Clinical Trials List
Protocol NumberCLCZ696A2319
2012-09-01 - 2013-12-31
Phase III
Terminated5
A randomized, 8-week, double-blind, parallel-group, active controlled, multicenter study to evaluate the efficacy and safety of the combination of LCZ696 200 mg + amlodipine 5 mg in comparison with amlodipine 5 mg in patients with essential hypertension not adequately responsive to amlodipine 5 mg monotherapy treatment.
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Trial Applicant
NOVARTIS (TAIWAN) CO., LTD.
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Sponsor
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- 黃惠君 Division of Cardiovascular Diseases
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Tse-Min Lu Division of Cardiovascular Diseases
- Wen-Chung Yu Division of Cardiovascular Diseases
- Shih-Hsien Sung Division of Cardiovascular Diseases
- 林幸榮 Division of Cardiovascular Diseases
- Kang-Ling Wang Division of Cardiovascular Diseases
The Actual Total Number of Participants Enrolled
0 Terminated
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 楊晨佳 Division of Cardiovascular Diseases
- Wen-Yuan Lin Division of Cardiovascular Diseases
- 陳業鵬 Division of Cardiovascular Diseases
- 盧炯睿 Division of Cardiovascular Diseases
- Po-Yen Ko Division of Cardiovascular Diseases
- Chih Hsueh Lin Division of Cardiovascular Diseases
- 謝禮全 Division of Cardiovascular Diseases
- Shih-Sheng Chang Division of Cardiovascular Diseases
The Actual Total Number of Participants Enrolled
0 Terminated
Condition/Disease
essential hypertension
Objectives
The purpose of this study is to assess whether LCZ696 when used in
combination with amlodipine will provide greater BP lowering benefit compared to
amlodipine monotherapy in Asian hypertensive patients not adequately responsive to
amlodipine monotherapy.
Test Drug
LCZ696
Active Ingredient
LCZ696
Dosage Form
Dosage
200
Endpoints
Efficacy assessments:
• Office Blood Pressure
• 24 Hour Ambulatory Blood Pressure
Other assessments:
• Vital signs
• Physical examination
• Hematology, biochemistry, urinalysis
• AEs/SAEs
• Office Blood Pressure
• 24 Hour Ambulatory Blood Pressure
Other assessments:
• Vital signs
• Physical examination
• Hematology, biochemistry, urinalysis
• AEs/SAEs
Inclution Criteria
Inclusion criteria
Patients eligible for inclusion in this study have to fulfill all of the following criteria:
1. Written informed consent must be obtained before any assessment is performed.
2. Male or female patients > 18 years of age.
3. Patients with mild-to-moderate essential hypertension, untreated or currently taking
antihypertensive therapy.
a. Untreated patients (either newly diagnosed or those patients with a history of
hypertension but have not been taking any antihypertensive drugs for at least 4 weeks
prior to Visit 1) must have an office msSBP ≥ 150 mmHg and < 180 mmHg at both
Visit 1 and Visit 101.
b. Pretreated patients (using antihypertensive treatment within 4 weeks prior to Visit 1)
must have an office msSBP ≥ 145 mmHg and < 180 mmHg after washout at Visit 101.
4. Patients that are not adequately responsive to amlodipine treatment: all patients must have
an office msSBP ≥ 145 mmHg and < 180 mmHg at the completion of the 4-week
amlodipine 5 mg active run-in epoch (at the randomization visit (Visit 201).
5. Patients must successfully complete ABPM and pass technical requirements at Visit 201
to be qualified for randomization.
6. Ability to communicate and comply with all study requirements and demonstrate good
medication compliance (≥ 80% compliance rate) during the run-in epoch.
