A randomized, double-blind, placebo-controlled, serial-cohort, single ascending dose of Xen2174 with bupivacaine interaction study administered intrathecally in healthy volunteers.

1. Healthy subjects aged 18-50 years at the time of informed consent.
2. Voluntary provision of written informed consent prior to any study procedure, indicative of understanding the purpose of the study and willing to participate in the study and comply with the study procedures and restrictions.

1. Subject has or had, in the opinion of the investigator, clinical significant abnormalities as found in the medical history, physical examination, electrocardiogram (ECG), laboratory profile and/or blood and urine.
2. Vital sign measurements outside the following ranges: (Individuals with values outside of these ranges may be enrolled if clinically acceptable to the investigator and sponsor):
•Body temperature, between 35.0ºC and 37.5ºC
•Systolic blood pressure, 90 to 140 mm Hg
•Diastolic blood pressure, 45 to 90 mm Hg
•Pulse rate, 40 to 100 bpm
3. Women of childbearing potential who refuse to use a medically acceptable form of contraception throughout the study. (Acceptable methods of contraception are as follows: oral or injectable hormonal contraceptives, intrauterine devices, vaginal hormonal rings, and only in combination with a male condom, a vaginal diaphragm, or cervical caps. Men are advised to use male condoms in addition to having their partner use another acceptable method during the study and for 3 months after the last dose.)
4. Women who are pregnant or lactating, or have a positive pregnancy test within 72 hours prior to randomization.
5. Presence or history of clinically significant psychiatric diseases, as judged by the investigator.
6. Any clinically relevant acute or chronic diseases which according to the investigator could interfere with the subject*s safety during the trial, or expose them to undue risk, or which could interfere with the study objectives.
7. Presence or history of clinically significant allergy or known hypersensitivity to any component of the investigational product.
8. Subjects having an abnormal EEG at screening.
9. Subjects who had ever had an abnormal EEG.
10. Subjects having a history or family history (first degree) of seizures or seizure disorder.
11. Subjects who had febrile seizure in childhood.
12. Subjects who had an episode of loss of consciousness for any reason other than a vasovagal reaction.
13. Subjects having a history of hydrocephalus, head injury or (repeated) blow(s) to the head, which in the opinion of the investigator might have resulted in an (undiagnosed) brain injury.
14. Subjects having a history of or presenting pseudo or psychogenic seizure;
15. Subjects having a history of meningitis/encephalitis or other infectious process affecting the brain, central, and/or peripheral nervous system;
16. Subjects having a history of haematological disorder such as leukaemia, lymphoma, purpura, clotting disorders, or conditions that affect bleeding or clotting time;
17. Subjects having a history or family history of ankylosing spondylitis, previous (lumbar) back surgery and/or spinal deformity;
18. Subjects having a local skin infection at the site of injection, or dermatological condition e.g. psoriasis that preclude aseptic preparation of the skin around the injection site;
19. Subjects indicating nociceptive tests intolerable at screening.
20. Has a body mass index (BMI) outside the following range: 18 to 30 kg/m2(inclusive). BMI = weight (kg)/height2 (m2).
21. Has positive serology for HIV, hepatitis B (surface antigen), and/or hepatitis C antibodies.
22. Has planned medical treatments between screening and follow-up visit.
23. Enrolment in any investigational study or intake of an investigational drug within 3 months prior to the start of the study or more than 4 times a year.
24. Current regular user of any illicit drugs or history of drug abuse. Subjects who have a positive drug screen at screening will be excluded.
25. Donation of blood/plasma outside limits of Sanquin Blood Supply Foundation guidelines.
26. Is not likely to co-operate in the study, and/or has poor compliance as anticipated by the investigator, or not consistently reachable in case of emergency.
27. Daily consumption of xanthine-containing products more than 8 units. Unwilling or unable to refrain from consumption of xanthine-containing foods or drinks from 1 days prior to admission and during the stay in the research unit. One caffeine unit is contained in the following items: one cup of coffee, two cans of cola, one glass of tea, * cup of energy drink (e.g., Red Bull) or three chocolate bars.
28. Unwilling or unable to refrain from intensive physical exercise from 48 hours prior to each study day until dismissal from CHDR.
29. History of alcohol abuse and/or excessive current use of alcohol (i.e., regular use of more than 21 units of alcohol/week for males and more than 14 units/week for females), and/or unwillingness or unable to refrain from products containing alcohol from 1 days before admission and during the stay in the research unit. Subjects who have a positive alcohol breath test at screening will be excluded.
30. Unwilling or unable to refrain from smoking during admission and the stay in the research unit.
31. Males who are unwilling to abstain from having unprotected sexual intercourse or donating sperm during the study and for 3 months after study.
32. Male*s partner is planning pregnancy within 3 months of last dosing.
33. Subjects previously treated with Xen2174.
34. Is unsuitable, in the opinion of the investigator, to participate in the study for any other reason.