Pain Algesia pain
Conditions
Interventions
During the course of the study, on every one of the study days, a subject will
get, in random order:
- &Delta
9-Tetrahydrocannabinol (&Delta
9-THC, Namisol®, ECP002A/5), provided by Echo
Pharmaceuticals, \ (2 tablets of 5 mg will be administered) and matching
placebo (ECP002A/5P, oral tablets)
- Paracetamol (1 g) and matching placebo, or
Sponsors
Centre for Human Drug Research
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Healthy 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 ECG, haematology, blood chemistry, and urinalysis; 2. Female subjects are required to have an intrauterine device, a contraceptive implant or are willing to continuously use oral contraceptives (i.e. skip their menstruation) during the study period; 3. 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; 4. Able to participate and willing to give written informed consent and to comply with the study restrictions.
Exclusion criteria
Exclusion criteria: 1. Legal incapacity or inability to understand or comply with the requirements of the study; 2. Clinically significant findings as determined by medical and psychiatric history taking, physical examination, ECG and vital signs; 3. Haemodynamic status at screening: systolic <100 and >160 mmHg, diastolic <50 and >95 mmHg, heart rate <45 and >100 bpm measured on the non-dominant (non-leading/non-writing hand) arm; 4. 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, paraesthesia, neuropathy, etc.); 5. Subjects indicating pain tests intolerable at screening or achieving tolerance at >80% of maximum input intensity for any pain test for cold, pressure and electrical tests; 6. Have a urine drug screen detecting illicit drug of abuse (morphine, benzodiazepines, cocaine, amphetamine, THC, methamphetamines, MDMA) or a positive alcohol breath test at screening; 7. 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; 8. History or clinical evidence of alcoholism or drug abuse; 9. Smoking of >5 cigarettes/day or equivalent and not able to abstain from smoking cigarettes during each stay at the CHDR clinic; 10. Use of prescription medication, over-the-counter medication, or herbal supplement within 7 days of nociceptive assessments; 11. Participation in a clinical trial within 90 days of screening or more than 4 times in the previous year; 12. Loss of blood >= 500 mL within 3 months (males) or 4 months (females) before screening; 13. Known hypersensitivity to the investigational drug or comparative drug or drugs of the same class, or any of their excipients; 14. Dark skin (Fitzpatrick skin type V or VI), wide-spread acne, tattoos or scarring on back; and/or 15. Subjects of childbearing potential who are unwilling or unable to use a highly effective barrier method of contraception for the duration of the study and for 3 months after the last dose of study treatment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pharmacodynamic endpoints - Thermal Pain (Normal Skin): Pain Detection Threshold (PDT). -Thermal Pain (UVB Skin): Pain Detection Threshold (PDT). - Electrical Stair (pre-cold pressor): Pain Tolerance Threshold (PTT). - Pressure Pain: Pain Tolerance Threshold (PTT). - Cold Pressor: Pain Tolerance Threshold (PTT). - VAS Feeling high | — |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacodynamic endpoints - Electrical Stair (pre-cold pressor): Pain Detection Threshold (PDT), Area Under the Visual Analogue Scale (VAS) pain Curve (AUC), and post-test VAS. - Electrical Stair (post-cold pressor): PDT, PTT, AUC, and post-test VAS. - Conditioned Pain Modulation Response (change from electrical stair pre- and post cold pressor): PDT, PTT, AUC. - Evoked potentials: somatosensory evoked potentials (SEP) using the electrical stimulus measuring peak-to-peak (PtP) somatosensory evoked potentials (SEP) amplitude in vertex EEG, or other exploratory endpoints. - Pressure Pain: PDT, AUC, and post-test VAS. - Cold Pressor: PDT, AUC, and post-test VAS. - VAS Bond & Lader (Alertness, mood, calmness) - VAS Bowdle (internal perception, external perception, *feeling high*) - Pharmaco-EEG: power (resting eyes closed, open and during pressure pain and cold pressor). - Adverse events, laboratory safety, blood pressure, pulse rate and ECG parameters Pharmacokinetic analysis will only be performed if relevant pharmacodynamic effect is observed. The following endpoints will be determined for Δ9-THC and its active metabolites 11-OH-THC and THC-COOH; promethazine and paracetamol. They will be derived by non-compartmental analysis of the plasma concentration-time data: - The area under the plasma concentration-time curve from zero to infinity(AUC0-inf); - The maximum plasma concentration (Cmax); - The area under the plasma concentration-time curve from zero to t of the last measured concentration above the limit of quantification (AUC0-last); - The time to reach maximum plasma concentration (tmax); - The terminal disposition rate constant (*z) with the respective half-life (t*). - Other parameters, including Vz/F, CL/F, and other parameters as appropriate, as well as dose adjusted parameters, may be determined. | — |
Countries
Netherlands
Outcome results
None listed