A Dose Escalation Study of a Combination Antihypertensive Drug in the Treatment of Various Groups of Patients Who do Not Respond to Single Drug Treatment of Their High Blood Pressure (BP CRUSH)

This study has been completed.
Sponsor:
Collaborator:
Integrium
Information provided by:
Daiichi Sankyo Inc.
ClinicalTrials.gov Identifier:
NCT00791258
First received: November 13, 2008
Last updated: September 30, 2010
Last verified: September 2010
  Purpose

The initial 12 week portion of this 20 week study will examine the ability of a combination of olmesartan medoxomil and amlodipine to lower the blood pressure of patients with high blood pressure who have not had sufficient blood pressure reduction using one anti-hypertension drug (monotherapy). The final 8 weeks of this 20 week study will examine the ability of a combination of olmesartan medoxomil, amlodipine and hydrochlorothiazide to lower blood pressure in the same patient population. All three medications being tested have been approved by the FDA for the treatment of high blood pressure, but only amlodipine and olmesartan are currently approved for use in combination form.


Condition Intervention Phase
Hypertension
Drug: amlodipine and olmesartan medoxomil tablets
Drug: hydrochlorothiazide tablets
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Prospective, Open-Label, Titration Study to Evaluate the Efficacy and Safety Safety of AZOR in Multiple Subgroups of Hypertensive Subjects Who Are Non-Responders to Anti-Hypertensive Monotherapy

Resource links provided by NLM:


Further study details as provided by Daiichi Sankyo Inc.:

Primary Outcome Measures:
  • The Percentage of Patients Who Achieve Seated Systolic Blood Pressure Goal (<140 mm Hg for Non-diabetics and <130 mm Hg for Diabetics) From Baseline to 12 Weeks [ Time Frame: baseline to 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The Percentage of Subjects Achieving Seated Diastolic BP Goal (<90 mmHg for Non-diabetics or < 80 mmHg for Subjects With Diabetes) From Baseline to 12 Weeks [ Time Frame: baseline to 12 weeks ] [ Designated as safety issue: No ]
  • The Percentage of Subjects Who Achieve BP Goal (<140/90 mmHg for Non-diabetics or <130/80 mmHg for Diabetics) From Baseline to 12 and 20 Weeks [ Time Frame: Baseline to 12 and 20 weeks ] [ Designated as safety issue: No ]
  • Change in Mean Seated Systolic Blood Pressure From Baseline to 4, 8, 12, 16, 20 Weeks [ Time Frame: Baseline to 4, 8, 12, 16, 20 weeks ] [ Designated as safety issue: No ]
  • Change in Mean Seated Diastolic Blood Pressure From Baseline to 4, 8, 12, 16, 20 Weeks [ Time Frame: Baseline to 4, 8, 12, 16, 20 weeks ] [ Designated as safety issue: No ]
  • Percentage of Patients Achieving Seated Diastolic Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks [ Time Frame: Baseline to 4, 8, 12, 16, 20 weeks ] [ Designated as safety issue: No ]
  • Percentage of Patients Achieving Seated Systolic Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks [ Time Frame: Baseline to 4, 8, 12, 16, 20 weeks ] [ Designated as safety issue: No ]
  • Percentage of Patients Achieving Seated Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks [ Time Frame: Baseline to 4, 8, 12, 16, 20 weeks ] [ Designated as safety issue: No ]
  • Percentage of Patients Achieving Seated Systolic Blood Pressure Reduction Ranges From Baseline to 4, 8, 12, 16, 20 Weeks [ Time Frame: Baseline to 4, 8, 12, 16, 20 weeks ] [ Designated as safety issue: No ]
  • Percentage of Patients Achieving Seated Diastolic Blood Pressure Reduction Ranges From Baseline to 4, 8, 12, 16, 20 Weeks [ Time Frame: Baseline to 4, 8, 12, 16, 20 weeks ] [ Designated as safety issue: No ]
  • Percentage of Participants Achieving the Mean Daytime Blood Pressure Goals, as Measured by Ambulatory Blood Pressure Monitor, From Baseline to 12 Weeks [ Time Frame: Baseline to 12 weeks ] [ Designated as safety issue: No ]
    Once the Ambulatory Blood Pressure Monitor (ABPM) has been applied, the dose of medication was taken and the subject wore the ABPM for a period of 24 hours. Daytime is defined as 8AM - 4PM.

  • Percentage of Participants Achieving the Mean Daytime Blood Pressure Goals, as Measured by Ambulatory Blood Pressure Monitor, From Baseline to 20 Weeks [ Time Frame: Baseline to 20 weeks ] [ Designated as safety issue: No ]
    Once the Ambulatory Blood Pressure Monitor (ABPM) has been applied, the dose of medication was taken and the subject wore the ABPM for a period of 24 hours. Daytime is defined as 8AM - 4PM.

  • Percentage of Participants Achieving the Mean Nighttime Blood Pressure Goals, as Measured by Ambulatory Blood Pressure Monitor, From Baseline to 12 Weeks [ Time Frame: Baseline to 12 weeks ] [ Designated as safety issue: No ]
    Once the Ambulatory Blood Pressure Monitor (ABPM) has been applied, the dose of medication was taken and the subject wore the ABPM for a period of 24 hours. Nighttime is defined as 10p.m. - 6 a.m.

  • Percentage of Participants Achieving the Mean Nighttime Blood Pressure Goals, as Measured by Ambulatory Blood Pressure Monitor, From Baseline to 20 Weeks [ Time Frame: Baseline to 20 weeks ] [ Designated as safety issue: No ]
    Once the Ambulatory Blood Pressure Monitor (ABPM) has been applied, the dose of medication was taken and the subject wore the ABPM for a period of 24 hours. Nighttime is defined as 10 p.m. - 6 a.m.

  • Percentage of Participants Achieving the Mean 24-hour Blood Pressure Goals, as Measured by Ambulatory Blood Pressure Monitor, From Baseline to 12 Weeks [ Time Frame: Baseline to 12 weeks ] [ Designated as safety issue: No ]
    Once the Ambulatory Blood Pressure Monitor (ABPM) has been applied, the dose of medication was taken and the subject wore the ABPM for a period of 24 hours.

  • Percentage of Participants Achieving the Mean 24-hour Blood Pressure Goals, as Measured by Ambulatory Blood Pressure Monitor, From Baseline to 20 Weeks [ Time Frame: Baseline to 20 weeks ] [ Designated as safety issue: No ]
    Once the Ambulatory Blood Pressure Monitor (ABPM) has been applied, the dose of medication was taken and the subject wore the ABPM for a period of 24 hours.

  • Change From Baseline to Week 12 in Ambulatory Systolic and Diastolic Blood Pressure Values [ Time Frame: Baseline to 12 weeks ] [ Designated as safety issue: No ]
    Once the Ambulatory Blood Pressure Monitor (ABPM) has been applied, the dose of medication was taken and the subject wore the ABPM for a period of 24 hours. Daytime is defined as 8 a.m. to 4 p.m. Nighttime is defined as 10 p.m. to 6 a.m.

  • Change From Baseline to Week 20 in Ambulatory Systolic and Diastolic Blood Pressure Values [ Time Frame: Baseline to 20 weeks ] [ Designated as safety issue: No ]
    Once the Ambulatory Blood Pressure Monitor (ABPM) has been applied, the dose of medication was taken and the subject wore the ABPM for a period of 24 hours. Daytime is defined as 8 a.m. to 4 p.m. Nighttime is defined as 10 p.m. to 6 a.m.

  • Percentage of African American/Black Patients Achieving Seated Systolic Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks [ Time Frame: Baseline to 4, 8, 12, 16, 20 weeks ] [ Designated as safety issue: No ]
  • Percentage of African American/Black Patients Achieving Seated Diastolic Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks [ Time Frame: Baseline to 4, 8, 12, 16, 20 weeks ] [ Designated as safety issue: No ]
  • Percentage of African American/Black Patients Achieving Seated Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks [ Time Frame: Baseline to 4, 8, 12, 16, 20 weeks ] [ Designated as safety issue: No ]
  • Percentage of African American/Black Patients Achieving Seated Systolic Blood Pressure Reduction Ranges From Baseline to 4, 8, 12, 16, 20 Weeks [ Time Frame: Baseline to 4, 8, 12, 16, 20 weeks ] [ Designated as safety issue: No ]
  • Percentage of African American/Black Patients Achieving Seated Diastolic Blood Pressure Reduction Ranges From Baseline to 4, 8, 12, 16, 20 Weeks [ Time Frame: Baseline to 4, 8, 12, 16, 20 weeks ] [ Designated as safety issue: No ]
  • Percentage of Asian Patients Achieving Seated Systolic Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks [ Time Frame: Baseline to 4, 8, 12, 16, 20 weeks ] [ Designated as safety issue: No ]
  • Percentage of Asain Patients Achieving Seated Diastolic Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks [ Time Frame: Baseline to 4, 8, 12, 16, 20 weeks ] [ Designated as safety issue: No ]
  • Percentage of Asian Patients Achieving Seated Systolic Blood Pressure Reduction Ranges From Baseline to 4, 8, 12, 16, 20 Weeks [ Time Frame: Baseline to 4, 8, 12, 16, 20 weeks ] [ Designated as safety issue: No ]
  • Percentage of Asian Patients Achieving Seated Diastolic Blood Pressure Reduction Ranges From Baseline to 4, 8, 12, 16, 20 Weeks [ Time Frame: Baseline to 4, 8, 12, 16, 20 weeks ] [ Designated as safety issue: No ]
  • Percentage of Hispanic Patients Achieving Seated Systolic Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks [ Time Frame: Baseline to 4, 8, 12, 16, 20 weeks ] [ Designated as safety issue: No ]
  • Percentage of Hispanic Patients Achieving Seated Diastolic Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks [ Time Frame: Baseline to 4, 8, 12, 16, 20 weeks ] [ Designated as safety issue: No ]
  • Percentage of Hispanic Patients Achieving Seated Systolic Blood Pressure Reduction Ranges From Baseline to 4, 8, 12, 16, 20 Weeks [ Time Frame: Baseline to 4, 8, 12, 16, 20 weeks ] [ Designated as safety issue: No ]
  • Percentage of Hispanic Patients Achieving Seated Diastolic Blood Pressure Reduction Ranges From Baseline to 4, 8, 12, 16, 20 Weeks [ Time Frame: Baseline to 4, 8, 12, 16, 20 weeks ] [ Designated as safety issue: No ]
  • Percentage of Elderly Patients Achieving Seated Systolic Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks [ Time Frame: Baseline to 4, 8, 12, 16, 20 weeks ] [ Designated as safety issue: No ]
  • Percentage of Elderly Patients Achieving Seated Diastolic Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks [ Time Frame: Baseline to 4, 8, 12, 16, 20 weeks ] [ Designated as safety issue: No ]
  • Percentage of Elderly Patients Achieving Seated Systolic Blood Pressure Reduction Ranges From Baseline to 4, 8, 12, 16, 20 Weeks [ Time Frame: Baseline to 4, 8, 12, 16, 20 weeks ] [ Designated as safety issue: No ]
  • Percentage of Elderly Patients Achieving Seated Diastolic Blood Pressure Reduction Ranges From Baseline to 4, 8, 12, 16, 20 Weeks [ Time Frame: Baseline to 4, 8, 12, 16, 20 weeks ] [ Designated as safety issue: No ]
  • Percentage of Type 2 Diabetic Patients Achieving Seated Systolic Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks [ Time Frame: Baseline to 4, 8, 12, 16, 20 weeks ] [ Designated as safety issue: No ]
  • Percentage of Type 2 Diabetic Patients Achieving Seated Diastolic Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks [ Time Frame: Baseline to 4, 8, 12, 16, 20 weeks ] [ Designated as safety issue: No ]
  • Percentage of Type 2 Diabetic Patients Achieving Seated Systolic Blood Pressure Reduction Ranges From Baseline to 4, 8, 12, 16, 20 Weeks [ Time Frame: Baseline to 4, 8, 12, 16, 20 weeks ] [ Designated as safety issue: No ]
  • Percentage of Type 2 Diabetic Patients Achieving Seated Diastolic Blood Pressure Reduction Ranges From Baseline to 4, 8, 12, 16, 20 Weeks [ Time Frame: Baseline to 4, 8, 12, 16, 20 weeks ] [ Designated as safety issue: No ]
  • Percentage of Obese Patients Achieving Seated Systolic Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks [ Time Frame: Baseline to 4, 8, 12, 16, 20 weeks ] [ Designated as safety issue: No ]
  • Percentage of Obese Patients Achieving Seated Diastolic Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks [ Time Frame: Baseline to 4, 8, 12, 16, 20 weeks ] [ Designated as safety issue: No ]
  • Percentage of Obese Patients Achieving Seated Systolic Blood Pressure Reduction Ranges From Baseline to 4, 8, 12, 16, 20 Weeks [ Time Frame: Baseline to 4, 8, 12, 16, 20 weeks ] [ Designated as safety issue: No ]
  • Percentage of Obese Patients Achieving Seated Diastolic Blood Pressure Reduction Ranges From Baseline to 4, 8, 12, 16, 20 Weeks [ Time Frame: Baseline to 4, 8, 12, 16, 20 weeks ] [ Designated as safety issue: No ]
  • Percentage of Patients With Metabolic Syndrome Achieving Seated Systolic Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks [ Time Frame: Baseline to 4, 8, 12, 16, 20 weeks ] [ Designated as safety issue: No ]
  • Percentage of Patients With Metabolic Syndrome Achieving Seated Diastolic Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks [ Time Frame: Baseline to 4, 8, 12, 16, 20 weeks ] [ Designated as safety issue: No ]
  • Percentage of Patients With Metabolic Syndrome Achieving Seated Systolic Blood Pressure Reduction Ranges From Baseline to 4, 8, 12, 16, 20 Weeks [ Time Frame: Baseline to 4, 8, 12, 16, 20 weeks ] [ Designated as safety issue: No ]
  • Percentage of Patients With Metabolic Syndrome Achieving Seated Diastolic Blood Pressure Reduction Ranges From Baseline to 4, 8, 12, 16, 20 Weeks [ Time Frame: Baseline to 4, 8, 12, 16, 20 weeks ] [ Designated as safety issue: No ]
  • Percentage of Participants Previously on a Dihydropyridine Calcium Channel Blocker Achieving the Blood Pressure Goals From Baseline to 12 Weeks [ Time Frame: Baseline to 12 weeks ] [ Designated as safety issue: No ]
  • Percentage of Participants Previously on a Dihydropyridine Calcium Channel Blocker Achieving the Blood Pressure Goals From Baseline to 20 Weeks [ Time Frame: Baseline to 20 weeks ] [ Designated as safety issue: No ]
  • Percentage of Participants Previously on a Diuretic Achieving the Blood Pressure Goals From Baseline to 12 Weeks [ Time Frame: Baseline to 12 weeks ] [ Designated as safety issue: No ]
  • Percentage of Participants Previously on a Diuretic Achieving the Blood Pressure Goals From Baseline to 20 Weeks [ Time Frame: Baseline to 20 weeks ] [ Designated as safety issue: No ]
  • Percentage of Participants Previously on an Angiotensin Converting Enzyme Inhibitor Achieving the Blood Pressure Goals From Baseline to 12 Weeks [ Time Frame: Baseline to 12 weeks ] [ Designated as safety issue: No ]
  • Percentage of Participants Previously on an Angiotensin Converting Enzyme Inhibitor Achieving the Blood Pressure Goals From Baseline to 20 Weeks [ Time Frame: Baseline to 20 weeks ] [ Designated as safety issue: No ]
  • Percentage of Participants Previously on an Angiotensin II Receptor Blocker Achieving the Blood Pressure Goals From Baseline to 12 Weeks [ Time Frame: Baseline to 12 weeks ] [ Designated as safety issue: No ]
  • Percentage of Participants Previously on an Angiotensin II Receptor Blocker Achieving the Blood Pressure Goals From Baseline to 20 Weeks [ Time Frame: Baseline to 20 weeks ] [ Designated as safety issue: No ]
  • Percentage of Participants Previously on a Beta Blocker Achieving the Blood Pressure Goals From Baseline to 12 Weeks [ Time Frame: Baseline to 12 weeks ] [ Designated as safety issue: No ]
  • Percentage of Participants Previously on a Beta Blocker Achieving the Blood Pressure Goals From Baseline to 20 Weeks [ Time Frame: Baseline to 20 weeks ] [ Designated as safety issue: No ]
  • Percentage of Participants Previously on a Nondihydropyridine Calcium Channel Blocker Achieving the Blood Pressure Goals From Baseline to 12 Weeks [ Time Frame: Baseline to 12 weeks ] [ Designated as safety issue: No ]
  • Percentage of Participants Previously on a Nondihydropyridine Calcium Channel Blocker Achieving the Blood Pressure Goals From Baseline to 20 Weeks [ Time Frame: Baseline to 20 weeks ] [ Designated as safety issue: No ]