Patients eligible for inclusion in this study have to fulfill all of the following criteria:
1. Written informed consent must be obtained before any assessment is performed.
2. Male or female patients > 18 years of age.
3. Patients with mild-to-moderate essential hypertension, untreated or currently taking
antihypertensive therapy.
a. Untreated patients (either newly diagnosed or those patients with a history of
hypertension but have not been taking any antihypertensive drugs for at least 4 weeks
prior to Visit 1) must have an office msSBP ≥ 150 mmHg and < 180 mmHg at both
Visit 1 and Visit 101.
b. Pretreated patients (using antihypertensive treatment within 4 weeks prior to Visit 1)
must have an office msSBP ≥ 145 mmHg and < 180 mmHg after washout at Visit 101.
4. Patients that are not adequately responsive to amlodipine treatment: all patients must have
an office msSBP ≥ 145 mmHg and < 180 mmHg at the completion of the 4-week
amlodipine 5 mg active run-in epoch (at the randomization visit (Visit 201).
5. Patients must successfully complete ABPM and pass technical requirements at Visit 201
to be qualified for randomization.
6. Ability to communicate and comply with all study requirements and demonstrate good
medication compliance (≥ 80% compliance rate) during the run-in epoch.
Exclusion Criteria
Exclusion criteria
Patients fulfilling any of the following criteria are not eligible for inclusion in this study. No
additional exclusions may be applied by the investigator, in order to ensure that the study
population will be representative of all eligible patients.
1. Women of child-bearing potential, defined as all women physiologically capable of
becoming pregnant, unless they are using highly effective methods of contraception
during dosing and for 5 times the terminal half-life of investigational treatment. Effective
contraception methods include:
• Total abstinence (when this is in line with the preferred and usual lifestyle of the
subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation
methods) and withdrawal are not acceptable methods of contraception
• Female sterilization (have had surgical bilateral oophorectomy with or without
hysterectomy) or tubal ligation at least six weeks before taking study treatment. In
case of oophorectomy alone, only when the reproductive status of the woman has
been confirmed by follow up hormone level assessment
• Male sterilization (at least 6 m prior to screening). For female subjects on the study,
the vasectomized male partner should be the sole partner for that subject
• Combination of any two of the following (a+b or a+c, or b+c):
a. Use of oral, injected or implanted hormonal methods of contraception or other
forms of hormonal contraception that have comparable efficacy (failure rate
<1%), for example hormone vaginal ring or transdermal hormone contraception.
• In case of use of oral contraception women should have been stable on the same
pill for a minimum of 3 months before taking study treatment
b. Placement of an intrauterine device (IUD) or intrauterine system (IUS)
c. Barrier methods of contraception: Condom or Occlusive cap (diaphragm or
cervical/vault caps) with spermicidal foam/gel/film/cream/ vaginal suppository
• Women are considered post-menopausal and not of child bearing potential if they
have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical
profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical
bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six
weeks ago. In the case of oophorectomy alone, only when the reproductive status of
the woman has been confirmed by follow up hormone level assessment is she
considered not of child bearing potential.
2. Pregnant or nursing (lactating) women, where pregnancy is defined as a state of a female
after conception and until the termination of gestation, confirmed by a positive hCG
laboratory test (≥ 5 mIU/ml).
3. Malignant or severe hypertension (grade 3 of WHO classification; msDBP ≥110 mmHg
and/or msSBP ≥ 180 mmHg).
4. History of angioedema, drug-related or otherwise.
5. 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 (PKD), drug-induced
hypertension, etc.
6. Transient ischemic cerebral attack (TIA) during the 12 months prior to Visit 1 or any
history of stroke.
7. History of myocardial infarction, coronary bypass surgery, or any percutaneous coronary
intervention (PCI) during the 12 months prior to Visit 1.
8. Current angina pectoris requiring pharmacological therapy (other than patients on a stable
dose of oral or topical nitrates).
9. Patients with Type 1 or Type 2 diabetes mellitus who are not well controlled based on the
investigator’s clinical judgment. Patients currently being treated for diabetes mellitus must
be on stable dose of antidiabetic medication for at least 4 weeks prior to Visit 1.
