Clinical trial NCT02182830: 24 Week Efficacy and Safety Study of Empagliflozin (BI 10773) in Hypertensive Black/African American Patients With Type 2 Diabetes Mellitus and Hypertension
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes Mellitus, Type 2
Hypertension
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
Collaborators: name: Eli Lilly and Company
First posted: 2014-07-08
Enrollment: 166
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Change From Baseline in Glycated Haemoglobin (HbA1c) (%) at 24 Weeks
timeFrame: baseline and 24 weeks
Secondary outcomes:
measure: Change From Baseline in Mean 24-hour Ambulatory Systolic Blood Pressure (SBP) at Week 12
timeFrame: baseline and 12 weeks
measure: Changes From Baseline in Trough Mean Ambulatory SBP at Week 12
timeFrame: baseline and 12 weeks
measure: Change From Baseline in Body Weight at Week 24
timeFrame: baseline and 24 weeks
measure: Change From Baseline in Trough Seated SBP at Week 12
timeFrame: baseline and 12 weeks
measure: Change From Baseline in Mean 24-hour Ambulatory SBP (mmHg) at Week 24
timeFrame: baseline and 24 weeks
measure: Change From Baseline in Mean 24-hour Ambulatory Diastolic Blood Pressure (DBP) at Week 12
timeFrame: baseline and 12 weeks
measure: Change From Baseline in Mean 24-hour Ambulatory DBP (mmHg) at Week 24
timeFrame: baseline and 24 weeks
measure: Change From Baseline in Trough Seated SBP (mmHg) at Week 24
timeFrame: baseline and 24 weeks
measure: Change From Baseline in Trough Seated DBP (mmHg) at Week 12
timeFrame: baseline and 12 weeks
measure: Change From Baseline in Trough Seated DBP (mmHg) at Week 24
timeFrame: baseline and 24 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Birmingham
country: United States
facility: Clinical Research Advantage, Inc./Rita B. Chuang, MD, LLC
state: Alabama
city: Huntsville
country: United States
facility: Longwood Research
state: Alabama
city: Mobile
country: United States
facility: Internal Medicine Center, LLC
state: Alabama
city: Mobile
country: United States
facility: Mobile Medical and Diagnostic Center
state: Alabama
city: Mobile
country: United States
facility: University of South Alabama
state: Alabama
city: Little Rock
country: United States
facility: Cardiology and Medicine Clinic
state: Arkansas
city: Little Rock
country: United States
facility: Larry Watkins, M .D.
state: Arkansas
city: Chula Vista
country: United States
facility: eStudySite
state: California
city: Lomita
country: United States
facility: Torrance Clinical Research Institute Inc.
state: California
city: Long Beach
country: United States
facility: Long Beach Center for Clinical Research
state: California
city: Los Angeles
country: United States
facility: MD Clinical Trials
state: California
city: Los Angeles
country: United States
facility: Office of Dr. Alexander Ford, M.D.
state: California
city: Orange
country: United States
facility: Diabetes Associates Medical Group
state: California
city: Riverside
country: United States
facility: Integrated Research Group, Inc.
state: California
city: Sacramento
country: United States
facility: Clinical Trials Research
state: California
city: Tustin
country: United States
facility: Orange County Research Center
state: California
city: Denver
country: United States
facility: Lynn Institute of Denver
state: Colorado
city: Hollywood
country: United States
facility: Pines Clinical Research Inc.
state: Florida
city: Jacksonville
country: United States
facility: UF Health Jacksonville
state: Florida
city: Jacksonville
country: United States
facility: Care Partners Clinical Research LLC
state: Florida
city: Opa-locka
country: United States
facility: Sunshine Research Center
state: Florida
city: Orlando
country: United States
facility: Central Florida Internist
state: Florida
city: Port Orange
country: United States
facility: Accord Clinical Research, LLC
state: Florida
city: Saint Petersburg
country: United States
facility: Meridien Research
state: Florida
city: Saint Petersburg
country: United States
facility: Alternative Solutions Medical Research and Prevention Center
state: Florida
city: Sanford
country: United States
facility: International Clinical Research - US, LLC
state: Florida
city: Tampa
country: United States
facility: Meridien Research
state: Florida
city: Atlanta
country: United States
facility: Grady Memorial Hospital
state: Georgia
city: Atlanta
country: United States
facility: Morehouse School of Medicine
state: Georgia
city: Atlanta
country: United States
facility: Atlanta Center
state: Georgia
city: Atlanta
country: United States
facility: Atlanta Clinical Research Centers
state: Georgia
city: Dunwoody
country: United States
facility: Albert F. Johary MD, PC
state: Georgia
city: Marietta
country: United States
facility: Sestron Clinical Research
state: Georgia
city: Marietta
country: United States
facility: Clinical Research Advantage, Inc./Rita B. Chuang, MD, LLC
state: Georgia
city: Sandy Springs
country: United States
facility: WR-Mount Vernon Clinical Research, LLC
state: Georgia
city: Stockbridge
country: United States
facility: Eagle's Landing Diabetes and Endocrinology
state: Georgia
city: Chicago
country: United States
facility: Cedar Crosse Research Center
state: Illinois
city: Chicago
country: United States
facility: John H. Stroger Jr. Hospital of Cook Country
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Brownsburg
country: United States
facility: Investigators Research Group, LLC
state: Indiana
city: Lake Charles
country: United States
facility: Centex Studies, Inc.
state: Louisiana
city: Metairie
country: United States
facility: Gulf Regional Research and Education Services, LLC
state: Louisiana
city: New Orleans
country: United States
facility: New Orleans Center for Clinical Research
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland School of Medicine
state: Maryland
city: Baltimore
country: United States
facility: American Institute of Research Studies
state: Maryland
city: Jackson
country: United States
facility: Phillips Medical Services, PLLC
state: Mississippi
city: Washington
country: United States
facility: Mercy Research
state: Missouri
city: Omaha
country: United States
facility: Quality Clinical Research Inc
state: Nebraska
city: Las Vegas
country: United States
facility: Accent Clinical Trials
state: Nevada
city: Albuquerque
country: United States
facility: Lovelace Scientific Resources, Inc.
state: New Mexico
city: Brooklyn
country: United States
facility: Offic of Dr. Eric Cheng
state: New York
city: Brooklyn
country: United States
facility: Healthwise Medical Associates
state: New York
city: Brooklyn
country: United States
facility: Modern Medical
state: New York
city: Buffalo
country: United States
facility: Erie County Medical Center
state: New York
city: Laurelton
country: United States
facility: Scott Research, Inc.
state: New York
city: New York
country: United States
facility: Medex Healthcare Research, Inc.
state: New York
city: Rosedale
country: United States
facility: Laurelton Heart Specialist, PC
state: New York
city: Charlotte
country: United States
facility: Metrolina Internal Medicine, PA
state: North Carolina
city: Greensboro
country: United States
facility: PhysiqueMed Clinical Trials
state: North Carolina
city: Greensboro
country: United States
facility: Triad Clinical Trials
state: North Carolina
city: High Point
country: United States
facility: Peters Medical Research
state: North Carolina
city: High Point
country: United States
facility: High Point Clinical Trials Center
state: North Carolina
city: New Bern
country: United States
facility: Coastal Carolina Health Care, P.A.
state: North Carolina
city: Columbus
country: United States
facility: Hometown Urgent Care
state: Ohio
city: Dayton
country: United States
facility: Dayton Clinical Research
state: Ohio
city: Oklahoma City
country: United States
facility: Today Clinical Research, Oklahoma City
state: Oklahoma
city: Media
country: United States
facility: Suburban Research Associates
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University School of Medicine
state: Pennsylvania
city: Charleston
country: United States
facility: Medical Research South
state: South Carolina
city: Columbia
country: United States
facility: TLM Medical Services, LLC
state: South Carolina
city: Columbia
country: United States
facility: Amistad Clinical Research Center
state: South Carolina
city: Greenville
country: United States
facility: Greenville Pharmaceutical Rsch
state: South Carolina
city: Greer
country: United States
facility: Mountain View Clinical Research
state: South Carolina
city: Moncks Corner
country: United States
facility: Berkley Family Practice
state: South Carolina
city: Rock Hill
country: United States
facility: Carolina Cardiology Clinical Research Institute, LLC
state: South Carolina
city: Varnville
country: United States
facility: Community Research Partners, Inc
state: South Carolina
city: Memphis
country: United States
facility: Memphis Veterans Affairs Medical Center
state: Tennessee
city: Memphis
country: United States
facility: The Green Clinic PC
state: Tennessee
city: Memphis
country: United States
facility: Southwind Medical Specialists
state: Tennessee
city: Memphis
country: United States
facility: University of Tennessee
state: Tennessee
city: Houston
country: United States
facility: Diagnostic Clinic of Houston
state: Texas
city: Houston
country: United States
facility: Cullen Family Practice, PLLC
state: Texas
city: Houston
country: United States
facility: Centex Studies, Inc.
state: Texas
city: Houston
country: United States
facility: Texas Center for Drug Development, Inc.
state: Texas
city: Houston
country: United States
facility: Kelsey-Seybold Clinic
state: Texas
city: Waco
country: United States
facility: Hillcrest Family Health Center
state: Texas
city: Arlington
country: United States
facility: Millennium Clinical Trials LLC
state: Virginia
city: Norfolk
country: United States
facility: York Clinical Research, LLC
state: Virginia
city: Richmond
country: United States
facility: Dominion Medical Associates, Inc.
state: Virginia
city: Richmond
country: United States
facility: Clinical Research Partners, LLC
state: Virginia
city: Milwaukee
country: United States
facility: Family Medical Clinic
state: Wisconsin
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.