A randomized, double-blind, double-dummy, single dose, 4-way cross-over study to develop an anti-cholinergic pharmacological challenge with mecamylamine in comparison to scopolamine

Recruitment & Eligibility

Status: Pending

Sex: Not specified

Target Recruitment: 12

Inclusion Criteria

1. Signed informed consent document
2. Healthy, male volunteers aged between 18 and 45 years
3. Body Mass Index between 18 kg/m2 and 32 kg/m2
4. Non-smokers for at least 1 year
5. Willingness to comply with study procedures and restrictions

Exclusion Criteria

1. Clinically relevant history of abnormal physical or mental health interfering with the study as determined by medical history taking and physical examinations obtained during the screening visit as judged by the investigator;
2. Clinically relevant abnormal laboratory results, electrocardiogram (ECG) and vital signs, or physical findings at screening (as judged by the investigator);
3. Presence of orthostatic hypotension as defined by a decrease of blood pressure >=10 mmHg systolic or >= 20 mmHg diastolic measured 2 min after standing up
4. Positive test for hepatitis B, C or HIV;
5. History of alcoholism or substance abuse within three years prior to screening;
6. Subjects unable to refrain from alcohol use from 24hours prior to dosing on Day 1 Periods 1-5 until discharge from the CRU for each study period;
7. Used tobacco and/or nicotine-containing products within one year of dosing on Day 1 Period 1;
8. Evidence of elevated blood pressure at screening of >140 mmHg systolic or >90 mmHg diastolic;
9. Subject is a habitual and heavy consumer of caffeinated beverages (more than 6 cups of coffee or equivalent/day) at screening and/or is not able to refrain from use of (methyl) xanthines (e.g. coffee, tea, cola, chocolate) from 12 hours prior to dosing until discharge from the CRU for each study period;
10. Positive urine drug screen (UDS) or alcohol or cotinine test at screening and/or Day 1 of each period;
11. Subject is unable to refrain from the use of concomitant medication which, in the opinion of the investigator, interferes with their ability to participate in the trial, from 7 days prior to dosing on Day 1 Period 1 until the follow-up study visit;
12. Subject has a history of severe allergies, or has had an anaphylactic reaction to prescription or non-prescription drugs or food;
13. History or clinical evidence of any disease and/or existence of any surgical or medical condition which might interfere with the absorption, distribution, metabolism or excretion of the study drugs (mecamylamine or scopolamine);
14. Currently using any nicotine replacement therapy, smoking cessation medications or remedies, including varenicline (Chantix ®) or have used any nicotinic products for smoking cessation within 3 months of screening; history of allergic reaction to nicotine-containing products
15. Participation in an investigational drug trial in the 3 months prior to administration of the initial dose of study drug (Day 1 Period 1) or more than 4 times per year;
16. Donation of blood/plasma outside limits of Sanquin Blood Supply Foundation guidelines of approximately 500 mL or significant blood loss;
17. Have a history of an allergic reaction to nicotine containing products;
18. Subject does not have veins suitable for canula placement on both arms;
19. Any other condition that in the opinion of the investigator would complicate or compromise the study, or the well being of the subject.