Multiple Dose, Dose Escalation Study of Varenicline Controlled Release Formulation in Adult Smokers

A Phase 1, Investigator And Subject Blind (Sponsor Open), Randomized, Placebo Controlled, Parallel Group, Multiple Dose Escalation Study To Evaluate The Safety, Tolerability And Pharmacokinetics Of Varenicline Amt-8 Controlled Release Formulation In Adult Smokers

The purpose of this study is to evaluate the safety, tolerability and pharmacokinetics of escalating multiple oral doses of varenicline AMT 8 controlled release formulation for 14 days in adult smokers.

Study Overview

• Status: Completed
• Conditions: Smoking Cessation
• Intervention / Treatment: Drug: Varenicline Tartrate; Drug: Varenicline Tartrate; Drug: Varenicline Tartrate; Drug: Varenicline Tartrate

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • East Grand Forks, Minnesota, United States, 58721
      • Pfizer Investigational Site
  • 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 and/or female subjects between the ages of 18 and 55 years, inclusive. Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure and pulse rate measurement, 12 lead ECG and clinical laboratory tests.
• Currently smoking and have smoked an average of at least 10 cigarettes per day during the past year, with no period of abstinence greater than 3 continuous months in the past year.

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).
• Pregnant or nursing women are excluded; women of childbearing potential (WOCBP) who are unwilling or unable to use an acceptable method of contraception as outlined in the protocol from at least 14 days prior to study medication administration until completion of protocol-required procedures are excluded.
• Subjects with an estimated creatinine clearance (CLcr) <80 mL/min derived using the method of Cockcroft and Gault.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Cohort 1; Subjects will be randomized to receive either experimental drug (N=9) or matching placebo (N=3).	Drug: Varenicline Tartrate; Varenicline 1.8 mg AMT-8 controlled release tablets administered twice a day for 14 days.; Drug: Varenicline Tartrate; Planned dose is Varenicline 2.4 mg AMT-8 controlled release tablets administered twice a day for 14 days. Actual dose may be adjusted based on emerging data from prior dose cohorts.; Drug: Varenicline Tartrate; Planned dose is Varenicline 3 mg AMT-8 controlled release tablets administered twice a day for 14 days. Actual dose may be adjusted based on emerging data from prior dose cohorts.; Drug: Varenicline Tartrate; The dose to be administered is not yet determined and will be based on emerging data from prior dose cohorts. The dose will be administered as Varenicline AMT-8 controlled release tablets twice a day for 14 days. The doses to be tested may be lower, higher or repeat a previously tested dose and may include a titration.
Other: Cohort 2; Subjects will be randomized to receive either experimental drug (N=9) or matching placebo (N=3).	Drug: Varenicline Tartrate; Varenicline 1.8 mg AMT-8 controlled release tablets administered twice a day for 14 days.; Drug: Varenicline Tartrate; Planned dose is Varenicline 2.4 mg AMT-8 controlled release tablets administered twice a day for 14 days. Actual dose may be adjusted based on emerging data from prior dose cohorts.; Drug: Varenicline Tartrate; Planned dose is Varenicline 3 mg AMT-8 controlled release tablets administered twice a day for 14 days. Actual dose may be adjusted based on emerging data from prior dose cohorts.; Drug: Varenicline Tartrate; The dose to be administered is not yet determined and will be based on emerging data from prior dose cohorts. The dose will be administered as Varenicline AMT-8 controlled release tablets twice a day for 14 days. The doses to be tested may be lower, higher or repeat a previously tested dose and may include a titration.
Other: Cohort 3; Subjects will be randomized to receive either experimental drug (N=9) or matching placebo (N=3).	Drug: Varenicline Tartrate; Varenicline 1.8 mg AMT-8 controlled release tablets administered twice a day for 14 days.; Drug: Varenicline Tartrate; Planned dose is Varenicline 2.4 mg AMT-8 controlled release tablets administered twice a day for 14 days. Actual dose may be adjusted based on emerging data from prior dose cohorts.; Drug: Varenicline Tartrate; Planned dose is Varenicline 3 mg AMT-8 controlled release tablets administered twice a day for 14 days. Actual dose may be adjusted based on emerging data from prior dose cohorts.; Drug: Varenicline Tartrate; The dose to be administered is not yet determined and will be based on emerging data from prior dose cohorts. The dose will be administered as Varenicline AMT-8 controlled release tablets twice a day for 14 days. The doses to be tested may be lower, higher or repeat a previously tested dose and may include a titration.
Other: Optional Cohort 4; Subjects will be randomized to receive either experimental drug (N=9) or matching placebo (N=3).	Drug: Varenicline Tartrate; Varenicline 1.8 mg AMT-8 controlled release tablets administered twice a day for 14 days.; Drug: Varenicline Tartrate; Planned dose is Varenicline 2.4 mg AMT-8 controlled release tablets administered twice a day for 14 days. Actual dose may be adjusted based on emerging data from prior dose cohorts.; Drug: Varenicline Tartrate; Planned dose is Varenicline 3 mg AMT-8 controlled release tablets administered twice a day for 14 days. Actual dose may be adjusted based on emerging data from prior dose cohorts.; Drug: Varenicline Tartrate; The dose to be administered is not yet determined and will be based on emerging data from prior dose cohorts. The dose will be administered as Varenicline AMT-8 controlled release tablets twice a day for 14 days. The doses to be tested may be lower, higher or repeat a previously tested dose and may include a titration.
Other: Optional Cohort 5; Subjects will be randomized to receive either experimental drug (N=9) or matching placebo (N=3).	Drug: Varenicline Tartrate; Varenicline 1.8 mg AMT-8 controlled release tablets administered twice a day for 14 days.; Drug: Varenicline Tartrate; Planned dose is Varenicline 2.4 mg AMT-8 controlled release tablets administered twice a day for 14 days. Actual dose may be adjusted based on emerging data from prior dose cohorts.; Drug: Varenicline Tartrate; Planned dose is Varenicline 3 mg AMT-8 controlled release tablets administered twice a day for 14 days. Actual dose may be adjusted based on emerging data from prior dose cohorts.; Drug: Varenicline Tartrate; The dose to be administered is not yet determined and will be based on emerging data from prior dose cohorts. The dose will be administered as Varenicline AMT-8 controlled release tablets twice a day for 14 days. The doses to be tested may be lower, higher or repeat a previously tested dose and may include a titration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetic endpoints include varenicline area under the curve from 0-24 hours (AUC24), maximum plasma concentration (Cmax),	Day 1 and Day 14
Safety endpoints include evaluation of clinical safety laboratory tests, supine vital signs, triplicate 12-lead ECGs and adverse events.	up to 14 days
Time of maximum plasma concentration (Tmax) on Day 1 and Day 14	Day 1 and Day 14
Minimum plasma concentration (Cmin), terminal half life (t1/2), observed accumulation ratio (Rac), peak:trough fluctuation (%PTF) on Day 14 only.	Day 14

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: October 1, 2007
• Primary Completion (Actual): February 1, 2008
• Study Completion (Actual): February 1, 2008

Study Registration Dates

• First Submitted: September 6, 2007
• First Submitted That Met QC Criteria: September 7, 2007
• First Posted (Estimate): September 10, 2007

Study Record Updates

• Last Update Posted (Estimate): January 11, 2010
• Last Update Submitted That Met QC Criteria: January 7, 2010
• Last Verified: January 1, 2010

More Information

Terms related to this study

• 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: A3051069