(duplicate) Non-interventional, PASS for patients prescribed JINARC fo

• Research type

  Research Study

• Full title

  A 9-year, Multicentre, Non-interventional, Postauthorisation Safety Study for Patients Prescribed JINARC® for Autosomal Dominant Polycystic Kidney Disease.

• IRAS ID

  225572

• Contact name

  Marco Avila

• Sponsor organisation

  Otsuka Pharmaceutical Europe Ltd

• Duration of Study in the UK

  6 years, 5 months, 1 days

• Research summary

  This PASS is a 6 year, multicentre, prospective, non-interventional study to assess the long-term safety profile of JINARC when prescribed to patients for Autosomal Dominant Polycystic Kidney Disease.

  JINARC (tolvaptan) is currently the only treatment option for slowing the progression of kidney disease in patients with ADPKD, rather than palliative. Study participation will be available to physicians who have completed the appropriate education in all countries in Europe where JINARC is launched and commercially available by prescription. Patients must have never taken tolvaptan previously to be eligible to participate in the study.

  Approximately 3000 patients will participate in the trial globally, with around 600 patients participating in the United Kingdom. Data will be collected from information from routine health check-ups collected from electronic medical records. In addition, a retrospective database analysis will be conducted to compare Adverse Events of special interest, such as glaucoma and skin neoplasms with non-treated patients.

  An Educational Materials Effectiveness Survey will also be conducted to assess physicians' level of awareness and understanding of the content of the educational material received. Physicians who participate in this survey will not be able to enrol patients for prospective follow-up.

  Lay summary of study results: This study was intended to explore the safety profile and usage of JINARC when used in the real-world setting in Europe, particularly with relation to the risk of liver injury that was identified in the interventional pre-registrational studies.
  The data presented in this report indicate that the risk mitigation methods are adequate to identify patients who develop hepatotoxicity and demonstrates the adequacy of the suggested liver monitoring for such events and of the suggested steps for the prescriber to take to protect the patient. The data also suggest that these recommended steps were followed, and patients were thus protected from progression to liver injury. Results show adequate clinical assessment of laboratory values where action was taken (drug withdrawal and interruption) in 79.1% of events. The remaining events the majority were considered mild or moderate and not related or recovered with continuous treatment.
  Of the 80 patients with ALT or AST levels ≥ 3 × ULN, only 3 (3.8%) patients were on strong CYP3A4 inhibitors; however, transaminase increase was not associated with concomitant medication. Additionally, only 5 out of 252 (2.0%) patients that ended treatment due to tolerability were also on CYP3A4 inhibitors at the time of treatment discontinuation. One of these patients was on strong CYP3A4 inhibitors while the other 4 patients were on moderate CYP3A4 inhibitors. No patient met Hy’s Law laboratory criteria, and no significant safety information was identified from the review of the data in 80 patients with confirmed ALT or AST levels ≥ 3 × ULN.
  Of the 2091 patients in the safety analysis population, prescribers for 122 (5.8%) patients did not adhere to the recommendations of the SmPC, predominantly including patients with a CKD stage of 5. The majority of patients (93.9%) initiated therapy at a starting dose of 60 mg as recommended in the SmPC.
  A total of 31 cases of pregnancy were identified over the duration of the study. No trends were observed in the use of JINARC in pregnant women.
  The average age at initiation was 43.0 years (range: 18 to 79 years), which is very similar to the ages in the interventional studies. Overall, 26.9% of the patients were over 50 years of age at initiation of JINARC in this study. This is important as the first phase 3 study (TEMPO 3:4) limited patients to below 50 years. Thus, the examination of the safety in this group is of particular interest. No differences were noted in the type and incidence of TEAEs experienced by patients who were ≥ 50 years old, and the experience was comparable to patients who were < 50 years old; including the incidence of potential liver injury.
  The 22 deaths reported in the study are unrelated to JINARC and at least 3 events (subarachnoid haemorrhage) are known complications of ADPKD.
  The additional risk minimisation measures implemented for JINARC have proven effective in mitigating the risk of liver injury. These, combined with the subsequent patient management and adherence to the SMPC, have resulted in no deaths related to liver injury.
  Overall, no new safety concerns have been identified.
  

• REC name

  North East - Newcastle & North Tyneside 2 Research Ethics Committee

• REC reference

  17/NE/0088

• Date of REC Opinion

  18 May 2017

• REC opinion

  Further Information Favourable Opinion