Study of Midazolam in Healthy Adults

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.

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.

Study Overview

• Status: Completed
• Conditions: Status Epilepticus
• Intervention / Treatment: Combination product: Midazolam; Drug: Seizalam

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Raleigh, North Carolina, United States, 27612
      • Wake Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 53 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Can understand and provide signed informed consent
2. Is a healthy male or healthy, non-pregnant, non-lactating female whose screening, physical exam, labs, vitals, and ECG are within normal range
3. Has a willingness to comply and be available for all protocol procedures
4. Is between age 18 and 55 years, inclusive on the day of injection
5. 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
6. 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®)
7. 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
8. Has a body mass index (BMI) ≥18.0 and ≤26.0 kg/m2 at screening
9. Has a negative urine drug screen
10. Has a negative breathalyzer test
11. 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
12. Subject agrees to not take any vitamins or supplements 48 hours prior to dosing
13. Is available for follow-up for the duration of the study

Exclusion Criteria:

1. Received treatment with another investigational drug within 28 days of initial dosing
2. Has a current or history of drug and /or alcohol abuse
3. Is pregnant or breastfeeding woman
4. Has hypersensitivity or allergy to midazolam
5. Has hypersensitivity or allergy to benzodiazepines
6. 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
7. Tests positive for HIV-1, HIV-2, HbsAg, hepatitis C antibody, or syphilis
8. Has had a blood donation in the 8 weeks prior to the study period start date

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Midazolam Injection; Midazolam injection, 10 mg	Combination product: Midazolam; Midazolam Injection, 10mg
Active Comparator: Seizalam™; Seizalam, 10 mg	Drug: Seizalam; Seizalam, 10 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Rafa Laboratories
• Collaborators: Ology Bioservices; Joint Project Management Office for Chemical, Biological, Radiological, and Nuclear Medical

Study record dates

Study Major Dates

• Study Start (Actual): June 9, 2021
• Primary Completion (Actual): September 17, 2021
• Study Completion (Actual): September 17, 2021

Study Registration Dates

• First Submitted: December 15, 2020
• First Submitted That Met QC Criteria: December 17, 2020
• First Posted (Actual): December 22, 2020

Study Record Updates

• Last Update Posted (Actual): March 17, 2022
• Last Update Submitted That Met QC Criteria: March 2, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Seizures; Status Epilepticus; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Midazolam
• Other Study ID Numbers: RLM-559-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes