Pharmacokinetics of Nicorandil 40 mg Extended-Release Capsules in Healthy Subjects Under Fasting and Fed Conditions.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Auxilius Pharma Sp. z o.o.

Participant type

Healthy volunteers

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Not possible to specify

Trial duration

27 Nov 2023 → 20 Dec 2023

Decision date (initial)

2023-11-03

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Auxilius Pharma Sp. z o.o.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Pharmacokinetic

− To characterize and compare the pharmacokinetics of nicorandil and its metabolite N-(2-hydroxyethyl) nicotinamide following a single-dose administration of nicorandil 40 mg extended-release capsules under fasting and fed conditions.
− To assess the effect of food on the pharmacokinetics of nicorandil and metabolite N-(2-hydroxyethyl) nicotinamide after single dose administration of nicorandil 40 mg extended-release capsules.

Secondary objectives 1

1. To assess the safety and tolerability of nicorandil 40 mg extended-release capsules dosed under fasting and fed conditions.

Conditions and MedDRA coding

No medical condition.

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Free written informed consent signed and dated 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 vital signs.
7. No clinically relevant abnormalities on 12-lead ECG.
8. No clinically relevant abnormalities on laboratory tests.
9. 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).
10. 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).
11. Willingness to accept and comply with all study procedures and restrictions.
12. 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, highly effective contraceptive method from at least 8 weeks prior to admission to the first study period until the end of the study.

Exclusion criteria 31

1. Known hypersensitivity/allergy reaction to the study drug substance or any of the excipients.
2. Known severe hypersensitivity reaction to any other drug.
3. 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.
4. History of glucose-6-phosphate dehydrogenase deficiency.
5. History of severe hypotension or shock.
6. History of acute pulmonary edema, heart failure, coronary artery disease or myocardial infarction.
7. History of orthostatic hypotension, collapse, fainting, syncope, or vasovagal reaction.
8. History of substance or alcohol abuse within the previous 2 years.
9. Use of contact lenses.
10. SBP <95 mmHg and/or DBP <45 mmHg.
11. Serum transaminases alanine aminotransferase (ALT) or aspartate aminotransferase (AST) above the upper limit of the normal range.
12. Estimated renal creatinine clearance (CLCr) below the lower limit of normal range, based on creatinine clearance calculation by the Cockcroft-Gault formula and normalized to an average body surface area of 1.73 m2.
13. Positive result in drugs-of-abuse or ethanol tests.
14. Use of a depot injection or an implant of any drug (except for contraceptives) within the previous 6 months.
15. Average weekly alcohol consumption of >14 units for males and >7 units for females within the previous 6 months.
16. Average daily consumption of methylxanthines-containing beverages or food (e.g., coffee, tea, cola, sodas, chocolate) equivalent to >500 mg of methylxanthines.
17. Participation in any clinical trial within the previous 2 months.
18. Participation in more than 2 clinical trials within the previous 12 months.
19. Blood donation or significant blood loss (≥ 450 mL) due to any reason or had plasmapheresis within the previous 2 months.
20. 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.
21. Veins unsuitable for intravenous puncture on either arm.
22. Difficulty in swallowing capsules or tablets.
23. If woman of childbearing potential (WOCBP), positive pregnancy test.
24. If woman, she is breast-feeding.
25. Any other condition that the Investigator considers to render the subject unsuitable for the study.
26. 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 the study drug.
27. Use of prescription or nonprescription medicinal products, such as vitamins, food supplements, or 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 the study drug or compromise subject safety.
28. Use of phosphodiesterase 5 inhibitors (e.g., sildenafil, tadalafil, vardenafil) and/or soluble guanylate cyclase stimulants (riociguat) within the previous week.
29. Positive result in drugs-of-abuse or ethanol tests.
30. If WOCBP, positive or inconclusive pregnancy test.
31. 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. Cmax, AUC0-t , AUC0-∞, Tmax, Tlag, λz, t1/2, CL/F, Vz/F, MRCmax and MRAUC0-t of nicorandil and N-(2-hydroxyethyl) nicotinamide will be the primary pharmacocinetic parameters.

Secondary endpoints 1

1. Occurrence of treatment-emergent adverse events (TEAEs). All vital signs, pulse oximetry, ECG, and laboratory tests results will be reported.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Auxilius Pharma Sp. z o.o.

Sponsor organisation

Auxilius Pharma Sp. z o.o.

Address

Ul. Ulica Hoza 86/410

City

Warsaw

Postcode

00-682

Country

Poland

Scientific contact point

Organisation

Auxilius Pharma Sp. z o.o.

Contact name

Dawid Chabowski

Public contact point

Organisation

Auxilius Pharma Sp. z o.o.

Contact name

Dawid Chabowski

Third parties 4

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 3 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