Pharmacokinetics of AUX-001 40mg Once-daily in Healthy Subjects Under Fasting and Fed Conditions

Pharmacokinetics of Nicorandil 40 mg Extended-Release Capsules: A Single-Dose, Open-Label, Randomized, Two-Sequence, Two-Treatment, Two-Period Crossover Study in Healthy Subjects Under Fasting and Fed Conditions

Exploratory, single-dose, open-label, pharmacokinetic study to establish uptake, plasma levels safety and tolerability of orally administered AUX-001 on an empty stomach (i.e, fasting) as well as after a meal (i.e. fed) in healthy volunteers.

Study Overview

• Status: Active, not recruiting
• Conditions: Chronic Stable Angina
• Intervention / Treatment: Drug: AUX-001 40mg once-daily

Detailed Description

This is a first-in-human, exploratory, single-dose, open-label pharmacokinetic study to explore the uptake, and systemic distribution of orally administered AUX-001 in healthy volunteers on an empty stomach (i.e, fasting) as well as after a meal (i.e. fed) in male and female healthy volunteers age 18 to 55 to establish pharmacokinetics, safety, tolerability and whether the medication can be given independent of any food effect.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• Portugal
  • Porto, Portugal, 4250-449
    • BlueClinical

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Free written informed consent signed and dated prior to any procedure required by the study.
2. Male or female subject between 18 and 55years, 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 EKG.
8. No clinically relevant abnormalities on laboratory tests.
9. Neg. test results on anti-HIV-1Ab and anti-HIV-2Ab, HbsAG and anti-HCVAb
10. Non-smoker or ex-smoker
11. Willingness to accept and comply with all study procedures and restrictions.
12. Female subject of a) non-child-bearing potential or b) of childbearing potential and agrees to use an accepted, highly effective contraceptive method until the end of the study.

Exclusion Criteria:

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A: fasting; AUX-001 40mg QD	Drug: AUX-001 40mg once-daily; AUX-001 (extended-release nicorandil) 40mg QD (once-daily); Other Names: Food effect
Experimental: Arm B: fed; AUX-001 40mg QD	Drug: AUX-001 40mg once-daily; AUX-001 (extended-release nicorandil) 40mg QD (once-daily); Other Names: Food effect

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the curve over 24 hours [AUC0-24h)] of nicorandil under fasting conditions	Total nicorandil plasma concentration over 24 hours under fasting conditions	24 hours
Area under the curve over 24 hours [AUC0-24h)] of nicorandil under fed conditions	Total nicorandil plasma concentration over 24 hours under fed conditions	24 hours
Maximum Plasma Concentration [Cmax] of nicorandil under fasting conditions	Peak plasma concentration under fasting conditions in mcg/ml	24 hours
Maximum Plasma Concentration [Cmax] of nicorandil under fed conditions	Peak plasma concentration under fed conditions in mcg/ml	24 hours
24 hour Area Under the Curve [AUC0-24h] of N-(2-hydroxyethyl) nicotinamide under fasting conditions	24 hour Total Plasma Concentration of nicorandil's main metabolite under fasting conditions	24 hours
24h hour Area Under the Curve [AUC0-24h] of N-(2-hydroxyethyl) nicotinamide under fed conditions	Total Plasma Concentration of nicorandil's main metabolite under fed conditions	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment-emergent adverse events [TEAE] under fasting conditions	Occurrence of treatment-emergent adverse events (TEAEs) including vital signs, pulse oximetry, EKG, liver function tests [LFT] under fasting conditions	24 hours
Treatment-emergent adverse events [TEAE] under fed conditions	Occurrence of treatment-emergent adverse events (TEAEs) including vital signs, pulse oximetry, EKG, liver function tests [LFT] under fed conditions	24 hours

Collaborators and Investigators

• Sponsor: Auxilius Pharma sp.z.o.o.
• Investigators: Principal Investigator: Marlene Fonseca, MD, Blueclinical, Ltd.; Study Director: Uwe P Tigör, MD, Auxilius Pharma

Study record dates

Study Major Dates

• Study Start (Actual): November 27, 2023
• Primary Completion (Estimated): February 8, 2024
• Study Completion (Estimated): February 10, 2024

Study Registration Dates

• First Submitted: December 20, 2023
• First Submitted That Met QC Criteria: January 31, 2024
• First Posted (Actual): February 8, 2024

Study Record Updates

• Last Update Posted (Actual): February 12, 2024
• Last Update Submitted That Met QC Criteria: February 8, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Safety; Pharmacokinetics; Bioavailability; Tolerability; Fasting; Fed
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Pain; Neurologic Manifestations; Chest Pain; Angina Pectoris; Angina, Stable
• Other Study ID Numbers: 2023-506085-31-00

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No