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 POD^TM) 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.