Trial Outcomes & Findings for Effects of Titrated Oral Tolvaptan 15-60 mg Once Daily (QD) on Cognitive and Neurological Function in Elderly Hyponatremic Patients (NCT NCT00550459)

NCT ID: NCT00550459

Last Updated: 2011-04-28

Results Overview

Change from baseline to Day 22 in sum of all speed domain Z-scores:Reaction Time (Simple=recognize "yes" 50 times;Choice=recognize "yes" or "no" 50 times;Digit Vigilance=match 45 digits);Psychomotor Speed (Morse Tapping=tap button for 30 seconds with right \& left hands);Processing Speed (Rapid Visual Information Processing=detect consecutive sequences of 3 odd or 3 even digits;Numeric Working Memory=recognize numbers from series of 5 digits among 30;Word Recognition=remember 15 prior learned words from 30 total;results age-matched to healthy controls from Cognitive Drug Research normative data

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 57 participants
• Primary outcome timeframe: baseline and Day 22
• Results posted on: 2011-04-28

Participant Flow

16 United States (US) sites/clinics; first subject signed informed consent on 9/11/07; last subject's final visit on 12/16/08

Participant milestones

Measure	Placebo Placebo tablet given once daily for 21 days	Tolvaptan (15-60 mg) Tolvaptan tablet 15-60 mg given once daily for 21 days
Overall Study STARTED	28	29
Overall Study COMPLETED	27	26
Overall Study NOT COMPLETED	1	3

Reasons for withdrawal

Measure	Placebo Placebo tablet given once daily for 21 days	Tolvaptan (15-60 mg) Tolvaptan tablet 15-60 mg given once daily for 21 days
Overall Study Adverse Event	0	2
Overall Study Withdrawal by Subject	1	1

Baseline Characteristics

Effects of Titrated Oral Tolvaptan 15-60 mg Once Daily (QD) on Cognitive and Neurological Function in Elderly Hyponatremic Patients

Baseline characteristics by cohort

Measure	Placebo n=28 Participants Placebo tablet given once daily for 21 days	Tolvaptan (15-60 mg) n=29 Participants Tolvaptan tablet 15-60 mg given once daily for 21 days	Total n=57 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	6 Participants n=5 Participants	6 Participants n=7 Participants	12 Participants n=5 Participants
Age, Categorical >=65 years	22 Participants n=5 Participants	23 Participants n=7 Participants	45 Participants n=5 Participants
Age Continuous	71.3 years STANDARD_DEVIATION 9.7 • n=5 Participants	71.1 years STANDARD_DEVIATION 10.2 • n=7 Participants	71.2 years STANDARD_DEVIATION 9.9 • n=5 Participants
Sex: Female, Male Female	19 Participants n=5 Participants	15 Participants n=7 Participants	34 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	14 Participants n=7 Participants	23 Participants n=5 Participants
Region of Enrollment United States	28 participants n=5 Participants	29 participants n=7 Participants	57 participants n=5 Participants

PRIMARY outcome

Timeframe: baseline and Day 22

Population: Analysis based upon observed cases (OC).

Change from baseline to Day 22 in sum of all speed domain Z-scores:Reaction Time (Simple=recognize "yes" 50 times;Choice=recognize "yes" or "no" 50 times;Digit Vigilance=match 45 digits);Psychomotor Speed (Morse Tapping=tap button for 30 seconds with right & left hands);Processing Speed (Rapid Visual Information Processing=detect consecutive sequences of 3 odd or 3 even digits;Numeric Working Memory=recognize numbers from series of 5 digits among 30;Word Recognition=remember 15 prior learned words from 30 total;results age-matched to healthy controls from Cognitive Drug Research normative data

Outcome measures

Measure	Placebo n=27 Participants Placebo tablet given once daily for 21 days	Tolvaptan (15-60 mg) n=26 Participants Tolvaptan tablet 15-60 mg given once daily for 21 days
Change From Baseline in the Neurocognitive Composite Score of Speed Domains (NCS-SD; Sum of All Correct Speed Domain Z-Scores)	0.20 Z-score Standard Deviation 0.61	0.39 Z-score Standard Deviation 0.49

SECONDARY outcome

Timeframe: baseline and Day 22

Population: ITT population with OC

Change from baseline in the individual neurocognitive domains Z-score for Reaction Time in Computer Tests (simple reaction time test, choice reaction time test, digit vigilance test); ITT population

Outcome measures

Measure	Placebo n=27 Participants Placebo tablet given once daily for 21 days	Tolvaptan (15-60 mg) n=26 Participants Tolvaptan tablet 15-60 mg given once daily for 21 days
Change From Baseline to Day 22 in the Individual Neurocognitive Domains Included in the Primary Endpoint: Reaction Time in Computer Tests	0.21 Z-score Standard Deviation 0.86	0.33 Z-score Standard Deviation 0.41

SECONDARY outcome

Timeframe: baseline and Day 22

Population: ITT population with OC

Change from baseline to Day 22 in the individual neurocognitive domains Z-score for Psychomotor Speed (mean tap rate of Morse tapping test); ITT population

Outcome measures

Measure	Placebo n=27 Participants Placebo tablet given once daily for 21 days	Tolvaptan (15-60 mg) n=26 Participants Tolvaptan tablet 15-60 mg given once daily for 21 days
Change From Baseline in the Individual Neurocognitive Domains Included in the Primary Endpoint: Psychomotor Speed Via Morse Tapping Test	0.04 Z-score Standard Deviation 0.36	0.31 Z-score Standard Deviation 0.46

SECONDARY outcome

Timeframe: baseline and Day 22

Population: ITT population with OC

Change from baseline to Day 22 in the individual neurocognitive domains Z-score for Processing Speed of Rapid Visual Information Processing Test, Numeric Working Memory Test, and Word Recognition Test; ITT population

Outcome measures

Measure	Placebo n=27 Participants Placebo tablet given once daily for 21 days	Tolvaptan (15-60 mg) n=26 Participants Tolvaptan tablet 15-60 mg given once daily for 21 days
Change From Baseline in the Individual Neurocognitive Domains Included in the Primary Endpoint: Processing Speed of Rapid Visual Information Processing Test, Numeric Working Memory Test, and Word Recognition Test	0.24 Z-score Standard Deviation 0.75	0.48 Z-score Standard Deviation 0.91

SECONDARY outcome

Timeframe: baseline and Day 22

Population: ITT population with OC

Change from Baseline to Day 22 in the overall Neurocognitive Composite Score (NCS)comprising the sum of 7 neurocognitive domain Z-scores (Reaction Time, Psychomotor Speed, Processing Speed, Continuity of Attention, Working Memory/Executive Functions, Quality of Episodic Verbal Memory, and Postural Stability); ITT population

Outcome measures

Measure	Placebo n=27 Participants Placebo tablet given once daily for 21 days	Tolvaptan (15-60 mg) n=26 Participants Tolvaptan tablet 15-60 mg given once daily for 21 days
Change From Baseline in Overall Neurocognitive Composite Score	0.19 Z-score Standard Deviation 0.39	0.30 Z-score Standard Deviation 0.39

SECONDARY outcome

Timeframe: baseline and Day 22

Population: ITT population with OC

Change from baseline to Day 22 in Gait Test (Timed Get-Up-and-Go Test=time it takes for a seated subject to rise from a chair, walk 3 meters, walk around an object and return to sit in chair. Values: under 10 sec (no difficulties), 10 to 20 sec (starting to have balance difficulty), over 30 sec (at high risk for falls and dependent in most activities of daily living and mobility); test assesses risk to elderly subjects of falling and higher scores in seconds indicate higher risk of falling; ITT population

Outcome measures

Measure	Placebo n=26 Participants Placebo tablet given once daily for 21 days	Tolvaptan (15-60 mg) n=23 Participants Tolvaptan tablet 15-60 mg given once daily for 21 days
Change From Baseline in Gait Test (Timed Get-Up-and-Go Test)	1.06 Seconds Standard Deviation 5.63	-0.43 Seconds Standard Deviation 1.54

SECONDARY outcome

Timeframe: baseline and Day 22

Population: ITT population with LOCF (this group includes missing values)

Change from baseline to Day 22 in Postural Stability Test Z-score (This test measures gross motor control. The ability to stand upright without moving is assessed using the SWAY meter that is modeled on the Wright Ataxiameter. A cord from the meter is attached to the subject who is required to stand as still as possible with feet apart and eyes closed for 1 minute. The test is then repeated with eyes open for 1 minute. The outcomes of these tests are combined and measured as a movement Z-score. Higher result=better postural stability); ITT population

Outcome measures

Measure	Placebo n=25 Participants Placebo tablet given once daily for 21 days	Tolvaptan (15-60 mg) n=23 Participants Tolvaptan tablet 15-60 mg given once daily for 21 days
Change From Baseline in Postural Stability Test	1.3 Z-score Standard Deviation 4.68	-0.35 Z-score Standard Deviation 2.33

SECONDARY outcome

Timeframe: Baseline and Day 22

Population: ITT population with OC

Change from Baseline to Day 22 in Serum Sodium; ITT population

Outcome measures

Measure	Placebo n=26 Participants Placebo tablet given once daily for 21 days	Tolvaptan (15-60 mg) n=26 Participants Tolvaptan tablet 15-60 mg given once daily for 21 days
Change From Baseline in Serum Sodium; ITT Population	2.23 mEq/L Standard Deviation 3.51	7.04 mEq/L Standard Deviation 3.39

SECONDARY outcome

Timeframe: 28 days

Population: Safety population defined as all randomized subjects who consumed at least 1 dose of trial medication

Incidence of abnormal systolic & diastolic blood pressure values post-baseline (abnormal systolic values: >=180 mmHg + increase of >=20 mmHg, <= 90 mmHg + decrease >=20 mmHg; abnormal diastolic values: >=105 mmHg+increase of >=15 mmHg, <=50 mmHg + decrease of >= 15 mmHg)

Outcome measures

Measure	Placebo n=28 Participants Placebo tablet given once daily for 21 days	Tolvaptan (15-60 mg) n=29 Participants Tolvaptan tablet 15-60 mg given once daily for 21 days
Number of Patients With Vital Sign Abnormalities: Blood Pressure	2 participants	0 participants

SECONDARY outcome

Timeframe: 28 days

Population: Safety population defined as all randomized subjects who consumed at least 1 dose of trial medication

Incidence of abnormal pulse rate post-baseline [abnormal values: >=120 beats per minute (bpm) + increase of >=15 bpm; <=50 bpm + decrease of >=15 bpm]

Outcome measures

Measure	Placebo n=28 Participants Placebo tablet given once daily for 21 days	Tolvaptan (15-60 mg) n=29 Participants Tolvaptan tablet 15-60 mg given once daily for 21 days
Number of Patients With Vital Sign Abnormalities: Pulse Rate	0 participants	0 participants

SECONDARY outcome

Timeframe: 28 days

Population: Safety population defined as all randomized subjects who consumed at least 1 dose of trial medication

Incidence of clinically significant body weight change post-baseline (defined as change upward or downward of >=7%)

Outcome measures

Measure	Placebo n=27 Participants Placebo tablet given once daily for 21 days	Tolvaptan (15-60 mg) n=29 Participants Tolvaptan tablet 15-60 mg given once daily for 21 days
Number of Patients With Vital Sign Abnormalities: Body Weight	1 participants	1 participants

