A Phase 1/2, Open-Label Study to Assess the Safety and Efficacy of ZYN002 Administered as a Transdermal Gel to Children and Adolescents with Fragile X Syndrome

Status

Active, not recruiting

Phases

Unknown

Study type

Interventional

Source

ANZCTR

Registry ID

ACTRN12617000150347

Acronym

ZYN2-CL-009

Enrollment

Registered

2017-01-27

Start date

2017-03-17

Completion date

2017-06-21

Last updated

2017-08-21

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

None listed

Brief summary

This is a phase 1/2, open label, multiple center, multiple dose study to assess the safety, and efficacy of ZYN002 administered as a transdermal gel for the treatment of children and adolescent patients ages 6 to 17 years with Fragile X Syndrome (FXS). Approximately 20 participants will be enrolled in this trial to assess the safety and efficacy of ZYN002 administered as a transdermal gel. The initial dose is 50 mg daily (QD) (Treatment A). Patients can have their dose adjusted up to 50 mg every 12 hours (Q12 H) after 2 weeks (Treatment B), and further up to 125 mg Q12 H (Treatment C) at Week 4. Through Week 6, dosing will be flexible (Treatment A, B or C) and, based on the Investigator judgement and the relevant assessments; the dose can be adjusted upward or downward as deemed appropriate. Patient safety will be monitored during study visits using standard measures, including physical exams, examination of skin at application site, vital signs (including oral or tympanic temperature), 12lead electrocardiograms (ECGs), a Modified Suicidality Checklist for FXS patient population, safety laboratory tests, urinalysis and Adverse Event (AE) monitoring. Each participants will be followed up 4 weeks post patient's last dose of study drug. If the participant has completed the Part 1 of this study (12 weeks of treatment) successfully and has shown a demonstrable response to ZYN-002, he/ she will have an opportunity to continue on to the Part 2 of the study which extends up to Week 64.

Interventions

A Phase 1/2, Open-Label Study to Assess the Safety and Efficacy of ZYN002 Administered as a Transdermal Gel to Children and Adolescents with Fragile X Syndrome This is a Phase 1/2, open-label, multiple-center, multiple-dose study, including a Part 1 and Part 2, to assess the safety and efficacy of ZYN002 administered as a transdermal gel for the treatment of children and adolescent patients ages 6 to 17 years with Fragile X Syndrome. Part 1: This study will have a screening period of up to 28 days prior to the study start, following which will be a 12 week titration/treatment period (Clinic visits every 2 weeks until week 12 i.e. Week 2, 4, 6, 8 and 12 except Week 10 which is conducted as a phone call) . A follow up phone visit be done 4 weeks post last dose. Following the Screening period, eligible patients will be enrolled in the titration period to receive ZYN002 50 mg daily (Treatment A) for 2 weeks. At Week 2, the patient will report to the investigative site at which time the Investigator will assess and determine if the patient should increase dose to Treatment B, ZYN002 50 mg every 12 hours (100 mg daily dose) or remain at Treatment A. At Week 4, the patient will report to the investigative site and the investigator may again choose to increase the dose of the patient from Treatment A to Treatment B or increase from Treatment B to Treatment C which is 125 mg applied every 12 hours (250 mg daily dose). The investigator may also choose to decrease the patient’s dose at this visit. Escalation of the dose will depend on the Investigator assessment of ZYN002 tolerability and patient improvement using the CGI-I, VAS for anxiety, hyperactivity and tantrum/mood lability, as well as interview with caregiver(s) and Investigator clinical judgement. Through Week 6, dosing will be flexible (Treatment A, B or C) and, based on the Investigator judgement and the relevant assessments; the dose can be adjusted upward or downward as deemed appropriate. By Week 6, all participants should be on their maintenance dose for the remainder of the treatment period. Part 2: This part of the study will have a treatment period of up to 64 weeks. Week 12 visit of the Part 1 of the study will be the first day of the Part 2. From then on, there will be visits at Week 16 and Week 25 and then quarterly visits (every 13 weeks) through Week 64. The dose of ZYN002 gel prescribed in this part of the study is the same as the maintenance dose prescribed in Part 1 which was decided based on the investigator’s judgement and relevant assessments that indicated if the participant was being benefitted from that dose or not. During Part 2 of the study also, the investigator may decide to change the dose of the study drug again, based on the participant's response. Participants who are not on anti-epileptic drugs (AEDs) will be allowed to discontinue study medication at week 64 without a taper, and the end of Part 2 visit can be completed at week 64 visit or once the necessary assessments are achieved. The study drug ZYN002 will be applied as a transdermal gel i.e. on the skin. The gel will be applied to clean, dry, intact skin of the shoulders and/or upper arms by the parent/caregiver using gloves. For times where non-compliance with study gel administration occurs, a missed dose can be taken up to 6 hr after the correct time for the missed dose (up to 18 hr after the last actual dose), but the next dose should be taken at the regular time (as little as 6 hours after the missed dose was taken). If a higher dose than is prescribed is administered, the parent/caregiver should notify the study doctor as soon as possible to determine appropriate actions.

