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Trial registered on ANZCTR


Registration number
ACTRN12612000088842
Ethics application status
Approved
Date submitted
23/12/2011
Date registered
18/01/2012
Date last updated
2/11/2012
Type of registration
Retrospectively registered

Titles & IDs
Public title
A Four-Part Study to Determine the Safety, Tolerability and Pharmacokinetics of the Oxette (Registered Trademark) Nicotine Inhaler, Including a Comparison with the Nicorette (Registered Trademark) Inhaler
Scientific title
A Four-Part Study to Determine the Safety, Tolerability and Pharmacokinetics of the Oxette (Registered Trademark) Nicotine Inhaler, Including a Comparison with the Nicorette (Registered Trademark) Inhaler
Secondary ID [1] 262637 0
Nil
Universal Trial Number (UTN)
Trial acronym
KC001
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Smoking Addiction 268346 0
Condition category
Condition code
Mental Health 285630 285630 0 0
Addiction

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study has been divided into four parts as described below. Part A: Single blind, randomised, multi dose-level study to evaluate the tolerability and pharmacokinetics of orally inhaled nicotine via the Oxette (Registered Trademark) Nicotine Inhaler pack at three doses of nicotine – low, medium and high. Two single different dose levels of nicotine will be inhaled using the device on a single study day, approximately 6 hrs apart. Part A High dose is 0.084% w/w Nicotine, Medium dose is 0.056% w/w Nicotine, Low dose is 0.028% w/w Nicotine. Part B:Open label/single blind, randomised, 3-way crossover study to evaluate the pharmacokinetics of two dose levels of the Oxette (Registered Trademark) Nicotine Inhaler pack in comparison to the Nicorette (Registered Trademark) Inhaler. Two single different dose levels of nicotine will be inhaled using the Oxette device and one single dose level of nicotine will be inhaled using the Nicorette device over 3 days. One dose will be inhaled per day. There will be approximately 18hr break before moving to the next dose. The 2 dose levels will be determined based on the data obtained from Part A. Part C: Open label study to evaluate the tolerability and venous pharmacokinetics of repeat doses of orally inhaled nicotine via the Oxette (Registered Trademark) Nicotine Inhaler system at one dose level of nicotine. One dose level of nicotine will be inhaled using the Oxette device twelve times a day for one day. The dose level will be determined based on the data obtained from Parts A and B. Subjects will only participate in one of the three parts. The Oxette Inhaler pack and the Nicorette Inhaler differ in appearance and formulation of the nicotine. The devices used to inhale the nicotine also differ in appearance and functionality. Part D: Open label, randomised, 2-way crossover study to determine the venous pharmacokinetics of orally inhaled nicotine at the medium dose level (0.056%w/w) delivered via the Oxette (Registered Trademark) Nicotine Inhaler device in comparison to the Nicorette (Registered Trademark) Inhaler (10mg).
Intervention code [1] 266985 0
Other interventions
Intervention code [2] 284052 0
Treatment: Drugs
Intervention code [3] 284053 0
Treatment: Other
Comparator / control treatment
Nicorette (Registered Trademark) Inhaler
Control group
Active

Outcomes
Primary outcome [1] 269224 0
To determine the pharmacokinetic profile of a single dose of the Oxette (Registered Trademark) Nicotine Inhaler pack at three nicotine strengths.
Timepoint [1] 269224 0
Various time points ranging from pre-dose to up to 300 minutes post-dose with safety follow-up + 8 days. The timepoints differ per study part.
Primary outcome [2] 269225 0
To compare the pharmacokinetic profile of the Oxette (Registered Trademark) Nicotine Inhaler pack with the Nicorette (Registered Trademark) Inhaler (10 mg).
Timepoint [2] 269225 0
Various time points ranging from pre-dose to up to 300 minutes post-dose with safety follow-up + 8 days. The timepoints differ per study part.
Primary outcome [3] 269226 0
To determine the pharmacokinetic profile of repeat dose of the Oxette (Registered Trademark) Nicotine Inhaler pack.
Timepoint [3] 269226 0
Various time points ranging from pre-dose to up to 300 minutes post-dose with safety follow-up + 8 days. The timepoints differ per study part.
Secondary outcome [1] 279159 0
To determine safety and tolerability of the Oxette (Registered Trademark) Nicotine Inhaler pack at a range of doses of nicotine. . This will be assessed by clinical assessments and medical tests.
Timepoint [1] 279159 0
Various time points over treatment day (s) with safety follow up at 8 days.
Secondary outcome [2] 279160 0
To determine effects following use of the Oxette (Registered Trademark) Nicotine Inhaler pack on craving satiation and smoking urges. To also determine the effect on aspects of nicotine withdrawal following use of the Oxette (Registered Trademark) Nicotine Inhaler pack.This will be assessed using patient questionnaires.
Timepoint [2] 279160 0
Various time points over treatment day (s) with safety follow up at 8 days.
Secondary outcome [3] 297948 0
A comparison of the plasma nicotine pharmacokinetic parameters (Cmax, Tmax and AUC) of orally inhaled nicotine delivered via the Oxette (Registered Trademark) Nicotine Inhaler device and the Nicorette (Registered Trademark) Inhaler.
Timepoint [3] 297948 0
Various time points ranging from pre-dose to up to 300 minutes post-dose with safety follow-up + 8 days. The timepoints differ per study part.

Eligibility
Key inclusion criteria
1. Smoking male or female with a minimum age of at least 18 years and maximum age of 55 years.
2.Smoke greater than or equal to 10 manufactured cigarettes per day for the last year.
3. Smoke within 1 hour of waking.
4. Expired carbon monoxide greater than 10ppm at screening.
5. Body weight of at least 50 kg with a BMI range of 18.5 – 32.
6. Availability of participant for the entire study period and willingness to adhere to protocol requirements, as evidenced by a signed, Informed Consent Form.
7. Normal findings in the physical examination, vital signs and a 12 lead ECG.
8. Women must be using one effective barrier method of contraception, be postmenopausal for at least 12 months prior to trial entry, or surgically sterile. Women of child-bearing potential must complete a serum pregnancy test prior to the first administration with a negative result.
Minimum age
18 Years
Maximum age
55 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Known or suspected history of hypersensitivity to nicotine.
2. History of confirmed chronic and/or serious pulmonary disease, including asthma or COPD.
3. History of a heart attack or stroke.
4. Females who are pregnant or breastfeeding.
5. Participants with any co-morbidity, which in the opinion of the Principal Investigator, might place them at undue risk or which could interfere with the interpretation of study data.
6. Presence or history of clinically significant cardiac or renal conditions.
7. Participants taking prescription anticoagulant or anti-platelet medication.
8. Participating in a clinical trial with an investigational drug within 30 days preceding this trial.
9. Blood donation within 45 days preceding this trial.
10.Participants who are known to have serum hepatitis or who are carriers of the hepatitis B surface antigen (HBsAg) or hepatitis C antibody or have a positive result to the test for Human Immunodeficiency Virus (HIV).
11. Participants who had a clinically significant positive drug screen result at either the screening visit or on admission. (A drug screen may only be repeated where methodological reasons are believed to have led to a false positive result).

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)
Part D: Each participant will be randomised to receive the medium dose level of orally inhaled nicotine (0.056%w/w) via the Oxette (Registered Trademark) Nicotine Inhaler device on one day, and a single dose of Nicorette (Registered Trademark) Inhaler (10mg) another day. The order in which treatment will be received will be randomised.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A randomisation list will be prepared by the biostatistician using a computerised method.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Part D: Each participant will attend the clinical trial unit on two consecutive days and will be randomized to receive one complete refill of Oxette (registered trademark) Nicotine Inhaler device at the medium dose level of nicotine (0.056%w/w) on one day, and one treatment of Nicorette (registered trademark) Inhaler (10 mg) on another day in random order.
Phase
Phase 1
Type of endpoint(s)
Pharmacokinetics / pharmacodynamics
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 267458 0
Commercial sector/Industry
Name [1] 267458 0
Kind Consumer Limited
Address [1] 267458 0
79 Clerkenwell Road
London
EC1R 5AR
United Kingdom
Country [1] 267458 0
United Kingdom
Primary sponsor type
Commercial sector/Industry
Name
Kind Consumer Limited
Address
79 Clerkenwell Road
London
EC1R 5AR
United Kingdom
Country
United Kingdom
Secondary sponsor category [1] 266504 0
Commercial sector/Industry
Name [1] 266504 0
Clinical Network Services
Address [1] 266504 0
L4, 88 Jephson St, Toowong, QLD 4066
Country [1] 266504 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 269433 0
Queensland Clinical Trials Network Inc.
(QCTN)
Ethics committee address [1] 269433 0
Queensland Clinical Trials Network Inc.
Human Research Ethics Committee
Level 3, 88 Jephson Street
Toowong QLD 4006
Ethics committee country [1] 269433 0
Australia
Date submitted for ethics approval [1] 269433 0
Approval date [1] 269433 0
04/11/2011
Ethics approval number [1] 269433 0
HREC 2011003

Summary
Brief summary
The purpose of this study is to determine how safe and tolerable the Oxette (Registered Trademark) Nicotine Inhaler Pack is. This includes the device and how the nicotine is absorbed into your body and the levels of nicotine in your blood. The study is also looking to compare the Oxette (Registered Trademark) Nicotine Inhaler Pack against the Nicorette (Registered Trademark) Inhaler (this product is approved and readily available as a stop smoking aid), to see how the levels of nicotine in your blood from each product compare. This study consists of 4 different parts. PART A: A total of 18 participants. Will receive 2 different doses of nicotine on one single day. PART B: A total of 24 participants. Will receive 2 different dose levels of nicotine over three separate days. PART C: A total of 18 participants. Will all receive the same single dose level of nicotine every hour for 12 hours. Part D: A total of 24 participants. Will attend the clinical trial unit on two consecutive days and will be randomised to receive one complete refill of Oxette (Registered Trademark) Nicotine Inhaler device at the medium dose level of nicotine (0.056%w/w) on one day, and one treatment of Nicorette (Registered Trademark) Inhaler (10mg) on another day in random order.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 32884 0
Address 32884 0
Country 32884 0
Phone 32884 0
Fax 32884 0
Email 32884 0
Contact person for public queries
Name 16131 0
Project Manager
Address 16131 0
Level 4 88 Jephson Street, Toowong Brisbane QLD 4066
Country 16131 0
Australia
Phone 16131 0
+61 7 3719 6000
Fax 16131 0
+61 7 3719 6011
Email 16131 0
cns@clinical.net.au
Contact person for scientific queries
Name 7059 0
Project Manager
Address 7059 0
Level 4 88 Jephson Street, Toowong Brisbane QLD 4066
Country 7059 0
Australia
Phone 7059 0
+61 7 3719 6000
Fax 7059 0
+61 7 3719 6011
Email 7059 0
cns@clinical.net.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary