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12-Week Placebo-controlled Study of Atogepant for the Preventive Treatment of Migraine in Participants With Episodic Migraine

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ClinicalTrials.gov Identifier: NCT03777059
Recruitment Status : Completed
First Posted : December 17, 2018
Results First Posted : July 9, 2021
Last Update Posted : July 9, 2021
Sponsor:
Information provided by (Responsible Party):
Allergan

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Prevention
Condition Episodic Migraine
Interventions Drug: Atogepant
Drug: Placebo
Enrollment 910
Recruitment Details  
Pre-assignment Details Participants diagnosed with episodic migraine were enrolled in one of 4 treatment arms: placebo, or atogepant 10 mg once daily (QD), 30 mg QD, 60 mg QD in Double-blind (DB) Treatment Period.
Arm/Group Title Placebo Atogepant 10 mg Atogepant 30 mg Atogepant 60 mg
Hide Arm/Group Description Placebo-matching atogepant tablets orally once daily for 12 weeks. Atogepant 10 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks. Atogepant 30 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks. Atogepant 60 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks.
Period Title: DB Treatment Period (Up to Week 12)
Started 223 222 230 235
Treated: Safety Population [1] 222 221 228 231
Completed [2] 201 193 207 204
Not Completed 22 29 23 31
Reason Not Completed
Adverse Event             6             9             4             6
Lack of Efficacy             1             0             0             1
Withdrawal by Subject             8             9             8             10
Lost to Follow-up             3             3             4             5
Pregnancy             0             1             0             0
Protocol Deviation             4             5             7             8
Reason Not Specified             0             2             0             1
[1]
Safety Population included all participants who received at least 1 dose of study intervention.
[2]
Out of 805 participants who completed DB Treatment Period, 683 participants did not complete follow-up since they rolled into study 3101-309-002 (NCT03939312), 183 entered Follow-Up Period.
Period Title: Follow-Up Period (Weeks 12 to 16)
Started 46 54 38 45
Completed 41 49 32 36
Not Completed 5 5 6 9
Reason Not Completed
Withdrawal by Subject             5             3             4             5
Lost to Follow-up             0             1             0             3
Protocol Deviation             0             1             1             0
Reason Not Specified             0             0             1             1
Arm/Group Title Placebo Atogepant 10 mg Atogepant 30 mg Atogepant 60 mg Total
Hide Arm/Group Description Placebo-matching atogepant tablets orally once daily for 12 weeks. Atogepant 10 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks. Atogepant 30 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks. Atogepant 60 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks. Total of all reporting groups
Overall Number of Baseline Participants 222 221 228 231 902
Hide Baseline Analysis Population Description
Safety Population included all participants who received at least 1 dose of study intervention.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 222 participants 221 participants 228 participants 231 participants 902 participants
40.3  (12.81) 41.4  (12.05) 42.1  (11.68) 42.5  (12.41) 41.6  (12.25)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 222 participants 221 participants 228 participants 231 participants 902 participants
Female
198
  89.2%
200
  90.5%
204
  89.5%
199
  86.1%
801
  88.8%
Male
24
  10.8%
21
   9.5%
24
  10.5%
32
  13.9%
101
  11.2%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 222 participants 221 participants 228 participants 231 participants 902 participants
American Indian or Alaska Native
0
   0.0%
1
   0.5%
1
   0.4%
1
   0.4%
3
   0.3%
Asian
2
   0.9%
2
   0.9%
1
   0.4%
7
   3.0%
12
   1.3%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
24
  10.8%
34
  15.4%
38
  16.7%
28
  12.1%
124
  13.7%
White
194
  87.4%
181
  81.9%
185
  81.1%
192
  83.1%
752
  83.4%
More than one race
2
   0.9%
3
   1.4%
3
   1.3%
2
   0.9%
10
   1.1%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
1
   0.4%
1
   0.1%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 222 participants 221 participants 228 participants 231 participants 902 participants
Hispanic
23
  10.4%
21
   9.5%
19
   8.3%
14
   6.1%
77
   8.5%
Non-Hispanic
199
  89.6%
200
  90.5%
209
  91.7%
217
  93.9%
825
  91.5%
Monthly Migraine Days   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Migraine days per month
Number Analyzed 214 participants 214 participants 223 participants 222 participants 873 participants
7.5  (2.39) 7.5  (2.46) 7.9  (2.32) 7.8  (2.31) 7.6  (2.37)
[1]
Measure Description: A migraine day was any calendar day on which the participant experienced a migraine headache qualified by duration or acute symptomatic medication use. The monthly (4-week) migraine days was defined as the total number of reported migraine days in diary divided by total number of days with diary records during each 4-week period and multiplied by 28. Each 4-week period was averaged.
[2]
Measure Analysis Population Description: mITT Population included all randomized participants who received at least 1 dose of study intervention, had an evaluable Baseline period of eDiary data, and had at least 1 evaluable post-baseline 4-week period of eDiary data during the Double-blind Treatment Period.
Monthly Headache Days   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Headache days per month
Number Analyzed 214 participants 214 participants 223 participants 222 participants 873 participants
8.4  (2.55) 8.4  (2.75) 8.8  (2.62) 9.0  (2.56) 8.7  (2.63)
[1]
Measure Description: A headache day is any calendar day on which the participant experienced a headache qualified by duration or acute symptomatic medication use. The monthly (4-week) headache days were defined as the total number of reported headache days in the diary divided by the total number of days with diary records during each 4-week period and multiplied by 28. Each 4-week period was averaged.
[2]
Measure Analysis Population Description: mITT Population included all randomized participants who received at least 1 dose of study intervention, had an evaluable Baseline period of eDiary data, and had at least 1 evaluable post-baseline 4-week period of eDiary data during the Double-blind Treatment Period.
Monthly Acute Medication Use   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Acute medication use days per month
Number Analyzed 214 participants 214 participants 223 participants 222 participants 873 participants
6.5  (3.15) 6.6  (2.99) 6.7  (3.02) 6.9  (3.17) 6.7  (3.08)
[1]
Measure Description: The monthly (4-week) acute medication use days was defined as the total number of reported acute medication use days in the diary divided by the total number of days with diary records during each 4-week period and multiplied by 28. Each 4-week period was averaged.
[2]
Measure Analysis Population Description: mITT Population included all randomized participants who received at least 1 dose of study intervention, had an evaluable Baseline period of eDiary data, and had at least 1 evaluable post-baseline 4-week period of eDiary data during the Double-blind Treatment Period.
MSQ v2.1 Role Function-Restrictive Domain Score   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Score on a scale
Number Analyzed 213 participants 212 participants 222 participants 222 participants 869 participants
46.8  (19.67) 44.9  (21.37) 44.0  (19.61) 46.8  (20.36) 45.6  (20.26)
[1]
Measure Description: Migraine-Specific Quality of Life Questionnaire, Version 2.1 (MSQ v2.1) is 14-item questionnaire to measure health-related quality-of-life impairments attributed to migraine, divided in 3 domains: role function-restrictive: how migraines limit daily social and work-related activities; role function-preventive: how migraines prevent these activities; and emotional function domain: emotions associated with migraines, using a 6-point scale, 1=none of the time and 6=all of the time. Domain scores were rescaled from 0 to 100, with higher scores indicating better migraine specific quality of life.
[2]
Measure Analysis Population Description: mITT Population included all randomized participants who received at least 1 dose of study intervention, had an evaluable Baseline period of eDiary data, and had at least 1 evaluable post-baseline 4-week period of eDiary data during the Double-blind Treatment Period. Number analyzed is the number of participants available for the analyses at Baseline.
Daily Activities Domain Score of the Activity Impairment in Migraine- Diary (AIM-D)   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Score on a scale
Number Analyzed 188 participants 191 participants 188 participants 192 participants 759 participants
15.2  (8.25) 15.5  (8.85) 16.9  (8.02) 15.9  (8.34) 15.9  (8.38)
[1]
Measure Description: AIM-D is a 9-item PRO measure that assesses the impact of migraine on performance of daily activities and physical impairment using a 6-point rating scale where 0=not difficult at all, 1=a little difficult, 2=somewhat difficult, 3=very difficult, 4=extremely difficult, and 5=I could not do it at all. The raw scores were transformed to 0-100 scale, with higher scores indicating greater impact of migraine. Baseline was defined as the monthly (averaged for a month) scores during the last 28 days.
[2]
Measure Analysis Population Description: mITT Population included all randomized participants who received at least 1 dose of study intervention, had an evaluable Baseline period of eDiary data, and had at least 1 evaluable post-baseline 4-week period of eDiary data during the Double-blind Treatment Period. Number analyzed is the number of participants available for the analyses at Baseline.
Monthly Physical Impairment Domain Score of the AIM-D   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Score on a scale
Number Analyzed 188 participants 191 participants 188 participants 192 participants 759 participants
11.2  (8.11) 11.7  (8.46) 13.0  (8.00) 11.6  (7.85) 11.9  (8.12)
[1]
Measure Description: AIM-D is a 9-item PRO measure that assesses the impact of migraine on performance of daily activities and physical impairment using a 6-point rating scale where 0=not difficult at all, 1=a little difficult, 2=somewhat difficult, 3=very difficult, 4=extremely difficult, and 5=I could not do it at all. The raw scores were transformed to 0-100 scale, with higher scores indicating greater impact of migraine. Baseline was defined as the monthly (averaged for a month) scores during the last 28 days.
[2]
Measure Analysis Population Description: mITT Population included all randomized participants who received at least 1 dose of study intervention, had an evaluable Baseline period of eDiary data, and had at least 1 evaluable post-baseline 4-week period of eDiary data during the Double-blind Treatment Period. Number analyzed is the number of participants available for the analyses at Baseline.
1.Primary Outcome
Title Change From Baseline in Mean Monthly Migraine Days Across the 12-Week Treatment Period
Hide Description Participants recorded daily duration of migraine in a diary. A migraine day was any calendar day on which the participant experienced a migraine headache qualified by duration or acute symptomatic medication use. The monthly (4-week) migraine days was defined as the total number of reported migraine days in diary divided by total number of days with diary records during each 4-week period and multiplied by 28. Each 4-week period was averaged. Baseline was defined as the number of migraine days during the last 28 days of the Baseline phase, from Day -28 to -1. Negative change from Baseline indicates improvement. A Mixed-effects model for repeated measures (MMRM) was used for analysis.
Time Frame Baseline (Day -28 to Day -1) to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population included all randomized participants who received at least 1 dose of study intervention, had an evaluable Baseline period of eDiary data, and had at least 1 evaluable post-baseline 4-week period of eDiary data during the Double-blind Treatment Period.
Arm/Group Title Placebo Atogepant 10 mg Atogepant 30 mg Atogepant 60 mg
Hide Arm/Group Description:
Placebo-matching atogepant tablets orally once daily for 12 weeks.
Atogepant 10 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks.
Atogepant 30 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks.
Atogepant 60 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks.
Overall Number of Participants Analyzed 214 214 223 222
Least Squares Mean (Standard Error)
Unit of Measure: migraine days per month
-2.48  (0.210) -3.69  (0.210) -3.86  (0.206) -4.20  (0.206)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Atogepant 10 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments MMRM model included Baseline monthly migraine days as a covariate, treatment group and visit (month) as fixed factors, and treatment group-by-visit and Baseline-by-visit as interaction terms, with an unstructured covariance matrix.
Method Mixed-effects Model for Repeated Measure
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -1.21
Confidence Interval (2-Sided) 95%
-1.78 to -0.64
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.291
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Atogepant 30 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments MMRM model included Baseline monthly migraine days as a covariate, treatment group and visit (month) as fixed factors, and treatment group-by-visit and Baseline-by-visit as interaction terms, with an unstructured covariance matrix.
Method Mixed-effects Model for Repeated Measure
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -1.38
Confidence Interval (2-Sided) 95%
-1.94 to -0.82
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.287
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Atogepant 60 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments MMRM model included Baseline monthly migraine days as a covariate, treatment group and visit (month) as fixed factors, and treatment group-by-visit and Baseline-by-visit as interaction terms, with an unstructured covariance matrix.
Method Mixed-effects Model for Repeated Measure
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -1.72
Confidence Interval (2-Sided) 95%
-2.28 to -1.15
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.288
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline in Mean Monthly Headache Days Across the 12-Week Treatment Period
Hide Description Participants recorded daily total duration of a headache in a diary. A headache day is any calendar day on which the participant experienced a headache qualified by duration or acute symptomatic medication use. The monthly (4-week) headache days were defined as the total number of reported headache days in the diary divided by the total number of days with diary records during each 4-week period and multiplied by 28. Each 4-week period was averaged. Baseline was defined as the number of migraine days during the last 28 days of the Baseline phase, from Day -28 to -1. Negative change from Baseline indicates improvement. MMRM was used for analysis.
Time Frame Baseline (Day-28 to Day -1) to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population included all randomized participants who received at least 1 dose of study intervention, had an evaluable Baseline period of eDiary data, and had at least 1 evaluable post-baseline 4-week period of eDiary data during the Double-blind Treatment Period.
Arm/Group Title Placebo Atogepant 10 mg Atogepant 30 mg Atogepant 60 mg
Hide Arm/Group Description:
Placebo-matching atogepant tablets orally once daily for 12 weeks.
Atogepant 10 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks.
Atogepant 30 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks.
Atogepant 60 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks.
Overall Number of Participants Analyzed 214 214 223 222
Least Squares Mean (Standard Error)
Unit of Measure: headache days per month
-2.52  (0.225) -3.94  (0.225) -4.04  (0.221) -4.23  (0.221)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Atogepant 10 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments MMRM model included Baseline monthly migraine days as a covariate, treatment group and visit (month) as fixed factors, and treatment group-by-visit and Baseline-by-visit as interaction terms, with an unstructured covariance matrix.
Method Mixed-effects Model for Repeated Measure
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -1.42
Confidence Interval (2-Sided) 95%
-2.03 to -0.81
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.311
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Atogepant 30 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments MMRM model included Baseline monthly migraine days as a covariate, treatment group and visit (month) as fixed factors, and treatment group-by-visit and Baseline-by-visit as interaction terms, with an unstructured covariance matrix.
Method Mixed-effects Model for Repeated Measure
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -1.53
Confidence Interval (2-Sided) 95%
-2.13 to -0.92
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.307
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Atogepant 60 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments MMRM model included Baseline monthly migraine days as a covariate, treatment group and visit (month) as fixed factors, and treatment group-by-visit and Baseline-by-visit as interaction terms, with an unstructured covariance matrix.
Method Mixed-effects Model for Repeated Measure
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -1.71
Confidence Interval (2-Sided) 95%
-2.32 to -1.10
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.309
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline in Mean Monthly Acute Medication Use Days Across the 12-Week Treatment Period
Hide Description Participants recorded allowed medication(s) to treat an acute migraine in the daily diary. The monthly (4-week) acute medication use days was defined as the total number of reported acute medication use days in the diary divided by the total number of days with diary records during each 4-week period and multiplied by 28. Each 4-week period was averaged. Baseline was defined as the number of acute medication use days during the last 28 days of the Baseline phase, from Day -28 to -1. A negative change from Baseline indicates improvement. MMRM was used for the analysis.
Time Frame Baseline (Day-28 to Day -1) to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population included all randomized participants who received at least 1 dose of study intervention, had an evaluable Baseline period of eDiary data, and had at least 1 evaluable post-baseline 4-week period of eDiary data during the Double-blind Treatment Period.
Arm/Group Title Placebo Atogepant 10 mg Atogepant 30 mg Atogepant 60 mg
Hide Arm/Group Description:
Placebo-matching atogepant tablets orally once daily for 12 weeks.
Atogepant 10 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks.
Atogepant 30 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks.
Atogepant 60 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks.
Overall Number of Participants Analyzed 214 214 223 222
Least Squares Mean (Standard Error)
Unit of Measure: acute medication use days per month
-2.35  (0.184) -3.66  (0.183) -3.68  (0.180) -3.85  (0.180)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Atogepant 10 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments MMRM model included Baseline monthly migraine days as a covariate, treatment group and visit (month) as fixed factors, and treatment group-by-visit and Baseline-by-visit as interaction terms, with an unstructured covariance matrix.
Method Mixed-effects Model for Repeated Measure
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -1.31
Confidence Interval (2-Sided) 95%
-1.81 to -0.82
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.254
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Atogepant 30 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments MMRM model included Baseline monthly migraine days as a covariate, treatment group and visit (month) as fixed factors, and treatment group-by-visit and Baseline-by-visit as interaction terms, with an unstructured covariance matrix.
Method Mixed-effects Model for Repeated Measure
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -1.33
Confidence Interval (2-Sided) 95%
-1.82 to -0.83
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.251
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Atogepant 60 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments MMRM model included Baseline monthly migraine days as a covariate, treatment group and visit (month) as fixed factors, and treatment group-by-visit and Baseline-by-visit as interaction terms, with an unstructured covariance matrix.
