Alogliptin Tablets Special Drug Use Surveillance: Mild Type 2 Diabetes Mellitus

• Sponsor: Takeda (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01964963
• Collaborator: (none)
• Enrollment: 19,192
• Location: 1
• Actual Duration (Months): 71.9
• Patients Per Site Per Month: 266.9

Study Details

Study Description

Brief Summary

The purpose of this study is to examine the safety and efficacy of long-term treatment with alogliptin (Nesina) in patients with mild type 2 diabetes mellitus in the routine clinical setting.

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes Mellitus	Drug: Alogliptin

Detailed Description

This is a special drug use surveillance on long-term use of alogliptin, designed to investigate the safety and efficacy of treatment with alogliptin in patients with mild type 2 diabetes mellitus in the routine clinical setting.

Participants will be patients with mild type 2 diabetes mellitus. The planned sample size is 20,000.

The usual adult dosage for oral use is 1 alogliptin tablet (25 mg of alogliptin) once daily.

Study Design

• Study Type: Observational
• Actual Enrollment: 19192 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Alogliptin (Nesina) Tablets Special Drug Use Surveillance: Mild Type 2 Diabetes Mellitus
• Actual Study Start Date: Aug 3, 2011
• Actual Primary Completion Date: Jul 31, 2017
• Actual Study Completion Date: Jul 31, 2017

Arms and Interventions

Arm	Intervention/Treatment
Alogliptin Alogliptin 25 mg, tablets, orally, once daily for up to 12 months. Participants will receive interventions as part of routine medical care.	Drug: Alogliptin; Alogliptin tablets; Other Names: Nesina SYR-322

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Who Had One or More Adverse Events [Up to Month 36]

2. Change From Baseline in Glycosylated Hemoglobin (HbA1c) [Baseline, and final assessment point (up to Month 36)]

   The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at final assessment point (up to Month 36) relative to baseline.

Secondary Outcome Measures

1. Change From Baseline in Fasting Blood Glucose [Baseline, and final assessment point (up to Month 36)]

   The change in the value of fasting blood glucose level collected at final assessment point (up to Month 36) relative to baseline.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

-Patients with Haemoglobin A1c (HbA1c) [Japan Diabetes Society (JDS) value] ≤7.0% at the time of enrolment (within 3 months before initiation of alogliptin therapy), regardless of the use of antidiabetic medication.

Exclusion Criteria:

-Patients contraindicated for alogliptin.

1. Patients with severe ketosis, diabetic coma or precoma, or type 1 diabetes mellitus.

2. Patients with severe infection, pre- or post-operative patients, or patients with serious traumatic injury.

3. Patients with a history of hypersensitivity to any ingredient of alogliptin.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Tokyo		Japan

Sponsors and Collaborators

• Takeda

Investigators

• Study Director: Study Director, Takeda

Study Documents (Full-Text)

• Study Protocol - Mar 2, 2017
• Statistical Analysis Plan - Feb 4, 2019

More Information

Publications

None provided.

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT01964963
• Other Study ID Numbers: 121-015; JapicCTI-132283
• First Posted: Oct 17, 2013
• Last Update Posted: Nov 21, 2019
• Last Verified: Nov 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Alogliptin

Study Results

Participant Flow

Recruitment Details	Participants took part in the study at 1406 investigative sites in Japan, from 03 August 2011 to 31 July 2017.
Pre-assignment Detail	Participants with a historical diagnosis of mild type 2 diabetes mellitus were enrolled. Participants received interventions as part of routine medical care.

Arm/Group Title	Alogliptin 25 mg
Arm/Group Description	Alogliptin 25 mg, tablets, orally, once daily for up to 12 months. Participants received interventions as part of routine medical care.
Period Title: Overall Study
STARTED	19192
COMPLETED	18249
NOT COMPLETED	943

