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Trial registered on ANZCTR


Registration number
ACTRN12617001028392
Ethics application status
Approved
Date submitted
23/06/2017
Date registered
17/07/2017
Date last updated
17/09/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
Study of ZYN001 (transdermal patch) in Healthy Volunteers
Scientific title
A Phase 1, Single-Center, Five-Period, Single and Multiple Dose, Double-Blind, Placebo-Controlled First-in-Man Study to Assess the Safety and Pharmacokinetics of ZYN001 Administered as a Transdermal Patch to Healthy Adults
Secondary ID [1] 292149 0
ZYN1-CL-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Peripheral neuropathic pain 303581 0
Fibromyalgia 303584 0
Condition category
Condition code
Neurological 302991 302991 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
ZYN001 transdermal patch contains 36mg of delta-9 tetrahydrocannabinol (THC). The patch will be applied to the right or left upper arm.

Phase 1: In Periods 1 to 3 qualified participants will be randomized to receive a ZYN001 patch or a placebo patch:
Period 1 – patch worn for 24 hours
Period 2 – patch worn for 3.5 days
Period 3 – patch worn for 7 days

Phase 2 of the study- two groups will receive multiple patch applications. Participants will be randomized to one of two treatment groups as indicated below:
Period 4 – patch worn for 3.5 days, repeated 4 times (4 applications) for a total of 14-days patch wear time.
Period 5 – patch worn for 7 days, repeated two times (2 applications) for a total of 14-days patch wear time.
Intervention code [1] 298292 0
Treatment: Drugs
Intervention code [2] 298293 0
Treatment: Devices
Comparator / control treatment
Placebo - matching patch with no active ingredient
Control group
Placebo

Outcomes
Primary outcome [1] 302365 0
To evaluate the safety and tolerability of ZYN001.
Assessed by: monitoring physical examinations, examination of skin application site, vital signs, 12-lead ECG, laboratory tests, neuropsychological tests and adverse events throughout the study. Possible adverse events could include- getting dizzy, loss of balance, change in heart rate or blood pressure, red or irritated eyes, feeling tired, pounding in chest or heart, dry mouth, jitters, headache, upset stomach, vomiting, sore throat, increased appetite, trouble concentrating, memory problems, confusion, depression, feeling paranoid, rash, trouble sleeping, blurry vision, ringing in the ears, diarrhea, and hallucinations.
Timepoint [1] 302365 0
Timepoint: Periods 1-5 subjects are confined to the research facility until the patch is removed and then return for PK draws and assessments over an additional 2 weeks at which time they will complete the End of Study Visit unless the skin irritation score is greater than ‘0’ or they test positive for THC. If this is the case, they will return to the research facility until the skin irritation score is equal to ‘0’ and they test negative for THC.

Period 4 subjects are confined for 5 days, return the evening of Day 7 and are confined until Day 9, returning the morning of Day 11 and released on Day 12 then they return for 4 PK draws and assessments over an additional 2 weeks at which time they will complete the End of Study visit unless the skin irritation score is greater than 0 or they test positive for THC. If this is the case they will return to the research facility until the skin irritation score equals 0 and they test negative for THC.

Study assessments are collected for all study periods as follows:
Physical Exam at Screening with a Targeted Physical Exam at Day -1, each day of dosing and EOS Visit
Vital Signs at Screening, Day -1, prior to each PK draw, and EOS Visit
Adverse Events are collected as reported throughout the study
Examination of skin application site at patch removal
Neuropsychological tests are completed at the following time points:
Period 1- Pre-dose, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 72, 144, 252, 336 hrs
Period 2- Pre-dose, 1, 2, 4, 6, 8, 10, 12, 16, 24, 48, 36, 72, 84, 144, 252, 336 and 408 hrs
Period 3- Pre-dose, 1r, 2, 4, 6, 8, 10, 12, 16 24, 48, 36, 72, 84, 96, 108, 120, 144, 168, 252, 336, 408 and 528 hrs
Period 4- Pre-dose, 1, 2, 4, 6, 8, 10, 12, 16, 24, 48, 36, 72, 84, 96, 108, 168, 180, 192, 252, 264, 276, 336, 408, 528, 600 and 672 hrs
Period 5- Pre-dose, 1, 2, 4, 6, 8, 10, 12, 16, 24, 48, 36, 72, 84, 96, 108, 120, 144, 168, 180, 192, 252, 336, 408, 528, 600 and 672 hrs
12 Lead ECG at Screening, patch application days, follow-up visits and EOS Visit
Laboratory tests at Screening, end of confinement, and EOS Visit
Secondary outcome [1] 335741 0
To evaluate the pharmacokinetics (PK) of delta 9-tetrahydrocannabinol (THC) and its major metabolites as assessed in plasma and urine after both single and multiple patch applications.

Assessed by: collecting blood and urine samples for analysis. PK parameters include-Cmax, Tmax, and AUC.
Timepoint [1] 335741 0
Plasma samples will be collected from the opposite arm of patch application, as follows:
Period 1- Pre-dose, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 72, 144, 252, 336 hrs
Period 2- Pre-dose, 1, 2, 4, 6, 8, 10, 12, 16, 24, 48, 36, 72, 84, 144, 252, 336 and 408 hrs
Period 3- Pre-dose, 1r, 2, 4, 6, 8, 10, 12, 16 24, 48, 36, 72, 84, 96, 108, 120, 144, 168, 252, 336, 408 and 528 hrs
Period 4- Pre-dose, 1, 2, 4, 6, 8, 10, 12, 16, 24, 48, 36, 72, 84, 96, 108, 168, 180, 192, 252, 264, 276, 336, 408, 528, 600 and 672 hrs
Period 5- Pre-dose, 1, 2, 4, 6, 8, 10, 12, 16, 24, 48, 36, 72, 84, 96, 108, 120, 144, 168, 180, 192, 252, 336, 408, 528, 600 and 672 hrs

For all study periods, urine samples will be collected at baseline. Complete urine samples will be collected for time intervals of: 0 to 12 hours, and 12 to 24 hours for Periods 1 to 3. For Period 4, 24-hour interval will start collection with the fourth patch application (Days 11 and 12) and Period 5 24-hour interval will start collection with the second patch application (Days 8 and 9).
Secondary outcome [2] 335744 0
Psychomotor ability, visual attention and task switching as assessed by Trail Making Test A and B
Timepoint [2] 335744 0
Trail Making Test A and B will be administered at the following time points:
Period 1- Pre-dose, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 72, 144, 252, 336 hrs
Period 2- Pre-dose, 1, 2, 4, 6, 8, 10, 12, 16, 24, 48, 36, 72, 84, 144, 252, 336 and 408 hrs
Period 3- Pre-dose, 1r, 2, 4, 6, 8, 10, 12, 16 24, 48, 36, 72, 84, 96, 108, 120, 144, 168, 252, 336, 408 and 528 hrs
Period 4- Pre-dose, 1, 2, 4, 6, 8, 10, 12, 16, 24, 48, 36, 72, 84, 96, 108, 168, 180, 192, 252, 264, 276, 336, 408, 528, 600 and 672 hrs
Period 5- Pre-dose, 1, 2, 4, 6, 8, 10, 12, 16, 24, 48, 36, 72, 84, 96, 108, 120, 144, 168, 180, 192, 252, 336, 408, 528, 600 and 672 hrs

