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

• ClinicalTrials.gov Identifier: NCT03624322
• Recruitment Status: Completed
• First Posted: August 10, 2018
• Last Update Posted: October 4, 2018
• Sponsor: Impel Pharmaceuticals
• Information provided by (Responsible Party): Impel Pharmaceuticals

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Acute Agitation	Drug: Zyprexa IM; Drug: Zydis; Drug: INP105; Device: I231 POD® Device	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 38 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention Model Description: 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
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Double-blind, placebo-controlled
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: August 5, 2018
• Actual Primary Completion Date: October 3, 2018
• Actual Study Completion Date: October 3, 2018

Arms and Interventions

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 Name: 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 Name: OLZ or placebo; Device: I231 POD® Device; Precision Olfactory Delivery (POD) device; Other Name: POD®

Outcome Measures

Primary Outcome Measures :

1. Safety and tolerability [ Time Frame: 30 days ]
   AEs and SAEs as assessed from baseline by physical exam, ECG, vital signs, and clinical laboratory results
2. PK profile of OLZ INP105 Tmax [ Time Frame: 72 hours ]
   Tmax
3. PK profile of OLZ INP105 Cmax [ Time Frame: 72 hours ]
   Cmax
4. PK profile of Zyprexa IM Tmax [ Time Frame: 72 hours ]
   Tmax
5. PK profile of Zyprexa IM Cmax [ Time Frame: 72 hrs ]
   Cmax
6. PK profile of Zyprexa Zydis Tmax [ Time Frame: 72 hours ]
   Tmax
7. PK profile of Zyprexa Zydis Cmax [ Time Frame: 72 hours ]
   Cmax
8. PD effects of INP105 vs placebo [ Time Frame: 72 hours ]
   Changes in motor function measured by PD assessment compared to overall PK profile following ascending doses of INP105
9. PD effects of Zyprexa IM [ Time Frame: 72 hours ]
   Changes in motor function measured by PD assessment compared to overall PK profile following a single dose of 5mg of Zyprexa IM
10. PD effects of Zyprexa Zydis [ Time Frame: 72 hours ]
    Changes in motor function measured by PD assessment compared to overall PK profile following a single 10mg dose of Zyprexa Zydis oral disintegrating wafer

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: All
• Gender Based Eligibility: Yes
• Gender Eligibility Description: Adult male (N=at least 9) and female (N=at least 9) 18 to 55 years of age (inclusive) at Screening
• Accepts Healthy Volunteers: Yes

Criteria

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

Contacts and Locations

Locations

Australia, Victoria

Nucleus Network Pty Ltd

Melbourne, Victoria, Australia, 3004

Sponsors and Collaborators

Impel Pharmaceuticals

Investigators

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

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Impel Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03624322
• Other Study ID Numbers: INP105-101
• First Posted: August 10, 2018
• Last Update Posted: October 4, 2018
• Last Verified: August 2018

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: Yes
• Device Product Not Approved or Cleared by U.S. FDA: Yes
• Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by Impel Pharmaceuticals:

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

Additional relevant MeSH terms:

Psychomotor Agitation; Dyskinesias; Neurologic Manifestations; Nervous System Diseases; Psychomotor Disorders; Neurobehavioral Manifestations; Olanzapine; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Gastrointestinal Agents; Antipsychotic Agents; Tranquilizing Agents; Central Nervous System Depressants; Psychotropic Drugs; Selective Serotonin Reuptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Serotonin Agents