E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10027599 |
E.1.2 | Term | Migraine |
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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 |
1. To evaluate the efficacy of MK-0974 co-administered with ibuprofen or acetaminophen/paracetamol compared to MK-0974 alone in the treatment of acute migraine, as measured by pain freedom at 2 hours post dose. 2. To evaluate the efficacy of MK-0974 co-administered with ibuprofen or acetaminophen/paracetamol compared to placebo in the treatment of acute migraine, as measured by pain freedom at 2 hours post dose. 3. To evaluate the safety and tolerability of MK-0974 co-administered with ibuprofen or acetaminophen/paracetamol in the treatment of acute migraine.
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E.2.2 | Secondary objectives of the trial |
1. To evaluate the efficacy of MK-0974 compared to placebo in the treatment of acute migraine, as measured by pain freedom at 2 hours post dose. 2. To evaluate the efficacy of MK-0974 co-administered with ibuprofen or acetaminophen/paracetamol compared to MK-0974 alone in the treatment of acute migraine, as measured by pain relief at 2 hours post dose.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. ≥18 years of age 2. History of migraine with or without aura > 1 year 3. ≥1 and ≤8 migraine days per month in the last 2 months that typically last from 4 to 72 hours untreated. 4. Willing to stay awake for at least 2 hours after administration of study medication
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E.4 | Principal exclusion criteria |
1. > 50 years old at age of migraine onset. Difficulty distinguishing migraine from other headaches 2. Predominantly mild migraine attacks or attacks that usually resolve spontaneously in < 2 hours 3. Basilar or hemiplegic migraine headache. 4. > 15 headache-days/month or has taken medication for acute migraine or other headache on > 10 days/month in last 3 months. 5. Changed dose of prophylactic medication in last 3 months 6. Within 3 months of screening, has had myocardial infarction, unstable angina, coronary artery bypass surgery or other revascularization procedure, stroke, or transient ischemic attack. 7. Uncontrolled hypertension (> 160/100 mm Hg), uncontrolled diabetes, HIV disease, or significant pulmonary, renal, hepatic, endocrine, or other systemic disease 8. Malignancy ≤ 5 years prior to signing consent except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer or prostate cancer. 9. History of gastric or small intestinal surgery, or disease that causes malabsorption. 10. Hypersensitivity to or previous SAE in response to ibuprofen or acetaminophen. 11. Other confounding pain syndromes (i.e., condition requiring daily use of opioids), psychiatric condition such as major depression based on the criteria such as DSM-IV, dementia or significant neurological disorders other than migraine 12. Any clinically significant disease that might confound the results of the study, complicate the interpretation of the study results, interfere with the patient’s participation for the full duration of the study, or pose an additional undue risk to the patient. 13. Score ≥2 on item 9 of the PHQ-9 14. Patient has taken any of the following medications in the time frame specified: Time Frame 1 month prior to screening (and also prohibited throughout the study period)
Therapy Potent CYP3A4 inhibitors cyclosporine, itraconazole, ketoconazole,, erythromycin, clarithromycin, telithromycin, nefazodone, HIV protease inhibitors Potent CYP3A4 inducers rifampicin, rifabutin, carbamazepine, phenytoin, barbiturates, systemic glucocorticoids, nevirapine, efavirenz, pioglitazone, primidone, St. Johns wort Specific CYP3A substrates astemizole, cisapride, pimozide, terfenadine
Concomitant use of other CYP3A4 substrates is permitted with caution (e.g., theophylline, ergot derivatives) Concomitant use of other CYP3A4 and P-gp substrates is permitted, however, these medications should be administered with appropriate caution due to the potential for drug-drug interaction (e.g. quinidine, theophylline, ergot derivatives).
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Efficacy Endpoint: Pain Freedom at 2 hours post dose, with pain freedom defined as a reduction in headache severity from Grade 3/2 at baseline to Grade 1/0. Primary Safety Variables: Safety and tolerability will be assessed by review of all safety parameters, including adverse experiences, laboratory values, ECG, and vital signs.
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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 | Yes |
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 | 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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 41 |
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 | 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 | 6 |
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 | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |