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Study to Evaluate the Safety and Tolerability of Treatment With Atogepant 60 mg Daily for the Prevention of Migraine in Participants With Episodic Migraine

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ClinicalTrials.gov Identifier: NCT03700320
Recruitment Status : Completed
First Posted : October 9, 2018
Results First Posted : June 15, 2021
Last Update Posted : June 15, 2021
Sponsor:
Information provided by (Responsible Party):
Allergan

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Episodic Migraine
Interventions Drug: Standard of Care (SOC) Migraine Preventive Medication
Drug: Atogepant
Enrollment 744
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Oral SOC Migraine Preventive Medication Atogepant 60 mg
Hide Arm/Group Description Oral standard of care (SOC) medication recognized as safe and effective for the prevention of migraine, based on investigator's judgement in consultation with the participant. Atogepant 60 mg tablet taken orally, once daily for 52 weeks.
Period Title: Overall Study
Started 198 546
Safety Population; Received Treatment 196 543
Entered Safety Follow-up 159 472
Completed 136 373
Not Completed 62 173
Reason Not Completed
Adverse Event             5             31
Lack of Efficacy             2             5
Withdrawal by Subject             29             75
Lost to Follow-up             16             23
Pregnancy             2             4
Protocol Deviation             7             31
Non-compliance with Study Drug             1             3
Reason not Specified             0             1
Arm/Group Title Oral SOC Migraine Preventive Medication Atogepant 60 mg Total
Hide Arm/Group Description Oral standard of care (SOC) medication recognized as safe and effective for the prevention of migraine, based on investigator's judgement in consultation with the participant. Atogepant 60 mg tablet taken orally, once daily for 52 weeks. Total of all reporting groups
Overall Number of Baseline Participants 196 543 739
Hide Baseline Analysis Population Description
Safety Population included all participants who received ≥1 dose of study intervention.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 196 participants 543 participants 739 participants
41.1  (12.09) 42.5  (12.03) 42.2  (12.05)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 196 participants 543 participants 739 participants
Female
172
  87.8%
479
  88.2%
651
  88.1%
Male
24
  12.2%
64
  11.8%
88
  11.9%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 196 participants 543 participants 739 participants
Hispanic or Latino
29
  14.8%
83
  15.3%
112
  15.2%
Not Hispanic or Latino
166
  84.7%
460
  84.7%
626
  84.7%
Unknown or Not Reported
1
   0.5%
0
   0.0%
1
   0.1%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 196 participants 543 participants 739 participants
American Indian or Alaska Native
0
   0.0%
3
   0.6%
3
   0.4%
Asian
5
   2.6%
12
   2.2%
17
   2.3%
Native Hawaiian or Other Pacific Islander
2
   1.0%
2
   0.4%
4
   0.5%
Black or African American
38
  19.4%
100
  18.4%
138
  18.7%
White
145
  74.0%
416
  76.6%
561
  75.9%
More than one race
5
   2.6%
10
   1.8%
15
   2.0%
Unknown or Not Reported
1
   0.5%
0
   0.0%
1
   0.1%
1.Primary Outcome
Title Percentage of Participants With at Least 1 Treatment Emergent Adverse Event (TEAE)
Hide Description An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A TEAE is an AE that occurs or worsens after receiving investigational study drug.
Time Frame From first dose up to the end of study (median treatment of 52 weeks) + 4 weeks follow-up
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population included all participants who received ≥1 dose of study intervention.
Arm/Group Title Oral SOC Migraine Preventive Medication Atogepant 60 mg
Hide Arm/Group Description:
Oral standard of care (SOC) medication recognized as safe and effective for the prevention of migraine, based on investigator's judgement in consultation with the participant.
Atogepant 60 mg tablet taken orally, once daily for 52 weeks.
Overall Number of Participants Analyzed 196 543
Measure Type: Number
Unit of Measure: percentage of participants
78.6 67.0
2.Secondary Outcome
Title Percentage of Participants With Clinically Significant Laboratory Values as Assessed by the Investigator
Hide Description Laboratory tests included tests of hematology, chemistry, and urinalysis. The investigator determined if the results were potentially clinically significant (PCS). Only categories with at least one participant are reported.
Time Frame From first dose up to the end of study (median treatment of 52 weeks) + 4 weeks follow-up
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population included all participants who received ≥1 dose of study intervention. Number analyzed is the number of participants with non-missing non-PCS baseline value and ≥1 post-baseline parameter assessment.
Arm/Group Title Oral SOC Migraine Preventive Medication Atogepant 60 mg
Hide Arm/Group Description:
Oral standard of care (SOC) medication recognized as safe and effective for the prevention of migraine, based on investigator's judgement in consultation with the participant.
Atogepant 60 mg tablet taken orally, once daily for 52 weeks.
Overall Number of Participants Analyzed 196 543
Measure Type: Number
Unit of Measure: percentage of participants
Eosinophils Absolute Cell Count (10^9/liter (L)): >2.0 × upper limit of normal (ULN) Number Analyzed 190 participants 531 participants
0.0 0.6
Hematocrit (RATIO): <0.9 × lower limit of normal (LLN) Number Analyzed 190 participants 531 participants
1.6 1.7
Hematocrit (RATIO): >1.1 × ULN Number Analyzed 190 participants 531 participants
0.0 0.2
Hemoglobin (gram (g)/L): <0.9 × LLN Number Analyzed 184 participants 521 participants
3.3 3.1
Lymphocytes Absolute Cell Count (10^9/L): <0.7 × LLN Number Analyzed 189 participants 530 participants
0.5 0.8
Lymphocytes Absolute Cell Count (10^9/L): >1.3 × ULN Number Analyzed 189 participants 530 participants
0.5 0.2
Monocytes Absolute Cell Count (10^9/L): <0.5 × LLN Number Analyzed 190 participants 531 participants
1.1 0.2
Neutrophils Absolute Cell Count (10^9/L): <0.7 × LLN Number Analyzed 189 participants 523 participants
2.1 2.3
Neutrophils Absolute Cell Count (10^9/L): >1.3 × ULN Number Analyzed 189 participants 523 participants
4.8 7.1
Platelet Count (Thrombocytes) (10^9/L): >1.5 × ULN Number Analyzed 189 participants 531 participants
0.5 0.2
Red Blood Cell Count (10^12/L): <0.9 × LLN Number Analyzed 188 participants 529 participants
3.2 2.1
White Blood Cell Count (10^9/L): <0.9 × LLN Number Analyzed 187 participants 526 participants
3.2 4.6
White Blood Cell Count (10^9/L): >1.5 × ULN Number Analyzed 187 participants 526 participants
1.1 0.6
Alanine Aminotransferase (serum glutamic-pyruvic transaminase (SGPT)) (Unit (U)/L): ≥3.0 × ULN Number Analyzed 190 participants 530 participants
1.6 1.9
Aspartate Aminotransferase (serum glutamic-oxaloacetic transaminase (SGOT)) (U/L): ≥3.0 × ULN Number Analyzed 190 participants 529 participants
2.1 1.5
Bicarbonate (HCO3) (millimole (mmol)/L): <0.9 × LLN Number Analyzed 190 participants 531 participants
1.6 0.8
Bilirubin, Total (micromole (umol)/L): ≥1.5 × ULN Number Analyzed 190 participants 530 participants
0.0 0.8
Blood Urea Nitrogen (mmol/L): >1.5 × ULN Number Analyzed 190 participants 531 participants
0.5 0.4
Creatine Kinase (U/L): >2.0 × ULN Number Analyzed 185 participants 525 participants
14.1 9.1
Creatinine (umol/L): >1.5 × ULN Number Analyzed 190 participants 531 participants
1.1 0.4
Glomerular Filtration Rate(GFR) Estimated Calculation:<60 milliliter(mL)/minute(min)/1.73 meter(m)^2 Number Analyzed 184 participants 503 participants
15.2 15.9
Glucose, Non-fasting (mmol/L): <0.8 × LLN Number Analyzed 188 participants 527 participants
5.3 4.2
Glucose, Non-fasting (mmol/L): >2.0 × ULN Number Analyzed 188 participants 527 participants
2.1 0.8
Lactate Dehydrogenase (U/L): >3.0 × ULN Number Analyzed 189 participants 529 participants
0.0 0.4
Phosphorus (mmol/L): <0.9 × LLN Number Analyzed 190 participants 530 participants
2.1 2.6
Phosphorus (mmol/L): >1.1 × ULN Number Analyzed 190 participants 530 participants
0.0 0.2
Potassium (mmol/L): <0.9 × LLN Number Analyzed 188 participants 525 participants
1.1 0.8
Potassium (mmol/L): >1.1 × ULN Number Analyzed 188 participants 525 participants
4.3 5.1
Protein, Total (g/L): <0.9 × LLN Number Analyzed 190 participants 531 participants
3.2 1.5
Uric Acid (Urate) (umol/L): >1.2 × ULN Number Analyzed 190 participants 531 participants
1.6 1.1
Urine Glucose At Least 1+ Number Analyzed 185 participants 526 participants
4.3 3.0
Urine Protein: At Least 1+ Number Analyzed 183 participants 497 participants
26.2 27.4
3.Secondary Outcome
Title Percentage of Participants With Clinically Significant Electrocardiogram (ECG) Findings as Assessed by the Investigator
Hide Description A standard 12-lead ECG was performed. The investigator determined if the result was potentially clinically significant. Only categories with at least one participant are reported.
