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

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 areEITHER drug-naïve (defined as absence of any oral antidiabetic therapy, glucagon likepeptide-1 (GLP-1) analog or insulin for 12 weeks, 16 weeks for pioglitazone prior torandomisation) 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 12weeks prior to randomization. Dose for metformin: maximum tolerated dose Themaximum daily dose of Sulfonylurea (SU) or DPP-4 inhibitor should not exceed thatstated 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) testingwith a mean SBP 135-175 mmHg prior to randomisation.

• Treatment with stable doses of at least one but not more than 4 antihypertensivemedication >= 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 GoodClinical Practice (GCP) and local legislation

Exclusion criteria:

• Uncontrolled hyperglycemia with a glucose level >270 mg/dl (>15.0 mmol/L) after anovernight fast during placebo run-in (includes Visit 2.1) and confirmed by a secondmeasurement (not on the same day).

• Exposure to any other antidiabetic medication within 12 weeks prior to randomisationother 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 growthis allowed).

• Mean seated Systolic Blood Pressure (SBP) ≥181 mmHg during placebo run-in visit andconfirmed 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 ofeither Ambulatory Blood Pressure Monitor (ABPM) and/or (BP) measurement device used inthe study.

• Night shift workers who routinely sleep during the daytime and/or whose work hoursinclude midnight.

• Diagnosis of autoimmune diabetes/Type I diabetes mellitus, monogenic (neonatal ormaturity onset diabetes of the young (MODY)) diabetes or Type I diabetes inadults/latent autoimmune diabetes of adults (LADA) per investigator or patient medicalhistory at the time of Visit 1 (screening).

• Known or suspected secondary hypertension (e.g. renal arterystenosis,phaeochromocytoma, Cushing's disease).

• History or evidence of hypertensive retinopathy (Keith-Wagener grade III or IV) and/orhypertensive encephalopathy.

• Clinically significant valvular heart disease or severe aortic stenosis in the opinionof the investigator.

• Acute coronary syndrome (non- ST wave elevated myocardial infarction (STEMI), STEMIand unstable angina pectoris), stroke or transient ischemic attack within 3 monthsprior to informed consent.

• Indication of liver disease, defined by serum levels of either AlanineAminotransferase (ALT) (Serum Glutamic Pyruvate Transaminase(SGPT)), AspartateAminotransferase (AST) (Serum Glutamic Oxaloacetic Transaminase (SGOT)), or alkalinephosphatase above 3 x upper limit of normal (ULN) as determined during screeningand/or run-in phase.

• Impaired renal function, defined as Estimated Glomerular Filtration Rate (eGFR)< 45ml/min/1.73m2 (moderate renal impairment, chronic kidney disease epidemiologycollaboration Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula) asdetermined during screening and/or run-in phase.

• Bariatric surgery within the past two years and other gastrointestinal surgeries thatinduce chronic malabsorption.

• Medical history of cancer (except for basal cell carcinoma) and/or treatment forcancer 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 celltrait 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 indosage of thyroid hormones within 6 weeks prior to informed consent or any otheruncontrolled endocrine disorder except Type 2 Diabetes Mellitus (T2DM) in the opinionof 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 ofbirth control, or do not plan to continue using this method throughout the studyand do not agree to submit to periodic pregnancy testing during participation inthe trial. Acceptable methods of birth control include tubal ligation,transdermal patch, intra uterine devices/systems (IUDs/IUSs), oral, implantableor injectable contraceptives, complete sexual abstinence (if acceptable by localauthorities), double barrier method and vasectomised partner.

• Alcohol, drug or confectionary liquorice abuse within the 3 months prior to informedconsent that would interfere with trial participation or any ongoing condition leadingto a decreased compliance to study procedures or study drug intake in theinvestigator's opinion.

• Intake of an investigational drug in another trial within 30 days prior to intake ofstudy medication in this trial; or participating in another trial (involving aninvestigational drug and/or follow-up) after discontinuing medication in that trial.

• Any other clinical condition that would jeopardize patient's safety whileparticipating in this clinical trial in the opinion of the investigator.