An Open-label, Two-Part, Partially Randomized Single-Dose Crossover Study Evaluating the Safety, Tolerability, and Pharmacokinetics of L-dipivefrin (IN-001) Sublingual Spray in Comparison to Epinephrine 0.3 mg Manual Intramuscular Injection and Epinephrine 0.3 mg Auto-injection in Healthy Adult Volunteers Under Fasted Conditions
This is an open-label, two-part study to assess the pharmacokinetics (PK) and pharmacodynamics (PD) of epinephrine administered as a single dose of L-dipivefrin (IN-001) sublingual spray in healthy adults. For both parts of the study, participants will undergo at least 10 hours of fasting prior to dosing. Part 1 of the study focuses on IN-001 dose/formulation exploration in a small number of participants (N=6) to help select the most appropriate dose/formulation to be used in Part 2 of the study in a larger number of participants (N=24).
• To participate in this trial, volunteers must meet all of the inclusion criteria listed below:
‣ Age \> 18 years of age and \< 45 years of age.
⁃ Women of childbearing potential or men with childbearing potential partners must agree that the participant and/or their partner will use the following effective methods of birth control from screening visit until 14 days after the last dose of study drug:
• Abstinence
∙ Hormonal contraceptives for at least one month prior to Screening
∙ Double barrier (e.g., diaphragm with spermicide, condom with spermicide)
∙ Intrauterine device (IUD)
∙ Surgically sterile (e.g., bilateral tubal ligation, total or partial hysterectomy, or bilateral oophorectomy)
⁃ Note: Females will be considered post-menopausal if they
∙ are at least 45 years of age with amenorrhea for at least one year, or
‣ received bilateral oophorectomy with or without a hysterectomy.
⁃ BMI \> 18.50 and \< 29.90 kg/m2 (using formula BMI = weight (kg)/height (m2).
⁃ All clinical laboratory test results (e.g., hematology, chemistry, urinalysis) are within normal limits or considered not clinically significant by Investigator.
⁃ Serum pseudocholinesterase activity is within normal limits or considered not clinically significant by Investigator.
⁃ Physical examination (excluding genital and rectal exams) is normal or considered not clinically significant by Investigator.
⁃ Vital signs measurements (pulse rate, blood pressure, temperature, and respiratory rate) are normal or considered not clinically significant by Investigator, while seated or semi-recumbent and after 5 minutes of rest. Normal vital sign ranges are listed below:
• Systolic blood pressure: 90 - 140 mmHg
∙ Diastolic blood pressure: 50 - 90 mmHg
∙ Pulse rate: 45 - 100 beats per minute (bpm)
∙ Oral body temperature: 35.0°C - 37.5°C
⁃ 12-lead electrocardiogram (ECG) is normal or considered not clinically significant by Investigator.
⁃ Participants must agree to not consume caffeine and/or xanthine containing products (i.e., coffee, tea, chocolate, caffeine-containing sodas, etc.), grapefruit and grapefruit containing products, and poppyseed containing foods within 48 hours prior to Period 1 check-in.
‣ Able to comply with study procedures, in the opinion of the Investigator(s).
‣ Willing to provide written consent for screening procedures. Legally authorized representatives will not be allowed to sign on behalf of participants in this trial.