pain Neuropathic pain
Conditions
Interventions
During the course of the study (part B), on every one of the study days, a
subject will get, in random order:
- Duloxetine 60mg
- Tramadol 100mg
- Placebo
Sponsors
Centre for Human Drug Research
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Part A 1. Healthy male subjects, 18 to 45 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 and urinanalysis. 2. Body mass index (BMI) between 18 and 30 kg/m2, inclusive. 3. Able to participate and willing to give written informed consent and to comply with the study restrictions.;Part B 1. Healthy male subjects, 18 to 45 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 Electrocardiogram (ECG), haematology, blood chemistry, and urinalysis 2. Body mass index (BMI) between 18 and 30 kg/m2, inclusive. 3. Able to participate and willing to give written informed consent and to comply with the study restrictions.
Exclusion criteria
Exclusion criteria: Part A 1. History or symptoms of any significant disease including (but not limited to), neurological, psychiatric, endocrine, cardiovascular, respiratory, gastrointestinal, hepatic, or renal disorder. 2. Positive test for drugs of abuse at screening or pre-dose. Positive tests at screening may be repeated once. 3. Use of any medications (prescription or over-the-counter [OTC]), vitamin, mineral, herbal, and dietary supplements within 14 days prior to first study day, or less than 5 half-lives (whichever is longer). Exceptions will only be made if the rationale is discussed and clearly documented by the Investigator. 4. Clinically significant abnormalities, as judged by the Investigator. 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. 5. Participation in an investigational drug or device study within 3 months prior to screening. 6. Concomitant disease or condition that could interfere with, or for which the treatment of might interfere with, the conduct of the study, or that would, in the opinion of the Investigator, pose an unacceptable risk to the subject in this study. 7. Any confirmed significant allergic reactions (urticaria or anaphylaxis) against capsaicin specific 8. Dark skin (Fitzpatrick skin type V - VI), wide-spread acne, tattoos or scarring on the volar forearm. 9. Subject indicating a Numeric Rating Scale (NRS)(0-10) of more than 8 at screening after administration of capsaicin. 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. 11. Consume, on average, >8 units/day of (methyl)xanthines (e.g. coffee, tea, cola, chocolate) and not able to refrain from use during each stay at the CHDR clinic. 12. Unwillingness or inability to comply with the study protocol for any other reason. 13. Subject indicating prekindling process intolerable ;Part B 1. Positive test for drugs of abuse at screening or pre-dose. Positive tests at screening may be repeated once. 2. History (within 3 months of screening) of alcohol consumption exceeding 2 standard drinks per day on average (1 standard drink = 10 grams of alcohol). Alcohol consumption will be prohibited during study confinement and at least 24 hours before screening, before dosing, and before each scheduled visit. 3. History or clinical evidence of alcoholism or drug abuse. 4. History or symptoms of any significant disease including (but not limited to), neurological, psychiatric, endocrine, cardiovascular, respiratory, gastrointestinal, hepatic, or renal disorder. 5. Positive Hepatitis B surface antigen (HBsAg), Hepatitis C antibody (HCV Ab), or human immunodeficiency virus antibody (HIV Ab) at screening. 6. Systolic blood pressure (SBP) greater than 145 or less than 90 mm Hg, and diastolic blood pressure (DBP) greater than 90 or less than 50 mm Hg. 7. Use of any medications (prescription or over-the-counter [OTC]), 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 discussed and clearly documented between the Investigator and the sponsor. 8. Clinically significant abnormalities, as judged by the Investigator, in laboratory t
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part A Erythema • Area of flare on capsaicin treated and control arm (mm2) • Intensity of flare on capsaicin treated and control arm (A.U.) • Increase in blood perfusion on capsaicin treated and control arm (%) Primary and secondary hyperalgesia • Thermal pain: peripheral sensitization capsaicin treated area - Pain Detection Threshold (PDT) (°C) • Thermal pain: peripheral sensitization control area - Pain Detection Threshold (PDT) (°C) • von Frey hair stimulation: Area of secondary hyperalgesia (mm2) Psychophysical • Detection thresholds in primary, secondary and control area (mA) (IES only) • Rate of detection in primary, secondary and control area (%) (IES only) • Slope of psychophysical curve in primary, secondary and control area (mA-1) (IES only) • Reaction time in primary, secondary and control area (ms) • Subjective pain perception after LS on primary, secondary and control area o LS-NRS: Numeric rating scale (0-10 with 0=no pain & 10=worst pain imaginable) o McGill Pain Questionnaire Electrophysiological • LEP and IESEP (in primary, secondary and control area) o Amplitude (µV ) of N1, N2, P1, P2, N2P2 peaks - For the following IES stimulus amplitudes: • 1x detection threshold • 1.5x detection threshold • 2x detection threshold o Latency (ms) of N1, N2, P1, P2, N2P2 peaks - For the following IES stimulus amplitudes: • 1x detection threshold • 1.5x detection threshold • 2x detection threshold • Regions of interest in time-frequency analysis in primary, secondary and control area using LS • Regions of interest in scalp distribution analysis in primary, secondary and control area using LS • Regions of interest in time-frequency analysis in primary, secondary and control area using IES • Regions of interest in scalp distribution analysis in primary, secondary and control area using IES Capsaicin pain • Cap-NRS: Numeric Rating Scale (0-10 with 0=no pain & 10=worst pain imaginable) Baseline is defined as the average or firs | — |
Countries
Netherlands
Outcome results
None listed