To Investigate the Safety and Tolerability of TC-5214 Following Oral Administration of Multiple Doses for up to 8 Days

A Phase 1, Single Center, Double-blind, Randomized, Placebo- Controlled, Parallel-group Study to Assess the Safety, Tolerability, and Pharmacokinetics of Oral TC-5214 (S-Mecamylamine) After Administration of Single and Multiple Ascending Doses for up to 8 Days in Healthy Male and Female Subjects

To investigate the safety and tolerability of TC-5214 following oral administration of single and multiple ascending doses compared to placebo.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Placebo; Drug: TC-5214; Drug: TC-5214

• Study Type: Interventional
• Enrollment (Anticipated): 72
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Overland Park, Kansas, United States
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male and nonpregnant, nonlactating female, with suitable veins for cannulation or repeated venipuncture
• Contraceptive use from the first dose of investigational product until12 weeks after their last dose
• Body mass index (BMI) between 19 and 32 kg/m2 and weigh at least 50 kg

Exclusion Criteria:

• History of any clinically significant medical, neurologic or psychiatric disease or disorder which, in the opinion of the Investigator and Sponsor, may either put the volunteer at risk because of participation in the study, or influence the results of
• History of gastrointestinal surgery (except for cholecystectomy and appendectomy) or unintentional rapid weight loss
• Volunteers with a history of suicide attempts in the past year and/or seen by the Investigator as having a significant history of risk of suicide or homicide, or considered at risk for suicide or homicide during the study

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; Each cohort will have 9 volunteers that will receive TC-5214	Drug: TC-5214; 4 mg tablet, oral, BID, group 1; Drug: TC-5214; TBD tablet, oral, BID, groups 2-6
Placebo Comparator: 2; Each cohort will have 3 volunteers that will receive placebo	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
safety and tolerability assessed by incidence and severity of AE's, abnormalities in vital sign assessments, ECG's, telemetry, clinical lab assessments, physical exams, neurological exams, suicidality evaluations, visual acuity tests and digital ECGs	Collected prior to treatment, during treatment and for 7-10 days following discharge. Volunteers will be monitored througout the study for adverse events.

Secondary Outcome Measures

Outcome Measure	Time Frame
To characterize the pharmacokinetics of TC-5214 in blood and urine after single and repeated oral doses by collecting blood and urine samples to measure drug concentration levels	Blood sampling, every in house day; urine collection ;Days -1 through Day 6, Days 8 through 11.
To assess the effect of food on the pharmacokinetics of TC-5214 following oral administration by collecting blood and urine samples to measure drug concentration levels.	Samples taken during the residential period at defined timepoints pre-dose and post-dose

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: David Mathews, MD, Quintiles, Inc.; Study Chair: Donna Holloway, Quintiles, Inc.

Publications and helpful links

General Publications

• Xu H, Henningsson A, Alverlind S, Tummala R, Toler S, Beaver JS, Al-Huniti N. Population pharmacokinetics of TC-5214, a nicotinic channel modulator, in phase I and II clinical studies. J Clin Pharmacol. 2014 Jun;54(6):707-18. doi: 10.1002/jcph.264. Epub 2014 Jan 16.

Study record dates

Study Major Dates

• Study Start: June 1, 2010
• Primary Completion (Actual): August 1, 2010
• Study Completion (Actual): August 1, 2010

Study Registration Dates

• First Submitted: June 7, 2010
• First Submitted That Met QC Criteria: June 15, 2010
• First Posted (Estimate): June 17, 2010

Study Record Updates

• Last Update Posted (Estimate): December 8, 2010
• Last Update Submitted That Met QC Criteria: December 6, 2010
• Last Verified: December 1, 2010

More Information

Terms related to this study

• Keywords: Safety; pharmacokinetics; Double-blind; randomized; placebo-controlled; parallel-group study
• Other Study ID Numbers: D4130C00006