INP105 Proof-of-concept Study for the Acute Treatment of Agitation in Adolescents and Young Adults With ASD (CALM 201)

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

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.

Study Overview

• Status: Terminated
• Conditions: Agitation in Adolescents and Young Adults With ASD
• Intervention / Treatment: Combination product: INP105; Combination product: Placebo

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Maine
    • Portland, Maine, United States, 04102
      • Maine Behavioral Healthcare
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: INP105; POD-olanzapine (INP105), 5 mg, single dose, to be delivered to each participant	Combination product: INP105; A single 5 mg dose of POD-OLZ (Precision Olfactory Delivery [POD®]-olanzapine); Other Names: POD-OLZ
Placebo Comparator: Placebo; POD-placebo, single dose, to be delivered to each participant	Combination product: Placebo; A single dose of POD-placebo (Precision Olfactory Delivery [POD®]-placebo); Other Names: POD-placebo; POD-PBO

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Agitation-Calmness Evaluation Scale (ACES) score at 30 minutes post-dose	The ACES is a 9 point scale that measures the degree of agitation versus sedation, ranging from a score of 1 "marked agitation" to 4 "normal" to 9 "unable to be aroused".	Pre-dose to 30 minutes post-dose
Change in Behavioral Activity Rating Scale (BARS) score at 30 minutes post-dose	The BARS is a 7 point scale measuring the degree of agitated behavior, ranging from 1 "difficult or unable to rouse" to 4 "quiet and awake (normal level of activity)" to 7 "violent, requires restraint.	Pre-dose to 30 minutes post-dose
Change in Overt Aggression Scale (OAS) score at 30 minutes post-dose	The OAS measures the degree of aggression, using 4 categories of aggression, defined as "verbal aggression", "aggression against objects", "aggression against self", and "aggression against other people". The higher a category is rated, the more severe the degree of aggression. The total score is the sum of the scores from the 4 categories.	Pre-dose to 30 minutes post-dose
Change in Positive and Negative Syndrome Scale - Excited Component (PEC) score at 30 minutes post-dose	The PEC describes 5 behaviors related to negative aspects of excitability; excitement, tension, hostility, uncooperativeness, poor impulse control. The rater scores each of these aspects from 1 (not present) to 7 (extreme), for a total score that can range from 5 to 35.	Pre-dose to 30 minutes post-dose
Change in irritability behavior frequency counts at 30 minutes post-dose	Persons with autism can often display repetitive behaviors. These repetitive behaviors, such as rocking, hitting, kicking, will be counted pre-dose and during intervals post-dose.	Pre-dose to 30 minutes post-dose
Clinical Global Impressions - Improvement (CGI-I) score at 30 minutes post-dose	The CGI-I is a 7 point scale that will be used to assess global improvement in the patient's condition on a scale that ranges from 0 "not assessed", 1 "very much improved" to 7 "very much worse".	Pre-dose to 30 minutes post-dose
Clinical Global Impressions - Efficacy (CGI-E) score at 30 minutes post-dose	The CGI-E is a scale that measures the efficacy of an intervention balanced by any negative side effects. Scores can range from 1 (vast improvement and no side effects) to 16 (unchanged or worse and side effects that outweigh therapeutic effect).	Pre-dose to 30 minutes post-dose
Change in modified Aberrant Behavior Checklist - Irritability Subscale (ABC-I) score at 60 minutes post-dose	The ABC-I lists15 behaviors, including aggression, tantrums, crying, seen with irritability and these are scored from 0 "absent" to 3 "severe". Score can therefore range from 0 to 45 (worst irritability).	Pre-dose and at 60 minutes post-dose
Time to reach an ACES score of 4 (normal) post-dosing	The length of time it will take the participant to move from a score of 2 or 1 on the ACES scale to a score of 4 will be determined.	Dosing until 120 minutes post-dose
Frequency of administering pharmaceutical rescue intervention within 120 minutes after dosing	The frequency of administering any pharmaceutical intervention other than the study intervention from dosing until 120 minutes after dosing will be recorded and compared for INP105 versus placebo.	Dosing until 120 minutes post-dose

Collaborators and Investigators

• Sponsor: Impel Pharmaceuticals
• Investigators: Study Chair: Stephen Shrewsbury, MD, Impel Pharmaceuticals; Principal Investigator: Matthew Siegel, MD, Maine Behavioral Healthcare; Principal Investigator: Craig Erickson, MD, Children's Hospital Medical Center, Cincinnati

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): June 23, 2022
• Primary Completion (Actual): March 31, 2023
• Study Completion (Actual): April 24, 2023

Study Registration Dates

• First Submitted: December 1, 2021
• First Submitted That Met QC Criteria: December 13, 2021
• First Posted (Actual): December 20, 2021

Study Record Updates

• Last Update Posted (Actual): September 28, 2023
• Last Update Submitted That Met QC Criteria: September 26, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: autism; olanzapine; agitation
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Dyskinesias; Psychomotor Disorders; Psychomotor Agitation
• Other Study ID Numbers: INP105-201

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No