Trial Outcomes & Findings for Long-term Use of Sonias Combination Tablets in Patients With Type 2 Diabetes Mellitus (NCT NCT02098733)

NCT ID: NCT02098733

Last Updated: 2016-04-15

Results Overview

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: 1168 participants
• Primary outcome timeframe: For 12 months
• Results posted on: 2016-04-15

Participant Flow

Participants took part in the study at 182 investigative sites in Japan from 15 June 2011 to 31 May 2014.

Participants with a historical diagnosis of type 2 diabetes mellitus for whom therapy with pioglitazone combined with glimepiride is suitable and long-term treatment is considered necessary were enrolled in one treatment group to receive pioglitazone/glimepiride 15 mg/1 mg or 30 mg/3 mg, orally once daily before or after breakfast.

Participant milestones

Measure	Pioglitazone/Glimepiride Pioglitazone/glimepiride 15 mg/1 mg or 30 mg/3 mg, orally once daily before or after breakfast.
Overall Study STARTED	1168
Overall Study COMPLETED	1158
Overall Study NOT COMPLETED	10

Reasons for withdrawal

Measure	Pioglitazone/Glimepiride Pioglitazone/glimepiride 15 mg/1 mg or 30 mg/3 mg, orally once daily before or after breakfast.
Overall Study Data Not Available	5
Overall Study Lost to Follow-up	5

Baseline Characteristics

Long-term Use of Sonias Combination Tablets in Patients With Type 2 Diabetes Mellitus

Baseline characteristics by cohort

Measure	Pioglitazone/Glimepiride n=1158 Participants Pioglitazone/glimepiride 15 mg/1 mg or 30 mg/3 mg, orally once daily before or after breakfast.
Breakdown of Complications Diabetic nephropathy	144 participants n=5 Participants
Breakdown of Complications Diabetic retinopathy	71 participants n=5 Participants
Breakdown of Complications Diabetic neuropathy	88 participants n=5 Participants
Age, Continuous	64.9 years STANDARD_DEVIATION 12.14 • n=5 Participants
Age, Customized <65 years	539 participants n=5 Participants
Age, Customized ≥65 years	619 participants n=5 Participants
Age, Customized ≥65 to <74 years	354 participants n=5 Participants
Age, Customized ≥75 years	265 participants n=5 Participants
Sex: Female, Male Female	439 Participants n=5 Participants
Sex: Female, Male Male	719 Participants n=5 Participants
Pregnancy Status <Females> Not pregnant	439 participants n=5 Participants
Pregnancy Status <Females> Pregnant	0 participants n=5 Participants
Weight	67.86 kg STANDARD_DEVIATION 14.281 • n=5 Participants
Weight Categorical <40 kg	7 participants n=5 Participants
Weight Categorical ≥40 to <50 kg	74 participants n=5 Participants
Weight Categorical ≥50 to <60 kg	223 participants n=5 Participants
Weight Categorical ≥60 to <70 kg	327 participants n=5 Participants
Weight Categorical ≥70 kg	427 participants n=5 Participants
Weight Categorical Unmeasured	100 participants n=5 Participants
Body Mass Index (BMI)	26.19 kg/m^2 STANDARD_DEVIATION 4.401 • n=5 Participants
BMI Categorical <18.5 kg/m^2	12 participants n=5 Participants
BMI Categorical ≥18.5 to <25 kg/m^2	422 participants n=5 Participants
BMI Categorical ≥25 to <30 kg/m^2	412 participants n=5 Participants
BMI Categorical ≥30 kg/m^2	165 participants n=5 Participants
BMI Categorical Unknown	147 participants n=5 Participants
Duration of Type 2 Diabetes	9.12 years STANDARD_DEVIATION 8.188 • n=5 Participants
Duration of Type 2 Diabetes, Categorical <2 years	92 participants n=5 Participants
Duration of Type 2 Diabetes, Categorical ≥2 to <5 years	160 participants n=5 Participants
Duration of Type 2 Diabetes, Categorical ≥5 to <10 years	262 participants n=5 Participants
Duration of Type 2 Diabetes, Categorical ≥10 years	274 participants n=5 Participants
Duration of Type 2 Diabetes, Categorical Unknown	370 participants n=5 Participants
Healthcare Category Outpatient	1155 participants n=5 Participants
Healthcare Category Inpatient	3 participants n=5 Participants
History of Allergies No	959 participants n=5 Participants
History of Allergies Yes	81 participants n=5 Participants
History of Allergies Unknown	118 participants n=5 Participants
Presence of Complications No	108 participants n=5 Participants
Presence of Complications Yes	1050 participants n=5 Participants
Breakdown of Complications Microangiopathy	227 participants n=5 Participants
Breakdown of Complications Hypertension	723 participants n=5 Participants
Breakdown of Complications Dyslipidaemia	787 participants n=5 Participants
Breakdown of Complications Hyperuricaemia	95 participants n=5 Participants
Breakdown of Complications Liver disease	154 participants n=5 Participants
Breakdown of Complications Renal disease	159 participants n=5 Participants
Breakdown of Complications Heart disease	134 participants n=5 Participants
Breakdown of Complications Cerebrovascular disease	76 participants n=5 Participants
Breakdown of Complications Malignant tumor	10 participants n=5 Participants
Breakdown of Complications Other	19 participants n=5 Participants
Presence of Medical History No	897 participants n=5 Participants
Presence of Medical History Yes	157 participants n=5 Participants
Presence of Medical History Unknown	104 participants n=5 Participants
Alcohol History (Drinking Alcohol-Containing Beverages Most Days) Yes	596 participants n=5 Participants
Alcohol History (Drinking Alcohol-Containing Beverages Most Days) No	375 participants n=5 Participants
Alcohol History (Drinking Alcohol-Containing Beverages Most Days) Unknown	187 participants n=5 Participants
Smoking Classification Never Smoked	516 participants n=5 Participants
Smoking Classification Current Smoker	191 participants n=5 Participants
Smoking Classification Ex-smoker	228 participants n=5 Participants
Smoking Classification Unknown	223 participants n=5 Participants
Compliance Rate with the Diet Regimen (At the Start of Treatment) ≥ 90%	285 participants n=5 Participants
Compliance Rate with the Diet Regimen (At the Start of Treatment) ≥ 70%	371 participants n=5 Participants
Compliance Rate with the Diet Regimen (At the Start of Treatment) ≥ 50%	286 participants n=5 Participants
Compliance Rate with the Diet Regimen (At the Start of Treatment) < 50%	91 participants n=5 Participants
Compliance Rate with the Diet Regimen (At the Start of Treatment) Undone or compliance status is unknown	125 participants n=5 Participants
Compliance rate with the Exercise Regimen (At the Start of Treatment) ≥ 90%	219 participants n=5 Participants
Compliance rate with the Exercise Regimen (At the Start of Treatment) ≥ 70%	279 participants n=5 Participants
Compliance rate with the Exercise Regimen (At the Start of Treatment) ≥ 50%	348 participants n=5 Participants
Compliance rate with the Exercise Regimen (At the Start of Treatment) < 50%	147 participants n=5 Participants
Compliance rate with the Exercise Regimen (At the Start of Treatment) Undone or compliance status is unknown	165 participants n=5 Participants
Timing of Initiation of Pioglitazone Before the Start of Study Treatment ≥ 3 months	104 participants n=5 Participants
Timing of Initiation of Pioglitazone Before the Start of Study Treatment < 3 months	17 participants n=5 Participants
Timing of Initiation of Pioglitazone Before the Start of Study Treatment Unknown	68 participants n=5 Participants
Timing of Initiation of Glimepiride Before the Start of Study Treatment ≥ 3 months	223 participants n=5 Participants
Timing of Initiation of Glimepiride Before the Start of Study Treatment < 3 months	42 participants n=5 Participants
Timing of Initiation of Glimepiride Before the Start of Study Treatment Unknown	73 participants n=5 Participants
Timing of Initiation of Pioglitazone and Glimepiride Before the Start of Study Treatment ≥ 3 months	347 participants n=5 Participants
Timing of Initiation of Pioglitazone and Glimepiride Before the Start of Study Treatment Other	60 participants n=5 Participants
Timing of Initiation of Pioglitazone and Glimepiride Before the Start of Study Treatment Unknown	151 participants n=5 Participants
Glycosylated Haemoglobin (HbA1c) at the Start of Study Treatment < 6.0%	35 participants n=5 Participants
Glycosylated Haemoglobin (HbA1c) at the Start of Study Treatment ≥ 6.0% to < 7.0%	274 participants n=5 Participants
Glycosylated Haemoglobin (HbA1c) at the Start of Study Treatment ≥ 7.0% to < 8.0%	427 participants n=5 Participants
Glycosylated Haemoglobin (HbA1c) at the Start of Study Treatment ≥ 8.0%	355 participants n=5 Participants
Glycosylated Haemoglobin (HbA1c) at the Start of Study Treatment Unknown	67 participants n=5 Participants
HbA1c at the Start of Study Treatment	7.71 percentage of glycosylated haemoglobin STANDARD_DEVIATION 1.313 • n=5 Participants

PRIMARY outcome

Timeframe: For 12 months

Population: All enrolled participants with available data.

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

Measure	Pioglitazone/Glimepiride n=1158 Participants Pioglitazone/glimepiride 15 mg/1 mg or 30 mg/3 mg, orally once daily before or after breakfast.
Number of Participants With Adverse Drug Reactions Hypoglycaemia	13 participants
Number of Participants With Adverse Drug Reactions Dizziness	4 participants
Number of Participants With Adverse Drug Reactions Dysgeusia	1 participants
Number of Participants With Adverse Drug Reactions Cardiac failure congestive	1 participants
Number of Participants With Adverse Drug Reactions Eructation	1 participants
Number of Participants With Adverse Drug Reactions Nausea	1 participants
Number of Participants With Adverse Drug Reactions Cholelithiasis	1 participants
Number of Participants With Adverse Drug Reactions Drug eruption	1 participants
Number of Participants With Adverse Drug Reactions Pruritus	2 participants
Number of Participants With Adverse Drug Reactions Swelling face	1 participants
Number of Participants With Adverse Drug Reactions Urticaria	1 participants
Number of Participants With Adverse Drug Reactions Face oedema	1 participants
Number of Participants With Adverse Drug Reactions Hunger	2 participants
Number of Participants With Adverse Drug Reactions Oedema	7 participants
Number of Participants With Adverse Drug Reactions Oedema peripheral	4 participants
Number of Participants With Adverse Drug Reactions Sudden death	1 participants
Number of Participants With Adverse Drug Reactions Headache	1 participants
Number of Participants With Adverse Drug Reactions Hypoaesthesia	1 participants
Number of Participants With Adverse Drug Reactions Cardiac failure	2 participants
Number of Participants With Adverse Drug Reactions Pleural effusion	1 participants
Number of Participants With Adverse Drug Reactions Feeling abnormal	1 participants
Number of Participants With Adverse Drug Reactions Blood creatine phosphokinase increased	1 participants
Number of Participants With Adverse Drug Reactions Alanine aminotransferase increased	1 participants
Number of Participants With Adverse Drug Reactions Blood triglycerides increased	1 participants
Number of Participants With Adverse Drug Reactions Blood glucose decreased	1 participants
Number of Participants With Adverse Drug Reactions Weight increased	8 participants

SECONDARY outcome

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

Population: All enrolled participants with data available.

Tabulated the changes from baseline in glycosylated hemoglobin (HbA1c) values 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

Measure	Pioglitazone/Glimepiride n=1059 Participants Pioglitazone/glimepiride 15 mg/1 mg or 30 mg/3 mg, orally once daily before or after breakfast.
Change From Baseline in Glycosylated Hemoglobin (HbA1c) Month 6 (n=893)	-0.55 percentage of glycosylated haemoglobin Standard Deviation 1.144
Change From Baseline in Glycosylated Hemoglobin (HbA1c) Month 9 (n=831)	-0.56 percentage of glycosylated haemoglobin Standard Deviation 1.107
Change From Baseline in Glycosylated Hemoglobin (HbA1c) Month 12 (n=462)	-0.57 percentage of glycosylated haemoglobin Standard Deviation 1.196
Change From Baseline in Glycosylated Hemoglobin (HbA1c) Final Assessment (n=1,054)	-0.57 percentage of glycosylated haemoglobin Standard Deviation 1.152
Change From Baseline in Glycosylated Hemoglobin (HbA1c) Month 3 (n=1016)	-0.45 percentage of glycosylated haemoglobin Standard Deviation 0.936

SECONDARY outcome

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

Population: All enrolled participants with data available.

Tabulated glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at each test time point or final visit relative to baseline.

Outcome measures

Measure	Pioglitazone/Glimepiride n=1059 Participants Pioglitazone/glimepiride 15 mg/1 mg or 30 mg/3 mg, orally once daily before or after breakfast.
Glycosylated Hemoglobin (HbA1c) At the start of treatment (n=1054)	7.70 percentage of glycosylated haemoglobin Standard Deviation 1.302
Glycosylated Hemoglobin (HbA1c) Month 3 (n=1016)	7.25 percentage of glycosylated haemoglobin Standard Deviation 1.102
Glycosylated Hemoglobin (HbA1c) Month 6 (n=893)	7.14 percentage of glycosylated haemoglobin Standard Deviation 1.059
Glycosylated Hemoglobin (HbA1c) Month 9 (n=831)	7.08 percentage of glycosylated haemoglobin Standard Deviation 0.995
Glycosylated Hemoglobin (HbA1c) Month 12 (n=462)	7.12 percentage of glycosylated haemoglobin Standard Deviation 1.077
Glycosylated Hemoglobin (HbA1c) Final Assessment (n=1054)	7.13 percentage of glycosylated haemoglobin Standard Deviation 1.100

SECONDARY outcome

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

Population: All enrolled participants with data available.

Tabulated the changes from baseline in fasting blood glucose level 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

Measure	Pioglitazone/Glimepiride n=1059 Participants Pioglitazone/glimepiride 15 mg/1 mg or 30 mg/3 mg, orally once daily before or after breakfast.
Change From Baseline in Fasting Blood Glucose Level Month 3 (n=331)	-16.7 mg/dL Standard Deviation 44.39
Change From Baseline in Fasting Blood Glucose Level Month 6 (n=287)	-14.3 mg/dL Standard Deviation 48.17
Change From Baseline in Fasting Blood Glucose Level Month 9 (n=273)	-15.7 mg/dL Standard Deviation 45.94
Change From Baseline in Fasting Blood Glucose Level Month 12 (n=462)	-12.5 mg/dL Standard Deviation 45.50
Change From Baseline in Fasting Blood Glucose Level Final Assessment (n=369)	-16.4 mg/dL Standard Deviation 47.41

SECONDARY outcome

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

Population: All enrolled participants with data available.

Tabulated fasting blood glucose level from baseline at each test time point.

Outcome measures

Measure	Pioglitazone/Glimepiride n=1059 Participants Pioglitazone/glimepiride 15 mg/1 mg or 30 mg/3 mg, orally once daily before or after breakfast.
Fasting Blood Glucose Level At the start of treatment (n=369)	147.2 mg/dL Standard Deviation 51.87
Fasting Blood Glucose Level Month 3 (n=331)	130.2 mg/dL Standard Deviation 43.18
Fasting Blood Glucose Level Month 6 (n=287)	131.7 mg/dL Standard Deviation 41.09
Fasting Blood Glucose Level Month 9 (n=273)	129.2 mg/dL Standard Deviation 36.71
Fasting Blood Glucose Level Month 12 (n=462)	126.8 mg/dL Standard Deviation 42.01
Fasting Blood Glucose Level Final Assessment (n=369)	130.9 mg/dL Standard Deviation 46.82

SECONDARY outcome

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

Population: All enrolled participants with data available.

Tabulated 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

Measure	Pioglitazone/Glimepiride n=1059 Participants Pioglitazone/glimepiride 15 mg/1 mg or 30 mg/3 mg, orally once daily before or after breakfast.
Change From Baseline in Fasting Insulin Level Month 3 (n=39)	-0.24 μU/dL Standard Deviation 1.376
Change From Baseline in Fasting Insulin Level Month 6 (n=32)	0.02 μU/dL Standard Deviation 1.163
Change From Baseline in Fasting Insulin Level Month 9 (n=30)	-0.60 μU/dL Standard Deviation 2.121
Change From Baseline in Fasting Insulin Level Month 12 (n=18)	0.58 μU/dL Standard Deviation 2.582
Change From Baseline in Fasting Insulin Level Final Assessment (n=46)	-0.01 μU/dL Standard Deviation 2.397

SECONDARY outcome

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

Population: All enrolled participants with data available.

Tabulated fasting insulin level at each test time point.

Outcome measures

Measure	Pioglitazone/Glimepiride n=1059 Participants Pioglitazone/glimepiride 15 mg/1 mg or 30 mg/3 mg, orally once daily before or after breakfast.
Fasting Insulin Level At the start of treatment (n=46)	5.78 μU/dL Standard Deviation 2.880
Fasting Insulin Level Month 3 (n=39)	5.38 μU/dL Standard Deviation 2.885
Fasting Insulin Level Month 6 (n=32)	5.48 μU/dL Standard Deviation 2.964
Fasting Insulin Level Month 9 (n=30)	5.40 μU/dL Standard Deviation 2.642
Fasting Insulin Level Month 12 (n=18)	6.57 μU/dL Standard Deviation 3.789
Fasting Insulin Level Final Assessment (n=46)	5.77 μU/dL Standard Deviation 3.238

