A Study in Migraine Prevention

• ClinicalTrials.gov Identifier: NCT01184508
• Recruitment Status: Terminated
• First Posted: August 19, 2010
• Results First Posted: September 12, 2018
• Last Update Posted: September 12, 2018
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

Study Description

Brief Summary:

The primary objective of this study is to measure the change in frequency of migraine attacks per 28 days in migraine patients being treated orally with LY2300559 for 12 weeks.

Condition or disease	Intervention/treatment	Phase
Migraine Headache	Drug: Placebo; Drug: LY2300559	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 87 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: A Randomized, Double-Blind, Placebo Controlled Proof of Concept Study of LY2300559 in Patients With Migraine
• Study Start Date: January 2011
• Actual Primary Completion Date: April 2012
• Actual Study Completion Date: April 2012

Arms and Interventions

Arm	Intervention/treatment
Experimental: LY2300559	Drug: LY2300559; 300 milligrams (mg) administered orally, once daily, for 12 weeks
Placebo Comparator: Placebo	Drug: Placebo; Administered orally, once daily, for 12 weeks

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline to 12 Week Endpoint in the Number of Migraine Attacks [ Time Frame: Baseline and Month 3 ]
   The definition of a migraine (a headache lasting 4 to 72 hours) was based on the International Headache Society (IHS) diagnostic criteria. The number of migraine attacks per month was normalized to a 28-day month and calculated as the (number of migraine attacks*28 days)/number of days in the specified month.

Secondary Outcome Measures :

1. Change From Baseline to 12 Week Endpoint in Severity of Migraine Intensity (Mild, Moderate, Severe) [ Time Frame: Baseline and Month 3 ]
   The participant-reported severity of migraines was rated on a 3-point categorical scale (Mild, Moderate, or Severe). Participants could report a severity of none (score = 0), mild (1), moderate (2), or severe (3). In general, if a headache was mild, daily activities could be resumed and little to no medication was taken. Moderate headaches required medication and effected daily activities. Severe headaches were debilitating and required medication. If a participant had multiple migraines during Month 3 (normalized to 28 days), the most severe migraine was analyzed.
2. Change From Baseline to 12 Week Endpoint in Average Duration of Migraine Symptoms [ Time Frame: Baseline and Month 3 ]
   The duration of migraine symptoms was the amount of time from the beginning of each individual migraine attack to the end of each migraine attack. Two attacks separated by <24 hours were considered part of the same migraine and duration was calculated as such. Migraine symptoms included photophobia, phonophobia, nausea, and vomiting. No data collected for aura and vomiting's migraine symptoms.
3. Mean Change From Baseline to 12 Week Endpoint in the Number of Migraine Days [ Time Frame: Baseline and Month 3 ]
   A migraine day was any day with a migraine attack (a headache lasting 4 to 72 hours). The number of migraine days per month was normalized to a 28-day month and calculated as the (number of migraine days*28)/number of days in the specified month.
4. Change From Baseline to 12 Week Endpoint in Clinical Global Impression of Improvement (CGI-I) [ Time Frame: Baseline(Day 28) and Week 12 (Day 84) ]
   The CGI-I was a 1-item scale that measured the clinician's perception of the improvement in migraine symptoms compared with the start of treatment. Scores ranged from 1 (very much improved) to 7 (very much worse). A score of 4 indicated no change.
5. Change From Baseline to 12 Week Endpoint in Patient's Global Impression of Improvement (PGI-I) [ Time Frame: Baseline (Day 28) and Week 12 (Day 84) ]
   The PGI-I was a 1-item scale that measured the participant's perception of improvement in migraine symptoms compared with the start of treatment. Scores ranged from 1 (very much improved) to 7 (very much worse). A score of 4 indicated no change.
6. Change From Baseline to 12 Week Endpoint in Migraine-Specific Quality of Life Questionnaire (MSQ) Score [ Time Frame: Baseline and Week 12 ]
   The MSQ was a 14-item self-administered scale that assessed the participant's perception of quality of life for 3 dimensions [role restriction or restrictive function (Items 1-7), role prevention or preventive function (Items 8-11), and emotional function (Items 12-14)]. Participants rated each item from 1 (none of the time) to 6 (all of the time). Since each item was presented as a negative statement, participant responses were recoded before item scores were calculated. Then, dimension scores were calculated as the sum of the recoded items for that specific dimension. Each dimension score was transformed into a score that ranged from 0 to 100. The transformation formula for the restrictive function = [(dimension score-7)*100]/35, for the preventive function = [(dimension score-4)*100]/20, and for the emotional function = [(dimension score-3)*100]/15. A lower score indicated a poorer quality of life associated with that domain.
7. Change From Baseline to 12 Week Endpoint in Migraine Interictal Burden Scale (MIBS-4) Overall Weighted Score [ Time Frame: Baseline and Week 12 ]
   MIBS-4 was a 4-item self-administered scale that assessed the impact of headaches on the participant's life between headache attacks. Each item measured a specific domain (impairment in work or school, impairment in family and social life, difficulty making plans or commitments, or emotional/affective and cognitive distress). For each item and domain, scores were weighted as follows: Don't know (0), Never (0), Rarely (1), Some of the time (2), Much of the time (3), and All of the time (4). The overall weighted score was the sum of the domain scores and ranged from 0 to 16. Higher scores indicated a greater impact of headaches on the participant's life between headache attacks.
8. Pharmacokinetics: Area Under the Plasma Concentration-Time Curve at the Steady State (AUCtau,ss) of LY2300559 [ Time Frame: Baseline and Week 8 (1 to 3 hours postdose), Weeks 2 and 4 (predose and 1 to 3 hours postdose), Week 12 (predose, 1 to 3 hours postdose, and 5 hours postdose) ]
9. Percentage of Participants Using Breakthrough Medications [ Time Frame: Month 3 ]
   Participants were allowed to use a pre-approved list of medications for the treatment of breakthrough migraines during the study, as long as the treatments were the same as those used and reported during the baseline period. Any medications or procedures to prevent migraines were not allowed. Percentage of participants = (number of participants using breakthrough medication/total number of participants)*100. Each month was normalized to a 28-day month.

Other Outcome Measures:

1. Change From Baseline to 12 Week Endpoint in Breakthrough Treatment Therapy for Acute Migraine Attacks [ Time Frame: Baseline, Week 12 ]
   Participants were allowed to use a pre-approved list of medications for the treatment of breakthrough migraines during the study, as long as the treatments were the same as those used and reported during the baseline period. Any medications or procedures to prevent migraines were not allowed. The mean number was calculated by the breakthrough (BH) medications (meds) per migraine used by each participant per month. Each month was normalized to a 28-day month.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Are migraine patients with migraine onset before 50 years of age
• Present with diagnosis of at least 1 year with migraine attack defined by International Headache Society (IHS) guidelines
• Have a frequency of 4 to 14 migraine attacks, with or without aura, per month (with no more than 14 headache days per month, migraine or non-migraine) for at least the last 6 months
• Female patients of childbearing potential must test negative for pregnancy at the time of enrollment and agree to use a reliable method of birth control during the study

Exclusion Criteria:

• Are currently enrolled in, or discontinued within the previous 6 months from a migraine clinical trial involving an investigational drug or device or off-label use of a drug or device
• Are currently enrolled in, or discontinued within the previous 30 days from screening from a non-migraine clinical trial involving an investigational drug or device or off-label use of a drug or device, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
• Have previously completed or withdrawn from this study or any other study investigating LY2300559
• Have known allergies to LY2300559 or related compounds (such as montelukast)
• Are under treatment with medication or procedures for prevention of migraine, or are taking any other medications that are excluded by the protocol
• Have a history of alcohol or drug abuse/dependence within the past 3 months of screening or are currently using alcohol, drugs of abuse (including opioids, barbiturates, and marijuana), or any prescribed or over-the-counter medication in a manner that the investigator considers indicative of abuse/dependence
• Screen positive for drugs of abuse
• Patients with medication overuse headache as per IHS definition
• Have a body mass index (BMI) of less than 18.5 or greater than or equal to 35.0
• Have history or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs, constituting a risk when taking the study medication or interfering with the interpretation of the data
• Show evidence of serious active neuropsychiatric disease including, but not limited to, bipolar disorder, schizophrenia, psychosis, cluster B personality disorders [for example (eg), borderline personality disorder or narcissistic personality disorder], obsessive-compulsive disorder, or other serious mood, anxiety, depression, or substance/alcohol use disorders
• Have ever in his/her lifetime attempted suicide, have any recent suicidal ideation within the last 3 months, or are at significant risk to commit suicide, as judged by the investigator
• Show evidence or have history of neurological disease such as cerebral vascular accident, pseudotumor cerebri, multiple sclerosis, transient ischemic attack, syncopal episodes, encephalitis, or meningitis
• Have a history or seizures other than febrile
• Female patients who are pregnant or breast-feeding
• Females of childbearing potential who are not using a clinically acceptable method of birth control (eg, oral contraceptives or abstinence)
• Are unwilling or unable to comply with the use of a data collection device to directly record patient data
• Are otherwise unable to comply with the requirements of the study

Contacts and Locations

Locations

United States, Arizona

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Phoenix, Arizona, United States, 85004

United States, California

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Long Beach, California, United States, 90806

United States, Connecticut

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Fairfield, Connecticut, United States, 06824

United States, Florida

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Miami, Florida, United States, 33143

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

West Palm Beach, Florida, United States, 33407

United States, Michigan

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Ann Arbor, Michigan, United States, 48104

United States, Missouri

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Saint Louis, Missouri, United States, 63141

United States, Oregon

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Portland, Oregon, United States, 97210

United States, Pennsylvania

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Philadelphia, Pennsylvania, United States, 19107 5098

United States, Tennessee

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Nashville, Tennessee, United States, 37203

United States, Washington

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Seattle, Washington, United States, 98104

Puerto Rico

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

San Juan, Puerto Rico, 00923

Sponsors and Collaborators

Eli Lilly and Company

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9AM - 5 PM Eastern Time (UTC/GMT - 5 hours, EST); Eli Lilly and Company

More Information

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT01184508
• Other Study ID Numbers: 13313; I1N-MC-CDBE ( Other Identifier: Eli Lilly and Company )
• First Posted: August 19, 2010
• Results First Posted: September 12, 2018
• Last Update Posted: September 12, 2018
• Last Verified: August 2018

Keywords provided by Eli Lilly and Company:

classic with aura; common without aura; migraine; headache

Additional relevant MeSH terms:

Migraine Disorders; Headache; Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pain; Neurologic Manifestations