Trial Outcomes & Findings for Safety of Lixivaptan in Subjects Previously Treated With Tolvaptan for Autosomal Dominant Polycystic Kidney Disease (NCT NCT04152837)

Last Updated: 2023-04-10

Results Overview

Number of participants who develop serum ALT levels \>3 x ULN which are assessed by the independent Hepatic Events Review Committee (HERC) to be at least probably related to lixivaptan and result in the discontinuation of lixivaptan treatment. The independent HERC, after reviewing demographic, medical and medication history, safety data and other relevant data of participants who develop liver abnormalities, will determine the probable causality for liver chemistry test abnormalities of concern and the relatedness to lixivaptan using the Drug-Induced Liver Injury Network probability criteria (Fontana et al., 2009). The normal range of ALT was defined as 0-55 U/L.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

7 participants

Primary outcome timeframe

Up to 58 weeks

Results posted on

2023-04-10

Participant Flow

Participant milestones

Participant milestones
Measure	Lixivaptan After meeting entry criteria during a 1-3-week Screening Period, participants entered a 3-week no study drug Baseline Period to obtain baseline measurements. All participants who completed the Pre-Titration period entered a 3-6 week Titration Period following the Baseline Period, during which each individual participant was titrated with oral lixivaptan capsules administered twice daily to a dose that was tolerated and resulted in a reduced trough urine specific gravity (or until the maximum dose level was reached) for each individual. The minimum dose to enter the Maintenance Period was 100 mg BID, and the maximum was 200 mg BID. Treatment in the Maintenance Period was continued for up to 52 weeks.
Baseline Period (No Treatment) STARTED	7
Baseline Period (No Treatment) COMPLETED	6
Baseline Period (No Treatment) NOT COMPLETED	1
Titration Period STARTED	6
Titration Period COMPLETED	6
Titration Period NOT COMPLETED	0
Maintenance Period STARTED	6
Maintenance Period COMPLETED	2
Maintenance Period NOT COMPLETED	4
Follow-up Period STARTED	6
Follow-up Period COMPLETED	6
Follow-up Period NOT COMPLETED	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Lixivaptan After meeting entry criteria during a 1-3-week Screening Period, participants entered a 3-week no study drug Baseline Period to obtain baseline measurements. All participants who completed the Pre-Titration period entered a 3-6 week Titration Period following the Baseline Period, during which each individual participant was titrated with oral lixivaptan capsules administered twice daily to a dose that was tolerated and resulted in a reduced trough urine specific gravity (or until the maximum dose level was reached) for each individual. The minimum dose to enter the Maintenance Period was 100 mg BID, and the maximum was 200 mg BID. Treatment in the Maintenance Period was continued for up to 52 weeks.
Baseline Period (No Treatment) Baseline Failure	1
Maintenance Period Adverse Event	1
Maintenance Period Withdrawal by Subject	1
Maintenance Period Sponsor Termination of Study	2

Baseline Characteristics

Safety of Lixivaptan in Subjects Previously Treated With Tolvaptan for Autosomal Dominant Polycystic Kidney Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Safety Population n=6 Participants Baseline data were obtained from the Safety Population, which consisted of all participants who were treated with lixivaptan.
Age, Continuous	48.0 years STANDARD_DEVIATION 12.59 • n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants
Race (NIH/OMB) White	4 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	6 participants n=5 Participants
Body Mass Index	24.70 kg/m^2 STANDARD_DEVIATION 3.107 • n=5 Participants

PRIMARY outcome

Timeframe: Up to 58 weeks

Outcome measures

Outcome measures
Measure	Lixivaptan: Titration and Maintenance Periods n=6 Participants All participants who successfully completed the Baseline Period entered a 3-6-week Titration Period, during which each individual participant was titrated with oral lixivaptan capsules administered twice daily to a dose that was tolerated and resulted in a reduced trough urine specific gravity (or until the maximum dose level was reached) for each individual. The minimum dose to enter the Maintenance Period was 100 mg BID, and the maximum was 200 mg BID. Treatment in the Maintenance Period was continued for up to 52 weeks.
Number of Participants Who Develop Serum Alanine Aminotransferase (ALT) Levels >3 × ULN During the Titration or Maintenance Periods Assessed to be Related to Lixivaptan and Result in Discontinuation of Lixivaptan Treatment	1 Participants

SECONDARY outcome

Timeframe: Up to 58 weeks

Number of participants who develop serum ALT levels \>5 x ULN which are assessed by the independent HERC to be at least probably related to lixivaptan and result in the discontinuation of lixivaptan treatment. The independent HERC, after reviewing demographic, medical and medication history, safety data and other relevant data of participants who develop liver abnormalities, will determine the probable causality for liver chemistry test abnormalities of concern and the relatedness to lixivaptan using the Drug-Induced Liver Injury Network probability criteria (Fontana et al., 2009). The normal range of ALT was defined as 0-55 U/L.

Outcome measures

Outcome measures
Measure	Lixivaptan: Titration and Maintenance Periods n=6 Participants All participants who successfully completed the Baseline Period entered a 3-6-week Titration Period, during which each individual participant was titrated with oral lixivaptan capsules administered twice daily to a dose that was tolerated and resulted in a reduced trough urine specific gravity (or until the maximum dose level was reached) for each individual. The minimum dose to enter the Maintenance Period was 100 mg BID, and the maximum was 200 mg BID. Treatment in the Maintenance Period was continued for up to 52 weeks.
Number of Participants Who Develop Serum ALT Levels >5 × ULN During the Titration or Maintenance Periods Assessed to be Related to Lixivaptan and Result in Discontinuation of Lixivaptan Treatment	1 Participants

SECONDARY outcome

Timeframe: Up to 58 weeks

Number of participants who develop serum ALT levels \>3 x ULN which are assessed by the independent HERC to be at least probably related to lixivaptan and result in the dose reduction of lixivaptan treatment. The independent HERC, after reviewing demographic, medical and medication history, safety data and other relevant data of participants who develop liver abnormalities, will determine the probable causality for liver chemistry test abnormalities of concern and the relatedness to lixivaptan using the Drug-Induced Liver Injury Network probability criteria (Fontana et al., 2009). The normal range of ALT was defined as 0-55 U/L.

Outcome measures

Outcome measures
Measure	Lixivaptan: Titration and Maintenance Periods n=6 Participants All participants who successfully completed the Baseline Period entered a 3-6-week Titration Period, during which each individual participant was titrated with oral lixivaptan capsules administered twice daily to a dose that was tolerated and resulted in a reduced trough urine specific gravity (or until the maximum dose level was reached) for each individual. The minimum dose to enter the Maintenance Period was 100 mg BID, and the maximum was 200 mg BID. Treatment in the Maintenance Period was continued for up to 52 weeks.
Number of Participants Who Develop Serum ALT Levels >3 × ULN During the Titration or Maintenance Periods Assessed to be Related to Lixivaptan and Result in Dose Reduction of Lixivaptan Treatment	0 Participants

SECONDARY outcome

Timeframe: Up to 62 weeks

Number of participants with TEAEs during the Titration Period, the Maintenance Period, or the Follow-up Period.

Outcome measures

Outcome measures
Measure	Lixivaptan: Titration and Maintenance Periods n=6 Participants All participants who successfully completed the Baseline Period entered a 3-6-week Titration Period, during which each individual participant was titrated with oral lixivaptan capsules administered twice daily to a dose that was tolerated and resulted in a reduced trough urine specific gravity (or until the maximum dose level was reached) for each individual. The minimum dose to enter the Maintenance Period was 100 mg BID, and the maximum was 200 mg BID. Treatment in the Maintenance Period was continued for up to 52 weeks.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Titration and Maintenance Periods	6 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Follow-up Period	1 Participants

SECONDARY outcome

Timeframe: Up to 62 weeks

Number of participants with clinical laboratory findings (non-hepatic clinical chemistry, hematology, and urinalysis) recorded during the Titration Period, the Maintenance Period, or the Follow-up Period, and considered to be potentially clinically important.

Outcome measures

Outcome measures
Measure	Lixivaptan: Titration and Maintenance Periods n=6 Participants All participants who successfully completed the Baseline Period entered a 3-6-week Titration Period, during which each individual participant was titrated with oral lixivaptan capsules administered twice daily to a dose that was tolerated and resulted in a reduced trough urine specific gravity (or until the maximum dose level was reached) for each individual. The minimum dose to enter the Maintenance Period was 100 mg BID, and the maximum was 200 mg BID. Treatment in the Maintenance Period was continued for up to 52 weeks.
Number of Participants With Potentially Clinically Important Clinical Laboratory Findings Titration and Maintenance Periods	1 Participants
Number of Participants With Potentially Clinically Important Clinical Laboratory Findings Follow-up Period	0 Participants

SECONDARY outcome

Timeframe: Up to 62 weeks

Number of participants with vital signs findings (heart rate, diastolic and systolic blood pressure, weight) recorded during the Titration Period, the Maintenance Period, or the Follow-up Period, and considered to be potentially clinically important.

Outcome measures

Outcome measures
Measure	Lixivaptan: Titration and Maintenance Periods n=6 Participants All participants who successfully completed the Baseline Period entered a 3-6-week Titration Period, during which each individual participant was titrated with oral lixivaptan capsules administered twice daily to a dose that was tolerated and resulted in a reduced trough urine specific gravity (or until the maximum dose level was reached) for each individual. The minimum dose to enter the Maintenance Period was 100 mg BID, and the maximum was 200 mg BID. Treatment in the Maintenance Period was continued for up to 52 weeks.
Number of Participants With Potentially Clinically Important Vital Signs Findings Titration and Maintenance Periods	5 Participants
Number of Participants With Potentially Clinically Important Vital Signs Findings Follow-up Period	0 Participants

SECONDARY outcome

Timeframe: Up to 62 weeks

Population: The same participant experienced potentially clinically important ECG findings in the Baseline Period, in addition to during the Titration and Maintenance, and Follow-up Periods.

Number of participants with ECG findings recorded during the Titration Period, the Maintenance Period, or the Follow-up Period, and considered to be potentially clinically important (defined as a QT interval corrected for heart rate according to Fridericia's formula \[QTcF\] ≥ 450 msec).

Outcome measures

Outcome measures
Measure	Lixivaptan: Titration and Maintenance Periods n=6 Participants All participants who successfully completed the Baseline Period entered a 3-6-week Titration Period, during which each individual participant was titrated with oral lixivaptan capsules administered twice daily to a dose that was tolerated and resulted in a reduced trough urine specific gravity (or until the maximum dose level was reached) for each individual. The minimum dose to enter the Maintenance Period was 100 mg BID, and the maximum was 200 mg BID. Treatment in the Maintenance Period was continued for up to 52 weeks.
Number of Participants With Potentially Clinically Important 12-lead Electrocardiogram (ECG) Findings Baseline Period	1 Participants
Number of Participants With Potentially Clinically Important 12-lead Electrocardiogram (ECG) Findings Titration and Maintenance Periods	1 Participants
Number of Participants With Potentially Clinically Important 12-lead Electrocardiogram (ECG) Findings Follow-up Period	1 Participants

SECONDARY outcome

Timeframe: Up to 62 weeks

Baseline eGFR is defined as the mean of the 3 eGFR assessments obtained during the Baseline Period (if any values are missing, the remaining values will be used to determine the baseline eGFR). The endpoint eGFR is defined as the mean of 3 eGFR assessments obtained during the Follow-up Period (if any values are missing, the remaining values will be used to determine the endpoint eGFR). The change in eGFR from Baseline to Final Assessment will be provided.

Outcome measures

Outcome measures
Measure	Lixivaptan: Titration and Maintenance Periods n=6 Participants All participants who successfully completed the Baseline Period entered a 3-6-week Titration Period, during which each individual participant was titrated with oral lixivaptan capsules administered twice daily to a dose that was tolerated and resulted in a reduced trough urine specific gravity (or until the maximum dose level was reached) for each individual. The minimum dose to enter the Maintenance Period was 100 mg BID, and the maximum was 200 mg BID. Treatment in the Maintenance Period was continued for up to 52 weeks.
Change in Estimated Glomerular Filtration Rate (eGFR) From Baseline to Final Assessment	-4.3 mL/min/1.73m^2 Standard Deviation 2.7

Adverse Events

Titration and Maintenance Periods

Serious events: 2 serious events

Other events: 6 other events

Deaths: 0 deaths

Follow-up Period

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Titration and Maintenance Periods n=6 participants at risk All participants who completed the Titration Period and entered the Maintenance Period	Follow-up Period n=6 participants at risk All participants who entered the Follow-up Period, regardless of whether they had completed the Maintenance Period
Infections and infestations Bacteraemia	16.7% 1/6 • Number of events 1 • Adverse events were recorded from when participants had taken their first dose of lixivaptan in the Titration Period until the end of the study (maximum duration: 455 days)	0.00% 0/6 • Adverse events were recorded from when participants had taken their first dose of lixivaptan in the Titration Period until the end of the study (maximum duration: 455 days)
Investigations Alanine aminotransferase increased	16.7% 1/6 • Number of events 1 • Adverse events were recorded from when participants had taken their first dose of lixivaptan in the Titration Period until the end of the study (maximum duration: 455 days)	0.00% 0/6 • Adverse events were recorded from when participants had taken their first dose of lixivaptan in the Titration Period until the end of the study (maximum duration: 455 days)
Investigations Aspartate aminotransferase increased	16.7% 1/6 • Number of events 1 • Adverse events were recorded from when participants had taken their first dose of lixivaptan in the Titration Period until the end of the study (maximum duration: 455 days)	0.00% 0/6 • Adverse events were recorded from when participants had taken their first dose of lixivaptan in the Titration Period until the end of the study (maximum duration: 455 days)

