Alogliptin Tablets Specified Drug-use Survey Type 2 Diabetic Patients Receiving Combination Therapy With a Hypoglycemic Agent (e.g., Insulin Preparations or Rapid-acting Insulin Secretagogues)

Alogliptin (Nesina) Tablets Specified Drug-use Survey Type 2 Diabetes Mellitus: Combination Therapy With Hypoglycemic Drug (Insulin Preparation or Rapid-acting Insulin Secretagogues, Etc)

Status

Completed

Phases

Unknown

Study type

Observational

Source

ClinicalTrials.gov

Registry ID

NCT02221284

Enrollment

964

Registered

2014-08-20

Start date

2014-06-30

Completion date

2017-06-30

Last updated

2019-11-06

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Type 2 Diabetes Mellitus

Keywords

Pharmacological therapy

Brief summary

The purpose of this survey is to evaluate the safety and efficacy of long-term use of alogliptin tablets (Nesina Tablets) in type 2 diabetic patients who have had an inadequate response to hypoglycemic agents (e.g., insulin preparations or rapid-acting insulin secretagogues)\* in addition to dietary/exercise therapy. Participants will receive alogliptin as part of routine medical care. \* Patients receiving these hypoglycemic agents (excluding α-glucosidase inhibitors, thiazolidines, sulfonylureas, and biguanides) were excluded from existing specified drug-use surveys for alogliptin tablets.

Detailed description

This survey was designed to evaluate the safety and efficacy of long-term use of alogliptin tablets (Nesina Tablets) in type 2 diabetic patients who have had an inadequate response to hypoglycemic agents (e.g., insulin preparations or rapid-acting insulin secretagogues) in addition to dietary/exercise therapy. Participants will receive alogliptin as part of routine medical care. For adults, 25 mg of alogliptin is usually administered orally once daily.

Interventions

DRUGAlogliptin

Alogliptin tablets

Study design

Observational model

COHORT

Time perspective

PROSPECTIVE

Eligibility

Sex/Gender

ALL

Healthy volunteers

Inclusion criteria

-Type 2 diabetic patients meeting the following criteria are included in this survey: Patients who have had an inadequate response to the following medications/therapies: • Use of one hypoglycemic agent such as insulin preparations and rapid-acting insulin secretagogues, excluding other types of hypoglycemic agents (e.g., α-glucosidase inhibitors, thiazolidines, sulfonylureas, and biguanides)\*, in addition to dietary/exercise therapy \* For use of alogliptin tablets in combination with these agents, a specified drug-use survey is currently ongoing.

Exclusion criteria

-Type 2 diabetic patients who meet any of the following criteria are excluded from this survey: Patients with contraindications for alogliptin tablets 1. Those with severe ketosis, in a state of diabetic coma or precoma, or with type 1 diabetes mellitus \[Quickly rectifying hyperglycemia with administration of intravenous fluid or insulin is essential in these patients; therefore, administration of alogliptin tablets is not appropriate.\] 2. Those with severe infections, before or after surgery, or with serious trauma \[Controlling blood glucose with an injection of insulin is desirable for these patients; therefore, administration of alogliptin tablets is not appropriate.\] 3. Those with a history of hypersensitivity to any of the ingredients of alogliptin tablets

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Participants Who Had One or More Adverse Reactions	Up to Month 12	Adverse drug reactions are defined as adverse events (AEs) which are in the investigator's opinion of causal relationship to the study treatment. AEs are defined as any unfavorable and unintended signs, symptoms or diseases temporally associated with the use of a medicinal product reported from the first dose of study drug to the last dose of study drug.

