Comparative Bioavailability of Nilotinib 200 mg Hard Capsules in Healthy Subjects.

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] - Neoplasms [C04]

Trial duration

6 Oct 2022 → 11 Nov 2022

Decision date (initial)

2022-10-03

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, Pharmacokinetic, Safety

To explore the comparative bioavailability between Test and Reference products.

Secondary objectives 1

1. To assess the safety and tolerability of Test products.

Conditions and MedDRA coding

Primary Philadelphia-chromosome positive leukemia cells from chronic myelogenous leukemia (CML)

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 15

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 weight ≥48 kg and body mass index (BMI) of 18.5 to 30.0 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 (e.g. alcohol consumption, diet, exercise, contraception and medications).
11. 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 study period until at least 1 month after the last dose administration.
12. A male subject who is sexually active with a female partner of childbearing potential (pregnant or non-pregnant) must use contraception (condom) from admission to first study period until at least 1 month after the last study drug administration.
13. A male subject must ensure that his non-pregnant female partner of childbearing potential agrees to consistently and correctly use for the same period a highly effective method of contraception for the same period.
14. A male subject must be willing not to donate sperm from admission to first study period until at least 1 month after the last study drug administration.
15. Negative SARS-CoV-2 test or valid EU Digital COVID-19 Recovery Certificate.

Exclusion criteria 37

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 relevant hematological disorders.
6. History of cardiovascular events.
7. History of short QT syndrome, long QT syndrome, or clinically significant cardiac arrythmia.
8. Family history of sudden death before 40 years old, short or long QT syndrome.
9. Resting heart rate <50 bpm in ECG.
10. Baseline QTc interval >450 msec if man or >470 msec if woman, or <350 msec.
11. Clinically relevant abnormalities on hemogram.
12. Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) above the upper limit of 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 m2.
14. Serum potassium or magnesium below the lower limit of the normal range.
15. Serum lipase above the upper limit of normal range.
16. Positive result in drugs-of-abuse or ethanol tests.
17. Use of a depot injection or an implant of any drug (except for contraceptives) within the previous 6 months.
18. Average weekly alcohol consumption of >14 units for males and >7 units for females within the previous 6 months.
19. Average daily consumption of methylxanthines-containing beverages or food (e.g., coffee, tea, cola, sodas, chocolate) equivalent to >500 mg of methylxanthines.
20. Participation in any clinical trial within the previous 2 months.
21. Participation in more than 2 clinical trials within the previous 12 months.
22. Blood donation or significant blood loss (≥ 450 mL) due to any reason or had plasmapheresis within the previous 2 months.
23. 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.
24. Veins unsuitable for intravenous puncture on either arm.
25. Difficulty in swallowing capsules or tablets.
26. If woman, positive pregnancy test in serum.
27. If woman, she is breast-feeding.
28. Any other condition that the investigator considers to render the subject unsuitable for the study.
29. Any recent disease or condition or treatment that, according to an 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.
30. Use of prescription or nonprescription medicinal products, vitamins, food supplements or herbal supplements (including St John’s Wort) within the previous 4 weeks, unless in an investigator’s opinion the medication does not interfere with the pharmacokinetics of study drug or compromise subject safety.
31. Treatment with drugs known to prolong the QT interval within the previous 4 weeks.
32. Treatment with CYP3A4 enzyme-inducing or enzyme-inhibiting agents within the previous 4 weeks.
33. Consumption of any alcoholic product within the previous 48 hours.
34. Consumption of pineapple, Seville oranges, pomelo, pomegranate, starfruit or grapefruit products (fresh, canned, or frozen) within the previous 7 days.
35. Positive result in drugs-of-abuse or ethanol tests.
36. If woman, positive pregnancy test.
37. 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 endpoints will be estimated: Cmax; tmax; AUC) from pre-dose (time zero) to the last sampling time with quantifiable concentrations (AUC0-t); AUC from time zero to infinity (AUC0-∞); residual area or percentage of extrapolated part of AUC0-∞ (%AUCextrap); λz; and 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 3

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

Matilde Melo

Public contact point

Organisation

Bluepharma Industria Farmaceutica S.A.

Contact name

Matilde Melo

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