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

Hypertension Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02182830
• Other study ID #: 1245.29
• Status: Completed
• Phase: Phase 3
• Start date: July 25, 2014
• Est. completion date: May 18, 2017

Study information

• Verified date: June 2018
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 166
• Est. completion date: May 18, 2017
• Est. primary completion date: May 18, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Hypertension

Intervention

Drug:
• Empagliflozin low dose
starting dose 10mg; forced titration after 4 weeks 25mg dose
• placebo
starting dose 10mg; forced titration after 4 weeks 25mg dose
• Empagliflozin high dose
starting dose 10mg; forced titration after 4 weeks 25mg dose

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Boehringer Ingelheim	Eli Lilly and Company

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

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