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Trial registered on ANZCTR


Registration number
ACTRN12616001529437
Ethics application status
Approved
Date submitted
26/10/2016
Date registered
7/11/2016
Date last updated
30/05/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
A Two-Arm, Open-Label, Multi-Location, Single Center Study of the Craving Profile of the Nicotine Replacement Therapy Chrono Quit Smoking Solution (CQSS2; 21 mg) versus NiQuitin (registered trademark) Patch (21 mg) for Smoking Cessation in Treatment Seeking Subjects
Scientific title
A Two-Arm, Open-Label, Multi-Location, Single Center Study of the Craving Profile of the Nicotine Replacement Therapy Chrono Quit Smoking Solution (CQSS2; 21 mg) versus NiQuitin (registered trademark) Patch (21 mg) for Smoking Cessation in Treatment Seeking Subjects
Secondary ID [1] 290382 0
CR2016-006
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
cigarette addiction 300694 0
Condition category
Condition code
Mental Health 300539 300539 0 0
Addiction

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Nicotine Replacement Therapy System, the CQSS2:
The treatment period consists of 2 weeks (14 days) of treatment. On the evening before each day of the treatment period, nicotine Drug Cartridges are inserted into the CQSS2 Control Unit. The subject enters, changes, or confirms the “Wake Time” in the Control Unit, which will determine when dosing begins on the following morning. The CQSS2 is then adhered to the upper arm, mid-thigh, calf, or torso based upon subject preference, and worn for approximately 20–24 hours. A new CQSS2 is applied each day for the 14 day treatment.
One pouched Drug Cartridge will be used to administer 21 mg nicotine via a 5.4% w/v solution in an aqueous EtOH mixture per day. Metered pulses of 125 microliters of solution will automatically be delivered by the assembled CQSS2 (containing the Control Unit and Drug Cartridge) at Time = 0, 0.5, 1, 7, 7.5, and 13 hours. The mode of nicotine administration via the CQSS2 is transdermal.

Subjects will be assigned to one of two treatment arms: Arm A (n=40): CQSS2;
Arm B (n=40): NiQuitin (registered Trademark) Patch. The first 40 participants are enrolled into Arm B, and the next 40 participants are enrolled into Arm A.

On the day after the last dose of study drug, subjects will return any unused CQSS2 Drug Cartridges, the CQSS2 Control Unit, and any unused NiQuitin (registered trademark) Patches. Data will be retrieved from the Ecological Momentary Assessment (EMA) device and drug accountability will be conducted.
Intervention code [1] 296211 0
Treatment: Drugs
Comparator / control treatment
The NiQuitin (registered trademark) Patch is a commercially available adhesive wearable patch that delivers nicotine transdermally over 24 hours. The patch has a protective backing, a drug containing reservoir, a rate-controlling membrane, and an adhesive layer covered by the release liner. The treatment period consists of 2 weeks (14 days) with approximately 21 mg of nicotine delivered per day. The NiQuitin (registered trademark) Patch is applied each morning of the treatment period after waking and worn for approximately 24 hours.
Control group
Active

Outcomes
Primary outcome [1] 299957 0
To compare the craving profile in smokers (greater than or equal to 10 cigarettes/day) being treated with the CQSS2 versus the NiQuitin (registered trademark) Patch for smoking cessation

The study will use Ecological Momentary Assessment (EMA) methods. A handheld computer (EMA device) will prompt the subject for a response to questions regarding cravings, urges, and withdrawal symptoms. The device will also allow for self-reporting of temptation events (craving episodes), and provide reminder notifications.
Time based data will be collected as follows (the average score of responses to the individual questions within each domain will be used in the analyses):

Cravings: The craving assessment will occur randomly approximately 4–5 times during each day. Subjects will self-report when they are highly tempted to smoke (self-reported craving episodes).
Timepoint [1] 299957 0
The first 2 weeks of a quit attempt: The craving assessment will occur randomly approximately 4–5 times during each day.
Secondary outcome [1] 328666 0
To compare the morning and evening craving profiles in smokers (greater than or equal to 10 cigarettes/day) being treated with the CQSS2 versus the NiQuitin (registered trademark) Patch.

The study will use Ecological Momentary Assessment (EMA) methods. A handheld computer (EMA device) will prompt the subject for a response to questions regarding cravings, urges, and withdrawal symptoms. The device will also allow for self-reporting of temptation events (craving episodes), and provide reminder notifications.
Cravings will be assessed by a morning and evening report in the EMA. A Visual Analog Scale (VAS) will be used to assess cravings.
Timepoint [1] 328666 0
During the first 2 weeks of a quit attempt: On waking each morning and immediately prior to bed each day for the 2 weeks of the study treatment.
Secondary outcome [2] 328667 0
Safety assessment with standard Adverse Event evaluation for tolerability of the CQSS2.
Vital signs and skin irritation assessments will be monitored periodically throughout the active period of dosing for possible adverse events of: Bradycardia (resting pulse rate <40 beats per minute [bpm]); Tachycardia (resting pulse rate >120 bpm); Blood pressure <90 or >165 mmHg systolic; Blood pressure <45 or >105 mmHg diastolic. Skin irritation at the application sites will be assessed on an 8-point Skin Irritation Assessment scale. Safety evaluations, including physical examinations, vital signs, ECGs, laboratory testswill be performed.
Timepoint [2] 328667 0
Adverse events will be monitored from the time of the CQSS2 application until the last study visit on Day 15.
Secondary outcome [3] 328668 0
Assess the adhesive properties of the CQSS2.
The subjects will self-report each day through the Ecological Momentary Assessment (EMA) device if they needed to tape the CQSS2 to their body at any time during the study. [Note: Only shown on the EMA if response is “Completely come/fall off of your body” or “Start to come/fall off at the edges but stayed on”.]
Timepoint [3] 328668 0
Skin adherence for the CQSS2 will be assessed daily during the study.
Secondary outcome [4] 328669 0
Assess the urge and withdrawal profile in smokers (greater than or equal to 10 cigarettes/day) being treated with the CQSS2 versus the NiQuitin (registered trademark) Patch. This is a composite outcome.
Timepoint [4] 328669 0
During the first 2 weeks of a quit attempt: Urges will be evaluated using the Questionnaire on Smoking Urges (QSU). Participants will complete the QSU once a day. Withdrawal symptom severity assessments will occur randomly approximately 4–5 times during each day; withdrawal symptoms will also be assessed by a morning and evening report in the EMA (upon waking each morning and immediately prior to bed each day for the 2 weeks of the study treatment).

Eligibility
Key inclusion criteria
Smokers consuming on average more than or equal to 10 cigarettes per day for at least the past 6 months, confirmed by self report
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
infections
opiate use
males who consume more than 4 alcoholic beverages per day
females who consume more than 3 alcoholic beverages per day
skin tattoos

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
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
The non-inferiority margin was drawn from a study examining the effect of nicotine gum on cue induced craving intensity. A difference of 12.4 points was the average reduction in craving observed among subjects who reported that the degree of craving reduction experienced had not been “meaningful”. Thus, this degree of reduction is used as an estimate of the lower bound of a clinically significant reduction in craving (as based upon these results, a reduction of less than 12.4 points is unlikely to be clinically meaningful for the smoker). Assuming that the daily nicotine craving score has a standard deviation of 17.6, 36 subjects per arm will provide 84% of power to ensure that the upper limit of 95% confidence interval (CI) of treatment difference is less than the non inferiority margin of 12.4. Adjusting for a 10% loss of subjects, 40 subjects per arm (at least 80 subjects total) will be planned for this study. If dropout rates are higher than 10%, additional subjects may be enrolled to ensure that there are 36 evaluable subjects in each arm.

Efficacy analysis will be based on the per protocol (PP) analysis set. Daily craving scores from Day 1 through Day 14 will be analyzed using a mixed-effect model for repeated measures (MMRM) with average craving reporting during baseline monitoring period included as a covariate; and treatment, day, and treatment by day interaction as factors. Overall treatment difference and 95% CI will be estimated. If the upper CI is less than 12.4, the study will meet its non inferiority margin. Mean daily (i.e., Day 1 – Day 14) craving (adjusted for baseline craving) and associated 95% CIs will also be presented for both groups. If the study meets its non-inferiority margin, a superiority test at one-sided 0.025 will also be performed. Morning and evening craving scores, smoking urges (QSU), and withdrawal symptoms will also be analyzed using MMRM based on the PP analysis set.

