A randomized, double-blind, placebo-controlled, serial-cohort, single ascending dose of Xen2174 with bupivacaine interaction study administered intrathecally in healthy volunteers.
- Conditions
- pain after surgeryPost operative pain10007867
- Registration Number
- NL-OMON35341
- Lead Sponsor
- Xenome Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Withdrawn
- Sex
- Not specified
- Target Recruitment
- 44
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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Pharmacodynamics:<br /><br>Pain threshold and tolerance levels for each nociceptive test:<br /><br>-Pressure pain (muscle) (kPa),<br /><br>-Electrical pain (skin) (mA) single stimulus<br /><br>-Electrical pain (skin) (mA) repeated stimulus<br /><br>-Cold pressor pain (seconds)<br /><br>-Diffuse Noxious Inhibitory Control (difference of electrical pain before<br /><br>and after cold pressor task)<br /><br>EEG data<br /><br>Determination of the level and duration of sensory blockade due to bupivacaine<br /><br>-Pin Prick/ Cold discrimination<br /><br>Determintation of the level and duration of motor blockade due to bupivacaine<br /><br>-Modified Bromage scale<br /><br><br /><br>Pharmacokinetics:<br /><br>-CSF Bupivacaine PK<br /><br>-CSF Xen2174 PK<br /><br>-Plasma bupivacaine PK<br /><br>-Plasma Xen2174 PK</p><br>
- Secondary Outcome Measures
Name Time Method <p>Not applicable</p><br>