Clinical Study of Synthetic Cannabidiol in Children and Adolescents with 22q11.2 Deletion Syndrome

Exclusion Criteria26

• 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 three months after the last dose of study medication.
• a. 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, vasectomy, or intrauterine device.
• History of significant allergic condition, significant drug-related hypersensitivity, or allergic reaction to any compound or chemical class related to ZYN002 or its excipients.
• Exposure to any investigational drug or device less than or equal to 30 days prior to Screening or at any time during the study.
• Patient has alanine aminotransferase (ALT), aspartate aminotransferase (AST), or total bilirubin levels less than or equal to 2 times the upper limit of normal (ULN) or has alkaline phosphatase levels less than or equal to 3 times the ULN as determined from Screening safety laboratories.
• Use of cannabis or any THC or CBD-containing product within three months of Screening Visit or during the study.
• Patient has a positive drug screen for sympathomimetic amines (amphetamines (unless prescribed); benzodiazepines; buprenorphine; cannabinoids; methadone; cocaine (metabolites); and opiates; (excludes midazolam used at blood draws, and barbiturates used as AED medication), including ethanol.
• Patient is using the following AEDs: phenobarbital, ethosuximide, felbamate, or vigabatrin.
• Patient is using any strong inhibitor/inducer of CYP3A4 or sensitive substrate for CYP3A4 including but not limited to the following medications: midazolam (except single 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, and St. John’s Wort.
• Patient with diagnosis of known genetic disorder, other than 22qDS (i.e. Prader-Willi Syndrome, Angelman Syndrome, Fragile X Syndrome, Rett Syndrome etc.).
• Patient has diagnosis of DiGeorge or Velocardiofacial syndrome without the presence of 22qDS.
• Patient has a primary psychiatric diagnosis other than 22qDS or anxiety, including bipolar disorder, psychosis, schizophrenia, post-traumatic stress disorder (PTSD) or major depressive disorder.
• Patients is on stable treatment of >6 months of not more than two psychoactive medications at screening or throughout the study (with the exception of one psychoactive medication prescribed for sleep).
• Patient has an advanced, severe, or unstable disease that may interfere with the study outcome evaluations.
• Patient is expected to initiate or change pharmacologic or non-pharmacologic interventions during the course of the study.
• Patient has an acute or progressive neurological disease, or any psychiatric disorder or severe mental abnormalities that are likely to require changes in drug therapy or interfere with the objectives of the study or ability to adhere to protocol requirements.
• Patient has a positive result for the presence of HBsAg, HCV, or HIV antibodies.
• Patients at risk of needing cardiovascular surgical repair within the upcoming 12 months.
• Patient has unstable cardiovascular disease, such as advanced arteriosclerosis, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, cardiac conduction problems, exercise-related cardiac events including syncope and pre-syncope, risk factors for Torsades de pointes (TdP) (e.g., heart failure, hypokalemia, family history of Long QT Syndrome), other serious or other clinically unstable cardiac problems.
• Clinically unstable cardiovascular disease as indicated by history, physical examination or ECG.
• Presence of a moderate or severe surgically uncorrected structural cardiac abnormality.
• History of major congenital heart disease including those who had surgical repair. Congenital heart disease is defined by classification of complex (fontan circulation, hypoplastic left heart, double inlet ventricle, double outlet right ventricle, Eisenmenger’s syndrome, mitral atresia, tricuspid atresia, pulmonary atresia (with or without intact ventricular septum) , congenitally corrected transposition of great arteries, complete atrioventricular septal defect, truncus arteriosus, other single ventricle physiology, other cyanotic congenital heart disease), moderate (transposition of great vessels, tetralogy of fallot, total or partial anomalous pulmonary venous drainage, Ebstein’s anomaly, coarctation of aorta, aortic stenosis, pulmonary stenosis, ostium primum atrial septal defect, sinus of valsalva fistula/aneurysm) or simple (ventricular septal defect, atrial septal defect, persistent ductus arteriosus, mild pulmonary stenosis).
• 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 medication.
• Any skin disease or condition, including eczema, psoriasis, melanoma, acne, contact dermatitis, scarring, imperfections, lesions, tattoos, or discoloration, that may affect treatment application, application site assessments, or absorption of the study drug.
• History of treatment for, or evidence of, drug abuse within the past year.
• Patient responds “yes” to Question ‘4’ or ‘5’ on the C-SSRS (Children) during Screening or at any time on study.