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Efficacy, Safety, and Tolerability of Multiple Dosing Regimens of Oral Atogepant (AGN-241689) in Episodic Migraine Prevention

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ClinicalTrials.gov Identifier: NCT02848326
Recruitment Status : Completed
First Posted : July 28, 2016
Results First Posted : December 6, 2018
Last Update Posted : December 6, 2018
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 Migraine, With or Without Aura
Interventions Drug: Atogepant
Drug: Placebo-matching Atogepant
Enrollment 834
Recruitment Details  
Pre-assignment Details Participants diagnosed with migraine, with or without aura were enrolled in one of 6 treatment arms: placebo, or atogepant 10 mg once daily (QD), 30 mg QD, 60 mg QD, 30 mg twice daily (BID), or 60 mg BID.
Arm/Group Title Placebo Atogepant 10 mg QD Atogepant 30 mg QD Atogepant 60 mg QD Atogepant 30 mg BID Atogepant 60 mg BID
Hide Arm/Group Description Placebo-matching atogepant capsules orally twice daily in the morning and in the evening for 12 weeks. Atogepant 10 mg capsule orally once daily (QD) in the morning and one placebo-matching atogepant capsule orally once daily in the evening for 12 weeks. Atogepant 30 mg capsule orally once daily in the morning and one placebo-matching atogepant capsule orally once daily in the evening for 12 weeks. Atogepant 60 mg capsule orally once daily in the morning and one placebo-matching atogepant capsule orally in the evening for 12 weeks. Atogepant 30 mg capsule orally twice daily (BID); 1 capsule in the morning and 1 capsule in the evening for 12 weeks. Atogepant 60 mg capsule orally twice daily; 1 capsule in the morning and 1 capsule in the evening for 12 weeks.
Period Title: Treatment Period
Started 186 94 185 187 89 93
Safety Population: Received Study Drug 186 93 183 186 86 91
Completed 148 80 149 164 70 73
Not Completed 38 14 36 23 19 20
Reason Not Completed
Adverse Event             5             4             11             6             5             7
Withdrawal of Consent             20             6             9             6             9             6
Lost to Follow-up             5             1             11             7             2             3
Pregnancy             0             0             1             1             0             1
Protocol Violation             4             3             4             2             3             3
Non-compliance with Study Drug             4             0             0             1             0             0
Period Title: Safety Follow-up Period
Started 161 84 156 169 77 82
Completed 157 83 153 169 76 77
Not Completed 4 1 3 0 1 5
Reason Not Completed
Withdrawal of Consent             0             1             1             0             0             2
Lost to Follow-up             4             0             2             0             1             3
Arm/Group Title Placebo Atogepant 10 mg QD Atogepant 30 mg QD Atogepant 60 mg QD Atogepant 30 mg BID Atogepant 60 mg BID Total
Hide Arm/Group Description Placebo-matching atogepant capsules orally twice daily in the morning and in the evening for 12 weeks. Atogepant 10 mg capsule orally once daily (QD) in the morning and one placebo-matching atogepant capsule orally once daily in the evening for 12 weeks. Atogepant 30 mg capsule orally once daily in the morning and one placebo-matching atogepant capsule orally once daily in the evening for 12 weeks. Atogepant 60 mg capsule orally once daily in the morning and one placebo-matching atogepant capsule orally in the evening for 12 weeks. Atogepant 30 mg capsule orally twice daily (BID); 1 capsule in the morning and 1 capsule in the evening for 12 weeks. Atogepant 60 mg capsule orally twice daily; 1 capsule in the morning and 1 capsule in the evening for 12 weeks. Total of all reporting groups
Overall Number of Baseline Participants 186 93 183 186 86 91 825
Hide Baseline Analysis Population Description
Safety Population included all participants who received at least 1 dose of study treatment.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 186 participants 93 participants 183 participants 186 participants 86 participants 91 participants 825 participants
40.5  (11.7) 39.4  (12.4) 41.0  (13.6) 40.4  (11.7) 38.5  (11.2) 39.7  (11.9) 40.1  (12.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 186 participants 93 participants 183 participants 186 participants 86 participants 91 participants 825 participants
Female
154
  82.8%
82
  88.2%
166
  90.7%
156
  83.9%
73
  84.9%
83
  91.2%
714
  86.5%
Male
32
  17.2%
11
  11.8%
17
   9.3%
30
  16.1%
13
  15.1%
8
   8.8%
111
  13.5%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
White Number Analyzed 186 participants 93 participants 183 participants 186 participants 86 participants 91 participants 825 participants
137
  73.7%
69
  74.2%
145
  79.2%
133
  71.5%
73
  84.9%
71
  78.0%
628
  76.1%
Black or African American Number Analyzed 186 participants 93 participants 183 participants 186 participants 86 participants 91 participants 825 participants
45
  24.2%
20
  21.5%
29
  15.8%
44
  23.7%
11
  12.8%
19
  20.9%
168
  20.4%
Asian Number Analyzed 186 participants 93 participants 183 participants 186 participants 86 participants 91 participants 825 participants
1
   0.5%
1
   1.1%
2
   1.1%
3
   1.6%
1
   1.2%
0
   0.0%
8
   1.0%
American Indian or Alaska Native Number Analyzed 186 participants 93 participants 183 participants 186 participants 86 participants 91 participants 825 participants
3
   1.6%
0
   0.0%
1
   0.5%
2
   1.1%
0
   0.0%
0
   0.0%
6
   0.7%
Native Hawaiian/Other Pacific Islander Number Analyzed 186 participants 93 participants 183 participants 186 participants 86 participants 91 participants 825 participants
0
   0.0%
0
   0.0%
2
   1.1%
0
   0.0%
0
   0.0%
0
   0.0%
2
   0.2%
Multiple Races Number Analyzed 186 participants 93 participants 183 participants 186 participants 86 participants 91 participants 825 participants
0
   0.0%
3
   3.2%
4
   2.2%
4
   2.2%
1
   1.2%
1
   1.1%
13
   1.6%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Hispanic or Latino Number Analyzed 186 participants 93 participants 183 participants 186 participants 86 participants 91 participants 825 participants
29
  15.6%
15
  16.1%
32
  17.5%
25
  13.4%
13
  15.1%
13
  14.3%
127
  15.4%
Not Hispanic or Latino Number Analyzed 186 participants 93 participants 183 participants 186 participants 86 participants 91 participants 825 participants
157
  84.4%
78
  83.9%
151
  82.5%
161
  86.6%
73
  84.9%
78
  85.7%
698
  84.6%
Migraine Days (Migraine/Probable Migraine Headache Days)   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Migraine days per month
Number Analyzed 178 participants 92 participants 182 participants 177 participants 79 participants 87 participants 795 participants
7.81  (2.51) 7.63  (2.51) 7.64  (2.37) 7.74  (2.59) 7.38  (2.43) 7.62  (2.56) 7.67  (2.49)
[1]
Measure Description: A migraine day was any calendar day on which the participant experienced a migraine headache qualified by duration and acute symptomatic medication use. The 4-week migraine days=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.
[2]
Measure Analysis Population Description: Modified-intent-to-treatment (mITT) Population included all randomized participants who received at least 1 dose of study treatment, had an evaluable baseline period of diary data, and had at least 1 evaluable post-baseline 4-week (Weeks 1-4, 5-8, and 9-12) of diary data.
1.Primary Outcome
Title Change From Baseline in Mean Monthly Migraine Days (Migraine/Probable Migraine Headache 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 and acute symptomatic medication use. The 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. Negative change from Baseline indicates improvement.
Time Frame Baseline (First 28 Days of Screening/Baseline Period) 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 treatment, had an evaluable baseline period of diary data, and had at least 1 evaluable post-baseline 4-week (Weeks 1-4, 5-8, and 9-12) of diary data.
Arm/Group Title Placebo Atogepant 10 mg QD Atogepant 30 mg QD Atogepant 60 mg QD Atogepant 30 mg BID Atogepant 60 mg BID
Hide Arm/Group Description:
Placebo-matching atogepant capsules orally twice daily in the morning and in the evening for 12 weeks.
Atogepant 10 mg capsule orally once daily (QD) in the morning and one placebo-matching atogepant capsule orally once daily in the evening for 12 weeks.
Atogepant 30 mg capsule orally once daily in the morning and one placebo-matching atogepant capsule orally once daily in the evening for 12 weeks.
Atogepant 60 mg capsule orally once daily in the morning and one placebo-matching atogepant capsule orally in the evening for 12 weeks.
Atogepant 30 mg capsule orally twice daily (BID); 1 capsule in the morning and 1 capsule in the evening for 12 weeks.
Atogepant 60 mg capsule orally twice daily; 1 capsule in the morning and 1 capsule in the evening for 12 weeks.
Overall Number of Participants Analyzed 178 92 182 177 79 87
Least Squares Mean (Standard Error)
Unit of Measure: migraine days per month
-2.85  (0.23) -4.00  (0.32) -3.76  (0.23) -3.55  (0.23) -4.23  (0.35) -4.14  (0.33)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Atogepant 10 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0039
Comments Mixed-effects model for repeated measures (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.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -1.15
Confidence Interval (2-Sided) 95%
-1.93 to -0.37
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.40
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Atogepant 30 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0056
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.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -0.91
Confidence Interval (2-Sided) 95%
-1.55 to -0.27
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.33
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Atogepant 60 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0325
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.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -0.70
Confidence Interval (2-Sided) 95%
-1.35 to -0.06
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.33
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Atogepant 30 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0010
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.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -1.39
Confidence Interval (2-Sided) 95%
-2.21 to -0.56
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.42
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Atogepant 60 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0016
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.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -1.29
Confidence Interval (2-Sided) 95%
-2.09 to -0.49
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.41
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 and acute symptomatic medication use. The 4-week (monthly) headache days was 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. Negative change from Baseline indicates improvement.
Time Frame Baseline (First 28 Days of Screening/Baseline Period) 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 treatment, had an evaluable baseline period of diary data, and had at least 1 evaluable post-baseline 4-week (Weeks 1-4, 5-8, and 9-12) of diary data.
Arm/Group Title Placebo Atogepant 10 mg QD Atogepant 30 mg QD Atogepant 60 mg QD Atogepant 30 mg BID Atogepant 60 mg BID
Hide Arm/Group Description:
Placebo-matching atogepant capsules orally twice daily in the morning and in the evening for 12 weeks.
Atogepant 10 mg capsule orally once daily (QD) in the morning and one placebo-matching atogepant capsule orally once daily in the evening for 12 weeks.
Atogepant 30 mg capsule orally once daily in the morning and one placebo-matching atogepant capsule orally once daily in the evening for 12 weeks.
Atogepant 60 mg capsule orally once daily in the morning and one placebo-matching atogepant capsule orally in the evening for 12 weeks.
Atogepant 30 mg capsule orally twice daily (BID); 1 capsule in the morning and 1 capsule in the evening for 12 weeks.
Atogepant 60 mg capsule orally twice daily; 1 capsule in the morning and 1 capsule in the evening for 12 weeks.
Overall Number of Participants Analyzed 178 92 182 177 79 87
Least Squares Mean (Standard Error)
Unit of Measure: headache days per month
-2.93  (0.25) -4.31  (0.35) -4.17  (0.25) -3.86  (0.25) -4.23  (0.38) -4.32  (0.36)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Atogepant 10 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0014
Comments MMRM model included baseline monthly headache days as a covariate, treatment group and visit (month) as fixed factors, and treatment group-by-visit and baseline-by-visit as interaction terms.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -1.38
Confidence Interval (2-Sided) 95%
-2.23 to -0.54
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.43
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Atogepant 30 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0005
Comments MMRM model included baseline monthly headache days as a covariate, treatment group and visit (month) as fixed factors, and treatment group-by-visit and baseline-by-visit as interaction terms.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -1.24
Confidence Interval (2-Sided) 95%
-1.94 to -0.55
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.36
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Atogepant 60 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0087
Comments MMRM model included baseline monthly headache days as a covariate, treatment group and visit (month) as fixed factors, and treatment group-by-visit and baseline-by-visit as interaction terms.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -0.94
Confidence Interval (2-Sided) 95%
-1.64 to -0.24
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.36
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Atogepant 30 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0044
Comments MMRM model included baseline monthly headache days as a covariate, treatment group and visit (month) as fixed factors, and treatment group-by-visit and baseline-by-visit as interaction terms.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -1.30
Confidence Interval (2-Sided) 95%
-2.20 to -0.41
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.46
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Atogepant 60 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0017
Comments MMRM model included baseline monthly headache days as a covariate, treatment group and visit (month) as fixed factors, and treatment group-by-visit and baseline-by-visit as interaction terms.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -1.39
Confidence Interval (2-Sided) 95%
-2.26 to -0.53
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.44
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Percentage of Participants With at Least a 50% Reduction in Mean Monthly Migraine Days (Migraine/Probable Migraine Headache 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 and acute symptomatic medication use. The 4-week migraine days=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 (First 28 Days of Screening/Baseline Period) 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 treatment, had an evaluable baseline period of diary data, and had at least 1 evaluable post-baseline 4-week (Weeks 1-4, 5-8, and 9-12) of diary data.
Arm/Group Title Placebo Atogepant 10 mg QD Atogepant 30 mg QD Atogepant 60 mg QD Atogepant 30 mg BID Atogepant 60 mg BID
Hide Arm/Group Description:
Placebo-matching atogepant capsules orally twice daily in the morning and in the evening for 12 weeks.
Atogepant 10 mg capsule orally once daily (QD) in the morning and one placebo-matching atogepant capsule orally once daily in the evening for 12 weeks.
Atogepant 30 mg capsule orally once daily in the morning and one placebo-matching atogepant capsule orally once daily in the evening for 12 weeks.
Atogepant 60 mg capsule orally once daily in the morning and one placebo-matching atogepant capsule orally in the evening for 12 weeks.
Atogepant 30 mg capsule orally twice daily (BID); 1 capsule in the morning and 1 capsule in the evening for 12 weeks.
Atogepant 60 mg capsule orally twice daily; 1 capsule in the morning and 1 capsule in the evening for 12 weeks.
Overall Number of Participants Analyzed 178 92 182 177 79 87
Measure Type: Number
Unit of Measure: percentage of participants
40.4 57.6 53.3 52.0 58.2 62.1
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Atogepant 10 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0617
Comments Generalized linear mixed model (GLMM) for repeated measures with fixed factors(treatment group,visit), covariates(baseline migraine days), interactions(treatment group;baseline migraine days by visit) with an unstructured covariance matrix.
Method GLMM for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.50
Confidence Interval (2-Sided) 95%
0.98 to 2.31
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Atogepant 30 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0369
Comments GLMM for repeated measures with fixed factors (treatment group, visit), covariates (baseline migraine days), interactions (treatment group by visit; baseline migraine days by visit) with an unstructured covariance matrix.
Method GLMM for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.46
Confidence Interval (2-Sided) 95%
1.02 to 2.08
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Atogepant 60 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0512
Comments GLMM for repeated measures with fixed factors (treatment group, visit), covariates (baseline migraine days), interactions (treatment group by visit; baseline migraine days by visit) with an unstructured covariance matrix.
Method GLMM for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.42
Confidence Interval (2-Sided) 95%
1.00 to 2.03
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Atogepant 30 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0113
Comments GLMM for repeated measures with fixed factors (treatment group, visit), covariates (baseline migraine days), interactions (treatment group by visit; baseline migraine days by visit) with an unstructured covariance matrix.
Method GLMM for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.83
Confidence Interval (2-Sided) 95%
1.15 to 2.91
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Atogepant 60 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0019
Comments GLMM for repeated measures with fixed factors (treatment group, visit), covariates (baseline migraine days), interactions (treatment group by visit; baseline migraine days by visit) with an unstructured covariance matrix.
Method GLMM for repeated measure
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.03
Confidence Interval (2-Sided) 95%
1.30 to 3.18
Estimation Comments [Not Specified]
4.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 4-week (monthly) 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. A negative change from Baseline indicates improvement.
Time Frame Baseline (First 28 Days of Screening/Baseline Period) 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 treatment, had an evaluable baseline period of diary data, and had at least 1 evaluable post-baseline 4-week (Weeks 1-4, 5-8, and 9-12) of diary data.
Arm/Group Title Placebo Atogepant 10 mg QD Atogepant 30 mg QD Atogepant 60 mg QD Atogepant 30 mg BID Atogepant 60 mg BID
Hide Arm/Group Description:
Placebo-matching atogepant capsules orally twice daily in the morning and in the evening for 12 weeks.
Atogepant 10 mg capsule orally once daily (QD) in the morning and one placebo-matching atogepant capsule orally once daily in the evening for 12 weeks.
Atogepant 30 mg capsule orally once daily in the morning and one placebo-matching atogepant capsule orally once daily in the evening for 12 weeks.
Atogepant 60 mg capsule orally once daily in the morning and one placebo-matching atogepant capsule orally in the evening for 12 weeks.
Atogepant 30 mg capsule orally twice daily (BID); 1 capsule in the morning and 1 capsule in the evening for 12 weeks.
Atogepant 60 mg capsule orally twice daily; 1 capsule in the morning and 1 capsule in the evening for 12 weeks.
Overall Number of Participants Analyzed 178 92 182 177 79 87
Least Squares Mean (Standard Error)
Unit of Measure: acute medication use days per month
-2.42  (0.21) -3.71  (0.29) -3.86  (0.20) -3.53  (0.21) -3.77  (0.31) -3.64  (0.29)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Atogepant 10 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments MMRM model included baseline monthly acute medication use days as a covariate, treatment group and visit (month) as fixed factors, and treatment group-by-visit and baseline-by-visit as interaction terms.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -1.30
Confidence Interval (2-Sided) 95%
-1.99 to -0.60
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.35
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Atogepant 30 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments MMRM model included baseline monthly acute medication use days as a covariate, treatment group and visit (month) as fixed factors, and treatment group-by-visit and baseline-by-visit as interaction terms.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -1.44
Confidence Interval (2-Sided) 95%
-2.01 to -0.87
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.29
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Atogepant 60 mg QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments MMRM model included baseline monthly acute medication use days as a covariate, treatment group and visit (month) as fixed factors, and treatment group-by-visit and baseline-by-visit as interaction terms.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -1.11
Confidence Interval (2-Sided) 95%
-1.68 to -0.54
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.29
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Atogepant 30 mg BID
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 acute medication use days as a covariate, treatment group and visit (month) as fixed factors, and treatment group-by-visit and baseline-by-visit as interaction terms.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -1.35
Confidence Interval (2-Sided) 95%
-2.08 to -0.62
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.37
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Atogepant 60 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0007
Comments MMRM model included baseline monthly acute medication use days as a covariate, treatment group and visit (month) as fixed factors, and treatment group-by-visit and baseline-by-visit as interaction terms.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -1.22
Confidence Interval (2-Sided) 95%
-1.93 to -0.52
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.36
Estimation Comments [Not Specified]
Time Frame Up to Week 16
Adverse Event Reporting Description Safety population, all randomized participants who received at least 1 dose of study treatment, 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 QD Atogepant 30 mg QD Atogepant 60 mg QD Atogepant 30 mg BID Atogepant 60 mg BID
Hide Arm/Group Description Placebo-matching atogepant capsules orally twice daily in the morning and in the evening for 12 weeks. Atogepant 10 mg capsule orally once daily (QD) in the morning and one placebo-matching atogepant capsule orally once daily in the evening for 12 weeks. Atogepant 30 mg capsule orally once daily in the morning and one placebo-matching atogepant capsule orally once daily in the evening for 12 weeks. Atogepant 60 mg capsule orally once daily in the morning and one placebo-matching atogepant capsule orally in the evening for 12 weeks. Atogepant 30 mg capsule orally twice daily (BID); 1 capsule in the morning and 1 capsule in the evening for 12 weeks. Atogepant 60 mg capsule orally twice daily; 1 capsule in the morning and 1 capsule in the evening for 12 weeks.
