A Study to Assess Safety and Tolerability as Well as Absorption and Excretion of TC-5214 in Medically Stable Elderly Subjects

A Phase I, Double-blind, Placebo-controlled, Parallel Group Study to Assess the Safety, Tolerability and Pharmacokinetics of TC-5214 Given as Multiple Ascending Oral Doses in Medically Stable Elderly Subjects

The purpose of the study is to assess safety, tolerability and pharmacokinetics of TC-5214 in medically stable elderly subjects following multiple oral doses.

Study Overview

• Status: Completed
• Conditions: Elderly Subjects 65 Years and Older, Healthy or With a Stable Disease and Treatment.
• Intervention / Treatment: Drug: TC-5214; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• Sweden
  • Uppsala, Sweden
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Medically stable male and female subjects aged greater than or equal to 65 years with suitable veins for cannulation or repeated venipuncture. Subjects may have controlled chronic diseases such as hypertension, type 2 diabetes, osteoarthritis, stable chronic obstructive pulmonary disease, mild or moderate renal insufficiency (Estimated glomerular filtration rate (eGFR) per the Modified Diet in Renal Disease [MDRD] formula >50 mL/min/1.73 m2), rhinitis etc. as long as there has not been any significant changes in their medical condition or medications for the preceding 6 weeks. Classification of renal impairment will be based using an MDRD equation
• Male subjects who are sexually active must use a condom and their partner if of childbearing potential must use a reliable method of contraception from the first dose of investigational product until 3 months after their last dose
• Have a 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 (other than those previously defined as acceptable for this population, see inclusion criterion 1) which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or influence the results of the subject's ability to participate in the study: This includes seizure activity and repeated episodes of major depression
• Significant cardiovascular or cerebrovascular disease such as: a history of acute coronary syndrome; angina that has been symptomatic in the last 6 months; significant symptomatic arrhythmia; a stroke; transient ischemic attack that have occurred in the last 6 months
• History or presence of gastrointestinal or hepatic disease or any other condition known to interfere with absorption, distribution, metabolism or excretion of drugs
• Subjects who have type 2 diabetes must have an HbA1c of less than 8% according to the National Glycohemoglobin Standardization Program (NGSP) at screening
• Significant renal insufficiency as defined by eGFR per the MDRD formula <50 mL/min/1.73 m2 (individual eGFR measurements will be documented in the protocol).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; TC-5214	Drug: TC-5214; Tablet 1, 2, or 4 mg of TC-5213 will be given twice daily for 4 days and once on the 5th day.
Placebo Comparator: 2; Placebo matched to TC-5214	Drug: Placebo; Two subjects in each cohort will be given placebo.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of Adverse events	Range of 5 days
Neurological examinations	Range of 5 days
Visual acuity tests	Range of 5 days
Vital signs	Range of 5 days
Physical examinations	Range of 5 days
Laboratory parameters	Range of 5 days
Suicidality as assessed by the Columbia-Suicide Severity Rating Scale	Range of 5 days
Electrocardiograms	Range of 5 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetic variables of TC-5214 by assessment of drug concentrations in plasma	Range of 5 days

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Study Director: Hans A Eriksson, MD, AstraZeneca; Principal Investigator: Wolfgang Kuhn, MD, Quintiles Phase 1; Principal Investigator: Aslak Rautio, MD, Quintiles Hermelinen

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: January 1, 2011
• Primary Completion (Actual): May 1, 2011
• Study Completion (Actual): May 1, 2011

Study Registration Dates

• First Submitted: October 28, 2010
• First Submitted That Met QC Criteria: November 10, 2010
• First Posted (Estimate): November 11, 2010

Study Record Updates

• Last Update Posted (Estimate): June 28, 2012
• Last Update Submitted That Met QC Criteria: June 27, 2012
• Last Verified: January 1, 2011

More Information

Terms related to this study

• Keywords: Safety; tolerability; oral; healthy; stable disease; tablet
• Other Study ID Numbers: D4130C00013

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No