Bioequivalence of Eltrombopag 75 mg Film-Coated Tablets in Healthy Subjects Under Fed Conditions.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Bluepharma Industria Farmaceutica S.A.

Participant type

Healthy volunteers

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

30 May 2023 → 28 Jul 2023

Decision date (initial)

2023-03-15

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

BLUEPHARMA – Indústria Farmacêutica, S.A

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Bioequivalence

To demonstrate bioequivalence between Test and Reference products under fed conditions.

Secondary objectives 1

1. To assess the safety and tolerability of Test product under fed conditions.

Conditions and MedDRA coding

Aplastic anemia

Study design 1 period

Regulatory references

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

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 18.0 to 31.0 kg/m2, inclusive.
4. No clinically relevant diseases captured in medical history.
5. No clinically relevant abnormalities on physical examination.
6. No clinically relevant abnormalities on 12-lead ECG.
7. No clinically relevant abnormalities on clinical laboratory tests.
8. 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).
9. 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).
10. Willingness to accept and comply with all study procedures and restrictions.
11. A female subject is eligible if she meets 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 the first dose administration at least 1 week after the last dose administration.
12. Negative SARS-CoV-2 test or valid EU Digital COVID-19 Recovery Certificate.

Exclusion criteria 35

1. Eastern-/Southeastern-Asian (i.e., Chinese, Japanese, Taiwanese or Korean) subjects.
2. Known hypersensitivity/allergy reaction to the study drug substance or any of the excipients.
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’s safety.
5. History of splenectomy.
6. History of liver impairment.
7. History of thromboembolic event.
8. History of risk factors for thromboembolic events (e.g., inherited hypercoagulable disorders and auto-immune disorders with hypercoagulable states).
9. History of platelets disorders.
10. History of cataracts.
11. Platelets levels below the lower limit of the normal range or above 400 x10^9/L.
12. Serum transaminases alanine aminotransferase (ALT) or aspartate aminotransferase (AST) outside the normal range.
13. 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 m^2
14. Total bilirubin above the ULN.
15. Resting heart rate <50 bpm in ECG.
16. Baseline QTcF interval >450 msec if man or >470 msec if woman.
17. Positive result in drugs-of-abuse, ethanol or cotinine tests.
18. Use of a depot injection or an implant of any drug within the previous 6 months.
19. Average weekly alcohol consumption of >14 units for males and >7 units for females within the previous 6 months.
20. Average daily consumption of methylxanthines-containing beverages or food (e.g., coffee, tea, cola, sodas, chocolate) equivalent to >500 mg of methylxanthines.
21. Participation in any clinical trial within the previous 2 months.
22. Participation in more than 2 clinical trials within the previous 12 months.
23. Blood donation or significant blood loss (≥ 450 mL) due to any reason or had plasmapheresis within the previous 2 months.
24. 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.
25. Veins unsuitable for intravenous puncture on either arm.
26. Difficulty in swallowing capsules or tablets.
27. If woman, positive pregnancy test in serum.
28. If woman, she is breast-feeding.
29. Any other condition that the Investigator considers to render the subject unsuitable for the study.
30. 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.
31. Use of prescription or nonprescription medicinal products (such as vitamins, food supplements, mineral 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.
32. Consumption of pineapple, Seville oranges, pomelo, pomegranate, starfruit or grapefruit products (fresh, canned, or frozen) within the previous week.
33. Positive result in drugs-of-abuse, ethanol, or cotinine tests.
34. If woman, positive pregnancy test in urine.
35. Any other condition that the investigator considers to render the subject unsuitable for the study period.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The following pharmacokinetic parameters will be estimated: maximum observed plasma concentration (Cmax); time of occurrence of Cmax (Tmax); area under the plasma concentration versus time curve (AUC) from pre-dose (time zero) to 72 hours (AUC0-72); apparent terminal elimination rate constant (λz); and apparent terminal elimination half-life (t1/2).

Secondary endpoints 1

1. Safety will be evaluated through the assessment of adverse events (AEs), ECG, vital signs, and clinical laboratory tests.

Investigational products

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

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Bluepharma Industria Farmaceutica S.A.

Sponsor organisation

Bluepharma Industria Farmaceutica S.A.

Address

Sao Martinho Do Bispo

City

Coimbra

Postcode

3045-016

Country

Portugal

Scientific contact point

Organisation

Bluepharma Industria Farmaceutica S.A.

Contact name

Medical Affairs - Bluepharma Indústria Farmacêutica, S.A.

Public contact point

Organisation

Bluepharma Industria Farmaceutica S.A.

Contact name

Medical Affairs - Bluepharma Indústria Farmacêutica, S.A.

Third parties 3

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

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