Irbesartan and Amlodipine Combination in Controlling Blood Pressure (I-COMBO)

Study to Evaluate the Safety and Efficacy of Two Fixed Dose Combinations of Irbesartan / Amlodipine and Monotherapy After Eight Weeks of Treatment in Subjects With Uncomplicated Mild to Moderate Essential Hypertension

The primary objective is to compare the extent of reduction of mean Seated Diastolic Blood Pressure (SeDBP) at the end of 8 weeks between each Fixed Dose Combination (FDC), its individual constituents administered as monotherapy and placebo.

The secondary objectives are:

• to compare the reduction of mean Seated Systolic Blood Pressure (SeSBP) at the end of 8 weeks from baseline between each FDC, its individual constituents administered as monotherapy and placebo.
• to compare the reduction of mean SeDBP and SeSBP at 4 weeks from baseline between each FDC, its individual constituents administered as monotherapy and placebo.

Study Overview

• Status: Completed
• Conditions: Hypertension
• Intervention / Treatment: Drug: Placebo; Drug: IRBESARTAN (SR47436); Drug: Irbesartan / Amlodipine; Drug: Amlodipine

• Study Type: Interventional
• Enrollment (Actual): 270
• Phase: Phase 2

Contacts and Locations

Study Locations

• India
  • Mumbai, India
    • Sanofi-Aventis Administrative Office
• Korea, Republic of
  • Seoul, Korea, Republic of
    • Sanofi-Aventis Administrative Office
• Philippines
  • Makati City, Philippines
    • Sanofi-Aventis Administrative Office
• Taiwan
  • Taipei, Taiwan
    • 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:

• Subjects with uncomplicated mild to moderate essential hypertension (as per European Society of Cardiology Classification of Hypertension)

  • Treatment naïve subjects (newly diagnosed subjects or subjects currently only on lifestyle modification) with mean SeDBP of 95 to 109 mmHg at both screening and randomization visit (mean of 3 recordings at intervals of 1 minute) Or
  • Uncontrolled on any anti-hypertensive monotherapy and with mean SeDBP of 90 to 109 mmHg at screening and mean SeDBP of 95 to 109 mmHg at the randomization visit (mean of 3 recordings at intervals of 1 minute).
• Signed written informed consent obtained prior to inclusion in the study.
• Subjects willing to adhere to protocol and study requirements during the entire study duration.
• Subjects having no abnormalities in general physical examination.

Exclusion criteria:

• Subjects who are incapable of giving informed consent for the study.
• Subjects with SeDBP > or = 110mmHg and / or SeSBP > or = 180 mmHg measured at Doctor's office during screening or randomization visit
• Subjects having a difference of > 8 mmHg between any 2 of the 3 SeDBP measurements either at screening or at randomization.
• Subjects who are on any anti-hypertensive therapy and unable to discontinue the anti-hypertensive therapy safely for a period of at least 2 weeks as required by the protocol.
• Subjects who cannot be discontinued on medications prohibited by the protocol.
• Subjects on combination therapies for treatment of hypertension.
• Subjects with known documented secondary hypertension including (but not limited to) hypertension secondary to coarctation of aorta, hyperaldosteronism, unilateral or bilateral renal artery stenosis, Cushing's disease, pheochromocytoma, polycystic kidney disease, etc.
• Subjects with known diabetes (Type 1 or Type 2).

• Subjects with known documented complications of hypertension including (but not limited to):

  • Cardiovascular disease: Ischemic heart disease (angina, myocardial infarction), heart failure, peripheral vascular disease.
  • Cerebrovascular disease: Stroke, cerebral hemorrhage.
  • Ophthalmic: Retinal hemorrhage, impaired vision, retinal microaneurysms.
• Subjects with known severe renal impairment (creatinine clearance < 30 ml/min) calculated using the Cockcroft-Gault equation.
• Subjects with hyperkalemia (>5.1mmol/L) and/or hyponatremia (<133mmol/L).
• Subjects with known severe hepatic impairment (alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3 times the upper limit of normal or history of hepatic encephalopathy, esophageal varices, or portocaval shunt.
• Subjects with clinically significant abnormalities on ECG
• Subjects with any other clinical condition which, in the opinion of the Investigator, might interfere with administration of Irbesartan or Amlodipine and evaluation of the study objectives.
• Subjects with known history of allergy considered due to any of the study drugs or their components, including excipients (lactose) and preservatives.
• Subjects with known history of substance abuse (drug or alcohol dependency, alcohol, if not stopped, <20gms per day will be allowed during the study period).
• Subjects known positive for HIV 1 or 2 virus.
• Subjects with known or suspected impairment of the immune function, and/or receiving immunosuppressive therapy, or having received immunosuppressive therapy within 30 days prior to study entry.
• Subjects who have received any other investigational drug within 30 days before inclusion.
• Pregnant (demonstrating a positive serum (ß-HCG) pregnancy test at screening visit) or lactating female subjects.
• Subjects and partners unwilling to employ adequate contraception during the course of the study.

