A modeling and simulation-based assessment of the impact of confounding factors on the readout of a sildenafil survival trial in pulmonary arterial hypertension

AbstractSildenafil (REVATIO®) was approved for the treatment of adult Pulmonary Arterial Hypertension (PAH) in the US and the EU. A pediatric study has been performed and sildenafil was approved in the EU for pediatric PAH. The long-term extension of this study revealed good survival but also an increased mortality with the high dose of sildenafil compared to lower doses. As a consequence, FDA required Pfizer to evaluate REVATIO®’s effect on the risk of death in adults with PAH. Following FDA’s rationale a survival model was developed to characterize the exposure–mortality relationship and assess its potential impact on an ongoing survival trial in adults in the context of confounding factors. Clinical trial simulatio ns were performed to assess the design of the survival trial in adults (AFFILIATE, NCT02060487), expected to last approximately 8 years according to both assumptions: absence or presence of an exposure–mortality relationship and to quantify the impact of confounding factors on its readout. Simulat ions showed that the trial would be robust in most conditions. But its interpretation will depend on the number of confounding factors such as additional treatments attempting to control disease progression.Clinical trial identifier NCT00159913 for STARTS-1, NCT00159874 for STARTS-2
Source: Journal of Pharmacokinetics and Pharmacodynamics - Category: Drugs & Pharmacology Source Type: research

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Source: the Mail online | Health - Category: Consumer Health News Source Type: news
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Source: Biochimica et Biophysica Acta (BBA) Biomembranes - Category: Biochemistry Source Type: research
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Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
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Source: Jornal Vascular Brasileiro - Category: Surgery Source Type: research
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Source: Canadian Journal of Diabetes - Category: Endocrinology Source Type: research
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Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
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Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
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Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
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