A clinical trial of TEV-48125 versus Placebo for the Preventive Treatment of Chronic Migraine

Phase 1

• Conditions: Chronic Migraine; MedDRA version: 19.1Level: LLTClassification code 10066636Term: Chronic migraineSystem Organ Class: 100000004852; Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

• Registration Number: EUCTR2015-004549-23-CZ
• Lead Sponsor: Teva Branded Pharmaceutical Products R&D, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2016-05-13
• Last Update Posted: 17 July 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 1020

Inclusion Criteria

a. Males or females aged 18 to 70 years, inclusive, with migraine onset at =50 years of age
b. Patient signs and dates the informed consent document
c. Patient has history of migraine (according to International Classification of Headache Disorders, 3rd revision [ICHD-3] criteria [Classification Committee of the IHS, 2013]) or clinical judgment suggests a migraine diagnosis (not better accounted for by another ICHD-3 diagnosis) for =12 months prior to screening
d. Patient fulfills the following criteria for CM in prospectively collected baseline information during the 28-day run-in period:
- headache occurring on =15 days
- on =8 days, fulfilling any of the following:
o ICHD-3 diagnostic criteria C and D for 1.1 Migraine without aura
o ICHD-3 criteria B and C for 1.2 Migraine with aura
o Probable migraine (a migraine subtype where only 1 migraine criterion is missing)
o The patient used a triptan or ergot derivative to treat established headache.
e. Not using preventive medications (ie, at least 5 half-lives have passed since last use) or using no more than 1 preventive medication for migraine or other medical conditions (eg, propranolol used for hypertension) if the dose and regimen have been stable for at least 2 months prior to beginning the 28-day run-in period.
f. Body mass index of 17.5 to 37.5 kg/m2 and a total body weight between 45 and 120 kg, inclusive
g. All patients must be of nonchild bearing potential, defined as:
- women surgically sterile by documented complete hysterectomy, bilateral oophorectomy, or bitubal ligations or confirmed to be postmenopausal (at least 1 year since last menses and follicle-stimulating hormone above 35 U/L)
- men surgically sterile by documented vasectomy
or
if of childbearing potential, patients must meet any of the following criteria:
- Patients must simultaneously use 2 forms of highly effective contraception methods with their partners during the entire study period and for 7.5 months after the last dose of study drug.
- Sexual abstinence is only considered a highly effective method if defined as refraining from heterosexual intercourse in the defined period. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the subject. Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence for the duration of a study, and withdrawal are not acceptable methods of contraception.
h. Female patients of childbearing potential must have a negative serum beta-human chorionic gonadotropin (ß-HCG) pregnancy test at screening (confirmed by urine dipstick ß-HCG pregnancy test at baseline).
i. The patient demonstrated compliance with the electronic headache diary during the run-in period by entry of headache data on a minimum of 24 out of 28 days (~85% diary compliance).
j. The patient is in good health as determined by a medical and psychiatric history, medical examination, 12-lead electrocardiogram (ECG), serum chemistry, hematology, coagulation, and urinalysis.
k. The patient must be willing and able to comply with study restrictions, to remain at the clinic for the required duration during the study period, and to return to the clinic for the follow-up evaluation, as specified in this protocol.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adul

Exclusion Criteria

a. Patient has received onabotulinumtoxinA for migraine or for any medical or cosmetic reasons requiring injections in the head, face, or neck during the 4 months before screening.
b. Patient is using medications containing opioids (including codeine) or barbiturates (including butalbital/aspirin/caffeine, butalbital/paracetamol/caffeine, or any other combination containing butalbital) on more than 4 days per month for the treatment of migraine or for any other reason.
c. Patients who have previously failed (lack of efficacy) 2 or more of the clusters of the following medications for treatment of episodic migraine (EM) or CM after adequate therapeutic trial defined as use for at least 3 months at accepted migraine therapeutic doses:
- cluster A: divalproex sodium and sodium valproate
- cluster B: flunarizine and pizotifen
- cluster C: amitriptyline, nortriptyline, venlafaxine, and duloxetine
- cluster D: atenolol, nadolol, metoprolol, propranolol, and timolol
d. Patient has used an intervention/device (eg, scheduled nerve blocks and transcranial magnetic stimulation) for migraine during the last 2 months prior to screening.
e. Patient suffers from unremitting headaches, defined as having headaches for more than 80% of the time he/she is awake, and less than 4 days without headache per month. Daily headache is acceptable if patients have headaches 80% or less of the time they are awake on most days.
f. Clinically significant hematological, cardiac, renal, endocrine, pulmonary, gastrointestinal, genitourinary, neurologic, hepatic, or ocular disease, at the discretion of the investigator
g. Evidence or medical history of clinically significant psychiatric issues, including any suicide attempt in the past, or suicidal ideation with a specific plan in the past 2 years
h. History of clinically significant cardiovascular disease or vascular ischemia (such as myocardial, neurological [eg, cerebral ischemia], peripheral extremity ischemia, or other ischemic event) or thromboembolic events (arterial or venous thrombotic or embolic events), such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis, or pulmonary embolism
i. Known infection or history of human immunodeficiency virus, tuberculosis, or chronic hepatitis B or C infection
j. Past or current history of cancer in the past 5 years, except for appropriately treated nonmelanoma skin carcinoma
k. Pregnant or nursing females
l. History of hypersensitivity reactions to injected proteins, including monoclonal antibodies
m. Participation in a clinical study of a new chemical entity or a prescription medicine within 2 months prior to study drug administration or 5 half-lives, whichever is longer
n. Any prior exposure to a monoclonal antibody targeting the CGRP pathway (AMG 334, ALD304, LY2951742, or TEV-48125)
o. Any finding in the baseline 12-lead ECG considered clinically significant in the judgment of the investigator
p. Any finding that, in the judgment of the investigator, is a clinically significant abnormality, including serum chemistry, hematology, coagulation, and urinalysis test values (abnormal tests may be repeated for confirmation)
q. Hepatic enzymes (alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase) >1.5× the upper limit of the normal range (ULN) after confirmation in a repeat test or suspected hepatocellular damage that fulfills criteria for Hy’s law at screening
r. Serum creati

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified