CONCERTA - OROS Technology

Summary

• CONCERTA (methylphenidate HCl extended-release [MPH ER]) is an ER formulation of MPH utilizing an advanced version of the osmotic release oral system (OROS)^® drug delivery system designed to deliver MPH at a controlled rate. It resembles a conventional tablet in appearance.¹
• Twenty-two percent of the total MPH dose is released initially, and the remaining dose is released from 2 inner compartments over the remainder of the duration of action.²
• Because of the unique properties of OROS, CONCERTA must be swallowed whole and may not be crushed, chewed, or divided. Crushing or chewing CONCERTA compromises the delivery system leading to an unknown pharmacokinetic (PK) profile for MPH.¹
• Please see the CONCERTA Prescribing Information for complete information regarding recommended dosing guidelines and the OROS delivery system.¹
• Childress et al (2025) reported 2 single-dose, open-label, randomized, 4-period, 2-treatment replicate trials evaluating the PK profile and bioequivalence of 2 doses (72-mg and 54-mg) of ODX-MPH ER and equivalent doses of OROS-MPH ER in healthy volunteers under fasting conditions.³
  • In the 72-mg study, the values of the within-subject standard deviation of the reference product (s_WR) for the natural log-transformed maximum concentration (C_max), area under the concentration-time curve from time 0 to 3 hours after dosing (AUC_{0-3 h}), area under the concentration-time curve from time 3 to 7 hours after dosing (AUC_{3-7 h}), area under the concentration-time curve from 7 to 12 hours after dosing (AUC_{7-12 h}), and area under the concentration-time curve from time 0 extrapolated to infinity (AUC_inf) were 0.132, 0.149, 0.102, 0.144, and 0.1, respectively. In the 54-mg study, the corresponding s_WR values were 0.129, 0.139, 0.123, 0.14, and 0.104, respectively. The two one-sided tests procedure was applied in both studies, and the 90% confidence intervals (CIs) for these parameters were within the prespecified bioequivalence range.³
  • Overall, 65 treatment-emergent adverse events (TEAEs) in 21 participants were reported in the 72-mg trial, whereas 12 TEAEs in 10 participants were reported in the 54-mg trial.³

PRODUCT INFORMATION

The OROS system for CONCERTA consists of a semi-permeable tablet shell surrounding an osmotically active drug core. The tablet shell is covered by a drug overcoat. This drug overcoat contains 22% of the total dose of MPH. The core itself is divided into 3 compartments: two active layers containing the drug in different concentrations and a push layer containing pharmacologically inert, but osmotically active polymer ingredients. The two active layers contain the remaining 78% of the dose.²

The amount of MPH in the drug overcoat is approximately 4 mg for the 18-mg tablet, 6 mg for the 27-mg tablet, 8 mg for the 36-mg tablet, and 12 mg for the 54-mg tablet.²

For proprietary reasons, we cannot disclose the amount of MPH in each of the 2 active layers of the tablet, or the amount of MPH released per unit time.

CLINICAL DATA

PK Study

Childress et al (2025)³ reported 2 single-dose, open-label, randomized, 4-period, 2-treatment replicate trials that compared the PK profile and bioequivalence of 2 doses (72-mg and 54-mg) of ODX-MPH ER with those of equivalent doses of OROS-MPH ER in healthy volunteers under fasting conditions.

Study Design/Methods

• Eligible participants were healthy adult volunteers aged 18 to 45 years at the time of dosing, with a body mass index of 18 to 32 kg/m² and a body weight of at least 59 kg.
• In both trials, ODX-MPH ER and OROS-MPH ER were administered to the participants during 2 study periods to under fasting conditions.
• The first trial compared a 72-mg dose of ODX-MPH ER administered as a single tablet and a 72-mg dose of OROS-MPH ER administered as two 36-mg tablets. The second trial compared a 54-mg dose of ODX-MPH ER administered as a single tablet and a 54-mg dose of OROS-MPH ER administered as a single tablet.

Results

Overall, 56 participants (93%) in the 72-mg study and 34 participants (94%) in the 54-mg study completed at least 2 study periods and received at least 1 dose of OROS-MPH ER; these were included in the PK analysis. See Table: PK Parameters in the 2 Trials Comparing Different ODX-MPH ER Doses to Equivalent OROS-MPH ER Doses.

For the 72-mg study, the s_WR values for natural log-transformed C_max, AUC_{0-3 h}, AUC_{3-7 h}, AUC_{7-12 h}, and AUC_inf were 0.132, 0.149, 0.102, 0.144, and 0.1, respectively; for the 54-mg study, the corresponding s_WR values were 0.129, 0.139, 0.123, 0.14, and 0.104, respectively. The two one-sided tests procedure was applied in both studies. The 90% CIs for these parameters were within the prespecified range for establishing bioequivalence. See Table: Statistical Analysis of the Natural Log-Transformed Systemic Exposure Parameters After Dosing with ODX-MPH ER and OROS-MPH ER.

Safety

• In the 72-mg trial, 65 TEAEs were reported in 21 participants following dose administration. All TEAEs were mild or moderate in severity. See Table: Most Common TEAEs Reported in the 72-mg and 54-mg Trials.
  • Two participants experienced TEAEs of clinical significance. One participant was diagnosed with neutropenia during end-of-study clinical evaluations conducted 36 hours after ODX-MPH ER administration; the other participant experienced tachycardia during 3 study periods, occurring twice after ODX-MPH ER administration and once after OROS-MPH ER administration.
• In the 54-mg trial, 12 TEAEs were reported in 10 participants following dose administration. Among these 12 TEAEs, 1 was reported after dosing with ODX-MPH ER, whereas the remaining 11 were reported after dosing with OROS-MPH ER. Eleven TEAEs were mild and 1 TEAE was moderate in severity. See Table: Most Common TEAEs Reported in the 72-mg and 54-mg Trials.
  • Clinically significant TEAEs were reported in 2 participants. One participant was diagnosed with neutropenia and elevated creatine kinase during clinical laboratory evaluations conducted in the setting of an early termination, approximately 10 days after OROS-MPH ER administration; the other participant experienced tachycardia approximately 4 hours after ODX-MPH ER administration.

LITERATURE SEARCH

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent^® (and/or other resources, including internal/external databases) pertaining to this topic was conducted on 17 September 2026.