Trial Outcomes & Findings for Roll-over Study to Assess Safety of Lixivaptan in Participants With ADPKD Who Completed Study PA-ADPKD-303 (NCT NCT05208866)

NCT ID: NCT05208866

Last Updated: 2023-05-12

Results Overview

Number of participants who develop serum alanine aminotransferase (ALT) levels \>3 × the upper limit of normal (ULN) which are assessed by the independent Hepatic Events Review Committee (HERC) to be at least probably related to lixivaptan and resulted in 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

1 participants

Primary outcome timeframe

120 days (from Screening to the end of the Maintenance Treatment Period)

Results posted on

2023-05-12

Participant Flow

Participant milestones

Participant milestones
Measure
All Enrolled Participants
All participants who were enrolled in this study were included in this group.
Lixivaptan Re-titration Period
STARTED
1
Lixivaptan Re-titration Period
COMPLETED
1
Lixivaptan Re-titration Period
NOT COMPLETED
0
Maintenance Treatment Period
STARTED
1
Maintenance Treatment Period
COMPLETED
0
Maintenance Treatment Period
NOT COMPLETED
1
Follow-up Period
STARTED
1
Follow-up Period
COMPLETED
1
Follow-up Period
NOT COMPLETED
0

Reasons for withdrawal

Reasons for withdrawal
Measure
All Enrolled Participants
All participants who were enrolled in this study were included in this group.
Maintenance Treatment Period
Sponsor Termination of Study
1

Baseline Characteristics

Roll-over Study to Assess Safety of Lixivaptan in Participants With ADPKD Who Completed Study PA-ADPKD-303

Baseline characteristics by cohort

Baseline data not reported

PRIMARY outcome

Timeframe: 120 days (from Screening to the end of the Maintenance Treatment Period)

Number of participants who develop serum alanine aminotransferase (ALT) levels \>3 × the upper limit of normal (ULN) which are assessed by the independent Hepatic Events Review Committee (HERC) to be at least probably related to lixivaptan and resulted in 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
All Enrolled Participants
n=1 Participants
All participants who were enrolled in this study were included in this group.
Number of Participants Who Develop Serum ALT Levels >3 × ULN During the Lixivaptan Re-titration or Maintenance Treatment Periods Assessed to be Related to Lixivaptan and Resulted in Discontinuation of Lixivaptan Treatment
0 Participants

SECONDARY outcome

Timeframe: 120 days (from Screening to the end of the Maintenance Treatment Period)

Number of participants who develop serum ALT levels \>5 × ULN which are assessed by the independent HERC to be at least probably related to lixivaptan and resulted in 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
All Enrolled Participants
n=1 Participants
All participants who were enrolled in this study were included in this group.
Number of Participants Who Develop Serum ALT Levels >5 x ULN During the Lixivaptan Re-titration or Maintenance Treatment Periods Assessed to be Related to Lixivaptan and Resulted in Discontinuation of Lixivaptan Treatment
0 Participants

SECONDARY outcome

Timeframe: 120 days (from Screening to the end of the Maintenance Treatment Period)

Number of participants who develop serum ALT levels \>3 × ULN that were assessed by the independent HERC to be at least probably related to lixivaptan and resulted in 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
All Enrolled Participants
n=1 Participants
All participants who were enrolled in this study were included in this group.
Number of Participants Who Develop Serum ALT Values >3 × ULN During the Lixivaptan Re-titration or Maintenance Treatment Periods Assessed to be Related to Lixivaptan and Resulted in Dose Reduction of Lixivaptan Treatment
0 Participants

SECONDARY outcome

Timeframe: 140 days (from Screening to the end of the Follow-up Period)

Number of participants with TEAEs during the Lixivaptan Re-titration Period, the Maintenance Treatment Period, or the Follow-up Period.

Outcome measures

Outcome measures
Measure
All Enrolled Participants
n=1 Participants
All participants who were enrolled in this study were included in this group.
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Lixivaptan Re-titration and Maintenance Treatment Periods
1 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Follow-up Period
0 Participants

SECONDARY outcome

Timeframe: 140 days (from Screening to the end of the Follow-up Period)

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

Outcome measures

Outcome measures
Measure
All Enrolled Participants
n=1 Participants
All participants who were enrolled in this study were included in this group.
Number of Participants With Potentially Clinically Important Clinical Laboratory Findings
Lixivaptan Re-titration and Maintenance Treatment Periods
0 Participants
Number of Participants With Potentially Clinically Important Clinical Laboratory Findings
Follow-up Period
0 Participants

SECONDARY outcome

Timeframe: 140 days (from Screening to the end of the Follow-up Period)

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

Outcome measures

Outcome measures
Measure
All Enrolled Participants
n=1 Participants
All participants who were enrolled in this study were included in this group.
Number of Participants With Potentially Clinically Important Vital Signs Findings
Lixivaptan Re-titration and Maintenance Treatment Periods
0 Participants
Number of Participants With Potentially Clinically Important Vital Signs Findings
Follow-up Period
0 Participants

SECONDARY outcome

Timeframe: 140 days (from Screening to the end of the Follow-up Period)

Number of participants with ECG findings recorded during the Lixivaptan Re-titration Period, the Maintenance Treatment 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
All Enrolled Participants
n=1 Participants
All participants who were enrolled in this study were included in this group.
Number of Participants With Potentially Clinically Important 12-lead Electrocardiogram (ECG) Findings
Lixivaptan Re-titration and Maintenance Treatment Periods
0 Participants
Number of Participants With Potentially Clinically Important 12-lead Electrocardiogram (ECG) Findings
Follow-up Period
0 Participants

SECONDARY outcome

Timeframe: 140 days (from Screening to the end of the Follow-up Period)

Population: The annualized change in eGRF is provided for the only participant enrolled at the time of early termination of the study.

Baseline eGFR is defined as the mean of the 3 eGFR assessments obtained at Visits 25, 26 and 27 of study PA-ADPKD-303 (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
All Enrolled Participants
n=1 Participants
All participants who were enrolled in this study were included in this group.
Annualized Change in Estimated Glomerular Filtration Rate (eGFR) From Baseline to Final Assessment
14.6 mL/min/1.73m^2
Standard Deviation 0.0

Adverse Events

Titration and Maintenance Periods

Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths

Follow-up Period

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Titration and Maintenance Periods
n=1 participants at risk
All participants who completed the Lixivaptan Re-titration Period and entered the Maintenance Period
Follow-up Period
n=1 participants at risk
All participants who entered the Follow-up Period, regardless of whether they had completed the Maintenance Period
Skin and subcutaneous tissue disorders
Dermatitis contact
100.0%
1/1 • Number of events 1 • Adverse events were recorded from when participants had taken their first dose of lixivaptan in the Re-titration Period until the end of the study (maximum duration: 140 days)
0.00%
0/1 • Adverse events were recorded from when participants had taken their first dose of lixivaptan in the Re-titration Period until the end of the study (maximum duration: 140 days)
Injury, poisoning and procedural complications
Arthropod bite
100.0%
1/1 • Number of events 1 • Adverse events were recorded from when participants had taken their first dose of lixivaptan in the Re-titration Period until the end of the study (maximum duration: 140 days)
0.00%
0/1 • Adverse events were recorded from when participants had taken their first dose of lixivaptan in the Re-titration Period until the end of the study (maximum duration: 140 days)

Additional Information

Milena Kanova

Centessa Pharmaceuticals

Phone: +44 7780 430583

Results disclosure agreements

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

Restriction type: GT60