1 / 17

Methylphenidate Transdermal System (MTS): Safety Issues

Methylphenidate Transdermal System (MTS): Safety Issues. Robert Levin, M.D. Medical Officer Division of Psychiatry Products Center for Drug Evaluation and Research FDA. Initial Pivotal Studies: N17-018. MC, R, DB, PC, dose titration study ADHD; 6 to 12 years old 6-week. 4 Wk DB

jabari
Download Presentation

Methylphenidate Transdermal System (MTS): Safety Issues

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. Methylphenidate Transdermal System (MTS): Safety Issues Robert Levin, M.D. Medical Officer Division of Psychiatry Products Center for Drug Evaluation and Research FDA

  2. Initial Pivotal Studies: N17-018 • MC, R, DB, PC, dose titration study • ADHD; 6 to 12 years old • 6-week. 4 Wk DB • Started with 12.5 or 18.75 cm2 patch • Titration weekly • (range: 6.25 to 50 cm2) • Wear time: 12 hrs • Later, could decrease wear time to 8.5 to 9 hrs

  3. Initial Studies: N17-010 • MC, R, DB, PC dose titration 3-week study • ADHD; 6 to 12 years old • Started at 6.25 cm2 • Titrated weekly • Wear time: 12 hrs

  4. Initial Safety Issues (NA) • Excessive drug exposure at inappropriate times (evening) • Unacceptable safety profile • Anorexia • Weight loss • Insomnia • Excessive skin irritancy • Potential for skin sensitization

  5. Common AE in Initial Studies

  6. Recommendations by the Division • Decrease patch wear time (from 12 hrs) • Classroom study, PK/PD, time course of effect • Prospectively monitor insomnia w/ specific scale • Possible signal for skin sensitization with periods of use longer than the 6-week duration of the study. A skin exposure study of longer than 6-week duration would be helpful in investigating this potential signal • Use an active comparator

  7. New Studies for Resubmission Study N17-201: MC, R, DB, PC dose optimization and Analog classroom crossover study • 5-week open-label MTS treatment • 2-wk DB, PC phase Patch sizes: 12.5, 18.75, 25, and 37.5 cm2 Wear time: 9 hours Frequent PK and efficacy assessments

  8. New Study for Resubmission Study N17-302: MC, R, DB, PC and Active-controlled (Concerta) outpatient dose optimization study -Patch sizes: 12.5, 18.75, 25, and 37.5 cm2 -Wear time: 9 hours -Concerta doses: 18, 27, 36, and 54 mg

  9. Safety Findings • No deaths or serious adverse events • Discontinuations due to adverse events: Study 201: 8% of O-L group and 1% of PC group (all MTS) Tic (2) rash at site (2) anorexia (2) prolonged QT elevated BP & mood lability

  10. Discontinuations Due to AE in Study 302

  11. Adverse Events in 201 O-L Phase

  12. AE in Placebo-controlled Phase

  13. Adverse Events in Study 302

  14. Weight Loss • Trend toward weight loss in both studies (M & C) • Mean weight decreased in MTS groups (-1.3 to -2.2 lbs). Concerta group: (-2.1) • Decreases in mean z-scores for weight and BMI 201: decreased from -0.08 to -0.15 302 MTS: decreased from 0.05 to -0.21 302 Concerta: decreased from 0.28 to 0.04

  15. Sleep Ratings- CSHQ • Children’s Sleep Habits Questionnaire • Directed assessment; 33 items • Sleep quality, sleep latency, duration, disturbance, etc. • Study 201: in most dosing groups, sleep ratings improved in the O-L & PC phases • Study 302: sleep ratings improved in the MTS, Concerta, and placebo groups. • Subscales: bedtime resistance, delayed onset, sleep duration. Scores improved in all 3 treatment groups

  16. Tics & Twitching Twitching • Study 010: MTS (3%) vs. Placebo (0) • Study 018: MTS (7%) vs. Placebo (0) • In some cases, the investigator terms facial tics, buco-lingual tic, and mouth movements were coded to the preferred term “twitching” Tic: Study 201: 2%. Study 302: 7%; Concerta 1% • Discontinuations due to tic and twitching

  17. Dermatology Findings Skin sensitization study results: sensitization occurred in 13-22% of subjects. Thus, sensitized patients should not take MPH by any route again after sensitization. Dermal response- erythema or irritation at the application site • Study 201: PC phase: MTS (24- 30%) vs. PTS (3- 6%) • Study 302: mean dermal response score was higher than other groups at all visits

More Related