Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Alogliptin/Pioglitazone (Liovel) Combination Tablets Survey on Long-term Use in Patients With Type 2 Diabetes Mellitus

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01990300
Recruitment Status : Completed
First Posted : November 21, 2013
Results First Posted : January 18, 2019
Last Update Posted : January 18, 2019
Sponsor:
Information provided by (Responsible Party):
Takeda

Study Type Observational
Study Design Observational Model: Cohort;   Time Perspective: Prospective
Condition Type 2 Diabetes Mellitus
Intervention Drug: Alogliptin/Pioglitazone
Enrollment 3281
Recruitment Details Participants took part in the study at 445 investigative sites in Japan, from 28 November 2011 to 31 March 2015.
Pre-assignment Details 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.
Arm/Group Title Alogliptin/Pioglitazone
Hide Arm/Group Description 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.
Period Title: Overall Study
Started 3281
Completed 3139
Not Completed 142
Reason Not Completed
Case Report Forms Uncollected             89
Protocol Deviation             53
Arm/Group Title Alogliptin/Pioglitazone
Hide Arm/Group Description 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 Number of Baseline Participants 3139
Hide Baseline Analysis Population Description
Safety Analysis Set; The safety analysis set was defined as all participants who were enrolled and completed the study.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 3139 participants
64.7  (11.78)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3139 participants
Female
1188
  37.8%
Male
1951
  62.2%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Japan Number Analyzed 3139 participants
3139
Duration of Type 2 Diabetes Mellitus   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 2689 participants
7.56  (6.950)
[1]
Measure Description: Mean Duration between start of study and first time of diagnosis of type 2 diabetes mellitus was reported.
[2]
Measure Analysis Population Description: The number analyzed is the number of participants with data available for analysis.
Weight   [1] 
Mean (Standard Deviation)
Unit of measure:  Kilograms (kg)
Number Analyzed 1982 participants
68.87  (15.094)
[1]
Measure Analysis Population Description: The number analyzed is the number of participants with data available for analysis.
BMI   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 1847 participants
26.49  (4.592)
[1]
Measure Description: Body Mass Index = weight (kg)/[height (m)^2]
[2]
Measure Analysis Population Description: The number analyzed is the number of participants with data available for analysis.
Waist Circumference (Male)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1951 participants
<85 centimeter (cm)
108
   5.5%
≥85cm
317
  16.2%
Unknown
1526
  78.2%
[1]
Measure Analysis Population Description: This baseline characteristic was analyzed only in male participants.
Waist Circumference (Female)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1188 participants
<90cm
146
  12.3%
≥90cm
128
  10.8%
Unknown
914
  76.9%
[1]
Measure Analysis Population Description: This baseline characteristic was analyzed only in female participants.
Healthcare Category  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3139 participants
Outpatient
3113
  99.2%
Inpatient
26
   0.8%
Pregnancy Status (Not Pregnant)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1188 participants
1188
 100.0%
[1]
Measure Analysis Population Description: This baseline characteristic was analyzed only in female participants.
Medical Complications   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Had No Presence of Medical Complications Number Analyzed 3139 participants
441
  14.0%
Had Presence of Medical Complications Number Analyzed 3139 participants
2698
  86.0%
[1]
Measure Description: Complications defined as a disease or a health condition for each participant at the start of study. Complications were classified as congenital anomalies, endocrine disorders, hematologic disorders, psychiatric and nervous system disorders, cardiovascular disorders, respiratory disorders, gastrointestinal (GI) disorders, renal disease and other complications. Other complications included all complications except for those mentioned above.
Diabetic Complications  
Measure Type: Count of Participants
Unit of measure:  Participants
Had No Presence of Diabetic Complications Number Analyzed 3139 participants
2621
  83.5%
Had Presence of Diabetic Complications Number Analyzed 3139 participants
518
  16.5%
Concomitant Lifestyle-Related Disease  
Measure Type: Count of Participants
Unit of measure:  Participants
Had No Concomitant Lifestyle-Related Disease Number Analyzed 3139 participants
583
  18.6%
Had Concomitant Lifestyle-Related Disease Number Analyzed 3139 participants
2556
  81.4%
Concomitant Hepatic Disorder  
Measure Type: Count of Participants
Unit of measure:  Participants
Had No Concomitant Hepatic Disorder Number Analyzed 3139 participants
2662
  84.8%
Had Concomitant Hepatic Disorder Number Analyzed 3139 participants
477
  15.2%
Degree of Hepatic Dysfunction   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Normal Number Analyzed 3139 participants
1765
  56.2%
Grade 1 Number Analyzed 3139 participants
216
   6.9%
Grade 2 Number Analyzed 3139 participants
40
   1.3%
Grade 3 Number Analyzed 3139 participants
1
   0.0%
Unknown Number Analyzed 3139 participants
1117
  35.6%
[1]
Measure Description: Severity was determined using aspartate aminotransferase (AST) or alanine transaminase (ALT) values at the start of treatment with alogliptin. For the assessment of severity, the following categories were used and higher grades of serum AST or ALT were adopted. Normal: <50 international units per liter (IU/L) Grade 1: >=50 to <100 IU/L Grade 2: >=100 to <500 IU/L Grade 3: >=500 IU/L
Concomitant Renal Disorder  
Measure Type: Count of Participants
Unit of measure:  Participants
Had No Concomitant Renal Disorder Number Analyzed 3139 participants
2760
  87.9%
Had Concomitant Renal Disorder Number Analyzed 3139 participants
379
  12.1%
Degree of Renal Dysfunction (eGFR)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Normal Number Analyzed 3139 participants
462
  14.7%
Mild Number Analyzed 3139 participants
1090
  34.7%
Moderate Number Analyzed 3139 participants
411
  13.1%
Severe Number Analyzed 3139 participants
21
   0.7%
Unknown Number Analyzed 3139 participants
1155
  36.8%
[1]
Measure Description: Estimated glomerular filtration rate (eGFR) was calculated using variables of gender, age at the start of treatment, and serum creatinine values, and severity was determined based on the following categories. If the serum creatinine value at the start of treatment was not listed, the severity was reported as “unknown.” Normal: >=90 milliliter per min (mL/min)/1.73^2, Mild: >=60 mL/min/1.73^2 to <90 mL/min/1.73^2, Moderate: >=30 mL/min/1.73^2 to <60 mL/min/1.73^2, Severe: <30 mL/min/1.73^2 eGFR = 194 * Cr^-1.094 * (age)^-0.287 (* 0.739 if female) where Cr is creatinine value.
Degree of Renal Dysfunction (Cr)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Normal or Mild Number Analyzed 3139 participants
1933
  61.6%
Moderate Number Analyzed 3139 participants
49
   1.6%
Severe Number Analyzed 3139 participants
2
   0.1%
Unknown Number Analyzed 3139 participants
1155
  36.8%
[1]
Measure Description: Normal or Mild: =< 1.4 mg/dL (for male) or =< 1.2 mg/dL (for female), Moderate: >1.4 mg/dL to =< 2.4 mg/dL (for male) or >1.2 mg/dL to =< 2.0 mg/dL (for female), Severe: > 2.4 mg/dL (for male), > 2.0 mg/dL (for female). If the serum creatinine value (Cr) at the start of treatment was not listed, the severity was reported as “unknown.”
Concomitant Cardiac Disease  
Measure Type: Count of Participants
Unit of measure:  Participants
Had No Concomitant Cardiac Disease Number Analyzed 3139 participants
2828
  90.1%
Had Concomitant Cardiac Disease Number Analyzed 3139 participants
311
   9.9%
Concomitant Heart Failure  
Measure Type: Count of Participants
Unit of measure:  Participants
Had No Concomitant Heart Failure Number Analyzed 3139 participants
3134
  99.8%
Had Concomitant Heart Failure Number Analyzed 3139 participants
5
   0.2%
New York Heart Association (NYHA) Heart Failure Classification   [1] [2] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4 participants
Class I
3
  75.0%
Class II
1
  25.0%
[1]
Measure Description: NYHA functional classification ranges from Class I (Participants with cardiac disease but without resulting limitations of physical activity), Class II (Cardiac disease resulting in slight limitation of physical activity), Class III (Cardiac disease resulting in marked limitation of physical activity), Class IV (Cardiac disease resulting in inability to carry on any physical activity without discomfort).
[2]
Measure Analysis Population Description: 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  
Measure Type: Count of Participants
Unit of measure:  Participants
Had No Concomitant Stroke-Related Disease Number Analyzed 3139 participants
2979
  94.9%
Had Concomitant Stroke-Related Disease Number Analyzed 3139 participants
160
   5.1%
Concomitant Allergic Condition  
Measure Type: Count of Participants
Unit of measure:  Participants
Had No Concomitant Allergic Condition Number Analyzed 3139 participants
2954
  94.1%
Had Concomitant Allergic Condition Number Analyzed 3139 participants
185
   5.9%
Concomitant Malignant Tumor  
Measure Type: Count of Participants
Unit of measure:  Participants
Had No Concomitant Malignant Tumor Number Analyzed 3139 participants
3092
  98.5%
Had Concomitant Malignant Tumor Number Analyzed 3139 participants
47
   1.5%
Medical History   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Had No Presence of Medical History Number Analyzed 3139 participants
2523
  80.4%
Had Presence of Medical History Number Analyzed 3139 participants
347
  11.1%
Unknown Number Analyzed 3139 participants
269
   8.6%
[1]
Measure Description: Medical history defined as a disease or a health condition for each participant before start of the study. Medical history was classified as congenital anomalies, hematologic disorders, psychiatric and nervous system disorders, cardiovascular disorders, respiratory disorders, GI disorders, hepatic and biliary disorders, renal disease and other medical history. Other medical history included all medical history except for those mentioned above.
Predisposition to Hypersensitivity   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Had No Predisposition to Hypersensitivity Number Analyzed 3139 participants
2735
  87.1%
Had Predisposition to Hypersensitivity Number Analyzed 3139 participants
119
   3.8%
Unknown Number Analyzed 3139 participants
285
   9.1%
[1]
Measure Description: The baseline characteristic was analyzed in participants who had a liability or tendency to suffer from hypersensitivity.
Drinking Habits  
Measure Type: Count of Participants
Unit of measure:  Participants
Current Drinker Number Analyzed 3139 participants
900
  28.7%
Never Drank or Ex Drinker Number Analyzed 3139 participants
1538
  49.0%
Unknown Number Analyzed 3139 participants
701
  22.3%
Smoking Classification  
Measure Type: Count of Participants
Unit of measure:  Participants
Never Smoked Number Analyzed 3139 participants
1260
  40.1%
Current Smoker Number Analyzed 3139 participants
480
  15.3%
Ex-Smoker Number Analyzed 3139 participants
557
  17.7%
Unknown Number Analyzed 3139 participants
842
  26.8%
Haemoglobin A1c (HbA1c) [National Glycohemoglobin Standardization Program (NGSP)]   [1] 
Mean (Standard Deviation)
Unit of measure:  Percent HbA1c
Number Analyzed 2909 participants
7.63  (1.276)
[1]
Measure Analysis Population Description: The number analyzed is the number of participants with data available for analysis.
Alogliptin Status  
Measure Type: Count of Participants
Unit of measure:  Participants
Had No Doses of Alogliptin Number Analyzed 3139 participants
2092
  66.6%
Had Doses of Alogliptin Number Analyzed 3139 participants
1047
  33.4%
Pioglitazone Status  
Measure Type: Count of Participants
Unit of measure:  Participants
Had No Doses of Pioglitazone Number Analyzed 3139 participants
1402
  44.7%
Had Doses of Pioglitazone Number Analyzed 3139 participants
1737
  55.3%
1.Primary Outcome
Title Number of Participants Who Experience at Least One Adverse Events
Hide Description [Not Specified]
Time Frame Up to 12 Months
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set was defined as all participants who were enrolled and completed the study.
Arm/Group Title Alogliptin/Pioglitazone
Hide Arm/Group Description:
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 Number of Participants Analyzed 3139
Measure Type: Count of Participants
Unit of Measure: Participants
206
   6.6%
2.Primary Outcome
Title Changes From Baseline in Glycosylated Hemoglobin (HbA1c)
Hide Description Reported data are changes in HbA1c from baseline at Month 1, 3, 6, 12 and final assessment (up to 12 months).
Time Frame Baseline and Month 1, 3, 6, 12 and final assessment (up to 12 Months)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Alogliptin/Pioglitazone
Hide Arm/Group Description:
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 Number of Participants Analyzed 2830
Mean (Standard Deviation)
Unit of Measure: Percent HbA1c
Change in HbA1c at Month 1 Number Analyzed 2094 participants
-0.26  (0.651)
Change in HbA1c at Month 3 Number Analyzed 2380 participants
-0.58  (0.991)
Change in HbA1c at Month 6 Number Analyzed 2404 participants
-0.66  (1.081)
Change in HbA1c at Month 12 Number Analyzed 2372 participants
-0.66  (1.098)
Change in HbA1c at Final Assessment Number Analyzed 2830 participants
-0.65  (1.121)
3.Secondary Outcome
Title Changes From Baseline in Fasting Blood Glucose (FBG)
Hide Description Reported data are changes in fasting blood glucose level from baseline at Month 1, 3, 6, 12 and final assessment (up to 12 months).
Time Frame Baseline and Month 1, 3, 6, 12 and final assessment (up to 12 Months)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Alogliptin/Pioglitazone
Hide Arm/Group Description:
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 Number of Participants Analyzed 1554
Mean (Standard Deviation)
Unit of Measure: mg/dL
Change in FBG at Month 1 Number Analyzed 1052 participants
-14.7  (49.34)
Change in FBG at Month 3 Number Analyzed 1195 participants
-18.7  (50.24)
Change in FBG at Month 6 Number Analyzed 1243 participants
-18.4  (50.51)
Change in FBG at Month 12 Number Analyzed 1239 participants
-19.6  (50.93)
Change in FBG at Final Assessment Number Analyzed 1554 participants
-19.8  (53.31)
Time Frame Up to Month 12
Adverse Event Reporting Description 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.
 
Arm/Group Title Alogliptin/Pioglitazone
Hide Arm/Group Description 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.
All-Cause Mortality
Alogliptin/Pioglitazone
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Alogliptin/Pioglitazone
Affected / at Risk (%)
Total   4/3139 (0.13%) 
General disorders   
Death  1 [1]  1/3139 (0.03%) 
Infections and infestations   
Pneumonia  1  1/3139 (0.03%) 
Injury, poisoning and procedural complications   
Spinal compression fracture  1  1/3139 (0.03%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Lung neoplasm malignant  1  1/3139 (0.03%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 19.1
[1]
The reasons of events are not determined because assessment findings were insufficient to specify the reason.
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0.1%
Alogliptin/Pioglitazone
Affected / at Risk (%)
Total   56/3139 (1.78%) 
General disorders   
Oedema  1  32/3139 (1.02%) 
Oedema peripheral  1  8/3139 (0.25%) 
Investigations   
Weight increased  1  11/3139 (0.35%) 
Skin and subcutaneous tissue disorders   
Rash  1  5/3139 (0.16%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 19.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Director
Organization: Takeda
Phone: +1-877-825-3327
EMail: trialdisclosures@takeda.com
Layout table for additonal information
Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT01990300     History of Changes
Other Study ID Numbers: 136-011
JapicCTI-132302 ( Registry Identifier: JapicCTI )
First Submitted: November 15, 2013
First Posted: November 21, 2013
Results First Submitted: November 6, 2017
Results First Posted: January 18, 2019
Last Update Posted: January 18, 2019