Secondary

Measure	Time frame	Description
Number of Participants Achieving Specified HbA1c Level (< 7.0% and <6.0%)	Baseline, and final assessment point (up to Month 12)	The reported data were number of participants who achieved specified HbA1c Level (\< 7.0% and \<6.0%) during this study.
Change From Baseline in Laboratory Test Values (Fasting Blood Glucose Level)	Baseline, and final assessment point (up to Month 12)	The reported data were change from baseline in fasting blood glucose level.
Change From Baseline in Glycosylated Hemoglobin (HbA1c)	Baseline, and final assessment point (up to Month 12)	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 12) relative to baseline.
Change From Baseline in Laboratory Test Values (Homeostasis Model Assessment Ratio [HOMA-R])	Baseline, and final assessment point (up to Month 12)	The reported data were change from baseline in HOMA-R. HOMA-R measures insulin resistance, calculated by fasting insulin (μU/mL) multiplied by fasting glucose (mg/dL), and divided by a constant (405). A higher score indicates higher insulin resistance.
Change From Baseline in Laboratory Test Values (Homeostasis Model Assessment of Beta-cell Function [HOMA-β])	Baseline, and final assessment point (up to Month 12)	The reported data were change from baseline in HOMA-β. HOMA-β measures as following; HOMA-β = fasting insulin (μU/mL) ×360/{fasting glucose (mg/dL) - 63}.
Change From Baseline in Laboratory Test Values (Fasting Insulin Level)	Baseline, and final assessment point (up to Month 12)	The reported data were change from baseline in fasting insulin level.

Countries

Japan

Participant flow

Recruitment details

Participants took part in the study at 196 investigative sites in Japan, from 30 June 2014 to 30 June 2017. Data reports overall population, since data not collected separately per arm as specified in protocol.

Pre-assignment details

Enrolled participants had a diagnosis of type 2 diabetic mellitus and an inadequate response to hypoglycemic agents in addition to dietary/exercise therapy. Participants received interventions as part of routine medical care. Data reports overall population, since data not collected separately per arm as specified in protocol.

Participants by arm

Arm	Count
Alogliptin + Insulin Alogliptin 25 mg, tablets, orally, once daily for up to 12 months, along with insulin preparation within 3 months prior to the start of alogliptin treatment or during the alogliptin treatment period. Participants received interventions as part of routine medical care.	573
Alogliptin + Glinide Alogliptin 25 mg, tablets, orally, once daily for up to 12 months, along with rapid-acting insulin secretagogue (Glinide) within 3 months prior to the start of alogliptin treatment or during the alogliptin treatment period. Participants received interventions as part of routine medical care.	166
Alogliptin + SGLT-2 Inhibitor Alogliptin 25 mg, tablets, orally, once daily for up to 12 months, along with SGLT-2 inhibitor within 3 months prior to the start of alogliptin treatment or during the alogliptin treatment period. Participants received interventions as part of routine medical care.	102
Alogliptin + Other Alogliptin 25 mg, tablets, orally, once daily for up to 12 months, along without insulin preparations, glinide, or SGLT-2 inhibitor within 3 months prior to the start of alogliptin treatment or during the alogliptin treatment period. Participants received interventions as part of routine medical care.	62
Total	903

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Case Report Forms Uncollected	56
Overall Study	Protocol Deviation	5

Baseline characteristics

Characteristic	Alogliptin + Other	Alogliptin + Insulin	Alogliptin + Glinide	Alogliptin + SGLT-2 Inhibitor	Total
Age, Continuous	61.2 Years STANDARD_DEVIATION 14.31	65.6 Years STANDARD_DEVIATION 12.27	67.9 Years STANDARD_DEVIATION 11.71	61.0 Years STANDARD_DEVIATION 13.72	65.2 Years STANDARD_DEVIATION 12.65
BMI	25.90 kg/meter (m)^2 STANDARD_DEVIATION 4.312	24.40 kg/meter (m)^2 STANDARD_DEVIATION 4.037	24.22 kg/meter (m)^2 STANDARD_DEVIATION 3.515	26.71 kg/meter (m)^2 STANDARD_DEVIATION 4.38	24.69 kg/meter (m)^2 STANDARD_DEVIATION 4.065
Concomitant Allergic Condition Had Concomitant Allergic Condition	3 Participants	20 Participants	5 Participants	3 Participants	31 Participants
Concomitant Allergic Condition Had No Concomitant Allergic Condition	59 Participants	553 Participants	161 Participants	99 Participants	872 Participants
Concomitant Cardiac Disease Had Concomitant Cardiac Disease	8 Participants	106 Participants	12 Participants	6 Participants	132 Participants
Concomitant Cardiac Disease Had No Concomitant Cardiac Disease	54 Participants	467 Participants	154 Participants	96 Participants	771 Participants
Concomitant Diabetes Mellitus Had Concomitant Diabetes Mellitus	18 Participants	249 Participants	43 Participants	37 Participants	347 Participants
Concomitant Diabetes Mellitus Had No Concomitant Diabetes Mellitus	44 Participants	324 Participants	123 Participants	65 Participants	556 Participants
Concomitant Heart Failure Had Concomitant Heart Failure	1 Participants	27 Participants	0 Participants	1 Participants	29 Participants
Concomitant Heart Failure Had No Concomitant Heart Failure	61 Participants	546 Participants	166 Participants	101 Participants	874 Participants
Concomitant Hepatic Disorder Had Concomitant Hepatic Disorder	11 Participants	106 Participants	19 Participants	18 Participants	154 Participants
Concomitant Hepatic Disorder Had No Concomitant Hepatic Disorder	51 Participants	467 Participants	147 Participants	84 Participants	749 Participants
Concomitant Hyperlipidemia Had Concomitant Hyperlipidemia	33 Participants	312 Participants	98 Participants	64 Participants	507 Participants
Concomitant Hyperlipidemia Had No Concomitant Hyperlipidemia	29 Participants	261 Participants	68 Participants	38 Participants	396 Participants
Concomitant Hypertension Had Concomitant Hypertension	36 Participants	326 Participants	103 Participants	61 Participants	526 Participants
Concomitant Hypertension Had No Concomitant Hypertension	26 Participants	247 Participants	63 Participants	41 Participants	377 Participants
Concomitant Hyperuricaemia Had Concomitant Hyperuricaemia	2 Participants	51 Participants	21 Participants	9 Participants	83 Participants
Concomitant Hyperuricaemia Had No Concomitant Hyperuricaemia	60 Participants	522 Participants	145 Participants	93 Participants	820 Participants
Concomitant Malignant Tumor Had Concomitant Malignant Tumor	3 Participants	25 Participants	6 Participants	0 Participants	34 Participants
Concomitant Malignant Tumor Had No Concomitant Malignant Tumor	59 Participants	548 Participants	160 Participants	102 Participants	869 Participants
Concomitant Renal Disorder Had Concomitant Renal Disorder	13 Participants	161 Participants	27 Participants	29 Participants	230 Participants
Concomitant Renal Disorder Had No Concomitant Renal Disorder	49 Participants	412 Participants	139 Participants	73 Participants	673 Participants
Concomitant Stroke-Related Disease Had Concomitant Stroke-Related Disease	1 Participants	53 Participants	9 Participants	3 Participants	66 Participants
Concomitant Stroke-Related Disease Had No Concomitant Stroke-Related Disease	61 Participants	520 Participants	157 Participants	99 Participants	837 Participants
Degree of Hepatic Dysfunction Grade 1	4 Participants	25 Participants	7 Participants	5 Participants	41 Participants
Degree of Hepatic Dysfunction Grade 2	1 Participants	4 Participants	3 Participants	5 Participants	13 Participants
Degree of Hepatic Dysfunction Normal	36 Participants	404 Participants	94 Participants	63 Participants	597 Participants
Degree of Hepatic Dysfunction Unknown	21 Participants	140 Participants	62 Participants	29 Participants	252 Participants
Degree of Renal Dysfunction (Cr) Moderate	0 Participants	17 Participants	3 Participants	1 Participants	21 Participants
Degree of Renal Dysfunction (Cr) Moderate or Severe	0 Participants	19 Participants	3 Participants	1 Participants	23 Participants
Degree of Renal Dysfunction (Cr) Normal or Mild	42 Participants	431 Participants	94 Participants	78 Participants	645 Participants
Degree of Renal Dysfunction (Cr) Severe	0 Participants	2 Participants	0 Participants	0 Participants	2 Participants
Degree of Renal Dysfunction (Cr) Unknown	20 Participants	123 Participants	69 Participants	23 Participants	235 Participants
Degree of Renal Dysfunction (eGFR) Mild	22 Participants	235 Participants	38 Participants	38 Participants	333 Participants
Degree of Renal Dysfunction (eGFR) Moderate	4 Participants	118 Participants	28 Participants	18 Participants	168 Participants
