Phase 3 Multicenter, Randomized, Double-blind, Placebo-controlled Study of BOTOX (Botulinum Toxin Type A) for the Prevention of Migraine in Subjects With Episodic Migraine
Overview
- Phase
- Phase 3
- Intervention
- Placebo
- Conditions
- Episodic Migraine
- Sponsor
- AbbVie
- Enrollment
- 775
- Locations
- 133
- Primary Endpoint
- Change From Baseline in the Frequency of Monthly Migraine Days Across Months 5 and 6
- Status
- Terminated
- Last Updated
- 4 months ago
Overview
Brief Summary
Migraine is a neurological disease characterized by moderate or severe headache, associated with nausea, vomiting, and/or sensitivity to light and sound (International Classification of Headache Disorders, 2018). Migraine can be further categorized according to the frequency of attacks as episodic migraine (EM) or chronic migraine (CM). This study will assess the effects of BOTOX in preventing migraine in adult participants with EM.
BOTOX is being developed for the prevention of migraine in adults with episodic migraine (EM). Participants will be enrolled in 3 different treatment groups. There is 1 in 3 chance that participants will be assigned to receive placebo. Approximately 777 adult participants with EM will be enrolled in approximately 125 sites across the world.
Participants will receive intramuscular injections (injected into the muscle) of BOTOX or Placebo on Day 1 and Week 12. Eligible participants will receive BOTOX on Week 24 and Week 36.
There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.
Investigators
Eligibility Criteria
Inclusion Criteria
- •History of migraine headache disorder meeting International Classification of Headache Disorders (ICHD)-3 diagnostic criteria for migraine with aura or migraine without aura for \>= 12 months.
- •Onset of migraine before 50 years of age.
- •History of 6 to 14 migraine days/month in each of the 3 months prior to Visit
- •Six to 14 migraine/probable migraine days during the 4-week screening/baseline phase.
- •Less than 15 headache days/month in each of the 3 months prior to Visit 1 and during the 4-week screening/baseline phase.
Exclusion Criteria
- •Current diagnosis of chronic migraine according to ICHD-
- •History or current diagnosis of migraine with brainstem aura, retinal migraine, complications of migraine, chronic tension-type headache, trigeminal autonomic cephalalgias, hypnic headache, hemicrania continua, or new daily persistent headache.
- •History of headache attributed to another disorder (e.g., cervical dystonia, craniotomy, head/neck trauma) with exception that medication overuse headache per ICHD-3 criteria is allowed.
- •History of inadequate response to \> 4 prophylactic treatment for migraine, 2 of which have different mechanisms of action.
- •Female who is pregnant, breastfeeding, or considering becoming pregnant during the study or within 90 days after the last dose of study drug.
Arms & Interventions
Double-Blind Phase: Placebo
Participants received placebo for BOTOX intramuscular injections in the head/neck muscles on Day 1 and Week 12.
Intervention: Placebo
Double-Blind Phase: BOTOX 155 U
Participants received intramuscular injections of BOTOX 155 U in the head/neck muscles on Day 1 and Week 12.
Intervention: BOTOX
Double-Blind Phase: BOTOX 195 U
Participants received intramuscular injections of BOTOX 195 U in the head/neck muscles on Day 1 and Week 12.
Intervention: BOTOX
Open-Label Phase: BOTOX 195 U
Eligible participants received intramuscular injections of BOTOX 195 U in the head/neck muscles on Weeks 24 and 36.
Intervention: BOTOX
Outcomes
Primary Outcomes
Change From Baseline in the Frequency of Monthly Migraine Days Across Months 5 and 6
Time Frame: Baseline, Months 5-6
The frequency of monthly migraine days across Months 5 and 6 is calculated by taking the 2-month average of monthly migraine days over Months 5 and 6. Month 5 and Month 6 are the 28-day daily diary periods ending with Days 56 and Days 84 after the second study treatment intervention day with BOTOX or placebo injections, respectively. Negative changes from Baseline indicate improvement.
Number of Participants With Treatment-Emergent Adverse Events (AEs)
Time Frame: Double-Blind Phase (Week 0-24); Open-Label Phase (Week 24-48)
An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study drug. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent adverse events/treatment-emergent serious adverse events (TEAEs/TESAEs) are defined as any event that began or worsened in severity on or after the first dose of study drug.
Secondary Outcomes
- Change From Baseline in the Frequency of Monthly Headache Days Across Months 5 and 6(Baseline, Months 5-6)
- Percentage of Participants With ≥ 50% Reduction From Baseline in the Frequency of Monthly Migraine Days Across Months 5 and 6(Baseline, Months 5-6)
- Change From Baseline in the Frequency of Monthly Acute Headache Medication Days Across Months 5 and 6(Baseline, Months 5-6)
- Change From Baseline in Migraine-Specific Quality of Life Questionnaire Version 2.1 (MSQ v2.1) Role Function - Restrictive (RFR) Domain Score At Month 6(Baseline, Month 6)
- Change From Baseline in the Activity Impairment in Migraine - Diary (AIM-D) Physical Impairment Domain Score Across Months 5 and 6(Baseline, Months 5-6)
- Change From Baseline in the Total 6-item Headache Impact Test (HIT-6) Score Across Months 5 and 6(Baseline, Months 5-6)