Study design

Allocation

Non-randomised trial

Primary purpose

Treatment

Eligibility

Sex/Gender

All

Age

6 Years to 17 Years

Healthy volunteers

Inclusion criteria

Main Inclusion Criteria: 1. Male or female children and adolescents aged 6–17 years, inclusive, at the time of screening. 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 must be documented as acceptable by both the Investigator and Sponsor. 3. Patients must have a diagnosis of FXS through molecular documentation of Fragile X Mental Retardation 1 (FMR1) full mutation. 4. Patients have a Pediatric Anxiety Rating Scale-Revised (PARS-R) score of at least 11 at screening. 5. Patients have Clinical Global Impression Severity (CGI-S) score of at least 3 at screening. 6. Patients with a history of seizure disorders must currently be receiving treatment with a stable regimen of one or two AEDs or must be seizure-free for 3 years if not currently receiving AEDs. 7. Patients should be on a stable regimen for the 4 weeks preceding study enrollment of no more than 2 of the following AEDs: gabapentin, lamotrigine, levetiracetam, pregabalin, topiramate, lacosamide, eslicarbazepine, carbamazepine, oxcarbazepine, perampanel and zonisamide. Patients must remain on a stable AED dose throughout the study. 8. If patients are receiving non-pharmacological educational, behavioral, and/or dietary interventions, they must be stable and have been doing so for 2 months prior to screening. 9. Patients have a body mass index between 15–30 kg/m2. 10. Females of childbearing potential must have a negative serum pregnancy test at the Screening Visit and a negative urine pregnancy test at all designated visits. 11. Patients and parents/caregivers agree to abide by all study restrictions and comply with all study procedures. 12. Patients and parents/caregivers must be adequately informed of the nature and risks of the study and give written informed consent prior to screening. 13. Parents/caregiver(s) must provide written consent to assist in study drug administration. 14. In the Investigator’s opinion, patients and parents/caregivers are reliable and willing and able to comply with all protocol requirements and procedures (including scheduled visits and confinement periods).

Exclusion criteria

Main Exclusion Criteria: 1. Females who are pregnant, nursing, or planning a pregnancy; females of childbearing potential and male patients with a partner of childbearing potential who are unwilling or unable to use an acceptable method of contraception as outlined below for the duration of therapy and for 3 months after the last dose of study medication. Standard acceptable methods of contraception include abstinence or the use of a highly effective method of contraception, including hormonal contraception, diaphragm, cervical cap, vaginal sponge, condom, spermicide, vasectomy, or intrauterine device. 2. History of significant allergic condition, significant drug-related hypersensitivity, or allergic reaction to any compound or chemical class related to ZYN002 or its excipients. 3. Exposure to any investigational drug or device < 30 days prior to screening, or plans to take another investigational drug at any time during the study. 4. Use of cannabis or any THC or CBD-containing product within 4 weeks of Screening Visit or during the study. 5. Patient is using the following AEDs: clobazam, phenobarbital, phenytoin, ethosuximide, felbamate or vigabatrin. If a benzodiazepine (excluding clobazam) is being used as a rescue medication, it will be counted as an AED if used more than two days a week. 6. Patient is using the following medications: midazolam, oral ketoconazole, fluconazole, nefazadone, rifampin, alfentanil, alfuzosin, amiodarone, cyclosporine, dasatinib, docetaxol, eplerenone, ergotamine, everolimus, fentanyl, halofantrine, irinotecan, lapatinib, levomethadyl, lumefantrine, nilotinib, pimozide, quinidine, ranolazine, sirolimus, tacrolimus, temsirolimus, toremifene, tretinioin, vincristine, vinorelbine and St. John’s Wort. 7. Advanced, severe, or unstable disease that may interfere with the study outcome evaluations. 8. Plan to initiate or change pharmacologic or non-pharmacologic interventions during the course of the study. 9. Suffering from acute or progressive neurological disease, psychosis, schizophrenia or any psychiatric disorder or severe mental abnormalities (other than Fragile X Syndrome) that are likely to require changes in drug therapy or interfere with the objectives of the study or the ability to adhere to protocol requirements. 10. Use of more than one antipsychotic and one anti-anxiety medication. 11. Has suspected or confirmed cardiovascular disease. 12. Patients may not be taking minocycline for the past 30 days or throughout the study. 13. 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. 14. Any skin disease or condition, including eczema, psoriasis, melanoma, acne, contact dermatitis, scarring, or a tattoo, that may affect treatment application, application site assessments, or absorption of the study drug. 15. History of treatment for, or evidence of, drug abuse within the past year.

Outcome results