Time Frame Up to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population included all participants who received ≥1 dose of study intervention. Number analyzed is the number of participants with non-missing non-PCS baseline value and ≥1 post-baseline parameter assessment.
Arm/Group Title Oral SOC Migraine Preventive Medication Atogepant 60 mg
Hide Arm/Group Description:
Oral standard of care (SOC) medication recognized as safe and effective for the prevention of migraine, based on investigator's judgement in consultation with the participant.
Atogepant 60 mg tablet taken orally, once daily for 52 weeks.
Overall Number of Participants Analyzed 196 543
Measure Type: Number
Unit of Measure: percentage of participants
PR Interval, Single Beat millisecond (msec): ≥250 Number Analyzed 179 participants 513 participants
0.0 0.2
QTcB Interval, Single Beat (msec): Increase >60 from Baseline (BL) Number Analyzed 180 participants 514 participants
0.6 0.4
QTcF Interval, Single Beat (msec): Increase >60 from BL Number Analyzed 180 participants 514 participants
0.6 0.0
4.Secondary Outcome
Title Percentage of Participants With Clinically Significant Vital Sign Measurements as Assessed by the Investigator
Hide Description Vital sign measurements included sitting and standing blood pressure (BP), sitting and standing pulse rate, respiratory rate, temperature, and body weight. The investigator determined if the results were clinically significant. Only categories with at least one participant are reported.
Time Frame From first dose up to the end of study (median treatment of 52 weeks + 4 weeks follow-up)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population included all participants who received ≥1 dose of study intervention. Number analyzed is the number of participants with non-missing non-PCS baseline value and ≥1 post-baseline parameter assessment.
Arm/Group Title Oral SOC Migraine Preventive Medication Atogepant 60 mg
Hide Arm/Group Description:
Oral standard of care (SOC) medication recognized as safe and effective for the prevention of migraine, based on investigator's judgement in consultation with the participant.
Atogepant 60 mg tablet taken orally, once daily for 52 weeks.
Overall Number of Participants Analyzed 196 543
Measure Type: Number
Unit of Measure: percentage of participants
Systolic Blood Pressure (SBP) Sitting (millimeter of mercury(mmHg)):≤90 and Decrease of ≥20 from BL Number Analyzed 190 participants 531 participants
3.7 2.6
SBP Sitting (mmHg): ≥180 and Increase of ≥20 from BL Number Analyzed 190 participants 531 participants
0.0 0.4
SBP Standing (mmHg): ≤90 and Decrease of ≥20 from BL Number Analyzed 190 participants 531 participants
5.8 3.4
SBP Standing (mmHg): ≥180 and Increase of ≥20 from BL Number Analyzed 190 participants 531 participants
0.0 0.6
Standing - Sitting SBP (mmHg): ≤-20 Number Analyzed 189 participants 526 participants
13.8 11.4
Diastolic Blood Pressure (DBP) Sitting (mmHg): ≤50 and Decrease of ≥15 from BL Number Analyzed 190 participants 531 participants
3.2 0.6
DBP Sitting (mmHg): ≥105 and Increase of ≥15 from BL Number Analyzed 190 participants 531 participants
1.1 2.3
DBP Standing (mmHg): ≤50 and Decrease of ≥15 from BL Number Analyzed 190 participants 531 participants
1.1 0.9
DBP Standing (mmHg): ≥105 and Increase of ≥15 from BL Number Analyzed 190 participants 531 participants
5.8 4.0
Standing - Sitting DBP (mmHg): ≤-15 Number Analyzed 189 participants 528 participants
10.1 8.7
Pulse Rate (PR) Sitting (beats/min): ≤50 and Decrease of ≥15 from BL Number Analyzed 190 participants 531 participants
1.6 1.1
PR Standing (beats/min): ≤50 and Decrease of ≥15 from BL Number Analyzed 190 participants 531 participants
0.0 0.2
PR Standing (beats/min): ≥120 and Increase of ≥15 from BL Number Analyzed 190 participants 531 participants
2.6 1.3
Standing - Sitting PR (beats/min): ≥25 Number Analyzed 190 participants 528 participants
6.3 10.0
Weight (kg): Decrease of ≥7% from BL Number Analyzed 190 participants 531 participants
14.7 24.1
Weight (kg): Increase of ≥7% from BL Number Analyzed 190 participants 531 participants
12.6 7.3
5.Secondary Outcome
Title Number of Participants With Most Severe Columbia-Suicide Severity Rating Scale (C-SSRS) Assessing Suicidal Ideation or Suicidal Behavior
Hide Description The C-SSRS is a clinician-rated instrument that reports the severity of both suicidal ideation and behavior. Suicidal ideation was classified on a 5-item scale: 1 (wish to be dead), 2 (nonspecific active suicidal thoughts), 3 (active suicidal ideation with any methods [not plan] without intent to act), 4 (active suicidal ideation with some intent to act, without specific plan), and 5 (active suicidal ideation with specific plan and intent). Suicidal behavior is classified on a 5-item scale: 0 (no suicidal behavior), 1 (preparatory acts or behavior), 2 (aborted attempt), 3 (interrupted attempt), and 4 (actual attempt). More than 1 classification can be selected provided they represent separate episodes. (Minimum total score 0, maximum total score 5; higher total scores indicate more suicidal ideation and/or suicidal behavior). Only the most severe suicidal ideation and the most severe suicidal behavior counted during the treatment period for at least 1 participant are reported.
Time Frame Up to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population included all participants who received ≥1 dose of study intervention.
Arm/Group Title Oral SOC Migraine Preventive Medication Atogepant 60 mg
Hide Arm/Group Description:
Oral standard of care (SOC) medication recognized as safe and effective for the prevention of migraine, based on investigator's judgement in consultation with the participant.
Atogepant 60 mg tablet taken orally, once daily for 52 weeks.
Overall Number of Participants Analyzed 196 543
Measure Type: Count of Participants
Unit of Measure: Participants
Suicidal Ideation (SI): Wish to be Dead
4
   2.0%
0
   0.0%
SI: Non-Specific Active Suicidal Thoughts
1
   0.5%
2
   0.4%
SI: Active SI with Some Intent to Act, Without Specific Plan
0
   0.0%
1
   0.2%
SI: Active SI With Specific Plan and Intent
0
   0.0%
2
   0.4%
Suicidal Behavior (SB): Actual Attempt
0
   0.0%
2
   0.4%
Time Frame From first dose up to the end of study (median treatment of 52 weeks + 4 weeks follow-up)
Adverse Event Reporting Description All-cause Mortality: Intent-to-treat (ITT) Population included all randomized participants. Adverse Events: Safety Population included all participants who received ≥1 dose of study intervention.
 
Arm/Group Title Oral SOC Migraine Preventive Medication Atogepant 60 mg
Hide Arm/Group Description Oral standard of care (SOC) medication recognized as safe and effective for the prevention of migraine, based on investigator's judgement in consultation with the participant. Atogepant 60 mg tablet taken orally, once daily for 52 weeks.
