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)

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

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.

Study Overview

• Status: Completed
• Conditions: Hypertension
• Intervention / Treatment: Drug: amlodipine and olmesartan medoxomil tablets; Drug: hydrochlorothiazide tablets

• Study Type: Interventional
• Enrollment (Actual): 999
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States
  • Arizona
    • Green Valley, Arizona, United States
    • Mesa, Arizona, United States
    • Sierra Vista, Arizona, United States
    • Tempe, Arizona, United States
    • Tucson, Arizona, United States
  • California
    • Anaheim, California, United States
    • Harbor City, California, United States
    • National City, California, United States
    • Tustin, California, United States
    • Westlake Village, California, United States
  • Colorado
    • Colorado Springs, Colorado, United States
    • Pueblo, Colorado, United States
  • Connecticut
    • Milford, Connecticut, United States
  • Florida
    • Boynton Beach, Florida, United States
    • Brooksville, Florida, United States
    • Clearwater, Florida, United States
    • DeLand, Florida, United States
    • Deerfield Beach, Florida, United States
    • Fort Lauderdale, Florida, United States
    • Kissimmee, Florida, United States
    • Pembroke Pines, Florida, United States
    • Saint Petersburg, Florida, United States
    • Sarasota, Florida, United States
    • Tampa, Florida, United States
  • Idaho
    • Boise, Idaho, United States
  • Illinois
    • Addison, Illinois, United States
    • Orland Park, Illinois, United States
  • Kansas
    • Wichita, Kansas, United States
  • Kentucky
    • Lexington, Kentucky, United States
  • Maryland
    • Columbia, Maryland, United States
    • Elkridge, Maryland, United States
    • Oxon Hill, Maryland, United States
    • Reisterstown, Maryland, United States
  • Michigan
    • Stevensville, Michigan, United States
  • Nebraska
    • Omaha, Nebraska, United States
  • Nevada
    • Las Vegas, Nevada, United States
  • New Jersey
    • Edison, New Jersey, United States
    • Sewell, New Jersey, United States
  • New Mexico
    • Albuquerque, New Mexico, United States
  • New York
    • Binghamton, New York, United States
  • North Carolina
    • Cary, North Carolina, United States
    • Charlotte, North Carolina, United States
    • Harrisburg, North Carolina, United States
    • Hickory, North Carolina, United States
    • High Point, North Carolina, United States
    • Raleigh, North Carolina, United States
    • Wilmington, North Carolina, United States
    • Winston-Salem, North Carolina, United States
  • Ohio
    • Cincinnati, Ohio, United States
    • Cleveland, Ohio, United States
  • Oklahoma
    • Norman, Oklahoma, United States
    • Oklahoma City, Oklahoma, United States
    • Tulsa, Oklahoma, United States
  • Oregon
    • Eugene, Oregon, United States
    • Portland, Oregon, United States
  • Pennsylvania
    • Havertown, Pennsylvania, United States
    • Jenkintown, Pennsylvania, United States
    • Pittsburgh, Pennsylvania, United States
  • South Carolina
    • Greenville, South Carolina, United States
    • Mount Pleasant, South Carolina, United States
  • Tennessee
    • New Tazewell, Tennessee, United States
  • Texas
    • Amarillo, Texas, United States
    • Austin, Texas, United States
    • Carrollton, Texas, United States
    • Corpus Christi, Texas, United States
    • Dallas, Texas, United States
    • Longview, Texas, United States
  • Utah
    • West Jordan, Utah, United States
  • Virginia
    • Norfolk, Virginia, United States
  • Washington
    • Walla Walla, Washington, United States
  • Wisconsin
    • Madison, Wisconsin, United States

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:

• >= 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 Names: AZOR Tablets; Drug: hydrochlorothiazide tablets; hydrochlorothiazide tablets may be administered orally, if necessary once daily, for up to 8 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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	baseline to 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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		baseline to 12 weeks
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		Baseline to 12 and 20 weeks
Change in Mean Seated Systolic Blood Pressure From Baseline to 4, 8, 12, 16, 20 Weeks		Baseline to 4, 8, 12, 16, 20 weeks
Change in Mean Seated Diastolic Blood Pressure From Baseline to 4, 8, 12, 16, 20 Weeks		Baseline to 4, 8, 12, 16, 20 weeks
Percentage of Patients Achieving Seated Diastolic Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks		Baseline to 4, 8, 12, 16, 20 weeks
Percentage of Patients Achieving Seated Systolic Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks		Baseline to 4, 8, 12, 16, 20 weeks
Percentage of Patients Achieving Seated Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks		Baseline to 4, 8, 12, 16, 20 weeks
Percentage of Patients Achieving Seated Systolic Blood Pressure Reduction Ranges From Baseline to 4, 8, 12, 16, 20 Weeks		Baseline to 4, 8, 12, 16, 20 weeks
Percentage of Patients Achieving Seated Diastolic Blood Pressure Reduction Ranges From Baseline to 4, 8, 12, 16, 20 Weeks		Baseline to 4, 8, 12, 16, 20 weeks
Percentage of Participants Achieving the Mean Daytime Blood Pressure Goals, as Measured by Ambulatory Blood Pressure Monitor, From Baseline to 12 Weeks	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.	Baseline to 12 weeks
Percentage of Participants Achieving the Mean Daytime Blood Pressure Goals, as Measured by Ambulatory Blood Pressure Monitor, From Baseline to 20 Weeks	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.	Baseline to 20 weeks
Percentage of Participants Achieving the Mean Nighttime Blood Pressure Goals, as Measured by Ambulatory Blood Pressure Monitor, From Baseline to 12 Weeks	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.	Baseline to 12 weeks
Percentage of Participants Achieving the Mean Nighttime Blood Pressure Goals, as Measured by Ambulatory Blood Pressure Monitor, From Baseline to 20 Weeks	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.	Baseline to 20 weeks
Percentage of Participants Achieving the Mean 24-hour Blood Pressure Goals, as Measured by Ambulatory Blood Pressure Monitor, From Baseline to 12 Weeks	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.	Baseline to 12 weeks
Percentage of Participants Achieving the Mean 24-hour Blood Pressure Goals, as Measured by Ambulatory Blood Pressure Monitor, From Baseline to 20 Weeks	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.	Baseline to 20 weeks
Change From Baseline to Week 12 in Ambulatory Systolic and Diastolic Blood Pressure Values	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.	Baseline to 12 weeks
Change From Baseline to Week 20 in Ambulatory Systolic and Diastolic Blood Pressure Values	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.	Baseline to 20 weeks
Percentage of African American/Black Patients Achieving Seated Systolic Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks		Baseline to 4, 8, 12, 16, 20 weeks
Percentage of African American/Black Patients Achieving Seated Diastolic Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks		Baseline to 4, 8, 12, 16, 20 weeks
Percentage of African American/Black Patients Achieving Seated Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks		Baseline to 4, 8, 12, 16, 20 weeks
Percentage of African American/Black Patients Achieving Seated Systolic Blood Pressure Reduction Ranges From Baseline to 4, 8, 12, 16, 20 Weeks		Baseline to 4, 8, 12, 16, 20 weeks
Percentage of African American/Black Patients Achieving Seated Diastolic Blood Pressure Reduction Ranges From Baseline to 4, 8, 12, 16, 20 Weeks		Baseline to 4, 8, 12, 16, 20 weeks
Percentage of Asian Patients Achieving Seated Systolic Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks		Baseline to 4, 8, 12, 16, 20 weeks
Percentage of Asain Patients Achieving Seated Diastolic Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks		Baseline to 4, 8, 12, 16, 20 weeks
Percentage of Asian Patients Achieving Seated Systolic Blood Pressure Reduction Ranges From Baseline to 4, 8, 12, 16, 20 Weeks		Baseline to 4, 8, 12, 16, 20 weeks
Percentage of Asian Patients Achieving Seated Diastolic Blood Pressure Reduction Ranges From Baseline to 4, 8, 12, 16, 20 Weeks		Baseline to 4, 8, 12, 16, 20 weeks
Percentage of Hispanic Patients Achieving Seated Systolic Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks		Baseline to 4, 8, 12, 16, 20 weeks
Percentage of Hispanic Patients Achieving Seated Diastolic Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks		Baseline to 4, 8, 12, 16, 20 weeks
Percentage of Hispanic Patients Achieving Seated Systolic Blood Pressure Reduction Ranges From Baseline to 4, 8, 12, 16, 20 Weeks		Baseline to 4, 8, 12, 16, 20 weeks
Percentage of Hispanic Patients Achieving Seated Diastolic Blood Pressure Reduction Ranges From Baseline to 4, 8, 12, 16, 20 Weeks		Baseline to 4, 8, 12, 16, 20 weeks
Percentage of Elderly Patients Achieving Seated Systolic Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks		Baseline to 4, 8, 12, 16, 20 weeks
Percentage of Elderly Patients Achieving Seated Diastolic Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks		Baseline to 4, 8, 12, 16, 20 weeks
Percentage of Elderly Patients Achieving Seated Systolic Blood Pressure Reduction Ranges From Baseline to 4, 8, 12, 16, 20 Weeks		Baseline to 4, 8, 12, 16, 20 weeks
Percentage of Elderly Patients Achieving Seated Diastolic Blood Pressure Reduction Ranges From Baseline to 4, 8, 12, 16, 20 Weeks		Baseline to 4, 8, 12, 16, 20 weeks
Percentage of Type 2 Diabetic Patients Achieving Seated Systolic Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks		Baseline to 4, 8, 12, 16, 20 weeks
Percentage of Type 2 Diabetic Patients Achieving Seated Diastolic Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks		Baseline to 4, 8, 12, 16, 20 weeks
Percentage of Type 2 Diabetic Patients Achieving Seated Systolic Blood Pressure Reduction Ranges From Baseline to 4, 8, 12, 16, 20 Weeks		Baseline to 4, 8, 12, 16, 20 weeks
Percentage of Type 2 Diabetic Patients Achieving Seated Diastolic Blood Pressure Reduction Ranges From Baseline to 4, 8, 12, 16, 20 Weeks		Baseline to 4, 8, 12, 16, 20 weeks
Percentage of Obese Patients Achieving Seated Systolic Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks		Baseline to 4, 8, 12, 16, 20 weeks
Percentage of Obese Patients Achieving Seated Diastolic Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks		Baseline to 4, 8, 12, 16, 20 weeks
Percentage of Obese Patients Achieving Seated Systolic Blood Pressure Reduction Ranges From Baseline to 4, 8, 12, 16, 20 Weeks		Baseline to 4, 8, 12, 16, 20 weeks
Percentage of Obese Patients Achieving Seated Diastolic Blood Pressure Reduction Ranges From Baseline to 4, 8, 12, 16, 20 Weeks		Baseline to 4, 8, 12, 16, 20 weeks
Percentage of Patients With Metabolic Syndrome Achieving Seated Systolic Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks		Baseline to 4, 8, 12, 16, 20 weeks
Percentage of Patients With Metabolic Syndrome Achieving Seated Diastolic Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks		Baseline to 4, 8, 12, 16, 20 weeks
Percentage of Patients With Metabolic Syndrome Achieving Seated Systolic Blood Pressure Reduction Ranges From Baseline to 4, 8, 12, 16, 20 Weeks		Baseline to 4, 8, 12, 16, 20 weeks
Percentage of Patients With Metabolic Syndrome Achieving Seated Diastolic Blood Pressure Reduction Ranges From Baseline to 4, 8, 12, 16, 20 Weeks		Baseline to 4, 8, 12, 16, 20 weeks
Percentage of Participants Previously on a Dihydropyridine Calcium Channel Blocker Achieving the Blood Pressure Goals From Baseline to 12 Weeks		Baseline to 12 weeks
Percentage of Participants Previously on a Dihydropyridine Calcium Channel Blocker Achieving the Blood Pressure Goals From Baseline to 20 Weeks		Baseline to 20 weeks
Percentage of Participants Previously on a Diuretic Achieving the Blood Pressure Goals From Baseline to 12 Weeks		Baseline to 12 weeks
Percentage of Participants Previously on a Diuretic Achieving the Blood Pressure Goals From Baseline to 20 Weeks		Baseline to 20 weeks
Percentage of Participants Previously on an Angiotensin Converting Enzyme Inhibitor Achieving the Blood Pressure Goals From Baseline to 12 Weeks		Baseline to 12 weeks
Percentage of Participants Previously on an Angiotensin Converting Enzyme Inhibitor Achieving the Blood Pressure Goals From Baseline to 20 Weeks		Baseline to 20 weeks
Percentage of Participants Previously on an Angiotensin II Receptor Blocker Achieving the Blood Pressure Goals From Baseline to 12 Weeks		Baseline to 12 weeks
Percentage of Participants Previously on an Angiotensin II Receptor Blocker Achieving the Blood Pressure Goals From Baseline to 20 Weeks		Baseline to 20 weeks
Percentage of Participants Previously on a Beta Blocker Achieving the Blood Pressure Goals From Baseline to 12 Weeks		Baseline to 12 weeks
Percentage of Participants Previously on a Beta Blocker Achieving the Blood Pressure Goals From Baseline to 20 Weeks		Baseline to 20 weeks
Percentage of Participants Previously on a Nondihydropyridine Calcium Channel Blocker Achieving the Blood Pressure Goals From Baseline to 12 Weeks		Baseline to 12 weeks
Percentage of Participants Previously on a Nondihydropyridine Calcium Channel Blocker Achieving the Blood Pressure Goals From Baseline to 20 Weeks		Baseline to 20 weeks

