Trial Outcomes & Findings for Specified Drug-Use Survey of Alogliptin and Metformin Hydrochloride Combination Tablets "Survey on Long-term Use in Type 2 Diabetes Mellitus Patients With Renal or Hepatic Impairment or Advanced Age" (NCT NCT03555565)
NCT ID: NCT03555565
Last Updated: 2023-09-13
Results Overview
An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.
Recruitment status
COMPLETED
Target enrollment
1026 participants
Primary outcome timeframe
Up to 12 months
Results posted on
2023-09-13
Participant Flow
Participants took part in the survey at 115 investigative sites in Japan, from 28 February 2017 to 31 October 2019.
Participants with a historical diagnosis of type 2 diabetes mellitus with renal or hepatic impairment or advanced age were enrolled. Participants received alogliptin and metformin hydrochloride combination tablets as part of a routine medical care.
Participant milestones
| Measure |
Alogliptin and Metformin Hydrochloride
Alogliptin 25 mg and metformin hydrochloride 500 mg, combination tablet, orally, once daily for up to 12 months. Participants received interventions as part of routine medical care.
|
|---|---|
|
Overall Study
STARTED
|
1026
|
|
Overall Study
COMPLETED
|
1011
|
|
Overall Study
NOT COMPLETED
|
15
|
Reasons for withdrawal
| Measure |
Alogliptin and Metformin Hydrochloride
Alogliptin 25 mg and metformin hydrochloride 500 mg, combination tablet, orally, once daily for up to 12 months. Participants received interventions as part of routine medical care.
|
|---|---|
|
Overall Study
Case Report Forms Uncollected
|
2
|
|
Overall Study
Protocol Deviation
|
13
|
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
Alogliptin and Metformin Hydrochloride
n=1011 Participants
Alogliptin 25 mg and metformin hydrochloride 500 mg, combination tablet, orally, once daily for up to 12 months. Participants received interventions as part of routine medical care.
|
|---|---|
|
Age, Continuous
|
68.0 Years
STANDARD_DEVIATION 11.33 • n=1011 Participants
|
|
Sex: Female, Male
Female
|
402 Participants
n=1011 Participants
|
|
Sex: Female, Male
Male
|
609 Participants
n=1011 Participants
|
|
Region of Enrollment
Japan
|
1011 Participants
n=1011 Participants
|
|
Duration of Diagnosis of Type 2 Diabetes Mellitus
|
8.64 Years
STANDARD_DEVIATION 7.297 • n=663 Participants • The number analyzed is the number of participants with data available for analysis.
|
|
Weight
|
66.13 Kilograms (kg)
STANDARD_DEVIATION 13.640 • n=692 Participants • The number analyzed is the number of participants with data available for analysis.
|
|
BMI
|
25.47 Kilogram (kg)/meter (m)^2
STANDARD_DEVIATION 3.996 • n=640 Participants • The number analyzed is the number of participants with data available for analysis.
|
|
Renal Impairment
Had No Renal Impairment
|
638 Participants
n=1011 Participants
|
|
Renal Impairment
Had Renal Impairment
|
373 Participants
n=1011 Participants
|
|
Hepatic Impairment
Had No Hepatic Impairment
|
545 Participants
n=1011 Participants
|
|
Hepatic Impairment
Had Hepatic Impairment
|
466 Participants
n=1011 Participants
|
|
Healthcare Category
Outpatient
|
1006 Participants
n=1011 Participants
|
|
Healthcare Category
Inpatient
|
5 Participants
n=1011 Participants
|
|
Predisposition to Hypersensitivity
Had No Predisposition to Hypersensitivity
|
826 Participants
n=1011 Participants
|
|
Predisposition to Hypersensitivity
Had Predisposition to Hypersensitivity
|
82 Participants
n=1011 Participants
|
|
Predisposition to Hypersensitivity
Unknown
|
103 Participants
n=1011 Participants
|
|
Medical Complications
Had No Medical Complications
|
56 Participants
n=1011 Participants
|
|
Medical Complications
Had Medical Complications
|
955 Participants
n=1011 Participants
|
|
Medical History
Had No Medical History
|
629 Participants
n=1011 Participants
|
|
Medical History
Had Medical History
|
267 Participants
n=1011 Participants
|
|
Medical History
Unknown
|
115 Participants
n=1011 Participants
|
|
Smoking Classification
Never Smoked
|
417 Participants
n=1011 Participants
|
|
Smoking Classification
Current Smoker
|
156 Participants
n=1011 Participants
|
|
Smoking Classification
Ex-Smoker
|
216 Participants
n=1011 Participants
|
|
Smoking Classification
Unknown
|
222 Participants
n=1011 Participants
|
|
Drinking Habits
Yes
|
246 Participants
n=1011 Participants
|
|
Drinking Habits
No
|
570 Participants
n=1011 Participants
|
|
Drinking Habits
Unknown
|
195 Participants
n=1011 Participants
|
|
Employment Status
Not Employed
|
495 Participants
n=1011 Participants
|
|
Employment Status
Employed
|
390 Participants
n=1011 Participants
|
|
Employment Status
Unknown
|
126 Participants
n=1011 Participants
|
|
Hemoglobin A1c (HbA1c) Level
|
7.336 Percent
STANDARD_DEVIATION 1.0710 • n=912 Participants • The number analyzed is the number of participants with data available for analysis.
|
|
Alogliptin-Equivalent Dose per Day Given Immediate Before the Study Drug
< 25 milligrams (mg)
|
14 Participants
n=576 Participants • The number analyzed is the number of participants with data available for analysis.
|
|
Alogliptin-Equivalent Dose per Day Given Immediate Before the Study Drug
25 mg
|
561 Participants
n=576 Participants • The number analyzed is the number of participants with data available for analysis.
|
|
Alogliptin-Equivalent Dose per Day Given Immediate Before the Study Drug
> 25 mg
|
1 Participants
n=576 Participants • The number analyzed is the number of participants with data available for analysis.
|
|
Metformin-Equivalent Dose per Day Given Immediately Before the Study Drug
< 500 mg
|
36 Participants
n=730 Participants • The number analyzed is the number of participants with data available for analysis.
|
|
Metformin-Equivalent Dose per Day Given Immediately Before the Study Drug
500 mg
|
505 Participants
n=730 Participants • The number analyzed is the number of participants with data available for analysis.
|
|
Metformin-Equivalent Dose per Day Given Immediately Before the Study Drug
> 500 mg
|
189 Participants
n=730 Participants • The number analyzed is the number of participants with data available for analysis.
|
|
Combination of Drugs for Type 2 Diabetes Mellitus Other than Alogliptin or Metformin
Not Combined
|
401 Participants
n=1011 Participants
|
|
Combination of Drugs for Type 2 Diabetes Mellitus Other than Alogliptin or Metformin
Combined
|
610 Participants
n=1011 Participants
|
|
Status of Treatment Compliance to Alogliptin Medication Within 3 Months prior to the Study Drug
≥ 90%
|
487 Participants
n=558 Participants • The number analyzed is the number of participants with data available for analysis.
|
|
Status of Treatment Compliance to Alogliptin Medication Within 3 Months prior to the Study Drug
≥ 70% and < 90%
|
46 Participants
n=558 Participants • The number analyzed is the number of participants with data available for analysis.
|
|
Status of Treatment Compliance to Alogliptin Medication Within 3 Months prior to the Study Drug
≥ 50% and < 70%
|
8 Participants
n=558 Participants • The number analyzed is the number of participants with data available for analysis.
|
|
Status of Treatment Compliance to Alogliptin Medication Within 3 Months prior to the Study Drug
< 50%
|
17 Participants
n=558 Participants • The number analyzed is the number of participants with data available for analysis.
|
|
Status of Treatment Compliance to Metformin Medication Within 3 Months prior to the Study Drug
≥ 90%
|
618 Participants
n=717 Participants • The number analyzed is the number of participants with data available for analysis.
|
|
Status of Treatment Compliance to Metformin Medication Within 3 Months prior to the Study Drug
≥ 70% and < 90%
|
67 Participants
n=717 Participants • The number analyzed is the number of participants with data available for analysis.
|
|
Status of Treatment Compliance to Metformin Medication Within 3 Months prior to the Study Drug
≥ 50% and < 70%
|
17 Participants
n=717 Participants • The number analyzed is the number of participants with data available for analysis.
|
|
Status of Treatment Compliance to Metformin Medication Within 3 Months prior to the Study Drug
< 50%
|
15 Participants
n=717 Participants • The number analyzed is the number of participants with data available for analysis.
|
PRIMARY outcome
Timeframe: Up to 12 monthsPopulation: Safety Analysis Set, The safety analysis set was defined as all participants who completed the survey.
An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.
Outcome measures
| Measure |
Alogliptin and Metformin Hydrochloride
n=1011 Participants
Alogliptin 25 mg and metformin hydrochloride 500 mg, combination tablet, orally, once daily for up to 12 months. Participants received interventions as part of routine medical care.
|
|---|---|
|
Percentage of Participants Who Had One or More Adverse Events
|
5.93 Percentage of Participants
|
SECONDARY outcome
Timeframe: Baseline, up to final assessment point (up to Month 12)Population: Efficacy assessment population, The efficacy assessment population was defined as participants who completed the survey and had efficacy data at baseline and post-baseline time points available.
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.
Outcome measures
| Measure |
Alogliptin and Metformin Hydrochloride
n=897 Participants
Alogliptin 25 mg and metformin hydrochloride 500 mg, combination tablet, orally, once daily for up to 12 months. Participants received interventions as part of routine medical care.
|
|---|---|
|
Change From Baseline in Glycosylated Hemoglobin (HbA1c)
|
-0.259 Percent
Standard Deviation 0.9633
|
SECONDARY outcome
Timeframe: Baseline, up to final assessment point (up to Month 12)Population: Efficacy assessment population, The efficacy assessment population was defined as participants who completed the survey and had efficacy data at baseline and post-baseline time points available.
The change in the value of fasting blood glucose collected at final assessment point (up to Month 12) relative to baseline.
Outcome measures
| Measure |
Alogliptin and Metformin Hydrochloride
n=468 Participants
Alogliptin 25 mg and metformin hydrochloride 500 mg, combination tablet, orally, once daily for up to 12 months. Participants received interventions as part of routine medical care.
|
|---|---|
|
Change From Baseline in Fasting Blood Glucose
|
-12.08 milligram/deciliter (mg/dL)
Standard Deviation 46.784
|
SECONDARY outcome
Timeframe: Baseline, up to final assessment point (up to Month 12)Population: Efficacy assessment population, The efficacy assessment population was defined as participants who completed the survey and had efficacy data at baseline and post-baseline time points available.
The change in the value of fasting insulin collected at final assessment point (up to Month 12) relative to baseline.
Outcome measures
| Measure |
Alogliptin and Metformin Hydrochloride
n=34 Participants
Alogliptin 25 mg and metformin hydrochloride 500 mg, combination tablet, orally, once daily for up to 12 months. Participants received interventions as part of routine medical care.
|
|---|---|
|
Change From Baseline in Fasting Insulin Level
|
1.21 microunit/milliliter (mcrU/mL)
Standard Deviation 13.852
|
Adverse Events
Alogliptin and Metformin Hydrochloride
Serious events: 4 serious events
Other events: 13 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
Alogliptin and Metformin Hydrochloride
n=1011 participants at risk
Alogliptin 25 mg and metformin hydrochloride 500 mg, combination tablet, orally, once daily for up to 12 months. Participants received interventions as part of routine medical care.
|
|---|---|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hepatocellular carcinoma
|
0.10%
1/1011 • Up to 12 months
At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to the survey treatment.
|
|
Cardiac disorders
Atrial fibrillation
|
0.10%
1/1011 • Up to 12 months
At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to the survey treatment.
|
|
Vascular disorders
Deep vein thrombosis
|
0.10%
1/1011 • Up to 12 months
At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to the survey treatment.
|
|
Gastrointestinal disorders
Large intestine polyp
|
0.10%
1/1011 • Up to 12 months
At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to the survey treatment.
|
Other adverse events
| Measure |
Alogliptin and Metformin Hydrochloride
n=1011 participants at risk
Alogliptin 25 mg and metformin hydrochloride 500 mg, combination tablet, orally, once daily for up to 12 months. Participants received interventions as part of routine medical care.
|
|---|---|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.10%
1/1011 • Up to 12 months
At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to the survey treatment.
|
|
Nervous system disorders
Dizziness
|
0.10%
1/1011 • Up to 12 months
At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to the survey treatment.
|
|
Cardiac disorders
Bundle branch block right
|
0.10%
1/1011 • Up to 12 months
At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to the survey treatment.
|
|
Cardiac disorders
Palpitations
|
0.10%
1/1011 • Up to 12 months
At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to the survey treatment.
|
|
Gastrointestinal disorders
Chronic gastritis
|
0.10%
1/1011 • Up to 12 months
At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to the survey treatment.
|
|
Gastrointestinal disorders
Constipation
|
0.10%
1/1011 • Up to 12 months
At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to the survey treatment.
|
|
Skin and subcutaneous tissue disorders
Cold sweat
|
0.10%
1/1011 • Up to 12 months
At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to the survey treatment.
|
|
Skin and subcutaneous tissue disorders
Drug eruption
|
0.10%
1/1011 • Up to 12 months
At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to the survey treatment.
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.10%
1/1011 • Up to 12 months
At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to the survey treatment.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.10%
1/1011 • Up to 12 months
At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to the survey treatment.
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
0.10%
1/1011 • Up to 12 months
At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to the survey treatment.
|
|
Renal and urinary disorders
Renal disorder
|
0.10%
1/1011 • Up to 12 months
At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to the survey treatment.
|
|
General disorders
Malaise
|
0.10%
1/1011 • Up to 12 months
At each visit the investigator had to document any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to the survey treatment.
|
Additional Information
Study Director
Takeda (Note: This product was divested to Teijin Pharma Limited in 2023)
Phone: +1-877-825-3327
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER