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

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

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

Study Overview

• Status: Completed
• Conditions: Smoking Cessation
• Intervention / Treatment: Drug: varenicline free base patch; Drug: varenicline free base patch; Drug: varenicline free base patch; Drug: varenicline free base patch; Drug: placebo patch; Drug: placebo patch

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • North Dakota
    • Fargo, North Dakota, United States, 58104
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1	Drug: varenicline free base patch; 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; Drug: varenicline free base patch; 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; Drug: varenicline free base patch; 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; Drug: varenicline free base patch; 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
Experimental: Cohort 2	Drug: varenicline free base patch; 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; Drug: varenicline free base patch; 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; Drug: varenicline free base patch; 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; Drug: varenicline free base patch; 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; Drug: placebo patch; Matched placebo transdermal delivery system will be applied to the skin once daily for 14 days; Drug: placebo patch; Matched placebo transdermal delivery systems will be applied to the skin, side by side, once daily for 14 days
Experimental: Cohort 3	Drug: varenicline free base patch; 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; Drug: varenicline free base patch; 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; Drug: varenicline free base patch; 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; Drug: varenicline free base patch; 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; Drug: placebo patch; Matched placebo transdermal delivery system will be applied to the skin once daily for 14 days; Drug: placebo patch; Matched placebo transdermal delivery systems will be applied to the skin, side by side, once daily for 14 days
Experimental: Cohort 4	Drug: varenicline free base patch; 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; Drug: varenicline free base patch; 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; Drug: varenicline free base patch; 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; Drug: varenicline free base patch; 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; Drug: placebo patch; Matched placebo transdermal delivery system will be applied to the skin once daily for 14 days; Drug: placebo patch; Matched placebo transdermal delivery systems will be applied to the skin, side by side, once daily for 14 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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)

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (Actual): March 1, 2011
• Study Completion (Actual): March 1, 2011

Study Registration Dates

• First Submitted: August 14, 2009
• First Submitted That Met QC Criteria: November 2, 2010
• First Posted (Estimate): November 4, 2010

Study Record Updates

• Last Update Posted (Estimate): October 14, 2011
• Last Update Submitted That Met QC Criteria: October 13, 2011
• Last Verified: October 1, 2011

More Information

Terms related to this study

• Keywords: varenicline transdermal percutaneous transcutaneous transdermal delivery system patch
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Nicotinic Agonists; Cholinergic Agonists; Varenicline
• Other Study ID Numbers: A3051142