10. Previous or current diagnosis of heart failure (NYHA Class II-IV).
11. Clinically significant valvular heart disease at Visit 1.
12. History or current diagnosis of the following cardiac abnormalities:
• Second or third degree AV block without a pacemaker.
• Clinically significant cardiac arrhythmias including uncontrolled atrial fibrillation
(ventricular rate ≥ 120 bpm).• History of familial long QT syndrome or family history of torsades de pointes.
13. Known active liver disease or cirrhosis or evidence of hepatic disease as determined by
ALT or AST > 2 times the upper limit of the normal (xULN) , or TBL > 2 xULN or AP >
1.5 xULN range at Visit 1, or a history of hepatic encephalopathy, a history of esophageal
varices, or a history of portocaval shunt.
14. Patients on renal dialysis or with history of renal transplatation.
15. Other significant laboratory findings at Visit 1 such as serum creatinine > 1.5 times the ULN, serum potassium > 5.5 mmol/L, or other clinically significant laboratory
abnormalities confirmed by repeat measurements at Visit 1 (at the investigator’s
discretion).
16. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
17. Any surgical or medical conditions that may significantly alter the absorption, distribution,
metabolism or excretion of any drug substance, but not limited to any of the following:
history of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy,
bowel resection, gastric bypass, gastric stapling, or gastric banding, currently active or
history of active inflammatory bowel disease within 12 months prior to Visit 1.
18. Any surgical or medical conditions that, in the opinion of the investigator, place the patient at higher risk from his/her participation in the study, or are likely to prevent the patient from complying with the requirements of the study or completing the trial period.
19. Patients unwilling or not able to discontinue safely the use of current antihypertensive medications during the study time period, as required by the protocol. Administration of any agent indicated for the treatment of hypertension after Visit 1, with the permitted exception of those antihypertensive medications requiring tapering down commencing at Visit 1 and completing by Visit 101.
20. Any contraindication or history of hypersensitivity to any of the study drugs (including active comparators) or to drugs with similar chemical structures.
21. History of drug or alcohol abuse within the last 1 year.
22. Night shift workers.
23. Upper arm circumference > 42 cm (because of ABPM assessment).
24. Use of other investigational drugs within 30 days or 5 half-lives of Visit 1, whichever is longer.
25. Patients who previously entered a LCZ696 study and had been randomized or enrolled to receive active drug treatment
26. Persons directly involved in the execution of this clinical study.
Patients fulfilling any of the following criteria are not eligible for inclusion in this study. No
additional exclusions may be applied by the investigator, in order to ensure that the study
population will be representative of all eligible patients.
1. Women of child-bearing potential, defined as all women physiologically capable of
becoming pregnant, unless they are using highly effective methods of contraception
during dosing and for 5 times the terminal half-life of investigational treatment. Effective
contraception methods include:
• Total abstinence (when this is in line with the preferred and usual lifestyle of the
subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation
methods) and withdrawal are not acceptable methods of contraception
• Female sterilization (have had surgical bilateral oophorectomy with or without
hysterectomy) or tubal ligation at least six weeks before taking study treatment. In
case of oophorectomy alone, only when the reproductive status of the woman has
been confirmed by follow up hormone level assessment
• Male sterilization (at least 6 m prior to screening). For female subjects on the study,
the vasectomized male partner should be the sole partner for that subject
• Combination of any two of the following (a+b or a+c, or b+c):
a. Use of oral, injected or implanted hormonal methods of contraception or other
forms of hormonal contraception that have comparable efficacy (failure rate
<1%), for example hormone vaginal ring or transdermal hormone contraception.
