Trial Outcomes & Findings for Long-term Use of Takepron Capsules on the Prevention of Recurrence of Gastric/Duodenal Ulcer in Patients Receiving Low-dose Aspirin (NCT NCT02099682)

NCT ID: NCT02099682

Last Updated: 2016-11-04

Results Overview

Frequency, severity, and time to onset of adverse drug reactions 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: 3366 participants
• Primary outcome timeframe: 12 months
• Results posted on: 2016-11-04

Participant Flow

Participants took part in the study at 460 investigative sites in Japan from August 2010 to January 2014 (N=3366).

Patients with a history of gastric or duodenal ulcers and requiring long-term use of low-dose aspirin were enrolled in the study.

Participant milestones

Measure	Lansoprazole 15 mg Lansoprazole 15 mg orally once daily
Overall Study STARTED	3366
Overall Study Safety Analysis Set (SAS)	3255
Overall Study COMPLETED	3255
Overall Study NOT COMPLETED	111

Reasons for withdrawal

Measure	Lansoprazole 15 mg Lansoprazole 15 mg orally once daily
Overall Study Data Not Available	51
Overall Study Lost to Follow-up	31
Overall Study Other	29

Baseline Characteristics

Long-term Use of Takepron Capsules on the Prevention of Recurrence of Gastric/Duodenal Ulcer in Patients Receiving Low-dose Aspirin

Baseline characteristics by cohort

Measure	Lansoprazole 15 mg n=3255 Participants Lansoprazole 15 mg orally once daily
Age, Continuous	72.4 years STANDARD_DEVIATION 11.02 • n=5 Participants
Sex: Female, Male Female	1399 Participants n=5 Participants
Sex: Female, Male Male	1856 Participants n=5 Participants
Purpose for Low-Dose Aspirin Use Angina pectoris	1182 participants n=5 Participants
Purpose for Low-Dose Aspirin Use Myocardial infarction	531 participants n=5 Participants
Purpose for Low-Dose Aspirin Use Transient ischaemic attack (TIA)	221 participants n=5 Participants
Purpose for Low-Dose Aspirin Use Cerebral infarction	1225 participants n=5 Participants
Purpose for Low-Dose Aspirin Use Post-coronary artery bypass (CABG)	106 participants n=5 Participants
Purpose for Low-Dose Aspirin Use PTCA	398 participants n=5 Participants
Purpose for Low-Dose Aspirin Use Other	316 participants n=5 Participants
Gastric or Duodenal Ulcer History Breakdown Gastric ulcer	2718 participants n=5 Participants
Gastric or Duodenal Ulcer History Breakdown Duodenal ulcer	313 participants n=5 Participants
Gastric or Duodenal Ulcer History Breakdown Unknown	252 participants n=5 Participants
Gastric or Duodenal Ulcer History: Time of Onset Within 6 months of study drug administration	213 participants n=5 Participants
Gastric or Duodenal Ulcer History: Time of Onset ≥ 6 months, < 1 year before start of treatment	138 participants n=5 Participants
Gastric or Duodenal Ulcer History: Time of Onset 1 year or longer before the start of treatment	977 participants n=5 Participants
Gastric or Duodenal Ulcer History: Time of Onset Unknown	1927 participants n=5 Participants
H. pylori infection Negative	425 participants n=5 Participants
H. pylori infection Positive	171 participants n=5 Participants
H. pylori infection Unknown	2659 participants n=5 Participants

PRIMARY outcome

Timeframe: 12 months

Population: Safety analysis set - All participants who received at least 1 dose of lansoprazole.

Frequency, severity, and time to onset of adverse drug reactions 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

Measure	Lansoprazole 15 mg n=3255 Participants Lansoprazole 15 mg orally once daily
Frequency of Adverse Drug Reactions Enteritis infectious	1 participants
Frequency of Adverse Drug Reactions Lymphoma	1 participants
Frequency of Adverse Drug Reactions Diabetes mellitus	1 participants
Frequency of Adverse Drug Reactions Anxiety	1 participants
Frequency of Adverse Drug Reactions Dizziness	2 participants
Frequency of Adverse Drug Reactions Dysgeusia	1 participants
Frequency of Adverse Drug Reactions Headache	1 participants
Frequency of Adverse Drug Reactions Loss of consciousness	1 participants
Frequency of Adverse Drug Reactions Sudden hearing loss	1 participants
Frequency of Adverse Drug Reactions Abdominal discomfort	1 participants
Frequency of Adverse Drug Reactions Abdominal distension	1 participants
Frequency of Adverse Drug Reactions Abdominal pain	1 participants
Frequency of Adverse Drug Reactions Colitis	1 participants
Frequency of Adverse Drug Reactions Constipation	2 participants
Frequency of Adverse Drug Reactions Diarrhoea	23 participants
Frequency of Adverse Drug Reactions Enterocolitis	1 participants
Frequency of Adverse Drug Reactions Gastrooesophageal reflux disease	1 participants
Frequency of Adverse Drug Reactions Haematochezia	1 participants
Frequency of Adverse Drug Reactions Nausea	4 participants
Frequency of Adverse Drug Reactions Colitis microscopic	3 participants
Frequency of Adverse Drug Reactions Hypoaesthesia oral	1 participants
Frequency of Adverse Drug Reactions Faeces soft	1 participants
Frequency of Adverse Drug Reactions Drug eruption	3 participants
Frequency of Adverse Drug Reactions Eczema	1 participants
Frequency of Adverse Drug Reactions Hypersensitivity vasculitis	1 participants
Frequency of Adverse Drug Reactions Pruritus	1 participants
Frequency of Adverse Drug Reactions Rash generalised	1 participants
Frequency of Adverse Drug Reactions Back pain	1 participants
Frequency of Adverse Drug Reactions Osteoporosis	1 participants
Frequency of Adverse Drug Reactions Renal failure chronic	1 participants
Frequency of Adverse Drug Reactions Sudden death	1 participants
Frequency of Adverse Drug Reactions Thirst	1 participants
Frequency of Adverse Drug Reactions Hepatic enzyme increased	1 participants
Frequency of Adverse Drug Reactions Glycosylated haemoglobin increased	1 participants
Frequency of Adverse Drug Reactions Weight decreased	1 participants
Frequency of Adverse Drug Reactions Fall	1 participants
Frequency of Adverse Drug Reactions Spinal fracture	1 participants

SECONDARY outcome

Timeframe: From baseline to 12 months

Population: Efficacy analysis set: all participants who took the study drug at least once excluding those with gastric ulcers or duodenal ulcers at initiation of study drug treatment, or participants for whom low-dose aspirin use during study drug treatment could not be confirmed.

Summary of data on the presence or absence of endoscopic examinations.

Outcome measures

Measure	Lansoprazole 15 mg n=3210 Participants Lansoprazole 15 mg orally once daily
Presence or Absence of Endoscopic Examinations With endoscopy	2773 participants
Presence or Absence of Endoscopic Examinations Without endoscopy	437 participants

SECONDARY outcome

Timeframe: From baseline to 12 months

Population: Efficacy analysis set: all participants who took the study drug at least once excluding those with gastric ulcers or duodenal ulcers at initiation of study drug treatment, or participants for whom low-dose aspirin use during study drug treatment could not be confirmed.

Summary of data on the presence or absence of gastric or duodenal ulcers.

Outcome measures

Measure	Lansoprazole 15 mg n=3210 Participants Lansoprazole 15 mg orally once daily
Presence of Gastric or Duodenal Ulcer Present	3190 participants
Presence of Gastric or Duodenal Ulcer Absent	20 participants

SECONDARY outcome

Timeframe: From baseline to 12 months

Population: Efficacy analysis set: all participants who took the study drug at least once excluding those with gastric ulcers or duodenal ulcers at initiation of study drug treatment, or participants for whom low-dose aspirin use during study drug treatment could not be confirmed.

Summary of data on the presence or absence of gastric or duodenal hemorrhagic lesions.

Outcome measures

Measure	Lansoprazole 15 mg n=3210 Participants Lansoprazole 15 mg orally once daily
Presence of Gastric or Duodenal Hemorrhagic Lesion Present	3201 participants
Presence of Gastric or Duodenal Hemorrhagic Lesion Absent	9 participants

SECONDARY outcome

Timeframe: From baseline to 12 months

Population: Efficacy analysis set: all participants who took the study drug at least once excluding those with gastric ulcers or duodenal ulcers at initiation of study drug treatment, or participants for whom low-dose aspirin use during study drug treatment could not be confirmed.

