THOR 201: A Proof-of-Concept Study Assessing Safety, Tolerability, PK and PD of L-dopa delivered to Parkinson’s Disease Patients in a Morning OFF Episode (in the presence of Dopa Decarboxylase Inhibitor)
Poster presented at World Parkinson’s Congress 2019 in Kyoto, Japan
Authors: Shrewsbury SB, Campbell J, Swardstrom M, Lehn A, Satterly KH, Hoekman J
Objective: Impel NeuroPharma has developed the patient-friendly, self or caregiver actuated Precision Olfactory Delivery (IMPEL PODTM) device to achieve consistent upper nasal cavity drug delivery, rapid systemic uptake and higher bioavailability relative to standard nasal sprays. This study with L-dopa for treatment of morning OFF episodes of Parkinson’s Disease (PD) assessed safety, tolerability, pharmacokinetics (PK) and pharmacodynamics of L-dopa administered with a dopa decarboxylase inhibitor (DCI).
Background: As PD progresses, the brain requires more frequent and higher doses of L-dopa, yet still patients suffer disabling OFF episodes due to L-dopa (the “platinum” standard treatment for PD) plasma fluctuations. INP103 is a drug-device combination product of a novel formulation of L-dopa delivered to the upper nasal cavity by the POD device.
Methods: A randomized, placebo controlled, single dose study was conducted in L-dopa-responsive PD patients in a morning OFF episode at 5 Movement Disorder Clinics with safety, tolerability and PK blood collections for 2 hours post dosing and repeated MDS-UPDRS assessments. INP103 at 35 mg, 70 mg and 140 mg per dose were assessed, pre-dosed 60 minutes ahead of test dosing with oral DCI (benserazide).
Results: To date, 2 cohorts have completed dosing. Blinded, drug related TEAE data from 12 active and 4 placebo dosed subjects revealed single episodes of: hypertension, sinus dryness, foggy head, mucus back of nose/throat, sneezing + coughing, drowsiness and nasal irritation and 2 episodes of headache. All AEs were mild, self-limiting and most lasted less than 1 hour. There were 3 (blinded) reports of slight post dosing dyskinesia in cohort 1, but no reports in cohort 2.
Conclusions: Satisfactory safety and tolerability results have allowed for 3 escalating doses of INP103 to be administered to PD patients in morning OFF episodes, with detailed collection and analysis of PK and pharmacodynamic data ongoing.