(Chronic) Pain
Conditions
Interventions
All subjects will receive one of the following treatments per visit in randomized order. All subjects will receive both treatments during the study. The treatments are as follows: 
Nefopam HCl 20mg i.v. for 15 minutes 
Oxycodone IR 20mg p.o.Matching placebo solution(s) and capsule(s)
Sponsors
Centre for Human Drug Research
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Signed informed consent prior to any study-mandated procedure.Healthy male or female subjects, 18 to 65 years of age, inclusive at screening.Body mass index (BMI) between 18 and 35 kg/m2, inclusive at screening, and with a minimum weight of 60kg. Has the ability to communicate well with the Investigator in the Dutch language and is willing to comply with the study restrictions.
Exclusion criteria
Exclusion criteria: Evidence of any active or chronic disease or condition that could interfere with, or for which the treatment 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.Systolic blood pressure (SBP) greater than 160 or less than 90 mmHg, and diastolic blood pressure (DBP) greater than 90 or less than 50 mmHg at screening.Use of any medications (prescription or over-the-counter [OTC]), within 7 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 permitted up to 2 days before study drug administration and screening period. Hormonal contraceptives are also an exception through the entirety of the study. Other exceptions will only be made if the rationale is clearly documented by the Investigator. Use of any vitamin, mineral, herbal, and dietary supplements within 7 days of study drug administration. Exceptions will only be made if the rationale is clearly documented by the Investigator.Participation in an investigational drug or device study, more than four times per year, and last dosing of previous study was within 30 days, or 5 half-lives (whichever is longest) prior to first dosing of this study.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. 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.Positive test for drugs of abuse at screening or during the study. Use of tobacco or nicotine products (>5 cigarettes per week or equivalent) up until 2 weeks prior to screening and unable to abstain from these products in the 2 weeks prior to screening.Any confirmed significant allergic reactions (urticaria or anaphylaxis) against any drug, or multiple drug allergies (non-active hay fever is acceptable).If a woman planning to become pregnant or breastfeeding during the study.History of epilepsy or any convulsions.History of acute glaucoma. Fitzpatrick skin type IV, V and VI, wide-spread acne, tattoos or scarring interfering with the area of interest for pain testing (volar forearm, lower leg).Subjects who indicated nociceptive tests are intolerable at screening or who have a heat pain detection threshold greater than or equal to 50 degrees Celcius. Subjects with a history of pathological scar formation (keloid, hypertrophic).Any other reason that the Investigator considered made the subject unsuitable to participate.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Difference in NRS score on normal skin between a single stimulation and the highest NRS score within a series of 10 consecutive stimulations (magnitude of TS = peak pain – first pain)Presence of allodynia as measured by cotton swab (NRS score)Area of secondary allodynia measured by von Frey stimulation (mm2)Difference in duration of induction of segmental sensitization on leg and volar forearm (min)Difference in area of induction of segmental sensitization on leg and volar forearm (mm2)Difference in NRS score on HFS-sensitized skin between a single stimulation and the highest NRS score within a series of 10 consecutive stimulations (magnitude of TS = peak pain – first pain)Primary hyperalgesia measured by von Frey stimulation (NRS score)Area of secondary allodynia measured by von Frey stimulation (mm2) Baseline pain measurements:Pressure Pain: Pain Detection Threshold (PDT) (kPa)Pain Tolerance Threshold (PTT) (kPa)Heat pain: PDT (ºC)Electrical ramp: PDT (mA) Pinprick test: Force needed to evoke PDT (mN)HFS induced secondary allodynia and temporal summation:Intensity of allodynia (cotton swab) on HFS-treated skin (NRS score)Allodynia (von Frey) on HFS-treated skin (mm2)Difference in NRS score between a single stimulation and the peak NRS score within a series of 10 consecutive stimulations for pinprick, electrical, heat and pressure stimulation on normal skin and HFS-treated skin (volar forearm and lower limbs)Skin-cut model:Primary hyperalgesia: difference in NRS after von Frey stimulationSecondary allodynia: difference in area (mm2) measured using von Frey stimulation | — |
Countries
Netherlands
Contacts
Public ContactM. Niesters
Centre for Human Drug Research
Outcome results
None listed