The Effect of Nicotine on Arousal, Cognition and Social Cognition in Young and Elderly Healthy Subjects.

Janssen (J&J Innovative Medicine)

Status and phase

Completed

Early Phase 1

Conditions

Cognition Disorders

Schizophrenia

Treatments

Drug: placebo

Other: A643 (nicotine)

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT01181934

CR017251

Details and patient eligibility

About

This study in young and elderly healthy subjects will investigate the effect of nicotine on arousal, cognitive task and social cognition after acute dose administration.

Full description

This is a double-blind (neither physician nor subject knows the name of the assigned drug), placebo-controlled, randomized (study drug assigned by chance), three-way-crossover trial (participants may receive different interventions sequentially during the trial) in young and elderly healthy volunteers. The three-way-crossover treatment phase will consist of three blinded treatment periods separated by a wash out period (the period allowed for the entire administered drug to be eliminated from the body) of 2 to 7 days. The study duration for each volunteer will be approximately 8 weeks. Each volunteer enrolled will be randomized to receive Treatment A (1mg nicotine per dosing), Treatment B (2mg nicotine per dosing) or Treatment C (placebo) during one of their treatment period. The study drug (nicotine or placebo) will be administered three times daily on Day 1 of each treatment phase as a mouth spray, separated 2 to 3 hours from each other (i.e. 0h; and 2 to 3h; and 4 to 6h post first dosing). Three different blocks of cognitive assessments will follow, one after each drug administration. Safety evaluations include adverse event monitoring, vital signs and clinical laboratory tests. Each volunteer participating will receive 3 identical study drug administrations per dosing day (2 to 3 hours from each other), resulting in an overall dose of 3 mg nicotine (Treatment A), 6 mg nicotine (Treatment B) or 0 mg nicotine (Treatment C) per dosing day. By the end of the study, after the 3-way crossover, each volunteer will have received 9 mg nicotine via mouth spray.

Enrollment

32 patients

Sex

All

Ages

18 to 75 years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

Man or woman between 18 and 30 years of age inclusive (Cohort 1 only)
Man or woman between 60 and 75 years of age, inclusive (Cohort 2 only)
Body mass index (BMI) between 18 and 35 kg/m2, inclusive (BMI = eight/height2)
Women must be: postmenopausal (for at least 12 months), surgically sterile (have had a hysterectomy or bilateral oophorectomy, tubal ligation, or otherwise be incapable of pregnancy), abstinent (at the discretion of the investigator/per local regulations), or if sexually active, be practicing a highly effective method of birth control and must agree to continue to use the same method of contraception throughout the study
Women of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test at admission (each study period)
Men must agree to use a condom at each sexual intercourse and to not donate sperm during the study and for 3 months after receiving the last dose of study drug. In addition, their female partners should also use an appropriate method of birth control for at least the same duration

Exclusion criteria

Female volunteers who are pregnant or breastfeeding
Clinically significant abnormal values for clinical chemistry, hematology or urinalysis at screening. It is expected that laboratory values will generally be within the normal range for the laboratory, though minor deviations, which are not considered to be of clinical significance to the investigator, are acceptable. Values of alanine aminotransferase (ALT)/aspartate aminotransferase (AST) < 2 fold Upper Limit of Normal will be allowed
Clinically significant abnormal physical examination, vital signs or 12-lead ECG at screening
History of epilepsy or fits or unexplained black-outs
Current dangerous or aggressive behavior
Clinically significant history of drug and/or food allergies
Recent history (within previous 6 months) of alcohol or drug abuse
Significant history of or current significant medical illness including (but not limited to) cardiac arrhythmias or other cardiac disease, hematological disease, bronchospastic respiratory disease, dyspnea, diabetes mellitus, renal or hepatic insufficiency, thyroid disease, infection, or any other illness that the investigator considers clinically significant should exclude the subject (Subjects with well-controlled hypertension will be allowed to participate)
Significant history of or current psychiatric or neurological illness
Smoking cigarettes (or equivalent) or the use of nicotine based products, within 3 months prior to study drug administration. Current use of any medication for smoking cessation such as nicotine replacement therapy, bupropion or varenicline
Positive urine screen for drugs of abuse at screening or admission