The objective of the current study is to investigate the efficacy, safety and tolerability of BI 10773 (10 mg and 25 mg/ once daily) compared to placebo given for 52 weeks as add-on preexisting antidiabetic therapy in patients with T2DM with…
ID
Source
Brief title
Condition
- Glucose metabolism disorders (incl diabetes mellitus)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Change from baseline in HbA1c after 24 weeks of treatment.
Secondary outcome
HbA1c:
* Change from baseline in HbA1c after 52 weeks of treatment
* Occurrence of treat to target efficacy response, that is an HbA1c of <7.0%
after 24 and 52 weeks of treatment ;
Occurrence of relative efficacy response (HbA1c lowering by a least 0.5% after
24 and 52 weeks of treatment;
Change from baseline in HbA1c by visit over time
FPG:
* Change from baseline in FPG after 24 and 52 weeks of treatment;
* Change from baseline in FPG by visit over time
Body weight and waist circumference: Change from baseline to week 24 and 52
Systolic and diastolic BP: Change from baseline to week 24 and 52.
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. The treatment to maintain the blood glucose levels within normal ranges
remains important, certainly also for patients with renal impairement
There is no cure for Diabetes Mellitus type 2, but it can be treated by a diet,
excercise, several oral medications and insulin. However, not all medications
are well tolerated and many compounds cause side-effects. BI 10773 is a SGLT-2
inhibitor that decreases the reabsorption of glucose by the kidneys, resulting
in excretion of this glucose by the urine. Previous studies have shown results
in decreased plasmaglucose and HbA1c levels.
Study objective
The objective of the current study is to investigate the efficacy, safety and
tolerability of BI 10773 (10 mg and 25 mg/ once daily) compared to placebo
given for 52 weeks as add-on preexisting antidiabetic therapy in patients with
T2DM with insufficient glycaemic control and
renal impairment.
Study design
Worldwide, 682 patients with diabetes mellitus type 2 and renal impairment will
be participating in this study. Patients will be devided into three groups
based on their eGFR at visit 1.
1. eGFR >= 60 en < 90 ml/min, in total 270 patients
2. eGFR >= 30 en < 60 ml/min, in total 352 patients
3. eGFR >= 15 en < 30 ml/min, in total 60 patients
Based on this stratification patients will be randomized to either 10 mg BI
10773, 25 mg BI 10773 or placebo. Patients will be assigned to the double-blind
treatment as follows:
* 10 mg BI 10773: 90 patients with eGFR >= 60 en < 90 ml/min
* 25 mg BI 10773: 90 patients with eGFR >= 60 en < 90 ml/min, 176 patients with
eGFR >= 30 en < 60 ml/min en 30 patients with eGFR >= 15 en < 30 ml/min
* placebo: 90 patients with eGFR >= 60 en < 90 ml/min, 176 patients with eGFR >=
30 en < 60 ml/min en 30 patients with eGFR >= 15 en < 30 ml/min
Treatment with trialmedication will be add-on treatment to the background
medication at visit 1. The treatment period is preceded by a 2-week placebo
run-in period, and concluded with a follow-up visit 1 week after study
termination (may be done by phone).
This is a randomized, double-blind, placebo controlled study.
Intervention
At visit 2, the 2-week once-daily two placebo tablets run-in period starts.
At visit 3, patients are randomized to either:
* once daily one tablet BI 10773 10 mg plus one placebo tablet
* once daily one tablet BI 10773 25 mg plus one placebo tablet
* once daily two placebo tablets
Study burden and risks
- Physical exam(visit 2, 7 en 10)
- Bloodpressure and pulse (all visits)
- Height and weight (visit 1), weight and waist-circumference (visit 3, 7 en 10
)
- ECG (visit 3, 7 en 10)
- Urin sampling (visit 1, 2, 3, 5, 7, 8, 9, 10 en follow up)
- Blood sampling (all visits)
- Diet and exercise counselling (visit 2 - 10)
- Food diary (three days before visits 2, 3, 5, 7 en 10)
- HBGM test (from visit 2 onwards, during run-in en follow up 1x/day, treatment
periond at least 1x/week)
- EQ-5D (visit 3, 4, 5, 7 en 10)
- Extra blood sampling at visit 7 after 1,5 and 8 hours for pk
- Pregnancy test if applicable (visit 1, 3, 5, 7 en 10)
Comeniusstraat 6
1817MS Alkmaar
NL
Comeniusstraat 6
1817MS Alkmaar
NL
Listed location countries
Age
Inclusion criteria
1. Diagnosis of type 2 diabetes mellitus prior to informed consent and a eGFR of <90 ml/min, as determined during screening and the run-in phase, using the Modification of Diet in Renal Disease (MDRD) equation.
2. Male and female patients on diet and exercise regimen who are pre-treated with any antidiabetic therapy (excluding only SGLT-2 inhibitors) and are on the maximum tolerated dose which has been unchanged for 12 weeks prior to randomisation.
3. HbA1c of >=7.0% and <10.0% at Visit 1 (screening).
4. Age >= 18 years.
5. BMI <= 45 kg/m2 (Body Mass Index) at Visit 1 (screening).
6. Signed and dated written informed consent by date of Visit 1 in accordance with Good Clinical Practice (GCP) and local legislation.;See also section 3.3.2 of the protocol
Exclusion criteria
1. 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).
2. Impaired renal function, defined as eGFR<15 ml/min using the MDRD equation.as determined during screening and/or the run-in phase
3. Renal impairment requiring any form of chronic dialysis.
4. Requiring acute dialysis within three months prior to informed consent.
5. Renal transplant recipient.
6. Acute coronary syndrome (non-STEMI, STEMI and unstable angina pectoris), stroke or Transient Ischemic Attack (TIA) within three months prior to informed consent.
7. Indication of liver disease, defined by serum levels of either Alanine transaminase (ALT) (SGPT), AST (SGOT), or alkaline phosphatase above 3 x upper limit of normal (ULN) as determined during screening and/or the run-in phase.
8. Bariatric surgery within the past two years and other gastrointestinal surgeries that induce chronic malabsorption.
9. Medical history of cancer (except for basal cell carcinoma) and/or treatment for cancer within the last five years.
10. Blood dyscrasias or any disorders causing hemolysis or unstable red blood cell (e.g. malaria, babesiosis, haemolytic anemia).
11. Contraindications to pre-existing background antidiabetic therapy according to the local label.
12. Treatment with anti-obesity drugs (e.g. sibutramine, orlistat) three 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.
13. Current treatment with systemic steroids at time of informed consent or change in dosage of thyroid hormones within six weeks prior to informed consent or any other uncontrolled endocrine disorder except T2DM.
14. 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 practising 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, sexual abstinence (if acceptable by local authorities), double barrier method and vasectomised partner.
15. Alcohol or drug abuse within the three 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.
16. Participation in another trial with an investigational drug within 30 days prior to informed consent.
17. Any other clinical condition that would jeopardize patients safety while participating in this clinical trial.;See also section 3.3.3 of the protocol
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 | EUCTR2009-016179-31-NL |
| ClinicalTrials.gov | NCTnummerwordtpasnaindieningverkregen |
| CCMO | NL32517.072.10 |