Long-term Daily Use of Trazenta® Tablets in Patients With Type 2 Diabetes Mellitus

• Sponsor: Boehringer Ingelheim (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01650259
• Collaborator: Eli Lilly and Company (Industry)
• Enrollment: 4,876
• Location: 1
• Actual Duration (Months): 61.7
• Patients Per Site Per Month: 79

Study Details

Study Description

Brief Summary

Study to investigate the safety and efficacy of long-term daily use of Trazenta® Tablets as monotherapy in patients with type 2 diabetes mellitus and to assess baseline characteristics of patients with type 2 diabetes mellitus starting Trazenta® Tablets or any other oral antidiabetic monotherapy (naïve or switched from prior therapy of different oral antidiabetic drug).

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 2	Drug: OAD; Drug: Trazenta

Study Design

• Study Type: Observational
• Actual Enrollment: 4876 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Post Marketing Surveillance on Long Term Drug Use of Trazenta® Tablets in Patients With Type 2 Diabetes Mellitus
• Actual Study Start Date: Jul 23, 2012
• Actual Primary Completion Date: Sep 5, 2017
• Actual Study Completion Date: Sep 14, 2017

Arms and Interventions

Arm	Intervention/Treatment
Oral antidiabetic drug (OAD)	Drug: OAD; OAD except Trazenta tablets
Trazenta	Drug: Trazenta; Linagliptin

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Adverse Drug Reactions (ADRs) [From start of the treatment until the end of this PMS, i.e. up to week 156]

   An adverse drug reactions (ADR) was defined as an adverse event (AE) if either the investigator or the sponsor (or both) assessed the causal relationship of Trazenta® Tablets either as "Yes", "Probably yes" or "Can't be denied".

Secondary Outcome Measures

1. Change From Baseline in HbA1c at the Last Observation During the Observation Period. [Baseline and 156 week or last observation]

   Change from baseline in Haemoglobin A1c (HbA1c) at the last observation during the observation period is presented as mean change from baseline and standard deviation (SD).

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria:

• Male and female patients with type 2 Diabetes Mellitus who have never been treated with Trazenta tablets / Linagliptin (monotherapy) before enrollment. (Trazenta group)

• Patients with type 2 Diabetes Mellitus starting any other oral antidiabetic monotherapy (naïve or switched from prior therapy of different oral antidiabetic drug (OAD)) except Trazenta tablets. (OAD group)

Exclusion criteria:

None

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		One Or Multiple Locations		Japan

Sponsors and Collaborators

• Boehringer Ingelheim
• Eli Lilly and Company

Investigators

• Study Chair: Boehringer Ingelheim, Boehringer Ingelheim

Study Documents (Full-Text)

• Study Protocol - Apr 4, 2013
• Statistical Analysis Plan - Nov 14, 2017

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: Boehringer Ingelheim
• ClinicalTrials.gov Identifier: NCT01650259
• Other Study ID Numbers: 1218.95
• First Posted: Jul 26, 2012
• Last Update Posted: Sep 18, 2019
• Last Verified: Sep 1, 2019

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

Study Results

Participant Flow

Recruitment Details	In this post marketing surveillance (PMS) study 4876 patients were registered: 2513 patients (Pts.) in Trazenta® Tablets group & 2363 patients in other Oral Antidiabetic Drug (OAD) group (grp). 2414 out of 2513 patients were treated (trt) with Trazenta® Tablets. For other OAD group only baseline data & no observation period.
Pre-assignment Detail	Non-interventional,observational prospective study based on newly collected data under routine medical practice with 1 grp of Pts. treated with long-term daily use of Trazenta® Tablets for evaluation of baseline,safety& efficacy data & another grp of Pts. treated with any other oral antidiabetic monotherapy for collection of baseline data only.

Arm/Group Title	Trazenta® Tablets	Other OAD
Arm/Group Description	Patients with type 2 diabetes mellitus were administered orally with 5 milligram (mg) of Trazenta® tablets for 156 weeks or until discontinuation.	Patients with type 2 diabetes mellitus who were treated with any other oral antidiabetic monotherapy except Trazenta® tablets
Period Title: Overall Study
STARTED	2513	2363
COMPLETED	1470	2128
NOT COMPLETED	1043	235

Baseline Characteristics

Arm/Group Title	Trazenta® Tablets	Other OAD	Total
Arm/Group Description	Patients with type 2 diabetes mellitus were administered orally with 5 milligram (mg) of Trazenta® tablets for 156 weeks or until discontinuation.	Patients with type 2 diabetes mellitus who were treated with any other oral antidiabetic monotherapy except Trazenta® tablets	Total of all reporting groups
Overall Participants	2233	2128	4361
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	66.7 (12.5)	65.3 (12.6)	66.0 (12.6)
Sex: Female, Male (Count of Participants)
Female	929 41.6%	910 42.8%	1839 42.2%
Male	1304 58.4%	1218 57.2%	2522 57.8%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Adverse Drug Reactions (ADRs)
Description	An adverse drug reactions (ADR) was defined as an adverse event (AE) if either the investigator or the sponsor (or both) assessed the causal relationship of Trazenta® Tablets either as "Yes", "Probably yes" or "Can't be denied".
Time Frame	From start of the treatment until the end of this PMS, i.e. up to week 156

Outcome Measure Data

Analysis Population Description

Safety Set (SS): SS includes all patients who had received treatment of Trazenta® Tablets as mono therapy except those who were found to have no observation after enrolment, invalid registration, or invalid contract.

Arm/Group Title	Trazenta® Tablets
Arm/Group Description	Patients with type 2 diabetes mellitus were administered orally with 5 milligram (mg) of Trazenta® tablets for 156 weeks or until discontinuation.
Measure Participants	2235
Number [Percentage of Participants]	10.74 0.5%

2. Secondary Outcome

Title	Change From Baseline in HbA1c at the Last Observation During the Observation Period.
Description	Change from baseline in Haemoglobin A1c (HbA1c) at the last observation during the observation period is presented as mean change from baseline and standard deviation (SD).
Time Frame	Baseline and 156 week or last observation

Outcome Measure Data

Analysis Population Description

Efficacy Set: A subset of the safety set, which includes all patients in the "safety set" except those who had no available efficacy data and/or who did not suffer from type 2 diabetes mellitus from the safety set.

Arm/Group Title	Trazenta® Tablets
Arm/Group Description	Patients with type 2 diabetes mellitus were administered orally with 5 milligram (mg) of Trazenta® tablets for 156 weeks or until discontinuation.
Measure Participants	2235
Mean (Standard Deviation) [percentage of HbA1c]	-0.67 (1.27)

Adverse Events

Time Frame	From first drug administration patient was observed until 156 weeks, up to 241 weeks.
Adverse Event Reporting Description	Safety Set (SS) (SS includes all patients who had received treatment of Trazenta® Tablets as mono therapy except those who were found to have no observation after enrolment, invalid registration, or invalid contract.) was used for adverse event reporting.
Arm/Group Title	Trazenta® Tablets
Arm/Group Description	Patients with type 2 diabetes mellitus were administered orally with 5 milligram (mg) of Trazenta® tablets for 156 weeks or until discontinuation.
All Cause Mortality
	Trazenta® Tablets
	Affected / at Risk (%)	# Events
Total	34/2235 (1.5%)
Serious Adverse Events
	Trazenta® Tablets
	Affected / at Risk (%)	# Events
Total	116/2235 (5.2%)
Blood and lymphatic system disorders
Polycythaemia	1/2235 (0%)
Cardiac disorders
Cardiac failure	4/2235 (0.2%)
Myocardial infarction	4/2235 (0.2%)
Angina pectoris	3/2235 (0.1%)
Angina unstable	3/2235 (0.1%)
Acute myocardial infarction	2/2235 (0.1%)
Cardiac failure congestive	2/2235 (0.1%)
Atrial fibrillation	1/2235 (0%)
Atrial flutter	1/2235 (0%)
Prinzmetal angina	1/2235 (0%)
Eye disorders
Cataract	1/2235 (0%)
Gastrointestinal disorders
Ileus	2/2235 (0.1%)
Enterocolitis	1/2235 (0%)
Haematemesis	1/2235 (0%)
Ileus paralytic	1/2235 (0%)
Intestinal obstruction	1/2235 (0%)
Intestinal perforation	1/2235 (0%)
Large intestine polyp	1/2235 (0%)
Mechanical ileus	1/2235 (0%)
General disorders
Death	4/2235 (0.2%)
Sudden death	2/2235 (0.1%)
Sudden cardiac death	1/2235 (0%)
Hepatobiliary disorders
Bile duct stenosis	1/2235 (0%)
Hepatic cirrhosis	1/2235 (0%)
Hepatitis acute	1/2235 (0%)
Infections and infestations
Pneumonia	3/2235 (0.1%)
Herpes zoster	2/2235 (0.1%)
Bacterial infection	1/2235 (0%)
Gangrene	1/2235 (0%)
Urinary tract infection	1/2235 (0%)
Injury, poisoning and procedural complications
Femur fracture	3/2235 (0.1%)
Fall	2/2235 (0.1%)
Subdural haematoma	2/2235 (0.1%)
Clavicle fracture	1/2235 (0%)
Femoral neck fracture	1/2235 (0%)
Patella fracture	1/2235 (0%)
Road traffic accident	1/2235 (0%)
Spinal compression fracture	1/2235 (0%)
Subarachnoid haemorrhage	1/2235 (0%)
Investigations
Biopsy liver	1/2235 (0%)
Blood creatinine increased	1/2235 (0%)
Blood urea increased	1/2235 (0%)
Blood uric acid increased	1/2235 (0%)
White blood cell count decreased	1/2235 (0%)
Metabolism and nutrition disorders
Diabetes mellitus	1/2235 (0%)
Diabetes mellitus inadequate control	1/2235 (0%)
Hypoalbuminaemia	1/2235 (0%)
Hypoglycaemia	1/2235 (0%)
Musculoskeletal and connective tissue disorders
Spinal column stenosis	1/2235 (0%)
Still's disease	1/2235 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer	5/2235 (0.2%)
Pancreatic carcinoma	3/2235 (0.1%)
Gastric cancer	2/2235 (0.1%)
Lymphoma	2/2235 (0.1%)
Rectosigmoid cancer	2/2235 (0.1%)
Bladder cancer	1/2235 (0%)
Breast cancer	1/2235 (0%)
Gastric cancer recurrent	1/2235 (0%)
Hepatic cancer recurrent	1/2235 (0%)
Lung neoplasm malignant	1/2235 (0%)
Prostate cancer	1/2235 (0%)
Renal cancer	1/2235 (0%)
Tongue neoplasm malignant stage unspecified	1/2235 (0%)
Nervous system disorders
Cerebral infarction	12/2235 (0.5%)
Dementia	5/2235 (0.2%)
Altered state of consciousness	1/2235 (0%)
Carotid artery occlusion	1/2235 (0%)
Dementia Alzheimer's type	1/2235 (0%)
Loss of consciousness	1/2235 (0%)
Parkinson's disease	1/2235 (0%)
Syncope	1/2235 (0%)
Psychiatric disorders
Alcoholism	1/2235 (0%)
Renal and urinary disorders
Chronic kidney disease	4/2235 (0.2%)
Acute kidney injury	3/2235 (0.1%)
Renal impairment	2/2235 (0.1%)
Respiratory, thoracic and mediastinal disorders
Asthma	2/2235 (0.1%)
Asphyxia	1/2235 (0%)
Aspiration	1/2235 (0%)
Hypoxia	1/2235 (0%)
Interstitial lung disease	1/2235 (0%)
Organising pneumonia	1/2235 (0%)
Pneumonia aspiration	1/2235 (0%)
Pulmonary embolism	1/2235 (0%)
Respiratory failure	1/2235 (0%)
Skin and subcutaneous tissue disorders
Rash	1/2235 (0%)
Vascular disorders
Aortic dissection	1/2235 (0%)
Circulatory collapse	1/2235 (0%)
Deep vein thrombosis	1/2235 (0%)
Hypotension	1/2235 (0%)
Peripheral arterial occlusive disease	1/2235 (0%)
Peripheral artery occlusion	1/2235 (0%)
Shock	1/2235 (0%)
Other (Not Including Serious) Adverse Events
	Trazenta® Tablets
	Affected / at Risk (%)	# Events
Total	0/2235 (0%)

Limitations/Caveats

The study was conducted in an unblinded manner and without controls. The explanatory power of the study results was limited and the study results should be interpreted with the necessary caution.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.