All-Cause Mortality
Oral SOC Migraine Preventive Medication Atogepant 60 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   0/198 (0.00%)   2/546 (0.37%) 
Hide Serious Adverse Events
Oral SOC Migraine Preventive Medication Atogepant 60 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   7/196 (3.57%)   24/543 (4.42%) 
Ear and labyrinth disorders     
Vertigo  1  0/196 (0.00%)  1/543 (0.18%) 
Gastrointestinal disorders     
Vomiting  1  0/196 (0.00%)  1/543 (0.18%) 
General disorders     
Non-cardiac chest pain  1  2/196 (1.02%)  0/543 (0.00%) 
Hepatobiliary disorders     
Cholecystitis  1  0/196 (0.00%)  1/543 (0.18%) 
Infections and infestations     
Beta haemolytic streptococcal infection  1  0/196 (0.00%)  1/543 (0.18%) 
Corona virus infection  1  0/196 (0.00%)  1/543 (0.18%) 
Pneumonia  1  0/196 (0.00%)  1/543 (0.18%) 
Sepsis  1  0/196 (0.00%)  1/543 (0.18%) 
Injury, poisoning and procedural complications     
Joint dislocation  1  0/196 (0.00%)  1/543 (0.18%) 
Overdose  1  0/196 (0.00%)  1/543 (0.18%) 
Rib fracture  1  0/196 (0.00%)  1/543 (0.18%) 
Metabolism and nutrition disorders     
Dehydration  1  0/196 (0.00%)  1/543 (0.18%) 
Electrolyte imbalance  1  0/196 (0.00%)  1/543 (0.18%) 
Musculoskeletal and connective tissue disorders     
Osteonecrosis  1  1/196 (0.51%)  0/543 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Adenocarcinoma of colon  1  0/196 (0.00%)  1/543 (0.18%) 
Basal cell carcinoma  1  0/196 (0.00%)  1/543 (0.18%) 
Malignant melanoma  1  0/196 (0.00%)  1/543 (0.18%) 
Neuroendocrine carcinoma metastatic  1  0/196 (0.00%)  1/543 (0.18%) 
Uterine leiomyoma  1 [1]  0/172 (0.00%)  1/479 (0.21%) 
Breast cancer  1  1/196 (0.51%)  0/543 (0.00%) 
Colon cancer metastatic  1  1/196 (0.51%)  0/543 (0.00%) 
Nervous system disorders     
Cervical radiculopathy  1  0/196 (0.00%)  1/543 (0.18%) 
Epilepsy  1  0/196 (0.00%)  1/543 (0.18%) 
Migraine  1  0/196 (0.00%)  1/543 (0.18%) 
Status migrainosus  1  0/196 (0.00%)  1/543 (0.18%) 
Transient global amnesia  1  0/196 (0.00%)  1/543 (0.18%) 
Product Issues     
Device malfunction  1  1/196 (0.51%)  0/543 (0.00%) 
Psychiatric disorders     
Anxiety  1  0/196 (0.00%)  1/543 (0.18%) 
Suicidal behaviour  1  0/196 (0.00%)  1/543 (0.18%) 
Suicide attempt  1  0/196 (0.00%)  1/543 (0.18%) 
Suicidal ideation  1  1/196 (0.51%)  0/543 (0.00%) 
Reproductive system and breast disorders     
Ovarian cyst  1 [1]  0/172 (0.00%)  1/479 (0.21%) 
Uterine haemorrhage  1 [1]  0/172 (0.00%)  1/479 (0.21%) 
Respiratory, thoracic and mediastinal disorders     
Acute respiratory distress syndrome  1  0/196 (0.00%)  1/543 (0.18%) 
Lung perforation  1  0/196 (0.00%)  1/543 (0.18%) 
Social circumstances     
Victim of crime  1  0/196 (0.00%)  1/543 (0.18%) 
Victim of homicide  1  0/196 (0.00%)  1/543 (0.18%) 
1
Term from vocabulary, MedDRA Version 22.0
Indicates events were collected by systematic assessment
[1]
Number of participants at risk are female participants as this adverse event is specific to females.
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Oral SOC Migraine Preventive Medication Atogepant 60 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   91/196 (46.43%)   197/543 (36.28%) 
Gastrointestinal disorders     
Constipation  1  6/196 (3.06%)  39/543 (7.18%) 
Nausea  1  12/196 (6.12%)  34/543 (6.26%) 
General disorders     
Fatigue  1  12/196 (6.12%)  14/543 (2.58%) 
Infections and infestations     
Upper respiratory tract infection  1  24/196 (12.24%)  56/543 (10.31%) 
Urinary tract infection  1  9/196 (4.59%)  28/543 (5.16%) 
Nasopharyngitis  1  10/196 (5.10%)  24/543 (4.42%) 
Investigations     
Weight increased  1  11/196 (5.61%)  7/543 (1.29%) 
Nervous system disorders     
Dizziness  1  22/196 (11.22%)  17/543 (3.13%) 
Paraesthesia  1  12/196 (6.12%)  8/543 (1.47%) 
Psychiatric disorders     
Anxiety  1  11/196 (5.61%)  15/543 (2.76%) 
1
Term from vocabulary, MedDRA Version 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: IR-CTRegistration@allergan.com
Layout table for additonal information
Responsible Party: Allergan
ClinicalTrials.gov Identifier: NCT03700320    
Other Study ID Numbers: 3101-302-002
First Submitted: September 25, 2018
First Posted: October 9, 2018
Results First Submitted: May 20, 2021
Results First Posted: June 15, 2021
Last Update Posted: June 15, 2021