The objective of this study is to assess the efficacy, safety, tolerability and pharmacokinetics (PK) of once daily oral doses of empagliflozin 2,5mg, 10mg and 25mg in patients with Type 1 diabetes mellitus (T1DM) as adjunctive to insulin therapy.…
ID
Source
Brief title
Condition
- Glucose metabolism disorders (incl diabetes mellitus)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary endpoint is the change from baseline in HbA1c after 26 weeks.
Secondary outcome
- incidence rate of symptomatic hypoglycaemic adverse events (AEs) with
confirmed plasma glucose < 54 mg/dL (< 3.0 mmol/L) and/or severe
hypoglycaemic AEs per patient-year from Week 5 to Week 26
- incidence rate of symptomatic hypoglycaemic AEs with confirmed plasma glucose
< 54 mg/dL (< 3.0 mmol/L) and/or severe hypoglycaemic AEs per patient-year from
Week 1 to Week 26
- change from baseline in body weight (kg) after 26 weeks
- change from baseline in total daily insulin dose (TDID), U/kg, after 26 weeks
- change from baseline in systolic blood pressure (SBP) after 26 weeks
- change from baseline in diastolic blood pressure (DBP) after 26 weeks
Background summary
Type 1 diabetes mellitus (T1DM) accounts for 5 to 10% of all cases of diabetes
mellitus. This disease is a complex disorder that requires constant attention
to diet, exercise, glucose monitoring, and insulin therapy to achieve good
glycaemic control. Most bodies recommend that adult patients with T1DM should
obtain glycated haemoglobin (HbA1c) * 7.0%. However, most patients generally
achieve HbA1c levels no lower than 8.0%. Hence, with the currently available
treatment options, patients with T1DM often fail to maintain adequate blood
glucose control. This may lead to acute conditions and debilitating secondary
complications including heart disease, blindness and kidney failure.
Empagliflozin has the potential to provide a novel approach to the treatment of
T1DM, as adjunctive therapy to insulin which may lead to a reduction of plasma
glucose levels.
Study objective
The objective of this study is to assess the efficacy, safety, tolerability and
pharmacokinetics (PK) of once daily oral doses of empagliflozin 2,5mg, 10mg and
25mg in patients with Type 1 diabetes mellitus (T1DM) as adjunctive to insulin
therapy. Empagliflozin is being compared to placebo.
Study design
In total, 960 patients with T1DM who meet the entry criteria will be entered
(randomised) in the trial.
This multi-national, randomised, placebo-controlled, double-blind, parallel
group study compares three doses of empagliflozin (2.5 mg, 10mg and 25mg) to
placebo in patients with T1DM as adjunctive to insulin therapy.
Patients will be enrolled (screened) in the trial once they have signed the
informed consent. All patients who are suitable after screening will undergo a
six week T1DM therapy optimisation period, followed by a two week open-label
placebo run-in period before randomisation. Patients who successfully complete
both of these periods will be randomised into the 26 week doubleblind treatment
period. After the treament periode, the study will be completed by a three week
follow-up period.
Intervention
Patients will start a two week placebo run-in period at visit 5.
Patients will be randomized to either Empagliflozin 2.5 mg, Empagliflozin 10
mg, Empagliflozine 25 mg or matching placebo (ratio 1:1:1:1) at visit 6.
Study burden and risks
Assuming a patient completed the trial, a patient will take part in the trial
for 38 weeks. The total burden will be about 18 hours. During the clinic visits
some assessments will be done (e.d. hight, weight, vital signs, ecg's, blood
samping, etc.) and the patient needs to regulary check his/hers glucose levels
and if necassary keton levels and complete the electronic diary on a daily
base. See section E4 for a complete description of all assessments.
During participation in this trial, a patient may experience side effects from
Empagliflozin as described in section E9. Since Empagliflozin is still under
investigation (phase III) new unknow side effects may occur. Due to the use of
Empagliflozin the glucose value may decrease and this might lead to unawareness
of diabetic ketoacidosis.
Comeniusstraat 6
Alkmaar 1817MS
NL
Comeniusstraat 6
Alkmaar 1817MS
NL
Listed location countries
Age
Inclusion criteria
- Signed and dated written informed consent
- Male or female patient receiving insulin for the treatment of documented diagnosis of type 1 diabetes mellitus (T1DM) for at least 1 year
- C-peptide value of < 0.7 ng/mL (0.23 nmol/L) at visit 2
- Use of Multiple Daily Injections (MDI) of insulin or insulin pump user with total daily insulin * 0.3 and * 1.5 U/kg
- Glycated haemoglobin (HbA1c) * 7.5% and * 10.0%
- Good understanding of T1DM
- Age * 18 years
- Body Mass Index (BMI) * 18.5 kg/m2
- Estimated glomerular filtration rate (eGFR) * 30 mL/min/1.73 m2
- Women of child-bearing potential must use highly effective methods of birth control
- Compliance with trial medication administration between 80% and 120% during placebo run-in period;Further inclusion criteria apply, see protocol section 3.3.2.
Exclusion criteria
- History of type 2 diabetes mellitus, maturity onset diabetes of the young (MODY), pancreatic surgery or chronic pancreatitis
- Pancreas, pancreatic islet cells or renal transplant recipient
- T1DM treatment with any other antihyperglycaemic drug except subcutaneous basal and bolus insulin within last 3 months
- Occurrence of severe hypoglycaemia within last 3 months prior to Visit 1 and until Visit 6
- Occurence of diabetic ketoacidosis within 3 months prior to Visit 1 and until Visit 6
- Irregular sleep/wake cycle
- Acute coronary syndrome, stroke or TIA within last 3 months
- Severe gastroparesis
- Brittle diabetes
- Liver disease
- Eating disorders
- Treatment with anti-obesity drugs, weight-loss surgery or aggressive diet regimen
- Treatment with systemic corticosteroids at Visit 1 and until Visit 6
- Change in dose of thyroid hormones within last 6 weeks to Visit 1 and until Visit 6
- Cancer or treatment for cancer in the last five years
- Blood dyscrasias or any disorders causing haemolysis or unstable red blood cells
- Women who are pregnant, nursing, or who plan to become pregnant whilst in the trial
- Alcohol or drug abuse
- Intake of an investigational drug in another trial within last 30 days;Further exclusion criteria apply, see protocol section 3.3.3.
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 | EUCTR2014-005256-26-NL |
| ClinicalTrials.gov | NCT02580591 |
| CCMO | NL53615.041.15 |