Alogliptin Tablets Special Drug Use Surveillance "Type 2 Diabetes Mellitus: Monotherapy/Combination Therapy With α-GI"

• Sponsor: Takeda (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01945216
• Collaborator: (none)
• Enrollment: 3,317
• Location: 1
• Actual Duration (Months): 63.8
• Patients Per Site Per Month: 52

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the safety and efficacy of long-term treatment with alogliptin (Nesina) in patients with type 2 diabetes mellitus who responded inadequately to diet therapy and exercise therapy alone, or a combination of diet therapy, exercise therapy, and α-glucosidase inhibitor.

In addition, examining the safety and efficacy of alogliptin in patients with renal impairment, information on the appropriate dosage of alogliptin according to the severity of impaired renal function should be collected.

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes Mellitus Who Have Been Examined at a Medical Institution	Drug: Alogliptin

Detailed Description

A special drug use surveillance is planned to examine the safety and efficacy of long-term use of alogliptin in patients with type 2 diabetes mellitus under the daily clinical use conditions.

Participants of this surveillance will be patients with type 2 diabetes mellitus who failed to respond adequately to diet therapy and exercise therapy alone or to a combination of diet therapy, exercise therapy, and α-glucosidase inhibitor. The planned sample size is 3,000 subjects.

The usual adult dosage for oral use is 1 alogliptin tablet (25 mg) once daily. Participants will receive the drug as part of routine medical care.

Study Design

• Study Type: Observational
• Actual Enrollment: 3317 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Alogliptin Tablets Special Drug Use Surveillance "Type 2 Diabetes Mellitus: Monotherapy/Combination Therapy With α-GI"
• Actual Study Start Date: Jul 8, 2010
• Actual Primary Completion Date: Oct 31, 2015
• Actual Study Completion Date: Oct 31, 2015

Arms and Interventions

Arm	Intervention/Treatment
Alogliptin 25mg, tablets, orally, once daily, up to 36 months	Drug: Alogliptin; Alogliptin tablets; Other Names: Nesina; SYR-322

Outcome Measures

Primary Outcome Measures

1. Number of Participants Who Experience at Least One Adverse Events [Up to Month 36]

2. Change From Baseline in Glycosylated Hemoglobin (HbA1c) [Baseline, Months 1, 3, 6, 12, 18, 24, 30, 36 and final assessment (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 month 36 relative to baseline.

Secondary Outcome Measures

1. Change From Baseline in Fasting Blood Glucose [Baseline, Months 1, 3, 6, 12, 18, 24, 30, 36 and final assessment (up to Month 36)]

   The change in the value of fasting blood glucose collected at 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 type 2 diabetes mellitus who have not adequately responded to any one of the following therapies:

1. Diet therapy and exercise therapy alone

2. In addition to diet therapy and exercise therapy, use of α-glucosidase inhibitor

Exclusion Criteria:

• Patients contraindicated for Nesina

1. Patients with severe ketosis, diabetic coma or precoma, or type 1 diabetes mellitus (these patients require prompt adjustment of hyperglycemia by fluid infusion and insulin, and hence use of Nesina is not appropriate.)

2. Patients with severe infection, pre- or post-operative patients, or patients with serious traumatic injury (blood glucose control by insulin injection is desirable for these patients, and hence use of Nesina is not appropriate.)

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Osaka		Japan

Sponsors and Collaborators

• Takeda

Investigators

• Study Director: Study Director, Takeda

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT01945216
• Other Study ID Numbers: 121-011; JapicCTI-132250; JapicCTI-R171018
• First Posted: Sep 18, 2013
• Last Update Posted: Nov 19, 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
• Keywords provided by Takeda: Drug therapy
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Alogliptin

Study Results

Participant Flow

Recruitment Details	Participants took part in the study at 608 investigative sites in Japan, from 8-July-2010 to 31-October-2015. Data reports overall population, since data not collected separately per arm as specified in protocol.
Pre-assignment Detail	Participants with type 2 diabetes mellitus who failed to respond adequately to diet and/or exercise therapy and α-glucosidase inhibitor were enrolled to receive Alogliptin as routine medical care. Treatments were not allocated at the start of the study. Thus, the Participant Flow cannot be presented "per Arm".

Arm/Group Title	Overall Population
Arm/Group Description	Alogliptin 25 milligram (mg), tablets, orally, once daily, up to 36 months along with an alpha-glucosidase inhibitor (α-GI), without an α-GI, or the other diabetic drugs from the start of administration of alogliptin and during the treatment period of alogliptin in routine medical care.
Period Title: Overall Study
STARTED	3317
COMPLETED	3218
NOT COMPLETED	99

Baseline Characteristics

Arm/Group Title	Alogliptin	Alogliptin + αGI	Alogliptin + Other	Total
Arm/Group Description	Alogliptin 25 mg, tablets, orally, once daily for up to 36 months in routine medical care. Participants in this group received no diabetic drugs within 3 months from the start of administration of alogliptin and during the treatment period of alogliptin.	Alogliptin 25 mg, tablets, orally, once daily for up to 36 months in routine medical care. Participants in this group received an α-GI within 3 months from the start of administration of alogliptin and during the treatment period of alogliptin.	Alogliptin 25 mg, tablets, orally, once daily for up to 12 months in routine medical care. Participants in this group did not receive an α-GI within 3 months from the start of administration of alogliptin or during the treatment period of alogliptin.	Total of all reporting groups
Overall Participants	1560	669	989	3218
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	65.0 (12.28)	67.1 (12.13)	64.0 (12.57)	65.1 (12.39)
Sex: Female, Male (Count of Participants)
Female	640 41%	286 42.8%	438 44.3%	1364 42.4%
Male	920 59%	383 57.2%	551 55.7%	1854 57.6%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (Count of Participants)
Japan	1560 100%	669 100%	989 100%	3218 100%
Time From Diagnosis of Type 2 Diabetes (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	3.45 (4.923)	8.10 (7.018)	5.03 (5.732)	4.91 (5.937)
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	160.22 (9.686)	159.33 (9.535)	160.18 (9.738)	160.02 (9.674)
Body Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	64.49 (13.699)	62.68 (13.005)	64.51 (14.046)	64.12 (13.681)
BMI (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	25.00 (4.225)	24.52 (4.277)	25.04 (4.190)	24.91 (4.229)
Waist Circumference (Male) (Count of Participants)
< 85cm	96 6.2%	55 8.2%	61 6.2%	212 6.6%
≥ 85cm	211 13.5%	80 12%	120 12.1%	411 12.8%
Unknown	613 39.3%	248 37.1%	370 37.4%	1231 38.3%
Waist Circumference (Female) (Count of Participants)
< 90cm	152 9.7%	65 9.7%	85 8.6%	302 9.4%
≥ 90cm	70 4.5%	37 5.5%	52 5.3%	159 4.9%
Unknown	418 26.8%	184 27.5%	301 30.4%	903 28.1%
Healthcare category (Count of Participants)
Out-patient	1524 97.7%	640 95.7%	942 95.2%	3106 96.5%
In-patient	3 0.2%	8 1.2%	11 1.1%	22 0.7%
In- to/from out-patient	33 2.1%	21 3.1%	36 3.6%	90 2.8%
Pregnancy Status (Count of Participants)
Not pregnant	640 41%	286 42.8%	438 44.3%	1364 42.4%
Pregnant	0 0%	0 0%	0 0%	0 0%
History of Allergy (Count of Participants)
Had no history of Allergy	1377 88.3%	583 87.1%	856 86.6%	2816 87.5%
Had history of Allergy	127 8.1%	57 8.5%	104 10.5%	288 8.9%
Unknown	56 3.6%	29 4.3%	29 2.9%	114 3.5%
Complications (Count of Participants)
Had No Complications	314 20.1%	61 9.1%	103 10.4%	478 14.9%
Had Complications	1246 79.9%	608 90.9%	886 89.6%	2740 85.1%
Diabetic Complications (Count of Participants)
Had No Diabetic Complications	1402 89.9%	506 75.6%	831 84%	2739 85.1%
Had Diabetic Complications	158 10.1%	163 24.4%	158 16%	479 14.9%
Hypertension Complications (Count of Participants)
Had No Hypertension Complications	676 43.3%	249 37.2%	383 38.7%	1308 40.6%
Had Hypertension Complications	884 56.7%	420 62.8%	606 61.3%	1910 59.4%
Hyperlipidemia Complications (Count of Participants)
Had No Hyperlipidemia Complications	715 45.8%	246 36.8%	375 37.9%	1336 41.5%
Had Hyperlipidemia Complications	845 54.2%	423 63.2%	614 62.1%	1882 58.5%
Hyperuricemia Complications (Count of Participants)
Had No Hyperuricemia Complications	1411 90.4%	611 91.3%	891 90.1%	2913 90.5%
Had Hyperuricemia Complications	149 9.6%	58 8.7%	98 9.9%	305 9.5%
Hepatic Dysfunction Complications (Count of Participants)
Had No Hepatic Dysfunction Complications	1322 84.7%	553 82.7%	799 80.8%	2674 83.1%
Had Hepatic Dysfunction Complications	238 15.3%	116 17.3%	190 19.2%	544 16.9%
Degree of Hepatic Dysfunction (Count of Participants)
Normal	986 63.2%	443 66.2%	596 60.3%	2025 62.9%
Grade 1	122 7.8%	36 5.4%	87 8.8%	245 7.6%
Grade 2	22 1.4%	10 1.5%	19 1.9%	51 1.6%
Grade 3	0 0%	0 0%	0 0%	0 0%
Unknown	430 27.6%	180 26.9%	287 29%	897 27.9%
Renal Dysfunction Complications (Count of Participants)
Had No Renal Dysfunction Complications	1427 91.5%	563 84.2%	861 87.1%	2851 88.6%
Had Renal Dysfunction Complications	133 8.5%	106 15.8%	128 12.9%	367 11.4%
Degree of Renal Dysfunction (eGFR) (Count of Participants)
Normal	249 16%	108 16.1%	189 19.1%	546 17%
Mild	667 42.8%	254 38%	361 36.5%	1282 39.8%
Moderate	190 12.2%	108 16.1%	121 12.2%	419 13%
Severe	28 1.8%	22 3.3%	25 2.5%	75 2.3%
Unknown	426 27.3%	177 26.5%	293 29.6%	896 27.8%
Degree of Renal Dysfunction (Cr) (Count of Participants)
Normal or Mild	1089 69.8%	466 69.7%	664 67.1%	2219 69%
Moderate	24 1.5%	7 1%	17 1.7%	48 1.5%
Severe	21 1.3%	19 2.8%	15 1.5%	55 1.7%
Unknown	426 27.3%	177 26.5%	293 29.6%	896 27.8%
Cardiac Disease Complications (Count of Participants)
Had No Cardiac Disease Complications	1417 90.8%	578 86.4%	870 88%	2865 89%
Had Cardiac Disease Complications	143 9.2%	91 13.6%	119 12%	353 11%
Heart Failure Complications (Count of Participants)
Had No Heart Failure Complications	1517 97.2%	649 97%	970 98.1%	3136 97.5%
Had Heart Failure Complications	43 2.8%	20 3%	19 1.9%	82 2.5%
New York Heart Association (NYHA) Heart Failure Classification (Count of Participants)
NYHA Class I	26 1.7%	13 1.9%	11 1.1%	50 1.6%
NYHA Class II	16 1%	5 0.7%	5 0.5%	26 0.8%
NYHA Class III	1 0.1%	1 0.1%	1 0.1%	3 0.1%
NYHA Class IV	0 0%	0 0%	0 0%	0 0%
Unknown	0 0%	1 0.1%	2 0.2%	3 0.1%
Stroke-Related Disorder Complications (Count of Participants)
Had No Stroke-Related Disorder Complications	1505 96.5%	613 91.6%	922 93.2%	3040 94.5%
Had Stroke-Related Disorder Complications	55 3.5%	56 8.4%	67 6.8%	178 5.5%
Allergic Disease Complications (Count of Participants)
Had No Allergic Disease Complications	1466 94%	627 93.7%	914 92.4%	3007 93.4%
Had Allergic Disease Complications	94 6%	42 6.3%	75 7.6%	211 6.6%
Malignancy Complications (Count of Participants)
Had No Malignancy Complications	1543 98.9%	661 98.8%	960 97.1%	3164 98.3%
Had Malignancy Complications	17 1.1%	8 1.2%	29 2.9%	54 1.7%
Medical history (Count of Participants)
Had No Medical History	1255 80.4%	501 74.9%	768 77.7%	2524 78.4%
Had Medical History	225 14.4%	126 18.8%	166 16.8%	517 16.1%
Unknown	80 5.1%	42 6.3%	55 5.6%	177 5.5%
Alcohol Consumption Classification (Count of Participants)
Drinking Almost Everyday	412 26.4%	158 23.6%	276 27.9%	846 26.3%
Not Drinking Almost Everyday	891 57.1%	383 57.2%	526 53.2%	1800 55.9%
Unknown	257 16.5%	128 19.1%	187 18.9%	572 17.8%
Smoking Classification (Count of Participants)
Never Smoked	737 47.2%	292 43.6%	414 41.9%	1443 44.8%
Current Smoker	227 14.6%	77 11.5%	155 15.7%	459 14.3%
Ex-Smoker	249 16%	153 22.9%	160 16.2%	562 17.5%
Unknown	347 22.2%	147 22%	260 26.3%	754 23.4%
Glycosylated Hemoglobin A1c (HbA1c) (Count of Participants)
HbA1c <6.0 percent	28 1.8%	24 3.6%	33 3.3%	85 2.6%
HbA1c >=6.0 to <7.0 percent	475 30.4%	134 20%	195 19.7%	804 25%
HbA1c >=7.0 to <8.0 percent	576 36.9%	270 40.4%	320 32.4%	1166 36.2%
HbA1c >=8.0 percent	351 22.5%	195 29.1%	345 34.9%	891 27.7%
Unknown	130 8.3%	46 6.9%	96 9.7%	272 8.5%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Who Experience at Least One Adverse Events
Time Frame	Up to Month 36

