Pioglitazone Tablets Special Drug Use Surveillance Combined Use of Biguanides / Long-term Treatment

Actos Tablets Special Drug Use Surveillance Combined Use of Biguanides / Long-term Treatment

Status

Completed

Phases

Unknown

Study type

Observational

Source

ClinicalTrials.gov

Registry ID

NCT02003014

Enrollment

899

Registered

2013-12-06

Start date

2009-02-28

Completion date

2012-01-31

Last updated

2016-11-10

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Type 2 Diabetes Mellitus

Keywords

Drug Therapy

Brief summary

To investigate the safety and efficacy of long-term treatment with pioglitazone (Actos tablets) in combination with biguanides (for 12 months after the start of pioglitazone tablets treatment) in patients with type 2 diabetes mellitus.

Detailed description

This is a special drug use surveillance with an observation period of 12 months designed to investigate the safety and efficacy of pioglitazone (Actos) in the routine clinical setting in patients with type 2 diabetes mellitus who responded inadequately to treatment with biguanides in addition to diet therapy and exercise therapy (planned sample size, 1000). The usual adult dosage is 15 to 30 mg of pioglitazone administered orally once daily before or after breakfast. Dose adjustment will be made according to gender, age, and symptoms with an upper limit of 45 mg.

Interventions

DRUGPioglitazone

Pioglitazone Tablets

Study design

Observational model

COHORT

Time perspective

PROSPECTIVE

Eligibility

Sex/Gender

ALL

Healthy volunteers

Inclusion criteria

1. Patients with type 2 diabetes mellitus who responded inadequately to treatment with biguanides in addition to diet therapy and exercise therapy 2. Patients with available HbA1c data within the 1 month prior to the start of Actos Tablets treatment 3. Patients likely to be available for a 12-month observation after the start of Actos Tablets treatment

Exclusion criteria

1. Patients who have received Actos Tablets within the past 3 months. 2. Patients who started treatment with biguanides and Actos Tablets simultaneously 3. Patients who discontinued biguanides and switched to Actos Tablets treatment. 4. Patients who received additional biguanides after the start of Actos Tablets treatment 5. Patients with contraindications to Actos Tablets treatment

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants Reporting One or More Adverse Drug Reactions	Baseline up to 12 months	Adverse drug reactions 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.
Number of Participants Reporting One or More Serious Adverse Drug Reactions	Baseline up to 12 months	Serious adverse drug reactions are defined as serious adverse events (SAEs) which are in the investigator's opinion of causal relationship to the study treatment. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.

Secondary

Measure	Time frame	Description
Change From Baseline in Body Weight	Baseline, Months 3, 6, 9, 12 and final assessment (up to Month 12)	Change relative to baseline in participant's weight measured at 3 months, 6 months, 9 months, 12 months or final visit (last visit for a participant in the study, up to Month 12).
Change From Baseline in Glycosylated Hemoglobin (HbA1c)	Baseline, Months 3, 6, 9, 12 and final assessment (up to Month 12)	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 3 months, 6 months, 9 months, 12 months or final visit (last visit for a participant in the study, up to Month 12) relative to baseline.
Change From Baseline Homeostasis Model Assessment of Insulin Resistance (HOMA-IR)	Baseline, Months 3, 6, 9, 12 and final assessment (up to Month 12)	The change between homeostasis model assessment of insulin resistance collected at 3 months, 6 months, 9 months, 12 months or final visit (last visit for a participant in the study, up to Month 12) relative to baseline. Homeostasis Model assessment of insulin resistance Measures insulin resistance, calculated by insulin times glucose, divided by a constant (22.5). A higher score indicates higher insulin resistance.
Change From Baseline in Immunoreactive Insulin (IRI)	Baseline, Months 3, 6, 9, 12 and final assessment (up to Month 12)	The change in the value of IRI (portion of insulin in blood measured by immunochemical methods for the hormone; presumed to represent the free \[unbound\] and biologically active fraction of total blood insulin) collected at 3 months, 6 months, 9 months, 12 months or final visit (last visit for a participant in the study, up to Month 12) relative to baseline.
Change From Baseline in Fasting Blood Glucose	Baseline, Months 3, 6, 9, 12 and final assessment (up to Month 12)	The change between the fasting blood glucose value collected at 3 months, 6 months, 9 months, 12 months or final visit (last visit for a participant in the study, up to Month 12) relative to baseline.

Participant flow

Recruitment details

Participants took part in the study at 152 investigative sites in Japan from 23 February 2009 to 31 January 2012.

Pre-assignment details

Participants with a historical diagnosis of type 2 diabetes mellitus who failed to respond adequately to treatment with biguanides were enrolled to receive pioglitazone 15 milligram (mg) - 30 mg for up to 12 months.

Participants by arm

Arm	Count
Pioglitazone Pioglitazone 15 mg - 30 mg, tablet, orally, once daily for up to 12 months in participants based upon the disease severity.	880
Total	880

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Case report forms uncollected	9
Overall Study	Investigator's transfer	4
Overall Study	Patient did not visit the study site	5
Overall Study	Treatment started after contract period	1

Baseline characteristics

Characteristic	Pioglitazone
Age, Continuous	58.9 years STANDARD_DEVIATION 11.69
Body Mass Index < 18.5 kilogram per square meter (kg/m^2)	14 participants
Body Mass Index >=18.5 to <25 kg/m^2	382 participants
Body Mass Index >=25 to <30 kg/m^2	346 participants
Body Mass Index >=30 kg/m^2	124 participants
Body Mass Index Unknown	14 participants
Breakdown of Complications Alcoholic liver injury	11 participants
Breakdown of Complications Cerebrovascular disease	38 participants
Breakdown of Complications Diabetic nephropathy	75 participants
Breakdown of Complications Diabetic neuropathy	58 participants
Breakdown of Complications Diabetic retinopathy	63 participants
Breakdown of Complications Dyslipidaemia	217 participants
Breakdown of Complications Heart disease	85 participants
Breakdown of Complications Hepatic steatosis	58 participants
Breakdown of Complications Hypertension	203 participants
Breakdown of Complications Liver disease (all types of liver disease)	79 participants
Breakdown of Complications Malignant tumor	8 participants
Breakdown of Complications Other	234 participants
Breakdown of Complications Other liver disease	19 participants
Breakdown of Complications Renal disease (including diabetic nephropathy)	85 participants
Breakdown of Complications Renal disease (other than diabetic nephropathy)	14 participants
Breakdown of Complications Viral liver injury	1 participants
Breakdown of Medical History Cerebrovascular disease	21 participants
Breakdown of Medical History Heart disease	20 participants
Breakdown of Medical History Liver disease	6 participants
Breakdown of Medical History Malignant tumor	23 participants
Breakdown of Medical History Other	154 participants
Breakdown of Medical History Renal disease	4 participants
Details Regarding Predisposition to Hypersensitivity Drug	12 participants
Details Regarding Predisposition to Hypersensitivity Food	5 participants
Details Regarding Predisposition to Hypersensitivity Other	7 participants
Drinking Habits Current drinker	346 participants
Drinking Habits Former drinker	46 participants
Drinking Habits None	474 participants
Drinking Habits Unknown	14 participants
Medical Complications Had no presence of medical complications	100 participants
Medical Complications Had presence of medical complications	780 participants
Medical History Had no presence of medical history	672 participants
Medical History Had presence of medical history	206 participants
Medical History Unknown	2 participants
Predisposition to Hypersensitivity Had no predisposition to hypersensitivity	856 participants
Predisposition to Hypersensitivity Had predisposition to hypersensitivity	24 participants
Pregnancy status Not pregnant	334 participants
Pregnancy status Pregnant	0 participants
Sex: Female, Male Female	334 Participants
Sex: Female, Male Male	546 Participants
Smoking Habits Current smoker	203 participants
Smoking Habits Former smoker	145 participants
Smoking Habits None	520 participants
Smoking Habits Unknown	12 participants
Time from diagnosis of type 2 diabetes >=10 years	354 participants
Time from diagnosis of type 2 diabetes >=5 to <10 years	239 participants
Time from diagnosis of type 2 diabetes Greater than equal to (>=) 1 to <5 years	194 participants
Time from diagnosis of type 2 diabetes Less than (<) 1 years	36 participants
Time from diagnosis of type 2 diabetes Unknown	57 participants
Weight < 40 kilogram (kg)	3 participants
Weight >=40 to <50 kg	54 participants
Weight >=50 to <60 kg	163 participants
Weight >=60 to <70 kg	268 participants
Weight >=70 kg	384 participants
Weight Unknown	8 participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	36 / 880
serious Total, serious adverse events	12 / 880

Outcome results

Primary

Number of Participants Reporting One or More Adverse Drug Reactions

Adverse drug reactions 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.

Time frame: Baseline up to 12 months

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

Arm	Measure	Value (NUMBER)
Pioglitazone	Number of Participants Reporting One or More Adverse Drug Reactions	79 participants

Primary

Number of Participants Reporting One or More Serious Adverse Drug Reactions

Serious adverse drug reactions are defined as serious adverse events (SAEs) which are in the investigator's opinion of causal relationship to the study treatment. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.

Time frame: Baseline up to 12 months

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

Arm	Measure	Value (NUMBER)
Pioglitazone	Number of Participants Reporting One or More Serious Adverse Drug Reactions	1 participants

Secondary

Change From Baseline Homeostasis Model Assessment of Insulin Resistance (HOMA-IR)

The change between homeostasis model assessment of insulin resistance collected at 3 months, 6 months, 9 months, 12 months or final visit (last visit for a participant in the study, up to Month 12) relative to baseline. Homeostasis Model assessment of insulin resistance Measures insulin resistance, calculated by insulin times glucose, divided by a constant (22.5). A higher score indicates higher insulin resistance.