A Study Evaluating the Absorption Of Varenicline Through The Skin Following Once Daily Application Of A Patch For 14 Days

Study Overview
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Brief Summary
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This study will evaluate the steady-state pharmacokinetics, safety and tolerability of a varenicline patch applied once daily to the skin for 14 days.

Official Title
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A Phase 1, Investigator And Subject Blind (Sponsor Open), Randomized, Placebo Controlled, Parallel Cohort, Escalating Multiple Dose Study To Evaluate The Safety, Tolerability And Pharmacokinetics Of A Varenicline Transdermal Delivery System In Adult Smokers

Conditions
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Smoking Cessation

Intervention / Treatment
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* Drug: varenicline free base patch
* Drug: varenicline free base patch
* Drug: placebo patch
* Drug: varenicline free base patch
* Drug: placebo patch
* Drug: varenicline free base patch
* Drug: placebo patch


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male or female adult cigarette smokers of any race Exclusion Criteria: Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing). Subjects with active suicidal ideation or suicidal behavior within 1 year prior to Screening as determined through the use of the C-SSRS (Columbia-Suicide Severity Rating Scale) or active ideation identified at Screening or Day 0. Any condition possibly affecting drug absorption through the skin (eg, psoriasis).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br> | Drug: varenicline free base patch<br>* varenicline transdermal delivery system (12.0 mg payload [drug amount loaded in each patch]) will be applied to the skin once daily for 14 days<br>|
| Experimental: Cohort 2<br> | Drug: varenicline free base patch<br>* varenicline transdermal delivery system (18.0 mg payload [drug amount loaded in each patch]) will be applied to the skin once daily for 14 days<br>Drug: placebo patch<br>* Matched placebo transdermal delivery system will be applied to the skin once daily for 14 days<br>|
| Experimental: Cohort 3<br> | Drug: varenicline free base patch<br>* varenicline transdermal delivery system (24.0 mg payload [drug amount loaded in each patch]) will be applied to the skin once daily for 14 days<br>Drug: placebo patch<br>* Matched placebo transdermal delivery system will be applied to the skin once daily for 14 days<br>|
| Experimental: Cohort 4<br> | Drug: varenicline free base patch<br>* 2 varenicline transdermal delivery systems (combined to achieve a maximum drug payload of 36 mg) will be applied to the skin, side by side once daily, for 14 days<br>Drug: placebo patch<br>* Matched placebo transdermal delivery systems will be applied to the skin, side by side, once daily for 14 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration-time curve (AUC24); observed maximum plasma concentration (Cmax) in a given dosing interval and time of maximum plasma concentration (Tmax) |  | Days 1, 7 and 14 | 
| Observed accumulation ratio (Rac) |  | Days 7 and 14 | 
| Observed minimum plasma concentration (Cmin) in a given dosing interval, and peak: trough fluctuation (PTF) |  | Days 7 and 14 | 
| Terminal half life (t1/2) |  | Day 14-Day 19 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dermal rating scores (as measured by the Rating Scale for Assessment of Application Site Dermal-Erythema, Edema and Irritation) |  | Days 1-14 (24 hpd); Days 1, 7-8 (1 and 12 hpd); Day 14 (1,6,12,24,48,72,96 and 120 hpd) | 
| VAS scores for nausea (using a Visual Analog Scale) |  | Days 1-19 (daily) | 
| Daily adhesion score (as measured by the Rating Scale for Adhesion) |  | Days 1-14 (12 and 24 hpd);Days 1, 7 and 14 (1 and 6 hpd) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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varenicline transdermal percutaneous transcutaneous transdermal delivery system patch