SECONDARY outcome

Timeframe: 28 days

Population: Safety population defined as all randomized subjects who consumed at least 1 dose of trial medication

Incidence of potentially clinically significant changes in body temperature post-baseline (defined as an increase of >=1.1 to >=38.3 degrees Celsius)

Outcome measures

Measure	Placebo n=28 Participants Placebo tablet given once daily for 21 days	Tolvaptan (15-60 mg) n=29 Participants Tolvaptan tablet 15-60 mg given once daily for 21 days
Number of Patients With Vital Sign Abnormalities: Body Temperature	1 participants	0 participants

SECONDARY outcome

Timeframe: 28 days

Population: Safety population defined as all randomized subjects who consumed at least 1 dose of trial medication

Incidence of clinically significant hemoglobin abnormalities post-baseline (normal range=11.8-16.8 g/dL)

Outcome measures

Measure	Placebo n=26 Participants Placebo tablet given once daily for 21 days	Tolvaptan (15-60 mg) n=29 Participants Tolvaptan tablet 15-60 mg given once daily for 21 days
Number of Patients With Hematology Laboratory Abnormalities: Hemoglobin	0 participants	1 participants

SECONDARY outcome

Timeframe: 28 days

Population: Safety population defined as all randomized subjects who consumed at least 1 dose of trial medication

Incidence of potentially clinically significant Activated Partial Thromboplastin Time (aPTT) levels post-baseline (normal range=22-34 seconds)

Outcome measures

Measure	Placebo n=27 Participants Placebo tablet given once daily for 21 days	Tolvaptan (15-60 mg) n=29 Participants Tolvaptan tablet 15-60 mg given once daily for 21 days
Number of Patients With Hematology Laboratory Abnormalities: Activated Partial Thromboplastin Time (aPTT)	1 participants	3 participants

SECONDARY outcome

Timeframe: 28 days

Population: Safety population defined as all randomized subjects who consumed at least 1 dose of trial medication

Incidence of potentially clinically significant lymphocyte count post-baseline (normal range = 16-46%)

Outcome measures

Measure	Placebo n=26 Participants Placebo tablet given once daily for 21 days	Tolvaptan (15-60 mg) n=29 Participants Tolvaptan tablet 15-60 mg given once daily for 21 days
Number of Patients With Hematology Laboratory Abnormalities: Lymphocytes	1 participants	2 participants

SECONDARY outcome

Timeframe: 28 days

Population: Safety population defined as all randomized subjects who consumed at least 1 dose of trial medication

Incidence of potentially clinically significant neutrophil count post-baseline (normal range=1.8-8 thousands/microliter)

Outcome measures

Measure	Placebo n=26 Participants Placebo tablet given once daily for 21 days	Tolvaptan (15-60 mg) n=29 Participants Tolvaptan tablet 15-60 mg given once daily for 21 days
Number of Patients With Hematology Laboratory Abnormalities: Neutrophils	2 participants	0 participants

SECONDARY outcome

Timeframe: 28 days

Population: Safety population defined as all randomized subjects who consumed at least 1 dose of trial medication

Incidence of potentially clinically significant BUN levels post-baseline (normal range=7-30 mg/dL)

Outcome measures

Measure	Placebo n=28 Participants Placebo tablet given once daily for 21 days	Tolvaptan (15-60 mg) n=29 Participants Tolvaptan tablet 15-60 mg given once daily for 21 days
Number of Patients With Serum Chemistry Laboratory Abnormalities: Blood Urea Nitrogen (BUN)	1 participants	2 participants

SECONDARY outcome

Timeframe: 28 days

Population: Safety population defined as all randomized subjects who consumed at least 1 dose of trial medication

Incidence of potentially clinically significant uric acid levels post-baseline (normal range=4-8.5 mg/dL)

Outcome measures

Measure	Placebo n=28 Participants Placebo tablet given once daily for 21 days	Tolvaptan (15-60 mg) n=29 Participants Tolvaptan tablet 15-60 mg given once daily for 21 days
Number of Patients With Serum Chemistry Laboratory Abnormalities: Uric Acid	0 participants	1 participants

SECONDARY outcome

Timeframe: 28 days

Population: Safety population defined as all randomized subjects who consumed at least 1 dose of trial medication

Incidence of potentially clinically significant cholesterol levels post-baseline (normal range=0-199 mg/dL)

Outcome measures

Measure	Placebo n=28 Participants Placebo tablet given once daily for 21 days	Tolvaptan (15-60 mg) n=29 Participants Tolvaptan tablet 15-60 mg given once daily for 21 days
Number of Patients With Serum Chemistry Laboratory Abnormalities: Cholesterol	0 participants	2 participants

SECONDARY outcome

Timeframe: 28 days

Population: Safety population defined as all randomized subjects who consumed at least 1 dose of trial medication

Incidence of potentially clinically significant glucose levels post-baseline (normal range=70-125 mg/dL)

Outcome measures

Measure	Placebo n=28 Participants Placebo tablet given once daily for 21 days	Tolvaptan (15-60 mg) n=29 Participants Tolvaptan tablet 15-60 mg given once daily for 21 days
Number of Patients With Serum Chemistry Laboratory Abnormalities: Glucose	2 participants	0 participants

SECONDARY outcome

Timeframe: 28 days

Population: Safety population defined as all randomized subjects who consumed at least 1 dose of trial medication

Incidence of potentially clinically significant magnesium levels post-baseline (normal range=1.2-2 mEq/L)

Outcome measures

Measure	Placebo n=28 Participants Placebo tablet given once daily for 21 days	Tolvaptan (15-60 mg) n=29 Participants Tolvaptan tablet 15-60 mg given once daily for 21 days
Number of Patients With Serum Chemistry Laboratory Abnormalities: Magnesium	0 participants	1 participants

SECONDARY outcome

Timeframe: 28 days

Population: Safety population defined as all randomized subjects who consumed at least 1 dose of trial medication

Incidence of potentially clinically significant ECG abnormalities (QT>500 msec) post-baseline

Outcome measures

Measure	Placebo n=28 Participants Placebo tablet given once daily for 21 days	Tolvaptan (15-60 mg) n=29 Participants Tolvaptan tablet 15-60 mg given once daily for 21 days
Number of Patients With Electrocardiogram (ECG) Abnormalities: QT >500 Milliseconds (Msec)	1 participants	0 participants

SECONDARY outcome

Timeframe: 28 days

Population: Safety population defined as all randomized subjects who consumed at least 1 dose of trial medication

Incidence of potentially clinically significant ECG abnormalities involving QRS interval (change > 100 msec)

Outcome measures

Measure	Placebo n=28 Participants Placebo tablet given once daily for 21 days	Tolvaptan (15-60 mg) n=29 Participants Tolvaptan tablet 15-60 mg given once daily for 21 days
Number of Patients With Electrocardiogram (ECG) Abnormalities: QRS Interval	1 participants	1 participants

SECONDARY outcome

Timeframe: 28 days

Population: Safety population defined as all randomized subjects who consumed at least 1 dose of trial medication

Incidence of potentially clinically significant ECG abnormalities (QTcB increase 30-60 msec)

Outcome measures

Measure	Placebo n=28 Participants Placebo tablet given once daily for 21 days	Tolvaptan (15-60 mg) n=29 Participants Tolvaptan tablet 15-60 mg given once daily for 21 days
Number of Patients With Electrocardiogram (ECG) Abnormalities: QTcB Increase 30-60 Msec	3 participants	4 participants

SECONDARY outcome

Timeframe: 28 days

Population: Safety population defined as all randomized subjects who consumed at least 1 dose of trial medication

Incidence of potentially clinically significant ECG abnormalities (QTcF increase 30-60 msec post-baseline)

