E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10029223 |
E.1.2 | Term | Neuralgia |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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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 |
We will examine whether ivabradine reduces the intensity of certain symptoms that are associated with nerve (neuropathic) pain. We can temporarily induce neuropathic pain in the skin of volunteers by applying a cream containing capsaicin: the chemical in chilli peppers that make it hot. This creates a warm area on the skin, and another area around it where changes in the nerves make it more sensitive. The changes in this area (known as the area of secondary hyperalgesia) can also be found in nerve pain. The changes can be measured with a technique called quantitative sensory testing. We will be particularly interested in measuring volunteers' response to heat, called the heat threshold, and whether this is altered by ivabradine. Ivabradine is a drug that is used to treat people with angina, but new evidence from experiments in animals suggests that it can profoundly reduce neuropathic pain. |
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E.2.2 | Secondary objectives of the trial |
The equipment that measures peoples' heat thresholds can also measure thresholds at which they can detect cool and warm sensations, and painful coldness. We will measure these parameters as well. We will need to map the area of sensitivity, by taking a digital photograph, and record the area over which the volunteers can feel changes in normal sensation, for example gentle brushing with cotton wool and gentle pressure. We will also ask the participants to score the pain elicited by the capsaicin by placing a cross on a 10cm scale. Generally, this is between two and three out of ten, so it might be that this study does not have sufficient power to detect a difference. What is important in this early study is to see if the ivabradine reduces the effects on the thresholds. If so, it would suggest that a larger clinical trial in patients would be worthwhile. …). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Volunteers who have given written, informed consent to participate. - Volunteers who can communicate fluently in English. |
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E.4 | Principal exclusion criteria |
- Volunteers not giving consent to participate. - Volunteers who cannot communicate fluently in English. - Volunteers with 1 arm - Volunteers who are allergic to ivabradine, capsaicin or Tegaderm. - Volunteers for whom ivabradine is contraindicated: namely sick sinus syndrome and concomitant use of CYP3A4 inhibitors such as ketoconazole, macrolide antibiotics, nefazodone and the anti-retrovirals nelfinavir and ritonavir. - Volunteers with any rash or broken skin on the forearm where capsaicin will be applied. - Volunteers with lactose intolerance. - Volunteers with a resting pulse rate of 59 beats per minute or less at screening or on the day of the study. - Volunteers who are pregnant - Volunteers who have any underlying medical condition such as migraine or epilepsy which may affect the study findings - Volunteers who smoke, take recreational drugs or consume more than the recommended allowance of alcohol units per week |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is volunteers' thresholds to heat, as as measured by quantitative sensory testing (contact heat evoked potentials, CHEPs). |
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E.5.2 | Secondary end point(s) |
The secondary endpoint is volunteers pain scores as measured by the VAS questionnaire. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
All data will be evaluated at following the last participant last visit. |
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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 | No |
E.6.7 | Pharmacodynamic | No |
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 | No |
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 | Yes |
E.8.1.4 | Double blind | No |
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 | 2 |
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 | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 1 |
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 | 0 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 20 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 20 |