose of study drug.
Minimum age
18 Years
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Patient is receiving any investigational drugs or using any experimental devices.
2. Patient has an ongoing serious adverse event (SAE) or has experienced a SAE in ZYN3-CL-03 that in the opinion of the investigator should exclude them from participation.
3. Patient has been less than 95% compliant with study medication in ZYN2-CL-03.
4. Patient demonstrates behavior indicating unreliability or inability to comply with the requirements of the protocol.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Not applicable as this is not a randomized trial
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
The safety and efficacy variables will be summarized descriptively for all patients in the open label extension study and also by the following dosing cohorts listed below which are based on the randomized treatment (total daily dose) received in the double-blind study (Placebo, ZYN002-195 mg, ZYN002-390 mg) and the initial treatment received (total daily dose) in the open-label extension study (ZYN002-390 mg). The dosing cohorts will be identified as: Placebo/390 mg, 195 mg/390 mg and 390 mg/390 mg, where the treatments are a double blind (DB) treatment dose (total daily dose)/initial open label treatment dose (total daily dose).

The pharmacokinetic variables for anti-epileptic drugs (AEDs) and CBD will be summarized descriptively for all patients in the open label extension study.

Additional dosing cohorts will be determined based on additional dose titrations that are occur during the open label trial.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/11/2016
Actual
3/11/2016
Date of last participant enrolment
Anticipated
Actual
4/07/2017
Date of last data collection
Anticipated
14/06/2019
Actual
31/08/2019
Sample size
Target
180
Accrual to date
Final
171
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 6806 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [2] 6807 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [3] 6808 0
Prince of Wales Private Hospital - Randwick
Recruitment hospital [4] 6809 0
Westmead Hospital - Westmead
Recruitment hospital [5] 6810 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [6] 6811 0
Royal Brisbane & Womens Hospital - Herston
Recruitment hospital [7] 6812 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [8] 6813 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment hospital [9] 6814 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment hospital [10] 6815 0
University of Sunshine Coast Health Clinics - Sippy Downs
Recruitment hospital [11] 9788 0
The Alfred - Prahran
Recruitment postcode(s) [1] 14469 0
3050 - Parkville
Recruitment postcode(s) [2] 14470 0
3084 - Heidelberg
Recruitment postcode(s) [3] 14471 0
2031 - Randwick
Recruitment postcode(s) [4] 14472 0
2145 - Westmead
Recruitment postcode(s) [5] 14473 0
2050 - Camperdown
Recruitment postcode(s) [6] 14474 0
4029 - Herston
Recruitment postcode(s) [7] 14475 0
5042 - Bedford Park
Recruitment postcode(s) [8] 14476 0
3168 - Clayton
Recruitment postcode(s) [9] 14477 0
3065 - Fitzroy
Recruitment postcode(s) [10] 14478 0
4556 - Sippy Downs
Recruitment postcode(s) [11] 18565 0
3004 - Prahran
Recruitment outside Australia
Country [1] 8306 0
New Zealand
State/province [1] 8306 0
Auckland, Wellington, Waikato and Christchurch

Funding & Sponsors
Funding source category [1] 294692 0
Commercial sector/Industry
Name [1] 294692 0
Zynerba Pharmaceuticals Inc.
Country [1] 294692 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Zynerba Pharmaceuticals Pty Ltd
Address
At the office of PriceWaterhouseCoopers, 2 Riverside Quay, Southbank VIC, 3006
Country
Australia
Secondary sponsor category [1] 293537 0
None
Name [1] 293537 0
Address [1] 293537 0
Country [1] 293537 0
Other collaborator category [1] 279265 0
Commercial sector/Industry
Name [1] 279265 0
Novotech (Australia) Pty Limited
Address [1] 279265 0
Level 3, 235 Pyrmont St
Pyrmont NSW 2009
Country [1] 279265 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296116 0
Melbourne Health Human Research Ethics Committee
Ethics committee address [1] 296116 0
The Royal Melbourne Hospital
Level 6 East
300 Grattan Street
Parkville 3050 Victoria
Ethics committee country [1] 296116 0
Australia
Date submitted for ethics approval [1] 296116 0
28/09/2016
Approval date [1] 296116 0
25/10/2016
Ethics approval number [1] 296116 0

Summary
Brief summary
This study is an open-label extension study to Protocol ZYN2-CL-03 (STAR1). The study aims to evaluate the long term effectiveness, safety, tolerability and blood levels of twice daily ZYN002 in addition to regular seizure medication for 24 months in up to 180 adults with partial onset seizures (POS) who have participated in study ZYN2-CL-03. This will be done by analysing a daily seizure and skin irritation diary, drug levels in the blood at various
times following drug administration, and side effects. Skin at the application sites will be checked to see if there is any irritation or reactions present after applications.

Who is if for? You may be eligible to join this study if have completed the 12 weeks of study treatment on protocol ZYN2-CL-03.

Study details: All participants will administer ZYN002 transdermal gel twice daily for 24 months.

What does study participation involve? Eligible patients can immediately transition after completing day 84 (at Week 12) of the double-blind study, ZYN2-CL-03, to the open label study, ZYN2-CL-004. All participants in this extension study will receive active ZYN002. This could be the first time a participant receives ZYN002, depending on which treatment they received in the previous study (ZYN2-CL-03).
After pre-dosing procedures are completed, patients will start study medication (Day 1). The first dose of study drug will be applied by the patient at this visit. Patients will be required to visit the clinic at Week 2 and Months 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, Adhoc and End of Study to have study procedures completed.
Participants will continue to record their seizure frequency and type in their daily diary.
At the clinic visits the following procedures will occur: blood sampling; review of daily diary, medications, adverse events and skin irritation; measurement of blood pressure, heart rate, breathing rate and temperature ; suicide risk; and possibly, a brief physical and neurological exam, pregnancy tests (females only, if applicable) and an ECG. Participants withhold their morning application until after blood sample collection at these visits. Additional out-patient visits may be required if there is skin irritation present at the application site.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 69602 0
Prof Terence O’Brien
Address 69602 0
Alfred Health 55 Commercial Rd Melbourne VIC 3004
Country 69602 0
Australia
Phone 69602 0
+61 3 8344 5490
Fax 69602 0
+61 3 9347 1863
Email 69602 0
[email protected]
Contact person for public queries
Name 69603 0
Carol O'Neill
Address 69603 0
Zynerba Pharmaceuticals, Inc.
80 West Lancaster Avenue
Devon, PA 19333
Country 69603 0
United States of America
Phone 69603 0
+1 484 581 7481
Fax 69603 0
-
Email 69603 0
[email protected]
Contact person for scientific queries
Name 69604 0
Donna Gutterman
Address 69604 0
Zynerba Pharmaceuticals, Inc.
80 West Lancaster Avenue
Devon, PA 19333
Country 69604 0
United States of America
Phone 69604 0
+1 484 581 7481
Fax 69604 0
-
Email 69604 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
confidential information


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
SourceTitleYear of PublicationDOI
Dimensions AIAdjunctive Transdermal Cannabidiol for Adults With Focal Epilepsy2022https://doi.org/10.1001/jamanetworkopen.2022.20189
N.B. These documents automatically identified may not have been verified by the study sponsor.