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

• 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: Allergan
• Information provided by (Responsible Party): Allergan

Tracking Information

• First Submitted Date: July 26, 2016
• First Posted Date: July 28, 2016
• Results First Submitted Date: November 13, 2018
• Results First Posted Date: December 6, 2018
• Last Update Posted Date: December 6, 2018
• Actual Study Start Date: September 6, 2016
• Actual Primary Completion Date: April 2, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 13, 2018)

Change From Baseline in Mean Monthly Migraine Days (Migraine/Probable Migraine Headache Days) Across the 12-Week Treatment Period [ Time Frame: Baseline (First 28 Days of Screening/Baseline Period) to Week 12 ]

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.

• Original Primary Outcome Measures (submitted: July 26, 2016): Change from Baseline in the Mean Number of Migraine/Probable Migraine Headache Days [ Time Frame: Baseline, Last 28 days of the treatment period ending with Week 12 ]

Current Secondary Outcome Measures (submitted: November 13, 2018)

• Change From Baseline in Mean Monthly Headache Days Across the 12-Week Treatment Period [ Time Frame: Baseline (First 28 Days of Screening/Baseline Period) to Week 12 ]
  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.
• 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 [ Time Frame: Baseline (First 28 Days of Screening/Baseline Period) to Week 12 ]
  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.
• Change From Baseline in Mean Monthly Acute Medication Use Days Across the 12-Week Treatment Period [ Time Frame: Baseline (First 28 Days of Screening/Baseline Period) to Week 12 ]
  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.

Original Secondary Outcome Measures (submitted: July 26, 2016)

• Change from Baseline in the Number of Headache Days [ Time Frame: Baseline, Last 28 days of the treatment period ending with Week 12 ]
• Percentage of Participants with at Least a 50% Reduction in Migraine/Probable Migraine Headache Days [ Time Frame: Baseline, Last 28 days of the treatment period ending with Week 12 ]
• Change from Baseline in the Activities of Daily Living (ADL) Domain Score of the ACM-I (Assessment of Chronic Migraine Impact) using a 24 Item Questionnaire [ Time Frame: Baseline, Week 12 ]
• Percentage of Participants "Satisfied" or "Extremely Satisfied" with Migraine Prevention [ Time Frame: Week 12 ]
• Change from Baseline in the Number of Triptan Use Days [ Time Frame: Baseline, Last 28 days of the treatment period ending with Week 12 ]
• Change from Baseline in the Headache Impact Test (HIT-6) Total Score at Week 12 using a 6-Question Assessment [ Time Frame: Baseline, Week 12 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Efficacy, Safety, and Tolerability of Multiple Dosing Regimens of Oral Atogepant (AGN-241689) in Episodic Migraine Prevention
• Official Title: A Phase 2/3, Multicenter, Randomized, Double-Blind, Placebo Controlled, Parallel-Group Study To Evaluate The Efficacy, Safety, And Tolerability Of Multiple Dosing Regimens Of Oral AGN-241689 In Episodic Migraine Prevention
• Brief Summary: This study will evaluate the safety and tolerability of the following doses of atogepant (AGN-241689): 10 mg once daily (QD), 30 mg QD, 30 mg twice daily (BID), 60 mg QD, and 60 mg BID for the prevention of episodic migraine and will characterize the dose/response relationship.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2; Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Prevention
• Condition: Migraine, With or Without Aura

Intervention

• Drug: Atogepant
  Atogepant capsule.
  Other Name: AGN-241689
• Drug: Placebo-matching Atogepant
  Placebo-matching atogepant capsule.

Study Arms

• Placebo Comparator: Placebo
  Placebo-matching atogepant capsule orally twice daily in the morning and in the evening for 12 weeks.
  Intervention: Drug: Placebo-matching Atogepant
• Experimental: Atogepant 10 mg QD
  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.
  Interventions:

  • Drug: Atogepant
  • Drug: Placebo-matching Atogepant
• Experimental: Atogepant 30 mg QD
  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.
  Interventions:

  • Drug: Atogepant
  • Drug: Placebo-matching Atogepant
• Experimental: Atogepant 30 mg BID
  Atogepant 30 mg capsule orally twice daily (BID); 1 capsule in the morning and 1 capsule in the evening for 12 weeks.
  Intervention: Drug: Atogepant
• Experimental: Atogepant 60 mg QD
  Atogepant 60 mg capsule orally once daily in the morning and one placebo-matching atogepant capsule orally in the evening for 12 weeks.
  Interventions:

  • Drug: Atogepant
  • Drug: Placebo-matching Atogepant
• Experimental: Atogepant 60 mg BID
  Atogepant 60 mg capsule orally twice daily; 1 capsule in the morning and 1 capsule in the evening for 12 weeks.
  Intervention: Drug: Atogepant

• Publications *: Goadsby PJ, Dodick DW, Ailani J, Trugman JM, Finnegan M, Lu K, Szegedi A. Safety, tolerability, and efficacy of orally administered atogepant for the prevention of episodic migraine in adults: a double-blind, randomised phase 2b/3 trial. Lancet Neurol. 2020 Sep;19(9):727-737. doi: 10.1016/S1474-4422(20)30234-9. Erratum In: Lancet Neurol. 2020 Nov;19(11):e10.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 5, 2018): 834
• Original Estimated Enrollment (submitted: July 26, 2016): 810
• Actual Study Completion Date: April 23, 2018
• Actual Primary Completion Date: April 2, 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Has at least a 1-year history of migraine with or without aura
• Age of the patient at the time of migraine onset < 50 years
• History of 4 to 14 migraine days (migraine/probable migraine headache days) per month on average in the 3 months prior to Visit 1 in the Investigator's judgment
• Demonstrated compliance with e-diary

Exclusion Criteria:

• Has a history of migraine accompanied by diplopia or decreased level of consciousness and retinal migraine
• Has a current diagnosis of chronic migraine, new persistent daily headache, trigeminal autonomic cephalgia (eg, cluster headache), or painful cranial neuropathy
• Difficulty distinguishing migraine headache from other headaches
• Has a history of malignancy in the prior 5 years, except for adequately treated basal cell or squamous cell skin cancer, or in situ cervical cancer
• Has a history of gastric or small intestinal surgery, or has a disease that causes malabsorption
• Has a history of hepatitis within previous 6 months
• Usage of opioids or barbiturates > 2 days/month, triptans or ergots ≥ 10 days/month, or simple analgesics (eg, aspirin, non-steroidal anti-inflammatory drugs [NSAIDs], acetaminophen) ≥ 15 days/month in the 3 months prior to Visit 1
• Pregnant or nursing females

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02848326
• Other Study ID Numbers: CGP-MD-01
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Allergan
• Original Responsible Party: Same as current
• Current Study Sponsor: Allergan
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Joel Trugman, MD; Allergan

• PRS Account: Allergan
• Verification Date: November 2018