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: Triple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Before randomization (common with other arms): There is an initial washout (placebo run-in) period of 2 weeks for subjects already on anti-hypertensive monotherapy. After randomization: 8 weeks of treatment with placebo once a day.	Drug: Placebo; Oral administration of a placebo once a day
Active Comparator: Irbesartan 150mg; Before randomization (common with other arms): There is an initial washout (placebo run-in) period of 2 weeks for subjects already on anti-hypertensive monotherapy. After randomization: 8 weeks of treatment with Irbesartan 150 mg once a day.	Drug: IRBESARTAN (SR47436); Oral administration of Irbesartan 150mg or 300mg once a day
Active Comparator: Irbesartan 150 mg / Amlodipine 5 mg; Before randomization (common with other arms): There is an initial washout (placebo run-in) period of 2 weeks for subjects already on anti-hypertensive monotherapy. After randomization: 8 weeks of treatment with Irbesartan 150 mg / Amlodipine 5 mg once a day.	Drug: Irbesartan / Amlodipine; Oral administration of Irbesartan 150 mg / Amlodipine 5mg or Irbesartan 300mg / Amlodipine 5mg once a day
Active Comparator: Amlodipine; Before randomization (common with other arms): There is an initial washout (placebo run-in) period of 2 weeks for subjects already on anti-hypertensive monotherapy. After randomization: 8 weeks of treatment with Amlodipine 5 mg once a day.	Drug: Amlodipine; Oral administration of Amlodipine 5mg once a day
Active Comparator: Irbesartan 300 mg; Active Comparator: Irbesartan Before randomization (common with other arms): There is an initial washout (placebo run-in) period of 2 weeks for subjects already on anti-hypertensive monotherapy. After randomization: 8 weeks of treatment with Irbesartan 300 mg once a day.	Drug: IRBESARTAN (SR47436); Oral administration of Irbesartan 150mg or 300mg once a day
Active Comparator: Irbesartan 300 mg / Amlodipine 5 mg; Before randomization (common with other arms): There is an initial washout (placebo run-in) period of 2 weeks for subjects already on anti-hypertensive monotherapy. After randomization: 8 weeks of treatment with Irbesartan 300 mg / Amlodipine 5 mg once a day.	Drug: Irbesartan / Amlodipine; Oral administration of Irbesartan 150 mg / Amlodipine 5mg or Irbesartan 300mg / Amlodipine 5mg once a day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Difference in mean change in SeDBP between each FDC, its individual constituents administered as monotherapy and placebo	At week 0, week 2, week 4 and week 8

Secondary Outcome Measures

Outcome Measure	Time Frame
Difference in mean change in SeSBP between each FDC, its individual constituents administered as monotherapy and placebo	At week 0, week 2, week 4 and week 8
Difference in mean change in SeDBP and SeSBP between each FDC, its individual constituents administered as monotherapy and placebo	At week 0, week 2, week 4

Collaborators and Investigators

• Sponsor: Sanofi
• Investigators: Study Director: Sanjay Aggarwal, MD, Sanofi

Study record dates

Study Major Dates

• Study Start: July 1, 2009
• Primary Completion (Actual): January 1, 2010
• Study Completion (Actual): January 1, 2010

Study Registration Dates

• First Submitted: July 30, 2009
• First Submitted That Met QC Criteria: July 30, 2009
• First Posted (Estimate): July 31, 2009

Study Record Updates

• Last Update Posted (Estimate): January 5, 2011
• Last Update Submitted That Met QC Criteria: January 4, 2011
• Last Verified: January 1, 2011

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_R_04320