To Assess Allisartan Isoproxil/Amlodipine in Patients With Essential Hypertension Uncontrolled With Amlodipine or Allisartan Isoproxil

Efficacy and Safety of Allisartan Isoproxil/Amlodipine in Patients With Essential Hypertension Uncontrolled With Amlodipine or Allisartan Isoproxil: A Phase III, Multicenter, Randomized, Double-blind, Parallel-controlled, 52-week Clinical Study

The main objective of the study will be to assess the efficacy and safety of Allisartan Isoproxil/Amlodipine (240 mg/5 mg) in patients with mild to moderate essential hypertension uncontrolled after 4-week treatment with Amlodipine besylate（5 mg) or Allisartan Isoproxil (240 mg).

Study Overview

• Status: Completed
• Conditions: Essential Hypertension
• Intervention / Treatment: Drug: Allisartan Isoproxil/Amlodipine group 1; Drug: Amlodipine group 1; Drug: Allisartan Isoproxil/Amlodipine group 2; Drug: Allisartan Isoproxil group 2

Detailed Description

Amlodipine belongs to the calcium channel blocker (CCB) class of drugs, which acts as an antihypertensive agent mainly via blocking calcium channels on the vascular smooth muscle cells to dilate blood vessels.

Allisartan Isoproxil belongs to the ARB class of drugs, which can effectively exert antihypertensive effects.

The combination of dihydropyridine CCBs and ARBs exerts synergistic antihypertensive effects.

• Study Type: Interventional
• Enrollment (Actual): 499
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100020
      • Beijing Chaoyang Hospital, Capital Medical University

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients 18-70 years old with mild to moderate essential hypertension;
• Untreated patients (either newly diagnosed essential hypertension or those patients with a history of hypertension but have not been taking any antihypertensive drugs for at least 2 weeks before the first visit) must have an office msSBP ≥ 150 mmHg and < 180 mmHg and DBP<110 mmHg;
• Patients who had not received regular treatment with Amlodipine Besylate (5 mg/day) (less than 4 weeks of medication intake or a history of missing doses for 5 or more days within the 4 weeks before screening) with the mean sitting blood pressure of 140 mmHg≤ SBP <180 mmHg and DBP<110 mmHg;
• Patients currently receiving other antihypertensive agents (non-study medications for at least 2 weeks prior to screening) with the mean sitting blood pressure of 140 mmHg≤ SBP <180 mmHg and DBP<110 mmHg, and the clinician determined that it was appropriate to switch to Amlodipine Besylate (5 mg/day);
• Patients who have been stably treated with Amlodipine Besylate (5 mg/day) for at least 4 weeks with the mean sitting blood pressure of 140 mmHg≤ SBP <180 mmHg and DBP<110 mmHg. During randomization for the double-blind treatment period, mean sitting blood pressure should be 140 mmHg≤ SBP <180 mmHg and DBP<110 mmHg;
• Participants enrolled in the ambulatory blood pressure monitoring (ABPM) study should have 24-hour mean ambulatory blood pressure ≥130/80 mmHg after 4 weeks of monotherapy treatment;

Exclusion Criteria:

