Bioavailability Study of Midazolam Administered as a Solution by Conventional Syringe or ZENEO®

NCT05026567 | Completed Phase 1

• 1 other identifier: CJTPKL172001
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Primary objective of this study is to describe the plasma pharmacokinetics of midazolam after single intramuscular injection on bare skin in the thigh by the needle-free injector Zeneo® compared to injection on bare skin in the thigh by a conventional syringe (Reference) in terms of relative bioavailability and bioequivalence.

Conditions

Healthy

Outcome Measures

Primary Outcomes (3)

• Area under the plasma concentration versus time curve, time zero to time of the last quantifiable concentration (AUC0-t)

  up to 36hours

• Area under the plasma concentration versus time curve, with extrapolation to infinity (AUC0-∞)

  up to 36hours

• Maximum observed plasma concentration Cmax

  up to 36hours

Secondary Outcomes (9)

• Time to peak drug concentration (Tmax) of midazolam

  up to 36 hours

• Terminal half-life (T1/2) of midazolam

  up to 36 hours

• Time to peak drug concentration (Tmax) of 1'OH-midazolam

  up to 36 hours

• Terminal half-life (T1/2) of 1'OH-midazolam

  up to 36 hours

• Maximum observed plasma concentration (Cmax) 1'OH-midazolam

  up to 36 hours

Study Arms (4)

Reference Product A

ACTIVE COMPARATOR

Drug: 2 ml of DORMICUM® Midazolam Hydrochloride (15 mg/3 mL)

Experimental B

EXPERIMENTAL

Combination Product: ZENEO® Midazolam (10 mg/0.625 mL) on bare skin in thigh

Experimental C

EXPERIMENTAL

Combination Product: ZENEO® Midazolam (10 mg / 0.625 mL) on bare skin in ventrogluteal area

Experiment D

EXPERIMENTAL

Combination Product: ZENEO® Midazolam (10 mg / 0.625 mL) through clothing in thigh

Interventions

2 ml of DORMICUM® Midazolam Hydrochloride (15 mg/3 mL) DRUG

Intramuscular injection

Reference Product A

ZENEO® Midazolam (10 mg/0.625 mL) on bare skin in thigh COMBINATION_PRODUCT

Intramuscular injection

Experimental B

ZENEO® Midazolam (10 mg / 0.625 mL) on bare skin in ventrogluteal area COMBINATION_PRODUCT

Intramuscular injection

Experimental C

ZENEO® Midazolam (10 mg / 0.625 mL) through clothing in thigh COMBINATION_PRODUCT

Intramuscular injection

Experiment D

Eligibility Criteria

• Age: 18 Years - 59 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy males and females, 18 to 59 years (inclusive) at screening.
• Body Mass Index (BMI) between 18.5 and 29.9 kg/m2 (inclusive).
• Body mass weight between 50 and 110 kg (inclusive)
• Medical history, vital signs, physical examination, standard 12-lead electrocardiogram (ECG) and laboratory investigations must be clinically acceptable or within laboratory reference ranges for the relevant laboratory tests, unless the investigator considers the deviation to be irrelevant for the purpose of the study.
• Non-smokers or past-smokers who stopped at least 3 months before the study.
• Female subject must be either of
• non-childbearing potential: post-menopausal (defined as at least 1 year without any menses) prior to Screening, or documented surgically sterile or status post hysterectomy (at least 1 month prior to Screening).
• or, if of childbearing potential, must have a negative serum pregnancy test at Screening and must use two forms of birth control (at least one of which must be a barrier method) starting at Screening and throughout the study period and for 28 days \[or 5 half-lives of the study drug whichever is longer\] after the final study drug administration. Acceptable forms of birth control include: placement of a non-hormonal intrauterine device or intrauterine system, 2) barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) or abstinence of male/female intercourse if it is a part of normal practice in her life.
• The use of hormonal contraception in this study is not allowed. For male subjects contraception is not needed during this study.
• Injection sites must be clear of tattoos, scars and moles.
• Signed written consent given for participation in the study.

You may not qualify if:

• Any history or evidence of any clinically significant cardiovascular, gastrointestinal, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal, and/or other major disease, as judged by the Investigator.
• Medical history of malignant disease (with the exception of localized skin or cervical carcinoma that had been excised and cured)
• Any clinically significant abnormality following the Investigator's review of the physical examination, ECG and clinical study protocol-defined clinical laboratory tests at screening or admission to the clinical unit.
• A pulse \< 40 or \> 100 bpm; mean systolic blood pressure \> 140 mmHg; mean diastolic blood pressure \> 90 mmHg (measurements taken in triplicate after subject has been resting in supine position for 5 minutes.
• A mean corrected QT interval using Fridericia's formula (QTcF) interval \> 450 ms at screening. If the mean QTcF exceeds the limits above, one additional triplicate ECG may be taken. If this triplicate also gives an abnormal result, the subject should be excluded.
• History of smoking within 3 months prior to the first admission to the clinical unit.
• History of drinking more than 21 units of alcohol per week (1 unit = 10 g pure alcohol = 250 ml of beer \[5%\] or 35 ml of spirits \[35%\] or 100 ml of wine \[12%\]) within 3 months prior to the first admission to the clinical unit.
• Any recreational use of drugs-of-abuse within 3 months prior to the first administration of an IMP.
• Use of any prescribed or non-prescribed drugs (including vitamins, natural and herbal remedies, e.g., St. John's Wort) in the 2 weeks prior to first study medication administration, except for the occasional use of paracetamol (up to 2 g/day)- except if it will not affect the study outcome at the discretion of the investigator.
• Use of drugs that induce hepatic enzymes (rifampicin, rifabutin, carbamazepine, phenobarbitone, phenytoin, primidone, and aminoglutethimide).
• Use of inhibitors of the CYP3A4 enzyme (including but not only clarithromycin, itraconazole, erythromycin, fluconazole, verapamil). (https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers)
• Participation in any clinical study within 3 months prior to the expected date of enrolment into the clinical study, provided that the clinical study did not entail a biological compound with a long half-life or participation in more than 3 clinical studies within 12 months.
• Treatment within the previous 3 months before the first administration of IMP with any drug with a well-defined potential for adversely affecting a major organ or system.
• A major illness during the 3 months before commencement of the screening period.
• Relevant history or laboratory or clinical findings indicative of acute or chronic disease, likely to influence study outcome.

Sponsors & Collaborators

• Crossject: lead

Study Sites (1)

FARMOVS Pty Ltd

Bloemfontein, 9301, South Africa

Location

Related Publications (1)

• Lacombe O, Pletan Y, Grouin JM, Brennan A, Gire O. Relative Bioavailability Study of Midazolam Intramuscularly Administered with the Needle-Free Auto-Injector ZENEO(R) in Healthy Adults. Neurol Ther. 2024 Aug;13(4):1155-1172. doi: 10.1007/s40120-024-00627-4. Epub 2024 May 28.

  PMID: 38806873 DERIVED

Study Officials

• EFW Krantz, PhD

  Farmovs

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 19, 2021
• First Posted: August 30, 2021
• Study Start: May 9, 2022
• Primary Completion: July 14, 2022
• Study Completion: July 15, 2022
• Last Updated: July 22, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

ZA (1)