Episodic cluster headache headache
Conditions
Interventions
Sponsors
Eli Lilly
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: 1. Male and female outpatients 18 to 65 years of age inclusive prior to signing informed consent. 2. At Visit 1, patients must have a history of episodic cluster headache and distinguished from chronic cluster headache as defined by IHS ICHD-3 beta (ICHD-3 2013). 3. At Visit 1, have a prior history of a cluster period lasting 6 weeks or greater. 4. At Visit 1, for patients currently in an active cluster period: a. In opinion of investigator, would be expected to continue in the current period for at least another 6 weeks based on previous cluster period history. b. They are not taking any excluded medications that require washout (see Criteria #9) Note: patients not meeting criteria a and b must be a screen fail, but they may be considered for re-screening 5. Not to be shared with potential patients: During SP II, have a baseline weekly cluster headache attack frequency (based on ePRO vendor eligibility report) preceding Visit 3 of: a. minimum of 1 cluster headache attack every other day and at least 4 total attacks b. maximum of 8 cluster headache attacks per day. Note: a patient with 2 or more consecutive days without an attack during the baseline assessment will be excluded. If a patient fails eligibility due to the occurrence of >8 cluster headache attacks per day, the patient may be considered for rescreen during their current cluster headache period, if, in the opinion of the investigator, the patient would be expected to continue in the current period for at least another 6 weeks based on previous cluster period history. If the patient is not expected to continue in the current period for another 6 weeks, the patient may be considered for rescreen during their next cluster headache period. 6. At Visit 1, are able to distinguish cluster headache attacks from other headaches (i.e. tension-type headaches, migraine). 7. Investigator judges the patient as reliable to follow all study procedures, keep all study visits, and be compliant with study requirements. 8. Women of child-bearing potential may participate in the study. a. Women of child-bearing potential must test negative for pregnancy (based on a serum pregnancy test) at the time of enrollment and must agree to use a reliable method of birth control during the study and for 5 months following the last dose of investigational product. b. Male patients agree to use a reliable method of birth control during the study and for 5 months following last dose of investigational product. c. Women not of child-bearing potential are those who are infertile due to surgical sterilization (at least 6 weeks after surgical bilateral oophorectomy with or without hysterectomy or at least 6 weeks after tubal ligation) confirmed by medical history, or menopause. 9. Have not taken any of the following excluded medications or other treatments for cluster headache within the time frame noted: a. use within 14 days prior to SP II of any of the following: dihydroergotamine or ergot derivatives; gabapentin; lithium; melatonin; methergine; topiramate; valproate; verapamil, opioids b. use within 30 days prior to SP II of any of the following: systemic or injected corticosteroids; occipital nerve block; any ot her cranial or extracranial nerve block; any neurostimulation treatment. Note: Patients are allowed to use only the following for acute/abortive treatment for their cluster headache attacks: high-flow oxygen; or
Exclusion criteria
Exclusion criteria: 13. Current enrollment in, or discontinuation within the last 30 days prior to Visit 1 from, a clinical trial involving any investigational drug or device, or concurrent enrollment in any other type of medical research judged not to be scientifically or medically compatible with this study. 14. Current use or any prior exposure to any CGRP antibody (including LY2951742), any antibody to the CGRP receptor, or antibody to nerve growth factor (NGF) including past participation in a clinical trial investigating CGRP, CGRP receptor, or NGF antibodies. 15. Patients who are taking other therapeutic antibodies or are expected to take during the course of the study (for example, adalimumab, infliximab, trastuzumab, bevacizumab, etc.). Prior use of other therapeutic antibodies is allowed if an adequate wash-out has occurred (>=5 half-lives) prior to SP II. 16. Any of the following headache-related or pain-related conditions are exclusionary* a. Current diagnosis of Medication Overuse Headache as defined by ICHD-3 beta within 3 months prior to Visit 3. Note: daily triptan use for daily cluster headache attacks is allowed provided it is not resulting in an MOH of some other headache type. b. Lifetime history of migraine variants that could implicate or could be confused with ischemia; specifically, hemiplegic (sporadic or familial) migraine, ophthalmoplegic migraine, and basilar-type migraine defined by ICHD-3 beta. c. Are taking indomethacin and/or are suspected of having another distinct trigeminal autonomic cephalalgia such as hemicrania continua, paroxysmal hemicrania, or shortlasting unilateral neuralgiform headache attacks (SUNCT or SUNA). d. Have other significant pain problem that might confound the study assessments in the opinion of the investigator. 17. Patients who have taken botulinum toxin type A or B, that was administered in the head or neck area, within 4 months of SP II for treatment of cluster headache or other disorders, or for cosmetic use. 18. Any (lifetime) history of deep brain stimulation. 19. Evidence of significant active or unstable psychiatric disease by medical history, such as bipolar disorder, schizophrenia, personality disorders, or other serious mood or anxiety disorders. Note: Patients with major depressive disorder or generalized anxiety disorder, whose disease state is considered stable and expected to remain stable throughout the course of the study, in the opinion of the investigator, may be considered for inclusion if they are not on excluded medication(s). 20. Are considered by the investigator to be at significant risk for suicide. 21. Women who are pregnant or nursing. 22. Any of the following cardiovascular-related conditions are exclusionary: a. Prior to Visit 3 (randomization), have ECGs showing acute abnormalities of: i. evidence of delayed ventricular repolarization including but not limited to a corrected QT (Bazett*s QT interval [QTcB]) interval >470 msec for women an >450 for men, and/or ii. ii. evidence of atrioventricular (AV) depolarization of PR>220, or conduction delay of QRS>120, and/or iii. iii. evidence of ischemia or any of the qualitative findings indicative of ST or J-point elevation, excluding those findings consistent with early repolarization (nonischemic). b. History of myocardial infarction (MI), unstable angina (UA), percutaneous coronary intervention, coronary artery bypass graft, or deep ve
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary endpoint will be mean change in weekly cluster headache attack frequency from baseline to Week 3 with LY2951742 compared with placebo. | — |
Secondary
| Measure | Time frame |
|---|---|
| Gated objective: Response is defined as a reduction from baseline of 50% or greater in the weekly cluster headache attack frequency. Efficacy: o The proportion of patients with a 50% or greater reduction in the weekly number of cluster headache attacks from baseline for each weekly interval through Week 8 o The proportion of patients with a 30% or greater reduction in the weekly number of cluster headache attacks from baseline for each weekly interval through Week 8 o Mean change in the weekly cluster headache attack frequency from baseline for each weekly interval through Week 8 o Proportion of patients reporting a score of 1 (*very much better*) or 2 (*much better*) on the Patient Global Impression of Improvement (PGI-I) at Week 4 and Week 8. Safety and tolerability: o spontaneously reported treatment-emergent adverse events (TEAEs) o serious adverse events (SAEs) o discontinuation rates o suicidal ideation and behaviors assessed by solicited questioning using the Columbia-Suicide Severity Rating Scale (C-SSRS). Pharmacokinetics/Pharmacodynamics (PK/PD): o The PK of LY2951742 will be evaluated based on serum levels of LY2951742 following administration of LY2951742 and the pharmacodynamics (PD) of LY2951742 will be evaluated based on plasma concentrations of CGRP prior to and following LY2951742 administration | — |
Countries
Belgium, Canada, Denmark, Finland, France, Germany, Greece, Italy, Netherlands, Spain, United Kingdom, United States of America
Outcome results
None listed