Safety and Tolerability of INP105 (Olanzapine by I231 POD® Device) Nasal Spray in Healthy Volunteers - SNAP 101

NCT03624322 | Completed Phase 1 DMC FDA Drug FDA Device

• 1 other identifier: INP105-101
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of INP105, which is an investigational drug-device combination product comprised of the drug component OLZ administered by a Precision Olfactory Delivery (POD®) nasal spray device (I231 POD® Device). The proposed indication for INP105 is the treatment of acute agitation associated with schizophrenia and bipolar I disorder.

Conditions

Acute Agitation

Keywords

Agitation; Schizophrenia; Bipolar I disorder; OLZ; Olanzapine; Zyprexa; POD® device

Outcome Measures

Primary Outcomes (10)

• Safety and tolerability

  AEs and SAEs as assessed from baseline by physical exam, ECG, vital signs, and clinical laboratory results

  30 days

• PK profile of OLZ INP105 Tmax

  Tmax

  72 hours

• PK profile of OLZ INP105 Cmax

  Cmax

  72 hours

• PK profile of Zyprexa IM Tmax

  Tmax

  72 hours

• PK profile of Zyprexa IM Cmax

  Cmax

  72 hrs

• PK profile of Zyprexa Zydis Tmax

  Tmax

  72 hours

• PK profile of Zyprexa Zydis Cmax

  Cmax

  72 hours

• PD effects of INP105 vs placebo

  Changes in motor function measured by PD assessment compared to overall PK profile following ascending doses of INP105

  72 hours

• PD effects of Zyprexa IM

  Changes in motor function measured by PD assessment compared to overall PK profile following a single dose of 5mg of Zyprexa IM

  72 hours

• PD effects of Zyprexa Zydis

  Changes in motor function measured by PD assessment compared to overall PK profile following a single 10mg dose of Zyprexa Zydis oral disintegrating wafer

  72 hours

Study Arms (2)

Period 1

ACTIVE COMPARATOR

Period 1 (n=36) assignment to 1 of 2 reference therapy treatment groups (Zyprexa 5mg IM or Zydis 10mg orally disintegrating wafer, 10mg) over 3 cohorts (single dose)

Drug: Zyprexa IM; Drug: Zydis

Period 2

EXPERIMENTAL

Period 2 (n=36) assignment to 1 of 3 IP treatment groups (INP105 of 5, 10, or 20mg or placebo) administered with the I231 POD® Device) over 3 cohorts (single dose)

Drug: INP105; Device: I231 POD® Device

Interventions

Zyprexa IM DRUG

5mg

Period 1

Zydis DRUG

10mg orally disintegrating wafer

Also known as: Zyprexa Zydis

Period 1

INP105 DRUG

Single, ascending doses of 5, 10, or 20mg capsules OLZ (olanzapine) or placebo (MCC)

Also known as: OLZ or placebo

Period 2

I231 POD® Device DEVICE

Precision Olfactory Delivery (POD) device

Also known as: POD®

Period 2

Eligibility Criteria

• Age: 18 Years - 55 Years
• Gender Eligibility Details: Adult male (N=at least 9) and female (N=at least 9) 18 to 55 years of age (inclusive) at Screening
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Adult male (N=at least 9) and female (N=at least 9) 18 to 55 years of age (inclusive) at Screening, in good general health, with no significant medical history and no clinically significant abnormalities on physical examination at Screening or before first dose of IP.
• Subjects must have a Body Mass Index (BMI) between 18 and 32 kg/m2 inclusive.
• Negative urine drug screen/alcohol breath test at Screening and Day -1. Repeat tests may be performed if false positive results are suspected.
• Subjects must have the ability and willingness to attend the necessary visits at the study centre.
• Written informed consent signed prior to entry into the study.
• Female subjects of childbearing potential, and male subjects and their partners, must agree to use adequate contraception, defined as complete abstinence, documented evidence of surgical sterilization or condom plus approved contraceptive method

You may not qualify if:

• Known hypersensitivity to Zyprexa IM, Zyprexa Zydis or any of the ingredients in them or in INP105 or the placebo.
• Recently (within 3 months) or currently taking Zyprexa (any formulation).
• Subjects taking medications known to inhibit or induce CYP1A2 at any time during the study period, and any subjects taking prescription medications, over the counter medications or supplements that, in the opinion of the Investigator, may impact the subject's response to INP105 or impact the subject's participation in the study. Oral contraceptives are permitted.
• Subjects with medical history of hypotension or currently taking anti-hypertensives at Screening or throughout the study.
• Current or recent smokers (\<3 months since quitting); inadvertent one-off smokers and social smokers will also be excluded.
• Females who are pregnant or lactating.
• Subjects with any underlying physical or psychological medical condition that, in the opinion of the Investigator, would make it unlikely that the subject will comply with the study.
• Abnormal and clinically significant laboratory test results.
• History or presence of alcohol or drug abuse within the 2 years prior to the first IP administration.
• Blood donation or significant blood loss within 60 days prior to the first IP administration.
• Plasma donation within 7 days prior to the first IP administration.
• Administration of IP in another trial within 30 days or 5 half-lives (whichever is longer) prior to the first IP administration.
• Significant surgery within the past 3 months prior to the first IP administration determined by the Investigator to be clinically relevant.
• Failure to satisfy the Investigator of fitness to participate for any other reason.
• Acute illness within 30 days prior to Day 1. Subjects with minor viral illnesses (for example, upper respiratory tract infection) within 30 days prior to Day 1 may be randomized if all symptoms are resolved by admission and at the discretion of the Investigator.

Sponsors & Collaborators

• Impel Pharmaceuticals: lead

Study Sites (1)

Nucleus Network Pty Ltd

Melbourne, Victoria, 3004, Australia

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 DERIVED

MeSH Terms

Conditions

Psychomotor Agitation; Schizophrenia

Interventions

Olanzapine

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; Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Stephen B Shrewsbury, MD

  Impel NeuroPharma

  STUDY DIRECTOR

• Niquita Tugiono, MD

  Nucleus Network Pty Ltd.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind, placebo-controlled
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Period 1 (n=36) assignment to 1 of 2 reference therapy treatment groups over 3 cohorts Period 2 (n=36) assignment to 1 of 3 IP treatment groups over 3 cohorts

Study Record Dates

• First Submitted: July 25, 2018
• First Posted: August 10, 2018
• Study Start: August 5, 2018
• Primary Completion: October 3, 2018
• Study Completion: October 3, 2018
• Last Updated: October 4, 2018

Record last verified: 2018-08

Locations

AU (1)