Phase 3
Completed N=166
24 Week Efficacy and Safety Study of Empagliflozin (BI 10773) in Hypertensive Black/African American Patients With Type 2 Diabetes Mellitus and Hypertension
Source: ClinicalTrials.gov NCT02182830 ↗Enrolled (actual)
166
Serious AEs
4.3%
Results posted
Jul 2018
Primary outcomePrimary: Change From Baseline in Glycated Haemoglobin (HbA1c) (%) at 24 Weeks — 0.07; -0.71 percentage of glycated haemoglobin — p=0.0002
◆ Published Evidence
Highly cited
101citations · ~14 / year
Antihyperglycemic and Blood Pressure Effects of Empagliflozin in Black Patients With Type 2 Diabetes Mellitus and Hypertension.
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.
Linked Publications (3)
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Antihyperglycemic and Blood Pressure Effects of Empagliflozin in Black Patients With Type 2 Diabetes Mellitus and Hypertension.
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The NEW-HOPE study and emerging therapies for difficult-to-control and resistant hypertension.
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Design of a 24-week trial of empagliflozin once daily in hypertensive black/African American patients with type 2 diabetes mellitus.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline in Glycated Haemoglobin (HbA1c) (%) at 24 Weeks |
0.07; -0.71 | 0.0002 sig |
| SECONDARY Change From Baseline in Mean 24-hour Ambulatory Systolic Blood Pressure (SBP) at Week 12 |
-0.90; -6.10 | 0.0117 sig |
| SECONDARY Changes From Baseline in Trough Mean Ambulatory SBP at Week 12 |
-1.00; -6.99 | 0.0237 sig |
| SECONDARY Change From Baseline in Body Weight at Week 24 |
-0.98; -2.21 | 0.0382 sig |
| SECONDARY Change From Baseline in Trough Seated SBP at Week 12 |
-3.94; -7.97 | 0.1215 |
| SECONDARY Change From Baseline in Mean 24-hour Ambulatory SBP (mmHg) at Week 24 |
-1.94; -10.33 | 0.0025 sig |
| SECONDARY Change From Baseline in Mean 24-hour Ambulatory Diastolic Blood Pressure (DBP) at Week 12 |
-0.37; -3.80 | 0.0069 sig |
| SECONDARY Change From Baseline in Mean 24-hour Ambulatory DBP (mmHg) at Week 24 |
-1.48; -6.38 | 0.0058 sig |
| SECONDARY Change From Baseline in Trough Seated SBP (mmHg) at Week 24 |
-2.83; -10.26 | 0.0036 sig |
| SECONDARY Change From Baseline in Trough Seated DBP (mmHg) at Week 12 |
-2.30; -4.14 | 0.2402 |
| SECONDARY Change From Baseline in Trough Seated DBP (mmHg) at Week 24 |
-1.30; -5.55 | 0.0053 sig |
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 malabsorp
Data sourced from ClinicalTrials.gov (NCT02182830) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.