All subjects who have had the CQSS2 or the NiQuitin (registered trademark) Patch applied (regardless of whether or not they complete the study) will be included in the safety analyses. Adverse event data will be coded with the Medical Dictionary for Regulatory Activities (MedDRA). The following data will be summarized: Incidence of AEs by System Organ Class (SOC) and preferred MedDRA terms; Descriptive statistics of the Skin Irritation Assessment, along with skin irritation AEs at the application site; Clinical laboratory data (including shift tables), vital signs, and 12-lead ECG data at each timepoint; Concomitant medications will be listed.

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)
TAS
Recruitment postcode(s) [1] 14553 0
7000 - Hobart

Funding & Sponsors
Funding source category [1] 294790 0
Commercial sector/Industry
Name [1] 294790 0
Chrono Therapeutics Australia PTY LTD
Address [1] 294790 0
C/-MPR Group PTY LTD
Floor 19, HWT Tower
40 City Road
Southbank
Victoria 3004
Country [1] 294790 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Chrono Therapeutics Australia PTY LTD
Address
C/-MPR Group PTY LTD
Floor 19, HWT Tower
40 City Road
Southbank
Victoria 3004
Country
Australia
Secondary sponsor category [1] 293633 0
University
Name [1] 293633 0
University of Tasmania, School of Medicine
Address [1] 293633 0
17 Liverpool Street
Hobart, Tasmania 7000

Country [1] 293633 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296194 0
Tasmania Health and Medical HREC
Ethics committee address [1] 296194 0
17 Liverpool Street
Hobart, TAS
7000
Ethics committee country [1] 296194 0
Australia
Date submitted for ethics approval [1] 296194 0
28/09/2016
Approval date [1] 296194 0
15/11/2016
Ethics approval number [1] 296194 0
H0016089

Summary
Brief summary
Over 35 million smokers try to quit smoking each year, yet less than 5% reach their 1-year anniversary. Numerous passive transdermal nicotine systems (reservoir and matrix) have been marketed over the past 13 years [i.e., Nicotrol (registered trademark), NicoDerm (registered trademark), CQ (registered trademark), Habitrol (registered trademark), ProStep (registered trademark), etc.]. These systems have been well characterized with regard to skin flux rates for nicotine Transdermal patches deliver 5 to 30 mg of nicotine over 24 hours, with the used patch still containing a significant amount of residual, undelivered nicotine. Chrono Therapeutics has developed an innovative programmable transdermal drug delivery system. The CQSS2 provides “off” periods (periods in which little to no nicotine is delivered), which is an advantage over existing systems that currently provide continuous delivery. Programmable drug delivery fulfills unmet medical needs in the treatment of critical diseases, based on the novel finding that patient compliance and medicinal efficacy can be enhanced with sequential bursts, or pulses, and are potentially more effective than traditional treatment regimens.
Trial website
None
Trial related presentations / publications
None
Public notes
None

Contacts
Principal investigator
Name 69890 0
Dr Stuart Ferguson
Address 69890 0
University of Tasmania School of Medicine
17 Liverpool Street
Hobart, TAS
7000 TAS
Country 69890 0
Australia
Phone 69890 0
+61 3 6226 4295
Fax 69890 0
Email 69890 0
Stuart.Ferguson@utas.edu.au
Contact person for public queries
Name 69891 0
Dr Stuart Ferguson
Address 69891 0
University of Tasmania School of Medicine
17 Liverpool Street
Hobart, TAS
7000 TAS

Country 69891 0
Australia
Phone 69891 0
+61 3 6226 4295
Fax 69891 0
Email 69891 0
Stuart.Ferguson@utas.edu.au
Contact person for scientific queries
Name 69892 0
Mrs Patricia Oto
Address 69892 0
Chrono Therapeutics Australia PTY LTD
3953 Point Eden Way,
Hayward, CA 94545
Country 69892 0
United States of America
Phone 69892 0
+1-925-286-6992
Fax 69892 0
Email 69892 0
poto@chronothera.com

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