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

Kokua Pharma Inc.

Status and phase: Completed; Phase 1

Conditions: Acute Allergic Reaction; Anaphylaxis

Treatments: Drug: Placebo; Drug: KP001

Study type: Interventional

Funder types: Other

Identifiers

NCT06963411

KP001-101

Details and patient eligibility

About

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

Full 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

Enrollment: 16 patients

Sex: All

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

1. Males or females, non-smoker (no use of tobacco or nicotine products within 3 months prior to screening), aged ≥ 18 to ≤ 45 years.
2. 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.
3. 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.
4. Normal lung function measured by spirometry.
5. Demonstrated ability to successfully complete pressurized metered dose inhaler (pMDI) training.
6. Demonstrated ability to successfully hold their breath for a minimum of 30 seconds.

Key Exclusion Criteria:

1. Positive urine drug screen, urine cotinine test, or alcohol breath test, at screening.
2. Known reaction or sensitivity to sympathomimetic amines, or idiosyncratic reaction to epinephrine or any of the ingredients of KP001, placebo.
3. History of anaphylaxis or other severe allergic reactions (e.g., angioedema)
4. 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.
5. 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.
6. 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.
7. Use of any tobacco or nicotine-containing products within 3 months prior to screening.
8. Use of any inhaled products, including vaping and water pipes (Hookahs) within 6 months prior to screening.
9. 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.
10. A depot injection or implant of any drug (other than hormonal contraceptives) within 3 months prior to dosing.
11. Monoamine oxidase (MAO) inhibitors within 30 days prior to dosing.
12. Positive test for human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBsAg) at screening.
13. Abnormal clinical laboratory findings, vital signs, or ECG
14. Females who are pregnant or lactating, or who have a positive pregnancy test at screening or admission.
15. 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.
16. 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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16 participants in 3 patient groups

Treatment Arm A: Two Treatments

Experimental group

Description:

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:

Drug: KP001

Drug: Placebo

Treatment Arm B: Four Treatments

Experimental group

Description:

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:

Drug: KP001

Drug: Placebo

Treatment Arm C: Breath Hold

Experimental group

Description:

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:

Drug: KP001

Drug: Placebo