A Phase 2 Study of BRP-180 in Patients with Narcolepsy

Exclusion Criteria29

• Concomitant diagnosis of other sleep disorders other than narcolepsy
• History of severe allergic or anaphylactic reactions, known intolerance, allergy or hypersensitivity reactions to bupropion.
• History of coronary disease, peripheral vascular disease, cerebrovascular accident, transient ischaemic attack, uncontrolled hypertension or signs/symptoms of ischaemic heart disease.
• Narcolepsy secondary to another neurological pathology or presence of a comorbid neurological pathology (multiple sclerosis, Steinert's myotonic dystrophy, head trauma, epilepsy)
• History of neurologic conditions such as seizures or convulsive disorders (including epilepsy), severe head injury or increased intracranial pressure. A history of childhood febrile seizures is allowed.
• Presence of current psychiatric condition or psychiatric condition leading to exclusion from the study based on the opinion of the Investigator/Sub-investigator.
• Malignancy within 5 years of screening visit (excluding non-melanoma skin cancer that has been resected).
• Current or prior diagnosis of bulimia or anorexia nervosa
• A calculated creatinine clearance of < 85 mL/minute at screening or pre randomisation according to the equation using Cockcroft and Gault.
• Liver function tests showing values for ALT or AST > 2.5 times ULN at Screening.
• Patients with Child-Pugh Class B and C liver disease, and Model for End-Stage Liver Disease (MELD) score = 10
• Evidence or history of clinically significant (in the opinion of the Investigator/Sub-Investigator) other cardiovascular, pulmonary, neurologic or renal disorders or hepatic, gastrointestinal, oral (difficulty swallowing / taking oral medication), haematological, endocrine, or psychiatric impairment/disorders.
• Any laboratory test results deemed clinically significant by the Investigator/Sub-Investigator or positive test serology test results for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, or human immunodeficiency virus (HIV) antigen and antibody at screening.
• CSSR-S score = 10 for the Columbia Suicide Severity Rating Scale (C-SSRS).
• Have undergone surgery requiring or have received (for any reason) anaesthetic within 42 days of Day 0, or planned surgery during the study.
• History of significant alcohol abuse within 1 year prior to screening or regular use of alcohol within 6 months prior to the screening visit that exceeds 14 units of alcohol per week (1 unit = 150 mL of wine, 375 mL of mid strength beer, or 30 mL of distilled alcohol 40%).
• Positive results for the urine drugs of abuse test or a positive alcohol breath test at screening or Day 0.
• Screening urine drug test/alcohol breath testing may be repeated once if deemed appropriate by the Investigator/Sub-Investigator.
• Unwilling or unable to abstain from recreational drug/substance use, from 48 hours before check-in until final study visit. This does not include nicotine containing substances.
• Use of medications for the timeframes specified below:
• a. Use of any over the counter product, herbal product, diet aid, or hormone supplement (except oral contraception pills) and hormone replacement therapy, within 14 days of the first study drug administration (Day 0) and throughout the duration of the study, unless approved by both the Investigator/Sub-Investigator and Medical Monitor (in writing). If necessary, paracetamol (acetaminophen) or ondansetron (or other 5-HT3 receptor antagonist) may be administered with the approval of the Investigator/Sub-Investigator.
• b. CNS depressants including opioids, sedative, anxiolytics, hypnotics, neuroleptics, phenothiazines, tranquilisers, skeletal muscle relaxants, sedating antihistamines or cimetidine within 42 days of the first study drug administration (Day 0).
• c. Monoamine Oxidase Inhibitors (MAOIs) within 42 days of the first study drug administration (Day 0).
• d. Use of macrolide antibiotics (e.g., Erythromycin), azole antifungal agents (e.g., Ketoconazole) or protease inhibitors (e.g., Ritonavir) within 42 days of the first study drug administration (Day 0). Thirty-day washout from these medications is required.
• e. Natural health products (including herbal remedies such as St. John’s wort, homeopathic and traditional medicines), and antacid preparations within 42 days of the first dose administration (Day 0) and throughout the duration of the study. Vitamins and dietary supplements used as nutritional supplements in non-therapeutic doses (judged by the qualified Investigator/Sub-Investigator) must be stopped at least 14 days before the first study drug administraion and throughout the duration of the study).
• f. Any drugs known to induce or inhibit hepatic and renal drug metabolism within 42 days of the first study drug administration (Day 0) and throughout the duration of the study.
• g. Use of any enzyme-modifying drugs and/or other products, including strong inhibitors of cytochrome P450 (CYP) enzymes (e.g., cimetidine, fluoxetine, quinidine, erythromycin, ciprofloxacin, fluconazole, ketoconazole, diltiazem and HIV antivirals) and strong inducers of CYP enzymes (e.g., barbiturates, carbamazepine, glucocorticoids, phenytoin, St. John´s Wort, and rifampicin) within 42 days of the first study drug administration (Day 0) and throughout the duration of the study.
• h. Treatment with another investigational drug, investigational device, or approved therapy for investigational use within 1 month or 5 half-lives of the specific drug/biologic (whichever is longer) prior the first study drug administration (Day 0) and throughout the duration of the study.
• Any reason which, in the opinion of the Investigator/Sub-Investigator, would prevent the patient from participating in the study.