Adverse Events

Pioglitazone/Glimepiride

Serious events: 23 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	Pioglitazone/Glimepiride n=1158 participants at risk Pioglitazone/glimepiride 15 mg/1 mg or 30 mg/3 mg, orally once daily before or after breakfast.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Oesophageal carcinoma	0.09% 1/1158 • For 12 months At each visit the investigator documented any occurrence of adverse events and abnormal laboratory findings. Any event reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic carcinoma	0.09% 1/1158 • For 12 months At each visit the investigator documented any occurrence of adverse events and abnormal laboratory findings. Any event reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.09% 1/1158 • For 12 months At each visit the investigator documented any occurrence of adverse events and abnormal laboratory findings. Any event reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.09% 1/1158 • For 12 months At each visit the investigator documented any occurrence of adverse events and abnormal laboratory findings. Any event reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Blood and lymphatic system disorders Anaemia	0.09% 1/1158 • For 12 months At each visit the investigator documented any occurrence of adverse events and abnormal laboratory findings. Any event reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders Hyperkalaemia	0.09% 1/1158 • For 12 months At each visit the investigator documented any occurrence of adverse events and abnormal laboratory findings. Any event reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders Marasmus	0.09% 1/1158 • For 12 months At each visit the investigator documented any occurrence of adverse events and abnormal laboratory findings. Any event reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Psychiatric disorders Completed suicide	0.09% 1/1158 • For 12 months At each visit the investigator documented any occurrence of adverse events and abnormal laboratory findings. Any event reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Cerebrovascular accident	0.09% 1/1158 • For 12 months At each visit the investigator documented any occurrence of adverse events and abnormal laboratory findings. Any event reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Convulsion	0.09% 1/1158 • For 12 months At each visit the investigator documented any occurrence of adverse events and abnormal laboratory findings. Any event reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Cardiac disorders Cardiac failure	0.09% 1/1158 • For 12 months At each visit the investigator documented any occurrence of adverse events and abnormal laboratory findings. Any event reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Cardiac disorders Cardiac failure congestive	0.09% 1/1158 • For 12 months At each visit the investigator documented any occurrence of adverse events and abnormal laboratory findings. Any event reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Mallory-Weiss syndrome	0.09% 1/1158 • For 12 months At each visit the investigator documented any occurrence of adverse events and abnormal laboratory findings. Any event reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Hepatobiliary disorders Cholelithiasis	0.09% 1/1158 • For 12 months At each visit the investigator documented any occurrence of adverse events and abnormal laboratory findings. Any event reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Hepatobiliary disorders Jaundice	0.09% 1/1158 • For 12 months At each visit the investigator documented any occurrence of adverse events and abnormal laboratory findings. Any event reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Hepatobiliary disorders Bile duct obstruction	0.09% 1/1158 • For 12 months At each visit the investigator documented any occurrence of adverse events and abnormal laboratory findings. Any event reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Renal and urinary disorders Calculus ureteric	0.09% 1/1158 • For 12 months At each visit the investigator documented any occurrence of adverse events and abnormal laboratory findings. Any event reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Renal and urinary disorders Nephrolithiasis	0.09% 1/1158 • For 12 months At each visit the investigator documented any occurrence of adverse events and abnormal laboratory findings. Any event reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Renal and urinary disorders Renal failure	0.09% 1/1158 • For 12 months At each visit the investigator documented any occurrence of adverse events and abnormal laboratory findings. Any event reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders Death	0.09% 1/1158 • For 12 months At each visit the investigator documented any occurrence of adverse events and abnormal laboratory findings. Any event reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders Drowning	0.09% 1/1158 • For 12 months At each visit the investigator documented any occurrence of adverse events and abnormal laboratory findings. Any event reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders Face oedema	0.09% 1/1158 • For 12 months At each visit the investigator documented any occurrence of adverse events and abnormal laboratory findings. Any event reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders Oedema	0.09% 1/1158 • For 12 months At each visit the investigator documented any occurrence of adverse events and abnormal laboratory findings. Any event reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders Sudden death	0.09% 1/1158 • For 12 months At each visit the investigator documented any occurrence of adverse events and abnormal laboratory findings. Any event reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Injury, poisoning and procedural complications Fall	0.09% 1/1158 • For 12 months At each visit the investigator documented any occurrence of adverse events and abnormal laboratory findings. Any event reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Injury, poisoning and procedural complications Road traffic accident	0.17% 2/1158 • For 12 months At each visit the investigator documented any occurrence of adverse events and abnormal laboratory findings. Any event reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Injury, poisoning and procedural complications Lumbar vertebral fracture	0.09% 1/1158 • For 12 months At each visit the investigator documented any occurrence of adverse events and abnormal laboratory findings. Any event reported by the participant or observed by the investigator 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

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