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

Phase 2TerminatedNCT05163717

Impel Pharmaceuticals8 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Eligibility

Sex: ALLMin age: 12 YearsMax age: 21 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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.

Time frame: 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.

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

Secondary Outcomes

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".