A Non Interventional Study to Monitor the Safety and Effectiveness of Trajenta (Linagliptin, 5 mg, q.d) in Korean Patients With Type 2 Diabetes Mellitus

• Sponsor: Boehringer Ingelheim (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01707147
• Collaborator: Eli Lilly and Company (Industry)
• Enrollment: 3,219
• Location: 1
• Actual Duration (Months): 55.8
• Patients Per Site Per Month: 57.7

Study Details

Study Description

Brief Summary

The aim of this study is to monitor safety and efficacy of treatment with linagliptin in Korean patients with type 2 diabetes mellitus in routine clinical settings.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 2	Drug: Trajenta tablet

Detailed Description

Study Design:

Post Marketing study- Observational study

Study Design

• Study Type: Observational
• Actual Enrollment: 3219 participants
• Observational Model: Other
• Time Perspective: Prospective
• Official Title: A Regulatory Requirement Non Interventional Study to Monitor the Safety and Effectiveness of Trajenta (Linagliptin, 5 mg, q.d) in Korean Patients With Type 2 Diabetes Mellitus(SELINA Study)
• Actual Study Start Date: Nov 16, 2012
• Actual Primary Completion Date: Jul 11, 2017
• Actual Study Completion Date: Jul 11, 2017

Arms and Interventions

Arm	Intervention/Treatment
Patients with Type 2 Diabetes Mellitus	Drug: Trajenta tablet; Linagliptin

Outcome Measures

Primary Outcome Measures

1. Percentage of Patients With Incidence of Adverse Events Who Had Taken at Least One Dose of Trajenta [Up to 26 weeks (long-term surveillance)]

   Percentage of patients with incidence of any adverse events who had taken at least one dose of Trajenta.

Secondary Outcome Measures

1. Change From Baseline After 24 Weeks in Glycosylated Hemoglobin (HbA1c) [Baseline and Week 24]

   Change from baseline after 24 weeks in Glycosylated Hemoglobin (HbA1c).

2. Percentage of Patients With Occurrence of Treat to Target Effectiveness Response, That is HbA1c Under Treatment of < 6.5% After 24 Weeks of Treatment [24 Weeks]

   Percentage of patients with occurrence of treat to target effectiveness response, that is HbA1c under treatment of < 6.5% after 24 weeks of treatment.

3. Percentage of Patients With Occurrence of Relative Effectiveness Response (HbA1c Lowering by at Least 0.5% After 24 Weeks of Treatment) [24 Weeks]

   Percentage of patients with occurrence of relative effectiveness response (HbA1c lowering by at least 0.5% after 24 weeks of treatment).

4. Change From Baseline After 24 Weeks in Fasting Plasma Glucose (FPG) [Baseline and Week 24]

   Change from baseline after 24 weeks in fasting plasma glucose (FPG).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 19 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria:

Patients who have been started on Trajenta in accordance with the approved label in Korea Patients who have signed on the data release consent form

Exclusion criteria:

Patients with previous exposure to Trajenta and current participation in clinical trials

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Multiple Locations		Korea, Republic of

Sponsors and Collaborators

• Boehringer Ingelheim
• Eli Lilly and Company

Investigators

• Study Chair: Boehringer Ingelheim, Boehringer Ingelheim

Study Documents (Full-Text)

• Statistical Analysis Plan - Aug 21, 2017
• Study Protocol - Feb 22, 2017

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: Boehringer Ingelheim
• ClinicalTrials.gov Identifier: NCT01707147
• Other Study ID Numbers: 1218.104
• First Posted: Oct 16, 2012
• Last Update Posted: Jan 11, 2019
• Last Verified: Jul 1, 2018

• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Linagliptin

Study Results

Participant Flow

Recruitment Details	A regulatory requirement prospective, non-interventional, open-label, multi-centre national study to monitor the safety and effectiveness of Trajenta (Linagliptin, 5 milligram (mg), once daily) in Korean patients with type 2 diabetes mellitus
Pre-assignment Detail	All patients were screened for eligibility to participate in the trial. Patients attended a specialist sites which ensured that they met all strictly implemented inclusion/exclusion criteria. Patients were not to be entered to trial if any one of the specific entry criteria was violated.

Arm/Group Title	Trajenta (Linagliptin) 5 mg
Arm/Group Description	Patients with type 2 diabetes mellitus were administered with Trajenta (Linagliptin) 5 mg once daily orally.
Period Title: Overall Study
STARTED	3219
COMPLETED	3119
NOT COMPLETED	100

Baseline Characteristics

Arm/Group Title	Trajenta (Linagliptin) 5 mg
Arm/Group Description	Patients with type 2 diabetes mellitus were administered with Trajenta (Linagliptin) 5 mg once daily orally.
Overall Participants	3119
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	61.24 (11.95)
Sex: Female, Male (Count of Participants)
Female	1450 46.5%
Male	1669 53.5%
Race and Ethnicity Not Collected (Count of Participants)

Outcome Measures

1. Primary Outcome

Title	Percentage of Patients With Incidence of Adverse Events Who Had Taken at Least One Dose of Trajenta
Description	Percentage of patients with incidence of any adverse events who had taken at least one dose of Trajenta.
Time Frame	Up to 26 weeks (long-term surveillance)

Outcome Measure Data

Analysis Population Description

Safety analysis set: This analysis set included all patients who were administrated Trajenta at least once, except patients violating inclusion/exclusion criteria, dosage administration or lost to follow up.

Arm/Group Title	Trajenta (Linagliptin) 5 mg
Arm/Group Description	Patients with type 2 diabetes mellitus were administered with Trajenta (Linagliptin) 5 mg once daily orally.
Measure Participants	3119
Number [Percentage of patients]	7.69

2. Secondary Outcome

Title	Change From Baseline After 24 Weeks in Glycosylated Hemoglobin (HbA1c)
Description	Change from baseline after 24 weeks in Glycosylated Hemoglobin (HbA1c).
Time Frame	Baseline and Week 24

Outcome Measure Data

Analysis Population Description

Effectiveness analysis set: This set includes all patients of the safety analysis set for whom HbA1c values were measured at both baseline and after drug administration.

Arm/Group Title	Trajenta (Linagliptin) 5 mg
Arm/Group Description	Patients with type 2 diabetes mellitus were administered with Trajenta (Linagliptin) 5 mg once daily orally.
Measure Participants	2171
Before drug administration	7.98 (1.51)
After drug administration	7.21 (1.22)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Trajenta (Linagliptin) 5 mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Paired t-test
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.77
	Confidence Interval	(2-Sided) 95%; -0.83 to -0.71
	Parameter Dispersion	Type: Standard Deviation; Value: 1.50
	Estimation Comments	p-value of paired t-test for change from baseline is presented. 95% confidence interval for the mean was calculated using t-distribution.

3. Secondary Outcome

Title	Percentage of Patients With Occurrence of Treat to Target Effectiveness Response, That is HbA1c Under Treatment of < 6.5% After 24 Weeks of Treatment
Description	Percentage of patients with occurrence of treat to target effectiveness response, that is HbA1c under treatment of < 6.5% after 24 weeks of treatment.
Time Frame	24 Weeks

Outcome Measure Data

Analysis Population Description

Effectiveness analysis set

Arm/Group Title	Trajenta (Linagliptin) 5 mg
Arm/Group Description	Patients with type 2 diabetes mellitus were administered with Trajenta (Linagliptin) 5 mg once daily orally.
Measure Participants	2171
Number [Percentage of patients]	26.02

4. Secondary Outcome

Title	Percentage of Patients With Occurrence of Relative Effectiveness Response (HbA1c Lowering by at Least 0.5% After 24 Weeks of Treatment)
Description	Percentage of patients with occurrence of relative effectiveness response (HbA1c lowering by at least 0.5% after 24 weeks of treatment).
Time Frame	24 Weeks

Outcome Measure Data

Analysis Population Description

Effectiveness analysis set

Arm/Group Title	Trajenta (Linagliptin) 5 mg
Arm/Group Description	Patients with type 2 diabetes mellitus were administered with Trajenta (Linagliptin) 5 mg once daily orally.
Measure Participants	2171
Number [Percentage of patients]	57.30

5. Secondary Outcome

Title	Change From Baseline After 24 Weeks in Fasting Plasma Glucose (FPG)
Description	Change from baseline after 24 weeks in fasting plasma glucose (FPG).
Time Frame	Baseline and Week 24

Outcome Measure Data

Analysis Population Description

Effectiveness analysis set: the patients with the data available for FPG

Arm/Group Title	Trajenta (Linagliptin) 5 mg
Arm/Group Description	Patients with type 2 diabetes mellitus were administered with Trajenta (Linagliptin) 5 mg once daily orally.
Measure Participants	2171
Before drug administration	161.19 (55.38)
After drug administration	143.51 (46.76)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Trajenta (Linagliptin) 5 mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Paired t-test
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-18.05
	Confidence Interval	(2-Sided) 95%; -20.98 to -15.12
	Parameter Dispersion	Type: Standard Deviation; Value: 61.84
	Estimation Comments	p-value of paired t-test for change from baseline is presented. 95% confidence interval for the mean was calculated using t-distribution.

Adverse Events

Time Frame	From the entire surveillance period until re-examination period, up to 6 years.
Arm/Group Title	Trajenta (Linagliptin) 5 mg
Arm/Group Description	Patients with type 2 diabetes mellitus were administered with Trajenta (Linagliptin) 5 mg once daily orally.
All Cause Mortality
	Trajenta (Linagliptin) 5 mg
	Affected / at Risk (%)	# Events
Total	2/3119 (0.1%)
Serious Adverse Events
	Trajenta (Linagliptin) 5 mg
	Affected / at Risk (%)	# Events
Total	49/3119 (1.6%)
Cardiac disorders
Cardiac failure congestive	2/3119 (0.1%)
Angina pectoris	1/3119 (0%)
Acute myocardial infarction	1/3119 (0%)
Angina unstable	1/3119 (0%)
Cardiac arrest	1/3119 (0%)
Ear and labyrinth disorders
Vertigo	2/3119 (0.1%)
Eye disorders
Diabetic retinopathy	1/3119 (0%)
Gastrointestinal disorders
Constipation	1/3119 (0%)
Abdominal pain upper	2/3119 (0.1%)
Enterocolitis	1/3119 (0%)
Ileus	1/3119 (0%)
General disorders
Chest pain	1/3119 (0%)
Pyrexia	1/3119 (0%)
Face oedema	1/3119 (0%)
Fatigue	1/3119 (0%)
Death	1/3119 (0%)
Hepatobiliary disorders
Cholecystitis acute	1/3119 (0%)
Cholangitis	1/3119 (0%)
Immune system disorders
Renal transplant failure	1/3119 (0%)
Infections and infestations
Gastroenteritis	1/3119 (0%)
Pneumonia	3/3119 (0.1%)
Herpes zoster	1/3119 (0%)
Cystitis	1/3119 (0%)
Pyelonephritis acute	1/3119 (0%)
Bronchitis	1/3119 (0%)
Vestibular neuronitis	1/3119 (0%)
Sepsis	1/3119 (0%)
Injury, poisoning and procedural complications
Meniscus injury	1/3119 (0%)
Pneumoconiosis	1/3119 (0%)
Metabolism and nutrition disorders
Hyperglycaemia	4/3119 (0.1%)
Decreased appetite	1/3119 (0%)
Dehydration	1/3119 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to liver	1/3119 (0%)
Acute leukaemia	1/3119 (0%)
Basal cell carcinoma	1/3119 (0%)
Non-small cell lung cancer	1/3119 (0%)
Pericardial effusion malignant	1/3119 (0%)
Gastric cancer	1/3119 (0%)
Rectal cancer	1/3119 (0%)
Pancreatic carcinoma	1/3119 (0%)
Nervous system disorders
Cerebral infarction	2/3119 (0.1%)
Dysarthria	1/3119 (0%)
Dementia Alzheimer's type	1/3119 (0%)
Renal and urinary disorders
Acute kidney injury	1/3119 (0%)
End stage renal disease	1/3119 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	4/3119 (0.1%)
Chronic obstructive pulmonary disease	1/3119 (0%)
Asthma	1/3119 (0%)
Skin and subcutaneous tissue disorders
Diabetic foot	1/3119 (0%)
Skin lesion	1/3119 (0%)
Other (Not Including Serious) Adverse Events
	Trajenta (Linagliptin) 5 mg
	Affected / at Risk (%)	# Events
Total	0/3119 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.