Comprehensive Add on Study in Japan

Study Overview
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Brief Summary
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The objective of the current study is to investigate the safety and efficacy of linagliptin (5mg / once daily) given for 52 weeks as add-on therapy to patients with type 2 diabetes mellitus and insufficient glycaemic control despite diet, exercise, and treatment with one approved antidiabetic drug.

Official Title
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An Open Label, Randomised, Parallel Group Safety and Efficacy Study of Linagliptin (5 mg Administered Orally Once Daily) Over 52 Weeks in Patients With Type 2 Diabetes Mellitus and Insufficient Glycaemic Control Despite Background Mono-therapy With an Approved Antidiabetic Drug

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Linagliptin
* Drug: Linagliptin
* Drug: Metformin
* Drug: Metformin
* Drug: Linagliptin
* Drug: Linagliptin
* Drug: Linagliptin


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Diagnosis of type 2 diabetes mellitus Male and female patients on diet and exercise regimen who are treated with one antidiabetic drug Exclusion criteria: Myocardial infarction, stroke, transient ischemic attack, or pulmonary embolism Impaired hepatic function Glitazone, glinide, and sulfonylurea group: renal failure or renal impairment defined as estimated glomerular filtration rate <30 ml/min (severe renal impairment) at Visit 1, Biguanide group: renal failure or renal impairment defined as estimated glomerular filtration rate <60 ml/min (moderate renal impairment) at Visit 1 Treatment with anti-obesity drugs

Ages Eligible for Study
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Minimum Age: 20 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bigu+Lina<br>biguanide plus linagliptin | Drug: Linagliptin<br>* Linagliptin once daily<br>|
| Experimental: Glin+Lina<br>glinide plus linagliptin | Drug: Linagliptin<br>* Linagliptin once daily<br>|
| Experimental: Glit+Lina<br>glitazone plus linagliptin | Drug: Linagliptin<br>* Linagliptin once daily<br>|
| Experimental: SU+Lina<br>sulfonylurea plus linagliptin | Drug: Linagliptin<br>* Linagliptin once daily<br>|
| Experimental: A-GI+Lina<br>alpha-glucosidase inhibitor plus linagliptin | Drug: Linagliptin<br>* Linagliptin once daily<br>|
| Active Comparator: SU+Met<br>sulfonylurea plus metformin | Drug: Metformin<br>* Metformin twice or three time per day<br>|
| Active Comparator: A-GI+Met<br>alpha-glucosidase inhibitor plus metformin | Drug: Metformin<br>* Metformin twice or three time per day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Adverse Events (AEs) | The number of patient with any AEs, patients with severe AE, patients with AEs leading to discontinuation of trial drug, and patients with Hypoglycaemic events | The first drug administration through 7 days after the last drug administration, up to 382 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glycosylated Haemoglobin A1c (HbA1c) | The change from baseline in HbA1c after 52 weeks of treatment. When the HbA1c after 52 weeks treatment was missing, the value from the measurements at the closest preceding visit replaced the missing value. | Baseline and 52 weeks |