Abstract Details

Title A Randomized, Double-Blind, Placebo-Controlled, Multiple Ascending Dose Pharmacokinetics (PK), Pharmacodynamics (PD), and Tolerability of LP352 in Healthy Subjects

Topic Epilepsy/Clinical Neurophysiology (EEG)

Presentation(s) P14 - Poster Session 14 (11:45 AM-12:45 PM)

Poster/Presentation
Number 10-002

Objective To evaluate PK, PD, safety, tolerability of multiple doses of LP352.

Background LP352 is a potent and selective 5-HT2c superagonist. LP352 is being developed for the treatment of developmental and epileptic encephalopathies.

Design/Methods This study enrolled healthy adults, ages 18 to 55 years and body mass index of 18.5-30.0 kg/m² in two parts. Subjects in one part received thrice daily (every 8 h) doses of powder-in-capsule without titration for 14 days, and in another part received the highest dose with 3-day titration. On PK sampling days, subjects fasted overnight prior to the morning dose. Serial plasma and prolactin samples were collected on Day 1 and Day 14, and urine samples were collected on Day 14. Safety was assessed continuously from signing of informed consent form through follow up visit.

Results Forty-three (16M, 27F) subjects were enrolled. LP352 was rapidly absorbed. Significant accumulation occurred upon multiple dosing TID. For the non-titration part, steady-state was achieved by Day 10, in most cases. At steady state, about 30% of the dose was eliminated by the renal route in 48 h (in non-titrated groups). Prolactin increased in a dose- and concentration-dependent manner, with greater increase seen after first dose. Three subjects discontinued due to adverse events. Majority of the treatment emergent adverse events (TEAEs) were mild to moderate. Most common were headache, somnolence, dizziness, dizziness postural, micturition urgency & orthostatic hypotension. Five TEAEs occurring in 3 subjects (all after cessation of LP352 dosing) were severe. One serious adverse event was reported after stopping treatment at the highest dose, consistent with abrupt discontinuation of serotonergic drugs. This subject accounted for 3 severe TEAEs.

Conclusions The data support further development in developmental & epileptic encephalopathies and other seizure disorders.

Authors/Disclosures
Philip Perera, MD PRESENTER	Dr. Perera has received personal compensation for serving as an employee of Longboard Pharmaceuticals. Dr. Perera has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Sage Therapeutics. Dr. Perera has stock in Longboard Pharmaceuticals. Dr. Perera has received personal compensation in the range of $100,000-$499,999 for serving as a Chief Medical Officer with Longboard Pharmaceuticals.
Dolly A. Parasrampuria, PhD (Longboard Pharmaceuticals)	Dr. PARASRAMPURIA has received personal compensation for serving as an employee of Longboard Pharmaceutical. Dr. PARASRAMPURIA has received personal compensation for serving as an employee of Johnson & Johnson. Dr. PARASRAMPURIA has stock in Longboard Pharmaceuticals. Dr. PARASRAMPURIA has stock in Longboard Pharmaceuticals.
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file

��ɫ��

��ɫ��