E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Episodic Cluster Headache |
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E.1.1.1 | Medical condition in easily understood language |
Excruciating headaches of extreme intensity |
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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 | 15.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10059133 |
E.1.2 | Term | Cluster headache |
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 |
The primary objective of this study is to assess the safety of R-verapamil. The safety assessments include: - adverse events - clinical laboratory measurements (chemistry and hematology) - vital signs - physical examinations - ECGs (will be obtained on Day 8 prior to the single 75 mg dose of R-verapamil and at 1 hour post dose and at the end of study visit)
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E.2.2 | Secondary objectives of the trial |
The secondary objective is to evaluate the effectiveness of R-verapamil in the prevention of episodic cluster headaches |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Participants will be healthy men and women between the ages of 18 and 65 • Participants in good health as determined by medical history and medical examination including vital signs and ECG. Serum biochemistry and hematology need to be normal • Participants with a diagnosis of episodic cluster headache as defined by the International Classification of Headache Disorders (2nd edition) • Participants must have a lifetime prevalence of at least 2 prior cluster bouts • Participants must experience at least 7 attacks/week during the run-in baseline period • Participants must have a typical cluster period lasting at least 1 month. Subjects must present in active cluster period and the expected remaining duration of the cluster bout must be at least 3 weeks from Baseline Day 1 visit • Participants with other headache types are eligible provided the subject is able to differentiate these headaches from cluster headaches • Participants are using or agree to use for the duration of participation a medically acceptable form of contraception (as determined by investigator), if female of child-bearing potential • Participants have a negative urine pregnancy test prior to study entry, if female of child-bearing potential • Participants is able to understand and comply with all study requirements • Participants provides written informed consent prior to any screening procedures being conducted
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E.4 | Principal exclusion criteria |
• Women who are pregnant or lactating • Participants who, in the investigators opinion, have a history of or have evidence of a medical or psychiatric condition that would expose them to an increased risk of a significant adverse event or would interfere with the assessments of efficacy and tolerability during this trial • Participants using any drug or having any medical condition which might interact adversely with, or interfere with the action of, the study medication • Participants who are allergic to or have shown hypersensitivity to verapamil or agents similar to verapamil • Participants who abuse opioids or have a history of significant drug or alcohol abuse within the past year as determined by investigator • Participants who have participated in an investigational drug trial in the 30 days prior to the screening visit • Participants with liver or kidney disease • Participants with cardiopathology contraindicating verapamil administration (second or third grade atrioventricular block, sinoatrial block, sinus node syndrome, heart rate <50/minute, or systolic blood pressure <90 mm Hg) • Participants with previous adynamic ileus • Participants with chronic cluster headache • Use of antipsychotic, antidepressants, lithium or other prophylactic treatment less than one month prior to inclusion
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in the average daily frequency of attacks. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Change in the average daily frequency of attacks between the baseline run-in period and the end of the 2 week treatment period |
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E.5.2 | Secondary end point(s) |
- Change in the average daily frequency of attacks - Change in intensity of attacks - Change in duration of attacks - Change in consumption of abortive agents - Patient acceptability of treatment on a 0-10 scale - Change in headache severity index - Change in Hit-6 disability score - R-verapamil-responders - Placebo-responders
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- Change in intensity of attacks, duration of attacks, headache severity index, Hit-6 disability score and in consumption of abortive agents by diary between the baseline run-in period and the end of the 1 and 2 week treatment periods - Patient acceptability of treatment on a 0-10 scale at the end of the 2 week treatment period. - R-verapamil-responders at the end of the 1 and 2 week treatment periods - Placebo-responders at the end of the 1 and 2 week treatment periods
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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 | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
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 | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
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 | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 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 | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |