Clinical trial NCT05163717: INP105 Proof-of-concept Study for the Acute Treatment of Agitation in Adolescents and Young Adults With ASD
Official title: A Phase 2a, Randomized, Double-Blind, Placebo-Controlled, Single Dose, 2-Way, 2-Period Crossover Safety and Exploratory Efficacy Study of INP105 (POD-OLZ) for the Acute Treatment of Agitation in Adolescents and Young Adults With Autism Spectrum Disorder
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Agitation in Adolescents and Young Adults With ASD
Keywords: agitation
olanzapine
autism
Lead sponsor: Impel Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2021-12-20
Enrollment: 8
Sex: ALL
Minimum age (years): 12
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: This is a Phase 2a, proof-of concept, 2-way, 2-period crossover, double-blind study to evaluate the safety and efficacy of INP105 as an acute treatment versus placebo in adolescents and young adults with autism spectrum disorder (ASD) experiencing agitation. Approximately 32 ASD patients who are currently being treated for agitation/aggression at several inpatient units specializing in behavioral treatment will be enrolled.

INP105 is a novel combination product that sprays a powder formulation of olanzapine to the upper nasal space. An earlier formulation showed a similar extent, but faster rate of absorption compared to the approved intramuscular product. In this study, 5 mg of olanzapine or placebo will be delivered nasally by this combination product to moderately or severely agitated participants.

Participants will undergo several screening assessments, including observation session(s) of episode(s) of agitation resulting from a frustration task (eg, a non-preferred activity). At least one observation session must result in a documented moderate to severe agitation episode prior to the participant being eligible to enroll in the study and be randomized to treatment.

The study will be conducted in 2 phases. A pilot phase will initially enroll at least 6 participants, who will receive both 5 mg INP105 (5 mg olanzapine) and placebo in random order, in the same crossover design as later participants. Participants will be dosed during a documented moderate to severe episode of agitation. Once 6 participants have completed both dosing periods and have at least 48 hours of post-dose safety data collected, a safety and preliminary efficacy analysis will be performed by an independent unblinded statistical group, and a summary report forwarded to a sponsor-led Data and Safety Review Committee (DSRC), who will remain blinded. Enrollment will be paused during the DSRC pilot phase safety and preliminary efficacy results review. Absent any concerning safety signals, the second phase will enroll all remaining participants. The DSRC may suggest revisions to the protocol, and the protocol amended and approved as necessary, prior to further participants being enrolled.


Eligibility criteria: Inclusion Criteria:

* Confirmed autism spectrum disorder diagnosis
* Admitted as an inpatient to a behavioral unit prior to informed consent
* Displays episodes of moderate to severe agitation

Exclusion Criteria:

* Hypersensitivity to olanzapine
* History of severe head trauma, stroke, endocrine disorder, or cardiovascular disease
* History of hypotension
* Currently on a chronic dose of olanzapine
* Currently taking ciprofloxacin, enoxacin, fluvoxamine, or carbamazepine

Primary outcomes:
measure: Incidence of adverse events and serious adverse events in the INP105 and placebo groups up to 48 hours post-dose
timeFrame: From dosing to 48 hours post dosing
measure: Overall incidence of adverse events and serious adverse events in the INP105 and placebo groups
timeFrame: From dosing to end of follow-up (7 days), or to the start of next blinded treatment (48 hours), as applicable
Secondary outcomes:
measure: Change in Agitation-Calmness Evaluation Scale (ACES) score at 30 minutes post-dose
timeFrame: Pre-dose to 30 minutes post-dose
measure: Change in Behavioral Activity Rating Scale (BARS) score at 30 minutes post-dose
timeFrame: Pre-dose to 30 minutes post-dose
measure: Change in Overt Aggression Scale (OAS) score at 30 minutes post-dose
timeFrame: Pre-dose to 30 minutes post-dose
measure: Change in Positive and Negative Syndrome Scale - Excited Component (PEC) score at 30 minutes post-dose
timeFrame: Pre-dose to 30 minutes post-dose
measure: Change in irritability behavior frequency counts at 30 minutes post-dose
timeFrame: Pre-dose to 30 minutes post-dose
measure: Clinical Global Impressions - Improvement (CGI-I) score at 30 minutes post-dose
timeFrame: Pre-dose to 30 minutes post-dose
measure: Clinical Global Impressions - Efficacy (CGI-E) score at 30 minutes post-dose
timeFrame: Pre-dose to 30 minutes post-dose
measure: Change in modified Aberrant Behavior Checklist - Irritability Subscale (ABC-I) score at 60 minutes post-dose
timeFrame: Pre-dose and at 60 minutes post-dose
measure: Time to reach an ACES score of 4 (normal) post-dosing
timeFrame: Dosing until 120 minutes post-dose
measure: Frequency of administering pharmaceutical rescue intervention within 120 minutes after dosing
timeFrame: Dosing until 120 minutes post-dose
Other outcomes:
Locations:
city: Portland
country: United States
facility: Maine Behavioral Healthcare
state: Maine
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
Study officials:
affiliation: Impel Pharmaceuticals
name: Stephen Shrewsbury, MD
role: STUDY_CHAIR
affiliation: Children's Hospital Medical Center, Cincinnati
name: Craig Erickson, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Maine Behavioral Healthcare
name: Matthew Siegel, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Shrewsbury SB, Hocevar-Trnka J, Satterly KH, Craig KL, Lickliter JD, Hoekman J. The SNAP 101 Double-Blind, Placebo/Active-Controlled, Safety, Pharmacokinetic, and Pharmacodynamic Study of INP105 (Nasal Olanzapine) in Healthy Adults. J Clin Psychiatry. 2020 Jun 30;81(4):19m13086. doi: 10.4088/JCP.19m13086.