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Richard Radnovich,1 Jill Heinz,1 Chris Ambrose,2 Elizabeth Stannard,2 Dmitri Lissin2 1Injury Care Research, Boise, ID, USA; 2Global Research and Development, Scilex Pharmaceuticals Inc, Palo Alto, CA, USACorrespondence: Dmitri LissinScilex Pharmaceuticals Inc, 960 San Antonio Road, Palo Alto, CA, 94306, USA, Tel +1 650-430-3238Email dlissin@scilexpharma.comPurpose: SP-102 is a novel epidural steroid injection (ESI) formulation of 10 mg dexamethasone sodium phosphate in a viscous gel solution. Repeat dosing of ESIs is possible if required for pain relief, but with consideration of hypothalamic–pituitary–adrenal (HPA) axis suppression from prolonged systemic exposure. This phase I/II study investigated the effect of initial and repeat SP-102 injections on HPA suppression and analgesia.Methods: Subjects with lumbosacral radiculopathy received an initial epidural SP-102 injection (T1) on day 1, followed by a repeat injection (T2) on ≥ 28 days later. To determine HPA suppression, area under the effect curve over 28 days and maximum change from baseline were calculated for cortisol, glucose levels, and white blood cell (WBC) count. Equivalent effect on HPA suppression of T1 relative to T2 was determined if the 90% CIs for ratios of these measures were within 80%– 125%. The effect of repeat injections on leg and back pain was also assessed.Results: Based on the responder analysis, all subjects had achieved a cortisol response by day 3 after initial injection and by day 2 after repeat injection. The repeat injection had similar effects on glucose levels and WBC count to the initial injection. Pain scores decreased after each injection and remained low for the 28-day follow-up, with some evidence of improved analgesic effect of the second dose compared with the first. There were no serious adverse events or discontinuations due to adverse events.Conclusion: The lack of cumulative effect and rapid resolution of HPA suppression following repeated SP-102 dosing suggests that consideration of HPA pharmacodynamics is not clinically relevant when making decisions regarding repeat dosing. SP-102 ESIs provided prolonged pain relief, with preliminary evidence of greater efficacy after repeat injection. A phase III trial is ongoing.Clinical Trial Identifier: ClinicalTrials.gov: NCT03613662.Keywords: epidural steroid injections, lubosacral radicuar pain, sciatica, neuropathic pain

Jeffrey Fudin,1– 3 Kip Vought,4 Kalpana Patel,4 Dmitri Lissin,4 Howard Maibach5 1Pain Management and PGY2 Pharmacy Pain Residency, Samuel Stratton Department of Veterans Affairs Medical Center, Albany, NY, USA; 2Remitigate Therapeutics, Delmar, NY, USA; 3Department of Pharmacy, Albany College of Pharmacy and Health Sciences, Albany, NY, USA; 4Clinical Development, Scilex Pharmaceuticals Inc, Palo Alto, CA, USA; 5Dermatology Department, University of California San Francisco, San Francisco, CA, USACorrespondence: Dmitri Lissin, Clinical Development, Scilex Pharmaceuticals Inc, 960 San Antonio Road, Palo Alto, CA, 94303, USA, Tel +1 650.516.4310, Email dlissin@scilexpharma.comPurpose: This study evaluates and compares the clinical adhesion performance of a prescription lidocaine topical system 1.8% versus two different over-the-counter (OTC) lidocaine patches 4% and an OTC combination menthol and lidocaine patch 1%/4% in human subjects.Patients and Methods: This study was an open-label, randomized, four-treatment, four-sequence, Phase 1 adhesion performance study in healthy adult volunteers (N = 24). Lidocaine topical system 1.8% (R) and the three OTC patch products (T1, T2, and T3) were separately applied for 12 hours. Adhesion of all products was scored at 0, 3, 6, 8, and 12 hours post-application.Results: There were no issues with the conduct of the study. Overall, the majority (≥ 59.1%) of subjects treated (“patched”) with the lidocaine topical system 1.8% (R) demonstrated ≥ 90% adhesion (FDA adhesion score 0) throughout the 12-hour administration period versus 27.3% of subjects treated with OTC lidocaine patch 4% (T1), 22.7% of subjects treated with OTC lidocaine patch 4% (T2), and 18.2% of subjects treated with OTC menthol/lidocaine patch 1%/4%. Only one subject (4.5%) treated with lidocaine topical system 1.8% was observed with < 75% adhesion (FDA adhesion score < 2) versus 11 (50.0%) and 10 (45.5%) for the two OTC lidocaine patches 4% (T1 and T2), respectively, and 13 (59.1%) subjects for the OTC menthol/lidocaine patch 1%/4%. There were no complete detachments observed for lidocaine topical system 1.8%, whereas 50.0% and 31.8% complete detachments were observed for the two OTC lidocaine patches 4% (T1 and T2), and 27.3% complete detachments were observed for the OTC menthol/lidocaine patch 1%/4%. No adverse events were observed for any of the treatments.Conclusion: Lidocaine topical system 1.8% demonstrated superior adhesion relative to the three lidocaine-containing OTC products over the 12-hour treatment period.Keywords: lidocaine topical system, lidocaine patch, menthol/lidocaine patch, over-the-counter, adhesion, postherpetic neuralgia, external analgesic

Kip Vought,1 Emileigh Greuber,1 Kalpana Patel,1 Charles Argoff,2 Dmitri Lissin1 1Global Research and Development and Medical Affairs, Scilex Pharmaceuticals Inc., Palo Alto, CA, USA; 2Department of Neurology, Albany Medical Center, Albany, NY, USACorrespondence: Dmitri Lissin Email dlissin@scilexpharma.comPurpose: This study compares the adhesion performance, pharmacokinetic profile, and safety of lidocaine topical system 1.8%, which is approved to treat postherpetic neuralgia, under conditions of swimming and showering versus normal conditions.Patients and Methods: This open-label, 3-period, 3-treatment crossover study randomized 24 healthy adults to receive one lidocaine topical system during each of three treatment periods; subjects either swam in a heated swimming pool for 15 minutes 4.0 hours post-product application (swimming), showered for 10 minutes 8.0 hours after product application (showering), or the product remained dry throughout the treatment period (normal conditions). The product was applied to the mid-upper back and was removed after 12 hours. The pharmacokinetic profile of each subject under water exposure conditions was compared to subjects under normal conditions. Skin irritation, adhesion, and adverse events were assessed.Results: Twenty-four (24) subjects enrolled and 23 completed the study. Exposure to water resulted in lifting of the topical systems. There were two complete detachments, as well as seven occurrences of major lifting (more than 50% detached) after water exposure. The topical systems were immediately pressed down and/or reapplied after observing lifting and remained adhered to for the rest of the 12-hour application period. No clinically relevant differences in systemic absorption were observed under either showering or swimming conditions. The topical systems were well tolerated, with only mild adverse events, none leading to discontinuation.Conclusion: These data show that while water exposure can cause the topical system to lift or detach, the lidocaine topical system 1.8% is capable of being reapplied and maintains adhesion for up to 12 hours of wear with no clinically significant changes in drug delivery.Clinicaltrials.gov: NCT04784728.Keywords: lidocaine topical system, postherpetic neuralgia, adhesion, water exposure