Trial Outcomes & Findings for Pioglitazone Tablets Special Drug Use Surveillance "Combined Use of Insulin Products / Long-term Treatment" (NCT NCT02068508)

NCT ID: NCT02068508

Last Updated: 2019-03-12

Results Overview

ADRs 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.

• Recruitment status: COMPLETED
• Target enrollment: 1067 participants
• Primary outcome timeframe: Up to Week 52
• Results posted on: 2019-03-12

Participant Flow

Participants took part in the study at 169 investigative sites in Japan, from 30-July-2009 to 30-June-2014.

Participants with a historical diagnosis of type 2 diabetes mellitus who failed to respond adequately to treatment with insulin therapy were enrolled to receive pioglitazone 15 milligram (mg) - 30 mg for up to 12 months. Participants received interventions as part of routine medical care.

Participant milestones

Measure	Pioglitazone Pioglitazone 15 mg - 30 mg, tablet, orally, once daily for up to 12 months in participants based upon the disease severity. Participants will receive interventions as part of routine medical care.
Overall Study STARTED	1067
Overall Study COMPLETED	1035
Overall Study NOT COMPLETED	32

Reasons for withdrawal

Measure	Pioglitazone Pioglitazone 15 mg - 30 mg, tablet, orally, once daily for up to 12 months in participants based upon the disease severity. Participants will receive interventions as part of routine medical care.
Overall Study Case report forms uncollected	27
Overall Study Patient did not visit the study site	1
Overall Study Protocol Violation	4

Baseline Characteristics

Pioglitazone Tablets Special Drug Use Surveillance "Combined Use of Insulin Products / Long-term Treatment"

Baseline characteristics by cohort

Measure	Pioglitazone n=1035 Participants Pioglitazone 15 mg - 30 mg, tablet, orally, once daily for up to 12 months in participants based upon the disease severity. Participants will receive interventions as part of routine medical care.
Age, Continuous	62.8 years STANDARD_DEVIATION 12.09 • n=5 Participants
Sex: Female, Male Female	477 Participants n=5 Participants
Sex: Female, Male Male	558 Participants n=5 Participants
Region of Enrollment Japan	1035 Participants n=5 Participants
Pregnancy Status Pregnant	0 Participants n=5 Participants
Pregnancy Status Not pregnant	477 Participants n=5 Participants
Duration of type 2 diabetes mellitus < 1 year	27 Participants n=5 Participants
Duration of type 2 diabetes mellitus ≥ 1 year < 5 years	98 Participants n=5 Participants
Duration of type 2 diabetes mellitus ≥ 5 years < 10 years	199 Participants n=5 Participants
Duration of type 2 diabetes mellitus ≥ 10 years	661 Participants n=5 Participants
Duration of type 2 diabetes mellitus Unknown	50 Participants n=5 Participants
Predisposition to Hypersensitivity Had Predisposition to Hypersensitivity	48 Participants n=5 Participants
Predisposition to Hypersensitivity Had No Predisposition to Hypersensitivity	983 Participants n=5 Participants
Predisposition to Hypersensitivity Unknown	4 Participants n=5 Participants
Drinking Habits Never Drank	661 Participants n=5 Participants
Drinking Habits Ex-Drinker	77 Participants n=5 Participants
Drinking Habits Current Drinker	280 Participants n=5 Participants
Drinking Habits Unknown	17 Participants n=5 Participants
Smoking Habits Never Smoked	687 Participants n=5 Participants
Smoking Habits Ex-Smoker	160 Participants n=5 Participants
Smoking Habits Current Smoker	162 Participants n=5 Participants
Smoking Habits Unknown	26 Participants n=5 Participants
Body Weight	65.849 kg STANDARD_DEVIATION 14.0584 • n=5 Participants
BMI	25.45 kg/m^2 STANDARD_DEVIATION 4.336 • n=5 Participants
Medical History Had Presence of Medical History	343 Participants n=5 Participants
Medical History Had No Presence of Medical History	683 Participants n=5 Participants
Medical History Unknown	9 Participants n=5 Participants
Medical Complications Had Presence of Medical Complications	957 Participants n=5 Participants
Medical Complications Had Presence of Medical No Complications	78 Participants n=5 Participants
Concomitant Hepatic Disease Had Concomitant Hepatic Disease	126 Participants n=5 Participants
Concomitant Hepatic Disease Had No Concomitant Hepatic Disease	909 Participants n=5 Participants
Concomitant Renal Disease Had Concomitant Renal Disease	423 Participants n=5 Participants
Concomitant Renal Disease Had No Concomitant Renal Disease	612 Participants n=5 Participants
Concomitant Cardiac Disease Had Concomitant Cardiac Disease	148 Participants n=5 Participants
Concomitant Cardiac Disease Had No Concomitant Cardiac Disease	887 Participants n=5 Participants
Diabetic Complications Had Diabetic Complications	633 Participants n=5 Participants
Diabetic Complications Had No Diabetic Complications	402 Participants n=5 Participants
Diet Therapy On Diet Therapy	1000 Participants n=5 Participants
Diet Therapy Not on Diet Therapy	34 Participants n=5 Participants
Diet Therapy Unknown	1 Participants n=5 Participants
Exercise Therapy On Exercise Therapy	932 Participants n=5 Participants
Exercise Therapy Not on Exercise Therapy	102 Participants n=5 Participants
Exercise Therapy Unknown	1 Participants n=5 Participants
Fasting Blood Glucose	172.0 mg/dL STANDARD_DEVIATION 65.49 • n=5 Participants
Haemoglobin A1c (HbA1c) [National Glycohemoglobin Standardization Program (NGSP)]	8.72 Percent STANDARD_DEVIATION 1.449 • n=5 Participants
Fasting Triglyceride	156.5 mg/dL STANDARD_DEVIATION 133.21 • n=5 Participants
HDL Cholesterol	55.92 mg/dL STANDARD_DEVIATION 17.205 • n=5 Participants
LDL Cholesterol	111.46 mg/dL STANDARD_DEVIATION 28.418 • n=5 Participants
Serum creatinine (Enzymatic method)	0.784 mg/dL STANDARD_DEVIATION 0.2853 • n=5 Participants
Urine protein (Qualitative) -	501 Participants n=5 Participants
Urine protein (Qualitative) ±	140 Participants n=5 Participants
Urine protein (Qualitative) ＋	101 Participants n=5 Participants
Urine protein (Qualitative) 2＋	66 Participants n=5 Participants
Urine protein (Qualitative) 3＋	30 Participants n=5 Participants
Urine protein (Qualitative) Unknown/No measuremen	197 Participants n=5 Participants
Urine albumin/Creatinine ratio	169.616 mg/gCR STANDARD_DEVIATION 535.5513 • n=5 Participants
Systolic Blood Pressure (SBP)	131.6 mmHg STANDARD_DEVIATION 15.17 • n=5 Participants
Diastolic Blood Pressure (DBP)	73.7 mmHg STANDARD_DEVIATION 10.53 • n=5 Participants

PRIMARY outcome

Timeframe: Up to Week 52

Population: The safety analysis set was defined as all participants who were enrolled and completed the study.

ADRs 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.

Outcome measures

Measure	Pioglitazone n=1035 Participants Pioglitazone 15 mg - 30 mg, tablet, orally, once daily for up to 12 months in participants based upon the disease severity. Participants will receive interventions as part of routine medical care.
Number of Participants Who Experience at Least One Adverse Drug Reactions (ADRs)	213 Participants

SECONDARY outcome

Timeframe: Baseline and Week 12, 24, 36, 52, and final assessment (up to Week 52)

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. Here number of participants analyzed was evaluable for this outcome measure.

Outcome measures

Measure	Pioglitazone n=1013 Participants Pioglitazone 15 mg - 30 mg, tablet, orally, once daily for up to 12 months in participants based upon the disease severity. Participants will receive interventions as part of routine medical care.
Change From Baseline in Fasting Blood Glucose Change at Week 12	-26.2 mg/dL Standard Deviation 60.97
Change From Baseline in Fasting Blood Glucose Change at Week 24	-23.9 mg/dL Standard Deviation 60.55
Change From Baseline in Fasting Blood Glucose Change at Week 36	-21.7 mg/dL Standard Deviation 64.72
Change From Baseline in Fasting Blood Glucose Change at Week 52	-21.4 mg/dL Standard Deviation 65.47
Change From Baseline in Fasting Blood Glucose Change at Final Assessment	-23.8 mg/dL Standard Deviation 69.96

SECONDARY outcome

Timeframe: Baseline and Week 12, 24, 36, 52, and final assessment (up to Week 52)

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. Here number of participants analyzed was evaluable for this outcome measure.

Outcome measures

Measure	Pioglitazone n=1013 Participants Pioglitazone 15 mg - 30 mg, tablet, orally, once daily for up to 12 months in participants based upon the disease severity. Participants will receive interventions as part of routine medical care.
Change From Baseline in Glycosylated Hemoglobin (HbA1c) Change at Week 12	-0.62 Percent Standard Deviation 1.024
Change From Baseline in Glycosylated Hemoglobin (HbA1c) Change at Week 24	-0.75 Percent Standard Deviation 1.210
Change From Baseline in Glycosylated Hemoglobin (HbA1c) Change at Week 36	-0.77 Percent Standard Deviation 1.192
Change From Baseline in Glycosylated Hemoglobin (HbA1c) Change at Week 52	-0.75 Percent Standard Deviation 1.169
Change From Baseline in Glycosylated Hemoglobin (HbA1c) Change at Final Assessment	-0.72 Percent Standard Deviation 1.236

SECONDARY outcome

Timeframe: Baseline and Week 12, 24, 36, 52, and final assessment (up to Week 52)

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. Here number of participants analyzed was evaluable for this outcome measure.

Outcome measures

Measure	Pioglitazone n=1013 Participants Pioglitazone 15 mg - 30 mg, tablet, orally, once daily for up to 12 months in participants based upon the disease severity. Participants will receive interventions as part of routine medical care.
Change From Baseline in Fasting Triglycerides Change at Week 12	-20.7 mg/dL Standard Deviation 90.24
Change From Baseline in Fasting Triglycerides Change at Week 24	-19.8 mg/dL Standard Deviation 109.61
Change From Baseline in Fasting Triglycerides Change at Week 36	-28.4 mg/dL Standard Deviation 123.98
Change From Baseline in Fasting Triglycerides Change at Week 52	-8.5 mg/dL Standard Deviation 115.86
Change From Baseline in Fasting Triglycerides Change at Final Assessment	-16.6 mg/dL Standard Deviation 128.17

SECONDARY outcome

Timeframe: Baseline and Week 12, 24, 36, 52, and final assessment (up to Week 52)

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. Here number of participants analyzed was evaluable for this outcome measure.

Outcome measures

Measure	Pioglitazone n=1013 Participants Pioglitazone 15 mg - 30 mg, tablet, orally, once daily for up to 12 months in participants based upon the disease severity. Participants will receive interventions as part of routine medical care.
Change From Baseline in HDL Cholesterol Change at Week 12	3.32 mg/dL Standard Deviation 8.898
Change From Baseline in HDL Cholesterol Change at Week 24	1.98 mg/dL Standard Deviation 9.628
Change From Baseline in HDL Cholesterol Change at Week 36	1.79 mg/dL Standard Deviation 9.868
Change From Baseline in HDL Cholesterol Change at Week 52	1.35 mg/dL Standard Deviation 8.940
Change From Baseline in HDL Cholesterol Change at Final Assessment	2.04 mg/dL Standard Deviation 9.358

SECONDARY outcome

Timeframe: Baseline and Week 12, 24, 36, 52, and final assessment (up to Week 52)

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. Here number of participants analyzed was evaluable for this outcome measure.

Outcome measures

Measure	Pioglitazone n=1013 Participants Pioglitazone 15 mg - 30 mg, tablet, orally, once daily for up to 12 months in participants based upon the disease severity. Participants will receive interventions as part of routine medical care.
Change From Baseline in LDL Cholesterol Change at Week 12	-0.96 mg/dL Standard Deviation 22.788
Change From Baseline in LDL Cholesterol Change at Week 24	-0.16 mg/dL Standard Deviation 24.239
Change From Baseline in LDL Cholesterol Change at Week 36	-0.68 mg/dL Standard Deviation 26.594
Change From Baseline in LDL Cholesterol Change at Week 52	-0.33 mg/dL Standard Deviation 25.258
Change From Baseline in LDL Cholesterol Change at Final Assessment	-0.82 mg/dL Standard Deviation 25.908

SECONDARY outcome

Timeframe: Baseline, Week 52, and final assessment (up to Week 52)

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. Here number of participants analyzed was evaluable for this outcome measure.

Number of participants who received study drug and specific daily dose of insulin product during the survey was reported. Daily dose of insulin was categorized by < 30 units, >= 30 and < 60 units, >= 60 and < 90 units, >= 90 units at each time points.

Outcome measures

Measure	Pioglitazone n=1013 Participants Pioglitazone 15 mg - 30 mg, tablet, orally, once daily for up to 12 months in participants based upon the disease severity. Participants will receive interventions as part of routine medical care.
Number of Participants Who Received Specific Daily Dose of Insulin Product at Each Time Points Baseline · < 30 units of insulin product	510 Participants
Number of Participants Who Received Specific Daily Dose of Insulin Product at Each Time Points Baseline · >= 30 and < 60 units of insulin product	359 Participants
Number of Participants Who Received Specific Daily Dose of Insulin Product at Each Time Points Baseline · >= 60 and < 90 units of insulin product	68 Participants
Number of Participants Who Received Specific Daily Dose of Insulin Product at Each Time Points Baseline · >= 90 units of insulin product	16 Participants
Number of Participants Who Received Specific Daily Dose of Insulin Product at Each Time Points Week 52 · < 30 units of insulin product	379 Participants
Number of Participants Who Received Specific Daily Dose of Insulin Product at Each Time Points Week 52 · >= 30 and < 60 units of insulin product	256 Participants
Number of Participants Who Received Specific Daily Dose of Insulin Product at Each Time Points Week 52 · >= 60 and < 90 units of insulin product	52 Participants
Number of Participants Who Received Specific Daily Dose of Insulin Product at Each Time Points Week 52 · >= 90 units of insulin product	10 Participants
Number of Participants Who Received Specific Daily Dose of Insulin Product at Each Time Points Final Assessment · < 30 units of insulin product	532 Participants
Number of Participants Who Received Specific Daily Dose of Insulin Product at Each Time Points Final Assessment · >= 30 and < 60 units of insulin product	363 Participants
Number of Participants Who Received Specific Daily Dose of Insulin Product at Each Time Points Final Assessment · >= 60 and < 90 units of insulin product	72 Participants
Number of Participants Who Received Specific Daily Dose of Insulin Product at Each Time Points Final Assessment · >= 90 units of insulin product	15 Participants

Adverse Events

Pioglitazone

Serious events: 11 serious events

Other events: 303 other events

Deaths: 0 deaths

Serious adverse events

Measure	Pioglitazone n=1035 participants at risk Pioglitazone 15 mg - 30 mg, tablet, orally, once daily for up to 12 months in participants based upon the disease severity. Participants will receive interventions as part of routine medical care.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.10% 1/1035 • Baseline up to Week 52 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 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) Pancreatic carcinoma	0.10% 1/1035 • Baseline up to Week 52 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 study treatment. Only ADRs were collected in this study. Participants may be represented in more than 1 category.
Metabolism and nutrition disorders Hypoglycaemia	0.19% 2/1035 • Baseline up to Week 52 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 study treatment. Only ADRs were collected in this study. Participants may be represented in more than 1 category.
Ear and labyrinth disorders Vertigo	0.10% 1/1035 • Baseline up to Week 52 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 study treatment. Only ADRs were collected in this study. Participants may be represented in more than 1 category.
Cardiac disorders Cardiac failure	0.19% 2/1035 • Baseline up to Week 52 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 study treatment. Only ADRs were collected in this study. Participants may be represented in more than 1 category.
Hepatobiliary disorders Hepatic function abnormal	0.10% 1/1035 • Baseline up to Week 52 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 study treatment. Only ADRs were collected in this study. Participants may be represented in more than 1 category.
Renal and urinary disorders Renal impairment	0.10% 1/1035 • Baseline up to Week 52 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 study treatment. Only ADRs were collected in this study. Participants may be represented in more than 1 category.
General disorders Generalised oedema	0.10% 1/1035 • Baseline up to Week 52 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 study treatment. Only ADRs were collected in this study. Participants may be represented in more than 1 category.
General disorders Oedema peripheral	0.10% 1/1035 • Baseline up to Week 52 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 study treatment. Only ADRs were collected in this study. Participants may be represented in more than 1 category.
Injury, poisoning and procedural complications Femoral neck fracture	0.10% 1/1035 • Baseline up to Week 52 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 study treatment. Only ADRs were collected in this study. Participants may be represented in more than 1 category.
Injury, poisoning and procedural complications Foot fracture	0.10% 1/1035 • Baseline up to Week 52 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 study treatment. Only ADRs were collected in this study. Participants may be represented in more than 1 category.
Injury, poisoning and procedural complications Ligament sprain	0.10% 1/1035 • Baseline up to Week 52 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 study treatment. Only ADRs were collected in this study. Participants may be represented in more than 1 category.

Other adverse events

Measure	Pioglitazone n=1035 participants at risk Pioglitazone 15 mg - 30 mg, tablet, orally, once daily for up to 12 months in participants based upon the disease severity. Participants will receive interventions as part of routine medical care.
Metabolism and nutrition disorders Hypoglycaemia	15.7% 163/1035 • Baseline up to Week 52 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 study treatment. Only ADRs were collected in this study. Participants may be represented in more than 1 category.
General disorders Face oedema	2.1% 22/1035 • Baseline up to Week 52 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 study treatment. Only ADRs were collected in this study. Participants may be represented in more than 1 category.
General disorders Oedema peripheral	10.0% 104/1035 • Baseline up to Week 52 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 study treatment. Only ADRs were collected in this study. Participants may be represented in more than 1 category.
Investigations Weight increased	1.4% 14/1035 • Baseline up to Week 52 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 study treatment. Only ADRs were collected in this study. Participants may be represented in more than 1 category.

Additional Information

Medical Director

Takeda

Phone: +1-877-825-3327

Email: trialdisclosures@takeda.com

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