| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
Healthy subjects (intended indication: pain)
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| E.1.1.1 | Medical condition in easily understood language |
| Study in healthy subjects to examine drug effects on biomarkers in experimental pain |
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| E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Anesthesia and Analgesia [E03] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10033371 |
| E.1.2 | Term | Pain |
| E.1.2 | System Organ Class | 10018065 - General disorders and administration site conditions |
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| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
1. To test if the percentage reduction of LEP amplitude 60 minutes post-drug administration differs in the tapentadol period as compared to the placebo period, at the non-sensitized forearm.
2. To test if the percentage reduction of PEP amplitude 60 minutes post-drug administration differs in the tapentadol period as compared to the placebo period, at the sensitized forearm.
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| E.2.2 | Secondary objectives of the trial |
1. To test if the percentage reduction of LEP amplitude 60 minutes post-drug administration differs in the pregabalin and/or lacosamide periods as compared to the placebo period, at the non-sensitized forearm.
2. To test if the percentage reduction of PEP amplitude 60 minutes post-drug administration differs in the pregabalin and/or lacosamide periods as compared to the placebo period, at the sensitized forearm.
3. To test if the percentage change in magnitude of theta oscillations 60 minutes post-drug administration differs in the tapentadol, pregabalin and/or lacosamide periods as compared to the placebo period. |
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal 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
- 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).
- 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 rate defined as <1% per year for at least 1 month prior to screening and agreement to use such a method during study participation and for an additional 4 weeks after the end of study drug administration: -combined (estrogen and progestogen containing) hormonal contraception, -progestogen-only hormonal contraception associated with inhibition of ovulation, -an intra-uterine device (hormone-free), -an intra-uterine hormone releasing system (IUS). A woman of non-childbearing potential may be included if surgically sterile (i.e., after hysterectomy or bilateral oophorectomy) or post-menopausal for at least 2 years.
- Right hand dominance (assessed using the Edinburgh Handedness Inventory, and defined as a score ≥60) |
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| E.4 | Principal exclusion criteria |
- Presence of any medical devices (e.g., cardiac pacemaker), implants or protheses unless it is beyond discussion that these will not put the subject's safety during the study at risk and will not interfere with the results of the study
- Known or suspected allergic reactions / hypersensitivity to components of lacosamide/Vimpat®.
- Second- or third-degree atrioventricular (AV) block.
- Known or suspected allergic reactions / hypersensitivity to components of pregabalin/Lyrica®.
- Known or suspected allergic reactions / hypersensitivity to components of tapentadol / Palexia®.
- Known contraindication for drugs with μ-opioid agonist activity, i.e., significant respiratory depression, acute or severe bronchial asthma or hypercapnia.
- Present or suspected paralytic ileus.
- Acute intoxication with alcohol, hypnotics, centrally acting analgesics, or psychotropic drugs.
- Not willing or able to abstain from changes in physical exercise activities during the Study.
- Any chronic pain condition or recent (i.e. within the preceding 2 years) history thereof.
- Migraine (at least 1 attack in the last 24 months).
- Recurrent headache or back pain on more than 5 days/month in the last 3 months.
- Caffeine consumption of more than 8 servings of coffee, tea, or other caffeinated drinks per day. Each serving is approximately 120mg of caffeine.
- Any relevant symptom of neurological dysfunction of the motor and sensory system that may interfere with the conduct of the study.
- Clinically-evident psychiatric diseases (e.g. depression, anxiety).
- History or symptoms of central nervous system disease or peripheral nerve lesions or dysfunction with sequelae that may impact the study assessments or that may deteriorate by one dose of a drug with anti- epileptic, noradrenergic or opioid activity.
- Focused neurological examination showing signs of abnormality.
- Active internal disease or sequelae of internal disease (e.g. diabetes mellitus, liver diseases, kidney diseases, cardiovascular diseases, hypo- or hyperthyroidism, hypertension etc.).
- Diseases or conditions known to interfere with the distribution, metabolism, or excretion of drugs.
- Clinically significant disease (e.g. medical history of infection with human immunodeficiency virus (HIV) Type 1 or Type 2, hepatitis B, or hepatitis C) or condition that may affect efficacy or safety assessments, or any other reasons which, in investigator ́s opinion, may preclude the subject ́s participation in the trial.
- Not willing or able to abstain from alcohol from 48 hours prior to any study period and until the end of the study period.
- Consumption of cannabis in the last 4 weeks prior to the study.
- Evidence or history of alcohol or drug (opioids, amphetamines, benzodiazepines, cannabinoids) abuse (as defined by ICD-10 or DSM IV) including positive or missing drugs of abuse screen (urine drugs of abuse test). Consumption of more than 21 alcohol units per week for male subjects and more than 14 units per week for female subjects (1 alcohol unit = 1 beer [12 oz/355 mL] = 1 wine [5 oz/150 mL] = 1 liquor [1.5 oz/40 mL] = 0.75 oz/20 mL alcohol).
- Habitually smoking more than 10 cigarettes, 2 cigars, or 2 pipes of tobacco per day within the last 6 months before enrollment in this trial. - Known or suspected of not being willing or able to comply with the requirements of the trial protocol or the instructions.
- Inability to communicate meaningfully with the trial site staff (e.g. insufficient language skills).
- Any person with direct involvement in the trial conduct; any person under the direct supervision of the investigator or dependent on the investigator.
- Blood loss of 500 mL or more (e.g., owing to blood donation) within 3 months before enrollment in this trial.
- Pregnancy, planned pregnancy or lactation.
- Presence of dermatological conditions in the test areas of the study that would prevent the proper application of study procedures, such as electrodes for HFS, pinprick (dermatitis, psoriasis, contact eczema, local changes of the skin due to regularly playing volleyball etc.). |
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| E.5 End points |
| E.5.1 | Primary end point(s) |
The first primary endpoint is the percentage of change in amplitude of the N2-P2 complex of LEPs at time-point T+60 min post-drug administration vs. the pre-drug time-point, at the non-sensitized arm.
The second primary endpoint is the percentage of change in amplitude of the N2-P2 complex of PEPs at time-point T+60 min post-drug administration vs. the pre-drug time-point, at the sensitized arm. |
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Endpoints are evaluated 60 min before (=pre-drug time point) and 60 min after (T+60) drug administration. |
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| E.5.2 | Secondary end point(s) |
1. The percentage of change in amplitude of ongoing theta-band EEG oscillations at time-point T+60 min post-drug administration vs. the pre-drug time-point.
2. The percentage of change in the intensity of the sensation elicited by laser stimulation of the non-sensitized forearm at time-point T+60 min post-drug administration vs. the pre-drug time-point.
3. - The percentage of change in the intensity of the sensation elicited by mechanical pinprick stimulation of the sensitized forearm at time-point T+60 min post-drug administration vs. the pre-drug time-point. |
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| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Endpoints are evaluated 60 min before (=pre-drug time point) and 60 min after (T+60) drug administration. |
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| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | No |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
| The trial is meant to investigate the effects of lacosamide, pregabalin and tapentadol on biomarkers of pain processing observed by non- invasive electro-encephalography (EEG) |
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| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | Yes |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 4 |
| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 4 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 7 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 7 |
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