Safety and Efficacy Study of a Triple Combination Therapy in Subjects With Hypertension
December 20, 2018 updated by: Daiichi Sankyo, Inc.
A Randomized, Double-Blind, Parallel Group Study Evaluating the Efficacy and Safety of Co-Administration of a Triple Combination Therapy of Olmesartan Medoxomil, Amlodipine Besylate and Hydrochlorothiazide in Subjects With Hypertension
To determine the effectiveness of four different strength combinations of three approved anti-hypertension therapies (olmesartan medoxomil, amlodipine, and hydrochlorothiazide) for lowering blood pressure.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
2500
Phase
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Ciales, Puerto Rico
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Guayama, Puerto Rico
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Ponce, Puerto Rico
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Rio Piedras, Puerto Rico
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Alabama
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Birmingham, Alabama, United States
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Columbiana, Alabama, United States
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Gulf Shores, Alabama, United States
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Hoover, Alabama, United States
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Huntsville, Alabama, United States
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Mobile, Alabama, United States
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Montgomery, Alabama, United States
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Muscle Shoals, Alabama, United States
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Tuscumbia, Alabama, United States
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Arizona
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Chandler, Arizona, United States
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Goodyear, Arizona, United States
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Lake Havasu City, Arizona, United States
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Mesa, Arizona, United States
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Peoria, Arizona, United States
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Phoenix, Arizona, United States
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Scottsdale, Arizona, United States
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Tucson, Arizona, United States
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Arkansas
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Hot Springs, Arkansas, United States
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Jonesboro, Arkansas, United States
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Little Rock, Arkansas, United States
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North Little Rock, Arkansas, United States
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Searcy, Arkansas, United States
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California
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Anaheim, California, United States
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Beverly Hills, California, United States
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Buena Park, California, United States
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Burbank, California, United States
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Carmichael, California, United States
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Chino, California, United States
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Chula Vista, California, United States
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Escondido, California, United States
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Greenbrae, California, United States
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Hollywood, California, United States
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Huntington Park, California, United States
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Long Beach, California, United States
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Los Angeles, California, United States
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Los Gatos, California, United States
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Merced, California, United States
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National City, California, United States
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Orange, California, United States
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Roseville, California, United States
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San Diego, California, United States
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San Jose, California, United States
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Santa Ana, California, United States
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Santa Monica, California, United States
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Temecula, California, United States
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West Palm Beach, California, United States
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Westlake Village, California, United States
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Colorado
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Denver, Colorado, United States
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Golden, Colorado, United States
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Pueblo, Colorado, United States
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Wheat Ridge, Colorado, United States
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Connecticut
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Danbury, Connecticut, United States
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Milford, Connecticut, United States
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Stamford, Connecticut, United States
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Trumbull, Connecticut, United States
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Waterbury, Connecticut, United States
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Florida
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Aventura, Florida, United States
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Boynton Beach, Florida, United States
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Bradenton, Florida, United States
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Brooksville, Florida, United States
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Cape Coral, Florida, United States
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Clearwater, Florida, United States
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Coral Gables, Florida, United States
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Crystal River, Florida, United States
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Daytona Beach, Florida, United States
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DeLand, Florida, United States
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Deerfield Beach, Florida, United States
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Delray Beach, Florida, United States
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Dunnellon, Florida, United States
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Fort Myers, Florida, United States
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Hialeah, Florida, United States
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Hollywood, Florida, United States
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Jacksonville, Florida, United States
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Jupiter, Florida, United States
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Kissimmee, Florida, United States
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Largo, Florida, United States
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Merritt Island, Florida, United States
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Miami, Florida, United States
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New Port Richey, Florida, United States
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Ocala, Florida, United States
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Palm Harbor, Florida, United States
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Pembroke Pines, Florida, United States
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Plantation, Florida, United States
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Port Orange, Florida, United States
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Saint Petersburg, Florida, United States
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Sarasota, Florida, United States
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South Miami, Florida, United States
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Tampa, Florida, United States
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W. Bradenton, Florida, United States
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Georgia
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Atlanta, Georgia, United States
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Augusta, Georgia, United States
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Columbus, Georgia, United States
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Savannah, Georgia, United States
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Suwanee, Georgia, United States
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Waycross, Georgia, United States
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Idaho
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Idaho Falls, Idaho, United States
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Illinois
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Chicago, Illinois, United States
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Gurnee, Illinois, United States
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Libertyville, Illinois, United States
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Indiana
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Evansville, Indiana, United States
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Indianapolis, Indiana, United States
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Kansas
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Newton, Kansas, United States
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Shawnee Mission, Kansas, United States
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Wichita, Kansas, United States
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Kentucky
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Madisonville, Kentucky, United States
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Mount Sterling, Kentucky, United States
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Munfordville, Kentucky, United States
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Paducah, Kentucky, United States
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Louisiana
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Kenner, Louisiana, United States
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Lake Charles, Louisiana, United States
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Metairie, Louisiana, United States
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New Orleans, Louisiana, United States
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Shreveport, Louisiana, United States
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Maryland
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Baltimore, Maryland, United States
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Elkridge, Maryland, United States
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Oxon Hill, Maryland, United States
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Massachusetts
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Brockton, Massachusetts, United States
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Haverhill, Massachusetts, United States
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West Yarmouth, Massachusetts, United States
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Michigan
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Benzonia, Michigan, United States
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Clarkston, Michigan, United States
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Paw Paw, Michigan, United States
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Southfield, Michigan, United States
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Traverse City, Michigan, United States
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Waterford, Michigan, United States
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Minnesota
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Brooklyn Center, Minnesota, United States
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Chaska, Minnesota, United States
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Saint Paul, Minnesota, United States
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Mississippi
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Olive Branch, Mississippi, United States
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Missouri
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Florissant, Missouri, United States
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Kansas City, Missouri, United States
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Saint Louis, Missouri, United States
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Montana
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Butte, Montana, United States
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Missoula, Montana, United States
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Nebraska
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Broken Bow, Nebraska, United States
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North Platte, Nebraska, United States
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Nevada
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Las Vegas, Nevada, United States
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New Jersey
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Berlin, New Jersey, United States
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Elizabeth, New Jersey, United States
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Voorhees, New Jersey, United States
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New York
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Buffalo, New York, United States
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Manlius, New York, United States
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Mineola, New York, United States
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New York, New York, United States
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Westfield, New York, United States
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North Carolina
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Calabash, North Carolina, United States
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Charlotte, North Carolina, United States
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Durham, North Carolina, United States
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Hickory, North Carolina, United States
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High Point, North Carolina, United States
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Raleigh, North Carolina, United States
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Salisbury, North Carolina, United States
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Statesville, North Carolina, United States
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Tabor City, North Carolina, United States
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Winston-Salem, North Carolina, United States
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North Dakota
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Fargo, North Dakota, United States
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Ohio
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Austintown, Ohio, United States
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Cincinnati, Ohio, United States
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Cleveland, Ohio, United States
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Columbus, Ohio, United States
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Euclid, Ohio, United States
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Franklin, Ohio, United States
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Kettering, Ohio, United States
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Lyndhurst, Ohio, United States
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Marion, Ohio, United States
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Mount Gilead, Ohio, United States
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Wadsworth, Ohio, United States
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Westlake, Ohio, United States
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Oklahoma
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Norman, Oklahoma, United States
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Oklahoma City, Oklahoma, United States
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Tulsa, Oklahoma, United States
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Oregon
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Eugene, Oregon, United States
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Medford, Oregon, United States
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Portland, Oregon, United States
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Pennsylvania
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Beaver, Pennsylvania, United States
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Bensalem, Pennsylvania, United States
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Downingtown, Pennsylvania, United States
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Erie, Pennsylvania, United States
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Harleysville, Pennsylvania, United States
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Jenkintown, Pennsylvania, United States
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Jersey Shore, Pennsylvania, United States
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Penndel, Pennsylvania, United States
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Philadelphia, Pennsylvania, United States
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Rhode Island
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Cranston, Rhode Island, United States
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East Providence, Rhode Island, United States
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Providence, Rhode Island, United States
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South Carolina
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Anderson, South Carolina, United States
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Charleston, South Carolina, United States
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Columbia, South Carolina, United States
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Murrells Inlet, South Carolina, United States
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Orangeburg, South Carolina, United States
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South Dakota
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Rapid City, South Dakota, United States
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Tennessee
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Bristol, Tennessee, United States
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Fayetteville, Tennessee, United States
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Knoxville, Tennessee, United States
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Memphis, Tennessee, United States
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Nashville, Tennessee, United States
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New Tazewell, Tennessee, United States
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Tullahoma, Tennessee, United States
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Texas
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Austin, Texas, United States
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Bedford, Texas, United States
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Corpus Christi, Texas, United States
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Houston, Texas, United States
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Hurst, Texas, United States
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Lake Jackson, Texas, United States
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Midland, Texas, United States
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Plano, Texas, United States
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Round Rock, Texas, United States
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San Antonio, Texas, United States
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Spring, Texas, United States
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Sugar Land, Texas, United States
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Temple, Texas, United States
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Waco, Texas, United States
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Utah
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Bountiful, Utah, United States
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Magna, Utah, United States
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Midvale, Utah, United States
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Salt Lake City, Utah, United States
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Sandy, Utah, United States
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Saratoga Springs, Utah, United States
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West Jordan, Utah, United States
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Virginia
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Norfolk, Virginia, United States
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Richmond, Virginia, United States
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Suffolk, Virginia, United States
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Washington
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Federal Way, Washington, United States
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Lakewood, Washington, United States
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Tacoma, Washington, United States
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Wisconsin
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Kenosha, Wisconsin, United States
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Madison, Wisconsin, United States
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 80 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Demonstrable hypertension defined as mean sitting trough cuff blood pressure ≥ 140/100 mmHg (SeSBP ≥ 140 mmHg and SeDBP ≥ 100mmHg) or mean sitting trough cuff BP ≥ 160/90 mmHg (SeSBP ≥ 160 mmHg and SeDBP ≥ 90mmHg).
Male or female newly diagnosed hypertensive subjects or currently on hypertension medication.
- Negative urine pregnancy test at screening
- Not lactating
- Do not plan to become pregnant during the study
Will practice birth control throughout the study by the following: oral or patch contraceptive, injectable or implantable contraceptive medication, intrauterine device, diaphragm or female condom plus spermicide
- Non childbearing potential must be classified by one of the following criteria
- Had a hysterectomy or tubal ligation at least 6 months prior to consent
- Has been postmenopausal for a least 1 year
Exclusion Criteria:
- Mean sitting trough cuff DBP <90 mmHg or mean sitting trough cuff SBP <140 mmHg (off antihypertensive medication).
- Subjects with uncontrolled hypertension taking multiple antihypertensive therapies (at the discretion of the investigator).
- Signs or symptoms which could exacerbate the occurrence of hypotension such as volume and salt depletion.
- History of hypertensive encephalopathy, stroke or transient ischemic attack (TIA).
- Participation in another clinical trial involving an investigational drug within one month prior to screening.
- History of myocardial infarction, percutaneous transluminal coronary revascularization, coronary artery bypass graft, and/or unstable angina within the past 6 months.
- Any history of New York Heart Association Class III or IV congestive heart failure (CHF). A history of New York Heart Association Class I or II CHF may be exclusionary at the discretion of the investigator.
- History of secondary hypertension including renal disease, pheochromocytoma, or Cushing's syndrome.
- Uncorrected coarctation of the aorta, bilateral renal artery stenosis, or unilateral renal artery stenosis in a solitary kidney.
- Evidence of symptomatic resting bradycardia.
- Evidence of hemodynamically significant cardiac valvular disease.
- Presence of heart block greater than first degree atrioventricular block, chronic atrial fibrillation or flutter.
- Uncontrolled Type I or Type II diabetes defined as HbA1c >9.0%. Diabetics must have documentation of HbA1c within 6 months of the Screening Visit. Undocumented subjects must have their HbA1c assessed prior to randomization. Note: Subjects with Type I or Type II diabetes controlled with insulin, diet or oral hypoglycemic agents on a stable dose for at least 30 days may be included.
- Evidence of liver disease as indicated by ALT and AST and/or total bilirubin >3 times the upper limit of normal.
- Severe renal insufficiency defined as a creatinine clearance (based on the Cockcroft-Gault formula) of <30 mL/min.
- Clinically significant laboratory elevations at Visit 1 that compromise subject safety, based on the investigator's judgment. Consideration should take into account the potential laboratory effects of the component blinded therapies.
- Positive for any one of the following tests: hepatitis B surface antigen, hepatitis C antibody (confirmed by radio immunobinding assay, RIBA) or HIV antibody (confirmed by western blot assay).
- Subjects with malignancy during the past 2 years excluding squamous cell or basal cell carcinoma of the skin.
- Known allergy to any of the medications used in the study.
- Subjects who require or are taking any concomitant medication, which may interfere with the objectives of the study (Refer to Section 5.2 for a listing of excluded medications).
- Pregnant or lactating females.
- Current history of drug or alcohol abuse.
- A subject with any medical condition, which in the judgment of the Investigator would jeopardize the evaluation of efficacy or safety and/or constitute a significant safety risk to the subject.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
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Experimental: OM40/AML10
olmesartan medoxomil 40mg and amlodipine 10mg
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40mg olmesartan medoxomil
Other Names:
Amlodipine 10mg
Other Names:
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Active Comparator: OM40/HCTZ25
olmesartan medoxomil 40mg and hydrochlorothiazide 25mg
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40mg olmesartan medoxomil
Other Names:
Hydrochlorothiazide 25mg
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|
Active Comparator: AML10/HCTZ25
amlodipine 10mg and hydrochlorothiazide 25mg
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Amlodipine 10mg
Other Names:
Hydrochlorothiazide 25mg
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|
Active Comparator: OM40/AML10/HCTZ25
olmesartan medoxomil 40mg, amlodipine 10mg, and hydrochlorothiazide 25mg
|
40mg olmesartan medoxomil
Other Names:
Amlodipine 10mg
Other Names:
Hydrochlorothiazide 25mg
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
|
Change From Baseline to Week 12 in Seated Diastolic Blood Pressure (SeDBP).
Time Frame: baseline to 12 weeks
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baseline to 12 weeks
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
|
Percentage of Subjects Who Reached Blood Pressure Goal (<140/90 mmHg; <130/80 mmHg for Subjects With Diabetes, Chronic Renal Disease, or Chronic Cardiovascular Disease)by 12 Weeks
Time Frame: Baseline to 12 weeks
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Baseline to 12 weeks
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Change in Mean 24-hour Ambulatory Blood Pressure From Baseline to Week 12 or Early Termination
Time Frame: Baseline to 12 weeks or early termination
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Baseline to 12 weeks or early termination
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Change in Seated Systolic Blood Pressure From Baseline to Week 12
Time Frame: Baseline to week 12
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Baseline to week 12
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Kereiakes DJ, Chrysant SG, Izzo JL Jr, Littlejohn T 3rd, Melino M, Lee J, Fernandez V, Heyrman R. Olmesartan/amlodipine/hydrochlorothiazide in participants with hypertension and diabetes, chronic kidney disease, or chronic cardiovascular disease: a subanalysis of the multicenter, randomized, double-blind, parallel-group TRINITY study. Cardiovasc Diabetol. 2012 Oct 30;11:134. doi: 10.1186/1475-2840-11-134.
- Chrysant SG, Littlejohn T 3rd, Izzo JL Jr, Kereiakes DJ, Oparil S, Melino M, Lee J, Fernandez V, Heyrman R. Triple-Combination therapy with olmesartan, amlodipine, and hydrochlorothiazide in black and non-black study participants with hypertension: the TRINITY randomized, double-blind, 12-week, parallel-group study. Am J Cardiovasc Drugs. 2012 Aug 1;12(4):233-43. doi: 10.1007/BF03261832.
- Oparil S, Melino M, Lee J, Fernandez V, Heyrman R. Triple therapy with olmesartan medoxomil, amlodipine besylate, and hydrochlorothiazide in adult patients with hypertension: The TRINITY multicenter, randomized, double-blind, 12-week, parallel-group study. Clin Ther. 2010 Jul;32(7):1252-69. doi: 10.1016/j.clinthera.2010.07.008.
- Chrysant SG, Oparil S, Melino M, Karki S, Lee J, Heyrman R. Efficacy and safety of long-term treatment with the combination of amlodipine besylate and olmesartan medoxomil in patients with hypertension. J Clin Hypertens (Greenwich). 2009 Sep;11(9):475-82. doi: 10.1111/j.1751-7176.2009.00159.x.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
May 1, 2008
Primary Completion (Actual)
April 1, 2009
Study Completion (Actual)
December 1, 2009
Study Registration Dates
First Submitted
March 28, 2008
First Submitted That Met QC Criteria
March 31, 2008
First Posted (Estimate)
April 1, 2008
Study Record Updates
Last Update Posted (Actual)
January 9, 2019
Last Update Submitted That Met QC Criteria
December 20, 2018
Last Verified
August 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
- CS8635-A-U301
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
- Statistical Analysis Plan (SAP)
- Informed Consent Form (ICF)
- Clinical Study Report (CSR)
- Analytic Code
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.