Secondary outcome [3] 336882 0
Cognitive function as assessed by Paced Auditory Serial Addition Test (PASAT)
Timepoint [3] 336882 0
Paced Auditory Serial Addition Test (PASAT) will be administered at the following time points:
Period 1- Pre-dose, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 72, 144, 252, 336 hrs
Period 2- Pre-dose, 1, 2, 4, 6, 8, 10, 12, 16, 24, 48, 36, 72, 84, 144, 252, 336 and 408 hrs
Period 3- Pre-dose, 1r, 2, 4, 6, 8, 10, 12, 16 24, 48, 36, 72, 84, 96, 108, 120, 144, 168, 252, 336, 408 and 528 hrs
Period 4- Pre-dose, 1, 2, 4, 6, 8, 10, 12, 16, 24, 48, 36, 72, 84, 96, 108, 168, 180, 192, 252, 264, 276, 336, 408, 528, 600 and 672 hrs
Period 5- Pre-dose, 1, 2, 4, 6, 8, 10, 12, 16, 24, 48, 36, 72, 84, 96, 108, 120, 144, 168, 180, 192, 252, 336, 408, 528, 600 and 672 hrs
Secondary outcome [4] 336883 0
Brain damage, dementia, age and depression as assessed by Digit Symbol Substitution Task (DSST)
Timepoint [4] 336883 0
Digit Symbol Substitution Task (DSST) will be administered at the following time points:
Period 1- Pre-dose, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 72, 144, 252, 336 hrs
Period 2- Pre-dose, 1, 2, 4, 6, 8, 10, 12, 16, 24, 48, 36, 72, 84, 144, 252, 336 and 408 hrs
Period 3- Pre-dose, 1r, 2, 4, 6, 8, 10, 12, 16 24, 48, 36, 72, 84, 96, 108, 120, 144, 168, 252, 336, 408 and 528 hrs
Period 4- Pre-dose, 1, 2, 4, 6, 8, 10, 12, 16, 24, 48, 36, 72, 84, 96, 108, 168, 180, 192, 252, 264, 276, 336, 408, 528, 600 and 672 hrs
Period 5- Pre-dose, 1, 2, 4, 6, 8, 10, 12, 16, 24, 48, 36, 72, 84, 96, 108, 120, 144, 168, 180, 192, 252, 336, 408, 528, 600 and 672 hrs
Secondary outcome [5] 336884 0
Subjective drug effects following acute cannabinoid administration as assessed by Drug Effect Questionnaire (DEQ).
Timepoint [5] 336884 0
Drug Effect Questionnaire (DEQ) will be administered at the following time points:
Period 1- Pre-dose, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 72, 144, 252, 336 hrs
Period 2- Pre-dose, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 84, 144, 252, 336 and 408 hrs
Period 3- Pre-dose, 1r, 2, 4, 6, 8, 10, 12, 16 24, 36, 48, 72, 84, 96, 108, 120, 144, 168, 252, 336, 408 and 528 hrs
Period 4- Pre-dose, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 84, 96, 108, 168, 180, 192, 252, 264, 276, 336, 408, 528, 600 and 672 hrs
Period 5- Pre-dose, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 84, 96, 108, 120, 144, 168, 180, 192, 252, 336, 408, 528, 600 and 672 hrs
Secondary outcome [6] 336885 0
The ability of your brain to focus on and react to particular details—matching colors, shapes, and/or fill interiors—while at the same time dismissing competing information will be assessed by the Divided Attention Test (DAT) .
Timepoint [6] 336885 0
Divided Attention Test (DAT) will be administered at the following time points:
Period 1- Pre-dose, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 72, 144, 252, 336 hrs
Period 2- Pre-dose, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 84, 144, 252, 336 and 408 hrs
Period 3- Pre-dose, 1r, 2, 4, 6, 8, 10, 12, 16 24, 36, 48, 72, 84, 96, 108, 120, 144, 168, 252, 336, 408 and 528 hrs
Period 4- Pre-dose, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 84, 96, 108, 168, 180, 192, 252, 264, 276, 336, 408, 528, 600 and 672 hrs
Period 5- Pre-dose, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 84, 96, 108, 120, 144, 168, 180, 192, 252, 336, 408, 528, 600 and 672 hrs

Secondary outcome [7] 336886 0
Thoughts or feelings relating to suicide over the past month will be assessed by the Columbia Suicide Severity Rating Scale (C-SSRS)
Timepoint [7] 336886 0
A Columbia Suicide Severity Rating Scale (C-SSRS) will be administered at Screening, and pre-dose for each patch application.
Secondary outcome [8] 336888 0
Drug abuse potential will be assessed by the Post Dose Questionnaire (Abuse Liability Assessments). This questionnaire has been specifically designed for this study.
Timepoint [8] 336888 0
Post Dose Questionnaire will be administered prior to each patch removal
Period 1: Day 2
Period 2: Day 4
Period 3: Day 8
Period 4: Days 4, 8, 15
Period 5: Days 8, 15

Eligibility
Key inclusion criteria
Healthy male or female adults, 18 to 55 years of age, inclusive, at the time of screening.
Judged by the investigator to be in generally good health at screening based upon the results of medical history, physical examination, laboratory profile, 12-lead ECG, and clinical laboratory test results.
Subject has a body mass index between 18-30 kg/m2.
Females of childbearing potential must have a negative pregnancy test at the Screening Visit and a negative pregnancy test prior to each treatment.
Subjects must be adequately informed of the nature and risks of the study and give written informed consent prior to screening.
Subject agrees to abide by all study restrictions and comply with all study procedures.
In the investigator’s opinion, the subject is reliable and is willing and able to comply with all protocol requirements and procedures (including out-patient scheduled visits and confinement periods)
Minimum age
18 Years
Maximum age
55 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Females who are pregnant, breast feeding or planning a pregnancy; females of childbearing potential and male subjects with a partner of childbearing potential, who are unwilling or unable to use an acceptable method of contraception as outlined in this protocol from at least 21 days prior to the first dose of study medication and for 28 days after the last dose of study medication.
Standard acceptable methods include abstinence or the use of a highly effective method of contraception, including; hormonal contraception, diaphragm, cervical cap, vaginal sponge, condom, vasectomy, intrauterine device.
Use of tobacco/nicotine-containing products within 4 weeks of the Screening Visit or during the study.
Use of any prescription drugs (except hormonal contraception), vitamins, or herbal supplements within 4 weeks prior to the Screening Visit or any OTC drugs/vitamins within 72 hours prior to the first dose of study medication, except those approved in advance by the study physician.
Use of cannabis or any THC containing product cannabidiol, a synthetic cannabinoid analogue (e.g., nabilone), or a synthetic endocannabinoid receptor agonist (e.g., Spice, K2), within four weeks of the Screening Visit or during the study.
Positive result for the presence of Hepatitis B surface antigen (HBsAG), Hepatitis C virus antibodies (HCV-Ab), or human immunodeficiency virus (HIV) antibodies.
Positive urine drug screen, including, cocaine, THC, barbiturates, amphetamines, methamphetamines, methylenedioxymethamphetamine, oxycodone, methadone, benzodiazepines, and opiates or positive breathalyzer test for ethanol.
Any clinically significant condition or abnormal findings at the Screening Visit that would, in the opinion of the investigator, preclude study participation or interfere with the evaluation of the study treatment.
Any skin disease or condition, including eczema, psoriasis, melanoma, acne or contact dermatitis, scarring, imperfections, lesions, tattoos or discoloration that may affect patch application, application site assessments, or affect absorption of the study drug.
Use of cosmetics or lotions on the upper arms during the study.
History of significant allergic condition, significant drug-related hypersensitivity, or allergic reaction to any adhesives, compound, or chemical class related to ZYN001 or its excipients.
Subject has taken caffeine, xanthine, or grapefruit products within 24 hours of dosing. Carbonated beverages will be prohibited during confinement at the research facility.
History of treatment for, or evidence of alcohol or drug abuse within the past year or regular alcohol consumption exceeding an average of two units of alcohol per day. Subjects are not allowed alcohol from 48 hours before the first dose of study treatment until the End of Study.
History or current diagnosis of a significant psychiatric disorder that would, in the opinion of the investigator, affect the subject’s ability to comply with the study requirements.
Subject has suspected or confirmed cardiovascular disease.
Participation in any investigational product or device study within 30 days prior to the Screening Visit, or is scheduled to participate in an investigational device or another investigational drug study, during the course of this study.
Patient has a history of actual suicide attempt in the last 5 years or more than one lifetime suicide attempt.
Patient responded “yes” to Question 4 or 5 of neurological questionnaire during Screening.
Current or past diagnosis of primary psychotic disorder, or positive family history (first degree relative) of psychotic disorder.
Demonstrates behavior indicating unreliability or inability to comply with the requirements of the protocol.

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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 1
Type of endpoint(s)
Safety
Statistical methods / analysis

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)
QLD
Recruitment hospital [1] 8313 0
Q-Pharm Pty - Clive Berghofer Research Centre (CBCRC) - Herston
Recruitment postcode(s) [1] 16377 0
4007 - Herston

Funding & Sponsors
Funding source category [1] 296681 0
Commercial sector/Industry
Name [1] 296681 0
Zynerba Pharmaceuticals Pty. Ltd
Address [1] 296681 0
Offices of PriceWaterhouseCoopers
2 Riverside Quay
Southbank VIC, 3006

Country [1] 296681 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Zynerba Pharmaceuticals Pty. Ltd
Address
Offices of PriceWaterhouseCoopers
2 Riverside Quay
Southbank VIC, 3006
Country
Australia
Secondary sponsor category [1] 295641 0
None
Name [1] 295641 0
Address [1] 295641 0
Country [1] 295641 0
Other collaborator category [1] 279598 0
Commercial sector/Industry
Name [1] 279598 0
Novotech (Australia) Pty Limited
Address [1] 279598 0
Level 3, 235 Pyrmont St
Pyrmont NSW 2009
Country [1] 279598 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 297910 0
Bellberry HREC
Ethics committee address [1] 297910 0
129 Glen Osmond Rd,
Eastwood SA 5063
Ethics committee country [1] 297910 0
Australia
Date submitted for ethics approval [1] 297910 0
29/03/2017
Approval date [1] 297910 0
05/06/2017
Ethics approval number [1] 297910 0

Summary
Brief summary
What is this study about? The purpose of this study is to investigate how safe and tolerable a single dose (worn for 24 hrs, 3.5 days or 7 days) and repeat doses (worn for 14 days) of ZYN001 transdermal delivery system is in healthy volunteers. The study will look at how the body absorbs, distributes, breaks down and then removes the study drug from your body. This will be done by analysing the levels of ZYN001 in your blood and urine at various times following drug administration. Your skin at the application sites will be checked to see if there is any irritation or reactions present when the ZYN001 patch is removed. The study will also investigate if ZYN001 affects your brain functioning by administering a number of neuropsychological tests.

Who is if for? You may be eligible to join this study if you are aged between 18 and 55 years and are in good health.

Study details: This study will investigate different formulation of patches containing ZYN001 compared to a placebo patch (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 administering the study treatment will not know whether you are receiving ZYN001 or a placebo patch.

What does study participation involve?
Initially, the study will investigate four (4) different patches in each study period. All patches will have the same amount of THC drug within a study period but the ingredients in the patches will be different.
You will report to the clinic the day before receiving treatment (Day -1). You will participate in either:
• Period 1 - one patch worn for 24 hours
• Period 2 - one patch worn for 3.5 days
• Period 3 - one patch worn for 7 days

OR, you will participate in either:
Period 4 - one patch applied and worn for 3.5 days, removed and patch #2 applied and worn for 3.5 days, removed and patch #3 applied and worn for 3.5 days, removed and patch #4 applied and removed 3.5 days later
Period 5 - one patch applied and worn for 7 days, removed and patch #2 applied and worn for 7 days

You will receive application of ZYN001 or a placebo patch. The patch will be applied to either your left or right upper arm.

Throughout the study you will have various medical tests (physical examinations, vital signs measured, ECG measured, neuropsychological tests) and will have several blood and urine samples collected for laboratory analysis.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 75434 0
Dr Paul Griffin
Address 75434 0
Q-Pharm Pty Limited, Level 5, 300C Herston Road, Herston QLD 4006
Country 75434 0
Australia
Phone 75434 0
+61 73845 3636
Fax 75434 0
Email 75434 0
P.Griffin@qpharm.com.au
Contact person for public queries
Name 75435 0
Ms Carol O’Neill
Address 75435 0
Zynerba Pharmaceuticals, Inc.
80 West Lancaster Avenue
Devon, PA 19333
Country 75435 0
United States of America
Phone 75435 0
+ 1 484-581-7481
Fax 75435 0
Email 75435 0
oneillc@zynerba.com
Contact person for scientific queries
Name 75436 0
Dr Donna Gutterman
Address 75436 0
VP, Medical Affairs
Zynerba Pharmaceuticals, Inc.
80 West Lancaster Avenue
Devon, PA 19333
Country 75436 0
United States of America
Phone 75436 0
+ 1 484-581-7481
Fax 75436 0
Email 75436 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