olanzapine intranasal (INP105) / Impel Pharma - LARVOL DELTA

CALM 201: INP105 Proof-of-concept Study for the Acute Treatment of Agitation in Adolescents and Young Adults With ASD (clinicaltrials.gov) - P2a | N=8 | Terminated | Sponsor: Impel Pharmaceuticals | N=32 ➔ 8 | Active, not recruiting ➔ Terminated; Busness reason's

Enrollment change • Trial termination • Autism Spectrum Disorder • Genetic Disorders

CALM 201: INP105 Proof-of-concept Study for the Acute Treatment of Agitation in Adolescents and Young Adults With ASD (clinicaltrials.gov) - P2a | N=32 | Active, not recruiting | Sponsor: Impel Pharmaceuticals | Recruiting ➔ Active, not recruiting | Trial completion date: Jul 2023 ➔ Mar 2023

Enrollment closed • Trial completion date • Autism Spectrum Disorder • Genetic Disorders

CALM 201: INP105 Proof-of-concept Study for the Acute Treatment of Agitation in Adolescents With ASD (clinicaltrials.gov) - P2a | N=32 | Recruiting | Sponsor: Impel NeuroPharma Inc. | Not yet recruiting ➔ Recruiting | Trial completion date: Jul 2022 ➔ Jul 2023 | Initiation date: Dec 2021 ➔ Jun 2022 | Trial primary completion date: Jul 2022 ➔ Jan 2023

Enrollment open • Trial completion date • Trial initiation date • Trial primary completion date • Autism Spectrum Disorder • Genetic Disorders

CALM 201: INP105 Proof-of-concept Study for the Acute Treatment of Agitation in Adolescents With ASD (clinicaltrials.gov) - P2a; N=32; Not yet recruiting; Sponsor: Impel NeuroPharma Inc.

Clinical • New P2a trial • Autism Spectrum Disorder • Genetic Disorders

The SNAP 101 Double-Blind, Placebo/Active-Controlled, Safety, Pharmacokinetic, and Pharmacodynamic Study of INP105 (Nasal Olanzapine) in Healthy Adults. (PubMed, J Clin Psychiatry) - P1 | "INP105 has rapid absorption and pharmacodynamic effects and may represent an effective, convenient, noninvasive, and well-tolerated alternative for treating acutely agitated patients by self- or caregiver administration in the home, community, or hospital environments."

Clinical • Journal • PK/PD data • Anesthesia • Hypotension

Impel NeuroPharma Announces Publication of Positive Results of SNAP 101 Study for INP105 for the Treatment of Acute Agitation in The Journal of Clinical Psychiatry (PRNewswire) - P1, N=38; SNAP101 (NCT03624322); Sponsor: Impel NeuroPharma Inc.; "The published results from the study...demonstrated that INP105 reached peak plasma levels (Tmax) approximately twice as fast as intramuscular olanzapine (Zyprexa®), and ten-times faster than orally-disintegrating tablets (ODT, Zyprexa Zydis®). Maximum and total plasma levels (Cmax and AUC) were similar to intramuscular delivery of the same dose and exceeded the total plasma levels for ODT. Additionally, pharmacodynamic measures of sedation, including Visual Analogue Scale (VAS), the Agitation and Calmness Evaluation Scale (ACES) and Digit Symbol Substitution Test (DSST) all showed a robust statistical significance compared to placebo."

P1 data • PK/PD data • CNS Disorders • Schizophrenia

The treatment of acute agitation associated with psychosis or mania: investigational drugs in early clinical development, clinical context and potential place in therapy. (PubMed, Expert Opin Investig Drugs) - "Two medications met the search criteria: dexmedetomidine film (BXCL501) and intranasal olanzapine (INP105). These agents are undergoing or have recently completed early phase clinical trials assessing safety and pharmacokinetics.Expert Opinion: Olanzapine is a well-known molecular entity in the psychiatric armamentarium but dexmedetomidine would be a new and unfamiliar agent for mental health providers. Nonetheless, although it is too early to make definitive statements about tolerability and efficacy, their unique administration mechanisms suggest that dexmedetomidine film and intranasal olanzapine may become valuable options for the rapid management of acute agitation in patients who are willing to cooperate with medication therapy."

Clinical • Journal

Snap 101: Randomized, Crossover, Active and Placebo-Controlled, Safety, Pharmacokinetic, and Pharmacodynamic Study of 3 Ascending Doses of Olanzapine Delivered by the Novel Precision Olfactory Delivery (POD) Device (ACNP 2019) - "Background: An estimated 1.7 million acute agitation events occur annually; OLZ IM is a preferred option due to a shorter Tmax than oral, but IM administration, predominantly administered in a hospital setting, can be painful, humiliating, invasive, and requires cooperation or restraint which reduces trust, increases healthcare worker injuries and may be interpreted as an assault. INP105 may offer non-invasive delivery of OLZ with rapid absorption and is well tolerated. OLZ exposure with INP105 was similar to IM delivery at the same dose, but achieved Tmax in half the time and exposure exceeded that of OLZ ODT at the same dose. PD measures of sedation and attention exhibited clinically meaningful effects with INP105 compared to placebo within 15 minutes."

Clinical • PK/PD data

Snap 101: Randomized, Crossover, Active and Placebo-Controlled, Safety, Pharmacokinetic, and Pharmacodynamic Study of Three Ascending Doses of INP105 - Novel Precision Olfactory Delivery (POD) of a Nasal Formulation of Olanzapine (ASCP 2019) - "This study demonstrated that Tmax for nasally administered INP105 was twice as fast as IM and 12 times faster than OLZ ODT with a comparable Cmax and AUC to the corresponding IM dose of OLZ. INP105, OLZ delivered by the POD device to the upper nasal cavity, is a needle-free, rapidly available investigational product with potential application in the management of acute agitation"

Clinical • PK/PD data

Snap 101: Randomized, Crossover, Active and Placebo-Controlled, Safety, Pharmacokinetic, and Pharmacodynamic Study of Three Ascending Doses of INP105 - Novel Precision Olfactory Delivery (POD) of a Nasal Formulation of Olanzapine (ASCP 2019) - "This study demonstrated that Tmax for nasally administered INP105 was twice as fast as IM and 12 times faster than OLZ ODT with a comparable Cmax and AUC to the corresponding IM dose of OLZ. INP105, OLZ delivered by the POD device to the upper nasal cavity, is a needle-free, rapidly available investigational product with potential application in the management of acute agitation"

Clinical • PK/PD data

SNAP 101: Randomized, Crossover, Active/PlaceboControlled, Safety and Pharmacokinetic/Pharmacodynamic Study of 3 Ascending Doses of POD® Olanzapine (APA 2019) - "Objectives: 1) Establish safety and tolerability of 3 doses of INP105 2) Compare PK data for olanzapine (OLZ) from 3 INP105 doses with OLZ IM (5 mg) and orally disintegrating tablets (OLZ-ODT) 10 mg 3) Establish and compare PD effects of INP105 to OLZ IM, OLZ-ODT and placebo 4) Explore PK/PD and dose-response relationships for INP105 Background: A survey of US Emergency Department (ED) staff in 2008 found 65% had witnessed physical attacks, 32% reported ?1 verbal threat per day and 18% had been assaulted once or more with a weapon but only 40% of EDs trained staff on how to respond. This study investigated POD delivery of OLZ prior to further studies to confirm it is rapidly effective treatment to abort episodes of acute agitation."

Clinical • PK/PD data

Impel Neuropharma to present data at 2019 American Psychiatric Association (APA) Annual Meeting (PRNewswire) - P1, N=38; NCT03624322; Sponsor: Impel NeuroPharma Inc.; "Impel NeuroPharma...today announced a poster presentation at the upcoming American Psychiatric Association (APA) Annual Meeting, to be held May 18 – 22, 2019 in San Francisco, California. Data highlighting the Company's Phase 1 safety, tolerability and pharmacokinetic/pharmacodynamic (PK/PD) study of INP105 will be presented.... Impel is planning to publish full results of the SNAP-101 trial in a peer-reviewed journal in the second half of 2019."

P1 data

Impel Neuropharma announces positive phase 1 trial for INP105 for the treatment of acute agitation in bipolar I disorder and schizophrenia (PRNewswire) - P1, N=38; SNAP101 (NCT03624322); Sponsor: Impel NeuroPharma Inc.; "Impel NeuroPharma...today announced positive results of a Phase 1 trial of INP105....Results demonstrated that INP105 reached peak plasma levels (Tmax) twice as fast as intramuscular olanzapine (Zyprexa®), and ten-times faster than orally-disintegrating tablets (ODT, Zyprexa Zydis®)....'We are excited that Impel NeuroPharma's drug-device clinical programs, including INP105, are progressing rapidly and we anticipate multiple data readouts and regulatory filings across the portfolio in the next 18-24 months.'"

P1 data • Regulatory