The effects of lacosamide, pregabalin and tapentadol on pain processing

INTERVENTION: Trade Name: Vimpat 100 mg film coated tablets Product Name: lacosamide Pharmaceutical Form: Tablet INN or Proposed INN: LACOSAMIDE CAS Number: 175481‐36‐4 Other descriptive name: Lacosamide Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 100‐ Pharmaceutical form of the placebo: Capsule, hard Route of administration of the placebo: Oral use Trade Name: Lyrica 75 mg hard capsules Product Name: Pregabalin Pharmaceutical Form: Capsule INN or Proposed INN: pregabalin CAS Number: 148553‐50‐8 Other descriptive name: PREGABALIN Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 75‐ Pharmaceutical form of the placebo: Capsule, hard Route of administration of the placebo: Oral use Trade Name: Palexia 50 mg film‐coated tablets Product Name: Tapentadol Pharmaceutical Form: Tablet INN or Proposed INN: Tapendadol hydrocloride CAS Number: 175591‐09‐0 Other descriptive name: TAPENTADOL HYDROCHLORIDE Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 50‐ Pharmaceutical form of the placebo: Capsule, hard Route of administration of the placebo: Oral use CONDITION: Healthy volunteers (intended indication: pain) ; MedDRA version: 20.0 Level: PT Classification code 10033371 Term: Pain System Organ Class: 10018065 ‐ General disorders and administration site conditions Therapeutic area: Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] ‐ Anesthesia and Analgesia [E03] SECONDARY OUTCOME: ; Timepoint(s) of evaluation of this end point: ‐1 hour post‐drug administration ; ‐changes from baseline within period; Secondary end point(s): Key secondary endpoints are defined like the two primary endpoints. However, here the defined time point is at the first imaging session, approx. 1h post dose. Other secondary endpoints are the changes from baseline (within period) in pin‐prick ratings reported by the subjects when stimulating the hyperalgesic area of skin and the primary endpoints (i.e. evoked neural activity response in the posterior insula, and the functional connectivity between the thalamus and the secondary somato‐sensory cortex in a centrally sensitized state, as measured by using pin‐prick stimulus‐evoked and resting BOLD signal) but for the comparison between tapentadol and placebo and between lacosamide and placebo. INCLUSION CRITERIA: Provision of signed and dated informed consent form Stated willingness to comply with all study procedures and regimens and availability for the duration of the study Caucasian male or female subjects, aged 18 years to 45 years Body mass index >18 kg/m2 and < 30 kg/m2 with a minimum body weight of 45.0 kg and a maximum of 100kg (for men and women) Ability to take oral medication For female subjects of childbearing potential: use of highly effective contraception with a low failure PRIMARY OUTCOME: ; Main Objective: 1. To test if the punctate evoked BOLD response in the posterior insula at 3 hours post‐drug administration differs in pregabalin period as compared to the placebo period, at the sensitized leg.; 2. To test if the resting state connectivity between SII and thalamus at 3 hours post‐drug administration in the presence of sensitization differs in the pregabalin period as compared to the placebo period.; ; Secondary Objective: 1. To test if the punctate evoked BOLD response in the posterior insula at 1 hour post‐drug administration differs in at least one analgesic treatment period as compared to the placebo period, at the sensitized leg.; 2. To test if the resting state connectivity between SII and thalamus at 1 hour post‐drug administration in the presence of sensitization differs in at least one analgesic treatment session as compared to the placebo session.; Primary end point(s): The primary endpoints are the evoked neural activity response in the posterior insula (first primary endpoint), and the functional connectivity between the thalamus and the secondary somato‐sensory cortex (SII, second primary endpoint) in a centrally sensitized state, as measured by using BOLD signal at the second imaging time point (approx. 3h post dose). Here we use 2 functional neuroimaging signals using the BOLD signal. First one is the BOLD signal evoked by the pin‐prick stimulus applied to the sensitized skin. The second is the BOLD signal obtained when the subjects are awake but resting. This resting BOLD signal will be used for assessing the functional connectivity between brain regions. The main outcome of interest is the comparison between pregabalin and placebo. Timepoint(s) of evaluation of this end point: 3 hour post‐drug administration Subjects must be in good health as determined by the medical history, physical and laboratory examinations and must not show any clinically significant deviations from reference ranges as determined by 12‐lead electrocardiogram (ECG), vital signs (blood pressure, pulse rate and respiratory rate) and laboratory parameters (renal and hepatic function)