Phase 1 Crossover Study Evaluating the Safety, Tolerability, and Pharmacokinetics of KP001 in Healthy Adult Volunteers
- Registration Number
- NCT06963411
- Lead Sponsor
- Kokua Pharma Inc.
- Brief Summary
The goal of this clinical trial is to evaluate the safety, tolerability, and pharmacokinetics (PK) of several KP001 dose regimens to identify a treatment regimen with a PK profile that safely meets or exceeds the PK profile of existing injected epinephrine products. The main questions it aims to answer are:
* To evaluate any carryover effect with a 7-day washout of different dose regimens of KP001 in healthy adult volunteers.
* To evaluate the safety, tolerability and PK of different dose regimens of KP001 in healthy adult volunteers.
* To explore the safety, tolerability and PK of one KP001 dose regimen without inhalation (breath holding).
Participants will:
* Be admitted to clinical research unit (Day -1) and receive treatment the following day (Day 1) and then will be discharged
* Visit the clinic on Days 2 \& 3 post dose for required assessments
* Visit the clinic 6 days post their last dose for dosing and repeated until 5 dosing visits have been completed
* Visit the clinic for a safety follow-up visit approximately 1 week from last dose administered
- Detailed Description
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
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 16
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Treatment Arm A: Two Treatments KP001 Subjects will receive two sets of treatments of 0.25 mg (2 inhalations of 0.125 mg each time) of KP001 (or matching placebo) over 2 visits separated by a 1-week washout period. Investigational Product (IP) will be delivered as 1 set of 2 inhalations (2 total) spaced approximately 10 seconds apart. Subjects will repeat Arm therefore total dose in mg for Arm = 0.5 mg. Treatment Arm A: Two Treatments Placebo Subjects will receive two sets of treatments of 0.25 mg (2 inhalations of 0.125 mg each time) of KP001 (or matching placebo) over 2 visits separated by a 1-week washout period. Investigational Product (IP) will be delivered as 1 set of 2 inhalations (2 total) spaced approximately 10 seconds apart. Subjects will repeat Arm therefore total dose in mg for Arm = 0.5 mg. Treatment Arm B: Four Treatments KP001 Subjects will receive four sets of treatments of 0.25 mg (2 inhalations of 0.125 mg each time), totaling 1.0mg of KP001 (or matching placebo) over 2 visits separated by a 1-week washout period. IP will be delivered as 4 sets of 2 inhalations (8 total) spaced approximately 10 seconds apart. Each set of 2 inhalations will be spaced approximately 2 minutes apart. Subjects will repeat Arm therefore total dose in mg for Arm = 2.0 mg. Treatment Arm B: Four Treatments Placebo Subjects will receive four sets of treatments of 0.25 mg (2 inhalations of 0.125 mg each time), totaling 1.0mg of KP001 (or matching placebo) over 2 visits separated by a 1-week washout period. IP will be delivered as 4 sets of 2 inhalations (8 total) spaced approximately 10 seconds apart. Each set of 2 inhalations will be spaced approximately 2 minutes apart. Subjects will repeat Arm therefore total dose in mg for Arm = 2.0 mg. Treatment Arm C: Breath Hold KP001 Subjects will receive 0.5 mg of KP001 (or matching placebo) delivered as 4 rapidly administered sequential inhalations (4 total), dosed approximately 5 seconds apart, spaced over approximately 15 seconds while holding their breath during the entire dosing treatment and after treatment for a total minimum 30 seconds (or longer) before exhaling. Total dose in mg for Arm = 0.5 mg. Treatment Arm C: Breath Hold Placebo Subjects will receive 0.5 mg of KP001 (or matching placebo) delivered as 4 rapidly administered sequential inhalations (4 total), dosed approximately 5 seconds apart, spaced over approximately 15 seconds while holding their breath during the entire dosing treatment and after treatment for a total minimum 30 seconds (or longer) before exhaling. Total dose in mg for Arm = 0.5 mg.
- Primary Outcome Measures
Name Time Method Area under the concentration-time curve from time zero to infinity (AUC0-inf) 1 hour pre-dose to 6 hours post-dose on Day 1, 8, 15, 22 and 29 Blood samples for PK collected at pre dose (-60, -30, -15 mins prior to dosing) and 1, 2, 3, 5, 7, 9, 12, 15, 20, 30, 45, 60, 90 min postdose and, 2-, 6 hours post-dose.
The maximal observed plasma concentration (Cmax) 1 hour pre-dose to 6 hours post-dose on Day 1, 8, 15, 22 and 29 Blood samples for PK collected at pre dose (-60, -30, -15 mins prior to dosing) and 1, 2, 3, 5, 7, 9, 12, 15, 20, 30, 45, 60, 90 min postdose and, 2-, 6 hours post-dose.
Area under the concentration-time curve from time zero to last measurable concentration (AUC0-t) 1 hour pre-dose to 6 hours post-dose on Day 1, 8, 15, 22 and 29 Blood samples for PK collected at pre dose (-60, -30, -15 mins prior to dosing) and 1, 2, 3, 5, 7, 9, 12, 15, 20, 30, 45, 60, 90 min postdose and, 2-, 6 hours post-dose.
Time when the maximal plasma concentration is observed (Tmax) 1 hour pre-dose to 6 hours post-dose on Day 1, 8, 15, 22 and 29 Blood samples for PK collected at pre dose (-60, -30, -15 mins prior to dosing) and 1, 2, 3, 5, 7, 9, 12, 15, 20, 30, 45, 60, 90 min postdose and, 2-, 6 hours post-dose.
Rate at which drug is removed from the body (Kel) 1 hour pre-dose to 6 hours post-dose on Day 1, 8, 15, 22 and 29 Blood samples for PK collected at pre dose (-60, -30, -15 mins prior to dosing) and 1, 2, 3, 5, 7, 9, 12, 15, 20, 30, 45, 60, 90 min postdose and, 2-, 6 hours post-dose.
Half-life of drug (T1/2) 1 hour pre-dose to 6 hours post-dose on Day 1, 8, 15, 22 and 29 Blood samples for PK collected at pre dose (-60, -30, -15 mins prior to dosing) and 1, 2, 3, 5, 7, 9, 12, 15, 20, 30, 45, 60, 90 min postdose and, 2-, 6 hours post-dose.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
Syneos HealthClinique Inc.
🇨🇦Quebec City, Quebec, Canada