Safety, tolerability, and dose limiting toxicity of lacosamide in patients with painful chronic pancreatitis

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ABSTRACT: Background: Chronic abdominal pain is the hallmark symptom of chronic pancreatitis (CP), with 50-80% of patients seeking medical attention for pain control. While several management options are potentially available, outcomes are often disappointing, and opioids remain a mainstay of therapy. Opioid-induced hyperalgesia (OIH) may occur, a phenomenon resulting in dose escalation, and appears to be due in part to the effect of opioids on pain- associated voltage-gated sodium channels. Lacosamide blocks and stabilizes these channels and may inhibit the effects of OIH. This may result in improved pain control with a decrease in opioid use. In pre-clinical and clinical trials with neuropathic pain, lacosamide reduced pain scores and was well tolerated. There are no data, however, evaluating the use of lacosamide in CP patients. Aims: 1. To evaluate the safety, tolerability and dose-limiting toxicity of adding lacosamide to opioid therapy in subjects with suspected and definite painful CP; 2. To assess the feasibility of performance of a pilot study adding lacosamide to opioid therapy in these subjects. As an exploratory aim, we will assess the efficacy of adding lacosamide to opioid therapy for the treatment of abdominal pain due to CP. Methods: This is a Phase 1 trial, utilizing the Bayesian optimal interval (BOIN) design to find the Maximum Tolerated Dose (MTD). The target dose- limiting toxicity (DLT) rate for the MTD is ɸ = 0.3 and the maximum sample size is 24. Given the small sample size, anticipated relatively short study period and potential for patient recruitment at several clinical centers, it is anticipated that all data will be accrued within 36 months of study initiation. Significance: This study will generate new knowledge regarding the safety, toxicity and dose-limiting toxicity of lacosamide in CP patients. It is anticipated that lacosamide will prove to be safe and well-tolerated. The results of this pilot study will then support proceeding with a phase 2 trial assessing the efficacy of lacosamide added to opioid therapy to alleviate abdominal pain from CP.