Method Mixed-effects Model for Repeated Measure
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -1.50
Confidence Interval (2-Sided) 95%
-2.00 to -1.01
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.252
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Percentage of Participants With at Least a 50% Reduction (Improvement) in 3-month Average of Monthly Migraine Days
Hide Description Participants recorded daily duration of migraine in a diary. A migraine day was any calendar day on which the participant experienced a migraine headache qualified by duration or acute symptomatic medication use. The monthly (4-week) migraine days is equal to total number of reported migraine days in diary divided by total number of days with diary records in each 4-week period multiplied by 28. Each 4-week period was averaged.
Time Frame Baseline (Day -28 to Day -1) to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population included all randomized participants who received at least 1 dose of study intervention, had an evaluable Baseline period (Day -28 to Day -1) of eDiary data, and had at least 1 evaluable post-baseline 4-week period (Weeks 1-4, 5-8, and 9-12) of eDiary data during the Double-blind Treatment Period.
Arm/Group Title Placebo Atogepant 10 mg Atogepant 30 mg Atogepant 60 mg
Hide Arm/Group Description:
Placebo-matching atogepant tablets orally once daily for 12 weeks.
Atogepant 10 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks.
Atogepant 30 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks.
Atogepant 60 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks.
Overall Number of Participants Analyzed 214 214 223 222
Measure Type: Number
Unit of Measure: percentage of participants
29.0 55.6 58.7 60.8
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Atogepant 10 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments Odds ratio and p-value was based on logistic regression with treatment group, Baseline value, and prior exposure to a migraine prevention medications with proven efficacy as explanatory variables.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.06
Confidence Interval (2-Sided) 95%
2.05 to 4.56
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Atogepant 30 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments Odds ratio and p-value was based on logistic regression with treatment group, Baseline value, and prior exposure to a migraine prevention medications with proven efficacy as explanatory variables.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.53
Confidence Interval (2-Sided) 95%
2.37 to 5.26
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Atogepant 60 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments Odds ratio and p-value was based on logistic regression with treatment group, Baseline value, and prior exposure to a migraine prevention medications with proven efficacy as explanatory variables.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.82
Confidence Interval (2-Sided) 95%
2.56 to 5.71
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change From Baseline in Migraine-Specific Quality of Life Questionnaire, Version 2.1 (MSQ v2.1) Role Function-Restrictive Domain Score at Week 12
Hide Description MSQ v2.1 is a 14-item questionnaire designed to measure health-related quality-of-life impairments attributed to migraine in the past 4 weeks. It is divided into three domains: role function-restrictive (questions 1-7, score range 7 to 42) assesses how migraines limit one's daily social and work-related activities; role function-preventive (questions 8-11, score ranges 4 to 24) assesses how migraines prevent these activities; and the emotional function (questions 12-14, score ranges 3 to 18) domain assesses the emotions associated with migraines. Participants respond to items using a 6-point scale where 1=none of the time and 6=all of the time. Raw dimension scores are computed as a sum of item responses and rescaled to a 0 to 100 scale, where higher scores from Baseline indicate better quality of life. MMRM was used for the analysis.
Time Frame Baseline (Day 1) to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population included all randomized participants who received at least 1 dose of study intervention, had an evaluable Baseline period of eDiary data, and had at least 1 evaluable post-baseline 4-week period of eDiary data during the Double-blind Treatment Period. Overall number analyzed is the number of participants with data available for analysis.
Arm/Group Title Placebo Atogepant 10 mg Atogepant 30 mg Atogepant 60 mg
Hide Arm/Group Description:
Placebo-matching atogepant tablets orally once daily for 12 weeks.
Atogepant 10 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks.
Atogepant 30 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks.
Atogepant 60 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks.
Overall Number of Participants Analyzed 198 186 203 201
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
20.45  (1.617) 30.35  (1.639) 30.53  (1.593) 31.25  (1.591)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Atogepant 10 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments MMRM model included Baseline monthly migraine days as a covariate, treatment group and visit (month) as fixed factors, and treatment group-by-visit and Baseline-by-visit as interaction terms, with an unstructured covariance matrix.
Method Mixed-effects Model for Repeated Measure
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value 9.90
Confidence Interval (2-Sided) 95%
5.45 to 14.36
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.270
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Atogepant 30 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments MMRM model included Baseline monthly migraine days as a covariate, treatment group and visit (month) as fixed factors, and treatment group-by-visit and Baseline-by-visit as interaction terms, with an unstructured covariance matrix.
Method Mixed-effects Model for Repeated Measure
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value 10.08
Confidence Interval (2-Sided) 95%
5.71 to 14.46
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.229
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Atogepant 60 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments MMRM model included Baseline monthly migraine days as a covariate, treatment group and visit (month) as fixed factors, and treatment group-by-visit and Baseline-by-visit as interaction terms, with an unstructured covariance matrix.
Method Mixed-effects Model for Repeated Measure
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value 10.80
Confidence Interval (2-Sided) 95%
6.42 to 15.18
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.231
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Change From Baseline in Mean Monthly Performance of Daily Activities Domain Score of the Activity Impairment in Migraine-Diary (AIM-D) Across the 12-Week Treatment Period
Hide Description The AIM-D is a 9-item PRO measure that assesses the impact of migraine on the performance of daily activities and physical impairment using a 6-point rating scale where 0=not difficult at all, 1=a little difficult, 2=somewhat difficult, 3=very difficult, 4=extremely difficult, and 5=I could not do it at all. The raw performance of daily activities domain scores were transformed to 0-100 scale, with higher scores indicating greater impact of migraine (higher disease burden). Baseline was defined as the monthly (averaged for a month) performance of daily activities domain score during the last 28 days of the Baseline period from Day -28 to -1. MMRM was used for the analysis.
Time Frame Baseline (Day -28 to Day -1) to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population included all randomized participants who received at least 1 dose of study intervention, had an evaluable Baseline period of eDiary data, and had at least 1 evaluable post-baseline 4-week period of eDiary data during the Double-blind Treatment Period. Overall number analyzed is the number of participants with data available for analysis.
Arm/Group Title Placebo Atogepant 10 mg Atogepant 30 mg Atogepant 60 mg
Hide Arm/Group Description:
Placebo-matching atogepant tablets orally once daily for 12 weeks.
Atogepant 10 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks.
Atogepant 30 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks.
Atogepant 60 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks.
Overall Number of Participants Analyzed 178 182 181 178
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
-6.09  (0.504) -7.28  (0.500) -8.63  (0.502) -9.41  (0.504)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Atogepant 10 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0856
Comments MMRM model included Baseline monthly migraine days as a covariate, treatment group and visit (month) as fixed factors, and treatment group-by-visit and Baseline-by-visit as interaction terms, with an unstructured covariance matrix.
Method Mixed-effects Model for Repeated Measure
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -1.19
Confidence Interval (2-Sided) 95%
-2.56 to 0.17
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.693
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Atogepant 30 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0003
Comments MMRM model included Baseline monthly migraine days as a covariate, treatment group and visit (month) as fixed factors, and treatment group-by-visit and Baseline-by-visit as interaction terms, with an unstructured covariance matrix.
Method Mixed-effects Model for Repeated Measure
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -2.54
Confidence Interval (2-Sided) 95%
-3.91 to -1.18
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.694
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Atogepant 60 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments MMRM model included Baseline monthly migraine days as a covariate, treatment group and visit (month) as fixed factors, and treatment group-by-visit and Baseline-by-visit as interaction terms, with an unstructured covariance matrix.
Method Mixed-effects Model for Repeated Measure
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -3.32
Confidence Interval (2-Sided) 95%
-4.68 to -1.96
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.694
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Change From Baseline in Mean Monthly Physical Impairment Domain Score of the Activity Impairment in Migraine- Diary (AIM-D) Across the 12-Week Treatment Period
Hide Description The AIM-D is a 9-item PRO measure that assesses the impact of migraine on the performance of daily activities and physical impairment using a 6-point rating scale where 0=not difficult at all, 1=a little difficult, 2=somewhat difficult, 3=very difficult, 4=extremely difficult, and 5=I could not do it at all. The raw physical impairment domain scores were transformed to 0-100 scale, with higher scores indicating greater impact of migraine (higher disease burden). Baseline was defined as the monthly (averaged for a month) physical impairment domain score during the last 28 days of the Baseline period from Day -28 to -1. MMRM was used for the analysis.
Time Frame Baseline (Day -28 to Day -1) to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population included all randomized participants who received at least 1 dose of study intervention, had an evaluable Baseline period of eDiary data, and had at least 1 evaluable post-baseline 4-week period of eDiary data during the Double-blind Treatment Period. Overall number analyzed is the number of participants with data available for analysis.
Arm/Group Title Placebo Atogepant 10 mg Atogepant 30 mg Atogepant 60 mg
Hide Arm/Group Description:
Placebo-matching atogepant tablets orally once daily for 12 weeks.
Atogepant 10 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks.
Atogepant 30 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks.
Atogepant 60 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks.
Overall Number of Participants Analyzed 178 182 181 178
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
-4.03  (0.439) -5.11  (0.436) -6.02  (0.438) -6.49  (0.439)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Atogepant 10 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0743
Comments MMRM model included Baseline monthly migraine days as a covariate, treatment group and visit (month) as fixed factors, and treatment group-by-visit and Baseline-by-visit as interaction terms, with an unstructured covariance matrix.
Method Mixed-effects Model for Repeated Measure
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -1.08
Confidence Interval (2-Sided) 95%
-2.27 to 0.11
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.605
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Atogepant 30 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0011
Comments MMRM model included Baseline monthly migraine days as a covariate, treatment group and visit (month) as fixed factors, and treatment group-by-visit and Baseline-by-visit as interaction terms, with an unstructured covariance matrix.
Method Mixed-effects Model for Repeated Measure
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -1.99
Confidence Interval (2-Sided) 95%
-3.18 to -0.80
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.606
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Atogepant 60 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments MMRM model included Baseline monthly migraine days as a covariate, treatment group and visit (month) as fixed factors, and treatment group-by-visit and Baseline-by-visit as interaction terms, with an unstructured covariance matrix.
Method Mixed-effects Model for Repeated Measure
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -2.46
Confidence Interval (2-Sided) 95%
-3.65 to -1.28
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.605
Estimation Comments [Not Specified]
Time Frame From first dose of study drug through end of study (Up to 16 weeks)
Adverse Event Reporting Description All-Cause Mortality is reported for all randomized participants. Safety Population, all participants who received at least 1 dose of study intervention, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.
 
Arm/Group Title Placebo Atogepant 10 mg Atogepant 30 mg Atogepant 60 mg
Hide Arm/Group Description Placebo-matching atogepant tablets orally once daily for 12 weeks. Atogepant 10 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks. Atogepant 30 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks. Atogepant 60 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks.
All-Cause Mortality
Placebo Atogepant 10 mg Atogepant 30 mg Atogepant 60 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/223 (0.00%)   0/222 (0.00%)   0/230 (0.00%)   0/235 (0.00%) 
Hide Serious Adverse Events
Placebo Atogepant 10 mg Atogepant 30 mg Atogepant 60 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/222 (0.90%)   2/221 (0.90%)   0/228 (0.00%)   0/231 (0.00%) 
Gastrointestinal disorders         
Gastric ulcer haemorrhage  1  1/222 (0.45%)  0/221 (0.00%)  0/228 (0.00%)  0/231 (0.00%) 
Nervous system disorders         
Brain injury  1  1/222 (0.45%)  0/221 (0.00%)  0/228 (0.00%)  0/231 (0.00%) 
Optic neuritis  1  0/222 (0.00%)  1/221 (0.45%)  0/228 (0.00%)  0/231 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Asthma  1  0/222 (0.00%)  1/221 (0.45%)  0/228 (0.00%)  0/231 (0.00%) 
Negative pressure pulmonary oedema  1  1/222 (0.45%)  0/221 (0.00%)  0/228 (0.00%)  0/231 (0.00%) 
1
Term from vocabulary, MedDRA: 22.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Atogepant 10 mg Atogepant 30 mg Atogepant 60 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   15/222 (6.76%)   34/221 (15.38%)   37/228 (16.23%)   32/231 (13.85%) 
Gastrointestinal disorders         
Constipation  1  1/222 (0.45%)  17/221 (7.69%)  16/228 (7.02%)  16/231 (6.93%) 
Nausea  1  4/222 (1.80%)  11/221 (4.98%)  10/228 (4.39%)  14/231 (6.06%) 
Infections and infestations         
Upper respiratory tract infection  1  10/222 (4.50%)  9/221 (4.07%)  13/228 (5.70%)  9/231 (3.90%) 
1
Term from vocabulary, MedDRA: 22.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
A disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 90 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Therapeutic Area, Head
Organization: Allergan
Phone: 714-246-4500
EMail: clinicaltrials@allergan.com
Layout table for additonal information
Responsible Party: Allergan
ClinicalTrials.gov Identifier: NCT03777059    
Other Study ID Numbers: 3101-301-002
First Submitted: December 13, 2018
First Posted: December 17, 2018
Results First Submitted: June 18, 2021
Results First Posted: July 9, 2021
Last Update Posted: July 9, 2021