Study of Midazolam in Healthy Adults

• ClinicalTrials.gov Identifier: NCT04679623
• Recruitment Status: Not yet recruiting
• First Posted: December 22, 2020
• Last Update Posted: March 29, 2021
• Sponsor: Rafa Laboratories
• Collaborators: Ology Bioservices; Joint Project Management Office for Chemical, Biological, Radiological, and Nuclear Medical
• Information provided by (Responsible Party): Rafa Laboratories

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Status Epilepticus	Combination Product: Midazolam; Drug: Seizalam	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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.
• Estimated Study Start Date: May 3, 2021
• Estimated Primary Completion Date: June 15, 2021
• Estimated Study Completion Date: July 20, 2021

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. number of participants with local injection site changes [ Time Frame: 28 days ]
2. number of participants with systemic changes in physical exam [ Time Frame: 28 days ]
3. number of participants with vital signs changes resulting in a serious adverse event [ Time Frame: 28 days ]
4. number of participants with ECG changes resulting in a serious adverse event [ Time Frame: 28 days ]
5. number of participants with laboratory changes resulting in a serious adverse event [ Time Frame: 28 days ]
6. time to reach Cmax (Tmax) will be obtained directly from the plasma concentration-time profile data for each patient following IM injection [ Time Frame: 28 days ]
7. The elimination rate constant (ke) will be estimated [ Time Frame: 28 days ]
8. 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-∞) [ Time Frame: 28 days ]

Secondary Outcome Measures :

1. Relative bioavailability will be obtained by analysis of Cmax [ Time Frame: 28 days ]
2. Relative bioavailability will be obtained by analysis of AUC0-last [ Time Frame: 28 days ]
3. Relative bioavailability will be obtained by analysis of AUC0-∞ [ Time Frame: 28 days ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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

Contacts and Locations

No Contacts or Locations Provided

More Information

• Responsible Party: Rafa Laboratories
• ClinicalTrials.gov Identifier: NCT04679623
• Other Study ID Numbers: RLM-559-01
• First Posted: December 22, 2020
• Last Update Posted: March 29, 2021
• Last Verified: March 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: Yes

Additional relevant MeSH terms:

Status Epilepticus; Seizures; Neurologic Manifestations; Nervous System Diseases; Midazolam; Adjuvants, Anesthesia; Hypnotics and Sedatives; Central Nervous System Depressants; Physiological Effects of Drugs; Anti-Anxiety Agents; Tranquilizing Agents; Psychotropic Drugs; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; GABA Modulators; GABA Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action