Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12623001317684
Ethics application status
Approved
Date submitted
19/10/2023
Date registered
15/12/2023
Date last updated
7/04/2024
Date data sharing statement initially provided
15/12/2023
Date results information initially provided
7/04/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Pharmacokinetics of Miist Nicotine Inhaler in healthy smokers
Scientific title
An open-label Phase 1 study to investigate the pharmacokinetics, safety and tolerability, and pharmacodynamics of nicotine administered in single and multiple inhalations via a novel Miist Nicotine Inhaler in healthy male smokers
Secondary ID [1] 310776 0
MNI-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Smoking cessation 331740 0
Condition category
Condition code
Mental Health 328487 328487 0 0
Addiction

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Study participants will receive 3 inhaled doses of the investigational nicotine replacement therapy (NRT) product as a self-administered dose via the Miist Nicotine Inhaler.
Study participants will receive training on how to use the Miist Nicotine Inhaler from the site research team. Training with a sham device will take place at the time of screening, at clinic check in and prior to each dose. The site research team will supervise each dose.
Study participants will be instructed to fully exhale. A flashing blue light will be visible when the device is ready. They will place the mouthpiece in their mouth and inhale firmly and deeply such that the steady blue light remains on, increasing their inhalation effort if the blue light stops or slowing their inhalation if a red light flashes. At the end of the dose delivery, the steady blue light will go off and the motor in the device will stop. The participant is to hold their breath for 5 seconds prior to exhaling and ending the dose.
The doses will be administered in increasing order of strength of nicotine, starting from 0.08 mg and increasing to 0.16 mg then 1.15 mg with a 120 minute (+15 minutes) washout period between each dose level.
Intervention code [1] 327181 0
Treatment: Drugs
Comparator / control treatment
No control group is included
Control group
Uncontrolled

Outcomes
Primary outcome [1] 336308 0
To determine the arterial blood plasma nicotine levels following single and multiple inhalations from the Miist Nicotine Inhaler
Timepoint [1] 336308 0
PK blood samples will be collected within 30 minutes before dosing, and at 0.5, 1, 1.5, 2, 3, 5, 7, 10, 15, 30, 60, and 120 minutes after dosing ends for each dose level
Secondary outcome [1] 427799 0
To demonstrate dose proportionality of escalating nicotine doses delivered via the Miist Nicotine Inhaler
Timepoint [1] 427799 0
PK blood samples will be collected within 30 minutes before dosing, and at 0.5, 1, 1.5, 2, 3, 5, 7, 10, 15, 30, 60, and 120 minutes after dosing ends for each dose level
Secondary outcome [2] 427800 0
To evaluate the safety and tolerability of the Miist Nicotine Inhaler
Timepoint [2] 427800 0
Adverse event collection will occur on Day -2 (one day prior to clinic check-in), Day -1 (check-in day at clinic), Day 1 (study day at clinic) and Day 8 (1 week after dosing day).
Secondary outcome [3] 427826 0
To evaluate the safety and tolerability of the Miist Nicotine Inhaler
Timepoint [3] 427826 0
Safety laboratory samples are collected and analysed at screening, Day -1 (at check into the clinic) and Day 1 (after all dosing is complete)
Secondary outcome [4] 427827 0
To evaluate the safety and tolerability of the Miist Nicotine Inhaler
Timepoint [4] 427827 0
ECG data is collected at Screening by a 12 -lead ECG. Throughout Day 1 (dosing day), prior to dosing until after the third inhaled dose of nicotine, the study participant will have their heart rhythm monitored by a continuous bedside ECG machine.
Secondary outcome [5] 427828 0
To evaluate the safety and tolerability of the Miist Nicotine Inhaler
Timepoint [5] 427828 0
Vital sign measurement is completed at screening, Day -1, and throughout Day 1 (dosing day). Throughout Day 1 (dosing day) vital signs will be measured 30 minutes prior to each dose and then 15, 30, 60, 90 and 120 minutes after each dose of nicotine.
Secondary outcome [6] 427829 0
To evaluate the safety and tolerability of the Miist Nicotine Inhaler
Timepoint [6] 427829 0
Oxygen saturation is measured at Screening, Day -1 and continuously throughout Day 1 (dosing day). Throughout Day 1 (dosing day) oxygen saturation will be measured 30 minutes prior to each dose and then 15, 30, 60, 90 and 120 minutes after each dose of nicotine.
Secondary outcome [7] 427830 0
To evaluate the safety and tolerability of the Miist Nicotine Inhaler
Timepoint [7] 427830 0
PEFR is collected throughout Day 1 (dosing day) prior to and after each dose. The PEFR is collected 30 minutes prior to each dose and 30 and 60 minutes after each dose.
Secondary outcome [8] 427831 0
To evaluate the safety and tolerability of the Miist Nicotine Inhaler
Timepoint [8] 427831 0
Physical examination is conducted at Screening, Day -1 (check-in day) and Day 1 (dosing day)
Secondary outcome [9] 427832 0
To evaluate the safety and tolerability of the Miist Nicotine Inhaler
Timepoint [9] 427832 0
Concomitant medications are collected at Screening, Day -1 (check in day), Day 1 (dosing day) and Day 8 (1 week after dosing day)
Secondary outcome [10] 427833 0
To evaluate the craving for smoking before and after each of the 3 nicotine doses
Timepoint [10] 427833 0
VAS craving score is collected at Baseline (prior to treatment) and after each inhaled nicotine dose

Eligibility
Key inclusion criteria
1. Male between 18 and 55 years of age, inclusive.
2. Cigarette smoker who smokes more than 10 cigarettes (tobacco cigarettes alone or in combination with e-cigarettes) a day and who has smoked for 1 year.
3. Able to abstain from smoking and use of other nicotine containing products (e.g., gum, patches or any other Nicotine Replacement Treatment product) for 12 hours prior to study dosing and for the duration of confinement in the Clinical Research Unit.
4. Have a Fagerström Test for Nicotine Dependence (FTND) score of at least 4.
5. Body weight above 50 kg and body mass index (BMI) in the range 19 to 35 kg per m2 (inclusive).
6. Willing and able to have an arterial line inserted and maintained for blood sampling for PK.
7. Healthy as determined by a licensed and experienced physician, based on a medical evaluation including medical history, physical examination, safety laboratory tests and cardiac monitoring. A potential participant with a clinical abnormality or laboratory parameters outside the normal reference range for the population being studied may be included only if the Investigator considers that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. The Investigator may discuss with the local MM and Sponsor representative as required.
8. Estimated glomerular filtration rate (eGFR) must be above 60 mL per min per 1.73 m2 (calculated using the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formula).
9. Normal standard 12-lead ECG parameters after at least 5 minutes resting in supine position
10. Normal vital signs after at least 5 minutes resting semi-supine:
11. Must agree to abstain from heterosexual intercourse for at least 12 hours following discharge from the Clinical Research Unit.
12. Provides written informed consent and is willing and able to undergo all study procedures and participate in the scheduled follow up teleconference call per protocol.
Minimum age
18 Years
Maximum age
55 Years
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria

1. Known or suspected history of allergy or sensitivity to nicotine or any other component of the inhaler.
2. A history of Hepatitis B, Hepatitis C or human immunodeficiency virus (HIV) infection and/or a positive pre-study HIV, Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
3. History of confirmed chronic and/or serious pulmonary disease, including asthma, or chronic obstructive pulmonary disease, a history of myocardial infarction or cerebrovascular accident, other clinically significant cardiac, liver or renal conditions, or any comorbidity that could place them at risk or interfere with the interpretation of the study data.
4. Participant with a diagnosed bleeding disorder or significant bruising or bleeding difficulties with blood draws or is unable to provide a blood sample without undue trauma or distress or has poor peripheral arterial and/or venous access.
5. Any other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with trial participation or IP administration or may interfere with the interpretation of trial results and, in the judgement of the Investigator or Sponsor, would make the participant inappropriate for entry into this trial.
6. Participant requiring any inhaled or anti-coagulant medications.
7. Inability to use the Miist Nicotine Inhaler correctly following training.
8. A positive pre-study drug or alcohol screen.
9. History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of more than 21 units for males.
10. Participation in a clinical trial within 30 days before dosing; use of any experimental therapy within 30 days or 5 half-lives prior to dosing, whichever is greater; or use of any biologic therapy within 12 weeks or 5 half-lives prior to dosing, whichever is greater.
11. Participant unable to provide written informed consent or participant under guardianship.
12. Unwilling or unable to follow protocol requirements.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised 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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis
This is an exploratory study. No formal statistical comparisons are planned, and all analyses will be descriptive in nature.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
9/01/2024
Actual
9/01/2024
Date of last participant enrolment
Anticipated
21/02/2024
Actual
22/02/2024
Date of last data collection
Anticipated
1/03/2024
Actual
29/02/2024
Sample size
Target
10
Accrual to date
Final
10
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 25727 0
The Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 41551 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 315007 0
Commercial sector/Industry
Name [1] 315007 0
Miist Therapeutics South Pty Ltd
Country [1] 315007 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Miist Therapeutics South Pty Ltd
Address
330 Collins St, Melbourne VIC 3000
Country
Australia
Secondary sponsor category [1] 317036 0
None
Name [1] 317036 0
Address [1] 317036 0
Country [1] 317036 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 313978 0
Central Adelaide Local Health Network HREC
Ethics committee address [1] 313978 0
Royal Adelaide Hospital, Port Rd, Adelaide 5000 South Australia
Ethics committee country [1] 313978 0
Australia
Date submitted for ethics approval [1] 313978 0
25/09/2023
Approval date [1] 313978 0
14/12/2023
Ethics approval number [1] 313978 0

Summary
Brief summary
This is a Phase 1, single centre, open-label study to investigate the PK profile, safety and tolerability and pharmacodynamics (PD) of single ascending doses of nicotine administered in single and multiple inhalations via a Miist Nicotine Inhaler in healthy male smokers. Study participants will receive 3 inhaled doses of the investigational nicotine replacement therapy (NRT) product. The doses will be administered via the novel Miist Nicotine Inhaler in increasing order of strength of nicotine, starting from 0.08 mg and increasing to 0.16 mg then 1.15 mg with a 120 minute (+15 minutes) washout period between each dose level.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 129998 0
Prof Guy Ludbrook
Address 129998 0
PARC Clinical Research, Royal Adelaide Hospital, Port Rd, Adelaide SA 5000
Country 129998 0
Australia
Phone 129998 0
+61 413817901
Fax 129998 0
Email 129998 0
guy.ludbrook@sa.gov.au
Contact person for public queries
Name 129999 0
Prof Guy Ludbrook
Address 129999 0
PARC Clinical Research, Royal Adelaide Hospital, Port Rd, Adelaide SA 5000
Country 129999 0
Australia
Phone 129999 0
+61 413817901
Fax 129999 0
Email 129999 0
guy.ludbrook@sa.gov.au
Contact person for scientific queries
Name 130000 0
Mr Jeff Schuster
Address 130000 0
Miist Therapeutics, 1800 Ferry Point, Alameda, CA 94501, USA
Country 130000 0
United States of America
Phone 130000 0
+15102582182
Fax 130000 0
Email 130000 0
jeff@mymiist.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


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.