Clinical trial NCT03624322: Safety and Tolerability of INP105 (Olanzapine by I231 POD® Device) Nasal Spray in Healthy Volunteers - SNAP 101
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Acute Agitation
Keywords: Agitation
Schizophrenia
Bipolar I disorder
OLZ
Olanzapine
Zyprexa
POD® device
Lead sponsor: Impel Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2018-08-10
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
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
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Safety and tolerability
timeFrame: 30 days
measure: PK profile of OLZ INP105 Tmax
timeFrame: 72 hours
measure: PK profile of OLZ INP105 Cmax
timeFrame: 72 hours
measure: PK profile of Zyprexa IM Tmax
timeFrame: 72 hours
measure: PK profile of Zyprexa IM Cmax
timeFrame: 72 hrs
measure: PK profile of Zyprexa Zydis Tmax
timeFrame: 72 hours
measure: PK profile of Zyprexa Zydis Cmax
timeFrame: 72 hours
measure: PD effects of INP105 vs placebo
timeFrame: 72 hours
measure: PD effects of Zyprexa IM
timeFrame: 72 hours
measure: PD effects of Zyprexa Zydis
timeFrame: 72 hours
Secondary outcomes:
Other outcomes:
Locations:
city: Melbourne
country: Australia
facility: Nucleus Network Pty Ltd
state: Victoria
Study officials:
affiliation: Impel NeuroPharma
name: Stephen B Shrewsbury, MD
role: STUDY_DIRECTOR
affiliation: Nucleus Network Pty Ltd.
name: Niquita Tugiono, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.