• In case of use of oral contraception women should have been stable on the same
pill for a minimum of 3 months before taking study treatment
b. Placement of an intrauterine device (IUD) or intrauterine system (IUS)
c. Barrier methods of contraception: Condom or Occlusive cap (diaphragm or
cervical/vault caps) with spermicidal foam/gel/film/cream/ vaginal suppository
• Women are considered post-menopausal and not of child bearing potential if they
have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical
profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical
bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six
weeks ago. In the case of oophorectomy alone, only when the reproductive status of
the woman has been confirmed by follow up hormone level assessment is she
considered not of child bearing potential.
2. Pregnant or nursing (lactating) women, where pregnancy is defined as a state of a female
after conception and until the termination of gestation, confirmed by a positive hCG
laboratory test (≥ 5 mIU/ml).
3. Malignant or severe hypertension (grade 3 of WHO classification; msDBP ≥110 mmHg
and/or msSBP ≥ 180 mmHg).
4. History of angioedema, drug-related or otherwise.
5. 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 (PKD), drug-induced
hypertension, etc.
6. Transient ischemic cerebral attack (TIA) during the 12 months prior to Visit 1 or any
history of stroke.
7. History of myocardial infarction, coronary bypass surgery, or any percutaneous coronary
intervention (PCI) during the 12 months prior to Visit 1.
8. Current angina pectoris requiring pharmacological therapy (other than patients on a stable
dose of oral or topical nitrates).
9. Patients with Type 1 or Type 2 diabetes mellitus who are not well controlled based on the
investigator’s clinical judgment. Patients currently being treated for diabetes mellitus must
be on stable dose of antidiabetic medication for at least 4 weeks prior to Visit 1.
10. Previous or current diagnosis of heart failure (NYHA Class II-IV).
11. Clinically significant valvular heart disease at Visit 1.
12. History or current diagnosis of the following cardiac abnormalities:
• Second or third degree AV block without a pacemaker.
• Clinically significant cardiac arrhythmias including uncontrolled atrial fibrillation
(ventricular rate ≥ 120 bpm).• History of familial long QT syndrome or family history of torsades de pointes.
13. Known active liver disease or cirrhosis or evidence of hepatic disease as determined by
ALT or AST > 2 times the upper limit of the normal (xULN) , or TBL > 2 xULN or AP >
1.5 xULN range at Visit 1, or a history of hepatic encephalopathy, a history of esophageal
varices, or a history of portocaval shunt.
14. Patients on renal dialysis or with history of renal transplatation.
15. Other significant laboratory findings at Visit 1 such as serum creatinine > 1.5 times the ULN, serum potassium > 5.5 mmol/L, or other clinically significant laboratory
abnormalities confirmed by repeat measurements at Visit 1 (at the investigator’s
discretion).
16. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
17. Any surgical or medical conditions that may significantly alter the absorption, distribution,
metabolism or excretion of any drug substance, but not limited to any of the following:
history of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy,
bowel resection, gastric bypass, gastric stapling, or gastric banding, currently active or
history of active inflammatory bowel disease within 12 months prior to Visit 1.
18. Any surgical or medical conditions that, in the opinion of the investigator, place the patient at higher risk from his/her participation in the study, or are likely to prevent the patient from complying with the requirements of the study or completing the trial period.
19. Patients unwilling or not able to discontinue safely the use of current antihypertensive medications during the study time period, as required by the protocol. Administration of any agent indicated for the treatment of hypertension after Visit 1, with the permitted exception of those antihypertensive medications requiring tapering down commencing at Visit 1 and completing by Visit 101.
20. Any contraindication or history of hypersensitivity to any of the study drugs (including active comparators) or to drugs with similar chemical structures.
21. History of drug or alcohol abuse within the last 1 year.
22. Night shift workers.
23. Upper arm circumference > 42 cm (because of ABPM assessment).
24. Use of other investigational drugs within 30 days or 5 half-lives of Visit 1, whichever is longer.
25. Patients who previously entered a LCZ696 study and had been randomized or enrolled to receive active drug treatment
26. Persons directly involved in the execution of this clinical study.
The Estimated Number of Participants
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Taiwan
50 participants
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Global
236 participants
