A Study of Galcanezumab in Participants With Chronic Cluster Headache

Number of cluster headache attacks was recorded daily by study participants in their ePRO Diary, Baseline and 12 weeks of daily data during double-blind treatment phase will be converted into 14-calendar day intervals: the baseline 14-day interval, Weeks 1/2, 3/4, 5/6, 7/8, 9/10, and 11/12. Next, the biweekly interval results were adjusted to 7-day (weekly) interval in order to report the outcome as weekly frequency. Overall mean change from baseline is derived from mixed model repeated measures (MMRM) analysis. Least Square (LS) means were calculated using MMRM model with treatment, sex, verapamil use, pooled investigative site, week, baseline, and treatment by week as fixed effects.

Time frame: Baseline, Week 1 through Week 12

Population: All randomized participants who received at least 1 dose of study drug, and had baseline and at least one post baseline value.

Treatment emergent (TE) ADA evaluable participant is considered to be TE ADA+ if the subject has at least one post-baseline titer that is a 4-fold or greater increase in titer from baseline measurement. If baseline result is ADA Not Present, then the participant is TE ADA+ if there is at least one post-baseline result of ADA present with titer \>= 1: 20.

Time frame: Baseline, Week 1 through Week 12

Population: All randomized participants who received at least one dose of study drug and had non-missing baseline ADA result, and at least one non-missing post baseline ADA result.

PGI-I requests participants to mark the box that best describes their cluster headache condition since they started taking the medicine. The options in the displayed boxes are represented on a 7-point scale, with 1 = very much better, 2 = much better, 3 = a little better, 4 = no change, 5 = a little worse, 6 = much worse, and 7 = very much worse. Percentage of participants were derived with a generalized linear mixed model repeated measures method with treatment, sex, verapamil use, baseline cluster headache attack category, month, and treatment by month as fixed effects.

Time frame: Week 4

Population: All randomized participants who received at least one dose of study drug and had PGI-I measurement at Week 4.

PGI-I requests participants to mark the box that best describes their cluster headache condition since they started taking the medicine. The options in the displayed boxes are represented on a 7-point scale, with 1 = very much better, 2 = much better, 3 = a little better, 4 = no change, 5 = a little worse, 6 = much worse, and 7 = very much worse. Percentage of participants were derived with a generalized linear mixed model repeated measures method with treatment, sex, verapamil use, baseline cluster headache attack category, month, and treatment by month as fixed effects.

Time frame: Week 8

Population: All randomized participants who received at least one dose of study drug and had PGI-I measurement at Week 8.

PGI-I requests participants to mark the box that best describes their cluster headache condition since they started taking the medicine. The options in the displayed boxes are represented on a 7-point scale, with 1 = very much better, 2 = much better, 3 = a little better, 4 = no change, 5 = a little worse, 6 = much worse, and 7 = very much worse. Percentage of participants were derived with a generalized linear mixed model repeated measures method with treatment, sex, verapamil use, baseline cluster headache attack category, month, and treatment by month as fixed effects.

Time frame: Week 12

Population: All randomized participants who received at least one dose of study drug and had PGI-I measurement at week 12.

A 30% responder is any participant who has a ≥30% reduction from baseline in the weekly number of cluster headache attacks in a 14-day interval. Weeks 1/2, 3/4, 5/6, 7/8, 9/10, and 11/12. Mean percentage of participants is derived from the average of weeks 1/2 to weeks 11/12 from generalized linear mixed model repeated measures method with treatment, sex, verapamil use, week, treatment by week, and baseline as fixed effects. .

Time frame: Baseline, Week 1 through Week 12

Population: All randomized participants who received at least 1 dose of study drug, and had baseline and at least 1 post baseline value.

A 50% responder is any participant who has a ≥50% reduction from baseline in the weekly number of cluster headache attacks in a 14-day interval: Weeks 1/2, Weeks 3/4, Weeks 5/6, Weeks 7/8, Weeks 9/10, and Weeks 11/12. Mean percentage of participants is derived from the average of weeks 1/2 to weeks 11/12 from generalized linear mixed model repeated measures method with treatment, sex, verapamil use, week, treatment by week, and baseline as fixed effects.

Time frame: Baseline, Week 1 through Week 12

Population: All randomized participants who received at least 1 dose of study drug, and had baseline and at least 1 post baseline value.

Sustained Response is defined as a 50% or greater reduction in the weekly cluster attack frequency from baseline to Weeks 3/4 and maintained at Weeks 5/6, Weeks 7/8, Weeks 9/10, and Weeks 11/12. Percentage of participants with a sustained response was analyzed using Koch's nonparametric randomization-based analysis of covariance method. This method adjusted for pooled investigative site by including it as a stratification variable. It also adjusted for sex, verapamil use and baseline value.

Time frame: Baseline, Week 3 through Week 12

Population: All randomized participants who received at least 1 dose of study drug, had a baseline, and at least one post baseline value.

C-SSRS captures the occurrence, severity, and frequency of suicide-related thoughts and behaviors during the assessment period. The scale includes suggested questions to solicit the type of information needed to determine if a suicide-related thought or behavior occurred. Some questions are binary responses (yes/no) and some are on a scale of 1 (low severity) to 5 (high severity). Suicidal behavior: a yes answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide.

Time frame: Week 1 through Week 12

Population: All randomized participants who received at least one dose of study drug and had at least one post baseline C-SSRS assessment.

C-SSRS captures the occurrence, severity, and frequency of suicide-related thoughts and behaviors during the assessment period. The scale includes suggested questions to solicit the type of information needed to determine if a suicide-related thought or behavior occurred. Some questions are binary responses (yes/no) and some are on a scale of 1 (low severity) to 5 (high severity). Suicidal ideation: a yes answer to any of 5 suicidal ideation questions: wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with any methods without intent to act, active suicidal ideation with some intent to act without specific plan, active suicidal ideation with specific plan and intent.

Time frame: Week 1 through Week 12

Population: All randomized participants who received at least one dose of study drug and had at least one post baseline C-SSRS assessment.

Pharmacokinetics (PK): Serum Concentration of Galcanezumab

Time frame: Week 2

Population: All randomized participants who received at least 1 dose of study drug and had evaluable galcanezumab PK samples at Week 2.

Pharmacokinetics (PK): Serum Concentration of Galcanezumab

Time frame: Week 4

Population: All randomized participants who received at least 1 dose of study drug and had evaluable galcanezumab PK samples at Week 4.

Pharmacokinetics (PK): Serum Concentration of Galcanezumab

Time frame: Week 8

Population: All randomized participants who received at least 1 dose of study drug and had evaluable galcanezumab PK samples at Week 8.

Pharmacokinetics (PK): Serum Concentration of Galcanezumab

Time frame: Week 12

Population: All randomized participants who received at least 1 dose of study drug and had evaluable galcanezumab PK samples at Week 12.