Novel treatment combination for neuropathic pain in healthy male volunteers Other
Conditions
Interventions
The study consists of four identical study periods, Day -1 up to Day 2, each separated by a 1-week wash-out
Each study period, subjects will receive one of the four treatment options in randomized ord
Sponsors
Centre for Human Drug Research
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Inclusion criteria
Inclusion criteria: 1. Healthy subjects, 18 to 65 years of age, inclusive. Healthy status is defined by absence of evidence of any active or chronic disease following a detailed medical and surgical history, a complete physical examination including vital signs, 12-lead ECG, haematology, blood chemistry, and urinalysis 2. Body mass index (BMI) between 18 and 30 kg/m², inclusive, and with a minimum weight of 50 kg and a maximum weight of 100 kg 3. Able to participate and willing to give written informed consent and 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 findings in the resting ECG at screening defined as: a. QTcF> 450 or 470 or 100 bpm) c. Personal or family history of congenital long QT syndrome or sudden death; d. ECG with QRS and/or T wave judged to be unfavourable for a consistently accurate QT measurement (e.g., neuromuscular artefact that cannot be readily eliminated, arrhythmias, indistinct QRS onset, low amplitude T wave, merged T- and U-waves, prominent U waves); e. Evidence of atrial fibrillation, atrial flutter, complete branch block, Wolf-Parkinson-White Syndrome, or cardiac pacemaker 6. Use of any medications (prescription or over-the-counter [OTC]), within 14 days of study drug administration, or less than 5 half-lives (whichever is longer). Exceptions are paracetamol (up to 4 g/day) and ibuprofen (up to 1g/day), which are allowed up to 2 days before screening and 2 days before each study drug administration. Other exceptions will only be made if the rationale is clearly documented by the investigator. 7. Use of any vitamin, mineral, herbal, and dietary supplements within 7 days of study drug administration, or less than 5 half-lives (whichever is longer). Exceptions will only be made if the rationale is clearly documented by the investigator. 8. Participation in an investigational drug or device study (last dosing of previous study was within 90 days prior to first dosing of this study). 9. History of abuse of addictive substances (alcohol, illegal substances) or current use of more than 21 units (for males) or 14 units (for females) of alcohol per week, drug abuse, or regular user of sedatives, hypnotics, tranquilizers, or any other addictive agent 10. Positive test for drugs of abuse at screening or pre-dose. 11. Alcohol will not be allowed from at least 24 hours before screening or each admission. 12. Current use of tobacco or nicotine products and unable to abstain from use of these products within the previous 3 months before the first dose administration. 13. Is demonstrating excess in caffeine consumption (more than eight cups of coffee or equivalent per day). 14. Any confirmed significant allergic reactions (urti
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Analgesic effects measured using the following pre-dose up to 9 h post-dose: 1. Pressure Pain: Pain Detection Threshold (PDT), Pain Tolerance Threshold (PTT), Area Under the Curve (AUC), post-test Visual Analogue Scale (VAS) 2. Heat pain (pre-cold pressor: unexposed/normal and UVB-exposed skin, the latter only for subjects with MED lower than 355 mJ/cm² at screening): PDT, and post-test VAS. 3. Cold Pressor: PDT, PTT, Area Above the Curve (AAC), post-test VAS 4. Electrical Stair test: PDT, PTT, AUC, post-test VAS 5. Electrical burst test: PDT, PTT, AUC, post-test VAS 6. Conditioned Pain Modulation (CPM) Response (change from heat pain pre-and post-cold pressor): PDT 7. Short Form McGill Pain Questionnaire (SFMPQ) for pressure pain, heat pain, cold pressor, electrical stair test and electrical burst test. | — |
Secondary
| Measure | Time frame |
|---|---|
| To evaluate the drug-sensitive central nervous system (CNS) functioning of morphine, pregabalin and the two drugs as combination by biomarker profiling and the NeuroCart at pre-dose up to 9 h post-dose: 1. Body sway: antero-posterior sway (mm); 2. Visual Analog Scales (VAS) according to Bond and Lader to assess: 2.1. mood (mm), 2.2. alertness (mm), and 2.3. calmness (mm). 3. Visual Analog Scales (VAS) according to Bowdle to assess: 3.1. Feeling high (mm) 3.2. Internal perception (mm) 3.3. External perception(mm) 4. N-back 4.1. Average reaction time (ms) (zero-, one-, two-back) 4.2. Number of correct targets (zero-, one-, two-back) 4.3. Number of incorrect targets (zero-, one-, two-back) 4.4. Number of faulty non-target responses (zero-, one-, two-back) 5. Adaptive Tracking: Average performance (%); 6. Visual Verbal Learning Test (VVLT) memory testing 6.1. Immediate recall trial 3 (number correct) 6.2. Delayed recall (number correct) 6.3. Delayed recognition (number correct) 6.4. Delayed recognition (reaction time correct) (msec) 7. Electroencephalography: Frequency ranges for spectral analysis, Delta, Theta, Alpha, Beta, Gamma 8. Simple Reaction Time Task (SRT): Reaction time (ms) Questionnaires: 9. State-Trait Anxiety Inventory (STAI): State anxiety score 10. Brief Symptom Inventory (BSI) 10.1 General somatic symptoms 10.2 Cognitive symptom so Inter personal sensitivity 10.3 Depressed mood 10.4 Anxiety 10.5 Hostility 10.6 Phobic anxiety 10.7 Paranoid thoughts 10.8 Psychoticism 10.9 Global severity index To evaluate the blood pharmacokinetic parameters of morphine, pregabalin and the two drugs as a combination at pre-dose up to 24h post-dose: 11. PK parameters of morphine (and metabolitemorphine-6-glucuronide), pregabalin by noncompartmental analysis of the plasma concentration-time data: AUCinf, AUClast, CL(/F), Cmax, t1/2, tlag, tmax, Vz(/F) To evaluate the safety and tolerability of morphine, pregabalin and the two drugs as combination at Day-1 up to the | — |
Countries
Netherlands
Contacts
Public ContactWouter Bakker
Outcome results
None listed