24 Week Efficacy and Safety Study of Empagliflozin (BI 10773) in Hypertensive Black/African American Patients With Type 2 Diabetes Mellitus and Hypertension

A Randomised, Double-blind, Placebo-controlled, Parallel Group, Efficacy and Safety Study of Empagliflozin (10mg, 25mg) Administered Orally, Once Daily Over 24 Weeks in Hypertensive Black/African American Patients With Type 2 Diabetes Mellitus

This trial is designed to investigate the efficacy and safety of empagliflozin compared with placebo in hypertensive black/African Americans with type 2 Diabetes Mellitus. Since hyperglycaemia and hypertension are key risk factors for both micro- and macrovascular complications, assessment of both glucose and BP lowering effects of empagliflozin in hypertensive African American patients with type 2 Diabetes Mellitus could provide clinically highly relevant, new information for the use of empagliflozin.

Essential hypertension is four times more common in African Americans than in Caucasians.

One of the risk factors for hypertension is sodium sensitivity and approximately one third of the essential hypertensive population is responsive to sodium intake. There is a higher association of hypertension with sodium sensitivity in African American patients with type 2 Diabetes Mellitus.

The treatment duration of this trial (24 weeks) will enable assessment of the clinically relevant endpoint of a decrease in HbA1c, a well accepted measurement of chronic glycaemic control and the key secondary endpoints of decreases in systolic BP (SBP) and diastolic BP (DBP) at 12 and 24 weeks.

Study Overview

• Status: Completed
• Conditions: Hypertension; Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: Empagliflozin low dose; Drug: Empagliflozin high dose; Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 166
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • University of Alabama at Birmingham
    • Birmingham, Alabama, United States, 35211
      • Clinical Research Advantage, Inc./Rita B. Chuang, MD, LLC
    • Huntsville, Alabama, United States, 35801
      • Longwood Research
    • Mobile, Alabama, United States, 36617
      • University of South Alabama
    • Mobile, Alabama, United States, 36608
      • Internal Medicine Center, LLC
    • Mobile, Alabama, United States, 36617
      • Mobile Medical and Diagnostic Center
  • Arkansas
    • Little Rock, Arkansas, United States, 72204
      • Cardiology and Medicine Clinic
    • Little Rock, Arkansas, United States, 72205
      • Larry Watkins, M .D.
  • California
    • Chula Vista, California, United States, 91911
      • eStudySite
    • Lomita, California, United States, 90717
      • Torrance Clinical Research Institute Inc.
    • Long Beach, California, United States, 90807
      • Long Beach Center For Clinical Research
    • Los Angeles, California, United States, 90025
      • MD Clinical Trials
    • Los Angeles, California, United States, 90035
      • Office of Dr. Alexander Ford, M.D.
    • Orange, California, United States, 92868
      • Diabetes Associates Medical Group
    • Riverside, California, United States, 92506
      • Integrated Research Group, Inc.
    • Sacramento, California, United States, 95821
      • Clinical Trials Research
    • Tustin, California, United States, 92780
      • Orange County Research Center
  • Colorado
    • Denver, Colorado, United States, 80246
      • Lynn Institute of Denver
  • Florida
    • Hollywood, Florida, United States, 33024
      • Pines Clinical Research Inc.
    • Jacksonville, Florida, United States, 32277
      • Care Partners Clinical Research LLC
    • Jacksonville, Florida, United States, 32207
      • Uf Health Jacksonville
    • Opa-locka, Florida, United States, 33054
      • Sunshine Research Center
    • Orlando, Florida, United States, 32811
      • Central Florida Internist
    • Port Orange, Florida, United States, 32129
      • Accord Clinical Research, LLC
    • Saint Petersburg, Florida, United States, 33709
      • Meridien Research
    • Saint Petersburg, Florida, United States, 33711
      • Alternative Solutions Medical Research and Prevention Center
    • Sanford, Florida, United States, 32771
      • International Clinical Research - US, LLC
    • Tampa, Florida, United States, 33634
      • Meridien Research
  • Georgia
    • Atlanta, Georgia, United States, 30303
      • Grady Memorial Hospital
    • Atlanta, Georgia, United States, 30310
      • Morehouse School of Medicine
    • Atlanta, Georgia, United States, 30331
      • Atlanta Center
    • Atlanta, Georgia, United States, 30342
      • Atlanta Clinical Research Centers
    • Dunwoody, Georgia, United States, 30338
      • Albert F. Johary MD, PC
    • Marietta, Georgia, United States, 30060
      • Sestron Clinical Research
    • Marietta, Georgia, United States, 30067
      • Clinical Research Advantage, Inc./Rita B. Chuang, MD, LLC
    • Sandy Springs, Georgia, United States, 30328
      • WR-Mount Vernon Clinical Research, LLC
    • Stockbridge, Georgia, United States, 30281
      • Eagle's Landing Diabetes and Endocrinology
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
    • Chicago, Illinois, United States, 60607
      • Cedar Crosse Research Center
    • Chicago, Illinois, United States, 60612
      • John H. Stroger Jr. Hospital of Cook Country
  • Indiana
    • Brownsburg, Indiana, United States, 46112
      • Investigators Research Group, LLC
  • Louisiana
    • Lake Charles, Louisiana, United States, 70601
      • Centex Studies, Inc.
    • Metairie, Louisiana, United States, 70002
      • Gulf Regional Research and Education Services, LLC
    • New Orleans, Louisiana, United States, 70119
      • New Orleans Center for Clinical Research
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland School of Medicine
    • Baltimore, Maryland, United States, 21218
      • American Institute of Research Studies
  • Mississippi
    • Jackson, Mississippi, United States, 39209
      • Phillips Medical Services, PLLC
  • Missouri
    • Washington, Missouri, United States, 63090-4700
      • Mercy Research
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Quality Clinical Research Inc
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Accent Clinical Trials
  • New Mexico
    • Albuquerque, New Mexico, United States, 87108
      • Lovelace Scientific Resources, Inc.
  • New York
    • Brooklyn, New York, United States, 11206
      • Healthwise Medical Associates
    • Brooklyn, New York, United States, 11207
      • Modern Medical
    • Brooklyn, New York, United States, 11203-1203
      • Offic of Dr. Eric Cheng
    • Buffalo, New York, United States, 14215
      • Erie County Medical Center
    • Laurelton, New York, United States, 11413
      • Scott Research, Inc.
    • New York, New York, United States, 10036
      • Medex Healthcare Research, Inc.
    • Rosedale, New York, United States, 11422
      • Laurelton Heart Specialist, PC
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Metrolina Internal Medicine, PA
    • Greensboro, North Carolina, United States, 27410
      • Triad Clinical Trials
    • Greensboro, North Carolina, United States, 27405
      • PhysiqueMed Clinical Trials
    • High Point, North Carolina, United States, 27265
      • High Point Clinical Trials Center
    • High Point, North Carolina, United States, 27262
      • Peters Medical Research
    • New Bern, North Carolina, United States, 28562
      • Coastal Carolina Health Care, P.A.
  • Ohio
    • Columbus, Ohio, United States, 43214
      • Hometown Urgent Care
    • Dayton, Ohio, United States, 45406
      • Dayton Clinical Research
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73129
      • Today Clinical Research, Oklahoma City
  • Pennsylvania
    • Media, Pennsylvania, United States, 19063
      • Suburban Research Associates
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University School of Medicine
  • South Carolina
    • Charleston, South Carolina, United States, 29407
      • Medical Research South
    • Columbia, South Carolina, United States, 29204
      • TLM Medical Services, LLC
    • Columbia, South Carolina, United States, 29223
      • Amistad Clinical Research Center
    • Greenville, South Carolina, United States, 29615
      • Greenville Pharmaceutical Rsch
    • Greer, South Carolina, United States, 29651
      • Mountain View Clinical Research
    • Moncks Corner, South Carolina, United States, 29461
      • Berkley Family Practice
    • Rock Hill, South Carolina, United States, 29732
      • Carolina Cardiology Clinical Research Institute, LLC
    • Varnville, South Carolina, United States, 29944
      • Community Research Partners, Inc
  • Tennessee
    • Memphis, Tennessee, United States, 38163
      • University of Tennessee
    • Memphis, Tennessee, United States, 38125
      • Southwind Medical Specialists
    • Memphis, Tennessee, United States, 38104
      • Memphis Veterans Affairs Medical Center
    • Memphis, Tennessee, United States, 38119
      • The Green Clinic PC
  • Texas
    • Houston, Texas, United States, 77004
      • Diagnostic Clinic of Houston
    • Houston, Texas, United States, 77081
      • Texas Center for Drug Development, Inc.
    • Houston, Texas, United States, 77058
      • Centex Studies, Inc.
    • Houston, Texas, United States, 77051
      • Cullen Family Practice, PLLC
    • Houston, Texas, United States, 77096
      • Kelsey-Seybold Clinic
    • Waco, Texas, United States, 76710
      • Hillcrest Family Health Center
  • Virginia
    • Arlington, Virginia, United States, 22203
      • Millennium Clinical Trials LLC
    • Norfolk, Virginia, United States, 23510
      • York Clinical Research, LLC
    • Richmond, Virginia, United States, 23235
      • Clinical Research Partners, LLC
    • Richmond, Virginia, United States, 23219
      • Dominion Medical Associates, Inc.
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53216
      • Family Medical Clinic

