Trial Outcomes & Findings for Alogliptin/Pioglitazone (Liovel) Combination Tablets Survey on Long-term Use in Patients With Type 2 Diabetes Mellitus (NCT NCT01990300)
NCT ID: NCT01990300
Last Updated: 2023-09-18
Results Overview
Recruitment status
COMPLETED
Target enrollment
3281 participants
Primary outcome timeframe
Up to 12 Months
Results posted on
2023-09-18
Participant Flow
Participants took part in the study at 445 investigative sites in Japan, from 28 November 2011 to 31 March 2015.
Participants with a historical diagnosis of type 2 diabetes mellitus were enrolled to receive Alogliptin/Pioglitazone 25 milligram (mg)/ 15 mg or 25 mg / 30 mg combination tablet orally, once daily for up to 12 months.
Participant milestones
| Measure |
Alogliptin/Pioglitazone
Alogliptin/Pioglitazone 25 mg/ 15 mg or 25 mg/ 30 mg combination tablet, orally, once daily for up to 12 months in participants based upon the disease severity. Participants received interventions as part of routine medical care.
|
|---|---|
|
Overall Study
STARTED
|
3281
|
|
Overall Study
COMPLETED
|
3139
|
|
Overall Study
NOT COMPLETED
|
142
|
Reasons for withdrawal
| Measure |
Alogliptin/Pioglitazone
Alogliptin/Pioglitazone 25 mg/ 15 mg or 25 mg/ 30 mg combination tablet, orally, once daily for up to 12 months in participants based upon the disease severity. Participants received interventions as part of routine medical care.
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|---|---|
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Overall Study
Case Report Forms Uncollected
|
89
|
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Overall Study
Protocol Deviation
|
53
|
Baseline Characteristics
The number analyzed is the number of participants with data available for analysis.
Baseline characteristics by cohort
| Measure |
Alogliptin/Pioglitazone
n=3139 Participants
Alogliptin/Pioglitazone 25 mg/ 15 mg or 25 mg/ 30 mg combination tablet, orally, once daily for up to 12 months in participants based upon the disease severity. Participants received interventions as part of routine medical care.
|
|---|---|
|
Age, Continuous
|
64.7 Years
STANDARD_DEVIATION 11.78 • n=3139 Participants
|
|
Sex: Female, Male
Female
|
1188 Participants
n=3139 Participants
|
|
Sex: Female, Male
Male
|
1951 Participants
n=3139 Participants
|
|
Region of Enrollment
Japan
|
3139 Participants
n=3139 Participants
|
|
Duration of Type 2 Diabetes Mellitus
|
7.56 Years
STANDARD_DEVIATION 6.950 • n=2689 Participants • The number analyzed is the number of participants with data available for analysis.
|
|
Weight
|
68.87 kilograms (kg)
STANDARD_DEVIATION 15.094 • n=1982 Participants • The number analyzed is the number of participants with data available for analysis.
|
|
BMI
|
26.49 kg/m^2
STANDARD_DEVIATION 4.592 • n=1847 Participants • The number analyzed is the number of participants with data available for analysis.
|
|
Waist Circumference (Male)
<85 centimeter (cm)
|
108 Participants
n=1951 Participants • This baseline characteristic was analyzed only in male participants.
|
|
Waist Circumference (Male)
≥85cm
|
317 Participants
n=1951 Participants • This baseline characteristic was analyzed only in male participants.
|
|
Waist Circumference (Male)
Unknown
|
1526 Participants
n=1951 Participants • This baseline characteristic was analyzed only in male participants.
|
|
Waist Circumference (Female)
<90cm
|
146 Participants
n=1188 Participants • This baseline characteristic was analyzed only in female participants.
|
|
Waist Circumference (Female)
≥90cm
|
128 Participants
n=1188 Participants • This baseline characteristic was analyzed only in female participants.
|
|
Waist Circumference (Female)
Unknown
|
914 Participants
n=1188 Participants • This baseline characteristic was analyzed only in female participants.
|
|
Healthcare Category
Outpatient
|
3113 Participants
n=3139 Participants
|
|
Healthcare Category
Inpatient
|
26 Participants
n=3139 Participants
|
|
Pregnancy Status (Not Pregnant)
|
1188 Participants
n=1188 Participants • This baseline characteristic was analyzed only in female participants.
|
|
Medical Complications
Had No Presence of Medical Complications
|
441 Participants
n=3139 Participants
|
|
Medical Complications
Had Presence of Medical Complications
|
2698 Participants
n=3139 Participants
|
|
Diabetic Complications
Had No Presence of Diabetic Complications
|
2621 Participants
n=3139 Participants
|
|
Diabetic Complications
Had Presence of Diabetic Complications
|
518 Participants
n=3139 Participants
|
|
Concomitant Lifestyle-Related Disease
Had No Concomitant Lifestyle-Related Disease
|
583 Participants
n=3139 Participants
|
|
Concomitant Lifestyle-Related Disease
Had Concomitant Lifestyle-Related Disease
|
2556 Participants
n=3139 Participants
|
|
Concomitant Hepatic Disorder
Had No Concomitant Hepatic Disorder
|
2662 Participants
n=3139 Participants
|
|
Concomitant Hepatic Disorder
Had Concomitant Hepatic Disorder
|
477 Participants
n=3139 Participants
|
|
Degree of Hepatic Dysfunction
Normal
|
1765 Participants
n=3139 Participants
|
|
Degree of Hepatic Dysfunction
Grade 1
|
216 Participants
n=3139 Participants
|
|
Degree of Hepatic Dysfunction
Grade 2
|
40 Participants
n=3139 Participants
|
|
Degree of Hepatic Dysfunction
Grade 3
|
1 Participants
n=3139 Participants
|
|
Degree of Hepatic Dysfunction
Unknown
|
1117 Participants
n=3139 Participants
|
|
Concomitant Renal Disorder
Had No Concomitant Renal Disorder
|
2760 Participants
n=3139 Participants
|
|
Concomitant Renal Disorder
Had Concomitant Renal Disorder
|
379 Participants
n=3139 Participants
|
|
Degree of Renal Dysfunction (eGFR)
Normal
|
462 Participants
n=3139 Participants
|
|
Degree of Renal Dysfunction (eGFR)
Mild
|
1090 Participants
n=3139 Participants
|
|
Degree of Renal Dysfunction (eGFR)
Moderate
|
411 Participants
n=3139 Participants
|
|
Degree of Renal Dysfunction (eGFR)
Severe
|
21 Participants
n=3139 Participants
|
|
Degree of Renal Dysfunction (eGFR)
Unknown
|
1155 Participants
n=3139 Participants
|
|
Degree of Renal Dysfunction (Cr)
Normal or Mild
|
1933 Participants
n=3139 Participants
|
|
Degree of Renal Dysfunction (Cr)
Moderate
|
49 Participants
n=3139 Participants
|
|
Degree of Renal Dysfunction (Cr)
Severe
|
2 Participants
n=3139 Participants
|
|
Degree of Renal Dysfunction (Cr)
Unknown
|
1155 Participants
n=3139 Participants
|
|
Concomitant Cardiac Disease
Had No Concomitant Cardiac Disease
|
2828 Participants
n=3139 Participants
|
|
Concomitant Cardiac Disease
Had Concomitant Cardiac Disease
|
311 Participants
n=3139 Participants
|
|
Concomitant Heart Failure
Had No Concomitant Heart Failure
|
3134 Participants
n=3139 Participants
|
|
Concomitant Heart Failure
Had Concomitant Heart Failure
|
5 Participants
n=3139 Participants
|
|
New York Heart Association (NYHA) Heart Failure Classification
Class I
|
3 Participants
n=4 Participants • The baseline measure was analyzed only for participants who had complications of heart failure. Data of one participant was not collected throughout this study.
|
|
New York Heart Association (NYHA) Heart Failure Classification
Class II
|
1 Participants
n=4 Participants • The baseline measure was analyzed only for participants who had complications of heart failure. Data of one participant was not collected throughout this study.
|
|
Concomitant Stroke-Related Disease
Had No Concomitant Stroke-Related Disease
|
2979 Participants
n=3139 Participants
|
|
Concomitant Stroke-Related Disease
Had Concomitant Stroke-Related Disease
|
160 Participants
n=3139 Participants
|
|
Concomitant Allergic Condition
Had No Concomitant Allergic Condition
|
2954 Participants
n=3139 Participants
|
|
Concomitant Allergic Condition
Had Concomitant Allergic Condition
|
185 Participants
n=3139 Participants
|
|
Concomitant Malignant Tumor
Had No Concomitant Malignant Tumor
|
3092 Participants
n=3139 Participants
|
|
Concomitant Malignant Tumor
Had Concomitant Malignant Tumor
|
47 Participants
n=3139 Participants
|
|
Medical History
Had No Presence of Medical History
|
2523 Participants
n=3139 Participants
|
|
Medical History
Had Presence of Medical History
|
347 Participants
n=3139 Participants
|
|
Medical History
Unknown
|
269 Participants
n=3139 Participants
|
|
Predisposition to Hypersensitivity
Had No Predisposition to Hypersensitivity
|
2735 Participants
n=3139 Participants
|
|
Predisposition to Hypersensitivity
Had Predisposition to Hypersensitivity
|
119 Participants
n=3139 Participants
|
|
Predisposition to Hypersensitivity
Unknown
|
285 Participants
n=3139 Participants
|
|
Drinking Habits
Current Drinker
|
900 Participants
n=3139 Participants
|
|
Drinking Habits
Never Drank or Ex Drinker
|
1538 Participants
n=3139 Participants
|
|
Drinking Habits
Unknown
|
701 Participants
n=3139 Participants
|
|
Smoking Classification
Never Smoked
|
1260 Participants
n=3139 Participants
|
|
Smoking Classification
Current Smoker
|
480 Participants
n=3139 Participants
|
|
Smoking Classification
Ex-Smoker
|
557 Participants
n=3139 Participants
|
|
Smoking Classification
Unknown
|
842 Participants
n=3139 Participants
|
|
Haemoglobin A1c (HbA1c) [National Glycohemoglobin Standardization Program (NGSP)]
|
7.63 Percent HbA1c
STANDARD_DEVIATION 1.276 • n=2909 Participants • The number analyzed is the number of participants with data available for analysis.
|
|
Alogliptin Status
Had No Doses of Alogliptin
|
2092 Participants
n=3139 Participants
|
|
Alogliptin Status
Had Doses of Alogliptin
|
1047 Participants
n=3139 Participants
|
|
Pioglitazone Status
Had No Doses of Pioglitazone
|
1402 Participants
n=3139 Participants
|
|
Pioglitazone Status
Had Doses of Pioglitazone
|
1737 Participants
n=3139 Participants
|
PRIMARY outcome
Timeframe: Up to 12 MonthsPopulation: The safety analysis set was defined as all participants who were enrolled and completed the study.
Outcome measures
| Measure |
Alogliptin/Pioglitazone
n=3139 Participants
Alogliptin/Pioglitazone 25 mg/ 15 mg or 25 mg/ 30 mg combination tablet, orally, once daily for up to 12 months in participants based upon the disease severity. Participants received interventions as part of routine medical care.
|
|---|---|
|
Number of Participants Who Experience at Least One Adverse Events
|
206 Participants
|
PRIMARY outcome
Timeframe: Baseline and Month 1, 3, 6, 12 and final assessment (up to 12 Months)Population: The efficacy assessment population was defined as participants who completed the study and had efficacy data at baseline and post-baseline time points available. The number analyzed is the number of participants with data available for analysis at the given time-point.
Reported data are changes in HbA1c from baseline at Month 1, 3, 6, 12 and final assessment (up to 12 months).
Outcome measures
| Measure |
Alogliptin/Pioglitazone
n=2830 Participants
Alogliptin/Pioglitazone 25 mg/ 15 mg or 25 mg/ 30 mg combination tablet, orally, once daily for up to 12 months in participants based upon the disease severity. Participants received interventions as part of routine medical care.
|
|---|---|
|
Changes From Baseline in Glycosylated Hemoglobin (HbA1c)
Change in HbA1c at Month 1
|
-0.26 Percent HbA1c
Standard Deviation 0.651
|
|
Changes From Baseline in Glycosylated Hemoglobin (HbA1c)
Change in HbA1c at Month 3
|
-0.58 Percent HbA1c
Standard Deviation 0.991
|
|
Changes From Baseline in Glycosylated Hemoglobin (HbA1c)
Change in HbA1c at Month 6
|
-0.66 Percent HbA1c
Standard Deviation 1.081
|
|
Changes From Baseline in Glycosylated Hemoglobin (HbA1c)
Change in HbA1c at Month 12
|
-0.66 Percent HbA1c
Standard Deviation 1.098
|
|
Changes From Baseline in Glycosylated Hemoglobin (HbA1c)
Change in HbA1c at Final Assessment
|
-0.65 Percent HbA1c
Standard Deviation 1.121
|
SECONDARY outcome
Timeframe: Baseline and Month 1, 3, 6, 12 and final assessment (up to 12 Months)Population: The efficacy assessment population was defined as participants who completed the study and had efficacy data at baseline and post-baseline time points available. The number analyzed is the number of participants with data available for analysis at the given time-point.
Reported data are changes in fasting blood glucose level from baseline at Month 1, 3, 6, 12 and final assessment (up to 12 months).
Outcome measures
| Measure |
Alogliptin/Pioglitazone
n=1554 Participants
Alogliptin/Pioglitazone 25 mg/ 15 mg or 25 mg/ 30 mg combination tablet, orally, once daily for up to 12 months in participants based upon the disease severity. Participants received interventions as part of routine medical care.
|
|---|---|
|
Changes From Baseline in Fasting Blood Glucose (FBG)
Change in FBG at Month 1
|
-14.7 mg/dL
Standard Deviation 49.34
|
|
Changes From Baseline in Fasting Blood Glucose (FBG)
Change in FBG at Month 3
|
-18.7 mg/dL
Standard Deviation 50.24
|
|
Changes From Baseline in Fasting Blood Glucose (FBG)
Change in FBG at Month 6
|
-18.4 mg/dL
Standard Deviation 50.51
|
|
Changes From Baseline in Fasting Blood Glucose (FBG)
Change in FBG at Month 12
|
-19.6 mg/dL
Standard Deviation 50.93
|
|
Changes From Baseline in Fasting Blood Glucose (FBG)
Change in FBG at Final Assessment
|
-19.8 mg/dL
Standard Deviation 53.31
|
Adverse Events
Alogliptin/Pioglitazone
Serious events: 4 serious events
Other events: 56 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Alogliptin/Pioglitazone
n=3139 participants at risk
Alogliptin/Pioglitazone 25 mg/ 15 mg or 25 mg/ 30 mg combination tablet, orally, once daily for up to 12 months in participants based upon the disease severity. Participants received interventions as part of routine medical care.
|
|---|---|
|
Infections and infestations
Pneumonia
|
0.03%
1/3139 • Up to Month 12
At each visit the investigator had to document any occurrence of adverse drug reactions (ADRs). Any events reported by the participant or observed by the investigator were recorded, irrespective of the relation to study treatment. Only ADRs were collected in this study. Participants may be represented in more than 1 category.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm malignant
|
0.03%
1/3139 • Up to Month 12
At each visit the investigator had to document any occurrence of adverse drug reactions (ADRs). Any events reported by the participant or observed by the investigator were recorded, irrespective of the relation to study treatment. Only ADRs were collected in this study. Participants may be represented in more than 1 category.
|
|
General disorders
Death
|
0.03%
1/3139 • Up to Month 12
At each visit the investigator had to document any occurrence of adverse drug reactions (ADRs). Any events reported by the participant or observed by the investigator were recorded, irrespective of the relation to study treatment. Only ADRs were collected in this study. Participants may be represented in more than 1 category.
|
|
Injury, poisoning and procedural complications
Spinal compression fracture
|
0.03%
1/3139 • Up to Month 12
At each visit the investigator had to document any occurrence of adverse drug reactions (ADRs). Any events reported by the participant or observed by the investigator were recorded, irrespective of the relation to study treatment. Only ADRs were collected in this study. Participants may be represented in more than 1 category.
|
Other adverse events
| Measure |
Alogliptin/Pioglitazone
n=3139 participants at risk
Alogliptin/Pioglitazone 25 mg/ 15 mg or 25 mg/ 30 mg combination tablet, orally, once daily for up to 12 months in participants based upon the disease severity. Participants received interventions as part of routine medical care.
|
|---|---|
|
General disorders
Oedema
|
1.0%
32/3139 • Up to Month 12
At each visit the investigator had to document any occurrence of adverse drug reactions (ADRs). Any events reported by the participant or observed by the investigator were recorded, irrespective of the relation to study treatment. Only ADRs were collected in this study. Participants may be represented in more than 1 category.
|
|
General disorders
Oedema peripheral
|
0.25%
8/3139 • Up to Month 12
At each visit the investigator had to document any occurrence of adverse drug reactions (ADRs). Any events reported by the participant or observed by the investigator were recorded, irrespective of the relation to study treatment. Only ADRs were collected in this study. Participants may be represented in more than 1 category.
|
|
Investigations
Weight increased
|
0.35%
11/3139 • Up to Month 12
At each visit the investigator had to document any occurrence of adverse drug reactions (ADRs). Any events reported by the participant or observed by the investigator were recorded, irrespective of the relation to study treatment. Only ADRs were collected in this study. Participants may be represented in more than 1 category.
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.16%
5/3139 • Up to Month 12
At each visit the investigator had to document any occurrence of adverse drug reactions (ADRs). Any events reported by the participant or observed by the investigator were recorded, irrespective of the relation to study treatment. Only ADRs were collected in this study. Participants may be represented in more than 1 category.
|
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