Migraine Disorders
Conditions
Brief summary
The purpose of this study is to assess ALD403 in the prevention of migraine headache in frequent episodic migraineurs.
Interventions
DRUGALD403
DRUGPlacebo
Sponsors
Alder Biopharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of migraine at ≤ 50 years of age (ICHD-II, 2004 Section 1) * History of migraine ≥ 12 months with * ≤ 14 headache days of which at least 4 have to be migraine days (migraine days count as headache days) in each 28 day period in the 3 months prior to screening * During the 28 days following the screening visit, the subject experiences ≤ 14 headache days of which at least 4 have to be migraine days (migraine days count as headache days) as recorded in the eDiary * No use of any botulinum toxin for migraine or for any other medical/cosmetic reasons requiring injections in the head, face, or neck 4 months prior to screening and during the 28 day period prior to randomization * Headache eDiary was completed on at least 25 of the 28 days prior to randomization
Exclusion criteria
* Confounding pain syndromes, e.g. fibromyalgia, complex regional pain syndrome or any pain syndrome that requires regular analgesia * Psychiatric conditions that are uncontrolled and untreated, including conditions that are not controlled for a minimum of 6 months prior to screening * History or diagnosis of complicated migraine (ICHD- II, 2004 Section 1), chronic tension-type headache, hypnic headache, cluster headache, hemicrania continua, new daily persistent headache, migraine with brainstem aura, sporadic and familial hemiplegic migraine * Unable to differentiate migraine from other headaches * Have any clinically significant concurrent medical condition * Receipt of any monoclonal antibody treatment within 6 months of screening (within or outside a clinical trial) * Previously dosed with ALD403 or any monoclonal antibody targeting the CGRP pathway
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Monthly Migraine Days (Weeks 1-12) | Week 1-12 | Monthly migraine days are summarized in 28-day intervals, and averaged across Weeks 1-12 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 50% Migraine Responder Rate | Week 1-12 | Participants with an average reduction in migraine days of at least 50% over Weeks 1 to 12, as compared with baseline |
| Percentage of Participants With a Migraine on the Day After Dosing | 1 day | The percentage of participants with a migraine on the day after dosing, where Day 0 is treatment day and Day 1 is the day after dosing |
| 75% Headache Responder Rate | Week 1-12 | Participants with an average reduction in headache days of at least 75% over Weeks 1 to 12, as compared with baseline. |
| 50% Headache Responder Rate | Week 1-12 | Participants with an average reduction in headache days of at least 50% over Weeks 1 to 12, as compared with baseline. |
| 100% Migraine Responder Rate | Week 1-12 | Participants with a reduction in migraine days of 100% over Weeks 1 to 12, as compared with baseline |
| 100% Headache Responder Rate | Week 1-12 | Participants with a reduction in headache days of 100% over Weeks 1 to 12, as compared with baseline. |
| Change From Baseline in Acute Migraine Medication Days (Weeks 1-12) | Week 1-12 | The change in number of days with any triptan or ergotamine use as recorded in the eDiary. |
| Change From Baseline in Average Daily Migraine Prevalence to Week 4 | Baseline to Week 4 | The change in the percentage of days where a participant has a migraine from baseline to Week 4. |
| Change From Baseline to Week 12 in Percentage of Migraines With Use of Acute Medication | Week 1-12 | The percentage of migraines with acute medication usage. Participants with no migraines will be included with a rate of zero. |
| 75% Migraine Responder Rate | Week 1-12 | Participants with an average reduction in migraine days of at least 75% over Weeks 1 to 12, as compared with baseline. |
| Change From Baseline in Monthly Headache Days (Weeks 1-12) | Week 1-12 | Monthly headache days are summarized in 28-day intervals, and averaged across Weeks 1-12. |
| Percent of Headaches With Severe Intensity | Week 1-12 | Summary of percent of headaches with severe intensity over Weeks 1-12. |
| Percent of Migraines With Severe Intensity | Week 1-12 | Summary of percent of migraines with severe intensity over Week 1-12. |
| Change From Baseline in Monthly Migraine Hours (Weeks 1-12) | Week 1-12 | Migraine hours are the sum of the duration of migraines within 4 week intervals, and the average 4 week duration within 12 week intervals. |
| Change From Baseline in Monthly Headache Hours, Weeks 1-12 | Week 1-12 | Headache hours are the sum of the duration of headaches within 4 week intervals, and the average 4 week duration within 12 week intervals. |
| Change From Baseline of Short Form Health Survey (SF-36 v 2.0) Scale Scores | Baseline to Week 12 | The SF-36 is a health survey containing 36 questions consisting of eight scaled scores to measure quality of life over the past 4 weeks. All scales are on a range of 0 to 100, with 0 being the worst and 100 being the best. Scales are reported separately. Increases from baseline indicate improvement. |
| Health Related Quality of Life (EQ-5D-5L) at Week 12 | Week 12 | The EQ-5D-5L is a descriptive system of health-related quality of life states consisting of 5 dimension/questions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) each of which can take one of five responses. The responses record five levels of severity (no problems/slight problems/moderate problems/severe problems/extreme problems) within a particular EQ-5D dimension. |
| Change in Baseline of Allodynia Symptom Checklist-12 (ASC-12) Total Score | Baseline to Week 12 | The ASC-12 includes 12 questions about the frequency of various allodynia symptoms in association with headache attacks. For individuals with more than one type of headache, questions are directed to the most severe type of headache. Each item is measured in a Likert type scale option with response categories: Does not apply to me, never, rarely, less than half the time, and half the time or more. ASC items were scored as 0 (i.e., never, rarely or does not apply to me), 1 (less than half the time), and 2 (half the time or more), yielding scores that ranged from 0 to 24. If a single item is missing, it is scored as a 0. If more than one item is missing the total score will be missing. The interpretation of the total score is, 0-2: none; 3-5: mild; 6-8: moderate; greater than or equal to 9: severe. |
| Change From Baseline to Week 12 in Percentage of Headaches With Use of Acute Medication | Week 1-12 | The percentage of headaches with acute medication usage. Participants with no headaches will be included with a rate of zero. |
Countries
Georgia, United States
Participant flow
Pre-assignment details
A total of 2413 participants signed the ICF, of which 898 participants met the entry criteria and were randomized into the trial.
Participants by arm
| Arm | Count |
|---|---|
| 300 mg ALD403 Participants were randomized to receive a single 300 mg IV infusion of ALD403 on Days 0, 84 (Week 12), 168 (Week 24) and 252 (Week 36). | 224 |
| 100 mg ALD403 Participants were randomized to receive a single 100 mg IV infusion of ALD403 on Days 0, 84 (Week 12), 168 (Week 24) and 252 (Week 36). | 223 |
| 30 mg ALD403 Participants were randomized to receive a single 30 mg IV infusion of ALD403 on Days 0, 84 (Week 12), 168 (Week 24) and 252 (Week 36). | 219 |
| Placebo Participants were randomized to receive a single placebo IV infusion on Days 0, 84 (Week 12), 168 (Week 24) and 252 (Week 36). | 222 |
| Total | 888 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 3 | 2 | 1 |
| Overall Study | Lack of Efficacy | 2 | 3 | 2 | 8 |
| Overall Study | Lost to Follow-up | 22 | 16 | 12 | 17 |
| Overall Study | Other | 1 | 5 | 3 | 3 |
| Overall Study | Physician Decision | 1 | 1 | 3 | 0 |
| Overall Study | Study Burden | 10 | 16 | 12 | 22 |
| Overall Study | Withdrawal by Subject | 16 | 9 | 20 | 9 |
Baseline characteristics
| Characteristic | 300 mg ALD403 | 100 mg ALD403 | 30 mg ALD403 | Placebo | Total |
|---|---|---|---|---|---|
| Age, Continuous | 40.2 years STANDARD_DEVIATION 11.72 | 40.0 years STANDARD_DEVIATION 10.66 | 39.1 years STANDARD_DEVIATION 11.54 | 39.9 years STANDARD_DEVIATION 11.67 | 39.8 years STANDARD_DEVIATION 11.39 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 40 Participants | 42 Participants | 45 Participants | 34 Participants | 161 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 184 Participants | 181 Participants | 174 Participants | 188 Participants | 727 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Number of migraine days | 7.8 Days STANDARD_DEVIATION 2.59 | 7.5 Days STANDARD_DEVIATION 2.6 | 7.9 Days STANDARD_DEVIATION 2.7 | 7.5 Days STANDARD_DEVIATION 2.42 | 7.7 Days STANDARD_DEVIATION 2.58 |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 27 Participants | 17 Participants | 31 Participants | 30 Participants | 105 Participants |
| Race (NIH/OMB) More than one race | 5 Participants | 7 Participants | 5 Participants | 5 Participants | 22 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 2 Participants | 2 Participants | 6 Participants |
| Race (NIH/OMB) White | 187 Participants | 196 Participants | 180 Participants | 181 Participants | 744 Participants |
| Region of Enrollment Georgia | 39 Participants | 39 Participants | 25 Participants | 37 Participants | 140 Participants |
| Region of Enrollment United States | 185 Participants | 184 Participants | 194 Participants | 185 Participants | 748 Participants |
| Sex: Female, Male Female | 199 Participants | 179 Participants | 185 Participants | 186 Participants | 749 Participants |
| Sex: Female, Male Male | 25 Participants | 44 Participants | 34 Participants | 36 Participants | 139 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 224 | 0 / 223 | 0 / 219 | 0 / 222 |
| other Total, other adverse events | 44 / 224 | 44 / 223 | 44 / 219 | 41 / 222 |
| serious Total, serious adverse events | 3 / 224 | 4 / 223 | 4 / 219 | 6 / 222 |
Outcome results
Primary
Change From Baseline in Monthly Migraine Days (Weeks 1-12)
Monthly migraine days are summarized in 28-day intervals, and averaged across Weeks 1-12
Time frame: Week 1-12
Population: Full Analysis Population - all randomized participants who received investigational product or placebo
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 300 mg ALD403 | Change From Baseline in Monthly Migraine Days (Weeks 1-12) | -4.3 Migraine Days | Standard Deviation 3.42 |
| 100 mg ALD403 | Change From Baseline in Monthly Migraine Days (Weeks 1-12) | -3.9 Migraine Days | Standard Deviation 3.23 |
| 30 mg ALD403 | Change From Baseline in Monthly Migraine Days (Weeks 1-12) | -4.1 Migraine Days | Standard Deviation 3.22 |
| Placebo | Change From Baseline in Monthly Migraine Days (Weeks 1-12) | -3.1 Migraine Days | Standard Deviation 3.7 |
p-value: 0.000195% CI: [-1.68, -0.54]ANCOVA
p-value: 0.018295% CI: [-1.25, -0.12]ANCOVA
p-value: 0.004695% CI: [-1.39, -0.25]ANCOVA
Secondary
100% Headache Responder Rate
Participants with a reduction in headache days of 100% over Weeks 1 to 12, as compared with baseline.
Time frame: Week 1-12
Population: Full Analysis Population - all randomized participants who received investigational product or placebo
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 300 mg ALD403 | 100% Headache Responder Rate | 6 Participants |
| 100 mg ALD403 | 100% Headache Responder Rate | 0 Participants |
| 30 mg ALD403 | 100% Headache Responder Rate | 4 Participants |
| Placebo | 100% Headache Responder Rate | 2 Participants |
Secondary
100% Migraine Responder Rate
Participants with a reduction in migraine days of 100% over Weeks 1 to 12, as compared with baseline
Time frame: Week 1-12
Population: Full Analysis Population - all randomized participants who received investigational product or placebo
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 300 mg ALD403 | 100% Migraine Responder Rate | 9 Participants |
| 100 mg ALD403 | 100% Migraine Responder Rate | 1 Participants |
| 30 mg ALD403 | 100% Migraine Responder Rate | 4 Participants |
| Placebo | 100% Migraine Responder Rate | 4 Participants |
Secondary
50% Headache Responder Rate
Participants with an average reduction in headache days of at least 50% over Weeks 1 to 12, as compared with baseline.
Time frame: Week 1-12
Population: Full Analysis Population - all randomized participants who received investigational product or placebo
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 300 mg ALD403 | 50% Headache Responder Rate | 113 Participants |
| 100 mg ALD403 | 50% Headache Responder Rate | 98 Participants |
| 30 mg ALD403 | 50% Headache Responder Rate | 98 Participants |
| Placebo | 50% Headache Responder Rate | 74 Participants |
Secondary
50% Migraine Responder Rate
Participants with an average reduction in migraine days of at least 50% over Weeks 1 to 12, as compared with baseline
Time frame: Week 1-12
Population: Full Analysis Population - all randomized participants who received investigational product or placebo
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 300 mg ALD403 | 50% Migraine Responder Rate | 125 Participants |
| 100 mg ALD403 | 50% Migraine Responder Rate | 110 Participants |
| 30 mg ALD403 | 50% Migraine Responder Rate | 112 Participants |
| Placebo | 50% Migraine Responder Rate | 83 Participants |
p-value: 0.000195% CI: [9.8, 28]Cochran-Mantel-Haenszel
p-value: 0.008595% CI: [3.2, 21.5]Cochran-Mantel-Haenszel
p-value: 0.006495% CI: [3.7, 22]Cochran-Mantel-Haenszel
Secondary
75% Headache Responder Rate
Participants with an average reduction in headache days of at least 75% over Weeks 1 to 12, as compared with baseline.
Time frame: Week 1-12
Population: Full Analysis Population - all randomized participants who received investigational product or placebo
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 300 mg ALD403 | 75% Headache Responder Rate | 42 Participants |
| 100 mg ALD403 | 75% Headache Responder Rate | 28 Participants |
| 30 mg ALD403 | 75% Headache Responder Rate | 34 Participants |
| Placebo | 75% Headache Responder Rate | 23 Participants |
Secondary
75% Migraine Responder Rate
Participants with an average reduction in migraine days of at least 75% over Weeks 1 to 12, as compared with baseline.
Time frame: Week 1-12
Population: Full Analysis Population - all randomized participants who received investigational product or placebo
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 300 mg ALD403 | 75% Migraine Responder Rate | 66 Participants |
| 100 mg ALD403 | 75% Migraine Responder Rate | 49 Participants |
| 30 mg ALD403 | 75% Migraine Responder Rate | 55 Participants |
| Placebo | 75% Migraine Responder Rate | 36 Participants |
p-value: 0.000795% CI: [5.8, 21.2]Cochran-Mantel-Haenszel
p-value: 0.112695% CI: [-1.4, 13.3]Cochran-Mantel-Haenszel
p-value: 0.027295% CI: [1, 15.9]Cochran-Mantel-Haenszel
Secondary
75% Migraine Responder Rate
Participants with an average reduction in migraine days of at least 75% over Weeks 1 to 4, as compared with baseline.
Time frame: Week 1-4
Population: Full Analysis Population - all randomized participants who received investigational product or placebo
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 300 mg ALD403 | 75% Migraine Responder Rate | 70 Participants |
| 100 mg ALD403 | 75% Migraine Responder Rate | 68 Participants |
| 30 mg ALD403 | 75% Migraine Responder Rate | 67 Participants |
| Placebo | 75% Migraine Responder Rate | 45 Participants |
p-value: 0.006695% CI: [3.2, 19.3]Cochran-Mantel-Haenszel
p-value: 0.011295% CI: [2.4, 18.6]Cochran-Mantel-Haenszel
p-value: 0.01795% CI: [1.8, 17.8]Cochran-Mantel-Haenszel
Secondary
Change From Baseline in Acute Migraine Medication Days (Weeks 1-12)
The change in number of days with any triptan or ergotamine use as recorded in the eDiary.
Time frame: Week 1-12
Population: Full Analysis Population - all randomized participants who received investigational product or placebo
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 300 mg ALD403 | Change From Baseline in Acute Migraine Medication Days (Weeks 1-12) | -0.8 days | Standard Deviation 1.77 |
| 100 mg ALD403 | Change From Baseline in Acute Migraine Medication Days (Weeks 1-12) | -0.9 days | Standard Deviation 2 |
| 30 mg ALD403 | Change From Baseline in Acute Migraine Medication Days (Weeks 1-12) | -0.6 days | Standard Deviation 1.62 |
| Placebo | Change From Baseline in Acute Migraine Medication Days (Weeks 1-12) | -0.4 days | Standard Deviation 1.27 |
Secondary
Change From Baseline in Average Daily Migraine Prevalence to Week 4
The change in the percentage of days where a participant has a migraine from baseline to Week 4.
Time frame: Baseline to Week 4
Population: Full Analysis Population - all randomized participants who received investigational product or placebo
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 300 mg ALD403 | Change From Baseline in Average Daily Migraine Prevalence to Week 4 | -14.9 percentage of days with migraine | Standard Deviation 19.78 |
| 100 mg ALD403 | Change From Baseline in Average Daily Migraine Prevalence to Week 4 | -13.8 percentage of days with migraine | Standard Deviation 19.27 |
| 30 mg ALD403 | Change From Baseline in Average Daily Migraine Prevalence to Week 4 | -15.1 percentage of days with migraine | Standard Deviation 17.83 |
| Placebo | Change From Baseline in Average Daily Migraine Prevalence to Week 4 | -9.7 percentage of days with migraine | Standard Deviation 19.33 |
Secondary
Change From Baseline in Monthly Headache Days (Weeks 1-12)
Monthly headache days are summarized in 28-day intervals, and averaged across Weeks 1-12.
Time frame: Week 1-12
Population: Full Analysis Population - all randomized participants who received investigational product or placebo
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 300 mg ALD403 | Change From Baseline in Monthly Headache Days (Weeks 1-12) | -4.5 headache days | Standard Deviation 3.96 |
| 100 mg ALD403 | Change From Baseline in Monthly Headache Days (Weeks 1-12) | -4.0 headache days | Standard Deviation 3.3 |
| 30 mg ALD403 | Change From Baseline in Monthly Headache Days (Weeks 1-12) | -4.4 headache days | Standard Deviation 3.24 |
| Placebo | Change From Baseline in Monthly Headache Days (Weeks 1-12) | -3.3 headache days | Standard Deviation 3.51 |
Secondary
Change From Baseline in Monthly Headache Hours, Weeks 1-12
Headache hours are the sum of the duration of headaches within 4 week intervals, and the average 4 week duration within 12 week intervals.
Time frame: Week 1-12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 300 mg ALD403 | Change From Baseline in Monthly Headache Hours, Weeks 1-12 | -42.0 headache hours | Standard Deviation 56.67 |
| 100 mg ALD403 | Change From Baseline in Monthly Headache Hours, Weeks 1-12 | -34.2 headache hours | Standard Deviation 49.19 |
| 30 mg ALD403 | Change From Baseline in Monthly Headache Hours, Weeks 1-12 | -38.8 headache hours | Standard Deviation 50.45 |
| Placebo | Change From Baseline in Monthly Headache Hours, Weeks 1-12 | -24.5 headache hours | Standard Deviation 48.15 |
Secondary
Change From Baseline in Monthly Migraine Hours (Weeks 1-12)
Migraine hours are the sum of the duration of migraines within 4 week intervals, and the average 4 week duration within 12 week intervals.
Time frame: Week 1-12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 300 mg ALD403 | Change From Baseline in Monthly Migraine Hours (Weeks 1-12) | -42.9 migraine hours | Standard Deviation 49.91 |
| 100 mg ALD403 | Change From Baseline in Monthly Migraine Hours (Weeks 1-12) | -35.3 migraine hours | Standard Deviation 47.85 |
| 30 mg ALD403 | Change From Baseline in Monthly Migraine Hours (Weeks 1-12) | -37.8 migraine hours | Standard Deviation 50.17 |
| Placebo | Change From Baseline in Monthly Migraine Hours (Weeks 1-12) | -23.8 migraine hours | Standard Deviation 50.91 |
Secondary
Change From Baseline of Short Form Health Survey (SF-36 v 2.0) Scale Scores
The SF-36 is a health survey containing 36 questions consisting of eight scaled scores to measure quality of life over the past 4 weeks. All scales are on a range of 0 to 100, with 0 being the worst and 100 being the best. Scales are reported separately. Increases from baseline indicate improvement.
Time frame: Baseline to Week 12
Population: Full Analysis Population - all randomized participants who received investigational product or placebo. The Week 12 scores only include participants who completed the Week 12 visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 300 mg ALD403 | Change From Baseline of Short Form Health Survey (SF-36 v 2.0) Scale Scores | Role Physical | 3.0 score on a scale | Standard Deviation 6.54 |
| 300 mg ALD403 | Change From Baseline of Short Form Health Survey (SF-36 v 2.0) Scale Scores | Physical Functioning | 0.9 score on a scale | Standard Deviation 5.78 |
| 300 mg ALD403 | Change From Baseline of Short Form Health Survey (SF-36 v 2.0) Scale Scores | Bodily Pain | 4.5 score on a scale | Standard Deviation 8.27 |
| 300 mg ALD403 | Change From Baseline of Short Form Health Survey (SF-36 v 2.0) Scale Scores | General Health | 1.2 score on a scale | Standard Deviation 6.78 |
| 300 mg ALD403 | Change From Baseline of Short Form Health Survey (SF-36 v 2.0) Scale Scores | Vitality | 2.3 score on a scale | Standard Deviation 7.91 |
| 100 mg ALD403 | Change From Baseline of Short Form Health Survey (SF-36 v 2.0) Scale Scores | Bodily Pain | 4.3 score on a scale | Standard Deviation 8.37 |
| 100 mg ALD403 | Change From Baseline of Short Form Health Survey (SF-36 v 2.0) Scale Scores | Physical Functioning | 1.2 score on a scale | Standard Deviation 6.88 |
| 100 mg ALD403 | Change From Baseline of Short Form Health Survey (SF-36 v 2.0) Scale Scores | Role Physical | 2.3 score on a scale | Standard Deviation 7.65 |
| 100 mg ALD403 | Change From Baseline of Short Form Health Survey (SF-36 v 2.0) Scale Scores | General Health | 0.7 score on a scale | Standard Deviation 7.22 |
| 100 mg ALD403 | Change From Baseline of Short Form Health Survey (SF-36 v 2.0) Scale Scores | Vitality | 1.8 score on a scale | Standard Deviation 8.36 |
| 30 mg ALD403 | Change From Baseline of Short Form Health Survey (SF-36 v 2.0) Scale Scores | Role Physical | 2.4 score on a scale | Standard Deviation 7.72 |
| 30 mg ALD403 | Change From Baseline of Short Form Health Survey (SF-36 v 2.0) Scale Scores | Bodily Pain | 3.5 score on a scale | Standard Deviation 9.12 |
| 30 mg ALD403 | Change From Baseline of Short Form Health Survey (SF-36 v 2.0) Scale Scores | Physical Functioning | 0.9 score on a scale | Standard Deviation 6.74 |
| 30 mg ALD403 | Change From Baseline of Short Form Health Survey (SF-36 v 2.0) Scale Scores | Vitality | 0.2 score on a scale | Standard Deviation 8.61 |
| 30 mg ALD403 | Change From Baseline of Short Form Health Survey (SF-36 v 2.0) Scale Scores | General Health | 0.6 score on a scale | Standard Deviation 7.54 |
| Placebo | Change From Baseline of Short Form Health Survey (SF-36 v 2.0) Scale Scores | Physical Functioning | 0.3 score on a scale | Standard Deviation 6.43 |
| Placebo | Change From Baseline of Short Form Health Survey (SF-36 v 2.0) Scale Scores | General Health | 0.0 score on a scale | Standard Deviation 6.52 |
| Placebo | Change From Baseline of Short Form Health Survey (SF-36 v 2.0) Scale Scores | Bodily Pain | 2.3 score on a scale | Standard Deviation 8.7 |
| Placebo | Change From Baseline of Short Form Health Survey (SF-36 v 2.0) Scale Scores | Vitality | 1.7 score on a scale | Standard Deviation 7.43 |
| Placebo | Change From Baseline of Short Form Health Survey (SF-36 v 2.0) Scale Scores | Role Physical | 2.2 score on a scale | Standard Deviation 6.78 |
Secondary
Change From Baseline to Week 12 in Percentage of Headaches With Use of Acute Medication
The percentage of headaches with acute medication usage. Participants with no headaches will be included with a rate of zero.
Time frame: Week 1-12
Population: Full Analysis Population - all randomized participants who received investigational product or placebo
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 300 mg ALD403 | Change From Baseline to Week 12 in Percentage of Headaches With Use of Acute Medication | 63.09 percentage of acute medication headaches | Standard Deviation 36.87 |
| 100 mg ALD403 | Change From Baseline to Week 12 in Percentage of Headaches With Use of Acute Medication | 66.85 percentage of acute medication headaches | Standard Deviation 33.65 |
| 30 mg ALD403 | Change From Baseline to Week 12 in Percentage of Headaches With Use of Acute Medication | 67.84 percentage of acute medication headaches | Standard Deviation 33.59 |
| Placebo | Change From Baseline to Week 12 in Percentage of Headaches With Use of Acute Medication | 70.95 percentage of acute medication headaches | Standard Deviation 33.43 |
Secondary
Change From Baseline to Week 12 in Percentage of Migraines With Use of Acute Medication
The percentage of migraines with acute medication usage. Participants with no migraines will be included with a rate of zero.
Time frame: Week 1-12
Population: Full Analysis Population - all randomized participants who received investigational product or placebo
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 300 mg ALD403 | Change From Baseline to Week 12 in Percentage of Migraines With Use of Acute Medication | 62.08 percentage of acute medication migraines | Standard Deviation 38.46 |
| 100 mg ALD403 | Change From Baseline to Week 12 in Percentage of Migraines With Use of Acute Medication | 66.58 percentage of acute medication migraines | Standard Deviation 34.13 |
| 30 mg ALD403 | Change From Baseline to Week 12 in Percentage of Migraines With Use of Acute Medication | 69.11 percentage of acute medication migraines | Standard Deviation 33.72 |
| Placebo | Change From Baseline to Week 12 in Percentage of Migraines With Use of Acute Medication | 71.44 percentage of acute medication migraines | Standard Deviation 34.59 |
Secondary
Change in Baseline of Allodynia Symptom Checklist-12 (ASC-12) Total Score
The ASC-12 includes 12 questions about the frequency of various allodynia symptoms in association with headache attacks. For individuals with more than one type of headache, questions are directed to the most severe type of headache. Each item is measured in a Likert type scale option with response categories: Does not apply to me, never, rarely, less than half the time, and half the time or more. ASC items were scored as 0 (i.e., never, rarely or does not apply to me), 1 (less than half the time), and 2 (half the time or more), yielding scores that ranged from 0 to 24. If a single item is missing, it is scored as a 0. If more than one item is missing the total score will be missing. The interpretation of the total score is, 0-2: none; 3-5: mild; 6-8: moderate; greater than or equal to 9: severe.
Time frame: Baseline to Week 12
Population: Full Analysis Population - all randomized participants who received investigational product or placebo. The Week 12 scores only include participants who completed the Week 12 visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 300 mg ALD403 | Change in Baseline of Allodynia Symptom Checklist-12 (ASC-12) Total Score | -1.6 score on a scale | Standard Deviation 4.22 |
| 100 mg ALD403 | Change in Baseline of Allodynia Symptom Checklist-12 (ASC-12) Total Score | -1.8 score on a scale | Standard Deviation 3.9 |
| 30 mg ALD403 | Change in Baseline of Allodynia Symptom Checklist-12 (ASC-12) Total Score | -1.6 score on a scale | Standard Deviation 3.95 |
| Placebo | Change in Baseline of Allodynia Symptom Checklist-12 (ASC-12) Total Score | -1.7 score on a scale | Standard Deviation 4.33 |
Secondary
Health Related Quality of Life (EQ-5D-5L) at Week 12
The EQ-5D-5L is a descriptive system of health-related quality of life states consisting of 5 dimension/questions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) each of which can take one of five responses. The responses record five levels of severity (no problems/slight problems/moderate problems/severe problems/extreme problems) within a particular EQ-5D dimension.
Time frame: Week 12
Population: Full Analysis Population - all randomized participants who received investigational product or placebo. The Week 12 scores only include participants who completed the Week 12 visit.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| 300 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Anxiety/Depression | Moderate problems | 3 Participants |
| 300 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Self-care | Slight problems | 2 Participants |
| 300 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Pain/Discomfort | Slight problems | 75 Participants |
| 300 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Mobility | Slight problems | 21 Participants |
| 300 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Usual Activities | Severe problems | 0 Participants |
| 300 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Self-care | Moderate problems | 0 Participants |
| 300 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Anxiety/Depression | Severe problems | 1 Participants |
| 300 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Mobility | Extreme problems | 0 Participants |
| 300 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Anxiety/Depression | No problems | 158 Participants |
| 300 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Self-care | Severe problems | 0 Participants |
| 300 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Pain/Discomfort | Moderate problems | 19 Participants |
| 300 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Mobility | No problems | 183 Participants |
| 300 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Usual Activities | Extreme problems | 0 Participants |
| 300 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Self-care | Extreme problems | 0 Participants |
| 300 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Pain/Discomfort | No problems | 113 Participants |
| 300 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Anxiety/Depression | Extreme problems | 0 Participants |
| 300 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Pain/Discomfort | Extreme problems | 0 Participants |
| 300 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Usual Activities | No problems | 177 Participants |
| 300 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Usual Activities | Moderate problems | 2 Participants |
| 300 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Mobility | Moderate problems | 4 Participants |
| 300 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Self-care | No problems | 206 Participants |
| 300 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Usual Activities | Slight problems | 29 Participants |
| 300 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Mobility | Severe problems | 0 Participants |
| 300 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Anxiety/Depression | Slight problems | 46 Participants |
| 300 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Pain/Discomfort | Severe problems | 1 Participants |
| 100 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Usual Activities | No problems | 173 Participants |
| 100 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Usual Activities | Moderate problems | 10 Participants |
| 100 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Mobility | No problems | 181 Participants |
| 100 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Pain/Discomfort | Moderate problems | 24 Participants |
| 100 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Usual Activities | Severe problems | 0 Participants |
| 100 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Anxiety/Depression | Severe problems | 2 Participants |
| 100 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Usual Activities | Extreme problems | 1 Participants |
| 100 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Mobility | Severe problems | 1 Participants |
| 100 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Pain/Discomfort | Slight problems | 65 Participants |
| 100 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Pain/Discomfort | No problems | 116 Participants |
| 100 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Anxiety/Depression | Slight problems | 38 Participants |
| 100 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Mobility | Extreme problems | 0 Participants |
| 100 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Anxiety/Depression | Extreme problems | 1 Participants |
| 100 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Anxiety/Depression | Moderate problems | 9 Participants |
| 100 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Self-care | No problems | 201 Participants |
| 100 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Self-care | Slight problems | 4 Participants |
| 100 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Anxiety/Depression | No problems | 156 Participants |
| 100 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Self-care | Moderate problems | 1 Participants |
| 100 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Mobility | Slight problems | 18 Participants |
| 100 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Self-care | Severe problems | 0 Participants |
| 100 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Pain/Discomfort | Extreme problems | 0 Participants |
| 100 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Self-care | Extreme problems | 0 Participants |
| 100 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Pain/Discomfort | Severe problems | 1 Participants |
| 100 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Usual Activities | Slight problems | 22 Participants |
| 100 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Mobility | Moderate problems | 6 Participants |
| 30 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Self-care | No problems | 198 Participants |
| 30 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Mobility | No problems | 181 Participants |
| 30 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Mobility | Slight problems | 16 Participants |
| 30 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Mobility | Moderate problems | 3 Participants |
| 30 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Mobility | Severe problems | 1 Participants |
| 30 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Mobility | Extreme problems | 0 Participants |
| 30 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Self-care | Slight problems | 3 Participants |
| 30 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Self-care | Moderate problems | 0 Participants |
| 30 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Self-care | Severe problems | 0 Participants |
| 30 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Self-care | Extreme problems | 0 Participants |
| 30 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Usual Activities | No problems | 176 Participants |
| 30 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Usual Activities | Slight problems | 21 Participants |
| 30 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Usual Activities | Moderate problems | 3 Participants |
| 30 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Usual Activities | Severe problems | 1 Participants |
| 30 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Pain/Discomfort | No problems | 123 Participants |
| 30 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Usual Activities | Extreme problems | 0 Participants |
| 30 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Pain/Discomfort | Slight problems | 57 Participants |
| 30 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Pain/Discomfort | Moderate problems | 18 Participants |
| 30 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Pain/Discomfort | Severe problems | 3 Participants |
| 30 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Pain/Discomfort | Extreme problems | 0 Participants |
| 30 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Anxiety/Depression | No problems | 168 Participants |
| 30 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Anxiety/Depression | Slight problems | 24 Participants |
| 30 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Anxiety/Depression | Moderate problems | 8 Participants |
| 30 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Anxiety/Depression | Severe problems | 0 Participants |
| 30 mg ALD403 | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Anxiety/Depression | Extreme problems | 1 Participants |
| Placebo | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Usual Activities | No problems | 172 Participants |
| Placebo | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Mobility | Moderate problems | 4 Participants |
| Placebo | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Pain/Discomfort | Severe problems | 2 Participants |
| Placebo | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Self-care | Extreme problems | 0 Participants |
| Placebo | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Self-care | Severe problems | 0 Participants |
| Placebo | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Anxiety/Depression | Extreme problems | 1 Participants |
| Placebo | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Pain/Discomfort | Extreme problems | 0 Participants |
| Placebo | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Self-care | Moderate problems | 0 Participants |
| Placebo | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Self-care | Slight problems | 3 Participants |
| Placebo | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Anxiety/Depression | Severe problems | 0 Participants |
| Placebo | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Anxiety/Depression | No problems | 151 Participants |
| Placebo | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Mobility | Slight problems | 15 Participants |
| Placebo | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Anxiety/Depression | Slight problems | 38 Participants |
| Placebo | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Self-care | No problems | 195 Participants |
| Placebo | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Mobility | Extreme problems | 0 Participants |
| Placebo | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Mobility | No problems | 179 Participants |
| Placebo | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Pain/Discomfort | No problems | 110 Participants |
| Placebo | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Usual Activities | Extreme problems | 0 Participants |
| Placebo | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Anxiety/Depression | Moderate problems | 8 Participants |
| Placebo | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Pain/Discomfort | Slight problems | 68 Participants |
| Placebo | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Usual Activities | Severe problems | 0 Participants |
| Placebo | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Usual Activities | Moderate problems | 7 Participants |
| Placebo | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Mobility | Severe problems | 0 Participants |
| Placebo | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Pain/Discomfort | Moderate problems | 18 Participants |
| Placebo | Health Related Quality of Life (EQ-5D-5L) at Week 12 | Usual Activities | Slight problems | 19 Participants |
Secondary
Percentage of Participants With a Migraine on the Day After Dosing
The percentage of participants with a migraine on the day after dosing, where Day 0 is treatment day and Day 1 is the day after dosing
Time frame: 1 day
Population: Full Analysis Population - all randomized participants who received investigational product or placebo
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 300 mg ALD403 | Percentage of Participants With a Migraine on the Day After Dosing | 13.9 Percentage of participants |
| 100 mg ALD403 | Percentage of Participants With a Migraine on the Day After Dosing | 14.8 Percentage of participants |
| 30 mg ALD403 | Percentage of Participants With a Migraine on the Day After Dosing | 17.3 Percentage of participants |
| Placebo | Percentage of Participants With a Migraine on the Day After Dosing | 22.5 Percentage of participants |
p-value: 0.0159Cochran-Mantel-Haenszel
p-value: 0.0312Cochran-Mantel-Haenszel
p-value: 0.1539Cochran-Mantel-Haenszel
Secondary
Percent of Headaches With Severe Intensity
Summary of percent of headaches with severe intensity over Weeks 1-12.
Time frame: Week 1-12
Population: Full Analysis Population - all randomized participants who received investigational product or placebo
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 300 mg ALD403 | Percent of Headaches With Severe Intensity | 17.06 percentage of severe intensity headaches | Standard Deviation 22.03 |
| 100 mg ALD403 | Percent of Headaches With Severe Intensity | 19.84 percentage of severe intensity headaches | Standard Deviation 24.83 |
| 30 mg ALD403 | Percent of Headaches With Severe Intensity | 21.20 percentage of severe intensity headaches | Standard Deviation 26.6 |
| Placebo | Percent of Headaches With Severe Intensity | 21.68 percentage of severe intensity headaches | Standard Deviation 22.67 |
Secondary
Percent of Migraines With Severe Intensity
Summary of percent of migraines with severe intensity over Week 1-12.
Time frame: Week 1-12
Population: Full Analysis Population - all randomized participants who received investigational product or placebo
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 300 mg ALD403 | Percent of Migraines With Severe Intensity | 19.07 percentage of severe intensity migraines | Standard Deviation 23.46 |
| 100 mg ALD403 | Percent of Migraines With Severe Intensity | 22.23 percentage of severe intensity migraines | Standard Deviation 26.3 |
| 30 mg ALD403 | Percent of Migraines With Severe Intensity | 24.43 percentage of severe intensity migraines | Standard Deviation 28.15 |
| Placebo | Percent of Migraines With Severe Intensity | 26.01 percentage of severe intensity migraines | Standard Deviation 24.99 |