None listed
Conditions
Brief summary
What is this study about? The purpose of this study is to investigate how safe and tolerable repeat doses (applied daily for 7 days) of ZYN002 transdermal gel is in healthy volunteers and patients with epilepsy. 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 ZYN002 in your blood and urine at various times following drug administration. Your skin at the application sites and your hands will be checked to see if there is any irritation or reactions present after ZYN002 application. The study will also investigate neuropsychological effects that ZYN002 may have 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 either in general good health or have epilepsy with partial onset seizures that is stable. Study details: This study will investigate various 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 administering the study treatment 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, which could be up to 28 days before your study treatment. One confinement period starting on the evening before dosing and lasting until 36 hours after the last study treatment on the 8th study day. This will require eight (8) nights in the clinic. Two out-patient clinic visits following the confinement period on Days 9, Day 10, Day 11 and the End of Study Visit on Day 13. These visits will be at 48, 72, 96, 72 and 144 hours after the last application of the study treatment on Day 7. Additional out-patient visits may be required if there is any skin irritation present at the study treatment application sites. 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.
Interventions
During the first part of the study with 24 participants ,periods 1 and 2, participants will be randomised to one of four treatment groups as indicated below.
Treatment A – (2 tubes of 5 g = 10 g) of 2.5% ZYN002 applied once daily for 7 days (Period 1 – Healthy Volunteers)
Treatment B – (2 tubes of 5 g = 10 g) of 2.5% ZYN002 applied twice daily for 7 days (Period 2 – Healthy Volunteers)
Treatment C – (2 tubes of 5 g = 10 g) of Placebo gel applied once (Period 1) or twice daily (Period 2) for 7 d
During the first part of the study with 24 participants ,periods 1 and 2, participants will be randomised to one of four treatment groups as indicated below. Treatment A – (2 tubes of 5 g = 10 g) of 2.5% ZYN002 applied once daily for 7 days (Period 1 – Healthy Volunteers) Treatment B – (2 tubes of 5 g = 10 g) of 2.5% ZYN002 applied twice daily for 7 days (Period 2 – Healthy Volunteers) Treatment C – (2 tubes of 5 g = 10 g) of Placebo gel applied once (Period 1) or twice daily (Period 2) for 7 days. Participants will receive the same number of treatments of placebo gel as the number of active study drug in order to keep the study blinded. Treatment D – (2 tubes of 5 g = 10 g) of 1.0% ZYN002 applied twice daily for 7 days (Period 2 – Healthy Volunteers) During the second part of the study (Period 3 – Patients with Epilepsy) with 12 participants, participants will receive the highest tolerated dose (Treatment A or B or D) from the first part of the study or placebo (Treatment C). ZYN002 or placebo will be applied to the skin on the left and right shoulder and/or upper arm as a single application. The gel will be thoroughly massaged into the left and right shoulders and/or upper arms by the participant. Once the participant has completed their treatment application they will be instructed to wash their hands thoroughly with soap and water to remove any residual gel. Participants will be instructed to not lay or lean on either shoulder/arm, for at least 30 minutes post dosing. Once the application sites are dry each participant will wear a long sleeved t-shirt. Participants will be provided a clean t-shirt on a daily basis. Subjects will be permitted to shower more than 1 hour prior to each morning’s dosing. All doses supervised by study staff at study site. Subjects are confined during the dosing period.
Sponsors
Zynerba Pharmaceuticals Inc.
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy male or female adults, 18-55 years of age, inclusive, at the time of screening for subjects enrolling in Periods 1 and 2; and male or female patients having a diagnosis of epilepsy with partial onset seizures, 18 – 55 years of age, inclusive, at the time of screening for patients enrolling in Period 3. 2. Judged by the investigator to be in generally good health at screening based upon the results of a medical history, physical examination, 12-lead ECG, and clinical laboratory test results. Laboratory results outside of the reference range, but acceptable must be documented as not clinically significant (NCS) at the discretion of the investigator. 3. Patients enrolled for Period 3 must have a diagnosis of epilepsy with partial onset seizures with or without associated generalized tonic-clonic seizures (so called secondarily generalized seizures). Patients having ONLY generalized tonic-clonic seizures may be included ONLY if these seizures are considered to be a manifestation of partial onset seizures. The Patient’s epilepsy should be stable, i.e., currently seizure-free OR controlled by one or two antiepileptic drugs [AEDs] with an average monthly seizure frequency of less than 5 seizures per month. 4. The patient should have a confirmed epilepsy diagnosis for at least one year, with a history of assessments, such as electroencephalogram (EEG), scan (either computed tomography [CT] or magnetic resonance imaging [MRI]), and narrative, including detailed descriptions of each seizure type from the physician who manages the patient’s epilepsy. The historical baseline of seizures over the previous 8 weeks should show a reasonably stable pattern of seizure occurrence without clustering of seizures. 5. Patients enrolled in Period 3 must be on a stable dose (no changes in AED regimen for the 4 weeks preceding study enrollment) of no more than two approved AEDs limited to: carbamazepine, clonazepam, gabapentin, lacosamide, lamotrigine, levetiracetam, pregabalin, topiramate, valproate, valproic acid, or zonisamide. Patients must remain on a stable AED dose regimen throughout the study. 6. Subjects in Periods 1-2 have a body mass index between 18-30 kg/m2. Patients in Period 3 have a body mass index between 18-32 kg/m2. 7. Females of childbearing potential must have a negative pregnancy test at the Screening Visit and on Day -1. 8. Subject/patient agrees to abide by all study restrictions and comply with all study procedures. 9. Subject/patient must be adequately informed of the nature and risks of the study and give written informed consent prior to screening. 10. In the investigator’s opinion, the subject/patient is reliable and is willing and able to comply with all protocol requirements and procedures (including keeping an accurate seizure diary, scheduled visits and confinement periods).
Exclusion criteria
1. Females who are pregnant, nursing or planning a pregnancy; females 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. a. 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. 2. Patients with epilepsy enrolled in Period 3 cannot have a history of status epilepticus or the occurrence of seizure clusters (bouts of seizures so close together that an accurate seizure counts are not possible). 3. Use of tobacco/nicotine-containing products within one month of Screening Visit or during study. 4. Use of the following AEDs: clobazam, ethosuximide, oxcarbazepine, phenytoin, phenobarbital, tiagabine, or vigabatrin. 5. For subjects in Period 1 and 2 use of any prescription drugs except hormonal contraception or herbal supplements within four weeks prior to the Screening Visit or any OTC drugs/vitamins within 72 hours prior to first dose of study medication. 6. For patients in Period 3 use of any prescription drugs except hormonal contraception, AEDs, antidepressants (except citalopram, vilazodone, and trazodone) or herbal supplements within four weeks prior to the Screening Visitor any OTC drugs/vitamins within 72 hours prior to first dose of study medication. 7. Use of cannabis or any CBD-containing product within 4 weeks of Screening Visit or during the study. 8. Positive result for the presence of HBsAg, HCAb, or HIV antibodies. 9. Positive drug screen for ethanol, cocaine, delta-9-tetrahydrocannabinol (THC), barbiturates, amphetamines, benzodiazepines (except clonazepam when prescribed as an AED medication), and opiates. 10. 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. 11. Any skin disease or condition, including eczema, psoriasis, melanoma, acne or contact dermatitis, scarring, imperfections, lesions, tattoos, or discoloration that may affect treatment application, application site assessments, or affect absorption of the study drug. 12. Use of cosmetics or lotions on the shoulder/upper arms during the study. 13. History of significant allergic condition, significant drug-related hypersensitivity, or allergic reaction to any adhesives, compound, or chemical class related to ZYN002 or its excipients. 14. Has taken grapefruit products within the last four weeks or during the study. 15. 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. 16. 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. 17. Has suspected or confirmed cardiovascular disease. 18. Participation in any investigational product or device study within 30 days prior to Screening Visit (except ZYN2-CL-01 study), or is scheduled to participate in an investigational device or another investigational drug study during the course of this study. 19. Demonstrates behavior indicating unreliability or inability to comply with the requirements of the protocol.
Outcome results
None listed