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

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

Official Title
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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

Conditions
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Elderly Subjects 65 Years and Older, Healthy or With a Stable Disease and Treatment.

Intervention / Treatment
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* Drug: TC-5214
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Safety, tolerability, healthy, stable disease, oral, tablet