(386) A novel proof of concept, placebo controlled, randomised withdrawal study, demonstrating the safety and efficacy of CNV1014802 in patients with trigeminal neuralgia

Abstract

Trigeminal neuralgia (TN) is a rare, episodic severe facial pain condition (Zakrzewska et al. 2014). Pharmacological treatment of TN is dominated by the use of sodium channel blockers such as carbamazepine or oxcarbazepine (Cruccu et al. 2008). However, whilst effective these drugs suffer poor tolerability profiles, several drug-drug interactions and require careful up-titration and monitoring. CNV1014802 is a novel CNS-penetrant Nav1.7 selective, state dependent sodium channel blocker. CNV1014802 was well tolerated in clinical studies conducted so far and can be administered at an immediate therapeutic dose, without the need for lengthy titration. This Phase 2 trial utilised a randomised withdrawal design to assess efficacy and safety (Zakrzewska et al.). Following a 7 day run in, where patients were partially washed out of their existing pain medications and baseline scores were collected (number of paroxysmal attacks and associated pain), there was a 21 day open-label CNV1014802 150mg TID treatment phase. 29 patients who met “responder” criteria were randomised into a 28 day double-blind placebo-controlled phase. Patients were assessed weekly and discontinued from the study if they met “treatment failure” criteria. The primary end point was the number of treatment failures on CNV1014802 versus the number of treatment failures on placebo in the double-blind phase. Secondary end points included: Kaplan-Meier analysis of time to failure, number and pain severity of TN paroxysms, daily TN Pain Intensity-NRS, PGIC, CGIC, and safety assessments. CNV1014802 displayed favourable effects on efficacy compared to placebo with all of the study efficacy endpoints, including measures of pain and global functioning. CNV1014802 was well tolerated and there were no clinically significant trends to changes in laboratory tests, BP, heart rate or ECG parameters associated with CNV1014802. The efficacy and safety results from this trial support further development of CNV1014802 for the treatment of TN.