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Trial registered on ANZCTR


Registration number
ACTRN12616000824460
Ethics application status
Approved
Date submitted
7/06/2016
Date registered
23/06/2016
Date last updated
5/06/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
A Single-Center, Randomized, Open-Label, Two-Period, Cross Over, Pharmacokinetic Study to Assess the Relative Bioavailability of Nicotine Delivered by the Chrono Quit Smoking Solution (CQSS1) versus NicoDerm (Registered Trademark) CQ (Registered Trademark) Patch
Scientific title
A Single-Center, Randomized, Open-Label, Two-Period, Cross Over, Pharmacokinetic Study to Assess the Relative Bioavailability of Nicotine Delivered by the Chrono Quit Smoking Solution (CQSS1) versus NicoDerm (Registered Trademark) CQ (Registered Trademark) Patch in Smokers
Secondary ID [1] 289222 0
PK2016-004
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
cigarette addiction 298779 0
Condition category
Condition code
Mental Health 298834 298834 0 0
Addiction

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Nicotine Replacement Therapy System
Dosing period consists of 3 days with approximately 21 mg of nicotine delivered transdermally per day using the Chrono Quit Smoking Solution (CQSS1). Doses of 5.4% nicotine formulation delivered transdermally via the CQSS1 worn either on the upper arm or mid-thigh at programmed intervals of T0 (upon waking in the morning), T0.5, T1, T7, T7.5, and T13 hours each day. The dosing timepoints are consistent across 3 consecutive days. Each CQSS1 is worn for 24 hours and is changed once daily upon waking. The washout period between study treatments is 2 days. Participants are required to stay in the clinic for 8 days. The treatment will not be titrated. The treatment will be adapted to subject’s wake-up time. The CQSS1 treatments will be administered by the health care provider.
Placement of the CQSS1 on the subject will be randomized to mid-thigh and taped, upper arm and taped, mid-thigh not taped, upper arm not taped. Additionally, subjects will be randomized to the sequence CQSS1 then NicoDerm or NicoDerm then CQSS1. Body location and taping status will remain the same throughout the study for each subject. Pharmacokinetic and skin irritation assessment using an 8-point visual scale will be used.
Intervention code [1] 294757 0
Treatment: Drugs
Comparator / control treatment
NicoDerm (Registered Trademark) CQ (Registered Trademark) Patch product is a commercially-available adhesive patch that provides nicotine transdermally over 24 hours. The study dosing period consists of 1 day with application of approximately 21 mg nicotine total. The NicoDerm (Registered Trademark) CQ (Registered Trademark) Patch is applied to either the upper arm or mid-thigh in the morning of the dosing period at the time of dosing initiation, and worn for 24 hours. The treatment will not be personalized, titrated, or adapted to individuals. NicoDerm treatments will be administered by the health care provider.
Subjects will be randomized to mid-thigh and taped, upper arm and taped, mid-thigh not taped, upper arm not taped. Additionally, subjects will be randomized to the sequence CQSS1 then NicoDerm or NicoDerm then CQSS1. Body location and taping status will remain the same throughout the study for each subject.
Control group
Active

Outcomes
Primary outcome [1] 298312 0
Evaluate relative bioavailability of nicotine delivered by the CQSS1 vs NicoDerm with PK analysis. This is a composite to include: Geometric mean ratios (test/reference) and 90% confidence intervals (CIs) for maximum plasma concentration (Cmax), area under the plasma concentration-versus-time curve (AUC) from time 0 to 24 hours (AUC0-24), and AUC extrapolated to infinity (AUC0-infinity).
Timepoint [1] 298312 0
CQSS1 (Study Treatment A) for Days 1 and 3 of treatment:
Blood draws at T0, every 20 minutes for the first 2 hours, T2.5 hours, T3 hours, hourly thereafter through hour 17, every 2 hours thereafter through 23 hours, and T24 hours.
CQSS1 (Study Treatment A) for Day 2 of treatment:
Blood draws at T15 hours and T24 hours.
NicoDerm CQ Patch (Study Treatment B) 1 day of treatment:
Blood draws immediately prior to patch application, every 20 minutes for first 2 hours, T2.5 hours, T3 hours, hourly thereafter through Hour 17, every 2 hours through hour 23, and then 24 hours after patch application.
Primary outcome [2] 298313 0
Evaluate if the amount of nicotine delivered by the CQSS1 vs NicoDerm treatments (single dose) are equivalent. The 90 percent CIs for the geometric mean ratio (test/reference) for AUC0-infinity must fall between 80 and 125 percent.
Timepoint [2] 298313 0
CQSS1 (Study Treatment A) for Days 1 and 3 of treatment:
Blood draws at T0, every 20 minutes for the first 2 hours, T2.5 hours, T3 hours, hourly thereafter through hour 17, every 2 hours thereafter through 23 hours, and T24 hours.
CQSS1 (Study Treatment A) for Day 2 of treatment:
Blood draws at T15 hours and T24 hours.

NicoDerm CQ Patch (Study Treatment B) 1 day of treatment:
Blood draws immediately prior to patch application, every 20 minutes for first 2 hours, T2.5 hours, T3 hours, hourly thereafter through hour 17, every 2 hours through hour 23, and then 24 hours after patch application.
Secondary outcome [1] 323831 0
Safety assessment with standard Adverse Event evaluation for tolerability of the CQSS1. Vital signs and skin irritation assessments will be monitored periodically throughout the active period of dosing for possible adverse events of: Bradycardia (pulse rate <40 beats per minute [bpm]), Tachycardia (pulse rate >120 bpm), Blood pressure <90 or >165 mmHg systolic, Blood pressure <45 or >105 mmHg diastolic, fever, generalized skin rash, abdominal pain, confusion, and pale skin. A skin irritation assessment using an 8-point visual scale will be used.
Timepoint [1] 323831 0
Daily throughout the study on treatment and washout days and at the safety follow-up visit 7 to 10 days from the last dose.
Secondary outcome [2] 324218 0
The skin adhesion assessment 5-point scale is validated and provided in US FDA Guidance, Assessing Adhesion with Transdermal Delivery Systems and Topical Patches, June 2016. The skin adhesion assessment of the CQSS1 will be completed by the health care professional.
Timepoint [2] 324218 0
Adherence assessment for the CQSS1 using a 5-point scale will be conducted each day immediately prior to initiation of dosing, at T6, T12, and T18 hours post-application, and immediately prior to the CQSS1 removal.

Eligibility
Key inclusion criteria
Non-treatment seeking smokers, smoking 11 cigarettes or more per day.
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
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Randomisation scheme will be computer generated. Individual treatment allocations will be provided to the study pharmacist in sealed opaque envelopes.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Subjects are randomized in a 1:1 ratio to one of two sequences that determines the order in which the study treatments, CQSS1 or NicoDerm, are administered (AB vs BA), the location of device placement (upper arm or mid-thigh), and whether or not the device/patch will be taped or not taped. Simple randomization using a randomization table created by computer software will be conducted.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 2
Type of endpoint(s)
Pharmacokinetics
Statistical methods / analysis
Descriptive statistics. The sample size calculation is based on the assumption that the variability of nicotine delivered by the CQSS1 is the same as that of nicotine delivered by the NicoDerm CQ Patch. Based on 20% intra-subject variability for the AUCs with a geometric mean ratio of 0.90 between nicotine delivered by the CQSS1 vs. NicoDerm CQ and at least 90% power with a 5% alpha (1-sided) ratio of geometric means within the range of 0.80 and 1.25, the sample size for this crossover study is 32 subjects, including 6 incompletes.

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)
VIC
Recruitment hospital [1] 5803 0
Nucleus Network - Melbourne
Recruitment postcode(s) [1] 13246 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 293612 0
Commercial sector/Industry
Name [1] 293612 0
Chrono Therapeutics Australia PTY LTD
Address [1] 293612 0
C/-MPR Group PTY LTD
Floor 19, HWT Tower
40 City Road
Southbank
Victoria 3004
Country [1] 293612 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] 292431 0
Commercial sector/Industry
Name [1] 292431 0
Nucleus Network Limited (Trading as Centre for Clinical Studies)
Address [1] 292431 0
5th Floor Burnet Tower, 89 Commercial Road, Melbourne
Victoria 3004
Country [1] 292431 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295053 0
The Alfred Ethics Committee
Ethics committee address [1] 295053 0
Commercial Road
Melbourne, Victoria 3004
Ethics committee country [1] 295053 0
Australia
Date submitted for ethics approval [1] 295053 0
23/06/2016
Approval date [1] 295053 0
09/08/2016
Ethics approval number [1] 295053 0

Summary
Brief summary
Phase 2, single-center, randomized, open-label, two-period, cross-over, PK study to assess the relative bioavailability of nicotine in non-treatment seeking healthy smokers following 1 day of nicotine from the drug delivery system (CQSS1) and the NicoDerm CQ Patch. Additionally, the steady-state PK profile of nicotine delivered by the CQSS1 will be determined following 3 days of nicotine delivery. Skin adhesion, application site location, taping, safety, and tolerability will be evaluated
Trial website
none
Trial related presentations / publications
none
Public notes
none

Contacts
Principal investigator
Name 65874 0
Dr Jason Lickliter
Address 65874 0
Nucleus Network 5th Floor Burnet Tower 89 Commercial Road Melbourne
Victoria 3004
Country 65874 0
Australia
Phone 65874 0
+61 (3) 9076 8900
Fax 65874 0
+61 3 9076 8911
Email 65874 0
J.Lickliter@nucleusnetwork.com.au
Contact person for public queries
Name 65875 0
Mr Cameron Johnson
Address 65875 0
Nucleus Network 5th Floor Burnet Tower 89 Commercial Road Melbourne
Victoria 3004
Country 65875 0
Australia
Phone 65875 0
+61 3 9076 8900
Fax 65875 0
+61 3 9076 8911
Email 65875 0
C.Johnson@nucleusnetwork.com.au
Contact person for scientific queries
Name 65876 0
Mrs Patricia Oto
Address 65876 0
Chrono Therapeutics Australia PTY LTD
3953 Point Eden Way,
Hayward, CA 94545
Country 65876 0
United States of America
Phone 65876 0
+1-925-286-6992
Fax 65876 0
none
Email 65876 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