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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Smoking Cessation

Intervention / Treatment
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* Drug: Varenicline Tartrate
* Drug: Varenicline Tartrate
* Drug: Varenicline Tartrate
* Drug: Varenicline Tartrate
* Drug: Varenicline Tartrate


Participation Criteria
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Eligibility Criteria
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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.

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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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Cohort 1<br>Subjects will be randomized to receive either experimental drug (N=9) or matching placebo (N=3). | Drug: Varenicline Tartrate<br>* Varenicline 1.8 mg AMT-8 controlled release tablets administered twice a day for 14 days.<br>|
| Other: Cohort 2<br>Subjects will be randomized to receive either experimental drug (N=9) or matching placebo (N=3). | Drug: Varenicline Tartrate<br>* 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.<br>|
| Other: Cohort 3<br>Subjects will be randomized to receive either experimental drug (N=9) or matching placebo (N=3). | Drug: Varenicline Tartrate<br>* 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.<br>|
| Other: Optional Cohort 4<br>Subjects will be randomized to receive either experimental drug (N=9) or matching placebo (N=3). | Drug: Varenicline Tartrate<br>* 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.<br>|
| Other: Optional Cohort 5<br>Subjects will be randomized to receive either experimental drug (N=9) or matching placebo (N=3). | Drug: Varenicline Tartrate<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 |