Bioequivalence of Oxazepam 50 mg Orodispersible Tablets Versus Seresta® 50 mg Tablets in Healthy Subjects.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Laboratorios Lesvi S.L.

Participant type

Healthy volunteers

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

26 Dec 2022 → 27 Jan 2023

Decision date (initial)

2022-10-25

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Laboratorios Lesvi, S.L.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Bioequivalence, Safety

To compare the bioavailability and assess bioequivalence of Test product versus Reference product.

Secondary objectives 2

1. To assess the safety and tolerability of Test product.
2. To assess the palatability of Test product.

Conditions and MedDRA coding

No medical condition is being investigated. This is a comparative bioavailability study.

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

1. Free written informed consent prior to any procedure required by the study.
2. Male or female subject between 18 and 55 years, inclusive, at the time of signing the informed consent.
3. Body mass index (BMI) of 18.5 to 30.0 kg/m2, inclusive.
4. Resting respiratory rate between 8 and 20 cpm, inclusive.
5. No clinically relevant diseases captured in medical history.
6. No clinically relevant abnormalities on physical examination.
7. No clinically relevant abnormalities on vital signs.
8. No clinically relevant abnormalities on 12-lead ECG.
9. No clinically relevant abnormalities on clinical laboratory tests.
10. Negative test results for anti-Human Immunodeficiency virus 1 and 2 antibodies (anti-HIV-1Ab and anti-HIV-2Ab), Hepatitis B surface antigen (HBsAg) and anti-Hepatitis C virus antibodies (anti-HCVAb).
11. Non-smoker or ex-smoker (i.e., someone who abstained from using tobacco- or nicotine-containing products for at least 3 months prior to Screening).
12. Willingness to accept and comply with all study procedures and restrictions.
13. A female subject is eligible if she meets one of the following criteria: a) is of non-childbearing potential; or b) is of childbearing potential and agrees to use an accepted contraceptive method from at least 4 weeks prior to admission to the first treatment period until at least the end-of-study.
14. Negative SARS-CoV-2 test or valid EU Digital COVID-19 Recovery Certificate.

Exclusion criteria 30

1. Known hypersensitivity/allergy reaction to the study drug substance or any of the excipients.
2. Known rare hereditary problems of galactose intolerance, Lapp-lactase deficiency or glucose-galactose malabsorption.
3. Known severe hypersensitivity reaction to any other drug.
4. Any medical condition (e.g. gastrointestinal, renal or hepatic, including peptic ulcer, inflammatory bowel disease or pancreatitis) or surgical condition (e.g. cholecystectomy, gastrectomy) that may affect drug pharmacokinetics (absorption, distribution, metabolism or excretion) or subject safety.
5. History of respiratory insufficiency or sleep apnea.
6. History of myasthenia.
7. History of opioid, alcohol, or other drug dependence (excluding nicotine and caffeine).
8. History of psychiatric disorder.
9. Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) above the upper limit of the normal range.
10. Estimated renal creatinine clearance (CrCL) below 90 mL/min, based on creatinine clearance calculation by the Cockcroft-Gault formula and normalized to an average surface area of 1.73 m2.
11. Positive result in drugs-of-abuse or ethanol tests.
12. Use of a depot injection or an implant of any drug (all but contraceptives) within the previous 6 months.
13. Average weekly alcohol consumption of >14 units for males and >7 units for females within the previous 6 months.
14. Average daily consumption of methylxanthines-containing beverages or food (e.g. coffee, tea, cola, sodas, chocolate) equivalent to >500 mg methylxanthines.
15. Participation in any clinical trial within the previous 2 months.
16. Participation in more than 2 clinical trials within the previous 12 months.
17. Blood donation or significant blood loss (≥ 450 mL) due to any reason or had plasmapheresis within the previous 2 months.
18. Difficulty in fasting or any dietary restriction such as lactose intolerance, vegan, low-fat, low sodium, etc., that may interfere with the diet served during the study.
19. Veins unsuitable for intravenous puncture on either arm.
20. Difficulty in swallowing capsules or tablets.
21. For female subjects, positive pregnancy test in serum.
22. For female subjects, subject is breast-feeding.
23. Any other condition that the investigator considers rendering the subject unsuitable for the study.
24. Any recent disease or condition or treatment that, according to the investigator, would put the subject at undue risk due to study participation or occurred at a timeframe in which may interfere with the pharmacokinetics of study drug.
25. Use of prescription or nonprescription medicinal products (such as vitamins, food supplements and herbal supplements, including St John’s Wort) within the previous 2 weeks, unless in the investigator’s opinion the medication does not interfere with the pharmacokinetics of study drug or compromise subject safety.
26. Use of morphine derivatives (analgesics, antitussives or opioid substitution treatments), neuroleptics, barbiturics, other anxiolytics, hypnotics, sedative antidepressants, sedative antihistamines, central antihypertensives, baclofen or thalidomide within the previous 4 weeks.
27. Consumption of pineapple, Seville oranges, pomelo, pomegranate, starfruit or grapefruit products (fresh, canned, or frozen) within the previous 7 days.
28. Positive result in drugs-of-abuse or ethanol tests.
29. For female subjects, positive pregnancy test.
30. Any other condition that the investigator considers rendering the subject unsuitable for the study period.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Cmax and AUC0-t of oxazepam will be the primary pharmacokinetic parameters.

Secondary endpoints 2

1. Safety will be evaluated through the assessment of adverse events (AEs), ECG, vital signs, and clinical laboratory tests.
2. Palatability of test product will be assessed approximately 30 seconds and 5 minutes after placing the Oral Dispersible Tablet on the tongue.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Laboratorios Lesvi S.L.

Sponsor organisation

Laboratorios Lesvi S.L.

Address

Avinguda De Barcelona 69, Poligono Industrialde La Fuensanta Poligono Industrialde La Fuensanta

City

Sant Joan Despi

Postcode

08970

Country

Spain

Scientific contact point

Organisation

Laboratorios Lesvi S.L.

Contact name

Clinical Research Department

Public contact point

Organisation

Laboratorios Lesvi S.L.

Contact name

Clinical Research Department

Third parties 2

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 2 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications