| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Acute treatment of migraine, with or without aura, in children and adolescents, ages 6 to 17 years, who do not have a satisfactory response to prior treatment with nonsteroidal anti-inflammatory drugs (NSAIDS) or N-acetyl-p-aminophenol (APAP). |
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| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 12.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10066635 |
| E.1.2 | Term | Acute 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 rizatriptan compared to placebo in the treatment of acute migraine as measured by pain freedom at 2 hours in pediatric migraineurs between 12 and 17 years of age who have not, historically, achieved satisfactory response to treatment with NSAIDS or APAP. 2. To evaluate the safety and tolerability of rizatriptan in pediatric migraineurs between 12 and 17 years of age who have not, historically, achieved a satisfactory response to treatment with NSAIDS or APAP. |
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| E.2.2 | Secondary objectives of the trial |
| 1. To evaluate the efficacy of rizatriptan compared to placebo in the treatment of acute migraine as measured by pain relief at 2 hours in pediatric migraineurs between 12 and 17 years of age who have not, historically, achieved a satisfactory response to treatment with NSAIDS or APAP. 2. To evaluate the efficacy of rizatriptan compared to placebo in the treatment of acute migraine as measured by pain freedom at 2 hours in pediatric migraineurs between 6 and 17 years of age who have not, historically, achieved a satisfactory response to treatment with NSAIDS or APAP. 3. To evaluate the efficacy of rizatriptan compared to placebo in the treatment of acute migraine as measured by pain relief at 2 hours in pediatric migraineurs between 6 and 17 years of age who have not, historically, achieved a satisfactory response to treatment with NSAIDS or APAP. |
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
| 1. Patient is between 6 and 17 years of age inclusive at screening Visit 1. 2. Patient weighs ≥ 20 kg (44 pounds). 3. Patient has a history of migraine as defined by International Headache Society migraine definitions and meets the following criteria: a. Unilateral or bilateral migraine headache, with or without aura; b. History of migraine attacks for more than 6 months; c. Reports ≥ 1 to ≤ 8 moderate or severe migraine attacks per month in the 2 months prior to screening Visit 1. This also includes attacks which were treated early, while pain was mild, but which, in the patient’s judgment, would have progressed to moderate or severe if untreated. d. Duration of a typical untreated migraine attack (excluding sleep) is ≥ 3 hours. 4. Patient has had a history of migraine with or without aura for more than 6 months 5. Patient is either: a. of reproductive potential and agrees to maintain true abstinence* or use (or have their partner use) one of the listed highly effective methods of birth control within the projected duration of the study: hormonal contraceptives, intrauterine device (IUD), condoms, diaphragm, vasectomy. The use of barrier contraceptive (condom or diaphragm) should always be supplemented with the use of a spermicide. OR b. not of reproductive potential. For the purposes of this protocol, the following definitions apply: - A female patient who is not of reproductive potential is defined as: one who 1) has not reached menarche or 2) is 6 weeks post surgical bilateral oophorectomy, hysterectomy, or bilateral tubal ligation. - A male patient who is not of reproductive potential is defined as: one who has undergone a successful vasectomy. A successful vasectomy is defined as: 1) microscopic documentation of azoospermia, or 2) a vasectomy more than 2 years ago with no resultant pregnancy despite sexual activity post vasectomy. 6. Patient is willing to stay awake for at least 2 hours after administration of the first dose of study medication. 7. Patient has not experienced satisfactory relief from migraine pain with NSAIDs or APAP treatment, in the opinion of the investigator. 8. Patient is able to complete the migraine diary and is cooperative with completing the prestudy assessments. Patients who require help to read should be assisted by an adult; however, the patient will provide the actual written responses to the pain scale questions in the migraine diary. 9. The parent or guardian and patient agree to the patient’s participation in the study as indicated by parental/guardian signature on the consent form and patient assent (in accordance with local requirements). 10. For patients taking migraine prophylactic medication, treatment regimen is stable and has been taken for at least 3 months prior to Visit 1. * If abstinence is not a locally acceptable method of contraception, then another highly effective birth control method must be used. |
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| E.4 | Principal exclusion criteria |
| 1. Patient is pregnant (positive serum β-hCG test at screening) or breast-feeding, or is a female expecting to conceive within the projected duration of study participation. 2. Patient has a history of predominantly mild migraine attacks or migraines usually resolved spontaneously in less than 2 hours. 3. Patient has basilar or hemiplegic migraine headaches (For diagnostic criteria for basilar migraine, see Appendix 6.2) 4. Patient has >15 headache-days per month OR has taken medication for acute headache on more than 10 days per month in any of the 3 months prior to screening. 5. Patient has clinical, laboratory, or ECG evidence of uncontrolled hypertension, uncontrolled diabetes, HIV disease, any neoplastic disease, or other significant pulmonary, renal, hepatic, endocrine, neurological, or other systemic disease in the opinion of the investigator (e.g., epilepsy; systemic lupus erythematosus; Kawasaki disease; homozygous sickle cell anemia; recurrent syncope). 6. Patient has a history or clinical evidence of congenital heart disease suspected or confirmed; atherosclerotic disease; history of cerebrovascular pathology including stroke; Prinzmetal’s angina; cardiac arrhythmias requiring medication; or hypertension for age. 7. Patient has a history or current evidence of any clinically significant disease that according to the investigator might confound the results of the study [e.g., chronic pain syndromes (i.e., condition requiring daily use of opiates), major psychiatric diagnoses such as schizophrenia, bipolar disorder, or major depression] that 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. 8. Patient has either demonstrated hypersensitivity to or experienced a serious adverse event in response to rizatriptan. 9. Patient has demonstrated hypersensitivity to or experienced a serious adverse event in response to 3 or more pharmacologic classes of drugs (over-the-counter and prescription). 10. Patient did not experience satisfactory relief from migraine pain to prior treatment with 2 or more adequate courses of 5HT1 agonists. 11. Patient has a recent history (within the past year) or current evidence of drug or alcohol abuse or is a "recreational user" of illicit drugs. 12. Patient is currently taking monoamine oxidase inhibitors, methysergide, or propranolol, and is unable to tolerate withdrawal of these medications for the intervals required. 13. Patient is currently participating or has participated in a study with an investigational compound or device within 30 days of screening. (This includes studies using commercially available compounds or devices for investigational purposes, e.g., new indications). 14. Patient has abnormal screening laboratory values as per the guidelines listed below or other clinically significant, unexplained laboratory abnormality, according to the investigator: a. AST > 1.5 x upper limit of normal b. ALT > 1.5 x upper limit of normal c. Total bilirubin > 1.5 x upper limit of normal d. Serum creatinine > 1.5 x upper limit of normal 15. Patient is legally or mentally incapacitated. 16. Patient has undergone major surgery (in the opinion of the investigator) within 30 days of screening or has donated blood products or has had phlebotomy of > 300 ml within 8 weeks of signing informed consent, or intends to donate blood products or receive blood products within 30 days of screening and throughout the study. 17. Patient is unlikely to adhere to study procedures, keep appointments, or is planning to relocate during the study. |
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| The testing for the primary endpoint of involved patients will be conducted sequentially in a prespecified order, where Pain Freedom (PF) at 2 hours post Stage 2 dose, with pain freedom defined as a reduction in headache severity from Face 5/4/3 at Stage 2 baseline to Face 1. |
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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 | Yes |
| 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) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| 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.8.3 |
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 | 114 |
| 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 | Yes |
| 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 | 2 |
| 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 | 2 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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