Degree of Renal Dysfunction (eGFR) Moderate or Severe	4 Participants	130 Participants	29 Participants	18 Participants	181 Participants
Degree of Renal Dysfunction (eGFR) Normal	16 Participants	85 Participants	30 Participants	23 Participants	154 Participants
Degree of Renal Dysfunction (eGFR) Normal or Mild	38 Participants	320 Participants	68 Participants	61 Participants	487 Participants
Degree of Renal Dysfunction (eGFR) Severe	0 Participants	12 Participants	1 Participants	0 Participants	13 Participants
Degree of Renal Dysfunction (eGFR) Unknown	20 Participants	123 Participants	69 Participants	23 Participants	235 Participants
Drinking Habits No	39 Participants	377 Participants	92 Participants	57 Participants	565 Participants
Drinking Habits Unknown	9 Participants	86 Participants	25 Participants	22 Participants	142 Participants
Drinking Habits Yes	14 Participants	110 Participants	49 Participants	23 Participants	196 Participants
Duration of Diagnosis of Type-2 Diabetes Mellitus (Years)	7.45 Years STANDARD_DEVIATION 6.831	14.24 Years STANDARD_DEVIATION 10.858	9.03 Years STANDARD_DEVIATION 9.058	6.57 Years STANDARD_DEVIATION 6.911	12.26 Years STANDARD_DEVIATION 10.458
Healthcare Category Inpatient	5 Participants	34 Participants	5 Participants	1 Participants	45 Participants
Healthcare Category Outpatient	57 Participants	539 Participants	161 Participants	101 Participants	858 Participants
Height	162.4 Centimeters (cm) STANDARD_DEVIATION 9.02	160.0 Centimeters (cm) STANDARD_DEVIATION 9.7	160.2 Centimeters (cm) STANDARD_DEVIATION 10.12	164.3 Centimeters (cm) STANDARD_DEVIATION 9.38	160.6 Centimeters (cm) STANDARD_DEVIATION 9.78
Hemoglobin A1c (HbA1c)	8.78 Percent STANDARD_DEVIATION 2.053	8.44 Percent STANDARD_DEVIATION 1.662	7.60 Percent STANDARD_DEVIATION 1.051	7.66 Percent STANDARD_DEVIATION 1.379	8.21 Percent STANDARD_DEVIATION 1.612
Medical Complications Had Medical Complications	48 Participants	504 Participants	148 Participants	81 Participants	781 Participants
Medical Complications Had No Medical Complications	14 Participants	69 Participants	18 Participants	21 Participants	122 Participants
Medical History Had Medical History	12 Participants	125 Participants	28 Participants	5 Participants	170 Participants
Medical History Had No Medical History	47 Participants	411 Participants	123 Participants	95 Participants	676 Participants
Medical History Unknown	3 Participants	37 Participants	15 Participants	2 Participants	57 Participants
New York Heart Association (NYHA) Heart Failure Classification Class I	1 Participants	15 Participants	0 Participants	0 Participants	16 Participants
New York Heart Association (NYHA) Heart Failure Classification Class II	0 Participants	9 Participants	0 Participants	1 Participants	10 Participants
New York Heart Association (NYHA) Heart Failure Classification Unknown	0 Participants	3 Participants	0 Participants	0 Participants	3 Participants
Predisposition to Hypersensitivity Had No Predisposition to Hypersensitivity	56 Participants	508 Participants	141 Participants	98 Participants	803 Participants
Predisposition to Hypersensitivity Had Predisposition to Hypersensitivity	4 Participants	33 Participants	11 Participants	3 Participants	51 Participants
Predisposition to Hypersensitivity Unknown	2 Participants	32 Participants	14 Participants	1 Participants	49 Participants
Race and Ethnicity Not Collected	—	—	—	—	0 Participants
Region of Enrollment Japan	62 Participants	573 Participants	166 Participants	102 Participants	903 Participants
Sex: Female, Male Female	26 Participants	257 Participants	67 Participants	35 Participants	385 Participants
Sex: Female, Male Male	36 Participants	316 Participants	99 Participants	67 Participants	518 Participants
Smoking Classification Current Smoker	16 Participants	64 Participants	31 Participants	15 Participants	126 Participants
Smoking Classification Ex-Smoker	10 Participants	103 Participants	45 Participants	19 Participants	177 Participants
Smoking Classification Never Smoked	25 Participants	289 Participants	65 Participants	43 Participants	422 Participants
Smoking Classification Unknown	11 Participants	117 Participants	25 Participants	25 Participants	178 Participants
Waist Circumference (Female) < 90 cm	1 Participants	25 Participants	13 Participants	2 Participants	41 Participants
Waist Circumference (Female) >= 90 cm	1 Participants	15 Participants	3 Participants	2 Participants	21 Participants
Waist Circumference (Female) Unknown	24 Participants	217 Participants	51 Participants	31 Participants	323 Participants
Waist Circumference (Male) < 85 cm	1 Participants	15 Participants	12 Participants	2 Participants	30 Participants
Waist Circumference (Male) >= 85 cm	5 Participants	22 Participants	17 Participants	9 Participants	53 Participants
Waist Circumference (Male) Unknown	30 Participants	279 Participants	70 Participants	56 Participants	435 Participants
Weight	68.32 Kilograms (kg) STANDARD_DEVIATION 14.248	62.57 Kilograms (kg) STANDARD_DEVIATION 12.91	62.45 Kilograms (kg) STANDARD_DEVIATION 13.141	72.37 Kilograms (kg) STANDARD_DEVIATION 14.654	64.11 Kilograms (kg) STANDARD_DEVIATION 13.667

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk
deaths Total, all-cause mortality	3 / 573	0 / 166	0 / 102	0 / 62
other Total, other adverse events	10 / 573	2 / 166	0 / 102	0 / 62
serious Total, serious adverse events	3 / 573	0 / 166	0 / 102	0 / 62

Outcome results

Primary

Percentage of Participants Who Had One or More Adverse Reactions

Adverse drug reactions are defined as adverse events (AEs) which are in the investigator's opinion of causal relationship to the study treatment. AEs are defined as any unfavorable and unintended signs, symptoms or diseases temporally associated with the use of a medicinal product reported from the first dose of study drug to the last dose of study drug.

Time frame: Up to Month 12

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

Arm	Measure	Value (NUMBER)
Alogliptin + Insulin	Percentage of Participants Who Had One or More Adverse Reactions	5.41 Percentage of Participants
Alogliptin + Glinide	Percentage of Participants Who Had One or More Adverse Reactions	1.20 Percentage of Participants
Alogliptin + SGLT-2 Inhibitor	Percentage of Participants Who Had One or More Adverse Reactions	0.98 Percentage of Participants
Alogliptin + Other	Percentage of Participants Who Had One or More Adverse Reactions	0.00 Percentage of Participants

Secondary

Change From Baseline in Glycosylated Hemoglobin (HbA1c)

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 12) relative to baseline.