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

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

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)

Study Overview

• Status: Not yet recruiting
• Conditions: Resistant Hypertension
• Intervention / Treatment: Drug: Aprocitentan tablets(SYH9108); Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 382
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Clinical Trials Information Group officer; Phone Number: +86311-69085587; Email: ctr-contact@cspc.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female participants must be ≥18 years of age.
2. 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.
3. 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.
4. Participants are able to understand and cooperate in completing this trial, voluntarily participate in the trial, and sign the Informed Consent Form (ICF).

Exclusion Criteria:

1. Presence of secondary hypertension.
2. 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.
3. 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.
4. Have had unstable cardiac disease occurring within the period from 6 months prior to signing the ICF up to randomization.
5. Have received dialysis at any time prior to signing the ICF or prior to randomization.
6. Type 1 diabetes.
7. Compliance with any background antihypertensive drug or placebo is <80% or >120% during the run-in period.
8. 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.
9. 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.
10. Participated in other clinical trials and received at least one dose of study treatment within 12 weeks prior to signing the ICF.
11. 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.
12. History of drug abuse or alcohol abuse within 5 years prior to signing the ICF.
13. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; For oral administration. The placebo is identical to aprocitentan tablets(SYH9108) in appearance.
Experimental: Aprocitentan tablets(SYH9108)	Drug: Aprocitentan tablets(SYH9108); For oral administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in Sitting Systolic Blood Pressure (SiSBP) after 8 weeks of treatment.	To assess the effect of treatment with Aprocitentan tablets(SYH9108) versus placebo on SiSBP at Week 8.	Baseline and week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in SiSBP after 4 weeks of treatment	To assess the effect of treatment with Aprocitentan tablets(SYH9108) versus placebo.	Baseline and week 4
Change from baseline in Sitting Diastolic Blood Pressure (SiSDP) after 4 weeks of treatment.	To assess the effect of treatment with Aprocitentan tablets(SYH9108) versus placebo.	Baseline and week 4
Change from baseline in SiSDP after 8 weeks of treatment.	To assess the effect of treatment with Aprocitentan tablets(SYH9108) versus placebo.	Baseline and week 8
Change from baseline in ambulatory 24-hour average SBP after 4 weeks of treatment.	To assess the effect of treatment with Aprocitentan tablets(SYH9108) versus placebo.	Baseline and week 4
Change from baseline in ambulatory 24-hour average SDP after 4 weeks of treatment.	To assess the effect of treatment with Aprocitentan tablets(SYH9108) versus placebo.	Baseline and week 4
Change from baseline in ambulatory 24-hour average SBP after 8 weeks of treatment.	To assess the effect of treatment with Aprocitentan tablets(SYH9108) versus placebo	Baseline and week 8
Change from baseline in ambulatory 24-hour average SDP after 8 weeks of treatment.	To assess the effect of treatment with Aprocitentan tablets(SYH9108) versus placebo	Baseline and week 8
Change from baseline in ambulatory night-time average SBP after 4 weeks of treatment.	To assess the effect of treatment with Aprocitentan tablets(SYH9108) versus placebo.	Baseline and week 4
Change from baseline in ambulatory night-time average SDP after 4 weeks of treatment.	To assess the effect of treatment with Aprocitentan tablets(SYH9108) versus placebo.	Baseline and week 4
Change from baseline in ambulatory night-time average SBP after 8 weeks of treatment.	To assess the effect of treatment with Aprocitentan tablets(SYH9108) versus placebo.	Baseline and week 8
Change from baseline in ambulatory night-time average SDP after 8 weeks of treatment.	To assess the effect of treatment with Aprocitentan tablets(SYH9108) versus placebo.	Baseline and week 8
Change from baseline in ambulatory daytime average SBP after 4 weeks of treatment.	To assess the effect of treatment with Aprocitentan tablets(SYH9108) versus placebo.	Baseline and week 4
Change from baseline in ambulatory daytime average SDP after 4 weeks of treatment.	To assess the effect of treatment with Aprocitentan tablets(SYH9108) versus placebo.	Baseline and week 4
Change from baseline in ambulatory daytime average SBP after 8 weeks of treatment.	To assess the effect of treatment with Aprocitentan tablets(SYH9108) versus placebo.	Baseline and week 8
Change from baseline in ambulatory daytime average SDP after 8 weeks of treatment.	To assess the effect of treatment with Aprocitentan tablets(SYH9108) versus placebo.	Baseline and week 8
Number of Participants with Treatment Emergent Adverse Events (TEAEs).	AEs will be assessed using Mild/moderate/severe.	Baseline up to approximately Week 10
Number of Participants with Serious Adverse Events (SAEs).	AEs will be assessed using Mild/moderate/severe.	Baseline up to approximately Week 10

Collaborators and Investigators

• Sponsor: CSPC Zhongnuo Pharmaceutical (Shijiazhuang) Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): May 31, 2026
• Primary Completion (Estimated): December 28, 2029
• Study Completion (Estimated): May 31, 2030

Study Registration Dates

• First Submitted: May 29, 2026
• First Submitted That Met QC Criteria: June 3, 2026
• First Posted (Actual): June 9, 2026

Study Record Updates

• Last Update Posted (Actual): June 9, 2026
• Last Update Submitted That Met QC Criteria: June 3, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Resistant hypertension; rHTN; Aprocitentan; SYH9108
• Other Study ID Numbers: SYH9108-002

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