Study to Evaluate and Compare the Efficacy and Safety of AZM and AML Combined and Alone in Mild-to-moderate Essential Hypertensive Subjects

Celltrion Healthcare

Status and phase: Completed; Phase 3

Conditions: Essential Hypertension

Treatments: Drug: AZM X' mg + AML Y' mg; Drug: AZM X mg + AML Y mg; Drug: AML Y mg; Drug: AZM X' mg + AML Y mg; Drug: AML Y' mg; Drug: AZM X mg + AML Y' mg; Drug: AZM X mg; Drug: AZM X' mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT05385770

CT-L05-301

Details and patient eligibility

About

This is an 8-week, randomized, double-blind Phase 3, multicentre study to determine the optimal dose of AZM and AML in combination therapy and to compare efficacy and tolerability of the combined therapy to each of the monotherapy in essential hypertensive subjects who are not adequately controlled on AZM and AML monotherapy.

Enrollment: 890 patients

Sex: All

Ages: 19 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Subjects voluntarily agree to participate in the trial and signed the written ICF, after listening to the purpose, method, and effect of clinical trial
• Male or female adult subjects (Legal minimum age of adult requirement is country specific, and requirement of current country specific regulations will be applied) below the age of 75 years, inclusive
• Subjects with mild-to-moderate essential hypertension
• Subjects who are capable of understanding and complying with protocol requirements

Exclusion criteria

• Subjects who have msitSBP >180 mmHg or msitDBP >110 mmHg; Subjects who have difference in the blood pressure between 3 measurements (confirmed by a second set of three measurements; 3 sitting systolic BP (sitSBP) measurements differing by more than 20 mmHg or 3 sitting diastolic BP (sitDBP) measurements differing by more than 10 mmHg)
• Secondary hypertension, Symptomatic orthostatic hypotension
• Clinically significant Electrocardiogram (ECG) abnormalities, Severe heart disease, Clinically significant ventricular tachycardia, atrial fibrillation, atrial flutter or other clinically significant arrhythmia, Hypertrophic obstructive cardiomyopathy, severe obstructive coronary artery disease, aortic stenosis, hemodynamically relevant stenosis of the aortic or mitral valve
• Severe cerebrovascular disease, Known moderate or malignant retinopathy within the past 6 months; History of unexplained syncope within the prior 2 years, or a known syncopal disorder
• Significant thyroid disease, Type 1 or 2 diabetes mellitus with poor glucose control, Wasting disease, Autoimmune diseases, Connective tissue disease
• Subjects who have clinically significant laboratory abnormalities : creatinine clearance < 30 mL/min, serum creatinine > 2 mg/dL or > 200 μmol/L, serum potassium <3.5 mmol/L or > 5.5mmol/L, alanine aminotransferase or aspartate aminotransferase > 3 × upper limit normal (ULN)
• Any surgical or medical condition of the gastrointestinal tract that might significantly alter the absorption, distribution, metabolism, or excretion of the drug
• Positive for HIV, HCV Ab, and/or HBsAg
• History of drug or alcohol abuse within the past 1 year
• Subjects who are pregnant or lactating women, women suspected of being pregnant, women who wish to be pregnant during the study, or women of child-bearing potential who are not using medically acceptable methods of contraception
• Any chronic inflammatory condition needing chronic anti-inflammatory therapy, A known hypersensitivity to any main excipients and components of the investigational drugs or other drugs in the same class, Subjects who have previously experienced symptoms characteristic of angioedema during treatment with angiotensin-converting enzyme inhibitors or angiotensin II subtype 1 receptor blocker
• Subjects who have received any investigational product within 28 days prior to screening or is currently participating in another investigational study
• Subjects who are required to take excluded medications at any point during the study

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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890 participants in 8 patient groups

AZM Xmg

Active Comparator group

Description:

1\. AZM Xmg (4 weeks) Non-responder -\> AZM Xmg (8 weeks)

Treatment:

Drug: AZM X mg

AZM X'mg

Active Comparator group

Description:

1\. AZM X'mg (4 weeks) Non-responder -\> AZM X'mg (8 weeks)

Treatment:

Drug: AZM X' mg

AML Ymg

Active Comparator group

Description:

1\. AML Ymg (4 weeks) Non-responder -\> AML Ymg (8 weeks)

Treatment:

Drug: AML Y mg

AML Y'mg

Active Comparator group

Description:

1\. AML Y'mg (4 weeks) Non-responder -\> AML Y'mg (8 weeks)

Treatment:

Drug: AML Y' mg

AZM/AML X/Ymg

Active Comparator group

Description:

1. AZM Xmg (4 weeks) Non-responder -\> AZM Xmg + AML Ymg (8 weeks) 2. AML Ymg (4 weeks) Non-responder -\> AZM Xmg + AML Ymg (8 weeks)

Treatment:

Drug: AZM X mg

Drug: AML Y mg

Drug: AZM X mg + AML Y mg

AZM/AML X'/Ymg

Active Comparator group

Description:

1. AZM X'mg (4 weeks) Non-responder -\> AZM X'mg + AML Ymg (8 weeks) 2. AML Ymg (4 weeks) Non-responder -\> AZM X'mg + AML Ymg (8 weeks)

Treatment:

Drug: AZM X' mg

Drug: AZM X' mg + AML Y mg

Drug: AML Y mg

AZM/AML X/Y'mg

Active Comparator group

Description:

1. AZM Xmg (4 weeks) Non-responder -\> AZM Xmg + AML Y'mg (8 weeks) 2. AML Y'mg (4 weeks) Non-responder -\> AZM Xmg + AML Y'mg (8 weeks)

Treatment:

Drug: AZM X mg

Drug: AZM X mg + AML Y' mg

Drug: AML Y' mg

AZM/AML X'/Y'mg

Active Comparator group

Description:

1. AZM X'mg (4 weeks) Non-responder -\> AZM X'mg + AML Y'mg (8 weeks) 2. AML Y'mg (4 weeks) Non-responder -\> AZM X'mg + AML Y'mg (8 weeks)

Treatment:

Drug: AZM X' mg

Drug: AML Y' mg

Drug: AZM X' mg + AML Y' mg