E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
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 |
•To assess the efficacy of SB-705498 in treating moderate-severe migraine headache |
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E.2.2 | Secondary objectives of the trial |
•To investigate the safety and tolerability of single doses of 400mg and 800mg SB-705498 during a migraine attack •To investigate the pharmacokinetics of SB-705498 during a migraine attack •To explore the PK / PD relationship for SB-705498 in a migraine attack
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Female or male subjects aged 18 to 65. Women may be of child bearing potential or of non-child bearing potential. Women of child bearing potential must use an effective method of contraception (see below). Females of non-child bearing potential are defined as: • Post-menopausal females, being amenorrhoeic for at least 2 years with an appropriate clinical profile, e.g., age appropriate, history of vasomotor symptoms. However, if indicated this should be confirmed by oestradiol and FSH levels consistent with menopause (according to local laboratory ranges). • Pre-menopausal females with a documented hysterectomy (medical report verification) and/or bilateral oophorectomy. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment. 2. Subjects who are otherwise healthy suffering from moderate to severe migraine headache with or without aura as diagnosed according to ICHD criteria 1.1 and 1.2.1.[International Committee on the Classification of Headache Disorders, 2004] [Appendix 4]. Healthy subjects are defined as individuals who are free from clinically significant illness or disease as determined by their medical history (including family), physical examination, laboratory studies, and other tests 3. Subjects suffering 1 to 6 migraine attacks per month for at least the last 3 months. 4. Subject has had at least a 1 year history of migraine and the age of onset was prior to 50 years. 5. Subjects should have at least 48 h free of headache between migraine attacks. 6. During the attack to be treated with SB-705498 / placebo: • Patients should not have taken any treatment for their migraine prior to study medication. • The patient should not receive study medication unless their headache is of moderate to severe pain intensity. • The headache should not be treated unless, the patient would expect to continue experiencing a moderate/severe headache for 2 hours. 7. Pre-study screening and baseline ECG, which, in the opinion of the Principal Investigator has no abnormalities that will compromise safety in this study. 8. Clinical laboratory tests at screening showing no clinically significant abnormalities in the opinion of the Principal Investigator. 9. Signed and dated written informed consent prior to admission to the study. 10. The subject is able to understand and comply with protocol requirements, instructions and protocol-stated restrictions
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E.4 | Principal exclusion criteria |
1. Subject has headache for 15 days/month or greater in any of the three months (90 days) preceding the screening visit. 2. Subject has history of alcohol, substance or drug abuse within the last year. 3. Subject has taken a migraine prophylactic medication within 1 month of the screening visit. 4. Subject uses an opiate except codeine as first line acute treatment for migraine attacks. 5. Subjects who are known to be non-responders to any of the triptans, i.e. not reported any symptomatic relief following treatment with a triptan. 6. Subject has history of analgesic intake on 15 days per month for 3 months 7. Subject has history of ergotamine, triptan, opioid, or combination medication intake on 10 days per month on a regular basis for 3 months 8. Subject has taken any acute medication for migraine, including opiates, triptans, ergots, antiemetics and/or analgesics (e.g., aspirin, NSAIDs, Cox2 inhibitors) within 72 hours prior to dosing 9. Subject has uncontrolled hypertension at the Screening Visit, defined as persistent (after 3 readings) systolic blood pressure >140mmHg or diastolic blood pressure >90mmHg; measured after 5 min supine rest. 10. A history or presence of multiple cardiovascular risk factors such as, but not limited to family history, myocardial infarction, coronary artery disease, vasospastic angina, heart failure, cardiac arrhythmias or history or presence of cerebrovascular disease, including transient ischemic attack, stroke or peripheral arterial disease. 11. QTcB > 430 msec for men or > 450 msec for women on screening 12-lead ECG. 12. Participation in a trial with a new chemical entity within 3 months before the start of the study or participation in any other research trial within 30 days prior to the first dose of current study medication. 13. A history of drug or other allergy or any other reason that, in the opinion of the physician responsible, contraindicates their participation. Male subjects only: 1. An unwillingness of male subjects to abstain from sexual intercourse with pregnant or lactating women from the time of the first dose of study medication until five half-lives following administration of the last dose of study medication. 2. An unwillingness of the male subject to use a condom/spermicide in addition to having their female partner use another form of contraception such as IUD, diaphragm with spermicide, oral contraceptives, injectable progesterone, subdermal implants or a tubal ligation if the woman could become pregnant from the time of the first dose of study medication until 84 days following administration of the last dose of study medication. Female subjects of child bearing potential: 1. Female subjects who are pregnant, breast feeding, or have a positive serum pregnancy test or a positive urine pregnancy test either at screening or pre-dose on each dosing session. 2. An unwillingness of the female subject to use an appropriate form of contraception. Appropriate forms of contraception are defined as: a. Abstinence – The lifestyle of the female should be such that there is complete abstinence from intercourse from at least the commencement of their last normal period prior to the first dose of study medication and to continue until the first normal period (defined as normal for the woman, both in terms of duration and quantity of menses) after treatment or 15 days after the last dose of medication, whichever is the longest. b. One of the following methods is acceptable as the sole method of contraception if there is indisputable data that it is >99% effective otherwise it should be used with a barrier method (condom or occlusive cap {diaphragm or cervical/vault caps} used with spermicidal foam/gel/film/cream/suppository): • Established use of oral, injected or implanted hormonal methods of contraception from at least the commencement of their last normal period prior to the first dose of study medication. Subjects using hormonal contraception should use a barrier method in addition from the first dose of study medication until their next normal period following the end of the study. • Documented tubal ligation. • Documented placement of an intrauterine device (IUD) or intrauterine system (IUS). c. Male partner sterilisation (vasectomy) prior to the female subject's entry into the study and is the sole partner for that female subject. d. condom and occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/.
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E.5 End points |
E.5.1 | Primary end point(s) |
• Percentage of subjects who are pain free at 2 hrs post-dose (e.g., have moderate to severe pain at baseline and no pain at 2 hrs post-dose) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Information not present in EudraCT |
E.6.4 | Safety | Information not present in EudraCT |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Yes |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
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 | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
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 | |
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 months | 7 |