Study of Midazolam in Healthy Adults

Study Overview
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Brief Summary
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This study is a phase 1, open-label, crossover, comparison study to evaluate the safety and pharmacokinetics (PK) of a single IM administration of 10 mg midazolam using Rafa's auto-injector compared with seizalam in healthy adults. All subjects will participate in both study periods which will span 28 days following a pre study screening visit.

Official Title
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Phase 1, Open-Label, Comparison Study to Evaluate the Safety and Pharmacokinetics of a Single Intramuscular Administration of 10 mg Midazolam Using an Auto-Injector vs Marketed Midazolam Vials in Healthy Adults.

Conditions
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Status Epilepticus

Intervention / Treatment
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* Combination Product: Midazolam
* Drug: Seizalam


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Can understand and provide signed informed consent Is a healthy male or healthy, non-pregnant, non-lactating female whose screening, physical exam, labs, vitals, and ECG are within normal range Has a willingness to comply and be available for all protocol procedures Is between age 18 and 55 years, inclusive on the day of injection If the subject is female and of childbearing potential, she has a negative serum pregnancy test at screening and negative urine test within 24 hours prior to injection Note: A woman is considered of childbearing potential unless post-menopausal (≥ 1 year without menses) or surgically sterilized via bilateral oophorectomy, or hysterectomy or bilateral tubal ligation or successful Essure placement with documented confirmation test at least 3 months after the procedure If the subject is female and of childbearing potential, she agrees to practice abstinence from sexual intercourse with men or use acceptable contraception up to 1 month after the end of study visit Note: Acceptable contraception methods are restricted to effective devices (approved oral contraceptives, Intrauterine Contraceptive Devices, NuvaRing®) If the subject is male, he agrees to practice abstinence from sexual intercourse with women or use acceptable contraception up to 1 month after the end of study visit Has a body mass index (BMI) ≥18.0 and ≤26.0 kg/m2 at screening Has a negative urine drug screen Has a negative breathalyzer test Subject is not taking any medications or St. John's wort and agrees to avoid grapefruit juice and alcohol until study completion on Day 28 Subject agrees to not take any vitamins or supplements 48 hours prior to dosing Is available for follow-up for the duration of the study Exclusion Criteria: Received treatment with another investigational drug within 28 days of initial dosing Has a current or history of drug and /or alcohol abuse Is pregnant or breastfeeding woman Has hypersensitivity or allergy to midazolam Has hypersensitivity or allergy to benzodiazepines Has a history of cardiovascular, pulmonary, neurological, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, or psychiatric disease or any other reason, in the opinion of the investigator, that the patient should not participate Tests positive for HIV-1, HIV-2, HbsAg, hepatitis C antibody, or syphilis Has had a blood donation in the 8 weeks prior to the study period start date

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Midazolam Injection<br>Midazolam injection, 10 mg | Combination Product: Midazolam<br>* Midazolam Injection, 10mg<br>|
| Active Comparator: Seizalam™<br>Seizalam, 10 mg | Drug: Seizalam<br>* Seizalam, 10 mg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| number of participants with local injection site changes |  | 28 days | 
| number of participants with systemic changes in physical exam |  | 28 days | 
| number of participants with vital signs changes resulting in a serious adverse event |  | 28 days | 
| number of participants with ECG changes resulting in a serious adverse event |  | 28 days | 
| number of participants with laboratory changes resulting in a serious adverse event |  | 28 days | 
| time to reach Cmax (Tmax) will be obtained directly from the plasma concentration-time profile data for each patient following IM injection |  | 28 days | 
| The elimination rate constant (ke) will be estimated |  | 28 days | 
| The AUC from time 0 to the time of the last measurable concentration (AUC0-last) and the AUC from time zero to infinite time (AUC0-∞) |  | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relative bioavailability will be obtained by analysis of Cmax |  | 28 days | 
| Relative bioavailability will be obtained by analysis of AUC0-last |  | 28 days | 
| Relative bioavailability will be obtained by analysis of AUC0-∞ |  | 28 days |