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:

• Diagnosis of Type 2 Diabetes Mellitus (T2DM) prior to informed consent.

• Male and female black/African American patients on diet and exercise regimen who are EITHER drug-naïve (defined as absence of any oral antidiabetic therapy, glucagon like peptide-1 (GLP-1) analog or insulin for 12 weeks, 16 weeks for pioglitazone prior to randomisation) OR pre-treated with stable dose of

  • Metformin only, or
  • Sulfonylurea only, or
  • Dipeptidyl peptidase-4 (DPP-4) inhibitor only, or
  • metformin plus sulfonylurea, or
  • metformin plus DPP-4 inhibitor. Treatment has to be unchanged for a minimum of 12 weeks prior to randomization. Dose for metformin: maximum tolerated dose The maximum daily dose of Sulfonylurea (SU) or DPP-4 inhibitor should not exceed that stated in the local label.
• HbA1c of >= 7.0% (53 mmol/mol) and ≤ 11.0% (97 mmol/mol) at Visit 1 (screening).
• Mean seated Systolic Blood Pressure (SBP) 140-180 mmHg at Visit 1 (screening).
• Successful completion of baseline Ambulatory Blood Pressure Monitor (ABPM) testing with a mean SBP 135-175 mmHg prior to randomisation.
• Treatment with stable doses of at least one but not more than 4 antihypertensive medication >= 4 weeks prior to randomisation.
• Age >= 18 years at Visit 1 (screening)
• Signed and dated written informed consent by date of Visit 1 in accordance with Good Clinical Practice (GCP) and local legislation

Exclusion criteria:

• Uncontrolled hyperglycemia with a glucose level >270 mg/dl (>15.0 mmol/L) after an overnight fast during placebo run-in (includes Visit 2.1) and confirmed by a second measurement (not on the same day).
• Exposure to any other antidiabetic medication within 12 weeks prior to randomisation other than metformin, sulfonylurea, Dipeptidyl peptidase-4 (DPP-4) inhibitor, metformin plus sulfonylurea or metformin plus DPP-4 inhibitor.
• Current hypertension treatment with oral Minoxidil (topical minoxidil for hair growth is allowed).
• Mean seated Systolic Blood Pressure (SBP) ≥181 mmHg during placebo run-in visit and confirmed by a second measurement (not on the same day) preferably within one day.
• Upper arm circumference that exceeds the upper circumference level of the cuff size of either Ambulatory Blood Pressure Monitor (ABPM) and/or (BP) measurement device used in the study.
• Night shift workers who routinely sleep during the daytime and/or whose work hours include midnight.
• Diagnosis of autoimmune diabetes/Type I diabetes mellitus, monogenic (neonatal or maturity onset diabetes of the young (MODY)) diabetes or Type I diabetes in adults/latent autoimmune diabetes of adults (LADA) per investigator or patient medical history at the time of Visit 1 (screening).
• Known or suspected secondary hypertension (e.g. renal artery stenosis,phaeochromocytoma, Cushing's disease).
• History or evidence of hypertensive retinopathy (Keith-Wagener grade III or IV) and/or hypertensive encephalopathy.
• Clinically significant valvular heart disease or severe aortic stenosis in the opinion of the investigator.
• Acute coronary syndrome (non- ST wave elevated myocardial infarction (STEMI), STEMI and unstable angina pectoris), stroke or transient ischemic attack within 3 months prior to informed consent.
• Indication of liver disease, defined by serum levels of either Alanine Aminotransferase (ALT) (Serum Glutamic Pyruvate Transaminase(SGPT)), Aspartate Aminotransferase (AST) (Serum Glutamic Oxaloacetic Transaminase (SGOT)), or alkaline phosphatase above 3 x upper limit of normal (ULN) as determined during screening and/or run-in phase.
• Impaired renal function, defined as Estimated Glomerular Filtration Rate (eGFR)< 45 ml/min/1.73m2 (moderate renal impairment, chronic kidney disease epidemiology collaboration Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula) as determined during screening and/or run-in phase.
• Bariatric surgery within the past two years and other gastrointestinal surgeries that induce chronic malabsorption.
• Medical history of cancer (except for basal cell carcinoma) and/or treatment for cancer within the last 5 years.
• Blood dyscrasias or any disorders causing hemolysis or unstable Red Blood Cells (e.g. malaria, babesiosis, haemolytic anaemia, thalassemia, sickle cell anaemia (sickle cell trait is allowed)).
• Medical history and signs and symptoms of diabetic autonomic neuropathy.
• Treatment with anti-obesity drugs 3 months prior to randomisation (i.e. surgery, aggressive diet regimen, etc.) leading to unstable body weight.
• Current treatment with systemic steroids at time of informed consent or change in dosage of thyroid hormones within 6 weeks prior to informed consent or any other uncontrolled endocrine disorder except Type 2 Diabetes Mellitus (T2DM) in the opinion of the investigator.

• Pre-menopausal women (last menstruation <=1 year prior to informed consent) who:

  • are nursing or pregnant or
  • are of child-bearing potential and are not practicing an acceptable method of birth control, or do not plan to continue using this method throughout the study and do not agree to submit to periodic pregnancy testing during participation in the trial. Acceptable methods of birth control include tubal ligation, transdermal patch, intra uterine devices/systems (IUDs/IUSs), oral, implantable or injectable contraceptives, complete sexual abstinence (if acceptable by local authorities), double barrier method and vasectomised partner.
• Alcohol, drug or confectionary liquorice abuse within the 3 months prior to informed consent that would interfere with trial participation or any ongoing condition leading to a decreased compliance to study procedures or study drug intake in the investigator's opinion.
• Intake of an investigational drug in another trial within 30 days prior to intake of study medication in this trial; or participating in another trial (involving an investigational drug and/or follow-up) after discontinuing medication in that trial.
• Any other clinical condition that would jeopardize patient's safety while participating in this clinical trial in the opinion of the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Empagliflozin; starting dose 10mg; forced titration after 4 weeks 25mg dose	Drug: Empagliflozin low dose; starting dose 10mg; forced titration after 4 weeks 25mg dose; Drug: Empagliflozin high dose; starting dose 10mg; forced titration after 4 weeks 25mg dose
PLACEBO_COMPARATOR: Placebo; starting dose 10mg; forced titration after 4 weeks 25mg dose	Drug: placebo; starting dose 10mg; forced titration after 4 weeks 25mg dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Glycated Haemoglobin (HbA1c) (%) at 24 Weeks	Change from baseline in HbA1c (%) at 24 weeks is presented. The term "baseline" refers to the last observation prior to randomisation of the patient. Means presented are the adjusted means. Restricted maximum likelihood (REML)-based mixed model repeated measures (MMRM) model is used in the statistical analysis.	baseline and 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Mean 24-hour Ambulatory Systolic Blood Pressure (SBP) at Week 12	Change from baseline in mean 24-hour ambulatory Systolic blood pressure SBP at Week 12 is presented. The term "baseline" refers to the last observation prior to randomisation of the patient. Means presented are the adjusted means. This is a key secondary endpoint	baseline and 12 weeks
Changes From Baseline in Trough Mean Ambulatory SBP at Week 12	Changes from baseline in trough mean ambulatory SBP at Week 12 is presented. The term "baseline" refers to the last observation prior to randomisation of the patient. Means presented are the adjusted means. This is a key secondary endpoint	baseline and 12 weeks
Change From Baseline in Body Weight at Week 24	Changes from baseline in body weight at Week 24 is presented. The term "baseline" refers to the last observation prior to randomisation of the patient. Means presented are the adjusted means. This is a key secondary endpoint	baseline and 24 weeks
Change From Baseline in Trough Seated SBP at Week 12	Change from baseline in trough seated SBP (mmHg) at Week 12 is presented. The term "baseline" refers to the last observation prior to randomisation of the patient. Means presented are the adjusted means. This is a key secondary endpoint	baseline and 12 weeks
Change From Baseline in Mean 24-hour Ambulatory SBP (mmHg) at Week 24	Change from baseline in mean 24-hour ambulatory SBP (mmHg) at Week 24 is secondary endpoint. The term "baseline" refers to the last observation prior to randomisation of the patient. Means presented are the adjusted means.	baseline and 24 weeks
Change From Baseline in Mean 24-hour Ambulatory Diastolic Blood Pressure (DBP) at Week 12	Change from baseline in mean 24-hour ambulatory DBP (mmHg) at Week 12. The term "baseline" refers to the last observation prior to randomisation of the patient. Means presented are the adjusted means.	baseline and 12 weeks
Change From Baseline in Mean 24-hour Ambulatory DBP (mmHg) at Week 24	Change from baseline in mean 24-hour ambulatory DBP (mmHg) at Week 24 is secondary endpoint. The term "baseline" refers to the last observation prior to randomisation of the patient. Means presented are the adjusted means.	baseline and 24 weeks
Change From Baseline in Trough Seated SBP (mmHg) at Week 24	Change from baseline in trough seated SBP (mmHg) at Week 24 is secondary endpoint. The term "baseline" refers to the last observation prior to randomisation of the patient. Means presented are the adjusted means.	baseline and 24 weeks
Change From Baseline in Trough Seated DBP (mmHg) at Week 12	Change from baseline in trough seated DBP (mmHg) at Week 12 is secondary endpoint. The term "baseline" refers to the last observation prior to randomisation of the patient. Means presented are the adjusted means.	baseline and 12 weeks
Change From Baseline in Trough Seated DBP (mmHg) at Week 24	Change from baseline in trough seated DBP (mmHg) at Week 24 is secondary endpoint. The term "baseline" refers to the last observation prior to randomisation of the patient. Means presented are the adjusted means.	baseline and 24 weeks

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim
• Collaborators: Eli Lilly and Company

Publications and helpful links

General Publications

• Ferdinand KC, Harrison D, Johnson A. The NEW-HOPE study and emerging therapies for difficult-to-control and resistant hypertension. Prog Cardiovasc Dis. 2020 Jan-Feb;63(1):64-73. doi: 10.1016/j.pcad.2019.12.008. Epub 2020 Jan 8.
• Ferdinand KC, Izzo JL, Lee J, Meng L, George J, Salsali A, Seman L. Antihyperglycemic and Blood Pressure Effects of Empagliflozin in Black Patients With Type 2 Diabetes Mellitus and Hypertension. Circulation. 2019 Apr 30;139(18):2098-2109. doi: 10.1161/CIRCULATIONAHA.118.036568.
• Ferdinand KC, Seman L, Salsali A. Design of a 24-week trial of empagliflozin once daily in hypertensive black/African American patients with type 2 diabetes mellitus. Curr Med Res Opin. 2018 Feb;34(2):361-367. doi: 10.1080/03007995.2017.1405800. Epub 2017 Nov 29.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 25, 2014
• Primary Completion (ACTUAL): May 18, 2017
• Study Completion (ACTUAL): May 18, 2017

Study Registration Dates

• First Submitted: July 3, 2014
• First Submitted That Met QC Criteria: July 3, 2014
• First Posted (ESTIMATE): July 8, 2014

Study Record Updates

• Last Update Posted (ACTUAL): July 31, 2018
• Last Update Submitted That Met QC Criteria: July 4, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Hypertension; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Empagliflozin
• Other Study ID Numbers: 1245.29