Other adverse events

Additional Information

Milena Kanova

Centessa Pharmaceuticals

Phone: +44 7780 430583

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Measure	Titration and Maintenance Periods n=6 participants at risk All participants who completed the Titration Period and entered the Maintenance Period	Follow-up Period n=6 participants at risk All participants who entered the Follow-up Period, regardless of whether they had completed the Maintenance Period
Gastrointestinal disorders Abdominal pain	16.7% 1/6 • Number of events 1 • Adverse events were recorded from when participants had taken their first dose of lixivaptan in the Titration Period until the end of the study (maximum duration: 455 days)	0.00% 0/6 • Adverse events were recorded from when participants had taken their first dose of lixivaptan in the Titration Period until the end of the study (maximum duration: 455 days)
Gastrointestinal disorders Abdominal pain upper	16.7% 1/6 • Number of events 1 • Adverse events were recorded from when participants had taken their first dose of lixivaptan in the Titration Period until the end of the study (maximum duration: 455 days)	0.00% 0/6 • Adverse events were recorded from when participants had taken their first dose of lixivaptan in the Titration Period until the end of the study (maximum duration: 455 days)
Gastrointestinal disorders Constipation	16.7% 1/6 • Number of events 1 • Adverse events were recorded from when participants had taken their first dose of lixivaptan in the Titration Period until the end of the study (maximum duration: 455 days)	0.00% 0/6 • Adverse events were recorded from when participants had taken their first dose of lixivaptan in the Titration Period until the end of the study (maximum duration: 455 days)
Gastrointestinal disorders Dyspepsia	16.7% 1/6 • Number of events 1 • Adverse events were recorded from when participants had taken their first dose of lixivaptan in the Titration Period until the end of the study (maximum duration: 455 days)	0.00% 0/6 • Adverse events were recorded from when participants had taken their first dose of lixivaptan in the Titration Period until the end of the study (maximum duration: 455 days)
Gastrointestinal disorders Nausea	16.7% 1/6 • Number of events 1 • Adverse events were recorded from when participants had taken their first dose of lixivaptan in the Titration Period until the end of the study (maximum duration: 455 days)	0.00% 0/6 • Adverse events were recorded from when participants had taken their first dose of lixivaptan in the Titration Period until the end of the study (maximum duration: 455 days)
General disorders Malaise	0.00% 0/6 • Adverse events were recorded from when participants had taken their first dose of lixivaptan in the Titration Period until the end of the study (maximum duration: 455 days)	16.7% 1/6 • Number of events 1 • Adverse events were recorded from when participants had taken their first dose of lixivaptan in the Titration Period until the end of the study (maximum duration: 455 days)
General disorders Oedema peripheral	16.7% 1/6 • Number of events 1 • Adverse events were recorded from when participants had taken their first dose of lixivaptan in the Titration Period until the end of the study (maximum duration: 455 days)	0.00% 0/6 • Adverse events were recorded from when participants had taken their first dose of lixivaptan in the Titration Period until the end of the study (maximum duration: 455 days)
General disorders Peripheral swelling	16.7% 1/6 • Number of events 1 • Adverse events were recorded from when participants had taken their first dose of lixivaptan in the Titration Period until the end of the study (maximum duration: 455 days)	0.00% 0/6 • Adverse events were recorded from when participants had taken their first dose of lixivaptan in the Titration Period until the end of the study (maximum duration: 455 days)
Infections and infestations Bacteraemia	16.7% 1/6 • Number of events 1 • Adverse events were recorded from when participants had taken their first dose of lixivaptan in the Titration Period until the end of the study (maximum duration: 455 days)	0.00% 0/6 • Adverse events were recorded from when participants had taken their first dose of lixivaptan in the Titration Period until the end of the study (maximum duration: 455 days)
Infections and infestations COVID-19	16.7% 1/6 • Number of events 1 • Adverse events were recorded from when participants had taken their first dose of lixivaptan in the Titration Period until the end of the study (maximum duration: 455 days)	0.00% 0/6 • Adverse events were recorded from when participants had taken their first dose of lixivaptan in the Titration Period until the end of the study (maximum duration: 455 days)
Infections and infestations Pneumonia	16.7% 1/6 • Number of events 1 • Adverse events were recorded from when participants had taken their first dose of lixivaptan in the Titration Period until the end of the study (maximum duration: 455 days)	0.00% 0/6 • Adverse events were recorded from when participants had taken their first dose of lixivaptan in the Titration Period until the end of the study (maximum duration: 455 days)
Injury, poisoning and procedural complications Tendon rupture	16.7% 1/6 • Number of events 1 • Adverse events were recorded from when participants had taken their first dose of lixivaptan in the Titration Period until the end of the study (maximum duration: 455 days)	0.00% 0/6 • Adverse events were recorded from when participants had taken their first dose of lixivaptan in the Titration Period until the end of the study (maximum duration: 455 days)
Investigations Alanine aminotransferase increased	16.7% 1/6 • Number of events 1 • Adverse events were recorded from when participants had taken their first dose of lixivaptan in the Titration Period until the end of the study (maximum duration: 455 days)	0.00% 0/6 • Adverse events were recorded from when participants had taken their first dose of lixivaptan in the Titration Period until the end of the study (maximum duration: 455 days)
Investigations Aspartate aminotransferase increased	16.7% 1/6 • Number of events 1 • Adverse events were recorded from when participants had taken their first dose of lixivaptan in the Titration Period until the end of the study (maximum duration: 455 days)	0.00% 0/6 • Adverse events were recorded from when participants had taken their first dose of lixivaptan in the Titration Period until the end of the study (maximum duration: 455 days)
Investigations Blood pressure increased	16.7% 1/6 • Number of events 1 • Adverse events were recorded from when participants had taken their first dose of lixivaptan in the Titration Period until the end of the study (maximum duration: 455 days)	0.00% 0/6 • Adverse events were recorded from when participants had taken their first dose of lixivaptan in the Titration Period until the end of the study (maximum duration: 455 days)
Investigations Transaminases increased	16.7% 1/6 • Number of events 1 • Adverse events were recorded from when participants had taken their first dose of lixivaptan in the Titration Period until the end of the study (maximum duration: 455 days)	0.00% 0/6 • Adverse events were recorded from when participants had taken their first dose of lixivaptan in the Titration Period until the end of the study (maximum duration: 455 days)
Investigations Weight increased	16.7% 1/6 • Number of events 1 • Adverse events were recorded from when participants had taken their first dose of lixivaptan in the Titration Period until the end of the study (maximum duration: 455 days)	0.00% 0/6 • Adverse events were recorded from when participants had taken their first dose of lixivaptan in the Titration Period until the end of the study (maximum duration: 455 days)
Metabolism and nutrition disorders Iron deficiency	16.7% 1/6 • Number of events 1 • Adverse events were recorded from when participants had taken their first dose of lixivaptan in the Titration Period until the end of the study (maximum duration: 455 days)	0.00% 0/6 • Adverse events were recorded from when participants had taken their first dose of lixivaptan in the Titration Period until the end of the study (maximum duration: 455 days)
Musculoskeletal and connective tissue disorders Back pain	16.7% 1/6 • Number of events 1 • Adverse events were recorded from when participants had taken their first dose of lixivaptan in the Titration Period until the end of the study (maximum duration: 455 days)	0.00% 0/6 • Adverse events were recorded from when participants had taken their first dose of lixivaptan in the Titration Period until the end of the study (maximum duration: 455 days)
Musculoskeletal and connective tissue disorders Knee deformity	16.7% 1/6 • Number of events 1 • Adverse events were recorded from when participants had taken their first dose of lixivaptan in the Titration Period until the end of the study (maximum duration: 455 days)	0.00% 0/6 • Adverse events were recorded from when participants had taken their first dose of lixivaptan in the Titration Period until the end of the study (maximum duration: 455 days)
Musculoskeletal and connective tissue disorders Neck pain	16.7% 1/6 • Number of events 1 • Adverse events were recorded from when participants had taken their first dose of lixivaptan in the Titration Period until the end of the study (maximum duration: 455 days)	0.00% 0/6 • Adverse events were recorded from when participants had taken their first dose of lixivaptan in the Titration Period until the end of the study (maximum duration: 455 days)
Musculoskeletal and connective tissue disorders Patellofemoral pain syndrome	16.7% 1/6 • Number of events 1 • Adverse events were recorded from when participants had taken their first dose of lixivaptan in the Titration Period until the end of the study (maximum duration: 455 days)	0.00% 0/6 • Adverse events were recorded from when participants had taken their first dose of lixivaptan in the Titration Period until the end of the study (maximum duration: 455 days)
Nervous system disorders Carpal tunnel syndrome	16.7% 1/6 • Number of events 1 • Adverse events were recorded from when participants had taken their first dose of lixivaptan in the Titration Period until the end of the study (maximum duration: 455 days)	0.00% 0/6 • Adverse events were recorded from when participants had taken their first dose of lixivaptan in the Titration Period until the end of the study (maximum duration: 455 days)
Nervous system disorders Dizziness	16.7% 1/6 • Number of events 1 • Adverse events were recorded from when participants had taken their first dose of lixivaptan in the Titration Period until the end of the study (maximum duration: 455 days)	0.00% 0/6 • Adverse events were recorded from when participants had taken their first dose of lixivaptan in the Titration Period until the end of the study (maximum duration: 455 days)
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/6 • Adverse events were recorded from when participants had taken their first dose of lixivaptan in the Titration Period until the end of the study (maximum duration: 455 days)	16.7% 1/6 • Number of events 1 • Adverse events were recorded from when participants had taken their first dose of lixivaptan in the Titration Period until the end of the study (maximum duration: 455 days)
Respiratory, thoracic and mediastinal disorders Dyspnoea	16.7% 1/6 • Number of events 1 • Adverse events were recorded from when participants had taken their first dose of lixivaptan in the Titration Period until the end of the study (maximum duration: 455 days)	0.00% 0/6 • Adverse events were recorded from when participants had taken their first dose of lixivaptan in the Titration Period until the end of the study (maximum duration: 455 days)
Skin and subcutaneous tissue disorders Alopecia	16.7% 1/6 • Number of events 1 • Adverse events were recorded from when participants had taken their first dose of lixivaptan in the Titration Period until the end of the study (maximum duration: 455 days)	0.00% 0/6 • Adverse events were recorded from when participants had taken their first dose of lixivaptan in the Titration Period until the end of the study (maximum duration: 455 days)