The objective of the current study is to investigate the efficacy, safety and tolerability of BI10773 (25mg once daily) compared to glimepriride (1-4mg daily) given for 104 weeks with a 104-week extention period in patients with type 2 diabetes…
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 52 weeks and 104 weeks of treatment.
Secondary outcome
- Change in body weight from baseline after 52 weeks and 104 weeks of treatment.
- Occurrence of confirmed syptomatic hypoglycaemic events during 52 weeks and
104 weeks of treatment.
- Changes in blood pressure (SBP and DBP) from baseline, after 52 weeks and 104
weeks of treatment.
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 levels.
Study objective
The objective of the current study is to investigate the efficacy, safety and
tolerability of BI10773 (25mg once daily) compared to glimepriride (1-4mg
daily) given for 104 weeks with a 104-week extention period in patients with
type 2 diabetes mellitus and insufficient glycaemic control despite metformin.
The study is designed to show non-inferiority of BI 10773 to glimepiride.
Study design
About 1400 patients with Diabetes Mellitus type 2 will participate in this
study worldwide . Half of them will receive treatment with
25 mg BI 10773 daily, the other half will receive treatment with glimepiride
(1-4 mg daily).
The treatment will be add-on to the stable background treatment of metformin.
The treatment period is preceded by a 2-week placebo run-in period, and
concluded with a follow-up visit 4 weeks after study medication termination.
This is a randomized, double blind, double dummy, active controlled, parallel
group, noninferiority study.
Intervention
At visit 2, the 2-week once-daily placebo run-in period starts.
At visit 3, patients are randomized to either once daily BI 10773 25 mg, or
once daily glimepiride (uptitrated to a maximum of 4 mg daily).
Ratio BI 10773 : glimepiride = 1:1.
Study burden and risks
Assuming a treatment period of 104 weeks, this would at most be the following :
- Physical examination: visits 2, 10, 14, 18 and 22
- Urine sample: visits 1, 2, 3, 6, 8, 10, 12, 14, 16, 18, 20, 22 and 23
- Blood sample: all visits (PK sampling at visits 6 and 8)
- Vital signs: all visits
- Height (visit 1), weight and waist: visits 1, 3, 6, 8, 10, 12, 14, 16, 18,
20, 22 and 23
- Diet and excercise counselling: visits 2-21
- Diet dairy: 3 days prior to visits 2, 3, 6, 8, 10,12, 14, 16, 18, 20 and 22
- ECG: visits 3, 10, 14, 18 and 22
- Questionnaires EQ-5D and DTSQ: visits 3, 5, 8, 10, 12, 16, 18 and 22
- HBGM test: starting from visit 2 until the end of the study (during run-in
and follow up at least once daily, otherwise at least once per week but
preferably on a daily basis)
In addition, for patients who participate in the MTT substudy:
- MTT: visits 3, 8, 10, 14, 18, 22 and 23
- 8-point glusose test: prior to visits 3, 8, 10, 14, 18 and 22
Comeniusstraat 6
ALKMAAR 1817 MS
NL
Comeniusstraat 6
ALKMAAR 1817 MS
NL
Listed location countries
Age
Inclusion criteria
(see paragraph 3.3.2 of the protocol for the complete list)
1. Diagnosis of type 2 diabetes mellitus prior to informed consent
2. Male and female patients on diet and exercise regimen who are
pre-treated with immediate release metformin unchanged for 12 weeks prior to
randomisation. Minimum dose for metformin: > <= 1500 mg/day or maximum tolerated
dose (the investigator must have documented the reason why up-titration to ><= 1500
mg/day was not possible) or maximum dose according to local label.
3. HbA1c of *7.0% and * 10% at Visit 1
4. Age * 18yrs
5. BMI * 45 kg/m2 (Body Mass Index) at Visit 1
6. Signed and dated written informed consent by date of Visit 1 in accordance with GCP and
local legislation
Exclusion criteria
(see paragraph 3.3.3 of the protocol for the complete list)
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 after an
overnight fast using another device (not on the same day).
2. Any other antidiabetic drug within 12 weeks prior to randomisation except immediate release metformin
3. Acute coronary syndrome (non-STEMI, STEMI, unstable AP) Stroke or TIA within 3
months prior to informed consent.
4. Indication of liver disease, defined by serum levels of either ALT (SGPT), AST
(SGOT), or alkaline phosphatase above 3 x upper limit of normal (ULN) as determined at Visit 1
5. Impaired renal function, defined as eGFR<60 ml/min (moderate to severe renal impairment using MDRD formula)
6. Bariatric surgery within the past two years and other gastrointestinal surgeries that induce chronic malabsorption
7. Medical history of cancer (except for basal cell carcinoma) and/or treatment for cancer within the last 5 years
8. Blood dyscrasias or any disorders causing haemolysis or unstable Red Blood Cell (e.g. malaria, babesiosis, haemolytic anaemia)
9. Contraindications including hypersensitivity known to metformin or sulfonylureas according to the local label
10. 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
11. 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 T2DM. (Treatment with local and inhaled steroids is allowed)
12. 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
13. Alcohol or drug 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
14. Intake of an investigational drug in another trial within 30 days prior to intake of
study medication in this trial.
15. Any other clinical condition that would jeopardize patients safety while participating in
this clinical trial
Design
Recruitment
Medical products/devices used
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 | EUCTR2009-016244-39-NL |
| ClinicalTrials.gov | NCT01167881 |
| CCMO | NL32259.072.10 |