Bioequivalence Study of Different Aprocitentan Tablet Formulations

A Single-center, Open-label, Randomized, Two-way Crossover Phase 1 Study to Compare the Single-dose Pharmacokinetics of Different Tablet Formulations of Aprocitentan in Healthy Subjects

The main purpose is to study the pharmacokinetics of aprocitentan (ACT-132577) using 2 different tablet formulations. The clinical pharmacology data will be used to determine bioequivalence of 2 different tablet formulations.

Study Overview

• Status: Completed
• Conditions: Healthy Subjects
• Intervention / Treatment: Drug: Aprocitentan (Formulation A); Drug: Aprocitentan (Formulation B)

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• Czechia
  • Pilsen, Czechia, 323 00
    • CEPHA s.r.o.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Signed informed consent in a language understandable to the participant prior to any study-mandated procedure.
• Healthy male or female participant aged between 18 and 55 years (inclusive) at Screening.
• Body Mass Index of 18.0 to 30.0 kg/m2 (inclusive) at Screening.
• Systolic blood pressure (SBP) 100-140 mmHg, Diastolic blood pressure (DBP) 60-90 mmHg, and pulse rate 60-100 bpm (inclusive), measured on the dominant arm, after 5 min in the supine position at Screening and on Day 1 pre-dose of the first period.
• Woman of Childbearing Potential who has a negative serum pregnancy test at Screening and a negative urine pregnancy test on Day -1 of the first period. She must agree to consistently and correctly use (from Screening, during the entire study, and for at least 30 days after the last study treatment administration) a highly effective method of contraception with a failure rate of less than 1% per year.
• Woman of non-childbearing potential, i.e., postmenopausal (defined as 12 consecutive months with no menses without an alternative medical cause; in addition, an FSH test must be performed at Screening to further support postmenopausal status), with previous bilateral salpingectomy, bilateral salpingo oophorectomy or hysterectomy, or with premature ovarian failure (confirmed by a specialist), XY genotype, uterine agenesis.

Exclusion Criteria:

• Pregnant or lactating woman.
• Previous administration of aprocitentan.
• Known hypersensitivity to endothelin receptor antagonists or to excipients used in any of the formulations.
• History of major medical or surgical disorders which, in the opinion of the investigator, are likely to interfere with the absorption, distribution, metabolism, or excretion of the study treatments (appendectomy and herniotomy allowed, cholecystectomy not allowed).
• Acute, ongoing, recurrent, or chronic systemic disease able to interfere with the evaluation of the study results.
• Clinically relevant findings on the physical examination at Screening and on Day -1 of the first period.
• Clinically relevant findings in clinical laboratory tests (hematology and clinical chemistry) at Screening and on Day -1 of the first period.
• Previous treatment with any prescribed medications (including vaccines) or over-the-counter medications (including herbal medicines such as St John's Wort, homeopathic preparations, vitamins, and minerals) within 3 weeks or 5 terminal elimination half-lives (t½; whichever is longer) prior to first study treatment administration.
• Legal incapacity or limited legal capacity at Screening.
• Positive COVID-19 test, if performed (subject to current epidemiological regulations in the Czech Republic) during the screening period.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Aprocitentan (reference product); 25 mg film-coated tablet	Drug: Aprocitentan (Formulation A); A single oral dose of 25 mg.; Other Names: ACT-132577
Experimental: Aprocitentan (test product); 25 mg film-coated tablet	Drug: Aprocitentan (Formulation B); A single oral dose of 25 mg.; Other Names: ACT-132577

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum plasma concentration (Cmax) of aprocitentan	Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 10.
The area under the plasma concentration-time curve from zero to time t of the last measured concentration above the limit of quantification (AUC0-t) of aprocitentan	Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 10.
Area under the plasma concentration-time curve from zero to infinity (AUC0-inf) of aprocitentan	Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 10.

Secondary Outcome Measures

Outcome Measure	Time Frame
Treatment-emergent adverse events	From study treatment administration on Day 1 up to last assessment at End of Period (Day 10).

Collaborators and Investigators

• Sponsor: Idorsia Pharmaceuticals Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): February 2, 2022
• Primary Completion (Actual): March 27, 2022
• Study Completion (Actual): April 7, 2022

Study Registration Dates

• First Submitted: January 5, 2022
• First Submitted That Met QC Criteria: January 5, 2022
• First Posted (Actual): January 19, 2022

Study Record Updates

• Last Update Posted (Actual): November 23, 2022
• Last Update Submitted That Met QC Criteria: November 22, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: ID-080-110; 2021-005090-11 (EudraCT Number)

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