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Completed

NCT Number: NCT04281342

To Study the Effect of Aprocitentan on the Electrical Activity of the Heart in Healthy Men and Women

To demonstrate that multiple-dose administration of oral therapeutic and supratherapeutic doses of aprocitentan do not have a clinically relevant effect on the QT interval.

Completed

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Key information

Conditions

Age range

18 year–55 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

CRS Clinical Research Services Mannheim GmbH

Mannheim, Baden-Wurttemberg, 68167, Germany

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Signed informed consent in a language understandable to the subject prior to any study-mandated procedure.
  • Ability to communicate well with the investigator, in a language understandable to the subject, and to understand and comply with the requirements of the study.
  • No clinically significant findings on the physical examination at screening.
  • Body mass index 18.0 to 30.0 kg/m2 (inclusive) at screening.
  • Systolic blood pressure 90-140 mmHg, diastolic blood pressure 50-90 mmHg, and pulse rate 50-90 bpm (all inclusive), measured on the same arm, after 5 minutes in the supine position at screening.
  • 12-lead safety ECG: QTcF less than 450 ms for male subjects and less than 470 ms for female subjects, QRS less than 110 ms, PR less than 220 ms, and resting HR greater than 50 bpm and less than 90 bpm with no clinically relevant abnormalities on 12-lead ECG after at least 5 min in the supine position at Screening and on Day 1 pre-dose of Period 1.
  • No clinically relevant findings in clinical laboratory tests (hematology, clinical chemistry) at screening.
  • Negative results from urine drug screen, urine cotinine test, and breath alcohol tests at screening and on Day -1 of each period.
  • A woman of childbearing potential (WoCBP) is eligible only if the following applies:
  • Negative serum pregnancy test at screening.
  • Negative urine pregnancy test on Day -1 of each period.
  • Agreement to consistently and correctly use a highly effective method of contraception from screening up to at least 30 days after last study treatment administration in the last period with in-between periods included.
  • Women of non-childbearing potential (WoNCBP) must meet at least one of the following criteria:
  • Previous bilateral salpingectomy, salpingo-oophorectomy or hysterectomy,
  • Confirmed premature ovarian failure,
  • Post-menopausal.

Exclusion criteria

  • Pregnant or lactating women.
  • Previous exposure to aprocitentan or macitentan.
  • Known hypersensitivity to aprocitentan or macitentan or any of the drug product excipients, or treatments of the same class.
  • Any contraindication or known hypersensitivity to moxifloxacin or any of the drug product excipients or to other fluoroquinolone antibiotics.
  • Known hypersensitivity or allergy to natural rubber latex.
  • 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 treatment (appendectomy and herniotomy allowed, cholecystectomy not allowed).
  • Acute, ongoing, recurrent, or chronic systemic disease able to interfere with the evaluation of the study.
  • Previous treatment with any prescribed medications (including vaccines) or over-the-counter (OTC) medications (including herbal medicines such as St John's Wort, homeopathic preparations, vitamins, and minerals) within 2 weeks or 5 t½ (whichever is longer) prior to first study treatment administration with the exception of contraceptives in female subjects.
  • History or presence of rhythm disorders (e.g., sinoatrial heart block, sick-sinus syndrome, second- or third-degree atrioventricular block, long QT syndrome, symptomatic bradycardia, atrial flutter, or atrial fibrillation) or hypokalemia.
  • Legal incapacity or limited legal capacity at screening.

Treatment and study plan

Aprocitentan 25 mg

Drug

Repeated administration of a 25 mg oral dose of aprocitentan, once daily from Day 1 to Day 10, followed by 18 days of observation.

Other names: ACT-132577

Aprocitentan 100 mg

Drug

Repeated administration of a 100 mg oral dose of aprocitentan, once daily from Day 1 to Day 10, followed by 18 days of observation.

Other names: ACT-132577

Matching Placebo

Drug

Repeated administration of an oral dose of aprocitentan-matching placebo, once daily from Day 1 to Day 10, followed by 18 days of observation.

Moxifloxacin control to establish assay sensitivity

Other

Repeated administration of an oral dose of aprocitentan-matching placebo, once daily from Day 1 to Day 9. On Day 10, oral administration of one single 400 mg moxifloxacin tablet open-label, followed by 18 days of observation.

Primary outcomes

  1. Placebo-corrected change from baseline in QT interval corrected with Fridericia's formula (ΔΔQTcF)

    Time frame: Multiple predefined time points related to study treatment administration on Day 1 and Day 10 to 11 of each treatment.

Secondary outcomes

  1. Aprocitentan trough plasma concentrations (Ctrough)

    Time frame: Day 2 to Day 9

  2. Aprocitentan plasma Cmax, first dose

    Time frame: Pre-defined times on the first dosing day (Day 1) up to 15 hours after last dose

  3. Aprocitentan plasma Cmax, steady state

    Time frame: Pre-defined times on the last dosing day (Day 10) up to 15 hours after last dose

  4. Area under the plasma concentration-time curve (AUCτ) during a dosage interval (τ) of aprocitentan

    Time frame: Day 1 to Day 10

  5. Aprocitentan attainment of steady-state conditions

    Time frame: Day 1 to Day 10

  6. Accumulation index between the first and the last dosing day of aprocitentan

    Time frame: Day 1; Day 10

Sponsors and collaborators

Lead sponsor

Idorsia Pharmaceuticals Ltd.

Industry

Registry information

Official study title

Prospective, Single-center, Randomized, Double-blind, Placebo- and Moxifloxacin-controlled, 4-way Crossover Phase 1 Study to Assess the Effect of Multiple Therapeutic and Supratherapeutic Doses of Aprocitentan on the QT Interval Duration in Healthy Subjects

Important dates

Study start
2020
Primary completion
2021
Study completion
2021
First posted
Feb 24, 2020
Registry last updated
Nov 23, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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