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Oxcarbazepine Extended Release OXC XR

Oxcarbazepine Extended Release OXC XR. Janet K. Johnson, Ph.D. Director, Clinical Research Supernus Pharmaceuticals, Inc. ASENT Pipeline Projects Session March 5, 2010. Development of OXC XR. Supernus Pharmaceuticals, Inc

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Oxcarbazepine Extended Release OXC XR

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  1. Oxcarbazepine Extended ReleaseOXC XR Janet K. Johnson, Ph.D. Director, Clinical Research Supernus Pharmaceuticals, Inc. ASENT Pipeline Projects Session March 5, 2010

  2. Development of OXC XR • Supernus Pharmaceuticals, Inc • Small pharmaceutical company with proprietary drug delivery methodology • Experience with CNS products (ADHD, epilepsy) as Shire Labs • OXC as candidate for XR development • Effective doses 600 – 2400mg/d • Increase response rate with increase in dose • Highest doses associated with significant AEs

  3. OXC v Placebo, Barcs Study% Seizure Free N=174~ N=178 50%* 40%* N=169 26%* N=173 8% 22% 3% 10% 0.6% Median % seizure reduction Epilepsia, 41(12):1597, 2000 *p=0.0001 compared to placebo ~ includes 47 pts at 1800 mg; 73% of patients on 2400mg dropped from the study or decreased to 1800mg

  4. Relationship between a given serum MHD level and the presence/absence of an AE (ROC curve analysis) (n = total number of MHD samples). Striano et al, Epilepsy Research 2006, 69(2):170-176

  5. Incentives for Development of OXC XR • Current Formulation • BID dosing • Association of AEs with peak levels • Possible Advantages of XR Formulation • QD dosing – may increase compliance • Lower peak – may increase tolerablity

  6. Solutrol Receding Solid Interface Drug + Polymer Core Solubilized Drug Release Path Hydrated Polymer Layer

  7. Solutrol Receding Solid Interface Drug + Polymer Core Solubilized Drug Release Path

  8. Solutrol vs pH Dependent Dissolution OXC solubility 15 mg/mL at pH 1.0 0.22 mg/mL at pH7.0

  9. OXC XR vs IR at Steady StateHealthy Normal Volunteers, 7 days, 1200mg, crossover

  10. OXC XR vs IR at Steady State (7 days, 1200mg) PK studies of OXC XR vs IR OXC XR - Food Effect (single 600mg dose)

  11. OXC XR vs OXC IR - Steady StateNumber of AEs, Total Nervous & GI Systems 190 120 54 53 24 19

  12. 804P103 - Comparative Steady StateAEs Experienced by >10% of Subjects

  13. OXC XR Phase 3 Study Design 360 adult patients, 90+ sites, 8 countries Refractory partial seizures, 1-3 AEDs Baseline of ≥ 3 countable seizures/28d Seizure classification reviewed by Epilepsy Study Consortium QD, 1:1:1, Placebo: 1200mg OXC XR: 2400mg OXC XR 8 wk baseline, 4 wk titration, 12 wk treatment, 3 wk taper Option for 1 year open-label follow-on study 1Efficacy = % change seizures/28d, OXC XR vs Placebo 2Efficacy = % seizure-free, other efficacy, safety, QOL

  14. BASELINE TREATMENT Maintenance Conversion Screening Titration 2400 mg/d 1800 1800 1200 1200 mg/d 1200 600 600 Placebo 1 3 4 5 6 VISIT 2 7 WEEK 1 3 4 5 -8 to -1 2 9 13 17 18 19 3 weeks 12 weeks 4 weeks 8 weeks SEIZURE DIARY 804P301 Study Design 6 Seizure Identification Form PK Sampling

  15. Development of XR, CR for Epilepsy Supernus status Development of OXC XR for partial epilepsy QD formulation, 80% AUC, Cmax vs OXC IR Lower incidence of AEs in PK study of HNV at 1200mg Possible greater utility of high dose (2400mg) Ongoing Phase 3 placebo-controlled study in adults Ongoing PK study in pediatrics Development of Topiramate Controlled Release

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