Hepatic Monitoring for Pazopanib

Sponsor
GlaxoSmithKline
Study ID
NCT01449825
Status
Completed

Conditions

  • Carcinoma, Renal Cell

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

Study Details

Pazopanib is approved by the FDA and EMA as targeted therapy for the indication of advanced renal cell carcinoma (RCC). Hepatic safety events were observed in the pazopanib pivotal clinical trial and the U.S. pazopanib label information contains a 'black box warning' regarding hepatotoxicity. These clinical observations have prompted GSK to undertake a proactive pharmacovigilance strategy focused on hepatic safety that goes beyond spontaneous reporting of adverse events. The goals of the study are to assess prescriber compliance with pazopanib label guidelines for liver monitoring among patients with RCC, as well as to quantify and characterize the hepatic safety profile of the product in real-world clinical practice compared to other anti-vascular endothelial growth factor (anti-VEGF) drugs. As part of regulatory commitments, GSK will conduct parallel epidemiologic analyses in different patient populations as represented in multiple databases of electronic medical records. To enhance accrual of data, GSK will conduct this safety surveillance program simultaneously across datasets in order to detect and characterize all cases of liver enzyme elevations in diverse populations of patients receiving pazopanib. Two additional goals of this study are to evaluate the incidence of cases of combinations of liver enzyme elevations indicative of Hy's Law and drug-induced acute liver failure among users of pazopanib compared to users of other anti-VEGF drugs. This research effort will be coordinated by an external coordinating center. An epidemiologic cohort study design, nested in several databases of electronic medical information, will be employed for the research questions. Following the availability of pazopanib in the relevant medical care system, the study will collect retrospective data at regular intervals over the course of four years among persons exposed to pazopanib and other anti-VEGF agents. Each patient will be characterized based on additional available information in the database (e.g., demographics, concomitant medications). Elevations in liver enzymes will be identified through laboratory data captured in these databases. Potential Hy's Law and acute liver failure cases will be identified through established screening criteria, and screen-positive cases will be reviewed by an adjudication committee of hepatologists for final determination of drug-associated causality.

Key Dates

First listed
Oct 10, 2011
Start date
Dec 31, 2010
Status verified
Apr 2014
Primary completion
Dec 31, 2013
Completion
Dec 31, 2013

Study Design

Enrollment
1 participants (actual)

Arms

  • Arm: Prescriber compliance group
    Adult (18+ years) new users of pazopanib with an indication of RCC evaluated for prescriber compliance
  • Arm: Incidence of liver chemistry test (LCT) elevation group
    Adult (18+ years) new users of pazopanib, sunitinib, bevacizumab, and sorafenib in monotherapy who have a baseline LCT evaluated for LCT elevations
  • Arm: Incidence of drug induced liver injury (DILI) cases group
    Adult (18+ years) new users of pazopanib, sunitinib, bevacizumab, and sorafenib with RCC (as defined by ICD-9 codes) longitudinally followed up in order to capture occurrences of LCT elevations consistent with Hy's Law to evaluate for drug-induced liver injury
  • Arm: Incidence of cases of ALF group
    Adult (18+ years) new users of pazopanib, sunitinib, bevacizumab, and sorafenib with RCC (as defined by ICD-9 codes) longitudinally followed up in order to capture occurrences of ICD-9 codes indicative of possible ALF to evaluate for drug-induced liver injury

Primary Outcome Measure

Prescriber compliance with pazopanib label guidelines for liver monitoring [ Time Frame: Over four years of treatment with pazopanib ]

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