Study of Efficacy and Safety of Irbesartan/Amlodipine 4 Fixed Combination Therapy in Hypertensive Patients Uncontrolled on Irbesartan or Amlodipine Monotherapy

A Prospective Open-label Multicentre Study of Efficacy and Safety of Irbesartan/Amlodipine 4 Fixed Combination Therapy in Hypertensive Patients Uncontrolled on Irbesartan 150 mg or Amlodipine 5 mg Monotherapy

Primary Objective:

- To assess the proportion of patients with controlled Office Blood Pressure Measurements (OBPM), defined as Systolic blood pressure < 140 mmHg and Diastolic blood pressure <90mmHg, at the end of the study

Secondary Objectives:

• To examine over time the antihypertensive effect of the 4 doses of the fixed combination therapy irbesartan/amlodipine on OBPM (SBP (systolic blood pressure) and DBP (diastolic blood pressure)
• To examine the proportion of patients with controlled OBPM (systolic BP<140 mm Hg and diastolic BP<90 mmHg) of the different dose groups over time
• To determine the incidence and severity of adverse events.

Study Overview

• Status: Completed
• Conditions: Hypertension
• Intervention / Treatment: Drug: Irbesartan/Amlodipine (150/5mg); Drug: Irbesartan/Amlodipine (150/10mg); Drug: Irbesartan/Amlodipine (300/5mg); Drug: Irbesartan/Amlodipine (300/10mg)

Detailed Description

16 weeks

• V1 (week 0): Inclusion visit.
• V2 (Week 4): Irbesartan/amlodipine 150/5 mg fixed combination visit
• V3 (Week 8): 1st dose escalation for patients in whom OBPM is not controlled (SBP ≥ 140 mmHg or DBP ≥ 90mmHg,
• V4 (Week 12): 2nd Dose escalation visit for patients in whom OBPM is not controlled (SBP ≥ 140 mmHg or DBP ≥ 90mmHg
• V5 (Week 16): End of study visit

• Study Type: Interventional
• Enrollment (Actual): 158
• Phase: Phase 3

Contacts and Locations

Study Locations

• Russian Federation
  • Moscow, Russian Federation
    • Sanofi-Aventis Administrative Office

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria :

• Men and women ≥18 years old
• Established essential hypertension
• Treated with irbesartan 150 mg or amlodipine 5 mg as monotherapy for at least 2 weeks
• With uncontrolled systolic BP (blood pressure) defined as ≥140 mm Hg assessed by OBPM (office blood pressure measurements)
• Signed written informed consent obtained prior to inclusion to the study

Exclusion criteria:

• Mean systolic BP ≥180 mm Hg and/or mean diastolic BP ≥110 mm Hg by OBPM on Visit 1
• Known or suspected causes of secondary hypertension
• Patients with bilateral artery stenosis, renal artery stenosis in a solitary kidney, renal transplant or only has one functioning kidney
• Known contraindications or hypersensitivity to either amlodipine or irbesartan or to the combination
• History of angioedema related to the administration of an angiotensin II receptor antagonist or any combination of the drugs used
• Severe hepatic impairment (Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) >5 times the upper normal limit (ULN) or history of hepatic encephalopathy, esophageal varices or portocaval shunt)
• Severe renal impairment (glomerular filtration rate <30 ml/min)
• Concomitant use of any other antihypertensive treatment except of Irbesartan and Amlodipine
• Administration of any other investigational drug within 30 days before inclusion
• Presence of any other conditions that would restrict or limit the patient participation for the duration of the study
• Pregnant or breast feeding women
• Women of childbearing potential unable or unwilling to use an acceptable method to avoid pregnancy for the entire study period
• Patient is the investigator or any sub-investigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the protocol

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Irbesartan/Amlodipine 150/5 mg fixed combination; 1 tablet once daily in the morning for 4 weeks Patient will be first treated with irbesartan 150mg or amlodipine 5mg, 1 tablet /day for 4 weeks. If OBPM is controlled on monotherapy at week 4 (SBP <140 mmHg and DBP<90 mmHg), patient will be withdrawn from the study	Drug: Irbesartan/Amlodipine (150/5mg); Pharmaceutical form: tablet Route of administration: oral
Experimental: Irbesartan/Amlodipine 150/10 mg fixed combination; 1 tablet once daily in the morning for 4 weeks	Drug: Irbesartan/Amlodipine (150/10mg); Pharmaceutical form: tablet Route of administration: oral
Experimental: Irbesartan/Amlodipine 300/5 mg fixed combination; 1 tablet once daily in the morning for 4 weeks	Drug: Irbesartan/Amlodipine (300/5mg); Pharmaceutical form: tablet Route of administration: oral
Experimental: Irbesartan/Amlodipine 300/10 mg fixed combination; 1 tablet once daily in the morning for 4 weeks. If OBPM is controlled at week 12, patients will continue on the same therapy until the end of the study	Drug: Irbesartan/Amlodipine (300/10mg); Pharmaceutical form:tablet Route of administration: oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion of patients with controlled OBPM (SBP<140 mmHg and DBP<90 mmHg) at the end of the study	up to 16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with adverse events		up to 16 weeks
Proportion of patients with controlled OBPM by visit and treatment group	at Visit 3 (Week 8), at Visit 4 (Week 12) and at Visit 5 (Week 16)	up to 16 weeks
Mean change in OBPM between 2 visits	Visit 2 (Week 4) and Visit 5 (Week 16), Visit 2 (Week 4) and Visit 4 (week 12), Visit 2 (Week 4) and Visit 5 (Week 16), Visit 3 (Week 8) and Visit 4 (Week 12), Visit 3 (Week 8) and Visit 5 (Week 16)	up to 16 weeks
Number of patients who discontinue from the study due to adverse events		up to 16 weeks
Number of patients with abnormal liver function	As measured by AST, ALT, total bilirubin and serum creatinine	up to 16 weeks

Collaborators and Investigators

• Sponsor: Sanofi

Study record dates

Study Major Dates

• Study Start: May 1, 2012
• Primary Completion (Actual): January 1, 2013
• Study Completion (Actual): January 1, 2013

Study Registration Dates

• First Submitted: June 19, 2012
• First Submitted That Met QC Criteria: June 19, 2012
• First Posted (Estimate): June 21, 2012

Study Record Updates

• Last Update Posted (Estimate): January 18, 2013
• Last Update Submitted That Met QC Criteria: January 17, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; 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; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Amlodipine; Irbesartan
• Other Study ID Numbers: IRBES_L_05887; U1111-1117-9116 (Other Identifier: UTN)