Randomized, Open-label, Single-Dose, Two-treatment, Two-period, Cross-over, Pivotal Bioequivalence Study Comparing Amoxicilin/Clavulanic acid powder for oral suspension 600 mg/42.9 mg/5 mL to Augemntin ES 600 mg/42.9 mg/5 mL powder for oral suspension in Healthy Adult Male and Female Volunteers under Fed Conditions.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Tarchominskie Zaklady Farmaceutyczne Polfa S.A.

Participant type

Healthy volunteers

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Bacterial Infections and Mycoses [C01]

Trial duration

27 Sep 2023 → 13 Nov 2023

Decision date (initial)

2023-08-24

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic

The primary objective is: Assessment of bioequivalence of Test versus Reference in healthy volunteers under fed conditions.

Secondary objectives 1

1. Evaluation of safety and tolerability of amoxicillin and clavulanic acid in healthy volunteers under fed conditions.

Conditions and MedDRA coding

Not applicable (submitted trial is a bioequivalence study in healthy subjects).

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Healthy males and non-pregnant and no breast-feeding females , ≥ 18 and ≤ 60 years of age and weight more than 50.0 kg (on the day of Informed Consent). Caucasian race.
2. Non-smoker or past-smoker (who has stopped smoking at least 6 months before the first dosing).
3. Body Mass Index (BMI) ≥ 18.5 and ≤ 30.0 kg/m2 inclusive (on the day of screening).
4. Subject is available for the whole study and has provided his/her written informed consent.
5. Subjects in good health, as determined by screening medical history, physical examination, vital signs assessments (heart rate, systolic and diastolic blood pressure, and body temperature) and 12-lead ECG. Minor deviations outside the reference ranges will be acceptable, if deemed not clinically significant by the Investigator.
6. All laboratory screening results within the normal range or deemed clinically insignificant by the Investigator.
7. Acceptance of use of highly effective contraceptive measures during the whole study by female subjects of childbearing potential and contraceptive measures during the whole study by male subjects.
8. The subject speaks and understands Czech fluently.

Exclusion criteria 34

1. 1. Acute or chronic diseases and/or clinical finding which may interfere with the aims of the study or with the drug’s safety, tolerability, bioavailability and/or pharmacokinetics of the IMP.
2. 2. Existing gastrointestinal diseases, renal or hepatic diseases and/or pathological findings, which might interfere with the drug’s safety, tolerability, absorption and/or pharmacokinetics.
3. 3. History or presence of serious clinical illness that can impact the fate of drugs (their absorption and/or distribution and/or metabolism and/or elimination).
4. 4. History of severe allergy or allergic reactions to the study drugs or related drugs or any of the excipients.
5. 5. Clinically significant illness within 28 days before the first dosing, including major surgery.
6. 6. Serious mental disease and/or inability to cooperate with clinical team.
7. 7. Orthostatic hypotension in history or during the screening procedure.
8. 8. Drug, alcohol (≥ 40 g per day pure ethanol for men or ≥ 20 g per day pure ethanol for women), solvents or caffeine abuse.
9. 9. Use of organ-toxic drugs within 90 days before the first dosing (e.g. any drug with a welldefined potential for toxicity to a major organ or system such as chloramphenicol, which may cause bone marrow suppression).
10. 10. Use of systemic drugs known to alter hepatic metabolism within 90 days prior to the first dosing.
11. 11. Any systemic prescription treatment within 28 days before the first dosing, except hormonal contraceptives or hormone replacement therapy taken without significant changes in dose for 90 days prior to the first dosing.
12. 12. Any systemic over-the-counter (OTC) drug treatment and/or vitamins and/or herbal treatment and/or food supplements within 14 days before the first dosing.
13. 13. Donation or loss of at least 500 mL of blood within 90 days or donation of plasma or platelets within 14 days before the first dosing.
14. 14. Getting a tattoo, body piercing or any cosmetic treatment involving skin penetration within 90 days before the screening unless evaluated by Investigator as non-significant for inclusion in the study.
15. 15. Positive results of drugs of abuse in urine at screening and at check-in.
16. 16. Positive result of alcohol breath test at screening and at check-in.
17. 17. Positive result of urine cotinine test at screening.
18. 18. Body temperature is > 36.9 °C at screening and at check-in.
19. 19. Sitting blood pressure after a minimum of 5 minutes of rest is out of the range of 90-140 mmHg for systolic BP and/or 60-90 mmHg for diastolic BP and/or heart rate out of the range of 50- 100 bpm during the screening procedure.
20. 20. Any significant clinical abnormality, including a positive result of HBsAg and/or HCV and/or HIV test during screening procedure.
21. 21. Anaemia, haemoglobin below 120 g/L for women and 130 g/L for men at screening.
22. 22. Positive result of blood pregnancy test at screening or positive urine pregnancy test at check-in or breast-feeding or lack of results of pregnancy test.
23. 23. State of veins on upper extremities does not allow or complicates blood collection.
24. 24. Less than 30 days between exit procedure in previous study and the first dosing in this study.
25. 25. Presence or history of atopic eczema.
26. 26. Known glucose-galactose malabsorption.
27. 27. Estimation of glomerular filtration (GF-MDRD-1) bellow 1 mL/s at the screening.
28. 28. Any history of known Augmentin-associated jaundice/hepatic dysfunction.
29. 29. Any known active mononucleosis.
30. 30. History of previous hypersensitivity reaction to penicillins, cephalosporins or other betalactam antibiotics.
31. 31. History of phenylketonuria or a known hypersensitivity to aspartame.
32. 32. Subject was vaccinated against COVID-19 less than 14 days before the screening and/or subject plans to be vaccinated against COVID-19 during the study.
33. 33. Subjects was hospitalized for COVID-19 related reasons.
34. 34. Positive PCR for SARS-CoV-02 or positive antigen test, if required for safety reasons before hospitalization in the study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. AUC(0-t), and Cmax of AXL and CLA

Secondary endpoints 1

1. tmax, λz, t1/2, AUC(0-∞) and AUCres of AXL and CLA

Investigational products

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

Test 1

Comparator 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Tarchominskie Zaklady Farmaceutyczne Polfa S.A.

Sponsor organisation

Tarchominskie Zaklady Farmaceutyczne Polfa S.A.

Address

Ul. Aleksandra Fleminga 2

City

Warsaw

Postcode

03-176

Country

Poland

Scientific contact point

Organisation

Tarchominskie Zaklady Farmaceutyczne Polfa S.A.

Contact name

Clinical Research Manager

Public contact point

Organisation

Tarchominskie Zaklady Farmaceutyczne Polfa S.A.

Contact name

Clinical Research Specialist

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 4 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