SNAP 101: Randomized, Crossover, Active/Placebo- Controlled, Safety and PK/PD Study of 3 Ascending Doses of POD® Olanzapine
Poster presented at APA 2019 Annual Meeting. No. 162, page 793.
Poster Presenter: Stephen Shrewsbury
Co-Authors: Meghan Swardstrom, Kelsey Satterly,Jacki Campbell, John Gillies, John Hoekman, Niquita Tugiono, Jasna Hocevar-Trnka
Objectives: 1) Establish safety and tolerability of 3 doses of INP105 2) Compare PK data for olanzapine (OLZ) from 3 INP105 doses with OLZ IM (5 mg) and orally disintegrating tablets (OLZ-ODT) 10 mg 3) Establish and compare PD effects of INP105 to OLZ IM, OLZ-ODT and placebo 4) Explore PK/PD and dose-response relationships for INP105
Background: A survey of US Emergency Department (ED) staff in 2008 found 65% had witnessed physical attacks, 32% reported ?1 verbal threat per day and 18% had been assaulted once or more with a weapon but only 40% of EDs trained staff on how to respond. An estimated 1.7 million events/year occur for which OLZ IM is a preferred option due to a shorter Tmax than oral, but IM administration can be painful, humiliating, invasive and requires cooperation, or restraint which reduces trust, increases healthcare worker injuries and may be interpreted as an assault. In addition, heavily medicated patients may then require “boarding” until sedative effects have worn off. Oral treatment is preferred but has slower onset of effect and requires observation of the medicated patient. INP105 is a drug-device combination product of OLZ powder delivered by the Precision Olfactory Delivery (POD®) device to the vascular rich upper nasal space. It is being developed for rapid control of agitation in a cooperative or uncooperative patient (by a caregiver administered dose) to provide fast onset of relief in an accessible dosage form without a needle. INP105 may also be suitable for early use by patients who have insight into their condition and recognize early symptoms of agitation. This may avoid escalating agitation leading to violence and injury to the patient, their caregivers and/or healthcare workers.
Methods: Randomized, double-blind, placebo- and active comparator-controlled, ascending-dose, 2-way, 2 period, incomplete block, crossover Phase 1 trial to compare the safety, tolerability, PK and PD of 3 doses of INP105 (5 mg, 10 mg and 15 mg) or placebo with either OLZ IM (5 mg) or OLZ-ODT (10 mg). Period 1 is open label; Period 2 is double-blind with at least 14 days between periods. Dose escalation will be staggered to allow a safety monitoring committee to assess tolerability of INP105 between doses. All subjects will be observed as in-patients for at least 72 hours post-dosing with follow-up occurring 4, 5 and 14 days after dosing in both periods.
Study design:[Image of complex study design]
Results: 36 subjects were dosed and SMCs 1 and 2 reviewed safety data in real time and approved dose escalation. PD and PK data is being collected, reviewed and analyzed – and will be presented at the APA meeting.
Conclusions: This study investigated POD delivery of OLZ prior to further studies to confirm it is rapidly effective treatment to abort episodes of acute agitation.
Citation: Shrewsbury S, Swardstrom M, Satterly K, Campbell J, Gillies J, Hoekman J, Tugiono N, Hocevar-Trnka J. SNAP 101: Randomized, Crossover, Active/Placebo-Controlled, Safety and Pharmacokinetic/Pharmacodynamic Study of 3 Ascending Doses of POD® Olanzapine. Poster presented at the American Psychiatric Association 2019 Annual Meeting in San Francisco.