| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
Acute migraine
Migraña Aguda |
|
| 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 a single dose of BGG492 vs. placebo in patients with acute migraine using the Migraine Patient Diary
?To evaluate the safety and tolerability of single oral doses of 250 mg BGG492 in migraine patients |
|
| E.2.2 | Secondary objectives of the trial |
?To evaluate the improvement in pain score, sustained response rate, pain-free rate, and sustained pain-free rate using the Migraine Patient Diary
?To determine the pharmacokinetic profile of BGG492 in patients with acute migraine and to explore the PK/PD relationship |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1.Healthy male and female subjects age 18 to 60 years of age included, and in good health as determined by past medical history, physical examination, vital signs, electrocardiogram, and laboratory tests at screening.
2.Patients must have a diagnosis of migraine and have experienced episodes of migraine, with or without aura (International Headache Society categories 1.1 and 1.2) for at least one year prior to study entry, and should experience moderate or severe migraine.
3.Patients are required to be able to distinguish migraine from other types of headache.
4.Patients must have more than 4 but not more than 15 migraine episodes per month for each of the six months prior to the study.
5.Patients must have used triptans in their past medical history.
6.Patients must have had migraine onset before 50 years of age.
7.At Screening, and Baseline, vital signs (systolic and diastolic blood pressure and pulse rate) will be assessed in the sitting position after the subject has rested for at least three (3) minutes, and again when required after three (3) minutes in the standing position. Vital signs should not have a clinically significant deviation from acceptable limits. Investigators can be guided by the following ranges:
oral body temperature between 35.0-37.5 °C
systolic blood pressure, 90-140 mm Hg
diastolic blood pressure, 50-90 mm Hg
pulse rate, 40 - 90 bpm
When blood pressure and pulse will be taken again after 3 minutes standing, there shall be no more than a 20 mm Hg drop in systolic or 10 mm Hg drop in diastolic blood pressure and increase in heart rate (>20 bpm) associated with clinical manifestation of postural hypotension.
All blood pressure measurements at other time-points should be assessed with the subject seated, unless stated otherwise in the protocol design, and utilizing the same arm for each determination.
8.Female subjects of childbearing potential must be using two acceptable methods of contraception, (e.g., intra-uterine device plus condom, diaphragm plus condom, etc.), from the time of screening and for the duration of the study, through study completion and for 30 days following study completion. Use of the oral contraceptive pill is permitted.
Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
Postmenopausal females must have had no regular menstrual bleeding for at least one (1) year prior to initial dosing. Menopause will be confirmed by a plasma FSH level of >40 IU/L at screening.
Female subjects who report surgical sterilization must have had the procedure at least six (6) months prior to initial dosing. Surgical sterilization procedures should be supported with clinical documentation made available to the sponsor and noted in the Relevant Medical History / Current Medical Conditions section of the CRF.
All female subjects must have negative pregnancy test results at screening and at each baseline.
If female subjects have male partners who have undergone vasectomy, the vasectomy must have occurred more than six (6) months prior to first dosing.
9.Male subjects must be using a two acceptable methods of contraception , (e.g., spermicidal gel plus condom) for the entire duration of the study, up to the Study Completion visit, and refrain from fathering a child in the three (3) months following the last study drug administration.
Periodic abstinence and withdrawal are not acceptable methods of contraception.
10.Subjects must weigh at least 50 kg to participate in the study, and must have a body mass index (BMI) within the range of 18 to 32 kg/m2. See Appendix 3 of this protocol for BMI ranges.
11.Able to communicate well with the investigator, to understand and comply with the requirements of the study. Understand and sign the written informed consent. |
|
| E.4 | Principal exclusion criteria |
1.Diagnosis of basilar, ophthalmoplegic or hemiplegic migraine.
2.Experience of non-migraine headaches on more than 6 days per month in the past 6 months.
3.Patients having taken any treatment for the migraine attack prior to arrival at the clinic for study drug administration.
4.Patients receiving regular treatment during the four (4) weeks preceding the study with psychoactive drugs (e.g. hypnotics, benzodiazepines, neuroleptics, antidepressants).
5.Patients using (or having used within four (4) weeks before initial dosing) migraine prophylactic treatments that interact with PGP (P-glycoprotein), e.g., Amitriptylin and Metoprolol.
