Safety and Tolerability of INP105 (Olanzapine by I231 POD® Device) Nasal Spray in Healthy Volunteers - SNAP 101 (SNAP101)

Phase1 Randomized, Double-Blind, Placebo/Active-Controlled, SAD, 2-Way, Incomplete Block, 2-Period Crossover, Safety, Tolerability, PK/PD Study of 3 Doses INP105 (Olanzapine Delivered by I231 POD® Device) Nasal Spray in Healthy Volunteers

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.

Study Overview

• Status: Completed
• Conditions: Acute Agitation
• Intervention / Treatment: Drug: Zyprexa IM; Drug: Zydis; Drug: INP105; Device: I231 POD® Device

Detailed Description

This is a randomized, double-blind, placebo- and active-controlled, ascending-dose, 2-way, 2- period, incomplete block, crossover, Phase 1 trial to compare the safety, tolerability, PK and PD of 3 single doses of INP105 with the safety, tolerability, PK and PD of 1 dose of Zyprexa IM (5 mg) and 1 dose of oral Zyprexa Zydis (10 mg). Randomization for Periods 1 and 2 will occur for each subject on Day 1.

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Nucleus Network Pty Ltd

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 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.
2. Subjects must have a Body Mass Index (BMI) between 18 and 32 kg/m2 inclusive.
3. Negative urine drug screen/alcohol breath test at Screening and Day -1. Repeat tests may be performed if false positive results are suspected.
4. Subjects must have the ability and willingness to attend the necessary visits at the study centre.
5. Written informed consent signed prior to entry into the study.
6. 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

Exclusion Criteria:

1. Known hypersensitivity to Zyprexa IM, Zyprexa Zydis or any of the ingredients in them or in INP105 or the placebo.
2. Recently (within 3 months) or currently taking Zyprexa (any formulation).
3. 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.
4. Subjects with medical history of hypotension or currently taking anti-hypertensives at Screening or throughout the study.
5. Current or recent smokers (<3 months since quitting); inadvertent one-off smokers and social smokers will also be excluded.
6. Females who are pregnant or lactating.
7. 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.
8. Abnormal and clinically significant laboratory test results.
9. History or presence of alcohol or drug abuse within the 2 years prior to the first IP administration.
10. Blood donation or significant blood loss within 60 days prior to the first IP administration.
11. Plasma donation within 7 days prior to the first IP administration.
12. Administration of IP in another trial within 30 days or 5 half-lives (whichever is longer) prior to the first IP administration.
13. Significant surgery within the past 3 months prior to the first IP administration determined by the Investigator to be clinically relevant.
14. Failure to satisfy the Investigator of fitness to participate for any other reason.
15. 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.
16. Any nasal congestion, deviated septum, or physical blockage in either nostril.
17. Positive for human immunodeficiency virus (HIV), Hepatitis B or Hepatitis C

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
Active Comparator: Period 1; 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; 5mg; Drug: Zydis; 10mg orally disintegrating wafer; Other Names: Zyprexa Zydis
Experimental: Period 2; 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; Single, ascending doses of 5, 10, or 20mg capsules OLZ (olanzapine) or placebo (MCC); Other Names: OLZ or placebo; Device: I231 POD® Device; Precision Olfactory Delivery (POD) device; Other Names: POD®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Impel Pharmaceuticals
• Investigators: Study Director: Stephen B Shrewsbury, MD, Impel NeuroPharma; Principal Investigator: Niquita Tugiono, MD, Nucleus Network Pty Ltd

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): August 5, 2018
• Primary Completion (Actual): October 3, 2018
• Study Completion (Actual): October 3, 2018

Study Registration Dates

• First Submitted: July 25, 2018
• First Submitted That Met QC Criteria: August 6, 2018
• First Posted (Actual): August 10, 2018

Study Record Updates

• Last Update Posted (Actual): October 4, 2018
• Last Update Submitted That Met QC Criteria: October 3, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: Schizophrenia; Agitation; Bipolar I disorder; Olanzapine; Zyprexa; OLZ; POD® device
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Dyskinesias; Psychomotor Disorders; Psychomotor Agitation; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Olanzapine
• Other Study ID Numbers: INP105-101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes