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

• Status: Not yet recruiting
• Trial end date: 2022-03-01
• Target enrollment: 0
• Participant gender: All

Summary

Primary objective of this study is

• To demonstrate whether an intramuscular (i.m.) injection of the test product (10 mg / 0.625 mL) on bare skin in the thigh, and the i.m. injection of either the reference product, HYPNOVEL® (10 mg/ 2 mL) or the i.m. injection of 2mL of the reference product, DORMICUM® (15 mg/ 3 mL) or the i.m injection of 2mL of the reference product, DORMICUM® (5 mg/ 1 mL) administered with a conventional syringe in the thigh on bare skin, are bioequivalent

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Crossject
• Treatments: Midazolam

Criteria

Inclusion Criteria:

1. Healthy males and females, 18 to 59 years (inclusive) at screening.

2. Body Mass Index (BMI) between 18.5 and 29.9 kg/m2 (inclusive).

3. Body mass weight between 65 and 110 kg (inclusive)

4. 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.

5. Non-smokers or past-smokers who stopped at least 3 months before the study.

6. 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.

7. Injection sites must be clear of tattoos, scars and moles.

8. Signed written consent given for participation in the study.

Exclusion Criteria:

A subject will not be eligible for study participation if he/she meets any of the following criteria:

1. 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.

2. Medical history of malignant disease (with the exception of localized skin or cervical carcinoma that had been excised and cured)

3. 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.

4. 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.

5. 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.

6. History of smoking within 3 months prior to the first admission to the clinical unit.

7. 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.

8. Any use of drugs-of-abuse within 3 months prior to the first admission to the clinical unit.

9. 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.

10. 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 t1/2 or participation in more than 3 clinical studies within 12 months.

11. 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.

12. A major illness during the 3 months before commencement of the screening period.

13. Relevant history or laboratory or clinical findings indicative of acute or chronic disease, likely to influence study outcome.

14. Any significant blood loss, donated one unit (450 m) of blood or more, or received a transfusion of any blood or blood products within 60 days, or donated plasma within 7 days prior to the first admission to the clinical unit.

15. History of hypersensitivity or allergy to the IMP or its excipients or any related medication.

16. The subject has any other condition, which in the opinion of the Investigator precludes the subject's participation in the clinical study, including any conditions mentioned in contraindication, special warnings and precautions for use, in the summary of product characteristics of the IMP.

17. Positive serology test for hepatitis B surface antigen, hepatitis C virus antibodies or human immunodeficiency virus-1 and/or 2 antibodies.

18. Positive pregnancy test.

19. Positive urine screen for drugs of abuse. In case of a positive result the urine screen for drugs of abuse may be repeated once at the discretion of the investigator.

20. Positive urine screen for tobacco use.

21. Any specific investigational product safety concern.

22. Vulnerable subjects, e.g. persons in detention.

23. Employee of the sponsor, or CRO