Study of Efficacy and Safety of LCZ696/Amlodipine in Grade 1 and 2 Hypertension Patients Uncontrolled by LCZ696 Monotherapy

NCT06236061 | Completed Phase 3

• 1 other identifier: CLAZ696B11302
• Study Type: interventional
• Target: 718
• Locations: 1 country
• Sites: 43

Brief Summary

This CLAZ696B11302 study is composed of two parts; the Core part including double-blind period, and the open-label extension (OLE) part which is an open-label extension of the Core part. The purpose of the Core part is to demonstrate that LCZ696 (LCZ) when used in combination with amlodipine (AML), denoted as LCZ/AML, will provide greater blood pressure lowering benefit compared to LCZ monotherapy in patients with grade 1 and 2 hypertension not adequately controlled with LCZ monotherapy. The purpose of the OLE part is to assess the long-term safety, tolerability and efficacy of the treatment with LCZ/AML.

Conditions

Hypertension

Keywords

LCZ696; Phase 3; grade 1 and 2 hypertension; Amlodipine

Outcome Measures

Primary Outcomes (1)

• [Core Part] Change from baseline to Week 8 in msSBP

  Change from baseline to Week 8 in mean sitting systolic blood pressure (msSBP)

  Baseline, Week 8

Secondary Outcomes (12)

• [Core Part] Change from baseline to Week 8 in maSBP

  Baseline, Week 8

• [Core Part] Proportion of patients achieving a blood pressure control after 8 weeks of treatment

  8 weeks

• [Core Part] Change from baseline to Week 8 in msDBP

  Baseline, Week 8

• [Core Part] Change from baseline to Week 8 in maDBP

  Baseline, Week 8

• [Core Part] Proportion of patients achieving a msSBP response after 8 weeks of treatment

  8 weeks

Study Arms (4)

LCZ 200mg

ACTIVE COMPARATOR

Oral administration, 1 tablet of LCZ 200 mg daily, 4 capsules of Amlodipine placebo daily.

Drug: LCZ; Other: Placebo

LCZ 200mg + AML 2.5mg

EXPERIMENTAL

Oral administration, 1 tablet of LCZ 200 mg daily, 1 capsule of Amlodipine 2.5 mg daily and 3 capsules of Amlodipine placebo daily.

Drug: LCZ/AML 200 mg/2.5 mg; Other: Placebo

LCZ 200mg + AML 5mg

EXPERIMENTAL

Oral administration, 1 tablet of LCZ 200 mg daily, 2 capsules of Amlodipine 2.5 mg daily and 2 capsules of Amlodipine placebo daily.

Drug: LCZ/AML 200 mg/5 mg; Other: Placebo

LCZ 200mg + AML 10mg

EXPERIMENTAL

Oral administration, 1 tablet of LCZ 200 mg daily, 4 capsules of Amlodipine 2.5 mg daily.

Drug: LCZ/AML 200 mg/10 mg

Interventions

Placebo OTHER

Matching placebo of Amlodipine.

LCZ 200mg; LCZ 200mg + AML 2.5mg; LCZ 200mg + AML 5mg

LCZ DRUG

LCZ 200 mg

Also known as: LCZ696

LCZ 200mg

LCZ/AML 200 mg/2.5 mg DRUG

LCZ/AML 200 mg/2.5 mg

Also known as: LCZ696/Amlodipine

LCZ 200mg + AML 2.5mg

LCZ/AML 200 mg/5 mg DRUG

LCZ/AML 200 mg/5 mg

Also known as: LCZ696/Amlodipine

LCZ 200mg + AML 5mg

LCZ/AML 200 mg/10 mg DRUG

LCZ/AML 200 mg/10 mg

Also known as: LCZ696/Amlodipine

LCZ 200mg + AML 10mg

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Core Part)
• Patients with grade 1 and 2 essential hypertension, untreated or currently taking antihypertensive therapy
• 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)
• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (43)

Novartis Investigative Site

Nagoya, Aichi-ken, 4518511, Japan

Location

Novartis Investigative Site

Nagoya, Aichi-ken, 453-0804, Japan

Location

Novartis Investigative Site

Nagoya, Aichi-ken, 4540933, Japan

Location

Novartis Investigative Site

Nagoya, Aichi-ken, 4578511, Japan

Location

Novartis Investigative Site

Itoshima, Fukuoka, 8191104, Japan

Location

Novartis Investigative Site

Chitose, Hokkaido, 066-0032, Japan

Location

Novartis Investigative Site

Sapporo, Hokkaido, 30026, Japan

Location

Novartis Investigative Site

Sapporo, Hokkaido, 630826, Japan

Location

Novartis Investigative Site

Sapporo, Hokkaido, 630842, Japan

Location

Novartis Investigative Site

Akashi, Hyōgo, 674-0081, Japan

Location

Novartis Investigative Site

Amagasaki, Hyōgo, 660-0861, Japan

Location

Novartis Investigative Site

Tsukuba, Ibaraki, 3050861, Japan

Location

Novartis Investigative Site

Kamakura, Kanagawa, 247-0055, Japan

Location

Novartis Investigative Site

Kawasaki-shi, Kanagawa, 211-0041, Japan

Location

Novartis Investigative Site

Yokohama, Kanagawa, 231-0023, Japan

Location

Novartis Investigative Site

Yokohama, Kanagawa, 232-0064, Japan

Location

Novartis Investigative Site

Ōsaki, Miyagi, 989-6143, Japan

Location

Novartis Investigative Site

Sendai, Miyagi, 980-0011, Japan

Location

Novartis Investigative Site

Sendai, Miyagi, 9830039, Japan

Location

Novartis Investigative Site

Suita, Osaka, 5650853, Japan

Location

Novartis Investigative Site

Chiyoda City, Tokyo, 101-0041, Japan

Location

Novartis Investigative Site

Chuo Ku, Tokyo, 104-0031, Japan

Location

Novartis Investigative Site

Chuo-ku, Tokyo, 1030027, Japan

Location

Novartis Investigative Site

Hachiōji, Tokyo, 192-0046, Japan

Location

Novartis Investigative Site

Kiyose, Tokyo, 204-0021, Japan

Location

Novartis Investigative Site

Musashino, Tokyo, 1800022, Japan

Location

Novartis Investigative Site

Nerima Ku, Tokyo, 1770051, Japan

Location

Novartis Investigative Site

Setagaya-ku, Tokyo, 1550031, Japan

Location

Novartis Investigative Site

Shibuya City, Tokyo, 150-0013, Japan

Location

Novartis Investigative Site

Shinagawa-Ku, Tokyo, 141-0032, Japan

Location

Novartis Investigative Site

Shinjuku Ku, Tokyo, 160-0008, Japan

Location

Novartis Investigative Site

Shinjuku-ku, Tokyo, 1600017, Japan

Location

Novartis Investigative Site

Shinjuku-ku, Tokyo, 1690072, Japan

Location

Novartis Investigative Site

Suginami-ku, Tokyo, 166-0003, Japan

Location

Novartis Investigative Site

Toshima-Ku, Tokyo, 171-0021, Japan

Location

Novartis Investigative Site

Chuoh-ku, 104-0031, Japan

Location

Novartis Investigative Site

Fukuoka, 810-0021, Japan

Location

Novartis Investigative Site

Hiroshima, 732-0053, Japan

Location

Novartis Investigative Site

Kyoto, 615-8125, Japan

Location

Novartis Investigative Site

Osaka, 5300002, Japan

Location

Novartis Investigative Site

Osaka, 5320003, Japan

Location

Novartis Investigative Site

Osaka, 536-0008, Japan

Location

Novartis Investigative Site

Osaka, 550-0013, Japan

Location

MeSH Terms

Conditions

Hypertension; Lymphoma, Follicular

Interventions

sacubitril and valsartan sodium hydrate drug combination; Amlodipine

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Dihydropyridines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: In the Core part, Participant, care provider and Investigator will be masked. In the OLE part, no masking to anyone.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This study is composed of two parts; the Core part including double-blind period, and the open-label extension (OLE) part. The Core part is a parallel model, and the OLE is a sequential model.

Study Record Dates

• First Submitted: January 23, 2024
• First Posted: February 1, 2024
• Study Start: April 8, 2024
• Primary Completion: May 28, 2025
• Study Completion: December 23, 2025
• Last Updated: January 13, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share

Locations

JP (43)