A Phase 1, Randomized, Double-Blind, Placebo-Controlled Single Ascending Dose Study to Assess the Pharmacokinetics, Safety and Tolerability of CBD Inhalation Aerosol in Healthy Adult Volunteers

Exclusion Criteria31

• History of any clinically significant gastrointestinal, renal, hepatic, neurologic, hematologic, endocrine, oncologic, pulmonary, immunologic, or cardiovascular disease, Gilbert’s syndrome, or other condition which would jeopardize safety or impact validity of results (in the opinion the Principal Investigator or delegate);
• Participant has any documented clinically significant infection, injury, or illness within 1 month prior to screening.
• Participant has any documented history of, or currently active, seizure disorder or history of clinically significant head injury
• Participant has an active malignancy of any type or has been diagnosed with cancer within 5 years prior to screening (excluding squamous or basal cell carcinoma of the skin).
• Any laboratory test results deemed clinically significant by the 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.
• Known upper respiratory tract infection within 2 weeks or lower respiratory tract infection within 4 weeks prior to screening, or any current or recent respiratory conditions, in the opinion the Investigator, might significantly alter the pharmacodynamic response to study drug.
• History or presence of active lung disease (i.e. asthma, chronic obstructive pulmonary disease [COPD], pulmonary fibrosis, hemoptysis, bronchiectasis) or prior intubation for respiratory illness.
• History of active tuberculosis or presence of active or latent tuberculosis
• History or presence of clinically significant psychiatric disorder or mental illness, as determined by the Investigator based on medical history, clinical interview, and/or relevant medical records. This includes but is not limited to schizophrenia spectrum disorders, bipolar disorder, major depressive disorder of moderate or greater severity within the past 2 years, or any current psychiatric condition that, in the Investigator’s opinion, could confound study results or pose additional risk to the participant. Past psychiatric conditions in sustained remission (e.g., a single moderate episode of major depressive disorder more than 2 years ago without recurrence) will not be exclusionary unless, in the Investigator’s judgment, there is a high likelihood of relapse during study participation.
• History of inherent cardiac abnormalities based on the opinion of the Principal Investigator or delegate.
• Clinically significant ECG abnormalities (Fridericia’s corrected QT interval [QTcF] more than 450 ms for males and more than 470 ms for females), PR more than 220 ms, QRS interval more than 120 ms at screening.
• Testing for any out-of-range values may be repeated once at the discretion of the Investigator.
• Participant has any documented history of a medical condition that, in the opinion of the Investigator, would compromise the participant’s ability to inhale, absorb, metabolize, or excrete test product.
• Liver function test results elevated more than 1.5-fold above the upper limit of normal (ULN) for gamma glutamyl transferase (GGT), bilirubin (total, conjugated and unconjugated), alkaline phosphatase (ALP), aspartate aminotransferase (AST) or alanine aminotransferase (ALT). Participants with ALP and/or ALT/AST above the limits specified may be included, at the discretion of the Investigator, if the levels are unaccompanied by clinical signs and are determined to be normal variants.
• Testing for any out-of-range values may be repeated once at the discretion of the Investigator.
• A calculated creatinine clearance of less than 60 mL/minuteat Screening according to the equation using Cockcroft and Gault.
• Testing for any out-of-range laboratory tests values may be repeated once at the discretion of the Investigator.
• Positive urine drug screen, urine cotinine and alcohol breath test and at screening or check-in.
• Testing may be repeated once at the discretion of the Investigator.
• Known allergic reactions to any excipient in the formulations.
• History of significant abuse of drugs such as marijuana, cocaine, phencyclidine (PCP), crack, opioid derivatives including heroin, and amphetamine derivatives within 1 year prior to screening.
• Use of marijuana (directly or indirectly) within 90 days prior to drug administration and during the course of the study.
• History of alcohol abuse within 6 months prior to screening or excessive alcohol use within 6 months prior to screening. Excessive alcohol use is defined as regular consumption of more than 14 units of alcohol per week.
• Use of medications for the timeframes specified below, with the exception of medications exempted by the Investigator on a case-by-case basis because they are judged unlikely to affect the PK profile of the study drug or participant safety (e.g., topical drug products without significant systemic absorption):
• Prescription medications (except for hormonal contraceptives) within 14 days prior to the first dose until end of the study;
• Monoamine oxidase inhibitors (MAOIs) within 28 days prior to dosing;
• Over-the-counter products and natural health products (including herbal remedies such as St. John’s wort, homeopathic and traditional medicines), and antacid preparations within 14 days prior to the first dose up to end-of-study. Vitamins used as nutritional supplements in non-therapeutic doses (judged by the qualified Investigator or designee) may be accepted, but they must be stopped at least 48 hours before dosing and during the study.
• Any drugs known to induce or inhibit hepatic and renal drug metabolism within 30 days prior to the first dose.
• Participation in a clinical research study involving the administration of an investigational or marketed drug or device within 30 days (or a minimum of 5 half-lives, whichever is longer) prior to the first dose, administration of a biological product in the context of a clinical research study within 90 days prior to the first dose, or concomitant participation in an investigational study involving no drug or device administration.
• Donation of plasma or platelets within 7 days prior to dosing or donation or loss of 500 mL or more of whole blood within 56 days prior to Day -1.
• Any reason which, in the opinion of the Principal Investigator or delegate, would prevent the participant from participating in the study.