KemPharm Announces Preliminary Results from KP415 Pharmacokinetic Single and Multiple Dose Trial
Phase I Study Results Demonstrated Early Peak Exposure to d-Methylphenidate followed by Sustained Duration in both Single and Multiple Dose Settings
“We are very pleased to report that our proposed co-formulation of our proprietary extended release (ER) KP415 d-methylphenidate (d-MPH) prodrug together with immediate release (IR) d-MPH demonstrated expected PK parameters in this Phase I trial and is now being readied for further development in a safety and efficacy clinical trial later this year,” said
“There is a clear need for an extended-release methylphenidate product, with the potential benefit of early onset and longer total duration, as a treatment option for patients,” said
“Given that this Phase I study performed as anticipated, we remain on schedule to begin the single pivotal efficacy clinical trial of KP415 prior to the end of this year,” added Mickle. “Assuming the results of the pivotal trial are positive, we anticipate submitting a New Drug Application (NDA) with the
Summary of the Preliminary Results from Study KP415.109
The Phase 1 clinical trial (KP415.109) was designed to assess the relative pharmacokinetics (PK) of three different co-formulations of the KP415 ER prodrug in combination with IR d-MPH, compared with 54mg of Concerta (ER MPH), after oral administration of once-daily doses for 7-days under fasted conditions. Forty-eight healthy volunteers (12 per dosing group) were enrolled in and completed this open-label, multiple-dose, parallel-group PK clinical trial. Each co-formulation contained total equivalent amounts of 40 mg d-MPH. PK results were evaluated both on a single-dose basis (after the first day of dosing) and a multiple-dose basis over seven days.
Steady state was reached after a few days of dosing in all groups. The combination of 70% KP415 prodrug (the component with extended release (ER) characteristics) and 30% IR d-MPH resulted in a mean Day-7 d-MPH trough concentration (Cmin; pre-dose on Day-7) of 3.3 ng/mL and a mean Day-7 d-MPH peak concentration (Cmax) of 20.9 ng/mL, at a median Tmax of 1.5 hours.
On Day-7, the mean systemic exposure over the dosing interval (AUC0-24) for d-MPH was 208 ng•hr/mL for all completers and the mean terminal elimination plasma half-life (T1/2) of d-MPH was 8.9 hr. The mean accumulation ratios (Day-7/Day-1 ratios) for Cmin, Cmax and AUC0-24 were 1.31, 1.20 and 1.34, respectively. The combination of the 70%/30% KP415/d-MPH resulted in early peak d-MPH exposure followed by sustained d-MPH exposure, as desired for chronic, once-per-day treatment of ADHD in a pediatric population. Based on previously established PK of MPH-based products, KP415 may show an effect vs. placebo from 0.5 hours to 13 hours as substantial plasma concentrations of active MPH were measured during this time-period. This may provide both early onset of action with total duration that may exceed 12.5 hours based on available data.
Plasma concentrations of the inactive, intact KP415 prodrug molecule were measured after oral administration, which may contribute to the ER profile of KP415-derived d-MPH. Intact KP415 did not accumulate after multiple doses, and its mean T1/2 on Day-7 was 5.1 hours.
Both treatments were generally well-tolerated and there were no serious adverse events.
Caution Concerning Forward Looking Statements
This press release may contain forward-looking statements made in reliance upon the safe harbor provisions of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. Forward-looking statements include all statements that do not relate solely to historical or current facts, and can be identified by the use of words such as “may,” “will,” “expect,” “project,” “estimate,” “anticipate,” “plan,” “believe,” “potential,” “should,” “continue” or the negative versions of those words or other comparable words. These forward-looking statements include statements regarding the expected features and characteristics of KP415, the expected timing of the initiation and completion of clinical trials of KP415 and the expected timing for the any submission of a New Drug Application with the
Jason Rando/ Joshua Drumm, Ph. D. Tiberend Strategic Advisors, Inc.212-375-2665 / 2664 firstname.lastname@example.org email@example.com Media Contact: Daniel L. CohenExecutive VP, Government and Public Relations KemPharm, Inc.202-329-1825 firstname.lastname@example.org