Collaborators and Investigators

• Sponsor: Daiichi Sankyo, Inc.
• Collaborators: Integrium

Publications and helpful links

General Publications

• Nesbitt SD, Shojaee A, Maa JF, Weir MR. Efficacy of an amlodipine/olmesartan treatment algorithm in patients with or without type 2 diabetes and hypertension (a secondary analysis of the BP-CRUSH study). J Hum Hypertens. 2013 Jul;27(7):445-52. doi: 10.1038/jhh.2012.65. Epub 2012 Dec 20.
• Hsueh WA, Shojaee A, Maa JF, Neutel JM. Efficacy of amlodipine/olmesartan medoxomil +/- HCTZ in obese patients uncontrolled on antihypertensive monotherapy. Curr Med Res Opin. 2012 Nov;28(11):1809-18. doi: 10.1185/03007995.2012.740632. Epub 2012 Oct 30.

Study record dates

Study Major Dates

• Study Start: November 1, 2008
• Primary Completion (ACTUAL): August 1, 2009
• Study Completion (ACTUAL): September 1, 2009

Study Registration Dates

• First Submitted: November 13, 2008
• First Submitted That Met QC Criteria: November 13, 2008
• First Posted (ESTIMATE): November 14, 2008

Study Record Updates

• Last Update Posted (ACTUAL): January 9, 2019
• Last Update Submitted That Met QC Criteria: December 20, 2018
• Last Verified: September 1, 2010

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; Natriuretic Agents; Membrane Transport Modulators; Diuretics; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Sodium Chloride Symporter Inhibitors; Amlodipine; Olmesartan; Olmesartan Medoxomil; Hydrochlorothiazide
• Other Study ID Numbers: CS8663-404

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
• IPD Sharing Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• IPD Sharing Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR