Study of efficacy and safety of LCZ696/Amlodipine in grade 1 and 2 hypertension patients uncontrolled by LCZ696 monotherapy

JRCT ID: jRCT2031230703

Registered date:14/03/2024

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: essential hypertension
• Date of first enrollment: 08/04/2024
• Target sample size: 688
• Study type: Interventional

Intervention(s)

1. Core part, treatment for 12 weeks
Active Comparator: LCZ 200mg
Oral administration, 1 tablet of LCZ 200 mg daily, 4 capsules of Amlodipine placebo daily.
Intervention: Drug: LCZ
Experimental: LCZ 200mg + AML 2.5mg
Oral administration, 1 tablet of LCZ 200 mg daily, 1 capsule of Amlodipine 2.5 mg daily and 3 capsules of Amlodipine placebo daily.
Intervention: Drug: LCZ/AML
Experimental: LCZ 200mg + AML 5mg
Oral administration, 1 tablet of LCZ 200 mg daily, 2 capsules of Amlodipine 2.5 mg daily and 2 capsules of Amlodipine placebo daily.
Intervention: Drug: LCZ/AML
Experimental: LCZ 200mg + AML 10mg
Oral administration, 1 tablet of LCZ 200 mg daily, 4 capsules of Amlodipine 2.5 mg daily.
Intervention: Drug: LCZ/AML
2. OLE part, treatment fr 52 weeks
Experimental: LCZ 200mg + AML 2.5mg
Oral administration, 1 tablet of LCZ 200 mg daily, 1 capsule of Amlodipine 2.5 mg daily and 3 capsules of Amlodipine placebo daily.
Intervention: Drug: LCZ/AML
Experimental: LCZ 200mg + AML 5mg
Oral administration, 1 tablet of LCZ 200 mg daily, 2 capsules of Amlodipine 2.5 mg daily and 2 capsules of Amlodipine placebo daily.
Intervention: Drug: LCZ/AML
Experimental: LCZ 200mg + AML 10mg
Oral administration, 1 tablet of LCZ 200 mg daily, 4 capsules of Amlodipine 2.5 mg daily.
Intervention: Drug: LCZ/AML

Outcome(s)

• Primary Outcome: Change from baseline to Week 8 in mean sitting systolic blood pressure (msSBP)

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

- Patients with grade 1 and 2 essential hypertension, untreated or currently taking antihypertensive therapy
1. Untreated patients [either newly diagnosed with essential hypertension or those with a history of hypertension but have not been taking any antihypertensive drugs for 4 weeks prior to screening visit (Visit Scr)] must have a msSBP of >= 150 mmHg and < 180 mmHg at both screening (Visit Scr) and run-in visit (Visit Run-in)
2. Pretreated patients (taking antihypertensive drugs within 4 weeks prior to screening visit (Visit Scr)) must have msSBP < 180 mmHg at screening visit (Visit Scr), and msSBP >= 150 mmHg and < 180 mmHg at run-in visit (Visit Run-in)
- Patients who are not adequately responsive to LCZ 200 mg treatment must have a msSBP >= 140 mmHg and < 180 mmHg at the end of run-in/randomization visit
- Patients who are able to communicate well with the Investigator, to understand and comply with all study requirements, and demonstrate good medication compliance (>= 80% compliance rate) during the single-blind run-in period OLE part)
- Patients who have completed the Core part without permanent study drug discontinuation and who, as judged by the Investigator, are able to continue in the OLE part
- Patients who have msSBP < 160 mmHg and msDBP <100 mmHg at Visit W8 of the double-blind period

Exclude criteria

Core part)
- Patients currently on one or more antihypertensive medications in whom the Investigator considers that the medications cannot be safely discontinued for the duration of the Core part
- Severe hypertension (msSBP >= 180 mmHg and/or msDBP >= 110 mmHg at any visit prior to or at randomization), or malignant hypertension
- History or evidence of a secondary form of hypertension, including but not limited to any of the following: renal parenchymal hypertension, renovascular hypertension (unilateral or bilateral renal artery stenosis), coarctation of the aorta, primary hyperaldosteronism, Cushing's disease, pheochromocytoma, polycystic kidney disease, sleep apnea, and drug-induced hypertension
- Patients with Type 1 or Type 2 diabetes mellitus not well controlled based on the Investigator's clinical judgement
- Concomitant refractory angina pectoris [angina in setting of Coronary Artery Disease (CAD) which is uncontrolled by combination of optimal medical therapy, angioplasty or bypass surgery]
- Clinically significant valvular heart disease at screening
- Any history of stroke or hypertensive encephalopathy
- History of hypersensitivity to any of the study treatments or its excipients, ARBs or to drugs of similar chemical classes
- Use of other investigational drugs within 30 days or 5 half-lives of screening visit, whichever is longer OLE part)
- Any medical condition that in the opinion of the Investigator is likely to prevent the patient from safely tolerating LCZ/AML or complying with the requirements of the study
- Patients who have experience of angioedema event(s) which occurred and reported by the Investigator during the Core part of study
- Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test
- Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception while taking study treatment and for 10 days after stopping study treatment. Highly effective contraception methods are defined as same as the criteria for the Core part.

Related Information

• Primary Sponsor: Iwasaki Ryohei
• Secondary ID(s): NCT06236061