Clinical Study of Cannabidiol in Children, Adolescents, and Young Adults with Fragile X Syndrome

Inclusion Criteria:

• Male or female children and adolescents aged 3 to < 30 years, at the time ofScreening.

• Patient resides with caregiver who will continue to provide consistent carethroughout the study.

• Judged by the Investigator to be in generally good health at Screening based uponthe results of medical history, physical exam, 12-lead ECG and clinical laboratorytest results. -Laboratory results outside the reference range must be documented asnot clinically significant by both the Investigator and Sponsor.

• Participants must have a diagnosis of FXS through molecular documentation of fullmutation of the FMR1 gene documented through genetic testing at Screening.

• Patients with a history of seizure disorders must currently be receiving treatmentwith a stable regimen of no more than two anti-seizure medications (ASMs) for thefour weeks preceding study Screening; or must be seizure-free for one year if notcurrently receiving ASMs.

• Patients taking psychoactive medication(s) should be on a stable regimen of not morethan three such medications for at least fours weeks preceding Screening and mustmaintain that regimen throughout the study. Psychoactive medications include (butare not limited to) antipsychotics, antidepressants, anxiolytics, attention-deficit / hyperactivity disorder (ADHD) medications, and medications for sleep.

• If patients are receiving non-pharmacological, behavioral and/or dietaryinterventions, they must be stable and have been doing so for three months prior toscreening.

• Patients have a body mass index between 12-30 kg/m2 (inclusive) and patients with abody mass index >30 kg/m2 and <40 kg/m2 with normal liver function laboratory valuesand with no immediate family history of fatty liver disease.

• Females of childbearing potential must have a negative serum pregnancy test at theScreening Visit and a negative serum or urine pregnancy test at all designatedvisits.

• Patients and parents/caregivers must be adequately informed of the nature and risksof the study and given written informed consent prior to Screening.

• Patients and parents/caregivers agree to abide by all study restrictions and complywith all study procedures, and in the Investigator's opinion, are reliable andwilling and able to comply with all protocol requirements and procedures.

Exclusion Criteria:

• Females who are pregnant, nursing or planning a pregnancy; females of childbearingpotential and male patients with a partner of childbearing potential who areunwilling or unable to use an acceptable method of contraception as outlined belowfor the duration of therapy and for three months after the last dose of studymedication. Standard acceptable methods of contraception include abstinence (definedas refraining from heterosexual intercourse from screening to three months after thelast dose of study medication: abstinence only applicable for females <18 years) orthe use of a highly effective method of contraception, including hormonalcontraception, diaphragm, cervical cap, vaginal sponge, condom, spermicide,vasectomy, or intrauterine device. The reliability of sexual abstinence needs to beevaluated in relation to the duration of the clinical trial and the preferred andusual lifestyle of the subject. Periodic abstinence (calendar, symptothermal,post-ovulation methods) is not an acceptable method of contraception.

• Patient has transitioned to independent living or living in a residential facilitysuch as a university setting or congregate care.

• History of significant allergic condition, significant drug-relatedhypersensitivity, or allergic reaction to any compound or chemical class related toZYN002 or its excipients.

• Exposure to any investigational drug or device less than or equal to 30 days priorto Screening or at any time during the study.

• Alanine aminotransferase (ALT), aspartate aminotransferase (AST) or total bilirubinlevels greater than or equal to 2 times the upper limit of normal or alkalinephosphatase levels greater than or equal to 3 times the upper limit of normal.

• Use of cannabis or any THC or CBD-containing product within 3 months of ScreeningVisit or during the study (aside from ZYN002).

• Patient has a positive drug screen, including ethanol, cocaine, THC, barbiturates,amphetamines (unless prescribed), benzodiazepines (except midazolam or comparableadministered for blood draws and ECG collection), and opiates.

• Patient is using the following AEDs (medications for the treatment of seizures and/or epilepsy): clobazam, phenobarbital, ethosuximide, felbamate, carbamazepine,phenytoin, or vigabatrin.

• Patient is using a strong inhibitor/inducer of CYP3A4 or sensitive substrate ofCYP3A4 including but not limited to the following medications: midazolam (exceptsingle doses administered for the purposes of obtaining blood samples and ECG's),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, St. John's Wort, and grapefruitJuice/products.

• Patients may not be taking any benzodiazepines (except single doses administered forthe purposes of obtaining blood samples and ECGs) at screening or throughout thestudy.

• Patient is expected to initiate or change pharmacologic or non-pharmacologicinterventions during the course of the study.

• Patient has an advanced, severe, or unstable disease that may interfere with thestudy outcome evaluations.

• Patient has acute or progressive neurological disease, psychosis, schizophrenia orany other psychiatric disorder or severe mental abnormalities (other than FXS) thatare likely to require changes in drug therapy or interfere with the study objectivesor ability to adhere to protocol requirements.

• Patient has a positive result for the presence of HBsAg, HCV, or HIV antibodies.

• Patient has known history of cardiovascular disease, advanced arteriosclerosis,structural cardiac abnormality, cardiomyopathy, serious heart rhythm abnormalities,coronary artery disease, cardiac conduction problems, exercise-related cardiacevents including syncope and pre-syncope, risk factors for Torsades de pointes (TdP) (e.g., heart failure, hypokalemia, family history of Long QT Syndrome), or otherserious cardiac problems.

• Any clinically significant condition or abnormal findings at the Screening Visitthat would, in the opinion of the Investigator, preclude study participation orinterfere with the evaluation of the study medication.

• Any skin disease or condition including eczema, psoriasis, melanoma, acne, contactdermatitis, scarring, imperfections, lesions, tattoos, or discoloration that mayaffect treatment application, application site assessments or absorption of thetrial drug.

• History of treatment for, or evidence of, drug abuse within the past year.

• Previous participation in a ZYN002 study (with the exception of patients who werescreen failures in Study ZYN2-CL-016 and did not enter Study ZYN2-CL-017).

• Patient responds "yes" to Question 4 or 5 on the C-SSRS (Children) during Screeningor at any time on study.