Outcome measures

Measure	Placebo n=28 Participants Placebo tablet given once daily for 21 days	Tolvaptan (15-60 mg) n=29 Participants Tolvaptan tablet 15-60 mg given once daily for 21 days
Number of Patients With Electrocardiogram (ECG) Abnormalities: QTcF Increase 30-60 Msec	2 participants	3 participants

SECONDARY outcome

Timeframe: 28 days

Population: Safety population defined as all randomized subjects who consumed at least 1 dose of trial medication

Incidence of potentially clinically significant ECG abnormalities: ST Segment

Outcome measures

Measure	Placebo n=28 Participants Placebo tablet given once daily for 21 days	Tolvaptan (15-60 mg) n=29 Participants Tolvaptan tablet 15-60 mg given once daily for 21 days
Number of Patients With Electrocardiogram (ECG) Abnormalities: ST Segment	0 participants	2 participants

SECONDARY outcome

Timeframe: 28 days

Population: Safety population defined as all randomized subjects who consumed at least 1 dose of trial medication

Incidence of potentially clinically significant ECG abnormalities: T wave

Outcome measures

Measure	Placebo n=28 Participants Placebo tablet given once daily for 21 days	Tolvaptan (15-60 mg) n=29 Participants Tolvaptan tablet 15-60 mg given once daily for 21 days
Number of Patients With Electrocardiogram (ECG) Abnormalities: T Wave	1 participants	1 participants

SECONDARY outcome

Timeframe: 28 days

Population: Safety population defined as all randomized subjects who consumed at least 1 dose of trial medication

Incidence of potentially clinically significant ECG abnormalities: Right bundle branch block (RBBB), Left bundle branch block (LBBB), myocardial infarction (MI)

Outcome measures

Measure	Placebo n=28 Participants Placebo tablet given once daily for 21 days	Tolvaptan (15-60 mg) n=29 Participants Tolvaptan tablet 15-60 mg given once daily for 21 days
Number of Patients With Electrocardiogram (ECG) Abnormalities: Right Bundle Branch Block (RBBB), Left Bundle Branch Block (LBBB), Myocardial Infarction (MI)	0 participants	1 participants

SECONDARY outcome

Timeframe: 28 days

Population: Safety population defined as all randomized subjects who consumed at least 1 dose of trial medication

Incidence of potentially clinically significant ECG abnormalities: arrhythmia

Outcome measures

Measure	Placebo n=28 Participants Placebo tablet given once daily for 21 days	Tolvaptan (15-60 mg) n=29 Participants Tolvaptan tablet 15-60 mg given once daily for 21 days
Number of Patients With Electrocardiogram (ECG) Abnormalities: Arrhythmia	2 participants	6 participants

Adverse Events

Placebo

Serious events: 1 serious events

Other events: 13 other events

Deaths: 0 deaths

Tolvaptan (15-60 mg)

Serious events: 2 serious events

Other events: 17 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=28 participants at risk Placebo tablet given once daily for 21 days	Tolvaptan (15-60 mg) n=29 participants at risk Tolvaptan tablet 15-60 mg given once daily for 21 days
Gastrointestinal disorders Abdominal adhesions	0.00% 0/28 • 28 Days collection/elicitation of adverse event incidence	3.4% 1/29 • Number of events 1 • 28 Days collection/elicitation of adverse event incidence
Gastrointestinal disorders Abdominal distension	0.00% 0/28 • 28 Days collection/elicitation of adverse event incidence	3.4% 1/29 • Number of events 1 • 28 Days collection/elicitation of adverse event incidence
Cardiac disorders Bradycardia	3.6% 1/28 • Number of events 1 • 28 Days collection/elicitation of adverse event incidence	0.00% 0/29 • 28 Days collection/elicitation of adverse event incidence
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/28 • 28 Days collection/elicitation of adverse event incidence	3.4% 1/29 • Number of events 1 • 28 Days collection/elicitation of adverse event incidence
Gastrointestinal disorders Constipation	0.00% 0/28 • 28 Days collection/elicitation of adverse event incidence	3.4% 1/29 • Number of events 1 • 28 Days collection/elicitation of adverse event incidence
Gastrointestinal disorders Large intestinal obstruction	0.00% 0/28 • 28 Days collection/elicitation of adverse event incidence	3.4% 1/29 • Number of events 1 • 28 Days collection/elicitation of adverse event incidence
Gastrointestinal disorders Nausea	0.00% 0/28 • 28 Days collection/elicitation of adverse event incidence	3.4% 1/29 • Number of events 1 • 28 Days collection/elicitation of adverse event incidence
Gastrointestinal disorders Vomiting	0.00% 0/28 • 28 Days collection/elicitation of adverse event incidence	3.4% 1/29 • Number of events 1 • 28 Days collection/elicitation of adverse event incidence

Other adverse events

Measure	Placebo n=28 participants at risk Placebo tablet given once daily for 21 days	Tolvaptan (15-60 mg) n=29 participants at risk Tolvaptan tablet 15-60 mg given once daily for 21 days
Skin and subcutaneous tissue disorders Dermatitis	7.1% 2/28 • Number of events 2 • 28 Days collection/elicitation of adverse event incidence	0.00% 0/29 • 28 Days collection/elicitation of adverse event incidence
Nervous system disorders Dizziness	7.1% 2/28 • Number of events 4 • 28 Days collection/elicitation of adverse event incidence	6.9% 2/29 • Number of events 2 • 28 Days collection/elicitation of adverse event incidence
Gastrointestinal disorders Dry Mouth	0.00% 0/28 • 28 Days collection/elicitation of adverse event incidence	6.9% 2/29 • Number of events 2 • 28 Days collection/elicitation of adverse event incidence
General disorders Fatigue	7.1% 2/28 • Number of events 2 • 28 Days collection/elicitation of adverse event incidence	6.9% 2/29 • Number of events 2 • 28 Days collection/elicitation of adverse event incidence
Infections and infestations Nasopharyngitis	3.6% 1/28 • Number of events 1 • 28 Days collection/elicitation of adverse event incidence	6.9% 2/29 • Number of events 2 • 28 Days collection/elicitation of adverse event incidence
General disorders Oedema	0.00% 0/28 • 28 Days collection/elicitation of adverse event incidence	6.9% 2/29 • Number of events 2 • 28 Days collection/elicitation of adverse event incidence
General disorders Oedema peripheral	10.7% 3/28 • Number of events 4 • 28 Days collection/elicitation of adverse event incidence	6.9% 2/29 • Number of events 3 • 28 Days collection/elicitation of adverse event incidence
Renal and urinary disorders Pollakiuria	10.7% 3/28 • Number of events 3 • 28 Days collection/elicitation of adverse event incidence	13.8% 4/29 • Number of events 4 • 28 Days collection/elicitation of adverse event incidence
General disorders Thirst	7.1% 2/28 • Number of events 2 • 28 Days collection/elicitation of adverse event incidence	20.7% 6/29 • Number of events 6 • 28 Days collection/elicitation of adverse event incidence
Investigations Urine output increased	0.00% 0/28 • 28 Days collection/elicitation of adverse event incidence	10.3% 3/29 • Number of events 3 • 28 Days collection/elicitation of adverse event incidence
Investigations Weight decreased	0.00% 0/28 • 28 Days collection/elicitation of adverse event incidence	13.8% 4/29 • Number of events 4 • 28 Days collection/elicitation of adverse event incidence

Additional Information

Frank Czerwiec, MD, PhD; Sr. Director, Global Clinical Development

Otsuka Pharmaceutical Development & Commercialization, Inc.

Phone: (240) 683-3523

Email: frank.czerwiec@otsuka.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place