Summary of data on the presence or absence of gastric/duodenal ulcer gastric/duodenal hemorrhagic lesion.

Outcome measures

Measure	Lansoprazole 15 mg n=3210 Participants Lansoprazole 15 mg orally once daily
Presence of Either Gastric/Duodenal Ulcer, or Gastric/Duodenal Hemorrhagic Lesion Present	3186 participants
Presence of Either Gastric/Duodenal Ulcer, or Gastric/Duodenal Hemorrhagic Lesion Absent	24 participants

SECONDARY outcome

Timeframe: From baseline to 12 months

Population: Efficacy analysis set: all participants who took the study drug at least once excluding those with gastric ulcers or duodenal ulcers at initiation of study drug treatment, or participants for whom low-dose aspirin use during study drug treatment could not be confirmed.

Summary of data on the presence or absence of treatment for duodenal ulcers or hemorrhagic lesions.

Outcome measures

Measure	Lansoprazole 15 mg n=3210 Participants Lansoprazole 15 mg orally once daily
Treatment for Gastric/Duodenal Ulcer or Lesion Present	0 participants
Treatment for Gastric/Duodenal Ulcer or Lesion Absent	24 participants

SECONDARY outcome

Timeframe: From baseline to 12 months

Population: Efficacy analysis set: all participants who took the study drug at least once excluding those with gastric ulcers or duodenal ulcers at initiation of study drug treatment, or participants for whom low-dose aspirin use during study drug treatment could not be confirmed.

Summary of data on the details of treatment for gastric or duodenal ulcers or hemorrhagic lesions.

Outcome measures

Measure	Lansoprazole 15 mg n=3210 Participants Lansoprazole 15 mg orally once daily
Details of Treatment (Including Duplicates) for Gastric or Duodenal Ulcers or Hemorrhagic Lesions Takepron Capsule or OD Tablet 15 mg	15 participants
Details of Treatment (Including Duplicates) for Gastric or Duodenal Ulcers or Hemorrhagic Lesions Takepron Capsule or OD Tablet 30 mg	2 participants
Details of Treatment (Including Duplicates) for Gastric or Duodenal Ulcers or Hemorrhagic Lesions Rabeprazole tablet 10 mg	2 participants
Details of Treatment (Including Duplicates) for Gastric or Duodenal Ulcers or Hemorrhagic Lesions H2 receptor antagonist (oral)	1 participants
Details of Treatment (Including Duplicates) for Gastric or Duodenal Ulcers or Hemorrhagic Lesions Omeprazole (injection)	2 participants
Details of Treatment (Including Duplicates) for Gastric or Duodenal Ulcers or Hemorrhagic Lesions H2 receptor antagonist (injection)	1 participants
Details of Treatment (Including Duplicates) for Gastric or Duodenal Ulcers or Hemorrhagic Lesions Other peptic ulcer drugs	2 participants
Details of Treatment (Including Duplicates) for Gastric or Duodenal Ulcers or Hemorrhagic Lesions Endoscopic hemostasis	1 participants
Details of Treatment (Including Duplicates) for Gastric or Duodenal Ulcers or Hemorrhagic Lesions Other	5 participants

SECONDARY outcome

Timeframe: From baseline to 12 months

Population: Efficacy analysis set: all participants who took the study drug at least once excluding those with gastric ulcers or duodenal ulcers at initiation of study drug treatment, or participants for whom low-dose aspirin use during study drug treatment could not be confirmed.

Summary of data on the outcome of treatment for gastric or duodenal ulcers or hemorrhagic lesions.

Outcome measures

Measure	Lansoprazole 15 mg n=3210 Participants Lansoprazole 15 mg orally once daily
Treatment Outcome (Including Duplicates) for Gastric or Duodenal Ulcers or Hemorrhagic Lesions Rabeprazole 10 mg: Relief	1 participants
Treatment Outcome (Including Duplicates) for Gastric or Duodenal Ulcers or Hemorrhagic Lesions H2 receptor antagonist (orally): Recovery	1 participants
Treatment Outcome (Including Duplicates) for Gastric or Duodenal Ulcers or Hemorrhagic Lesions Takepron 15 mg: Recovery	9 participants
Treatment Outcome (Including Duplicates) for Gastric or Duodenal Ulcers or Hemorrhagic Lesions Takepron 15 mg: Relief	6 participants
Treatment Outcome (Including Duplicates) for Gastric or Duodenal Ulcers or Hemorrhagic Lesions Takepron 30 mg: Recovery	1 participants
Treatment Outcome (Including Duplicates) for Gastric or Duodenal Ulcers or Hemorrhagic Lesions Takepron 30 mg: Relief	1 participants
Treatment Outcome (Including Duplicates) for Gastric or Duodenal Ulcers or Hemorrhagic Lesions Rabeprazole 10 mg: Recovery	1 participants
Treatment Outcome (Including Duplicates) for Gastric or Duodenal Ulcers or Hemorrhagic Lesions H2 receptor antagonist (orally): Relief	1 participants
Treatment Outcome (Including Duplicates) for Gastric or Duodenal Ulcers or Hemorrhagic Lesions Omeprazole (injection): Recovery	1 participants
Treatment Outcome (Including Duplicates) for Gastric or Duodenal Ulcers or Hemorrhagic Lesions Omeprazole (injection): Relief	1 participants
Treatment Outcome (Including Duplicates) for Gastric or Duodenal Ulcers or Hemorrhagic Lesions H2 receptor antagonist (injection): Recovery	2 participants
Treatment Outcome (Including Duplicates) for Gastric or Duodenal Ulcers or Hemorrhagic Lesions H2 receptor antagonist (injection): Relief	1 participants
Treatment Outcome (Including Duplicates) for Gastric or Duodenal Ulcers or Hemorrhagic Lesions Other peptic ulcer drugs: Recovery	3 participants
Treatment Outcome (Including Duplicates) for Gastric or Duodenal Ulcers or Hemorrhagic Lesions Other peptic ulcer drugs: Relief	2 participants
Treatment Outcome (Including Duplicates) for Gastric or Duodenal Ulcers or Hemorrhagic Lesions Endoscopic hemostasis: Recovery	9 participants
Treatment Outcome (Including Duplicates) for Gastric or Duodenal Ulcers or Hemorrhagic Lesions Endoscopic hemostasis: Relief	6 participants
Treatment Outcome (Including Duplicates) for Gastric or Duodenal Ulcers or Hemorrhagic Lesions Other: Recovery	1 participants
Treatment Outcome (Including Duplicates) for Gastric or Duodenal Ulcers or Hemorrhagic Lesions Other: Relief	1 participants

Adverse Events

Lansoprazole 15 mg

Serious events: 126 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	Lansoprazole 15 mg n=3255 participants at risk；n=3225 participants at risk Lansoprazole 15 mg orally once daily
Injury, poisoning and procedural complications Femoral neck fracture	0.03% 1/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Injury, poisoning and procedural complications Femur fracture	0.03% 1/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Infections and infestations Appendicitis	0.03% 1/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Infections and infestations Gastroenteritis	0.03% 1/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Infections and infestations Pneumonia	0.28% 9/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Infections and infestations Pyelonephritis	0.06% 2/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Infections and infestations Sepsis	0.03% 1/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Infections and infestations Urinary tract infection	0.03% 1/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bile duct cancer	0.03% 1/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.03% 1/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer	0.12% 4/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastric cancer	0.12% 4/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lymphoma	0.06% 2/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal cancer	0.03% 1/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine cancer	0.03% 1/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon adenoma	0.03% 1/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.12% 4/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-small cell lung cancer	0.03% 1/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatocellular carcinoma	0.03% 1/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Blood and lymphatic system disorders Disseminated intravascular coagulation	0.03% 1/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Psychiatric disorders Agitation	0.03% 1/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Psychiatric disorders Psychosomatic disease	0.03% 1/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Nervous system disorders Carotid artery stenosis	0.03% 1/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Nervous system disorders Cerebellar infarction	0.03% 1/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Nervous system disorders Cerebral haemorrhage	0.06% 2/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Nervous system disorders Cerebral infarction	0.16% 5/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Nervous system disorders Convulsion	0.03% 1/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Nervous system disorders Dyslalia	0.03% 1/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Nervous system disorders Epilepsy	0.03% 1/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Nervous system disorders Hemiparesis	0.03% 1/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Nervous system disorders Intracranial aneurysm	0.03% 1/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Nervous system disorders Thrombotic cerebral infarction	0.03% 1/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Eye disorders Cataract	0.03% 1/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Ear and labyrinth disorders Sudden hearing loss	0.03% 1/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Cardiac disorders Angina pectoris	0.12% 4/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Cardiac disorders Angina unstable	0.06% 2/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Cardiac disorders Aortic valve stenosis	0.03% 1/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Cardiac disorders Atrial fibrillation	0.06% 2/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Cardiac disorders Cardiac failure	0.25% 8/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Cardiac disorders Cardiac failure acute	0.06% 2/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Cardiac disorders Cardiac failure congestive	0.19% 6/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Cardiac disorders Myocardial infarction	0.16% 5/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Cardiac disorders Ventricular arrhythmia	0.03% 1/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Cardiac disorders Acute coronary syndrome	0.03% 1/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Vascular disorders Aortic aneurysm rupture	0.09% 3/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Vascular disorders Aortic dissection	0.03% 1/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Vascular disorders Hypotension	0.03% 1/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Vascular disorders Aortic rupture	0.03% 1/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	0.03% 1/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.03% 1/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Respiratory, thoracic and mediastinal disorders Chronic respiratory failure	0.03% 1/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Respiratory, thoracic and mediastinal disorders Emphysema	0.03% 1/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.03% 1/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.03% 1/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.16% 5/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Gastrointestinal disorders Abdominal pain	0.03% 1/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Gastrointestinal disorders Colitis ischaemic	0.06% 2/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Gastrointestinal disorders Diarrhoea	0.06% 2/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Gastrointestinal disorders Gastric polyps	0.03% 1/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Gastrointestinal disorders Gastric ulcer	0.03% 1/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Gastrointestinal disorders Gastritis	0.03% 1/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Gastrointestinal disorders Ileal ulcer	0.03% 1/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Gastrointestinal disorders Inguinal hernia	0.03% 1/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Gastrointestinal disorders Intestinal obstruction	0.03% 1/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Gastrointestinal disorders Melaena	0.03% 1/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Gastrointestinal disorders Pancreatitis acute	0.03% 1/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Gastrointestinal disorders Rectal ulcer	0.03% 1/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Gastrointestinal disorders Large intestine polyp	0.03% 1/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Gastrointestinal disorders Alcoholic pancreatitis	0.03% 1/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Gastrointestinal disorders Haemorrhagic erosive gastritis	0.03% 1/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Hepatobiliary disorders Bile duct stone	0.03% 1/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Hepatobiliary disorders Cholecystitis	0.06% 2/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Hepatobiliary disorders Cholelithiasis	0.03% 1/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Hepatobiliary disorders Hepatic function abnormal	0.03% 1/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Hepatobiliary disorders Liver disorder	0.03% 1/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Skin and subcutaneous tissue disorders Hypersensitivity vasculitis	0.03% 1/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Musculoskeletal and connective tissue disorders Muscle haemorrhage	0.03% 1/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Musculoskeletal and connective tissue disorders Spinal osteoarthritis	0.03% 1/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Renal and urinary disorders Renal failure acute	0.03% 1/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Renal and urinary disorders Renal impairment	0.03% 1/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Reproductive system and breast disorders Breast mass	0.03% 1/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
General disorders Death	0.06% 2/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
General disorders Oedema peripheral	0.03% 1/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
General disorders Pyrexia	0.03% 1/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
General disorders Sudden death	0.03% 1/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
General disorders Sudden cardiac death	0.03% 1/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
General disorders Accidental device ingestion	0.03% 1/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Injury, poisoning and procedural complications Failure to anastomose	0.03% 1/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Injury, poisoning and procedural complications Fall	0.06% 2/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Injury, poisoning and procedural complications Road traffic accident	0.06% 2/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Injury, poisoning and procedural complications Subdural haematoma	0.03% 1/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Injury, poisoning and procedural complications Traumatic ulcer	0.03% 1/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Injury, poisoning and procedural complications Traumatic fracture	0.03% 1/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Injury, poisoning and procedural complications Skull fracture	0.03% 1/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Surgical and medical procedures Coronary angioplasty	0.03% 1/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Surgical and medical procedures Enterostomy	0.03% 1/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.
Cardiac disorders Cardiac failure chronic	0.03% 1/3225 • From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 12 months). 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.

Other adverse events

Adverse event data not reported

Additional Information

Medical Director, Clinical Science

Takeda

Phone: 800-778-2860

Email: clinicaltrialregistry@tpna.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