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

NCT05208866 | Terminated Phase 3 Results FDA Drug

• 1 other identifier: PA-ADPKD-304
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 3, open-label, roll-over study to demonstrate the continued hepatic and non-hepatic safety and renal efficacy of lixivaptan in participants with ADPKD who previously experienced abnormal liver chemistry test results while treated with tolvaptan, were permanently discontinued from the drug for that reason, and subsequently completed study PA-ADPKD-303, the open-label lead-in study with lixivaptan.

Conditions

Polycystic Kidney Disease, Adult

Outcome Measures

Primary Outcomes (1)

• 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

  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.

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

Secondary Outcomes (7)

• 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

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

• 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

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

• Number of Participants With Treatment-emergent Adverse Events (TEAEs)

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

• Number of Participants With Potentially Clinically Important Clinical Laboratory Findings

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

• Number of Participants With Potentially Clinically Important Vital Signs Findings

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

Study Arms (1)

Lixivaptan

EXPERIMENTAL

Lixivaptan capsules 100-200mg twice daily

Drug: Lixivaptan

Interventions

Lixivaptan DRUG

Oral vasopressin V2 receptor antagonist

Lixivaptan

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female participants with ADPKD who completed study PA-ADPKD-303
• Continued control of hypertension without the use of a diuretic
• Continued adherence to prohibitions on concomitant medications stated in the study PA-ADPKD-303 protocol
• Willing to practice acceptable methods of birth control (both males who have partners of child-bearing potential and females of childbearing potential).
• Able to provide informed consent.

You may not qualify if:

• Any contraindication to continued treatment with lixivaptan
• Clinically significant incontinence, overactive bladder, or urinary retention (e.g., benign prostatic hyperplasia)
• New York Heart Association Functional Class 3 or 4 heart failure or other significant cardiac or electrocardiogram (ECG) findings that could pose a safety risk to the participant
• Hypovolemia on physical examination at Screening
• The following laboratory results based on serum drawn at Visit 24 of PA-ADPKD-303:
• Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) values \>1.5 × ULN
• Total bilirubin values \>1.5 × ULN
• eGFR \<20 mL/min/1.73 m\^2 based on laboratory results from Visit 26 of PA-ADPKD-303
• A finding at Screening that precludes safe participation in the study or participants who are likely to be non-compliant with study procedures in the opinion of the Investigator or medical monitor

Sponsors & Collaborators

• Palladio Biosciences: lead
• Centessa Pharmaceuticals plc: collaborator

Study Sites (1)

Northeast Clinical Research Center, LLC

Bethlehem, Pennsylvania, 18107, United States

Location

Related Publications (1)

• Fontana RJ, Watkins PB, Bonkovsky HL, Chalasani N, Davern T, Serrano J, Rochon J; DILIN Study Group. Drug-Induced Liver Injury Network (DILIN) prospective study: rationale, design and conduct. Drug Saf. 2009;32(1):55-68. doi: 10.2165/00002018-200932010-00005.

  PMID: 19132805 BACKGROUND

MeSH Terms

Conditions

Polycystic Kidney, Autosomal Dominant

Interventions

lixivaptan

Condition Hierarchy (Ancestors)

Polycystic Kidney Diseases; Kidney Diseases, Cystic; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Ciliopathies; Genetic Diseases, Inborn

Limitations and Caveats

Efficacy and safety results are limited by the early termination of the trial and the small number of subjects. Early termination was due to a sponsor decision for reasons unrelated to safety.

Results Point of Contact

• Title: Milena Kanova
• Organization: Centessa Pharmaceuticals

milena.kanova@centessa.com

+44 7780 430583

Study Officials

• Nelson Kopyt, DO

  Northeast Clinical Research Center, LLC

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Single group, open-label study

Study Record Dates

• First Submitted: January 7, 2022
• First Posted: January 26, 2022
• Study Start: February 10, 2022
• Primary Completion: June 29, 2022
• Study Completion: July 29, 2022
• Last Updated: May 12, 2023
• Results First Posted: April 10, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)