INP105 Proof-of-concept Study for the Acute Treatment of Agitation in Adolescents and Young Adults With ASD

NCT05163717 | Terminated Phase 2 FDA Drug

• 1 other identifier: INP105-201
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 2

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.

Conditions

Agitation in Adolescents and Young Adults With ASD

Keywords

agitation; olanzapine; autism

Outcome Measures

Primary Outcomes (2)

• Incidence of adverse events and serious adverse events in the INP105 and placebo groups up to 48 hours post-dose

  All adverse events, serious or not, will be recorded from time of dosing with either INP105 or placebo up until 48 hours post-dose, or until the next treatment is given, which ever is sooner.

  From dosing to 48 hours post dosing

• Overall incidence of adverse events and serious adverse events in the INP105 and placebo groups

  All adverse events will be recorded as treatment emergent from after dosing until the next treatment, or until last study visit, as applicable.

  From dosing to end of follow-up (7 days), or to the start of next blinded treatment (48 hours), as applicable

Secondary Outcomes (10)

• Change in Agitation-Calmness Evaluation Scale (ACES) score at 30 minutes post-dose

  Pre-dose to 30 minutes post-dose

• Change in Behavioral Activity Rating Scale (BARS) score at 30 minutes post-dose

  Pre-dose to 30 minutes post-dose

• Change in Overt Aggression Scale (OAS) score at 30 minutes post-dose

  Pre-dose to 30 minutes post-dose

• Change in Positive and Negative Syndrome Scale - Excited Component (PEC) score at 30 minutes post-dose

  Pre-dose to 30 minutes post-dose

• Change in irritability behavior frequency counts at 30 minutes post-dose

  Pre-dose to 30 minutes post-dose

Study Arms (2)

INP105

EXPERIMENTAL

POD-olanzapine (INP105), 5 mg, single dose, to be delivered to each participant

Combination Product: INP105

Placebo

PLACEBO COMPARATOR

POD-placebo, single dose, to be delivered to each participant

Combination Product: Placebo

Interventions

INP105 COMBINATION_PRODUCT

A single 5 mg dose of POD-OLZ (Precision Olfactory Delivery \[POD®\]-olanzapine)

Also known as: POD-OLZ

INP105

Placebo COMBINATION_PRODUCT

A single dose of POD-placebo (Precision Olfactory Delivery \[POD®\]-placebo)

Also known as: POD-placebo, POD-PBO

Placebo

Eligibility Criteria

• Age: 12 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Impel Pharmaceuticals: lead

Study Sites (2)

Maine Behavioral Healthcare

Portland, Maine, 04102, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Related Publications (1)

• 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.

  PMID: 32609960 BACKGROUND

MeSH Terms

Conditions

Psychomotor Agitation; Autistic Disorder

Condition Hierarchy (Ancestors)

Dyskinesias; Neurologic Manifestations; Nervous System Diseases; Psychomotor Disorders; Neurobehavioral Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Aberrant Motor Behavior in Dementia; Behavioral Symptoms; Behavior; Autism Spectrum Disorder; Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders

Study Officials

• Stephen Shrewsbury, MD

  Impel Pharmaceuticals

  STUDY CHAIR

• Craig Erickson, MD

  Children's Hospital Medical Center, Cincinnati

  PRINCIPAL INVESTIGATOR

• Matthew Siegel, MD

  Maine Behavioral Healthcare

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2021
• First Posted: December 20, 2021
• Study Start: June 23, 2022
• Primary Completion: March 31, 2023
• Study Completion: April 24, 2023
• Last Updated: September 28, 2023

Record last verified: 2023-09

Locations

US (2)