Trial Outcomes & Findings for A Multicenter Trial to Investigate the Efficacy and Safety of Tolvaptan in Patients With Hyponatremia in SIADH (NCT NCT03048747)

Last Updated: 2020-11-02

Results Overview

The percentage of subjects with normalized serum sodium concentration, defined as ≥135 mEq/L, on the day after final IMP administration will be calculated versus the number of subjects with serum sodium concentration of \<135 mEq/L at baseline on Day 1 of the treatment period.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

16 participants

Primary outcome timeframe

Baseline, Day2, Day3, Day4, Day5, Day7, Day14, Day21, Day after final study medication

Results posted on

2020-11-02

Participant Flow

This trial was conducted in 16 participants from 31 trial sites in Japan.

Adults with a definite diagnosis of SIADH in reference to "Diagnostic and Treatment Manual of the Hypersecretion of Vasopressin (SIADH), Revised in 2011"

Participant milestones

Participant milestones
Measure	Tolvaptan Tolvaptan tablets at 7.5, 15, 30 (one tablet each), or 60 mg (two 30 mg tablets) will be orally administered once daily after breakfast for up to 30 days. Tolvaptan Oral Tablet: Tolvaptan tablets at 7.5, 15, 30 (one tablet each), or 60 mg (two 30 mg tablets) will be orally administered once daily after breakfast for up to 30 days.
Overall Study STARTED	16
Overall Study COMPLETED	11
Overall Study NOT COMPLETED	5

Reasons for withdrawal

Reasons for withdrawal
Measure	Tolvaptan Tolvaptan tablets at 7.5, 15, 30 (one tablet each), or 60 mg (two 30 mg tablets) will be orally administered once daily after breakfast for up to 30 days. Tolvaptan Oral Tablet: Tolvaptan tablets at 7.5, 15, 30 (one tablet each), or 60 mg (two 30 mg tablets) will be orally administered once daily after breakfast for up to 30 days.
Overall Study Adverse Event	2
Overall Study Participant Met Withdrawal Criteria	2
Overall Study Physician Decision	1

Baseline Characteristics

A Multicenter Trial to Investigate the Efficacy and Safety of Tolvaptan in Patients With Hyponatremia in SIADH

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tolvaptan n=16 Participants Tolvaptan tablets at 7.5, 15, 30 (one tablet each), or 60 mg (two 30 mg tablets) will be orally administered once daily after breakfast for up to 30 days. Tolvaptan Oral Tablet: Tolvaptan tablets at 7.5, 15, 30 (one tablet each), or 60 mg (two 30 mg tablets) will be orally administered once daily after breakfast for up to 30 days.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	1 Participants n=5 Participants
Age, Categorical >=65 years	15 Participants n=5 Participants
Age, Continuous	71.9 years STANDARD_DEVIATION 6.1 • n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants
Sex: Female, Male Male	13 Participants n=5 Participants
Race/Ethnicity, Customized Japanese	16 Participants n=5 Participants
Region of Enrollment Japan	16 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Day2, Day3, Day4, Day5, Day7, Day14, Day21, Day after final study medication

Population: Efficacy sample consisted of all participants who received at least one dose of study medication and have Baseline and at least one Post-Baseline efficacy evaluation.

Outcome measures

Outcome measures
Measure	Tolvaptan n=16 Participants Tolvaptan tablets at 7.5, 15, 30 (one tablet each), or 60 mg (two 30 mg tablets) will be orally administered once daily after breakfast for up to 30 days. Tolvaptan Oral Tablet: Tolvaptan tablets at 7.5, 15, 30 (one tablet each), or 60 mg (two 30 mg tablets) will be orally administered once daily after breakfast for up to 30 days.
Percentage of Subjects With Normalized Serum Sodium Concentration on the Day After Final IMP Administration Day2	43.8 percentage of participants
Percentage of Subjects With Normalized Serum Sodium Concentration on the Day After Final IMP Administration Day3	80 percentage of participants
Percentage of Subjects With Normalized Serum Sodium Concentration on the Day After Final IMP Administration Day4	80 percentage of participants
Percentage of Subjects With Normalized Serum Sodium Concentration on the Day After Final IMP Administration Day5	85.7 percentage of participants
Percentage of Subjects With Normalized Serum Sodium Concentration on the Day After Final IMP Administration Day7	92.9 percentage of participants
Percentage of Subjects With Normalized Serum Sodium Concentration on the Day After Final IMP Administration Day14	83.3 percentage of participants
Percentage of Subjects With Normalized Serum Sodium Concentration on the Day After Final IMP Administration Day21	81.8 percentage of participants
Percentage of Subjects With Normalized Serum Sodium Concentration on the Day After Final IMP Administration Day after final study medication	81.3 percentage of participants

SECONDARY outcome

Timeframe: Day2, Day3, Day4, Day5, Day7, Day14, Day21 and the day after final IMP administration

Population: Efficacy sample consisted of all participants who received at least one dose of study medication and have Baseline and at least one Post-Baseline efficacy evaluation.

The mean and standard error of measured values for serum sodium concentration on the day of fixing the maintenance dose and on the day after final IMP administration were calculated. The day of fixing the maintenance dose: Day2, Day3, Day4, Day5, Day7, Day14, and Day21

Outcome measures

Outcome measures
Measure	Tolvaptan n=16 Participants Tolvaptan tablets at 7.5, 15, 30 (one tablet each), or 60 mg (two 30 mg tablets) will be orally administered once daily after breakfast for up to 30 days. Tolvaptan Oral Tablet: Tolvaptan tablets at 7.5, 15, 30 (one tablet each), or 60 mg (two 30 mg tablets) will be orally administered once daily after breakfast for up to 30 days.
Change in Serum Sodium Concentration Day2	6.9 mEq/L Standard Error 2.6
Change in Serum Sodium Concentration Day3	8.1 mEq/L Standard Error 3.8
Change in Serum Sodium Concentration Day4	8.5 mEq/L Standard Error 4.6
Change in Serum Sodium Concentration Day5	8.8 mEq/L Standard Error 4.4
Change in Serum Sodium Concentration Day7	10.0 mEq/L Standard Error 4.5
Change in Serum Sodium Concentration Day14	10.8 mEq/L Standard Error 3.7
Change in Serum Sodium Concentration Day21	10.4 mEq/L Standard Error 6.0
Change in Serum Sodium Concentration Day after final study medication	11.0 mEq/L Standard Error 4.3

Adverse Events

Tolvaptan

Serious events: 5 serious events

Other events: 15 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Tolvaptan n=16 participants at risk Tolvaptan
Cardiac disorders Supraventricular extrasystoles	6.2% 1/16 • Adverse events were monitored from signing of the informed consent form until follow-up, up to 7 weeks on average. A serious adverse event (SAE) was an untoward medical occurrence that resulted in death or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or a new problem experienced by a participant when enrolled in a trial whether or not it was considered drug related by study physician.
Cardiac disorders Ventricular extrasystoles	6.2% 1/16 • Adverse events were monitored from signing of the informed consent form until follow-up, up to 7 weeks on average. A serious adverse event (SAE) was an untoward medical occurrence that resulted in death or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or a new problem experienced by a participant when enrolled in a trial whether or not it was considered drug related by study physician.
Infections and infestations Bacteraemia	6.2% 1/16 • Adverse events were monitored from signing of the informed consent form until follow-up, up to 7 weeks on average. A serious adverse event (SAE) was an untoward medical occurrence that resulted in death or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or a new problem experienced by a participant when enrolled in a trial whether or not it was considered drug related by study physician.
Musculoskeletal and connective tissue disorders Back pain	6.2% 1/16 • Adverse events were monitored from signing of the informed consent form until follow-up, up to 7 weeks on average. A serious adverse event (SAE) was an untoward medical occurrence that resulted in death or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or a new problem experienced by a participant when enrolled in a trial whether or not it was considered drug related by study physician.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung adenocarcinoma	12.5% 2/16 • Adverse events were monitored from signing of the informed consent form until follow-up, up to 7 weeks on average. A serious adverse event (SAE) was an untoward medical occurrence that resulted in death or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or a new problem experienced by a participant when enrolled in a trial whether or not it was considered drug related by study physician.
Nervous system disorders Loss of consciousness	6.2% 1/16 • Adverse events were monitored from signing of the informed consent form until follow-up, up to 7 weeks on average. A serious adverse event (SAE) was an untoward medical occurrence that resulted in death or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or a new problem experienced by a participant when enrolled in a trial whether or not it was considered drug related by study physician.
Nervous system disorders Paralysis of recurrent laryngeal nerve	6.2% 1/16 • Adverse events were monitored from signing of the informed consent form until follow-up, up to 7 weeks on average. A serious adverse event (SAE) was an untoward medical occurrence that resulted in death or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or a new problem experienced by a participant when enrolled in a trial whether or not it was considered drug related by study physician.
Vascular disorders Circulatory collapse	6.2% 1/16 • Adverse events were monitored from signing of the informed consent form until follow-up, up to 7 weeks on average. A serious adverse event (SAE) was an untoward medical occurrence that resulted in death or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or a new problem experienced by a participant when enrolled in a trial whether or not it was considered drug related by study physician.
Vascular disorders Haemorrhage	6.2% 1/16 • Adverse events were monitored from signing of the informed consent form until follow-up, up to 7 weeks on average. A serious adverse event (SAE) was an untoward medical occurrence that resulted in death or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or a new problem experienced by a participant when enrolled in a trial whether or not it was considered drug related by study physician.

Other adverse events

Other adverse events
Measure	Tolvaptan n=16 participants at risk Tolvaptan
Blood and lymphatic system disorders Anaemia	6.2% 1/16 • Adverse events were monitored from signing of the informed consent form until follow-up, up to 7 weeks on average. A serious adverse event (SAE) was an untoward medical occurrence that resulted in death or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or a new problem experienced by a participant when enrolled in a trial whether or not it was considered drug related by study physician.
Blood and lymphatic system disorders Neutropenia	12.5% 2/16 • Adverse events were monitored from signing of the informed consent form until follow-up, up to 7 weeks on average. A serious adverse event (SAE) was an untoward medical occurrence that resulted in death or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or a new problem experienced by a participant when enrolled in a trial whether or not it was considered drug related by study physician.
Blood and lymphatic system disorders Thrombocytopenia	6.2% 1/16 • Adverse events were monitored from signing of the informed consent form until follow-up, up to 7 weeks on average. A serious adverse event (SAE) was an untoward medical occurrence that resulted in death or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or a new problem experienced by a participant when enrolled in a trial whether or not it was considered drug related by study physician.
Cardiac disorders Cardiac failure congestive	6.2% 1/16 • Adverse events were monitored from signing of the informed consent form until follow-up, up to 7 weeks on average. A serious adverse event (SAE) was an untoward medical occurrence that resulted in death or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or a new problem experienced by a participant when enrolled in a trial whether or not it was considered drug related by study physician.
Cardiac disorders Supraventricular extrasystoles	6.2% 1/16 • Adverse events were monitored from signing of the informed consent form until follow-up, up to 7 weeks on average. A serious adverse event (SAE) was an untoward medical occurrence that resulted in death or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or a new problem experienced by a participant when enrolled in a trial whether or not it was considered drug related by study physician.
Cardiac disorders Ventricular extrasystoles	6.2% 1/16 • Adverse events were monitored from signing of the informed consent form until follow-up, up to 7 weeks on average. A serious adverse event (SAE) was an untoward medical occurrence that resulted in death or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or a new problem experienced by a participant when enrolled in a trial whether or not it was considered drug related by study physician.
Ear and labyrinth disorders Cerumen impaction	6.2% 1/16 • Adverse events were monitored from signing of the informed consent form until follow-up, up to 7 weeks on average. A serious adverse event (SAE) was an untoward medical occurrence that resulted in death or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or a new problem experienced by a participant when enrolled in a trial whether or not it was considered drug related by study physician.
Eye disorders Cataract	6.2% 1/16 • Adverse events were monitored from signing of the informed consent form until follow-up, up to 7 weeks on average. A serious adverse event (SAE) was an untoward medical occurrence that resulted in death or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or a new problem experienced by a participant when enrolled in a trial whether or not it was considered drug related by study physician.
Gastrointestinal disorders Anorectal disorder	6.2% 1/16 • Adverse events were monitored from signing of the informed consent form until follow-up, up to 7 weeks on average. A serious adverse event (SAE) was an untoward medical occurrence that resulted in death or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or a new problem experienced by a participant when enrolled in a trial whether or not it was considered drug related by study physician.
Gastrointestinal disorders Constipation	12.5% 2/16 • Adverse events were monitored from signing of the informed consent form until follow-up, up to 7 weeks on average. A serious adverse event (SAE) was an untoward medical occurrence that resulted in death or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or a new problem experienced by a participant when enrolled in a trial whether or not it was considered drug related by study physician.
Gastrointestinal disorders Dental caries	6.2% 1/16 • Adverse events were monitored from signing of the informed consent form until follow-up, up to 7 weeks on average. A serious adverse event (SAE) was an untoward medical occurrence that resulted in death or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or a new problem experienced by a participant when enrolled in a trial whether or not it was considered drug related by study physician.
Gastrointestinal disorders Diarrhoea	6.2% 1/16 • Adverse events were monitored from signing of the informed consent form until follow-up, up to 7 weeks on average. A serious adverse event (SAE) was an untoward medical occurrence that resulted in death or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or a new problem experienced by a participant when enrolled in a trial whether or not it was considered drug related by study physician.
Gastrointestinal disorders Dry mouth	6.2% 1/16 • Adverse events were monitored from signing of the informed consent form until follow-up, up to 7 weeks on average. A serious adverse event (SAE) was an untoward medical occurrence that resulted in death or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or a new problem experienced by a participant when enrolled in a trial whether or not it was considered drug related by study physician.
Gastrointestinal disorders Nausea	12.5% 2/16 • Adverse events were monitored from signing of the informed consent form until follow-up, up to 7 weeks on average. A serious adverse event (SAE) was an untoward medical occurrence that resulted in death or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or a new problem experienced by a participant when enrolled in a trial whether or not it was considered drug related by study physician.
Gastrointestinal disorders Vomiting	12.5% 2/16 • Adverse events were monitored from signing of the informed consent form until follow-up, up to 7 weeks on average. A serious adverse event (SAE) was an untoward medical occurrence that resulted in death or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or a new problem experienced by a participant when enrolled in a trial whether or not it was considered drug related by study physician.
General disorders Malaise	6.2% 1/16 • Adverse events were monitored from signing of the informed consent form until follow-up, up to 7 weeks on average. A serious adverse event (SAE) was an untoward medical occurrence that resulted in death or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or a new problem experienced by a participant when enrolled in a trial whether or not it was considered drug related by study physician.
General disorders Pyrexia	12.5% 2/16 • Adverse events were monitored from signing of the informed consent form until follow-up, up to 7 weeks on average. A serious adverse event (SAE) was an untoward medical occurrence that resulted in death or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or a new problem experienced by a participant when enrolled in a trial whether or not it was considered drug related by study physician.
General disorders Thirst	18.8% 3/16 • Adverse events were monitored from signing of the informed consent form until follow-up, up to 7 weeks on average. A serious adverse event (SAE) was an untoward medical occurrence that resulted in death or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or a new problem experienced by a participant when enrolled in a trial whether or not it was considered drug related by study physician.
Hepatobiliary disorders Hepatic function abnormal	6.2% 1/16 • Adverse events were monitored from signing of the informed consent form until follow-up, up to 7 weeks on average. A serious adverse event (SAE) was an untoward medical occurrence that resulted in death or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or a new problem experienced by a participant when enrolled in a trial whether or not it was considered drug related by study physician.
Infections and infestations Bacteaemia	6.2% 1/16 • Adverse events were monitored from signing of the informed consent form until follow-up, up to 7 weeks on average. A serious adverse event (SAE) was an untoward medical occurrence that resulted in death or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or a new problem experienced by a participant when enrolled in a trial whether or not it was considered drug related by study physician.
Infections and infestations Gingivitis	12.5% 2/16 • Adverse events were monitored from signing of the informed consent form until follow-up, up to 7 weeks on average. A serious adverse event (SAE) was an untoward medical occurrence that resulted in death or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or a new problem experienced by a participant when enrolled in a trial whether or not it was considered drug related by study physician.
Infections and infestations Periodontitis	6.2% 1/16 • Adverse events were monitored from signing of the informed consent form until follow-up, up to 7 weeks on average. A serious adverse event (SAE) was an untoward medical occurrence that resulted in death or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or a new problem experienced by a participant when enrolled in a trial whether or not it was considered drug related by study physician.
Infections and infestations Skin bacterial Infection	6.2% 1/16 • Adverse events were monitored from signing of the informed consent form until follow-up, up to 7 weeks on average. A serious adverse event (SAE) was an untoward medical occurrence that resulted in death or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or a new problem experienced by a participant when enrolled in a trial whether or not it was considered drug related by study physician.