6.Patients using (or having used within one (1) week before initial dosing) beta blockers or calcium channel blockers or any other prophylactic therapy for migraine.
7.Patients using (or having used within four (4) weeks before initial dosing) medications that are potent inhibitors or inducers of CYP3A4 or interacting with PGP
8.Patients using (or having used within two (2) weeks before initial dosing) medications to improve intestinal motility that are PGP inhibitors
9.Patients using (or having used within one (1) week before initial dosing drugs that are contra-indicated for sumatriptan, such as ergotamine-containing or ergot-type medications; MAO-A inhibitors and SSRIs
10.Any psychiatric condition (e.g., depression, schizophrenia) documented by past medical history which may put the patient at risk or interfere with efficacy assessments.
11.History or symptoms of ischemic heart disease or other vascular disease, angina pectoris, Wolff-Parkinson?White syndrome or other cardiac accessory conduction pathways or dysrhythmias, uncontrolled hypertension.
12.Smokers (use of tobacco products in the previous 3 months).
13.Use of any prescription drugs, herbal supplements, within four (4) weeks prior to initial dosing, and/or over-the-counter (OTC) medication, dietary supplements (vitamins included) within two (2) weeks prior to initial dosing. If needed, (i.e. an incidental and limited need) paracetamol is acceptable, but must be documented
14.Participation in any clinical investigation within four (4) weeks prior to initial dosing or longer if required by local regulations
.
15. Donation or loss of 400 ml or more of blood within eight (8) weeks prior to initial dosing, or longer if required by local regulation. Hemoglobin levels below 12.0 g/dl at screening.
16.Significant illness within two (2) weeks prior to initial dosing.
17.A past medical history of clinically significant ECG abnormalities.
18.Recent (within the last three [3] years) and/or recurrent history of autonomic dysfunction (e.g., recurrent episodes of fainting, palpitations, etc).
19.Recent (within the last three [3] years) and/or recurrent history of acute or chronic bronchospastic disease (including asthma and chronic obstructive pulmonary disease, treated or not treated).
20.History of multiple and recurring allergies or allergy to the investigational compound/compound class being used in this study.
21.Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of drugs, or which may jeopardize the subject in case of participation in the study.
22.Total WBC count which falls outside the range of 4500?11,000/µl, or platelets <100,000/µl at screening.
23.History of immunodeficiency diseases, including a positive HIV (ELISA and Western blot) test result.
24.A positive Hepatitis B surface antigen (HBsAg) or Hepatitis C test result.
25.History of drug or alcohol abuse within the 12 months prior to dosing, or evidence of such abuse as indicated by the laboratory assays conducted during the screening.
26. A hypersensitivity to sulfonamides.
27. History of stroke or TIA.
28. History of seizures.
29. History or presence of hereditary galactose intolerance, lactase deficiency or glucose-galactose malabsorption. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Efficacy assessments
Migraine Patient Diary: Day 1: pre-dose, 15, 30, 45, 60 and 90 min and 2, 3, 4 and 24 h after medication.
Safety and tolerability assessments
? Vital signs and body measurements
? Body height: Screening
? Body weight: Screening, Day 1, Study completion
? Body temperature: Screening, Day 1, Study completion
? Blood pressure, pulse rate: Screening, Day 1, Study completion
(Note that all measurements are sitting and after 3 minutes standing)
? ECG evaluation: Screening, Day 1, Study completion
? Hematology; Blood chemistry; Urinalysis: Screening, Day 1, Study completion
? Adverse events: from time of first administration of study drug until Study Completion. Adverse events occurring before starting study treatment but after signing the informed consent form are recorded on the Medical History/Current Medical Conditions Case Report Form.
? Serious adverse events: from time of consent until 4 weeks after Study Completion
? Concomitant medications/Significant non-drug therapies: Refer to entry criteria (Section 5.1) and Concomitant medication (Section 6.6.5) for details of recording requirements for allowed and restricted medications during the study. |
|
| 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 | Yes |
| 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 | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| 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) | 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) | Yes |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| 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.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 8 |
| 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 | Information not present in EudraCT |
| 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
| |
| 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 | 5 |
| E.8.9.1 | In the Member State concerned days | 0 |
| 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 | 5 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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