Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12618000966291
Ethics application status
Approved
Date submitted
5/06/2018
Date registered
7/06/2018
Date last updated
31/05/2019
Date data sharing statement initially provided
15/02/2019
Date results information initially provided
15/02/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
A placebo and comparator controlled phase 1, safety and tolerability study of 3 ascending doses of INP105 (intranasal OLZ by I231 POD® device).
Scientific title
A Phase 1, Randomized, Double-Blind, Placebo- and Active-Controlled, Single-Ascending-Dose, 2-Way, Incomplete Block, 2-Period Crossover, Safety, Tolerability, Pharmacokinetic (PK) and Pharmacodynamic (PD) Study of 3 Doses of INP105 (olanzapine delivered by I231 POD® Device) Nasal Spray in Healthy Volunteers
Secondary ID [1] 295033 0
INP105-101
Universal Trial Number (UTN)
Trial acronym
SNAP 101 (Safety and Tolerability of Intranasal POD-OLZ)
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Agitation in Schizophrenia 308061 0
Acute Agitation in Bipolar I Disorder 308198 0
Condition category
Condition code
Neurological 307116 307116 0 0
Other neurological disorders
Mental Health 307235 307235 0 0
Schizophrenia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Phase 1 trial to compare the safety, tolerability, PK and PD of 3 single ascending doses (SAD) of INP105 against 2 doses of intramuscular Zyprexa (5 mg or 10 mg) or 1 dose of oral Zyprexa Zydis (10 mg).

36 healthy volunteers (participants), male and female, 18-55 years will be enrolled in the study into 3 cohorts of 12. Each cohort will have 2 treatment periods with a 14-day wash-out in between.

The treatments are as follows:

Treatment Period 1:
Participants will be assigned to Cohort 1, 2 or 3 and in each of these three cohorts, participants will have an equal chance of being treated with one of the three following treatments: intramuscular 5 mg Zyprexa, intramuscular 10 mg Zyprexa or Oral Wafer 10mg Zypreza Zydis, followed by a 14-day wash-out period.

Treatment Period 2:
Participants will return to the clinic and depending on the cohort (1, 2 or 3) they are enrolled in during period 1, they will be randomised to receive the following via I231 POD® nasal spray:

Cohort 1: INP105 (5.0 mg OLZ) n=9 or Placebo n=3
Cohort 2: INP105 (10.0 mg OLZ) n=9 or Placebo n=3
Cohort 3: INP105 (20.0 mg OLZ) n=9 or Placebo n=3

All participants will be trained on the treatment delivery methods and clinic staff will observe all dosing activity.
Intervention code [1] 301366 0
Treatment: Drugs
Intervention code [2] 301367 0
Treatment: Devices
Comparator / control treatment
This study is both active and placebo controlled. The active comparator is a single dose of either Zyprexa IM (5 mg or 10 mg) or 1 dose of oral Zyprexa Zydis 10 mg.

Zyprexa (Olanzapine, OLZ) for IM and Oral administration has been approved for use in Australia for the treatment of chronic schizophrenia and bipolar I disorder for over 20 years. Zyprexa IM, is also an effective and safe approved treatment for acute agitation in schizophrenia.

Placebo is a colour-matched microcrystalline cellulose (MCC) delivered via the I231 POD Device in treatment period 2. Placebo will be delivered as 1, 2 or 4 actuations depending on the participant’s cohort assignment.

Control group
Placebo

Outcomes
Primary outcome [1] 306064 0
To establish the safety and tolerability profile of the 3 single-ascending-doses of INP105.

The safety assessments performed include:
- physical exams including nasal exams
- safety blood and urine tests
- ECGs
- Vital signs
Timepoint [1] 306064 0
Participants will be confined in the phase 1 unit for 72hrs after dosing in both treatment periods 1 and 2 for continuous observation and regular safety assessments. The participants again return to clinic on days 4,5 and 14 post dose for safety assessments.
Primary outcome [2] 306065 0
To compare pharmacokinetic (PK) data for OLZ from 3 single-ascending-doses of INP105 with the 2 doses of (intramuscular) Zyprexa IM (5 mg and 10 mg) and 1 dose of oral Zyprexa Zydis 10 mg;
Timepoint [2] 306065 0
Blood draws to assess PK measurements will be taken both pre and post dose at the following timepoints:
- pre-dose
- 5, 10, 15, 20, 30 and 45 mins post-dose
- 1, 2, 4, 6, 8, 12, 18, 24, 36, 48 and 60hrs post dose
- 4 and 5 days post dose.
Primary outcome [3] 306066 0
To establish and compare the pharmacodynamic (PD) effects of 3 single-ascending-doses of INP105 to those of 2 doses of Zyprexa IM and oral Zyprexa Zydis..
PD measurements comprise of the following assessments:
- Visual Analogue Scale (VAS).
- Agitation/Calmness Evaluation Scale (ACES).
- Digit Symbol Substitution Test (DSST).

