The objective of the current study is to investigate the efficacy and safety of BI 10773 (10 and 25 mg) compared to placebo on glucose control and bloodpressure over 12 weeks in hypertensive patients with diabetes mellitus type 2.
ID
Source
Brief title
Condition
- Other condition
- Glucose metabolism disorders (incl diabetes mellitus)
Synonym
Health condition
cardiovasculair, hypertensie
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint in this study is change from baseline in HbA1c after 12
weeks of treatment. Throughout the study protocol, the term **baseline** refers
to the last observation prior to randomization of the patient.
Secondary outcome
• Change from baseline in mean 24 hour systolic blood pressure after 12 weeks
of treatment
• Change from baseline in mean 24 hour diastolic blood pressure after 12 weeks
of treatment
• Proportion of patients with HbA1c < 7% after 12 weeks of treatment
• Change from baseline in fasting plasma glucose (FPG) after 12 weeks of
treatment
• Change from baseline in body weight after 12 weeks of treatment
• Change from baseline in daytime mean SBP after 12 weeks of treatment
• Change from baseline in daytime mean DBP after 12 weeks of treatment
• Change from baseline in nighttime mean SBP after 12 weeks of treatment
• Change from baseline in nighttime mean DBP after 12 weeks of treatment
• Change from baseline in trough mean sitting SBP after 12 weeks
• Change from baseline in trough mean sitting DBP after 12 weeks
• Change from baseline in orthostatic blood pressure after 12 weeks of
treatment
• Proportion of patients reaching BP<130/80 mmHg after 12 weeks of treatment
• Composite endpoint of the following conditions at week 12 (all three
fulfilled)
- Change from baseline HbA1c of more than -0.5%;
- Change from baseline in SBP of > -3 mmHg;
- Change from baseline in weight of > -2%
Background summary
Diabetes Mellitus type 2 is a disease which is characterized by increased blood
glucose levels. It is a condition that eventually causes damage in many organs
and tissues, resulting in a marked decrease of life expectancy and quality of
life. Therefore, treatment to maintain the blood
glucose levels within normal ranges remains important.
There is no cure for Diabetes Mellitus type 2, but it can be treated by a diet,
excercise, several oral medications and insulin. Not all
medications are well tolerated and many compounds cause side-effects. BI 10773
is a SGLT-2 inhibitor that decreases reabsorption of glucose
by the kidneys, resulting in excretion of this glucose by the urine. Previous
studies have shown that this results in decreased plasmaglucose and HbA1c.
Study objective
The objective of the current study is to investigate the efficacy and safety of
BI 10773 (10 and 25 mg) compared to placebo on glucose control and
bloodpressure over 12 weeks in hypertensive patients with diabetes mellitus
type 2.
Study design
About 1630 hypertension patients with diabetes mellitus type 2 will participate
in this study worldwide . It is expected that about 820 will meet the inclusion
and exclusioncriteria and will be randomized. Of them, 1/3 will receive
treatment with 10 mg BI 10773 once daily, 1/3 will receive treatment with 25 mg
BI 10773 once daily, and 1/3 will receive placebo for the duration of the
study. The treatment will be add-on to the stable background treatment, or
primary treatment for drug-naive patients. The 12 weeks treatment period is
preceded by a 2-week placebo run-in period, and concluded with a follow-up
visit 2 weeks after study medication termination.
This is a randomized, double-blind, placebo controlled study.
Intervention
At visit 2 all patients who meet the inclusion and exclusion criteria will
start the 2-week once daily placebo run-in period.
At visit 3 patients who still meet the inclusion and exclusion criteria, will
be randomized to either once daily BI 10773 10mg, once daily BI 10773 25mg, or
once daily placebo (ratio 1:1:1).
Study burden and risks
For patients who fully complete the study the following is applicable;
- Patients will receive diary to record the bloodglucose values, and a food
intake booklet to record all food and drink intake during the 3 days before
visit 3, 4 and 5
The following activities take place at the visits concerned;
- Physical examination (V2 en 5.2)
- Bloodpressure and pulse (V1, 2.1, 3, 4, 5.2 en 6)
- Height (V1), weight (V1, 3 en 5.2), waist circumference (V3 en 5.2)
- ECG (V3 en 5.2)
- Diet and exercise counselling (V2.1, 3, 4 en 5.2)
- Collection of urine and bloodsamples (V1, 2.1, 3, 4, 5.2 en 6)
- ABPM attachment for 24 hours (V2.2. en 5.1)
- Home blood glucose monitoring (from V2.1: during run-in and follow-up 1x/dag,
otherwise minimal 1x/week)
The following risks are associated with participation:
The following adverse events reported are possibly related to BI 10773: loss of
weight, pollakiuria/polyuria/nocturia and en genito-urinary tract infections,
thirst, dizziness and headache (source: investigator's brochure). As BI 10773
is still in phase III, new adverse events may appear that have not been
reported before. Because of the mechanism of action of BI 10773, the risk of
hypoglycaemic episodes is considered to be low.
Of all patients randomized, 1/3 will receive placebo. As a consequence, these
patients have a higher probability of not getting a potential treatment
benefit, i.e. no reduction in bloodpressure, no reduction of bloodglucose and
no reduction of HbA1c.
Also bloodsampling may result in any discomfort.
Comeniusstraat 6
1817 MS Alkmaar
NL
Comeniusstraat 6
1817 MS Alkmaar
NL
Listed location countries
Age
Inclusion criteria
- Diagnosis of diabetes mellitus type 2 prior to informed consent
- 18 years and older
- Patients on diet and exercise regimen who are drug-naïve or pre-treated with any oral
antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation. Pre-existing
antidiabetic therapy doses should be unchanged for 12 weeks (16 weeks for pioglitazone) prior
to randomisation, and insulin dose should not be changed within 12 weeks prior to
randomization by more than 10% from the baseline dose at randomisation (Visit 3).
- HbA1c: 53mmol/mol -86 mmol/mol at V1 (screening)
- Mean seated SBP 130-159mmHg and DBP 80-99 mmHg at V1 (screening)
- Treatment with stable doses of antihypertensive medication >= 4 weeks at Visit 1 (screening) and
throughout the screening/run-in phase
- BMI <= 45kg/m2
Exclusion criteria
- Uncontrolled hyperglycaemia with a glucose level >240 mg/dl (>13.3 mmol/L) after an overnight
fast during placebo run-in and confirmed by a second measurement (not on the same day)
- Mean seated SBP >=160 mmHg and/or mean seated DBP>=100 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
ABPM and/or BP measurement device used in the study
- Night shift workers who routinely sleep during the daytime and whose work hours include
midnight to 4:00 a.m.
- Current treatment and/or treatment within the last 16 weeks with Rosiglitazone
- Known or suspected secondary hypertension
- 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
- Acute coronary syndrome, stroke or TIA within 3 months prior to informed consent
- Indication of liver disease: ALT (SGPT), AST (SGOT), or alkaline phosphatase >= 3 x ULN as
determined during screening and/or run-in phase
- Impaired renal function, defined as eGFR< 60 ml/min 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 Cell
- Any contraindications to background antidiabetic medications according to the local label
- Any contraindications to background antihypertensive medications according to the local label
- Treatment with anti-obesity drugs 3 months prior to informed consent or any other treatment at
the time of screening (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 T2D
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2011-000347-25-NL |
| CCMO | NL36205.072.11 |
| Other | Wordt geregistreerd in ClinicalTrial.Gov. Nummer wordt pas na indiening verkregen. |