Background: CNTX-4975 is in phase 3 trials for treatment of moderate to severe pain associated with knee osteoarthritis (OA). PK data from prior studies of CNTX-4975 in subjects with moderate to severe knee OA pain suggest low systemic and short-term exposure, similar to the FDA-approved topical capsaicin 8% patch.
Objectives: We compared single-dose systemic exposure to trans- and cis-capsaicin following IA injection of CNTX-4975 (>99.5% trans-capsaicin, <0.5% total impurities) with 8% capsaicin patch in subjects with moderate to severe knee OA pain.
Methods: This open-label, crossover study enrolled adults aged 50–75 y with moderate to severe knee OA pain in ≥1 knee (most painful knee, index knee; nonindex knee, no to mild pain [0–1; NPRS 0–4 scale]). Subjects were randomized 1:1 to 2 sequences: A (CNTX-4975 1 mg IA, index knee) followed by B (topical capsaicin 8% patch, posterior rib cage for 60 min) or BA sequence, with ≥7-day washout between treatments. Plasma samples for trans- and cis-capsaicin concentration assays were taken before and at specified times after study treatment. PK parameters, including maximum observed plasma concentration (Cmax), area under the plasma concentration-time curve from time 0 to last quantifiable plasma concentration (AUC0-t) and to infinity (AUC0-∞), time to Cmax (Tmax), and half-life (t1/2), were determined. PK parameters were reported using descriptive statistics. Geometric means ratios of ln-transformed AUC0-t, AUC0-∞, and Cmax were evaluated using ANOVA.
Results: Sixteen subjects (median age, 62 y; female, 62.5%) were randomized to treatment (PK analysis population). Tmax showed more rapid absorption of trans-capsaicin from IA CNTX-4975 vs the topical patch (Table). AUC0-t and Cmax indicated greater trans-capsaicin exposure with CNTX-4975 vs the patch; however, exposure was short term, with mean t1/20.5 h. Cis-capsaicin concentrations were insufficient for calculating PK.
Conclusion: Trans-capsaicin from CNTX-4975 injection was rapidly absorbed and eliminated. The extent of systemic exposure to trans-capsaicin was significantly higher after CNTX-4975 vs the 8% capsaicin patch.
Disclosure of Interests: Randall Stevens Shareholder of: Centrexion Therapeutics Corp, Employee of: Centrexion Therapeutics Corp, Kimberly Guedes Employee of: Centrexion Therapeutics Corp, Eddie Armas: None declared, Valerie Smith Consultant for: Premier Research, Andrew Volosov Consultant for: Premier Research
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