Phase 1 Crossover Study Evaluating the Safety, Tolerability, and Pharmacokinetics of KP001 in Healthy Adult Volunteers

This study is a 5-period crossover design to evaluate the safety, tolerability, and PK of KP001 compared to placebo and to evaluate for the potential for carryover effect (Arms A & B). An exploratory 3rd arm (Arm C) will evaluate the PK of KP001 when breath holding to replicate an unconscious patient situation, and results will be used to design a possible future breath-holding study. Sequence will be either AABBC or BBAAC. Two doses of KP001 (0.25 mg or 1.0 mg) or placebo will be administered to 16 subjects (12 active and 4 placebo subjects) on two separate occasions, separated by a 1-week washout period. A third arm will evaluate one dose of KP001 (0.5 mg) PK while breath holding.

The total study duration for subjects will be up to 11 weeks, consisting of:

• Participation in up to 6-week screening period
• Attendance of 5 in-patient dosing visits, separated by 1 week
• Attendance of 1-week post-treatment follow up period

Key Inclusion Criteria:

• Males or females, non-smoker (no use of tobacco or nicotine products within 3 months prior to screening), aged ≥ 18 to ≤ 45 years.
• A Body Mass Index (BMI) ≥18.5 and ≤ 30 kg/m^2, with body weight, ≥ 50.0 kg for males and ≥ 45.0 kg for females.
• Healthy as defined by a) the absence of clinically significant illness and surgery within 4 weeks prior to study drug administration. b) the absence of clinically significant history of neurological, endocrine, cardiovascular, respiratory, hematological, immunological, psychiatric, gastrointestinal, renal, hepatic, and metabolic disease.
• Normal lung function measured by spirometry.
• Demonstrated ability to successfully complete pressurized metered dose inhaler (pMDI) training.
• Demonstrated ability to successfully hold their breath for a minimum of 30 seconds.

Key Exclusion Criteria:

• Positive urine drug screen, urine cotinine test, or alcohol breath test, at screening.
• Known reaction or sensitivity to sympathomimetic amines, or idiosyncratic reaction to epinephrine or any of the ingredients of KP001, placebo.
• History of anaphylaxis or other severe allergic reactions (e.g., angioedema)
• Surgical procedures within 90 days of admission that could result in confounding of results or additional risk to the subject, per the judgment of the Investigator.
• History or presence of alcohol abuse or drinking more than 2 standard drinks per day/10 standard drinks per week for women or 3 standard drinks per day/15 standard drinks per week for men; or a positive alcohol breath test at screening or admission.
• History or presence of drug abuse/dependence (not including nicotine and caffeine) within the previous 1 year or a positive urine drug test at screening or admission.
• Use of any tobacco or nicotine-containing products within 3 months prior to screening.
• Use of any inhaled products, including vaping and water pipes (Hookahs) within 6 months prior to screening.
• Use of any prescription medications within 14 days prior to admission, or over-the-counter medications (including herbal remedies and supplements) within 7 days prior to admission, with the exception of the occasional use of acetaminophen (up to 2 g daily), or an anticipated need to use them during the study.
• A depot injection or implant of any drug (other than hormonal contraceptives) within 3 months prior to dosing.
• Monoamine oxidase (MAO) inhibitors within 30 days prior to dosing.
• Positive test for human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBsAg) at screening.
• Abnormal clinical laboratory findings, vital signs, or ECG
• Females who are pregnant or lactating, or who have a positive pregnancy test at screening or admission.
• Donated plasma within 7 days prior to screening, or donation or loss of whole blood (excluding the volume drawn during screening for this study) as follows: 50 to 499 mL of whole blood within 30 days prior to screening, or ≥ 500 mL of whole blood within 56 days prior to screening.
• Participation in another clinical study involving an investigational drug within 30 days prior to screening, an investigational biologic within 90 days prior to screening, or current/planned participation in another interventional study during this study.