Pain and CNS assessments Evaluation PD effects
Conditions
Interventions
Sponsors
Centre for Human Drug Research
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Signed informed consent prior to any study-mandated procedure. 2. Healthy male subjects, 18 up and to 55 years of age, inclusive at screening. 3. Body mass index (BMI) between 18 and 30 kg/m2, inclusive at screening, and with a minimum weight of 50 kg. 4. All subjects must practice effective contraception during the study and be willing and able to continue contraception for at least 90 days after their last dose of study treatment. 5. Has the ability to communicate well with the investigator in the Dutch language and willing to comply with the study restrictions.
Exclusion criteria
Exclusion criteria: 1. Evidence of any active or chronic disease or condition that could interfere with, or for which the treatment of might interfere with, the conduct of the study, or that would pose an unacceptable risk to the subject in the opinion of the investigator (following a detailed medical history, physical examination, vital signs (systolic and diastolic blood pressure, pulse rate, body temperature) and 12-lead electrocardiogram (ECG)). Minor deviations from the normal range may be accepted, if judged by the investigator to have no clinical relevance. 2. Clinically significant abnormalities, as judged by the investigator, in laboratory test results (including hepatic and renal panels, complete blood count, chemistry panel and urinalysis). In the case of uncertain or questionable results, tests performed during screening may be repeated before randomization to confirm eligibility or judged to be clinically irrelevant for healthy subjects. 3. Positive Hepatitis B surface antigen (HBsAg), Hepatitis C antibody (HCV Ab), or human immunodeficiency virus antibody (HIV Ab) at screening. 4. Systolic blood pressure (SBP) greater than 140 or less than 90 mm Hg, and diastolic blood pressure (DBP) greater than 90 or less than 50 mm Hg at screening. 5. Abnormal relevant findings in the resting ECG at screening. 6. Participation in an investigational drug or device study (last dosing of previous study was within 90 days prior to first dosing of this study). 7. History of abuse of addictive substances (alcohol, illegal substances) or current use of more than 21 units alcohol per week, drug abuse, or regular user of sedatives, hypnotics, tranquilizers, or any other addictive agent 8. Positive test for drugs of abuse at screening. 9. Alcohol will not be allowed from at least 24 hours before screening or dosing. 10. Smoker of more than 10 cigarettes per day prior to screening or who use tobacco products equivalent to more than 10 cigarettes per day and unable to abstain from smoking whilst in the unit. 11. Excessive caffeine consumption (more than eight cups of coffee or equivalent per day 12. Any confirmed significant allergic reactions (urticaria or anaphylaxis) against any drug, multiple drug allergies (non-active hay fever is acceptable). 13. Loss or donation of blood over 500 mL within three months prior to screening or intention to donate blood or blood products during the study. 14. Any known factor, condition, or disease that might interfere with treatment compliance, study conduct or interpretation of the results such as drug or alcohol dependence or psychiatric disease. 15. Any current, clinically significant, known medical condition in particular any existing conditions that would affect sensitivity to cold (such as atherosclerosis, Raynaud*s disease, urticaria, hypothyroidism) or pain (disease that causes pain, hypesthesia, hyperalgesia, allodynia, paresthesia, neuropathy, etc.). 16. Subjects indicating pain tests intolerable at screening or achieving tolerance at >80% of maximum input intensity for the cold, pressure and electrical tests. 17. Subject indicating intolerable pain after capsaicin administration at screening. 18. History or presence of post-inflammatory hyperpigmentation. 19. Dark skin (Fitzpatrick skin type IV, V or VI), widespread acne, freckles
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change from baseline to each time point of measurement during each study period: • Pressure Pain: Pain Detection Threshold (PDT), Pain Tolerance Threshold (PTT), Area Under the Curve (AUC), post-test Visual Analogue Scale (VAS) • Cold Pressor: PDT, PTT, Area Above the Curve (AAC), post-test VAS • Electrical Stair and Burst (pre-cold pressor): PDT, PTT, AUC, post-test VAS • Conditioned Pain Modulation (CPM) Response (change from electrical stair pre- and post-cold pressor): PDT, PTT, AUC • Von Frey: Total area of secondary algesia (mm2) • Short Form McGill Pain Questionnaire (SF-MPQ) for all above pain tests, except von Frey test and CPM • Thermal pain (normal skin, capsaicin-sensitized skin and UVB-exposed skin (the latter only for subjects with MED lower than 355 mJ/cm2 at screening): PDT, and post-test VAS (mm). • SF-MPQ for thermal pain • Laser Speckle Contrast Imaging (LSCI) o Dermal blood flow in capsaicin treated and control arm (au) Observations at each time point of measurement during each study period: • Saccadic eye movements: o saccadic reaction time (second), o saccadic peak velocity (degrees/second), and o saccadic inaccuracy (%); • Smooth pursuit eye movements: o percentage of time the eyes of the subjects are in smooth pursuit of the target (%); • Adaptive tracking: o average performance (%); • Body sway: o antero-posterior sway (mm); • N-Back (working memory load) o Mean reaction time for zero-back, one-back and two-back (ms) o (nr correct - nr incorrect)/total for zero-back/one-back-two-back • Pupil size (Pupil- and cornea diameter left/right eye) o Pupil/iris ratio left/right eye • Visual Analog Scales (VAS) according to Bond and Lader to assess: o mood (mm) o alertness (mm) o calmness (mm) • Visual Analog Scales (VAS) according to Bowdle to assess: o Bowdle Psychotomimetic Effects Scores (mm) During each study period: • Visual Verbal Learning Test (VVLT) memory testing o Immediate recall trial 3 (number cor | — |
Secondary
| Measure | Time frame |
|---|---|
| N.a. | — |
Countries
Netherlands
Outcome results
None listed