Outcome Measure Data

Analysis Population Description

Safety Analysis Set was defined as all participants who were enrolled and completed the study.

Arm/Group Title	Alogliptin	Alogliptin + α-GI	Alogliptin + Other
Arm/Group Description	Alogliptin 25 mg, tablets, orally, once daily for up to 36 months in routine medical care. Participants in this group received no diabetic drugs within 3 months from the start of administration of alogliptin and during the treatment period of alogliptin.	Alogliptin 25 mg, tablets, orally, once daily for up to 36 months in routine medical care. Participants in this group received an α-GI within 3 months from the start of administration of alogliptin and during the treatment period of alogliptin.	Alogliptin 25 mg, tablets, orally, once daily for up to 12 months in routine medical care. Participants in this group did not receive an α-GI within 3 months from the start of administration of alogliptin or during the treatment period of alogliptin.
Measure Participants	1560	669	989
Count of Participants [Participants]	151 9.7%	98 14.6%	139 14.1%

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 month 36 relative to baseline.
Time Frame	Baseline, Months 1, 3, 6, 12, 18, 24, 30, 36 and final assessment (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. Reported group were Alogliptin and Alogliptin + α-GI and data for Alogliptin + Other were not collected as specified in protocol.

Arm/Group Title	Alogliptin	Alogliptin + α-GI
Arm/Group Description	Alogliptin 25 mg, tablets, orally, once daily for up to 36 months in routine medical care. Participants in this group received no diabetic drugs within 3 months from the start of administration of alogliptin and during the treatment period of alogliptin.	Alogliptin 25 mg, tablets, orally, once daily for up to 36 months in routine medical care. Participants in this group received an α-GI within 3 months from the start of administration of alogliptin and during the treatment period of alogliptin.
Measure Participants	1341	612
Change at Month 1	-0.45 (0.581)	-0.33 (0.708)
Change at Month 3	-0.79 (1.007)	-0.54 (1.074)
Change at Month 6	-0.84 (1.045)	-0.70 (1.128)
Change at Month 12	-0.83 (1.102)	-0.75 (1.054)
Change at Month 18	-0.81 (1.077)	-0.62 (1.190)
Change at Month 24	-0.82 (1.095)	-0.66 (1.214)
Change at Month 30	-0.83 (1.114)	-0.73 (1.271)
Change at Month 36	-0.84 (1.131)	-0.72 (1.318)
Change at Final Assessment	-0.81 (1.140)	-0.63 (1.381)

3. Secondary Outcome

Title	Change From Baseline in Fasting Blood Glucose
Description	The change in the value of fasting blood glucose collected at month 36 relative to baseline.
Time Frame	Baseline, Months 1, 3, 6, 12, 18, 24, 30, 36 and final assessment (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. Reported group were Alogliptin and Alogliptin + α-GI and data for Alogliptin + Other were not collected as specified in protocol.

Arm/Group Title	Alogliptin	Alogliptin + α-GI
Arm/Group Description	Alogliptin 25 mg, tablets, orally, once daily for up to 36 months in routine medical care. Participants in this group received no diabetic drugs within 3 months from the start of administration of alogliptin and during the treatment period of alogliptin.	Alogliptin 25 mg, tablets, orally, once daily for up to 36 months in routine medical care. Participants in this group received an α-GI within 3 months from the start of administration of alogliptin and during the treatment period of alogliptin.
Measure Participants	510	229
Change at Month 1	-22.9 (45.05)	-4.9 (41.17)
Change at Month 3	-21.7 (39.40)	-8.3 (36.58)
Change at Month 6	-19.1 (36.46)	-14.5 (49.90)
Change at Month 12	-23.1 (43.60)	-18.4 (41.37)
Change at Month 18	-21.1 (41.54)	-16.0 (46.75)
Change at Month 24	-19.9 (42.56)	-14.0 (42.09)
Change at Month 30	-24.4 (39.14)	-11.7 (52.27)
Change at Month 36	-23.0 (45.19)	-18.6 (48.80)
Change at Final Assessment	-24.5 (48.45)	-12.2 (51.25)

Adverse Events

Time Frame	Up to Month 36
Adverse Event Reporting Description	Reported data on Serious Adverse Events were serious adverse drug reactions since only serious adverse drug reactions were collected in this study as specified protocol. Participants may be represented in more than 1 category.
Arm/Group Title	Alogliptin		Alogliptin + αGI		Alogliptin + Other
Arm/Group Description	Alogliptin 25 mg, tablets, orally, once daily for up to 36 months in routine medical care. Participants in this group received no diabetic drugs within 3 months from the start of administration of alogliptin and during the treatment period of alogliptin.		Alogliptin 25 mg, tablets, orally, once daily for up to 36 months in routine medical care. Participants in this group received an α-GI within 3 months from the start of administration of alogliptin and during the treatment period of alogliptin.		Alogliptin 25 mg, tablets, orally, once daily for up to 12 months in routine medical care. Participants in this group did not receive an α-GI within 3 months from the start of administration of alogliptin or during the treatment period of alogliptin.
All Cause Mortality
	Alogliptin		Alogliptin + αGI		Alogliptin + Other
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/1560 (0.1%)		1/669 (0.1%)		2/989 (0.2%)
Serious Adverse Events
	Alogliptin		Alogliptin + αGI		Alogliptin + Other
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/1560 (0.1%)		2/669 (0.3%)		8/989 (0.8%)
Cardiac disorders
Myocardial infarction	0/1560 (0%)		1/669 (0.1%)		1/989 (0.1%)
Gastrointestinal disorders
Intestinal obstruction	0/1560 (0%)		0/669 (0%)		1/989 (0.1%)
General disorders
Sudden death	1/1560 (0.1%)		0/669 (0%)		0/989 (0%)
Death	0/1560 (0%)		0/669 (0%)		1/989 (0.1%)
Injury, poisoning and procedural complications
Fall	1/1560 (0.1%)		0/669 (0%)		0/989 (0%)
Road traffic accident	0/1560 (0%)		0/669 (0%)		1/989 (0.1%)
Tibia fracture	1/1560 (0.1%)		0/669 (0%)		0/989 (0%)
Metabolism and nutrition disorders
Hypoglycaemia	0/1560 (0%)		0/669 (0%)		1/989 (0.1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bile duct cancer	0/1560 (0%)		0/669 (0%)		1/989 (0.1%)
Hepatic neoplasm	0/1560 (0%)		0/669 (0%)		1/989 (0.1%)
Metastases to lymph nodes	0/1560 (0%)		0/669 (0%)		1/989 (0.1%)
Lung neoplasm	0/1560 (0%)		0/669 (0%)		1/989 (0.1%)
Nervous system disorders
Cerebral infarction	0/1560 (0%)		0/669 (0%)		1/989 (0.1%)
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease	0/1560 (0%)		1/669 (0.1%)		0/989 (0%)
Other (Not Including Serious) Adverse Events
	Alogliptin		Alogliptin + αGI		Alogliptin + Other
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	26/1560 (1.7%)		19/669 (2.8%)		23/989 (2.3%)
Hepatobiliary disorders
Hepatic function abnormal	6/1560 (0.4%)		6/669 (0.9%)		6/989 (0.6%)
Vascular disorders
Hypertension	20/1560 (1.3%)		13/669 (1.9%)		17/989 (1.7%)

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.