Linagliptin as Add on to Basal Insulin in the Elderly

Study Overview
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Brief Summary
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To investigate the efficacy, safety, and tolerability of linagliptin 5 milligrams once a day compared to placebo as as add-on therapy for 24 weeks to stable basal insulin treatment in elderly patients, 60 years of age and older, with Type 2 Diabetes Mellitus and insufficient glycaemic control.Stable background therapy of metformin and/or alpha-glucosidase inhibitors is also allowed. In addition, this trial will assess if linagliptin reduces the risk of hypoglycaemia when added to background basal insulin therapy. The treatment duration of this trial (24 weeks) will enable assessment of the clinically relevant endpoint of a decrease in glycosylated Haemoglobin, a well-accepted measurement of chronic glycaemic control.

Official Title
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A 24 Week Randomized, Double-blind, Placebo-controlled, Parallel Group, Efficacy and Safety Trial of Once Daily Linagliptin, 5 Milligrams Orally, as Add on to Basal Insulin in Elderly Type 2 Diabetes Mellitus Patients With Insufficient Glycaemic Control

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: placebo
* Drug: linagliptin


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Patients must sign and date an Informed Consent consistent with International Conference on Harmonisation and Good Clinical Practice guidelines and local regulations prior to any evaluation and participation in the trial. Male and female patients with a clinical diagnosis of Type 2 Diabetes Mellitus, at the time of Informed Consent, who are: 60 years of age or older at informed consent or Screen Visit, taking stable doses of basal or biosimilar basal insulin [strictly inclusive of: insulin neutral protamine Hagedorn and isophane insulin; Humalog Basal (a suspension of insulin lispro protamine); insulin degludec; insulin detemir; and insulin glargine] for at least 4 weeks prior to randomisation (Visit 3) with dose adjustments up to a maximum of plus or minus 20% of baseline being allowed, may or may not be taking metformin immediate release or extended release [if the patient is taking metformin, stable dose must be maintained for at least twelve weeks without dose adjustments prior to randomisation (Visit 3)], and may or may not be taking alpha-glucosidase inhibitors [acarbose, miglitol, and voglibose; if the patient is taking alpha-glucosidase inhibitors, stable dose must be maintained for at least twelve weeks without dose adjustments prior to randomisation (Visit 3)]. Patients must have an glycosylated Haemoglobin of 7.0% (53 millimoles per mole) to 10.0% (86 millimoles per mole) at the first visit (Screen). Patients must have a Body Mass Index of 45 kilogram/meter squared or less at the Screen Visit. In the investigator's opinion, patients must be reliable, compliant, and agree to cooperate with all planned future trial evaluations as explained in detail during the informed consent process and to be able to perform them. Exclusion criteria: Impaired cognitive ability as supported by the Saint Louis University Mental Status Examination, additional assessment if necessary, and verified by the investigator at the Screen Visit. Depressed mood as supported by a score of 10 or more on the Patient Health Questionnaire at the Screen Visit. Type 1 Diabetes Mellitus as determined by past medical records and history. Acute coronary syndrome (non-ST Elevation Myocardial Infarction, ST Elevation Myocardial Infarction, and/or unstable angina pectoris), stroke or transient ischemic attack within 3 months prior to Screen Visit. Indication of liver disease determined during Screen and/or Run-In Period, defined by a serum level above 3 times the upper limit of normal in any of the following: alanine aminotransferase, aspartate aminotransferase, or alkaline phosphatase. Bariatric, gastric bypass, and other gastrointestinal procedures or surgeries (including all types of gastric banding, restriction, and/or LapBand) with the objective of promoting weight loss within the past two years at Screen Visit. Medical history of cancer (except for resected non-invasive basal or squamous cell carcinoma) and/or treatment for cancer within the last 5 years. Blood dyscrasias or any disorders causing hemolysis or unstable red blood cells (malaria, babesiosis, haemolytic anaemia).

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: linagliptin 5 mg<br>patient to receive a tablet of linagliptin 5 mg each day | Drug: linagliptin<br>* 5 mg once a day<br>|
| Placebo Comparator: placebo<br>patient to receive a tablet of placebo matching linagliptin 5 mg | Drug: placebo<br>* placebo matching linagliptin 5 mg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Hemoglobin A1c (HbA1c) After 24 Weeks of Treatment. | This outcome has measured difference between HbA1c values from baseline to 24 weeks post treatment. The term 'baseline' refers to the last observation prior to the administration of any randomised study medication. HbA1c is a form of hemoglobin, a blood pigment that carries oxygen, which is bound to glucose. The term HbA1c also refers to glycated hemoglobin. High levels of HbA1c (Normal range is less than 6%) indicate poorer control of diabetes than level in normal range. | Baseline and Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients Experiencing at Least One Hypoglycaemia Accompanied by a Prespecified Glucose Value. | Hypoglycaemia accompanied by a prespecified glucose value is defined as any investigator reported hypoglycaemia (event or AE) with a reported blood glucose level of less than 54 milligram/deciLitre (3.0 millimole/Litre) or any investigator reported symptomatic hypoglycaemic AE with a reported blood glucose level of less or equal 70 milligram/deciLitre (3.9millimole/Litre) or any severe hypoglycaemic AE. Severe hypoglycaemia is an event that requires the assistance of another person to actively administer carbohydrates or glucagon because the patient is unable to take the substance on his or her own. The confidence intervals mentioned in measure of dispersion are exact 95% confidence interval by Clopper and Pearson. The percentage of patients with at least one hypoglycaemia accompanied by a glucose value less than 54mg/dL alone has also represented separately according American Diabetes Association definition of clinically significant hypoglycaemia. | 24 weeks | 
| Percentage of Patients With HbA1c<8.0% | This is the percentage of patients with HbA1c on treatment <8.0% after 24 weeks of treatment. The confidence intervals mentioned in measure of dispersion are exact 95% CI by Clopper and Pearson. | 24 weeks | 
| Percentage of Patients With HbA1c on Treatment <7.0% | This is the percentage of patients with HbA1c on treatment <7.0% after 24 weeks of treatment. The confidence intervals mentioned in measure of dispersion are exact 95% CI by Clopper and Pearson. | 24 weeks | 
| Percentage of Patients With HbA1c Lowering by at Least 0.5%. | The percentage of patients who attained lowering of HbA1c by ≥0.5% from baseline after 24 weeks of treatment were analysed. The confidence intervals mentioned in measure of dispersion are exact 95% CI by Clopper and Pearson. | 24 weeks | 
| Change From Baseline in Fasting Plasma Glucose (FPG) | This outcome has measured difference between FPG values from baseline to 24 weeks post treatment. The term 'baseline' refers to the last observation prior to the administration of any randomised study medication | Baseline and Week 24 |