• Patients with secondary hypertension;
• Patients with msSBP ≥180 mmHg and/or msDBP≥110 mmHg, or with hypertensive emergency or hypertensive urgency.
• Patients with history of heart failure (New York Heart Association (NYHA) Functional Classification class III and IV), acute coronary syndrome, percutaneous coronary intervention, or other serious heart diseases (such as cardiogenic shock, moderate or severe heart valvular disorders, atrioventricular block second or third degree, bradycardia (with a heart rate <50 beats per minute), severe arrhythmias) in the past 6 months.
• Patients with history of severe cerebrovascular diseases (such as hypertensive encephalopathy, cerebrovascular injury, stroke, transient ischemic attack) in the past 6 months.
• Patients with aortic aneurysm, aortic dissection, or dissecting aneurysm.
• Patients with renal artery stenosis or severe renal insufficiency (Cr>1.5 times the upper limit of normal).
• Patients with blood potassium >5.5 mmol/L.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Allisartan Isoproxil/Amlodipine group 1; Patients will be treated with one Allisartan Isoproxil/Amlodipine (240 mg/5 mg) tablet and one placebo of Amlodipine during the double-blind period (Week 4~Week 16) and one Allisartan Isoproxil/Amlodipine(240 mg/5 mg) tablet during the open-label period(Week 16~ Week 56) once daily.	Drug: Allisartan Isoproxil/Amlodipine group 1; One Allisartan Isoproxil/Amlodipine (240 mg/5 mg) tablet and one placebo of Amlodipine during the double-blind period (Week 4~Week 16). One Allisartan Isoproxil/Amlodipine(240 mg/5 mg) tablet during the open-label period(Week 16~ Week 56) once daily.
Active Comparator: Amlodipine group 1; Patients will be treated with one Amlodipine (5 mg) tablet and one placebo of Allisartan Isoproxil/Amlodipine(240 mg/5 mg) tablet during the double-blind period (Week 4~Week 16) and one Allisartan Isoproxil/Amlodipine(240 mg/5 mg) tablet during the open-label period(Week 16~ Week 56) once daily.	Drug: Amlodipine group 1; One Amlodipine (5 mg) tablet and one placebo of Allisartan Isoproxil/Amlodipine during the double-blind period (Week 4~Week 16). One Allisartan Isoproxil/Amlodipine(240 mg/5 mg) tablet during the open-label period(Week 16~ Week 56) once daily.
Experimental: Allisartan Isoproxil/Amlodipine group 2; Patients will be treated with one Allisartan Isoproxil/Amlodipine (240 mg/5 mg) tablet and one placebo of Allisartan Isoproxil tablet during the double-blind period (Week 4~Week 16) and one Allisartan Isoproxil/Amlodipine(240 mg/5 mg) tablet during the open-label period(Week 16~ Week 56) once daily.	Drug: Allisartan Isoproxil/Amlodipine group 2; One Allisartan Isoproxil/Amlodipine (240 mg/5 mg) tablet and one placebo of Allisartan Isoproxil (240 mg) during the double-blind period (Week 4~Week 16). One Allisartan Isoproxil/Amlodipine(240 mg/5 mg) tablet during the open-label period(Week 16~ Week 56) once daily.
Active Comparator: Allisartan Isoproxil group 2; Patients will be treated with one Allisartan Isoproxil (240 mg) and one placebo of Allisartan Isoproxil/Amlodipine(240 mg/5 mg) tablet during the double-blind period (Week 4~Week 16) and one Allisartan Isoproxil/Amlodipine(240 mg/5 mg) tablet during the open-label period(Week 16~ Week 56) once daily.	Drug: Allisartan Isoproxil group 2; One Allisartan Isoproxil (240 mg) and one placebo of Allisartan Isoproxil/Amlodipine (240 mg/5 mg) during the double-blind period (Week 4~Week 16). One Allisartan Isoproxil/Amlodipine(240 mg/5 mg) tablet during the open-label period(Week 16~ Week 56) once daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in mean sitting systolic blood pressure after 12 weeks of randomized, double-blind treatment	Twenty-four hour mean msSBP will be performed at baseline and week 12 of double-blind treatment	Baseline, week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in mean sitting diastolic blood pressure after 12 weeks of randomized, double-blind treatment	Twenty-four hour mean msDBP will be performed at baseline and week 12 of double-blind treatment	Baseline, week 12
Change from baseline in mean sitting systolic blood pressure and mean sitting diastolic blood pressure after 4 and 8 weeks of randomized, double-blind treatment	Twenty-four hour mean msSBP will be performed at baseline and week 4, week 8 of double-blind treatment	Baseline, week 4, week 8
The proportion of responders to antihypertensive treatment after 12 weeks of randomized, double-blind treatment	Responders is the ratio of the number of participants achieving SBP/DBP<140/90 mmHg or a reduction from baseline of >20 mmHg in mean systolic blood pressure and or >10 mmHg in mean diastolic blood pressure to the total number of participants in each group	Week 12
The proportion of patients meeting the mean sitting blood pressure target after 4, 8, and 12 weeks of randomized, double-blind treatment	Sitting blood pressure target is SBP/DBP<140/90 mmHg	Week 4, week 8, week 12

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportion of patients meeting the mean sitting blood pressure target after 20 weeks of extended treatment	Sitting blood pressure target is SBP/DBP<140/90 mmHg	Week 36
The proportion of patients meeting the mean sitting blood pressure target at the end of treatment	Sitting blood pressure target is SBP/DBP<140/90 mmHg	Week 56

Collaborators and Investigators

• Sponsor: Shenzhen Salubris Pharmaceuticals Co., Ltd.
• Investigators: Principal Investigator: Xinchun Yang, Ph.D, Beijing Chaoyang Hospital, Capital Medical University City:Beijing

Study record dates

Study Major Dates

• Study Start (Actual): April 29, 2021
• Primary Completion (Actual): August 16, 2022
• Study Completion (Actual): February 24, 2023

Study Registration Dates

• First Submitted: June 13, 2024
• First Submitted That Met QC Criteria: June 17, 2024
• First Posted (Actual): June 18, 2024

Study Record Updates

• Last Update Posted (Actual): June 28, 2024
• Last Update Submitted That Met QC Criteria: June 26, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: Essential hypertension; Amlodipine; Systolic BP; Allisartan Isoproxil; Diastolic BP
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Essential Hypertension; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Amlodipine
• Other Study ID Numbers: SAL0107A103

Drug and device information, study documents

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