A single blind, placebo controlled, multi-centre study to investigate the pharmacokinetics, safety, tolerability and pharmacodynamics of the TRPV1 antagonist SB-705498 against the pain of acute migraine
- Conditions
- acute migraine
- Registration Number
- EUCTR2005-004480-37-GB
- Lead Sponsor
- GlaxoSmithKline
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 0
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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years)
F.1.3.1 Number of subjects for this age range
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 met
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: •To assess the efficacy of SB-705498 in treating moderate-severe migraine headache ;Secondary Objective: •To investigate the safety and tolerability of single doses of 400mg and 800mg SB-705498 during a migraine attack<br>•To investigate the pharmacokinetics of SB-705498 during a migraine attack<br>•To explore the PK / PD relationship for SB-705498 in a migraine attack<br>;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)
- Secondary Outcome Measures
Name Time Method