Baseline Characteristics

Arm/Group Title	Alogliptin 25 mg
Arm/Group Description	Alogliptin 25 mg, tablets, orally, once daily for up to 12 months. Participants received interventions as part of routine medical care.
Overall Participants	18249
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	67.3 (11.41)
Sex: Female, Male (Count of Participants)
Female	7970 43.7%
Male	10279 56.3%
Race and Ethnicity Not Collected (Count of Participants)
Region of Enrollment (Number) [Number]
Japan	18249 100%
Number of Females who were not Pregnant (Count of Participants)
Count of Participants [Participants]	7970 43.7%
Duration of Diagnosis of Type 2 Diabetes Mellitus (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	6.03 (6.452)
Height (Centimeters (cm)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Centimeters (cm)]	159.6 (9.61)
Weight (Kilograms (kg)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Kilograms (kg)]	63.85 (13.324)
BMI (kg/meter (m)^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/meter (m)^2]	24.95 (4.067)
Healthcare Category (Count of Participants)
Outpatient	18069 99%
Inpatient	180 1%
Degree of Renal Dysfunction (Count of Participants)
Normal	14808 81.1%
Mild	2766 15.2%
Moderate	598 3.3%
Severe	77 0.4%
Medical Complications (Count of Participants)
Had No Presence of Medical Complications	2322 12.7%
Had Presence of Medical Complications	15927 87.3%
Concomitant Diabetes Mellitus (Count of Participants)
Had No Concomitant Diabetes Mellitus	16165 88.6%
Had Concomitant Diabetes Mellitus	2084 11.4%
Concomitant Hypertension (Count of Participants)
Had No Concomitant Hypertension	6764 37.1%
Had Concomitant Hypertension	11485 62.9%
Concomitant Hyperlipidemia (Count of Participants)
Had No Concomitant Hyperlipidemia	7303 40%
Had Concomitant Hyperlipidemia	10946 60%
Concomitant Hyperuricaemia (Count of Participants)
Had No Concomitant Hyperuricaemia	16614 91%
Had Concomitant Hyperuricaemia	1635 9%
Concomitant Hepatic Disorder (Count of Participants)
Had No Concomitant Hepatic Disorder	16266 89.1%
Had Concomitant Hepatic Disorder	1983 10.9%
Concomitant Renal Disorder (Count of Participants)
Had No Concomitant Renal Disorder	16572 90.8%
Had Concomitant Renal Disorder	1677 9.2%
Concomitant Cardiac Disease (Count of Participants)
Had No Concomitant Cardiac Disease	16032 87.9%
Had Concomitant Cardiac Disease	2217 12.1%
Concomitant Heart Failure (Count of Participants)
Had No Concomitant Heart Failure	17709 97%
Had Concomitant Heart Failure	540 3%
New York Heart Association (NYHA) Heart Failure Classification (Count of Participants)
Class I	354 1.9%
Class II	143 0.8%
Class III	26 0.1%
Class IV	7 0%
Unknown	10 0.1%
Concomitant Stroke-Related Disease (Count of Participants)
Had No Concomitant Stroke-Related Disease	17072 93.6%
Had Concomitant Stroke-Related Disease	1177 6.4%
Concomitant Allergic Condition (Count of Participants)
Had No Concomitant Allergic Condition	17224 94.4%
Had Concomitant Allergic Condition	1025 5.6%
Concomitant Malignant Tumor (Count of Participants)
Had No Concomitant Malignant Tumor	17832 97.7%
Had Concomitant Malignant Tumor	417 2.3%
Medical History (Count of Participants)
Had No Medical History	14497 79.4%
Had Medical History	2080 11.4%
Unknown	1672 9.2%
Predisposition to Hypersensitivity (Count of Participants)
Had No Predisposition to Hypersensitivity	15551 85.2%
Had Predisposition to Hypersensitivity	795 4.4%
Unknown	1903 10.4%
Drinking Habits (Count of Participants)
Yes	5440 29.8%
No	9156 50.2%
Unknown	3653 20%
Smoking Classification (Count of Participants)
Never Smoked	8089 44.3%
Current Smoker	2330 12.8%
Ex-Smoker	3326 18.2%
Unknown	4504 24.7%
Hemoglobin A1c (HbA1c) [National Glycohemoglobin Standardization Program (NGSP) Value] (Percentage of HbA1c) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Percentage of HbA1c]	6.88 (0.591)
Dietary Instruction (Count of Participants)
Instructed	15433 84.6%
Not Instructed	2816 15.4%
Exercise Instruction (Count of Participants)
Instructed	13909 76.2%
Not Instructed	4340 23.8%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Who Had One or More Adverse Events
Time Frame	Up to Month 36

Outcome Measure Data

Analysis Population Description

Safety Analysis Set; The safety analysis set was defined as all participants who completed the study.

Arm/Group Title	Alogliptin 25 mg
Arm/Group Description	Alogliptin 25 mg, tablets, orally, once daily for up to 12 months. Participants received interventions as part of routine medical care.
Measure Participants	18249
Number [Percentage of Participants]	10.54 0.1%

2. Primary Outcome

Title	Change From Baseline in Glycosylated Hemoglobin (HbA1c)
Description	The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at final assessment point (up to Month 36) relative to baseline.
Time Frame	Baseline, and final assessment point (up to Month 36)

Outcome Measure Data

Analysis Population Description

The efficacy assessment population was defined as participants who completed the study and had available efficacy data at baseline and post baseline. The number analyzed is the number of participants with data available for analysis at the given time-point.

