The objective of this study is to assess the efficacy, safety, tolerability and pharmacokinetics (PK) of once daily oral doses of empagliflozin 10 in patients with Type 1 diabetes mellitus (T1DM) as adjunctive to insulin therapy. Empagliflozin is…
ID
Source
Brief title
Condition
- Glucose metabolism disorders (incl diabetes mellitus)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The change from baseline in HbA1c after 26 weeks of treatment.
Secondary outcome
- 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 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 the percentage of time spent in target glucose range
of 70-180 mg/dL (3.9-10.0 mmol/L) as determined by continuous glucose
monitoring (CGM) in weeks 23 to 26.
- 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 10 in patients
with Type 1 diabetes mellitus (T1DM) as adjunctive to insulin therapy.
Empagliflozin is being compared to placebo.
Study design
In total, 720 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 2 doses of empagliflozin (10 mg and 25 mg) 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
6 week T1DM therapy optimisation period, followed by a 2 week open-label
placebo run-in period before randomisation. Patients who successfully complete
both of these periods will be randomised into the 52 week double-blind
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 10 mg, Empagliflozine 25 mg
of matching placebo (ratio 1:1:1) at visit 6.
Study burden and risks
Assuming a patients completes the trial, the following procedures will be
performed:
Hight:1x
Weight: 9x
Waist circumference: 5x
Vital signs (blood pressure and heart rate): 15x
Standard physical exam: 4x
ECG: 3x
Blood- and urine analysis: 10x
8-point plasma glucose profile (the patient should measure the glucose at least
8 times within a 24 hour period): 5x
Management of diet and physical activity: continuous throughout the study
Glucose home monitoring: starting at visit 2 and up to visit 17, the patient
needs to measure his glucose at least 4 times a day. Measurements need to be
recorded in the e-diary. At day 1 - 5, the patient needs to measure the glucose
at least 8 to 10 times a day including 1 measurement during the night.
Continuous Glucose Monitoring: 1 period of two weeks and 2 periods of four
weeks.
Completing the e-diary: at least once a day
DTSQ questionnaire: at visit 2, 6, 12 and 16
EQ-5D-5L questionnaire: at visit 6, 12 and 16
HFS-W questionnaire: at visit 2, 6, 12 and 16
HCRU questionnaire: at visit 6, 12 and 16
Comeniusstraat 6
Alkmaar 1817 MS
NL
Comeniusstraat 6
Alkmaar 1817 MS
NL
Listed location countries
Age
Inclusion criteria
- Male or female patient receiving insulin for the treatment of documented diagnosis of T1DM for at least 1 year at the time of Visit 1;- Fasting C-peptide value of 0.7 ng/mL (0.23 nmol/L) at Visit 2 measured by the central laboratory ;- Use of, and be willing, based on the Investigator's judgement, to continue throughout the duration of the trial, either:;--MDI of insulin consisting of at least one basal insulin injection and at least three daily bolus injections OR ;--CSII of any insulin type, with at least 5 months experience of using CSII prior to Visit 1;- HbA1c >= 7.5% en <= 10.0% at Visit 5 measured by the central laboratory;- Age >= 18 years at Visit 1;Additional inclusion criteria may apply
Exclusion criteria
- History of T2DM, 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 (e.g. metformin, alpha-glucosidase inhibitors, GLP-1 analogues, SGLT-2 inhibitors, pramlintide, inhaled insulin, pre-mixed insulins etc.) except subcutaneous basal and bolus insulin within 3 months prior to Visit 1 ;- Occurrence of severe hypoglycaemia involving coma and/or seizure that required hospitalisation or hypoglycaemia-related treatment by an emergency physician or paramedic within 3 months prior to Visit 1;- Occurence of severe DKA (i.e a pH < 7.0 or prolonged Intensive Care Unit admission exceeding two days) requiring hospitalisation within 3 months prior to Visit 1;Additional exclusion criteria may apply
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 | EUCTR2014-001922-14-NL |
| ClinicalTrials.gov | NCT02414958 |
| CCMO | NL52670.018.15 |