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THU0455 PHARMACOKINETICS (PK) OF A SINGLE INTRA-ARTICULAR (IA) INJECTION OF CNTX-4975 (TRANS-CAPSAICIN) VS TOPICAL 8% CAPSAICIN PATCH
  1. Randall Stevens1,
  2. Kimberly Guedes1,
  3. Eddie Armas2,
  4. Valerie Smith3,
  5. Andrew Volosov3
  1. 1Centrexion Therapeutics Corp, Boston, United States of America
  2. 2Well Pharma Medical Research Corp, Miami, United States of America
  3. 3Premier Research, Durham, United States of America

Abstract

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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