Trial Outcomes & Findings for Pioglitazone/Glimepiride (Sonias) Combination Tablets Special Drug Use Surveillance Survey in Patients With Type 2 Diabetes Mellitus Who Respond Poorly to Pioglitazone (NCT NCT02098746)

NCT ID: NCT02098746

Last Updated: 2016-10-18

Results Overview

Frequency of adverse drug reactions is defined as the number of participants with adverse drug reactions. Frequency, seriousness, and time to onset of adverse drug reactions were tabulated by each symptom. Adverse events 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. Among these, events which are considered possibly associated with a medicinal product are defined as adverse drug reactions.

Recruitment status

COMPLETED

Target enrollment

294 participants

Primary outcome timeframe

12 months

Results posted on

2016-10-18

Participant Flow

This observational study took part at 64 investigative sites in Japan from 15 June 2011 to 31 July 2014.

Participants with a diagnosis of type 2 diabetes mellitus receiving treatment with pioglitazone/glimepiride 15 mg/1 mg once daily in routine clinical practice, because pioglitazone alone was not considered effective, were enrolled in the study.

Participant milestones

Participant milestones
Measure
Pioglitazone/Glimepiride
Pioglitazone/glimepiride 15 mg/1 mg, orally once daily before or after breakfast.
Overall Study
STARTED
294
Overall Study
COMPLETED
289
Overall Study
NOT COMPLETED
5

Reasons for withdrawal

Reasons for withdrawal
Measure
Pioglitazone/Glimepiride
Pioglitazone/glimepiride 15 mg/1 mg, orally once daily before or after breakfast.
Overall Study
Changes of Investigator
2
Overall Study
Other Miscellaneous Reasons
1
Overall Study
Enrolled 15 Days After the First Dose
1
Overall Study
Data Not Available After Treatment
1

Baseline Characteristics

Pioglitazone/Glimepiride (Sonias) Combination Tablets Special Drug Use Surveillance Survey in Patients With Type 2 Diabetes Mellitus Who Respond Poorly to Pioglitazone

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Pioglitazone/Glimepiride
n=289 Participants
Pioglitazone/glimepiride 15 mg/1 mg, orally once daily before or after breakfast.
Age, Continuous
65.8 years
STANDARD_DEVIATION 12.56 • n=5 Participants
Age, Customized
<65 years
112 participants
n=5 Participants
Age, Customized
≥65 years
177 participants
n=5 Participants
Sex: Female, Male
Female
117 Participants
n=5 Participants
Sex: Female, Male
Male
172 Participants
n=5 Participants
Pregnancy Status (Females Only)
Not pregnant
117 participants
n=5 Participants
Pregnancy Status (Females Only)
Pregnant
0 participants
n=5 Participants
Duration of Type 2 Diabetes
6.19 years
STANDARD_DEVIATION 5.444 • n=5 Participants
Duration of Type 2 Diabetes, Categorical
<2 years
56 participants
n=5 Participants
Duration of Type 2 Diabetes, Categorical
≥2 to <5 years
44 participants
n=5 Participants
Duration of Type 2 Diabetes, Categorical
≥5 to <10 years
58 participants
n=5 Participants
Duration of Type 2 Diabetes, Categorical
≥10 years
49 participants
n=5 Participants
Duration of Type 2 Diabetes, Categorical
Unknown
82 participants
n=5 Participants
Categories of Health Care
Outpatient
287 participants
n=5 Participants
Categories of Health Care
Inpatient
2 participants
n=5 Participants
History of Allergy
No
239 participants
n=5 Participants
History of Allergy
Yes
29 participants
n=5 Participants
History of Allergy
Unknown
21 participants
n=5 Participants
Complications of Type 2 Diabetes
No
25 participants
n=5 Participants
Complications of Type 2 Diabetes
Yes
264 participants
n=5 Participants
Breakdown of Complications (Tabulated in Duplicate)
Microangiopathy
31 participants
n=5 Participants
Breakdown of Complications (Tabulated in Duplicate)
Diabetic nephropathy
17 participants
n=5 Participants
Breakdown of Complications (Tabulated in Duplicate)
Diabetic retinopathy
9 participants
n=5 Participants
Breakdown of Complications (Tabulated in Duplicate)
Diabetic neuropathy
12 participants
n=5 Participants
Breakdown of Complications (Tabulated in Duplicate)
Hypertension
175 participants
n=5 Participants
Breakdown of Complications (Tabulated in Duplicate)
Dyslipidaemia
175 participants
n=5 Participants
Breakdown of Complications (Tabulated in Duplicate)
Hyperuricaemia
29 participants
n=5 Participants
Breakdown of Complications (Tabulated in Duplicate)
Liver disease
25 participants
n=5 Participants
Breakdown of Complications (Tabulated in Duplicate)
Renal disease
18 participants
n=5 Participants
Breakdown of Complications (Tabulated in Duplicate)
Heart disease
17 participants
n=5 Participants
Breakdown of Complications (Tabulated in Duplicate)
Cerebrovascular disease
15 participants
n=5 Participants
Breakdown of Complications (Tabulated in Duplicate)
Malignant tumor
1 participants
n=5 Participants
Breakdown of Complications (Tabulated in Duplicate)
Other
12 participants
n=5 Participants
Presence of Medical History
No
228 participants
n=5 Participants
Presence of Medical History
Yes
39 participants
n=5 Participants
Presence of Medical History
Unknown
22 participants
n=5 Participants
Weight
65.64 kg
STANDARD_DEVIATION 13.662 • n=5 Participants
Weight, Categorical
<40 kg
1 participants
n=5 Participants
Weight, Categorical
≥40 to <50 kg
24 participants
n=5 Participants
Weight, Categorical
≥50 to <60 kg
57 participants
n=5 Participants
Weight, Categorical
≥60 to <70 kg
81 participants
n=5 Participants
Weight, Categorical
≥70 kg
87 participants
n=5 Participants
Weight, Categorical
Unmeasured
39 participants
n=5 Participants
Body Mass Index (BMI)
25.45 kg/m^2
STANDARD_DEVIATION 4.230 • n=5 Participants
BMI, Categorical
<18.5 kg/m^2
8 participants
n=5 Participants
BMI, Categorical
≥18.5 to <25 kg/m^2
107 participants
n=5 Participants
BMI, Categorical
≥25 to <30 kg/m^2
97 participants
n=5 Participants
BMI, Categorical
≥30 kg/m^2
30 participants
n=5 Participants
BMI, Categorical
Unknown
47 participants
n=5 Participants
History of Alcohol (Drinking Alcohol-Containing Beverages Nearly Every Day)
Yes
167 participants
n=5 Participants
History of Alcohol (Drinking Alcohol-Containing Beverages Nearly Every Day)
No
81 participants
n=5 Participants
History of Alcohol (Drinking Alcohol-Containing Beverages Nearly Every Day)
Unknown
41 participants
n=5 Participants
Smoking Classification
Never Smoked
134 participants
n=5 Participants
Smoking Classification
Current Smoker
54 participants
n=5 Participants
Smoking Classification
Ex-smoker
55 participants
n=5 Participants
Smoking Classification
Unknown
46 participants
n=5 Participants
Compliance Rate with the Diet Regimen (at the Start of Treatment with Sonias Combination Tablets LD)
≥ 90%
73 participants
n=5 Participants
Compliance Rate with the Diet Regimen (at the Start of Treatment with Sonias Combination Tablets LD)
≥ 70%
118 participants
n=5 Participants
Compliance Rate with the Diet Regimen (at the Start of Treatment with Sonias Combination Tablets LD)
≥ 50%
53 participants
n=5 Participants
Compliance Rate with the Diet Regimen (at the Start of Treatment with Sonias Combination Tablets LD)
< 50%
18 participants
n=5 Participants
Compliance Rate with the Diet Regimen (at the Start of Treatment with Sonias Combination Tablets LD)
Not performed or compliance status is unknown
27 participants
n=5 Participants
Compliance Rate with the Exercise Regimen (at Start of Treatment with Sonias Combination Tablets LD)
≥ 90%
49 participants
n=5 Participants
Compliance Rate with the Exercise Regimen (at Start of Treatment with Sonias Combination Tablets LD)
≥ 70%
97 participants
n=5 Participants
Compliance Rate with the Exercise Regimen (at Start of Treatment with Sonias Combination Tablets LD)
≥ 50%
76 participants
n=5 Participants
Compliance Rate with the Exercise Regimen (at Start of Treatment with Sonias Combination Tablets LD)
< 50%
36 participants
n=5 Participants
Compliance Rate with the Exercise Regimen (at Start of Treatment with Sonias Combination Tablets LD)
Not performed or compliance status is unknown
31 participants
n=5 Participants
Glycosylated hemoglobin A1c (HbA1c) (at Start of Treatment with Sonias Combination Tablets LD)
7.75 %
STANDARD_DEVIATION 1.493 • n=5 Participants
HbA1c, Categorical
< 6.0%
8 participants
n=5 Participants
HbA1c, Categorical
≥ 6.0% to < 7.0%
66 participants
n=5 Participants
HbA1c, Categorical
≥ 7.0% to < 8.0%
110 participants
n=5 Participants
HbA1c, Categorical
≥ 8.0%
80 participants
n=5 Participants
HbA1c, Categorical
Unknown
25 participants
n=5 Participants

PRIMARY outcome

Timeframe: 12 months

Population: The Safety Analysis Set (safety assessment population) included all patients who received at least one dose of pioglitazone/glimepiride (N=289).

Frequency of adverse drug reactions is defined as the number of participants with adverse drug reactions. Frequency, seriousness, and time to onset of adverse drug reactions were tabulated by each symptom. Adverse events 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. Among these, events which are considered possibly associated with a medicinal product are defined as adverse drug reactions.

Outcome measures

Outcome measures
Measure
Pioglitazone/Glimepiride
n=289 Participants
Pioglitazone/glimepiride 15 mg/1 mg, orally once daily before or after breakfast.
Frequency of Adverse Drug Reactions
Anaemia
1 participants
Frequency of Adverse Drug Reactions
Hypoglycaemia
7 participants
Frequency of Adverse Drug Reactions
Generalised oedema
1 participants
Frequency of Adverse Drug Reactions
Oedema
1 participants
Frequency of Adverse Drug Reactions
Weight increased
6 participants

PRIMARY outcome

Timeframe: 12 months

Population: The Safety Analysis Set (safety assessment population) included all patients who received at least one dose of pioglitazone/glimepiride (N=289).

Frequency of serious adverse drug reactions is defined at the number of participants with serious adverse drug reactions. Frequency of serious adverse drug reactions were tabulated by each symptom. Adverse events 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. A serious adverse event is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant. Among these, events which are considered possibly associated with a medicinal product are defined as adverse drug reactions.

Outcome measures

Outcome measures
Measure
Pioglitazone/Glimepiride
n=289 Participants
Pioglitazone/glimepiride 15 mg/1 mg, orally once daily before or after breakfast.
Frequency of Serious Adverse Drug Reactions
0 participants

SECONDARY outcome

Timeframe: Baseline, Months 3, 6, 9, 12 and at Final assessment

Population: The analysis was performed on the efficacy assessment population (N=250) with data available at the given time-point.

Tabulation of HbA1c values and the changes from Baseline at each test time point (test value at each test time point after Baseline - test value at Baseline). A negative change from Baseline indicates improvement.

Outcome measures

Outcome measures
Measure
Pioglitazone/Glimepiride
n=250 Participants
Pioglitazone/glimepiride 15 mg/1 mg, orally once daily before or after breakfast.
Change From Baseline in Glycosylated Hemoglobin (HbA1c)
Month 3 (n=234)
-0.83 percent
Standard Deviation 1.030
Change From Baseline in Glycosylated Hemoglobin (HbA1c)
Month 6 (n=190)
-0.84 percent
Standard Deviation 1.094
Change From Baseline in Glycosylated Hemoglobin (HbA1c)
Month 9 (n=177)
-0.83 percent
Standard Deviation 1.088
Change From Baseline in Glycosylated Hemoglobin (HbA1c)
Month 12 (n=84)
-0.62 percent
Standard Deviation 1.139
Change From Baseline in Glycosylated Hemoglobin (HbA1c)
Final Assessment (n=247)
-0.92 percent
Standard Deviation 1.285

SECONDARY outcome

Timeframe: Baseline, Months 3, 6, 9, 12 and at Final assessment

Population: The analysis was performed on the efficacy assessment population (N=250) with data available at the given time-point.

Tabulation of fasting blood glucose level and the changes from Baseline at each test time point (test value at each test time point after Baseline - test value at Baseline). A negative change from Baseline indicates improvement.

Outcome measures

Outcome measures
Measure
Pioglitazone/Glimepiride
n=250 Participants
Pioglitazone/glimepiride 15 mg/1 mg, orally once daily before or after breakfast.
Change From Baseline in Fasting Blood Glucose Level
Month 3 (n=76)
-15.9 mg/dL
Standard Deviation 35.99
Change From Baseline in Fasting Blood Glucose Level
Month 6 (n=59)
-23.2 mg/dL
Standard Deviation 40.11
Change From Baseline in Fasting Blood Glucose Level
Month 9 (n=53)
-12.7 mg/dL
Standard Deviation 37.60
Change From Baseline in Fasting Blood Glucose Level
Month 12 (n=28)
-17.0 mg/dL
Standard Deviation 20.42
Change From Baseline in Fasting Blood Glucose Level
Final Assessment (n=83)
-17.7 mg/dL
Standard Deviation 42.23

SECONDARY outcome

Timeframe: Baseline, Months 3, 6, 9, 12 and at Final assessment

Population: The analysis was performed on the efficacy assessment population (N=250) with data available at the given time-point.

Tabulation of fasting insulin level and the changes from Baseline at each test time point (test value at each test time point after Baseline - test value at Baseline). A negative change from Baseline indicates improvement. A positive change from Baseline indicates a worsening.

Outcome measures

Outcome measures
Measure
Pioglitazone/Glimepiride
n=250 Participants
Pioglitazone/glimepiride 15 mg/1 mg, orally once daily before or after breakfast.
Change From Baseline in Fasting Insulin Level
Month 3 (n=33)
1.66 μU/dL
Standard Deviation 9.419
Change From Baseline in Fasting Insulin Level
Month 6 (n=25)
-0.25 μU/dL
Standard Deviation 3.976
Change From Baseline in Fasting Insulin Level
Month 9 (n=17)
1.32 μU/dL
Standard Deviation 3.949
Change From Baseline in Fasting Insulin Level
Month 12 (n=15)
-0.29 μU/dL
Standard Deviation 3.489
Change From Baseline in Fasting Insulin Level
Final Assessment (n=39)
0.98 μU/dL
Standard Deviation 7.310

Adverse Events

Pioglitazone/Glimepiride

Serious events: 2 serious events
Other events: 0 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Pioglitazone/Glimepiride
n=289 participants at risk
Pioglitazone/glimepiride 15 mg/1 mg, orally once daily before or after breakfast.
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Renal neoplasm
0.35%
1/289 • 12 Months
Safety Analysis Set included all patients who received at least one dose of pioglitazone/glimepiride. At each visit the investigator documented any occurrence of adverse events. Any event that occurred during the observation period was recorded, irrespective of the relation to study treatment.
Cardiac disorders
Atrioventricular block complete
0.35%
1/289 • 12 Months
Safety Analysis Set included all patients who received at least one dose of pioglitazone/glimepiride. At each visit the investigator documented any occurrence of adverse events. Any event that occurred during the observation period was recorded, irrespective of the relation to study treatment.

Other adverse events

Adverse event data not reported

Additional Information

Medical Director

Takeda

Phone: +1-877-825-3327

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