A Single Dose, Fast State, Bioequivalence Study of CEFIXIMA ATB 400 mg Hard Capsules (Antibiotice S.A.) vs. CEFIXORAL® 400 mg Film Coated Tablets (A. Menarini Industrie Farmaceutiche Riunite s.r.l.)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Antibiotice S.A.

Participant type

Healthy volunteers

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08], Diseases [C] - Digestive System Diseases [C06], Diseases [C] - Otorhinolaryngologic Diseases [C09], Diseases [C] - Bacterial Infections and Mycoses [C01]

Trial duration

12 Jun 2023 → 2 Jul 2023

Decision date (initial)

2023-05-17

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Antibiotice S.A.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Bioequivalence

To compare rate and extent of absorption of CEFIXIMA ATB 400 mg hard capsules – Antibiotice S.A. (Test drug) versus CEFIXORAL® 400 mg film coated tablets – A. Menarini Industrie Farmaceutiche Riunite s.r.l. (Reference drug), administered in a single dose of 400 mg cefixime under fasting conditions in a 2 – way crossover bioequivalence study

Secondary objectives 1

1. a. To compare the secondary PK parameters of cefixime after single dose administration under fasting condition of 400 mg cefixime from CEFIXIMA ATB 400 mg hard capsules - Antibiotice S.A. (Test drug) versus CEFIXORAL® 400 mg film coated tablets – A. Menarini Industrie Farmaceutiche Riunite s.r.l. (Reference drug) b. To evaluate the safety and tolerability of investigated products.

Conditions and MedDRA coding

healthy subjects

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. • Informed consent given by subjects in written form, before the initiation of all other screening procedures; • Caucasian race, male/female; • Age between 18 and 55 years; • Body Mass Index (BMI) between 18.5 and 30 kg/m2; • Non – smokers/light smokers (less than 10 cigarettes / day, anamnestic); • Normal findings in the physical examination at screening; • Normal values for blood pressure and heart rate (SBP=100-140 mmHg, DBP = 60-90 mmHg, HR = 50-90 bpm) measured in supine position after 5 minutes of rest; • Normal/ not clinically significant changes in results of standard 12 – lead ECG at screening; • Normal/ not clinically significant changes in results of hematology, clinical chemistry and urinalysis tests, at screening; • Negative serum beta – HCG in female subjects; • Ability to understand the full nature and purpose of the study, including possible risks and side effects; • The subject is able to swallow the study medication; • Ability to cooperate with the Investigator and to fully comply with study requirements; • Affiliated to a social security system or to health insurance or is a beneficiary.

Exclusion criteria 2

1. • History of hypersensitivity to the investigational products (cefixime) or to other cephalosporins and/or to the drugs within the same pharmacological/chemical class; type I hypersensitivity reactions to beta – lactams (anaphylactic shock, angioedema); hypersensitivity to any inactive ingredients of the investigated drug; • History of severe allergic or anaphylactic reactions, bronchospasm or bronchial asthma (even without a history of anaphylaxis), DRESS syndrome, Stevens – Johnson syndrome, Lyell syndrome; • history of hypersensitivity to heparine; • Any food allergy, problems of galactose intolerance or glucose-galactose malabsorption, or any restriction that could contraindicate the subject's participation in the study; • Current or recent (within 3 months) gastrointestinal disease or symptoms (chronic diarrhea, inflammatory bowel disease – ulcerative colitis, Crohn’s disease), unresolved gastrointestinal symptoms (vomiting, diarrhea, etc.), hepatic or renal diseases or other conditions known to interfere with the absorption, distribution, metabolism or excretion of drug; • Documented medical history of tuberculosis at screening; • History of Clostridioides difficile infection; • Febrile illness within 4 days before the first dose or acute febrile illness before the first administration; • Known positive human immunodeficiency virus infection, active or chronic hepatitis B virus infection, and/or current hepatitis C virus (HCV) infection; subjects with a history of HCV infection who have achieved a documented sustained virologic response 12 weeks after completion of HCV therapy may be enrolled; • Major gastrointestinal surgery (except for appendectomy); • Relevant history or laboratory or clinical findings indicative of acute or chronic disease (cardiovascular, pulmonary, hematologic, metabolic, endocrinal, immunologic, neurological or psychiatric), that could contraindicate drug products administration or likely to influence study outcomes; • Positive testing for hepatitis B or C, HIV; • creatinine clearance <50 ml/hour; • values of AST, ALT, FAL > 2.5x UNL; • values of total bilirubin > 2.5x UNL; • Administration of any OTC drug, vitamins, or natural food supplements or any prescribed systemic or topical medication (except for topical products without systemic absorption) within the last 14 days or 5 half-lives (whichever is longer) prior to the first administration of the tested drug, except if this will not affect the outcome of the study; • Use within 30 days of dosing of any agent that is known to induce or inhibit rug metabolizing enzymes; • Administration of any antibiotics in the last 90 days prior to administration of study medication; • Vaccination with any vaccine within two weeks prior to screening; • Depot injection or implants of any drug within 3 months prior to administration of study medication; • Alcohol consumption or abuse, history of alcoholism or recovered alcoholics; • Regular smokers who smoke more than 10 cigarettes daily or have difficulty abstaining from smoking for the duration of each study period; • History of drug abuse or positive result for drug of abuse screening (amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine); • Participation in another clinical trial within the last 6 weeks prior to the first drug administration; • Donation of more than 450 ml blood within the last two months prior to the first drug administration; • Unsuitable veins for repeated venipuncture; • Unwillingness or inability to follow the procedures outlined in the protocol or inability to provide written informed consent; • Institutionalized persons. Additional exclusion criteria for females only: • Use of oral contraceptives; • Positive result for pregnancy testing; • Breast – feeding.
2. • Women of childbearing potential must have a negative serum beta human chorionic gonadotropin (β-HCG) pregnancy test performed within 10 days prior to the first IMP administration and a negative urine pregnancy test on the evening prior to each dose administration. • Women of childbearing potential must practice abstinence or be using an acceptable form of contraception throughout the duration of the study. Acceptable forms of contraception include the following:  Barrier methods containing or used in conjunction with a spermicidal agent, or Surgical sterilization • Women will not be considered of childbearing potential if one of the following is reported and documented on the medical history:  Postmenopausal with an absence of menses for at least one (1) year, or  Bilateral oophorectomy with or without a hysterectomy and an absence of bleeding for at least 6 months, or  Total hysterectomy

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Pharmacokinetics • Cmax, AUClast, AUCtotal

Secondary endpoints 2

1. a. pharmacokinetics • Tmax, thalf, kel and Residual area.
2. Safety endpoints include, but are not limited to, adverse events (AEs), (including serious adverse events [SAEs], severe AEs, and AEs leading to discontinuation of the study drug), and clinically significant changes from baseline in vital sign measurements, and clinical laboratory test results

Investigational products

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

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Antibiotice S.A.

Sponsor organisation

Antibiotice S.A.

Address

Str Valea Lupului Nr 1

City

Iasi

Postcode

707410

Country

Romania

Scientific contact point

Organisation

Antibiotice S.A.

Contact name

Clinical Trials Center

Public contact point

Organisation

Antibiotice S.A.

Contact name

Clinical Trials Center

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

Documents 1 file

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