Enrollment: 999
Study Start Date: November 2008
Study Completion Date: September 2009
Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Azor tablets and hydrochlorothiazide tablets (if necessary) will be administered for up to 20 weeks
Drug: amlodipine and olmesartan medoxomil tablets
amlodipine and olmesartan medoxomil tablets administered orally, once daily for up to 20 weeks
Other Name: AZOR Tablets
Drug: hydrochlorothiazide tablets
hydrochlorothiazide tablets may be administered orally, if necessary once daily, for up to 8 weeks

  Eligibility

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

Inclusion Criteria:

  • >= to 18 years of age
  • Hypertension uncontrolled on current monotherapy
  • Females:
  • negative serum pregnancy test at screening
  • post menopausal or have had a hysterectomy or tubal ligation or practicing approved methods of birth control

Exclusion Criteria:

  • Pregnant females
  • Uncontrolled hypertension with multiple drugs, except for hydrochlorothiazide/triamterene
  • Diabetes requiring insulin
  • Serious disorders that may limit the ability to evaluate the efficacy or safety of treatment
  • History of myocardial infarction, bypass graft, angioplasty or heart failure within the past 6 months
  • History of Class III or IV congestive heart failure
  • History of stroke or transient ischemic attack within the last 1 year
  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: NCT00791258

  Show 72 Study Locations
Sponsors and Collaborators
Daiichi Sankyo Inc.
Integrium
  More Information

No publications provided by Daiichi Sankyo Inc.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Diector of Medical Research and Strategy, Daiichi Sankyo
ClinicalTrials.gov Identifier: NCT00791258     History of Changes
Other Study ID Numbers: CS8663-404
Study First Received: November 13, 2008
Results First Received: September 2, 2010
Last Updated: September 30, 2010
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Hypertension
Vascular Diseases
Cardiovascular Diseases
Olmesartan medoxomil
Antihypertensive Agents
Hydrochlorothiazide
Amlodipine
Olmesartan
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Diuretics
Natriuretic Agents
Physiological Effects of Drugs
Sodium Chloride Symporter Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Calcium Channel Blockers
Vasodilator Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists

ClinicalTrials.gov processed this record on July 26, 2014