A Study Evaluating Aprocitentan Tablets(SYH9108) for the Treatment of Resistant Hypertension

Официальное название

A Multicenter, Randomized, Double-blind, Placebo-controlled Phase 3 Study of Aprocitentan Tablets in the Treatment of Resistant Hypertension

Обзор

Aprocitentan tablets are currently the only endothelin dual receptor antagonist approved internationally for the treatment of resistant hypertension.This is a multicenter, randomized, double-blind, placebo-controlled Phase 3 study to evaluate the efficacy and safety of aprocitentan tablets(SYH9108) in patients with treatment-resistant hypertension (rHTN)

Подробное описание

The study consists of a screening period (up to 2 weeks), a run-in period (4 weeks), a treatment period (8 weeks), and a follow-up period. During the study, all participants should continue their background antihypertensive medications (at the same agents and dosages as used within 4 weeks prior to screening) and maintain lifestyle interventions such as a low-salt diet.

Вмешательства

• Препарат Aprocitentan tablets(SYH9108)
  For oral administration
• Препарат Placebo
  For oral administration. The placebo is identical to aprocitentan tablets(SYH9108) in appearance.

Первичные конечные точки

• Change from baseline in Sitting Systolic Blood Pressure (SiSBP) after 8 weeks of treatment. [Срок оценки: Baseline and week 8]

Вторичные конечные точки (12)

• Change from baseline in SiSBP after 4 weeks of treatment [Срок оценки: Baseline and week 4]
• Change from baseline in Sitting Diastolic Blood Pressure (SiSDP) after 4 weeks of treatment. [Срок оценки: Baseline and week 4]
• Change from baseline in SiSDP after 8 weeks of treatment. [Срок оценки: Baseline and week 8]
• Change from baseline in ambulatory 24-hour average SBP after 4 weeks of treatment. [Срок оценки: Baseline and week 4]
• Change from baseline in ambulatory 24-hour average SDP after 4 weeks of treatment. [Срок оценки: Baseline and week 4]
• Change from baseline in ambulatory 24-hour average SBP after 8 weeks of treatment. [Срок оценки: Baseline and week 8]
• Change from baseline in ambulatory 24-hour average SDP after 8 weeks of treatment. [Срок оценки: Baseline and week 8]
• Change from baseline in ambulatory night-time average SBP after 4 weeks of treatment. [Срок оценки: Baseline and week 4]
• Change from baseline in ambulatory night-time average SDP after 4 weeks of treatment. [Срок оценки: Baseline and week 4]
• Change from baseline in ambulatory night-time average SBP after 8 weeks of treatment. [Срок оценки: Baseline and week 8]
• Change from baseline in ambulatory night-time average SDP after 8 weeks of treatment. [Срок оценки: Baseline and week 8]
• Change from baseline in ambulatory daytime average SBP after 4 weeks of treatment. [Срок оценки: Baseline and week 4]

Критерии участия

Критерии включения

• Male or female participants must be ≥18 years of age.
• Participants must have received stable doses of ≥3 antihypertensive agents from distinct pharmacological classes for at least 4 weeks prior to signing the ICF, with such therapy maintained until randomization.
• During the screening period and prior to randomization, SiSBP ≥140 mmHg with or without SiDBP ≥90 mmHg, and SiSBP <180 mmHg and SiDBP <110 mmHg.
• Participants are able to understand and cooperate in completing this trial, voluntarily participate in the trial, and sign the Informed Consent Form (ICF).

Критерии исключения

• Presence of secondary hypertension.
• Have had transient ischemic attack, stroke, unstable angina pectoris, or acute myocardial infarction occurring within the period from 12 months prior to signing the ICF up to randomization.
• From screening to prior to randomization, have presence of uncontrolled severe disease or life-threatening disease, or failure to recover from major surgery, or prior thyroid surgery, or presence of malignant tumor, or meeting the criteria for severe hepatic insufficiency at screening.
• Have had unstable cardiac disease occurring within the period from 6 months prior to signing the ICF up to randomization.
• Have received dialysis at any time prior to signing the ICF or prior to randomization.
• Type 1 diabetes.
• Compliance with any background antihypertensive drug or placebo is <80% or >120% during the run-in period.
• Use of endothelin receptor antagonists, antihypertensive drugs other than background medications, or other blood pressure-affecting drugs, or high-dose loop diuretics from 4 weeks prior to signing the ICF until randomization; or use of oligonucleotide antihypertensive agents within 1 year prior to signing the ICF.
• Hypersensitivity or suspected hypersensitivity to the excipients of the investigational product, endothelin receptor antagonists, or background antihypertensive drugs, or potential hypersensitivity to the investigational product.
• Participated in other clinical trials and received at least one dose of study treatment within 12 weeks prior to signing the ICF.
• Average night shifts are ≥ 2 times per week during the 4 weeks prior to signing the ICF, the screening period, the run-in period, or the anticipated study period.
• History of drug abuse or alcohol abuse within 5 years prior to signing the ICF.
• Any of the following test results during the screening period or prior to randomization:

1\) BMI≥37.5 kg/m2. 2) Hemoglobin < 100 g/L; 3) NT-proBNP ≥ 500 pg/mL; 4) QTcF: > 450 ms in males, > 470 ms in females; 5) eGFR < 15 mL/min/1.73 m²; 6) ALT or AST > 3 × ULN, or total bilirubin > 1.5 × ULN; 7) HbA1c > 8.0%; 8) TSH outside the normal range and FT3 and/or FT4 outside the normal range; 9) Positive HBsAg and positive HBV-DNA, or positive for any of anti-HCV antibody, anti-HIV antibody, anti-Treponema pallidum antibody.

14\. Female participants of childbearing potential who are pregnant, breastfeeding, or have a positive pregnancy test from signing the ICF until randomization; or female participants of childbearing potential and male participants who plan to conceive (including sperm or egg donation) and/or are unable to use effective contraceptive methods during the study period and within 30 days after the end of treatment.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07635914 · SYH9108-002

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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