All-Cause Mortality
Placebo Atogepant 10 mg QD Atogepant 30 mg QD Atogepant 60 mg QD Atogepant 30 mg BID Atogepant 60 mg BID
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/186 (0.00%)   0/93 (0.00%)   0/183 (0.00%)   0/186 (0.00%)   0/86 (0.00%)   0/91 (0.00%) 
Hide Serious Adverse Events
Placebo Atogepant 10 mg QD Atogepant 30 mg QD Atogepant 60 mg QD Atogepant 30 mg BID Atogepant 60 mg BID
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/186 (1.08%)   1/93 (1.08%)   2/183 (1.09%)   2/186 (1.08%)   0/86 (0.00%)   0/91 (0.00%) 
Hepatobiliary disorders             
Cholecystitis † 1  0/186 (0.00%)  1/93 (1.08%)  0/183 (0.00%)  0/186 (0.00%)  0/86 (0.00%)  0/91 (0.00%) 
Infections and infestations             
Ureteritis † 1  0/186 (0.00%)  0/93 (0.00%)  1/183 (0.55%)  0/186 (0.00%)  0/86 (0.00%)  0/91 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)             
Hodgkin's disease † 1  1/186 (0.54%)  0/93 (0.00%)  0/183 (0.00%)  0/186 (0.00%)  0/86 (0.00%)  0/91 (0.00%) 
Nervous system disorders             
Migraine † 1  0/186 (0.00%)  0/93 (0.00%)  1/183 (0.55%)  0/186 (0.00%)  0/86 (0.00%)  0/91 (0.00%) 
Pregnancy, puerperium and perinatal conditions             
Abortion † 1  0/186 (0.00%)  0/93 (0.00%)  0/183 (0.00%)  1/186 (0.54%)  0/86 (0.00%)  0/91 (0.00%) 
Psychiatric disorders             
Overdose † 1  0/186 (0.00%)  0/93 (0.00%)  0/183 (0.00%)  1/186 (0.54%)  0/86 (0.00%)  0/91 (0.00%) 
Major depression † 1  0/186 (0.00%)  0/93 (0.00%)  0/183 (0.00%)  1/186 (0.54%)  0/86 (0.00%)  0/91 (0.00%) 
Renal and urinary disorders             
Ureterolithiasis † 1  1/186 (0.54%)  0/93 (0.00%)  0/183 (0.00%)  0/186 (0.00%)  0/86 (0.00%)  0/91 (0.00%) 
1
Term from vocabulary, MedDRA 20.1
†
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 QD Atogepant 30 mg QD Atogepant 60 mg QD Atogepant 30 mg BID Atogepant 60 mg BID
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   36/186 (19.35%)   17/93 (18.28%)   47/183 (25.68%)   52/186 (27.96%)   21/86 (24.42%)   26/91 (28.57%) 
Gastrointestinal disorders             
Nausea † 1  9/186 (4.84%)  5/93 (5.38%)  13/183 (7.10%)  21/186 (11.29%)  7/86 (8.14%)  9/91 (9.89%) 
Constipation † 1  4/186 (2.15%)  2/93 (2.15%)  10/183 (5.46%)  9/186 (4.84%)  3/86 (3.49%)  6/91 (6.59%) 
General disorders             
Fatigue † 1  6/186 (3.23%)  1/93 (1.08%)  3/183 (1.64%)  5/186 (2.69%)  2/86 (2.33%)  9/91 (9.89%) 
Infections and infestations             
Upper respiratory tract infection † 1  14/186 (7.53%)  6/93 (6.45%)  13/183 (7.10%)  9/186 (4.84%)  4/86 (4.65%)  6/91 (6.59%) 
Nasopharyngitis † 1  4/186 (2.15%)  3/93 (3.23%)  10/183 (5.46%)  14/186 (7.53%)  1/86 (1.16%)  1/91 (1.10%) 
Investigations             
Blood creatine phosphokinase increased † 1  2/186 (1.08%)  3/93 (3.23%)  3/183 (1.64%)  2/186 (1.08%)  5/86 (5.81%)  2/91 (2.20%) 
1
Term from vocabulary, MedDRA 20.1
†
Indicates events were collected by systematic assessment
[Not Specified]
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
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Allergan
ClinicalTrials.gov Identifier: NCT02848326    
Other Study ID Numbers: CGP-MD-01
First Submitted: July 26, 2016
First Posted: July 28, 2016
Results First Submitted: November 13, 2018
Results First Posted: December 6, 2018
Last Update Posted: December 6, 2018