Timepoint [3] 306066 0
PD assessments will be taken both pre and post dose at the following timepoints:
- pre-dose
- 15,and 30 mins post-dose
- 1, 2, 4, 6, 8, 12, 24 and 48hrs post dose
Secondary outcome [1] 347463 0
To explore the PK/PD and dose-response relationships for 3 single-ascending-doses of INP105.
Timepoint [1] 347463 0
PK/PD assessments will be taken both pre and post dose at the following timepoints, inline with the PD schedule:
- pre-dose
- 15,and 30 mins post-dose
- 1, 2, 4, 6, 8, 12, 24 and 48hrs post dose

Eligibility
Key inclusion criteria
1) 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) Body mass index (BMI) between 18 and 32 kg/m2 inclusive;
3) Negative urine drug screen/alcohol breath test at Screening and Day -1;
4) 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.
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key 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) Participants taking medications known to inhibit or induce CYP1A2 at any time during the study period, and any participants taking prescription medications, over the counter medications or supplements that, in the opinion of the Investigator, may impact the subject’s response to olanzapine or impact the subject’s participation in the study. Oral contraceptives are permitted;
4) A 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) 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 tests;
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. Minor viral illnesses 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 HIV, Hepatitis B or Hepatitis C.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Crossover
Other design features
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis
No formal inferential statistics will be performed on safety assessments. Listings and summaries for all safety data will be presented using the Safety population (all participants dosed with IP).

Listings and summaries for all safety data may be presented using the PP population (participants who receive both treatment period doses) in the event of major differences in number of subjects per population. Descriptive statistics (mean, SD, median, minimum and maximum) will be calculated for summaries of continuous safety data and frequency counts and percentages (where appropriate) will be calculated for summaries of discrete/categorical safety data.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
6/08/2018
Actual
6/08/2018
Date of last participant enrolment
Anticipated
5/10/2018
Actual
15/09/2018
Date of last data collection
Anticipated
7/11/2018
Actual
3/10/2018
Sample size
Target
36
Accrual to date
Final
40
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 11014 0
Nucleus Network - Melbourne
Recruitment postcode(s) [1] 22805 0
3004 - Melbourne
Recruitment postcode(s) [2] 22807 0
3004 - St Kilda Road Melbourne

Funding & Sponsors
Funding source category [1] 299612 0
Commercial sector/Industry
Name [1] 299612 0
Impel® NeuroPharma Inc.
Country [1] 299612 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Clinical Network Services (CNS) Pty Ltd
Address
Level 2, 381 MacArthur Ave,
HAMILTON QLD 4007
Country
Australia
Secondary sponsor category [1] 298933 0
Commercial sector/Industry
Name [1] 298933 0
Impel® NeuroPharma Inc.
Address [1] 298933 0
201 Elliott Ave West,
Suite 260
Seattle, Washington 98119
USA
Country [1] 298933 0
United States of America

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300515 0
Alfred Hospital Ethics Commitee
Ethics committee address [1] 300515 0
89 Commercial Road
Melbourne
VIC 3004
Ethics committee country [1] 300515 0
Australia
Date submitted for ethics approval [1] 300515 0
06/06/2018
Approval date [1] 300515 0
05/07/2018
Ethics approval number [1] 300515 0

Summary
Brief summary
This research project is designed to test the safety, tolerability, pharmacokinetics (how the body processes the study drug) and pharmacodynamics (how the drug affects to body) of INP105. INP105 is a drug-device combination product; the drug is OLZ (Olanzapine); the device is the I231 Precision Olfactory Delivery (POD) device, which is a novel nasal (nose) spray.

Approximately 36 participants in general good health (with a minimum of 9 males and 9 females) will be enrolled and will be allocated to receive 2 treatments across 2 treatment periods. In the first treatment period participants will have an equal change of receiving 1 of 3 reference drugs: IM 5 mg Zyprexa, IM 10 mg Zyprexa or Oral Wafer 10mg Zypreza Zydis. In treatment period 2, participants will be allocated to receive either INP105 or placebo in a 3:1 ratio. The dose strength of INP105 (5, 10 to 20 mg) will depend on the cohort the participant is assigned.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 83910 0
Dr Jason Lickliter
Address 83910 0
Centre for Clinical Studies
Nucleus Network
89 Commercial Road
Melbourne, 3004
Country 83910 0
Australia
Phone 83910 0
+61 1800 243 733
Fax 83910 0
Email 83910 0
J.Lickliter@nucleusnetwork.com.au
Contact person for public queries
Name 83911 0
Dr Stephen Shrewsbury
Address 83911 0
Impel NeuroPharma
201 Elliott Avenue W, Suite 260
Seattle WA 98119
Country 83911 0
United States of America
Phone 83911 0
+1 2065681466
Fax 83911 0
Email 83911 0
sshrewsbury@impelnp.com
Contact person for scientific queries
Name 83912 0
Dr Stephen Shrewsbury
Address 83912 0
Impel NeuroPharma
201 Elliott Avenue W, Suite 260
Seattle WA 98119
Country 83912 0
United States of America
Phone 83912 0
+1 2065681466
Fax 83912 0
Email 83912 0
sshrewsbury@impelnp.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
All publications and data analyses etc from the INP105-101 study would be generated by and delivered to Impel. However we would expect the PI to review and sign off on both.


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.