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
Overview
- Phase
- Phase 1
- Intervention
- Zyprexa IM
- Conditions
- Acute Agitation
- Sponsor
- Impel Pharmaceuticals
- Enrollment
- 38
- Locations
- 1
- Primary Endpoint
- PK profile of OLZ INP105 Cmax
- Status
- Completed
- Last Updated
- 7 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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 -
- •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
Exclusion Criteria
- •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.
Arms & Interventions
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)
Intervention: Zyprexa IM
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)
Intervention: Zydis
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)
Intervention: INP105
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)
Intervention: I231 POD® Device
Outcomes
Primary Outcomes
PK profile of OLZ INP105 Cmax
Time Frame: 72 hours
Cmax
PK profile of Zyprexa IM Tmax
Time Frame: 72 hours
Tmax
Safety and tolerability
Time Frame: 30 days
AEs and SAEs as assessed from baseline by physical exam, ECG, vital signs, and clinical laboratory results
PK profile of OLZ INP105 Tmax
Time Frame: 72 hours
Tmax
PK profile of Zyprexa IM Cmax
Time Frame: 72 hrs
Cmax
PK profile of Zyprexa Zydis Tmax
Time Frame: 72 hours
Tmax
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
PK profile of Zyprexa Zydis Cmax
Time Frame: 72 hours
Cmax
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
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