Telmisartan (Micardis) and Amlodipine (Norvasc) - Factorial Design Study for the Treatment of Hypertension

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00281580
First received: January 24, 2006
Last updated: February 10, 2014
Last verified: February 2014
  Purpose

To demonstrate that Micardis and Norvasc when used together are more effective at lowering blood pre ssure.


Condition Intervention Phase
Hypertension
Drug: Amlodipine 5 mg
Drug: Placebo
Drug: Telmisartan 20 mg
Drug: Telmisartan 40 mg
Drug: Amlodipine 10 mg
Drug: Telmisartan 80 mg
Drug: Amlodipine 2.5 mg
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Double-dummy, Placebo-controlled, 4x4 Factorial Design Trial to Evaluate Telmisartan 20, 40 and 80 mg Tablets in Combination With Amlodipine 2.5, 5 and 10 mg Capsules After Eight Weeks of Treatment in Patients With Stage I or II Hypertension, With an ABPM Sub-study

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Change From Baseline at 8 Weeks in Seated Trough Cuff Mean Diastolic Blood Pressure (DBP) (Observed Telmisartan Effect) [ Time Frame: Baseline to end-of-study (up to 8 weeks) visit (Last Observation Carried Forward (LOCF)) ] [ Designated as safety issue: No ]
    Observed results

  • Change From Baseline at 8 Weeks in Seated Trough Cuff Mean DBP (Adjusted Telmisartan Effects) [ Time Frame: Baseline to end-of-study (up to 8 weeks) visit (LOCF) ] [ Designated as safety issue: No ]
    Results stem from an ANCOVA including the main effects of treatment with telmisartan, treatment with amlodipine, and country/region with baseline DBP included as a covariate.

  • Change From Baseline at 8 Weeks in Seated Trough Cuff Mean DBP (Observed Amlodipine Effects) [ Time Frame: Baseline to end-of-study (up to 8 weeks) visit (LOCF) ] [ Designated as safety issue: No ]
    Observed results

  • Change From Baseline at 8 Weeks in Seated Trough Cuff Mean DBP (Adjusted Amlodipine Effects) [ Time Frame: Baseline to end-of-study (up to 8 weeks) visit (LOCF) ] [ Designated as safety issue: No ]
    Results stem from an ANCOVA including the main effects of treatment with telmisartan, treatment with amlodipine, and country/region with baseline DBP included as a covariate.

  • Change From Baseline at 8 Weeks in Seated Trough Cuff Mean DBP (Observed Treatment Effects) [ Time Frame: End-of-study visit (LOCF) ] [ Designated as safety issue: No ]
    Observed results

  • Change From Baseline at 8 Weeks in Seated Trough Cuff Mean DBP (Adjusted Treatment Effects) [ Time Frame: Baseline to end-of-study (up to 8 weeks) visit (LOCF) ] [ Designated as safety issue: No ]
    Results stem from an ANCOVA including the main effects of treatment with telmisartan, treatment with amlodipine, and country/region with baseline DBP included as a covariate.

  • Change From Baseline at 8 Weeks in Seated Trough Cuff Mean DBP (Adjusted Treatment Effects, Excluding Pl) [ Time Frame: Baseline to end-of-study (up to 8 weeks) visit (LOCF) ] [ Designated as safety issue: No ]
    Results stem from an ANCOVA including the main effects of treatment with telmisartan, treatment with amlodipine, and country/region with baseline DBP included as a covariate.

  • Change From Baseline in Seated Trough Cuff Mean DBP (Observed Telmisartan Effect) [ Time Frame: Baseline to end-of-study (up to 8 weeks) visit (LOCF) ] [ Designated as safety issue: No ]
    Observed results

  • Change From Baseline in Seated Trough Cuff Mean DBP (Adjusted Telmisartan Effects) [ Time Frame: Baseline to end-of-study (up to 8 weeks) visit (LOCF) ] [ Designated as safety issue: No ]
    Results stem from an ANCOVA including the main effects of treatment with telmisartan, treatment with amlodipine, and country/region with baseline DBP included as a covariate.

  • Change From Baseline in Seated Trough Cuff Mean DBP (Observed Amlodipine Effects) [ Time Frame: Up to 8 weeks (LOCF) ] [ Designated as safety issue: No ]
    Observed results

  • Change From Baseline in Seated Trough Cuff Mean DBP (Adjusted Amlodipine Effects) [ Time Frame: Up to 8 weeks (LOCF) ] [ Designated as safety issue: No ]
    Results stem from an ANCOVA including the main effects of treatment with telmisartan, treatment with amlodipine, and country/region with baseline DBP included as a covariate.

  • Change From Baseline in Seated Trough Cuff Mean DBP (Observed Treatment Effects) [ Time Frame: Up to 8 weeks (LOCF) ] [ Designated as safety issue: No ]
    Observed results

  • Change From Baseline in Seated Trough Cuff Mean DBP (Adjusted Treatment Effects) [ Time Frame: Up to 8 weeks (LOCF) ] [ Designated as safety issue: No ]
    Results stem from an ANCOVA including the main effects of treatment with telmisartan, treatment with amlodipine, and country/region with baseline DBP included as a covariate.

  • Change From Baseline in Seated Trough Cuff Mean DBP (Adjusted Treatment Effects, Excluding Pl) [ Time Frame: Up to 8 weeks (LOCF) ] [ Designated as safety issue: No ]
    Results stem from an ANCOVA including the main effects of treatment with telmisartan, treatment with amlodipine, and country/region with baseline DBP included as a covariate.


Secondary Outcome Measures:
  • Change From Baseline at 8 Weeks in Seated Trough Cuff Mean Systolic Blood Pressure (SBP) [ Time Frame: Baseline to end-of-study (up to 8 weeks) visit (LOCF) ] [ Designated as safety issue: No ]
    Results stem from an ANCOVA including the main effects of treatment with telmisartan, treatment with amlodipine, and country/region with baseline SBP included as a covariate.

  • Change From Baseline at 8 Weeks in Standing Trough Cuff Mean DBP [ Time Frame: Baseline to end-of-study (up to 8 weeks) visit (LOCF) ] [ Designated as safety issue: No ]
    Results stem from an ANCOVA including the main effects of treatment with telmisartan, treatment with amlodipine, and country/region with baseline DBP included as a covariate.

  • Change From Baseline at 8 Weeks in Standing Trough Cuff Mean SBP [ Time Frame: Baseline to end-of-study (up to 8 weeks) visit (LOCF) ] [ Designated as safety issue: No ]
    Results stem from an ANCOVA including the main effects of treatment with telmisartan, treatment with amlodipine, and country/region with baseline SBP included as a covariate.

  • DBP Control [ Time Frame: End-of-study (up to 8 weeks) visit (LOCF) ] [ Designated as safety issue: No ]
    DBP control is defined as DBP < 90 mmHg - key combination therapies

  • DBP Response [ Time Frame: End-of-study (up to 8 weeks) visit (LOCF) ] [ Designated as safety issue: No ]
    DBP response is defined as DBP < 90 mmHg or a reduction of DBP of >= 10 mmHg - key combination therapies

  • SBP Response [ Time Frame: End-of-study (up to 8 weeks) visit (LOCF) ] [ Designated as safety issue: No ]
    SBP Response is defined as SBP < 140 mmHg or a reduction of SBP of >= 10 mmHg - key combination therapies

  • BP Normality [ Time Frame: End-of-study (up to 8 weeks) visit (LOCF) ] [ Designated as safety issue: No ]

    No: Mean seated SBP >=140 and/or mean seated DBP >=90 mmHg at trough High normal: mean seated SBP >=130 and <140 mmHg and mean seated DBP >=85 and <90 mmHg at trough Normal: mean seated SBP >=120 and <130 mmHg and mean seated DBP >=80 and <85 mmHg at trough Optimal: mean seated SBP < 120 mmHg and mean seated DBP <80 mmHg at trough

    - key combination therapies


  • Change From Baseline in ABPM Hourly Mean (Relative to Dosing) DBP [ Time Frame: End-of-study (up to 8 weeks) visit (LOCF) ] [ Designated as safety issue: No ]
    Observed results - key combination therapies

  • Change From Baseline in ABPM Hourly Mean (Relative to Dosing) SBP [ Time Frame: End-of-study (up to 8 weeks) visit (LOCF) ] [ Designated as safety issue: No ]
    Observed results - key combination therapies

  • Change From Baseline in ABPM 24-hour Mean DBP [ Time Frame: End-of-study (up to 8 weeks) visit (LOCF) ] [ Designated as safety issue: No ]
    Observed results - key combination therapies

  • Change From Baseline in ABPM 24-hour Mean SBP [ Time Frame: End-of-study (up to 8 weeks) visit (LOCF) ] [ Designated as safety issue: No ]
    Observed results - key combination therapies

  • Orthostatic Change in Trough Cuff Mean DBP [ Time Frame: Week 8 ] [ Designated as safety issue: No ]
    Calculated as seated minus standing for all patients - key combination therapies

  • Orthostatic Change in Trough Cuff Mean SBP [ Time Frame: Week 8 ] [ Designated as safety issue: No ]
    Calculated as seated minus standing for all patients - key combination therapies

  • Change From Baseline in Seated Trough Pulse Rate [ Time Frame: End-of-study visit (LOCF) ] [ Designated as safety issue: No ]
    Observed results for all patients - key combination therapies

  • Change From Baseline in Seated Trough Cuff Mean SBP [ Time Frame: Up to 8 weeks (LOCF) ] [ Designated as safety issue: No ]
    Results stem from an ANCOVA including the main effects of treatment with telmisartan, treatment with amlodipine, and country/region with baseline SBP included as a covariate.

  • Change From Baseline in Standing Trough Cuff Mean DBP [ Time Frame: Up to 8 weeks (LOCF) ] [ Designated as safety issue: No ]
    Results stem from an ANCOVA including the main effects of treatment with telmisartan, treatment with amlodipine, and country/region with baseline DBP included as a covariate.

  • Change From Baseline in Standing Trough Cuff Mean SBP [ Time Frame: Up to 8 weeks (LOCF) ] [ Designated as safety issue: No ]
    Results stem from an ANCOVA including the main effects of treatment with telmisartan, treatment with amlodipine, and country/region with baseline SBP included as a covariate.

  • DBP Control [ Time Frame: Up to 8 weeks (LOCF) ] [ Designated as safety issue: No ]
    DBP control is defined as DBP < 90 mmHg - key combination therapies

  • DBP Response [ Time Frame: Up to 8 weeks (LOCF) ] [ Designated as safety issue: No ]
    DBP response is defined as DBP < 90 mmHg or a reduction of DBP of >= 10 mmHg - key combination therapies

  • SBP Response [ Time Frame: Up to 8 weeks (LOCF) ] [ Designated as safety issue: No ]
    SBP Response is defined as SBP < 140 mmHg or a reduction of SBP of >= 10 mmHg - key combination therapies

  • BP Normality [ Time Frame: Up to 8 weeks (LOCF) ] [ Designated as safety issue: No ]

    No: Mean seated SBP >=140 and/or mean seated DBP >=90 mmHg at trough High normal: mean seated SBP >=130 and <140 mmHg and mean seated DBP >=85 and <90 mmHg at trough Normal: mean seated SBP >=120 and <130 mmHg and mean seated DBP >=80 and <85 mmHg at trough Optimal: mean seated SBP < 120 mmHg and mean seated DBP <80 mmHg at trough

    - key combination therapies


  • Change From Baseline in ABPM Hourly Mean (Relative to Dosing) DBP [ Time Frame: Up to 8 weeks (LOCF) ] [ Designated as safety issue: No ]
    Observed results for mod-sev patients - key combination therapies

  • Change From Baseline in ABPM 24-hour Mean DBP [ Time Frame: Up to 8 weeks (LOCF) ] [ Designated as safety issue: No ]
    Observed results for mod-sev patients - key combination therapies

  • Change From Baseline in ABPM 24-hour Mean SBP [ Time Frame: Up to 8 weeks (LOCF) ] [ Designated as safety issue: No ]
    Observed results for mod-sev patients - key combination therapies

  • Orthostatic Change in Trough Cuff Mean DBP [ Time Frame: Week 8 ] [ Designated as safety issue: No ]
    Calculated as seated minus standing for mod-sev patients - key combination therapies

  • Orthostatic Change in Trough Cuff Mean SBP [ Time Frame: Week 8 ] [ Designated as safety issue: No ]
    Calculated as seated minus standing for mod-sev patients - key combination therapies

  • Change From Baseline in Seated Trough Pulse Rate [ Time Frame: Up to 8 weeks (LOCF) ] [ Designated as safety issue: No ]
    Observed results for mod-sev patients - key combination therapies

  • Clinical Relevant Abnormalities for Laboratory Parameters and Electrocardiogram (ECG) [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Clinical relevant abnormalities for laboratory parameters and Electrocardiogram (ECG). New abnormal findings or worsening of baseline conditions were reported as Adverse Events related to treatment (cardiac disorders and investigations).


Other Outcome Measures:
  • Change From Baseline at 2,4,6,and 8 Weeks in Seated Trough Cuff DBP [ Time Frame: Baseline to nominal week over the trial ] [ Designated as safety issue: No ]
    Observed results for key combination therapies

  • BP Control [ Time Frame: End-of-study (up to 8 weeks) visit (LOCF) ] [ Designated as safety issue: No ]
    Percentage of responders (SBP<140 mmHg and DBP<90 mmHg) for all patients - key combination therapies

  • Change From Baseline in Seated Trough Cuff DBP [ Time Frame: Nominal week over the trial ] [ Designated as safety issue: No ]
    Observed results for mod-sev patients - key combination therapies

  • BP Control [ Time Frame: Up to 8 weeks (LOCF) ] [ Designated as safety issue: No ]
    Responders SBP<10 mmHg and DBP<90 mmHg) for mod-sev patients - key combination therapies


Enrollment: 1461
Study Start Date: April 2006
Primary Completion Date: March 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Placebo once daily for eight weeks
Drug: Placebo
Placebo to Telmisartan and Amlodipine once daily for eight weeks
Experimental: Telmisartan 20 mg
Telmisartan 20 mg once daily for eight weeks
Drug: Telmisartan 20 mg
Telmisartan 20 mg once daily for eight weeks
Experimental: Telmisartan 40 mg
Telmisartan 40 mg once daily for eight weeks
Drug: Telmisartan 40 mg
Telmisartan 40 mg once daily for eight weeks
Experimental: Telmisartan 80 mg
Telmisartan 80 mg once daily for eight weeks
Drug: Telmisartan 80 mg
Telmisartan 80 mg once daily for eight weeks
Experimental: Amlodipine 2.5 mg
Amlodipine 2.5 mg once daily for eight weeks
Drug: Amlodipine 2.5 mg
Amlodipine 2.5 mg once daily for eight weeks
Experimental: Amlodipine 5 mg
Amlodipine 5 mg once daily for eight weeks
Drug: Amlodipine 5 mg
amlodipine 5g once daily for eight weeks
Active Comparator: Amlodipine 10 mg
Amlodipine 5 mg for two weeks and forced titrated to amlodipine 10 mg for six weeks once daily
Drug: Amlodipine 5 mg
amlodipine 5g once daily for two weeks
Drug: Amlodipine 10 mg
Amlodipine 10 mg once daily for six weeks
Experimental: Telmisartan 20 / Amlodipine 2.5
Telmisartan 20/ Amlodipine 2.5 mg once daily for eight weeks
Drug: Telmisartan 20 mg
Telmisartan 20 mg once daily for eight weeks
Drug: Amlodipine 2.5 mg
Amlodipine 2.5 mg once daily for eight weeks
Experimental: Telmisartan 20 / Amlodipine 5
Telmisartan 20 / Amlodipine 5 mg once daily for eight weeks
Drug: Telmisartan 20 mg
Telmisartan 20 mg once daily for eight weeks
Drug: Amlodipine 5 mg
amlodipine 5mg once daily for eight weeks
Experimental: Telmisartan 20 / Amlodipine 10
Telmisartan 20 / Amlodipine 5 for two weeks and forced titrated to amlodipine 10 mg for six weeks
Drug: Amlodipine 10 mg
Amlodipine 10 mg once daily for six weeks
Drug: Telmisartan 20 mg
Telmisartan 20 mg once daily for eight weeks
Drug: Amlodipine 5 mg
Amlodipine 5 mg once daily for two weeks
Experimental: Telmisartan 40 / Amlodipine 2.5
Telmisartan 40 / Amlodipine 2.5 for eight weeks
Drug: Amlodipine 2.5 mg
Amlodipine 2.5 mg once daily for eight weeks
Drug: Telmisartan 40 mg
Telmisartan 40 mg once daily for eight weeks
Experimental: Telmisartan 40 / Amlodipine 5
Telmisartan 40 / Amlodipine 5 for eight weeks
Drug: Amlodipine 5 mg
Amlodipine 5 mg once daily for eight weeks
Drug: Telmisartan 40 mg
Telmisartan 40 mg once daily for eight weeks
Experimental: Telmisartan 40 / Amlodipine 10
Telmisartan 40 / Amlodipine 5 for two weeks and forced titrated to amlodipine 10 mg for six weeks
Drug: Telmisartan 40 mg
Telmisartan 40 mg once daily for eight weeks
Drug: Amlodipine 10 mg
Amlodipine 10 mg once daily for six weeks
Drug: Amlodipine 5 mg
Amlodipine 5 mg once daily for two weeks
Experimental: Telmisartan 80 / Amlodipine 2.5
Telmisartan 80 / Amlodipine 2.5 for eight weeks
Drug: Amlodipine 2.5 mg
Amlodipine 2.5 mg once daily for eight weeks
Drug: Telmisartan 80 mg
Telmisartan 80 mg once daily for eight weeks
Experimental: Telmisartan 80 / Amlodipine 5
Telmisartan 80 / Amlodipine 5 mg for eight weeks
Drug: Telmisartan 80 mg
Telmisartan 80 mg once daily for eight weeks
Drug: Amlodipine 5 mg
Amlodipine 5 mg once daily for eight weeks
Experimental: Telmisartan 80 / Amlodipine 10
Telmisartan 40 / Amlodipine 5 for two weeks and forced titrated to amlodipine 10 mg for six weeks
Drug: Amlodipine 5 mg
Amlodipine 5 mg once daily for two weeks
Drug: Telmisartan 80 mg
Telmisartan 80 mg once daily for eight weeks
Drug: Amlodipine 10 mg
Amlodipine 10 mg once daily for six weeks

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

Main Inclusion Criteria: Male and female patients >=18 years of age with Stage I or II hypertension defined as: a mean seated cuff diastolic blood pressure >=95 and <=119 mmHg Main

Exclusion criteria:

Exclusion Criteria:

  1. Patient is pregnant; breast-feeding; unwilling to use birth control during the study; has secondary hypertension; severe renal dysfunction; hepatic insufficiency; stroke within the last six months; myocardial infarction, cardiac surgery, percutaneous transluminal coronary angioplasty, unstable angina or coronary artery bypass graft within the past three months; unstable or uncontrolled diabetes for the past three months defined as a glucosylates hemoglobin (HbA1c) greater than ten percent ; history of angioedema or hypersensitivity related to either study drug.
  2. Systolic Blood Pressure (SBP) is greater than or equal to 180 millimeters of mercury (mmHg), Diastolic Blood Pressure (DBP) is greater than or equal to 110 mmHg.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00281580

  Show 136 Study Locations
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Additional Information:
No publications provided

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT00281580     History of Changes
Other Study ID Numbers: 1235.1, 2008-000874-19
Study First Received: January 24, 2006
Results First Received: November 18, 2009
Last Updated: February 10, 2014
Health Authority: Argentina:
Brazil:
Mexico:
South Africa:
United States: Food and Drug Administration

Additional relevant MeSH terms:
Hypertension
Vascular Diseases
Cardiovascular Diseases
Amlodipine
Telmisartan
Benzoates
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses
Vasodilator Agents
Antihypertensive Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Antifungal Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on July 20, 2014