Arm/Group Title	Alogliptin 25 mg
Arm/Group Description	Alogliptin 25 mg, tablets, orally, once daily for up to 12 months. Participants received interventions as part of routine medical care.
Measure Participants	16022
Mean (Standard Deviation) [Percent HbA1c]	-0.14 (0.777)

3. Secondary Outcome

Title	Change From Baseline in Fasting Blood Glucose
Description	The change in the value of fasting blood glucose level collected at final assessment point (up to Month 36) relative to baseline.
Time Frame	Baseline, and final assessment point (up to Month 36)

Outcome Measure Data

Analysis Population Description

The efficacy assessment population was defined as participants who completed the study and had available efficacy data at baseline and post baseline. The number analyzed is the number of participants with data available for analysis at the given time-point.

Arm/Group Title	Alogliptin 25 mg
Arm/Group Description	Alogliptin 25 mg, tablets, orally, once daily for up to 12 months. Participants received interventions as part of routine medical care.
Measure Participants	6031
Mean (Standard Deviation) [Milligram (mg)/ deciliter (dL)]	-5.8 (34.33)

Adverse Events

Time Frame	Up to Month 36
Adverse Event Reporting Description	At each visit the investigator had to document any occurrence of adverse events (AEs) and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Only adverse drug reactions (ADRs) were collected and reported on safety results sections here. ADRs are AEs which are in the investigator's opinion of causal relationship to the study treatment..
Arm/Group Title	Alogliptin 25 mg
Arm/Group Description	Alogliptin 25 mg, tablets, orally, once daily for up to 12 months. Participants received interventions as part of routine medical care.
All Cause Mortality
	Alogliptin 25 mg
	Affected / at Risk (%)	# Events
Total	20/18249 (0.1%)
Serious Adverse Events
	Alogliptin 25 mg
	Affected / at Risk (%)	# Events
Total	65/18249 (0.4%)
Cardiac disorders
Acute myocardial infarction	1/18249 (0%)
Cardiac failure	1/18249 (0%)
Cardiac failure acute	2/18249 (0%)
Cardiac failure congestive	1/18249 (0%)
Ventricular tachycardia	1/18249 (0%)
Gastrointestinal disorders
Anal fistula	1/18249 (0%)
Pancreatitis acute	3/18249 (0%)
General disorders
Death	3/18249 (0%)
Pyrexia	1/18249 (0%)
Sudden death	5/18249 (0%)
Hepatobiliary disorders
Cholangitis	1/18249 (0%)
Infections and infestations
Peritonitis	1/18249 (0%)
Pneumonia	2/18249 (0%)
Injury, poisoning and procedural complications
Fall	1/18249 (0%)
Subdural haematoma	2/18249 (0%)
Excoriation	1/18249 (0%)
Contusion	1/18249 (0%)
Investigations
C-reactive protein increased	1/18249 (0%)
White blood cell count increased	1/18249 (0%)
Metabolism and nutrition disorders
Cachexia	1/18249 (0%)
Hypoglycaemia	2/18249 (0%)
Marasmus	1/18249 (0%)
Musculoskeletal and connective tissue disorders
Rhabdomyolysis	1/18249 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bile duct cancer	1/18249 (0%)
Bladder cancer	1/18249 (0%)
Bladder neoplasm	1/18249 (0%)
Colon cancer	2/18249 (0%)
Diffuse large B-cell lymphoma	1/18249 (0%)
Gastric cancer	1/18249 (0%)
Neoplasm malignant	1/18249 (0%)
Oesophageal carcinoma	1/18249 (0%)
Ovarian cancer	1/18249 (0%)
Pancreatic carcinoma	2/18249 (0%)
Lung neoplasm malignant	1/18249 (0%)
Intraductal papillary mucinous neoplasm	1/18249 (0%)
Hepatic cancer	1/18249 (0%)
Hepatic cancer recurrent	1/18249 (0%)
Hepatocellular carcinoma	1/18249 (0%)
Nervous system disorders
Cerebellar haemorrhage	1/18249 (0%)
Cerebral infarction	2/18249 (0%)
Cerebrovascular accident	2/18249 (0%)
Epilepsy	1/18249 (0%)
Headache	1/18249 (0%)
Subdural hygroma	1/18249 (0%)
Psychiatric disorders
Completed suicide	1/18249 (0%)
Depression	1/18249 (0%)
Renal and urinary disorders
Diabetic nephropathy	2/18249 (0%)
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema	1/18249 (0%)
Other (Not Including Serious) Adverse Events
	Alogliptin 25 mg
	Affected / at Risk (%)	# Events
Total	41/18249 (0.2%)
Metabolism and nutrition disorders
Hypoglycaemia	41/18249 (0.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.