Injury, poisoning and procedural complications Fall	12.5% 2/16 • Adverse events were monitored from signing of the informed consent form until follow-up, up to 7 weeks on average. A serious adverse event (SAE) was an untoward medical occurrence that resulted in death or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or a new problem experienced by a participant when enrolled in a trial whether or not it was considered drug related by study physician.
Injury, poisoning and procedural complications Spinal compression fracture	6.2% 1/16 • Adverse events were monitored from signing of the informed consent form until follow-up, up to 7 weeks on average. A serious adverse event (SAE) was an untoward medical occurrence that resulted in death or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or a new problem experienced by a participant when enrolled in a trial whether or not it was considered drug related by study physician.
Injury, poisoning and procedural complications Wound	6.2% 1/16 • Adverse events were monitored from signing of the informed consent form until follow-up, up to 7 weeks on average. A serious adverse event (SAE) was an untoward medical occurrence that resulted in death or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or a new problem experienced by a participant when enrolled in a trial whether or not it was considered drug related by study physician.
Investigations Alanine aminotransferase increased	6.2% 1/16 • Adverse events were monitored from signing of the informed consent form until follow-up, up to 7 weeks on average. A serious adverse event (SAE) was an untoward medical occurrence that resulted in death or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or a new problem experienced by a participant when enrolled in a trial whether or not it was considered drug related by study physician.
Investigations Blood alanine phoshatase increased	6.2% 1/16 • Adverse events were monitored from signing of the informed consent form until follow-up, up to 7 weeks on average. A serious adverse event (SAE) was an untoward medical occurrence that resulted in death or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or a new problem experienced by a participant when enrolled in a trial whether or not it was considered drug related by study physician.
Investigations Blood creatinine increased	12.5% 2/16 • Adverse events were monitored from signing of the informed consent form until follow-up, up to 7 weeks on average. A serious adverse event (SAE) was an untoward medical occurrence that resulted in death or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or a new problem experienced by a participant when enrolled in a trial whether or not it was considered drug related by study physician.
Investigations Blood sodium increased	6.2% 1/16 • Adverse events were monitored from signing of the informed consent form until follow-up, up to 7 weeks on average. A serious adverse event (SAE) was an untoward medical occurrence that resulted in death or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or a new problem experienced by a participant when enrolled in a trial whether or not it was considered drug related by study physician.
Investigations Nuetrophil count decreased	6.2% 1/16 • Adverse events were monitored from signing of the informed consent form until follow-up, up to 7 weeks on average. A serious adverse event (SAE) was an untoward medical occurrence that resulted in death or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or a new problem experienced by a participant when enrolled in a trial whether or not it was considered drug related by study physician.
Investigations Platelet count decreased	12.5% 2/16 • Adverse events were monitored from signing of the informed consent form until follow-up, up to 7 weeks on average. A serious adverse event (SAE) was an untoward medical occurrence that resulted in death or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or a new problem experienced by a participant when enrolled in a trial whether or not it was considered drug related by study physician.
Investigations Weight decreased	12.5% 2/16 • Adverse events were monitored from signing of the informed consent form until follow-up, up to 7 weeks on average. A serious adverse event (SAE) was an untoward medical occurrence that resulted in death or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or a new problem experienced by a participant when enrolled in a trial whether or not it was considered drug related by study physician.
Investigations White blood cell count increased	6.2% 1/16 • Adverse events were monitored from signing of the informed consent form until follow-up, up to 7 weeks on average. A serious adverse event (SAE) was an untoward medical occurrence that resulted in death or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or a new problem experienced by a participant when enrolled in a trial whether or not it was considered drug related by study physician.
Metabolism and nutrition disorders Decreased appetite	18.8% 3/16 • Adverse events were monitored from signing of the informed consent form until follow-up, up to 7 weeks on average. A serious adverse event (SAE) was an untoward medical occurrence that resulted in death or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or a new problem experienced by a participant when enrolled in a trial whether or not it was considered drug related by study physician.
Metabolism and nutrition disorders Dehydration	6.2% 1/16 • Adverse events were monitored from signing of the informed consent form until follow-up, up to 7 weeks on average. A serious adverse event (SAE) was an untoward medical occurrence that resulted in death or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or a new problem experienced by a participant when enrolled in a trial whether or not it was considered drug related by study physician.
Metabolism and nutrition disorders hypocalcaemia	6.2% 1/16 • Adverse events were monitored from signing of the informed consent form until follow-up, up to 7 weeks on average. A serious adverse event (SAE) was an untoward medical occurrence that resulted in death or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or a new problem experienced by a participant when enrolled in a trial whether or not it was considered drug related by study physician.
Musculoskeletal and connective tissue disorders Back pain	6.2% 1/16 • Adverse events were monitored from signing of the informed consent form until follow-up, up to 7 weeks on average. A serious adverse event (SAE) was an untoward medical occurrence that resulted in death or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or a new problem experienced by a participant when enrolled in a trial whether or not it was considered drug related by study physician.
Musculoskeletal and connective tissue disorders musculoskeletal pain	6.2% 1/16 • Adverse events were monitored from signing of the informed consent form until follow-up, up to 7 weeks on average. A serious adverse event (SAE) was an untoward medical occurrence that resulted in death or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or a new problem experienced by a participant when enrolled in a trial whether or not it was considered drug related by study physician.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung adenocarcinoma	12.5% 2/16 • Adverse events were monitored from signing of the informed consent form until follow-up, up to 7 weeks on average. A serious adverse event (SAE) was an untoward medical occurrence that resulted in death or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or a new problem experienced by a participant when enrolled in a trial whether or not it was considered drug related by study physician.
Nervous system disorders Headache	6.2% 1/16 • Adverse events were monitored from signing of the informed consent form until follow-up, up to 7 weeks on average. A serious adverse event (SAE) was an untoward medical occurrence that resulted in death or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or a new problem experienced by a participant when enrolled in a trial whether or not it was considered drug related by study physician.
Nervous system disorders Loss of consciousness	6.2% 1/16 • Adverse events were monitored from signing of the informed consent form until follow-up, up to 7 weeks on average. A serious adverse event (SAE) was an untoward medical occurrence that resulted in death or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or a new problem experienced by a participant when enrolled in a trial whether or not it was considered drug related by study physician.
Nervous system disorders Paralysis recurrent Laryngeal nerve	6.2% 1/16 • Adverse events were monitored from signing of the informed consent form until follow-up, up to 7 weeks on average. A serious adverse event (SAE) was an untoward medical occurrence that resulted in death or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or a new problem experienced by a participant when enrolled in a trial whether or not it was considered drug related by study physician.
Psychiatric disorders Depressive symptom	6.2% 1/16 • Adverse events were monitored from signing of the informed consent form until follow-up, up to 7 weeks on average. A serious adverse event (SAE) was an untoward medical occurrence that resulted in death or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or a new problem experienced by a participant when enrolled in a trial whether or not it was considered drug related by study physician.
Psychiatric disorders Insomnia	6.2% 1/16 • Adverse events were monitored from signing of the informed consent form until follow-up, up to 7 weeks on average. A serious adverse event (SAE) was an untoward medical occurrence that resulted in death or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or a new problem experienced by a participant when enrolled in a trial whether or not it was considered drug related by study physician.
Renal and urinary disorders Bladder disoder	6.2% 1/16 • Adverse events were monitored from signing of the informed consent form until follow-up, up to 7 weeks on average. A serious adverse event (SAE) was an untoward medical occurrence that resulted in death or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or a new problem experienced by a participant when enrolled in a trial whether or not it was considered drug related by study physician.
Renal and urinary disorders Pollakiuria	6.2% 1/16 • Adverse events were monitored from signing of the informed consent form until follow-up, up to 7 weeks on average. A serious adverse event (SAE) was an untoward medical occurrence that resulted in death or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or a new problem experienced by a participant when enrolled in a trial whether or not it was considered drug related by study physician.
Respiratory, thoracic and mediastinal disorders Aspiration	6.2% 1/16 • Adverse events were monitored from signing of the informed consent form until follow-up, up to 7 weeks on average. A serious adverse event (SAE) was an untoward medical occurrence that resulted in death or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or a new problem experienced by a participant when enrolled in a trial whether or not it was considered drug related by study physician.
Respiratory, thoracic and mediastinal disorders Epistaxis	6.2% 1/16 • Adverse events were monitored from signing of the informed consent form until follow-up, up to 7 weeks on average. A serious adverse event (SAE) was an untoward medical occurrence that resulted in death or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or a new problem experienced by a participant when enrolled in a trial whether or not it was considered drug related by study physician.
Respiratory, thoracic and mediastinal disorders Hiccups	12.5% 2/16 • Adverse events were monitored from signing of the informed consent form until follow-up, up to 7 weeks on average. A serious adverse event (SAE) was an untoward medical occurrence that resulted in death or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or a new problem experienced by a participant when enrolled in a trial whether or not it was considered drug related by study physician.
Respiratory, thoracic and mediastinal disorders Productive cough	6.2% 1/16 • Adverse events were monitored from signing of the informed consent form until follow-up, up to 7 weeks on average. A serious adverse event (SAE) was an untoward medical occurrence that resulted in death or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or a new problem experienced by a participant when enrolled in a trial whether or not it was considered drug related by study physician.
Surgical and medical procedures Rapid correction of hyponatremia	6.2% 1/16 • Adverse events were monitored from signing of the informed consent form until follow-up, up to 7 weeks on average. A serious adverse event (SAE) was an untoward medical occurrence that resulted in death or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or a new problem experienced by a participant when enrolled in a trial whether or not it was considered drug related by study physician.
Vascular disorders Circulatory collapse	6.2% 1/16 • Adverse events were monitored from signing of the informed consent form until follow-up, up to 7 weeks on average. A serious adverse event (SAE) was an untoward medical occurrence that resulted in death or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or a new problem experienced by a participant when enrolled in a trial whether or not it was considered drug related by study physician.
Vascular disorders Haemorrhage	6.2% 1/16 • Adverse events were monitored from signing of the informed consent form until follow-up, up to 7 weeks on average. A serious adverse event (SAE) was an untoward medical occurrence that resulted in death or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or a new problem experienced by a participant when enrolled in a trial whether or not it was considered drug related by study physician.
Vascular disorders Hypotension	6.2% 1/16 • Adverse events were monitored from signing of the informed consent form until follow-up, up to 7 weeks on average. A serious adverse event (SAE) was an untoward medical occurrence that resulted in death or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or a new problem experienced by a participant when enrolled in a trial whether or not it was considered drug related by study physician.
Vascular disorders Orthostatic hypotension	6.2% 1/16 • Adverse events were monitored from signing of the informed consent form until follow-up, up to 7 weeks on average. A serious adverse event (SAE) was an untoward medical occurrence that resulted in death or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or a new problem experienced by a participant when enrolled in a trial whether or not it was considered drug related by study physician.

Additional Information

Director of Clinical Trials

Otsuka Pharmaceutical Co., LTD.

Phone: +81-3-6361-7366

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place