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

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ClinicalTrials.gov Identifier: NCT05163717
Recruitment Status : Recruiting
First Posted : December 20, 2021
Last Update Posted : June 29, 2022
Sponsor:
Information provided by (Responsible Party):
Impel NeuroPharma Inc.

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 with autism spectrum disorder (ASD) experiencing agitation. Approximately 32 ASD patients who are currently being treated for agitation/aggression at 2 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.


Condition or disease Intervention/treatment Phase
Agitation in Adolescents With Autism Spectrum Disorder Combination Product: INP105 Combination Product: Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 32 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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 With Autism Spectrum Disorder
Estimated Study Start Date : June 23, 2022
Estimated Primary Completion Date : January 2023
Estimated Study Completion Date : July 2023


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 Name: 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




Primary Outcome Measures :
  1. Incidence of adverse events and serious adverse events in the INP105 and placebo groups up to 48 hours post-dose [ Time Frame: From dosing to 48 hours post dosing ]
    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.

  2. Overall incidence of adverse events and serious adverse events in the INP105 and placebo groups [ Time Frame: From dosing to end of follow-up (7 days), or to the start of next blinded treatment (48 hours), as applicable ]
    All adverse events will be recorded as treatment emergent from after dosing until the next treatment, or until last study visit, as applicable.


Secondary Outcome Measures :
  1. Change in Agitation-Calmness Evaluation Scale (ACES) score at 30 minutes post-dose [ Time Frame: Pre-dose to 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".

  2. Change in Behavioral Activity Rating Scale (BARS) score at 30 minutes post-dose [ Time Frame: Pre-dose to 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.

  3. Change in Overt Aggression Scale (OAS) score at 30 minutes post-dose [ Time Frame: Pre-dose to 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.

  4. Change in Positive and Negative Syndrome Scale - Excited Component (PEC) score at 30 minutes post-dose [ Time Frame: Pre-dose to 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.

  5. Change in irritability behavior frequency counts at 30 minutes post-dose [ Time Frame: Pre-dose to 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.

  6. Clinical Global Impressions - Improvement (CGI-I) score at 30 minutes post-dose [ Time Frame: Pre-dose to 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".

  7. Clinical Global Impressions - Efficacy (CGI-E) score at 30 minutes post-dose [ Time Frame: Pre-dose to 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).

  8. Change in modified Aberrant Behavior Checklist - Irritability Subscale (ABC-I) score at 60 minutes post-dose [ Time Frame: Pre-dose and 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).

  9. Time to reach an ACES score of 4 (normal) post-dosing [ Time Frame: Dosing until 120 minutes post-dose ]
    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.

  10. Frequency of administering pharmaceutical rescue intervention within 120 minutes after dosing [ Time Frame: Dosing until 120 minutes post-dose ]
    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.



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Ages Eligible for Study:   12 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  • Currently diagnosed with a genetic or other syndromic form of neurodevelopmental disorder
  • Seizure in the past 6 months
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05163717


Contacts
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Contact: Stephen Shrewsbury, MD 206-568-1466 sshrewsbury@impelpharma.com

Locations
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United States, Maine
Maine Behavioral Healthcare Recruiting
Portland, Maine, United States, 04102
Contact: Matthew Siegel, MD    207-661-4618    Matthew.Siegel@mainehealth.org   
United States, Ohio
Cincinnati Children's Hospital Medical Center Recruiting
Cincinnati, Ohio, United States, 45229
Contact: Craig Erickson, MD    513-636-1150    Craig.Erickson@cchmc.org   
Sponsors and Collaborators
Impel NeuroPharma Inc.
Investigators
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Study Chair: Stephen Shrewsbury, MD Impel NeuroPharma Inc.
Principal Investigator: Craig Erickson, MD Children's Hospital Medical Center, Cincinnati
Principal Investigator: Matthew Siegel, MD Maine Behavioral Healthcare
Publications:
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Responsible Party: Impel NeuroPharma Inc.
ClinicalTrials.gov Identifier: NCT05163717    
Other Study ID Numbers: INP105-201
First Posted: December 20, 2021    Key Record Dates
Last Update Posted: June 29, 2022
Last Verified: June 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Impel NeuroPharma Inc.:
agitation
olanzapine
autism
Additional relevant MeSH terms:
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Psychomotor Agitation
Autistic Disorder
Autism Spectrum Disorder
Child Development Disorders, Pervasive
Neurodevelopmental Disorders
Mental Disorders
Dyskinesias
Neurologic Manifestations
Nervous System Diseases
Psychomotor Disorders
Neurobehavioral Manifestations