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Trial registered on ANZCTR


Registration number
ACTRN12616000510448
Ethics application status
Approved
Date submitted
4/04/2016
Date registered
20/04/2016
Date last updated
14/12/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
Study of ZYN002 (transdermal gel) in Patients with Partial Onset Seizures
Scientific title
A Phase 2A, Randomized, Double-Blind, Placebo-Controlled, Multiple Center, Multiple-Dose Study to Assess the Safety and Efficacy of ZYN002 Administered as a Transdermal Gel to Patients with Partial Onset Seizures (STAR 1)
Secondary ID [1] 288929 0
Zynerba ZYN2-CL-03
Universal Trial Number (UTN)
nil
Trial acronym
STAR 1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Epilepsy 298274 0
Condition category
Condition code
Neurological 298412 298412 0 0
Epilepsy

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will undergo an 8-week baseline period to document their seizures and the medications they are taking to treat their epilepsy. Following the baseline period, participants will receive one of three treatments as indicated below:
- Treatment A: ZYN002 – CBD 195 mg every 12 hours, or
- Treatment B: ZYN002 – CBD 97.5 mg every 12 hours, or
- Treatment C: placebo every 12 hours
for 12 weeks.

Participants will have their dose reduced by 50% at Week 13 and another 50% (only participants receiving Treatment A) at Week 14, with no further treatment administered from week 15.

ZYN002 or placebo gel will be applied to the skin of both the right and left shoulder and/or upper arms.

Participants will bring used and unused sachets to each visit for site to check treatment compliance.
Intervention code [1] 294397 0
Treatment: Drugs
Comparator / control treatment
Placebo - matching gel with no active ingredient
Control group
Placebo

Outcomes
Primary outcome [1] 297887 0
Composite Primary Outcome 1: To evaluate the efficacy of ZYN002 administered as a transdermal gel formulation for 12 weeks as adjunctive therapy for the treatment of partial onset seizures (POS).
Assessed by: monitoring seizure frequency and type in daily diary
Timepoint [1] 297887 0
Investigator will review daily diary at the end of the baseline period and at weeks 4, 8 and 12 post commencement of the study drug.
Secondary outcome [1] 322528 0
Secondary Outcome 1: To evaluate the safety and tolerability of ZYN002 in epilepsy patients receiving different treatments for POS.
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] 322528 0
Timepoint: safety and tolerability will be assessed at every study visit from Screening visit to End of study visit (Day 1, Weeks 2, 4, 6, 8, 12 and 15).

Eligibility
Key inclusion criteria
Eligible participants include males and non-pregnant, non-lactating females, with confirmed epilepsy, with Partial Onset Seizures (POS) for at least 5 years; who have on average at least three observable POS per month; who are being treated and maintained on a stable regimen of AED(s); who are able and willing to maintain a daily diary; and have an acceptable (protocol defined) body mass index (18-35 kg/m2).
Females of childbearing potential and males with a partner of childbearing potential must use an acceptable method of contraception, from at least 21 days prior to the first dose of study drug and for 28 days after the last dose of study drug. Participants must agree to comply with all study restrictions and procedures, provide written informed consent and, in the investigator’s opinion, be reliable.
Minimum age
18 Years
Maximum age
70 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Excluded are patients with a history of relevant allergic reactions; who have been exposed to any investigational drug or device in the last 30 days; who have used any marijuana-containing product within the last four weeks; who have changed tobacco product(s) use within the last 30 days; who have certain types of epilepsy or non-epileptic seizures within the last 5 years; who are using certain (protocol defined) AEDs or have changed AED regimen in the last 4 weeks; who have had epilepsy dietary therapy started within the last 3 months; who have any diseases or conditions that are likely to require changes in drug therapy during the study or interfere with the objectives of the study; who are at risk of suicide; who have Hepatitis or HIV; who have a positive drug screen for (protocol defined) drugs, including alcohol, or who have a history of alcohol or drug abuse.

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 trial site will screen and enroll patients that meet the study criteria. Once it is determined the patient qualifies to participate in the study the site will receive the randomization number for the participant. The randomization number does not denote the treatment the participant is receiving.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A randomization schedule has been prepared by a statistician. The software application SAS was used to generate the randomization codes. A series unique code has been issued on a per protocol allocation ratio of 1:1:1.
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 2
Type of endpoint(s)
Efficacy
Statistical methods / analysis
The sample size of 60 participants per treatment group is sufficient to have a power of 88% to detect a difference between active and placebo. To account for a possible screening failure rate of 15%, a total of 210 participants should be enrolled to ensure there will be 180 participants to randomize.
There will be one planned interim analysis when approximately 120 participants (67% of planned sample size) have completed the trial.
Efficacy:
All participants who receive at least one dose of study drug and have at least one post-baseline seizure assessment will be included in the efficacy analysis. The primary analysis, based on an analysis of covariance (ANCOVA) model, will be performed on seizure frequency. Pairwise comparisons of the two active treatments (Treatment A and Treatment B) to placebo (Treatment C) will be made using least squares (LS) means.
Pharmacokinetics:
All participants who receive at least one dose of study drug and have plasma concentration obtained from at least one of the three Maintenance Period evaluations will be included in the pharmacokinetic analysis.
Descriptive statistics (arithmetic mean, median, SD, minimum, maximum, coefficient of variation, geometric mean [plasma concentration]) for plasma concentrations and elapsed time will be presented by treatment group at nominal blood sampling times..
Safety Analyses:
All participants who receive at least one dose of study drug will be included in the safety analysis. AEs will be tabulated by treatment group and classified by system organ class and preferred term using the Medical Dictionary for Regulatory Affairs (MedDRA). For each preferred term, the two active groups will each be compared to the placebo group with a Fisher Exact test. Additionally, AEs will be tabulated overall (total number of AEs and total number of patients with AEs).


Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 5545 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [2] 6441 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [3] 6442 0
Prince of Wales Hospital - Randwick
Recruitment hospital [4] 6443 0
Westmead Hospital - Westmead
Recruitment hospital [5] 6444 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [6] 6445 0
Royal Brisbane & Womens Hospital - Herston
Recruitment hospital [7] 6446 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [8] 6447 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment hospital [9] 6448 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment hospital [10] 6449 0
University of Sunshine Coast Health Clinics - Sippy Downs
Recruitment postcode(s) [1] 14002 0
4556 - Sippy Downs
Recruitment outside Australia
Country [1] 8088 0
New Zealand
State/province [1] 8088 0
Auckland, Wellington, Waikato and Christchurch

Funding & Sponsors
Funding source category [1] 293278 0
Commercial sector/Industry
Name [1] 293278 0
Zynerba Pharmaceuticals Inc.
Address [1] 293278 0
80 West Lancaster Avenue
Suite 300
Devon, PA 19333
Country [1] 293278 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] 292081 0
None
Name [1] 292081 0
Address [1] 292081 0
Country [1] 292081 0
Other collaborator category [1] 278933 0
Commercial sector/Industry
Name [1] 278933 0
Novotech (Australia) Pty Limited
Address [1] 278933 0
Level 3, 235 Pyrmont St
Pyrmont NSW 2009
Country [1] 278933 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294754 0
MELBOURNE HEALTH HUMAN RESEARCH ETHICS COMMITTEE
Ethics committee address [1] 294754 0
The Royal Melbourne Hospital
Level 6 East
300 Grattan Street
Parkville 3050 Victoria
Ethics committee country [1] 294754 0
Australia
Date submitted for ethics approval [1] 294754 0
27/01/2016
Approval date [1] 294754 0
02/03/2016
Ethics approval number [1] 294754 0
HREC/16/MH/10

Summary
Brief summary
This study aims to investigate the effectiveness, safety, tolerability and blood levels, of twice daily ZYN002, in addition to regular seizure medication, for 12 weeks in 180 adults with partial onset seizures. 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 you are aged between 18 and 70 years, have epilepsy with partial onset seizures and are currently on a stable regimen of AED(s).

Study details: This study will investigate two doses of ZYN002 compared to a placebo gel (a treatment with no active ingredients which looks like the real thing but it is not). This study is ‘double-blind’ which means you and your study doctor, together with the study staff will not know whether you are receiving ZYN002 or placebo gel.

What does study participation involve? Your participation in the study includes a screening visit; a baseline period of up to 8-weeks; a 12 week study treatment period; dose reduction at Week 13 and 14; and an end of study (EOS) visit at Week 15. Participants should fast prior to four study visits. Participants will be instructed to record their seizure frequency and type in their daily diary.
During the baseline period, participants will record seizures in the daily diary, and blood samples will be collected at two visits. During the treatment period four clinic visits are required for: blood sampling; review of daily diary, medications, AEs 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. Two additional clinic visits are also required for blood sampling. Additional out-patient visits may be required if there is skin irritation present at the application site.

Trial website
Mediscreener website is no longer applicable as the study recruitment is now complete
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 64942 0
Prof Terence O’Brien
Address 64942 0
The Royal Melbourne Hospital
300 Grattan Street
Parkville 3050 Victoria
Country 64942 0
Australia
Phone 64942 0
+61 3 8344 5490
Fax 64942 0
+61 3 9347 1863
Email 64942 0
obrientj@unimelb.edu.au
Contact person for public queries
Name 64943 0
Ms Carol O’Neill
Address 64943 0
Zynerba Pharmaceuticals, Inc.
80 West Lancaster Avenue
Devon, PA 19333
Country 64943 0
United States of America
Phone 64943 0
+1 484-581-7481
Fax 64943 0
-
Email 64943 0
oneillc@zynerba.com
Contact person for scientific queries
Name 64944 0
Dr Donna Gutterman
Address 64944 0
Zynerba Pharmaceuticals, Inc.
80 West Lancaster Avenue
Devon, PA 19333
Country 64944 0
United States of America
Phone 64944 0
+1 484-581-7481
Fax 64944 0
-
Email 64944 0
guttermand@zynerba.com

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary