Migraine Disorders
Conditions
Keywords
COL-144, acute treatment, migraine
Brief summary
The purpose of this study is to evaluate the efficacy and safety of a range of oral doses of COL-144 in treating migraine headache, in order to select a dose or doses for further evaluation.
Detailed description
Migraine is a common chronic neurological disorder characterized by recurrent disabling episodes of moderate to severe headache accompanied by nausea, vomiting, photophobia, and phonophobia. Acute pharmacologic therapy for migraine aims to terminate the attack or reduce its severity. Analgesics are commonly used or, if these are ineffective, triptans. Since triptans are contraindicated in patients with coronary artery disease, uncontrolled hypertension, and cerebrovascular disease alternative medications are required for patients where simple analgesics do not work. COL-144 has no vasoconstrictor activity at clinically relevant concentrations and might meet this need. COL-144 was effective when given intravenously in a placebo-controlled dose-ranging study. This study investigates which dose of oral COL-144 is effective in the in acute treatment of migraine headache.
Interventions
DRUGLasmiditan
Oral application of one dose of either 50 mg lasmiditan,100 mg lasmiditan, 200 mg lasmiditan, 400 mg lasmiditan or placebo as the first treatment for a new migraine attack providing that any aura symptoms have resolved and the headache is either moderate or severe and has been so for less than 4 hours.
DRUGPlacebo
Placebo
Sponsors
CoLucid Pharmaceuticals
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Patients with migraine with or without aura fulfilling the IHS diagnostic criteria 1.1 and 1.2.1 (2004) * History of migraine of at least 1 year * Migraine onset before the age of 50 years * History of 1 - 8 migraine attacks per month * Male or female patients aged 18 to 65 years * Female patients of child-bearing potential must be using a highly effective form of contraception (e.g., combined oral contraceptive, IUD, abstinence, vasectomized partner) * Able and willing to give written informed consent * Able and willing to complete a migraine diary card to record details of the attack treated with study medication
Exclusion criteria
* History of life threatening or intolerable adverse reaction to any triptan * Use of prescription migraine prophylactic drugs within 15 days (30 days for flunarizine) prior to Screening Visit and during study participation * Using herbal preparations (e.g., feverfew, butterbur) for migraine prophylaxis * Using 5-HT reuptake inhibitors * Using drugs known to inhibit CYP450 enzymes (see Appendix 2 for details) * Pregnant or breast-feeding women * Women of child-bearing potential not using highly effective contraception * History or evidence of coronary artery disease, ischemic or hemorrhagic stroke, epilepsy or any other condition placing the patient at increased risk of seizures * History of hypertension (controlled or uncontrolled) * History of orthostatic hypotension * Current use of hemodynamically active cardiovascular drugs * History within the previous 3 years or current evidence of abuse of any drug, prescription or illicit, or alcohol * Significant renal or hepatic impairment * Previous participation in this clinical trial * Participation in any clinical trial of an experimental drug or device in the previous 30 days * Any medical condition or laboratory test which in the judgment of the investigator makes the patient unsuitable for the study * Known Hepatitis B or C or HIV infection * Patients who are employees of the sponsor * Relatives of, or staff directly reporting to, the investigator * Patients with known hypersensitivity to COL-144, other 5HT1F receptor agonists or to any excipient of COL-144 drug product * Patients who were treated with study medication in the COL MIG-201 study (Patients screened but not treated under that protocol are not excluded)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Headache Response | 2 hours postdose | Headache response is a binary response variable derived from the headache intensities recorded in the participant diary. Headache response is defined as a reduction in headache severity from moderate or severe at baseline to mild or no headache, at two hours after administration of study drug. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Headache Recurrence | up to 24 hours postdose | Participants who received study drug and which became pain free at 2 hours postdose and worsened again upto 24 hours post-dose. |
| Percentage of Participants With Headache Severity (4 Point Rating Scale) | 2 hours postdose | Headache severity was evaluated by the participant using the International Headache Society (IHS) four point headache severity rating scale (0=no pain, 1=mild pain, 2=moderate pain, and 3=severe pain) with a lower score being less severe and a higher score being more severe. |
| Percentage of Participants Who Have Symptoms of Nausea | 2 hours postdose | Percentage of participants who have symptoms of nausea two hours post treatment. |
| Percentage of Participants Who Have Symptoms Phonophobia | 2 hours postdose | Percentage of participants who have symptoms of phonophobia two hours post treatment. |
| Percentage of Participants Who Have Photophobia | 2 hours postdose | Percentage of participants who have symptoms of photophobia two hours post treatment. |
| Percentage of Participants With Vomiting | 2 hours postdose | Percentage of participants with vomiting 2 hours post treatment. |
| Disability (4 Point Scale: Not at All, Mild Interference, Marked Interference, Completely - Needs Bed Rest) | 2 hours postdose | The participant is asked How much is the migraine interfering with normal activities? on a 4 point scale 0-Not at all, 1-Mild interference, 2-Marked interference ,3-Completely needs bed rest, with a lower score having lower interference and higher score worse interference. |
| Percentage of Participants Who Used Rescue Medication | Postdose 2 through 24 hours | Rescue medication was permitted after completion of the 2 hour assessment if migraine did not respond (participant was not pain free). |
| Percentage of Participants Who Are Headache Free (Absence of Headache) After First Dose | 2 hours post dose | The percentage of participants defined as mild, moderate, or severe headache pain becoming none. |
| Actual Time to Headache Relief and Time to Pain Free | up to 24 hours postdose | The participant answered Did your migraine pain go away completely (pain free) within 24 hours of dosing and record the time. Actual time to meaningful pain relief and actual time to pain free will be censored at 24 hours if meaningful pain relief or pain free is documented to be greater than 24 hours after dosing and Did you experience meaningful relief (headache relief) from your migraine within 24 hours after dosing?. |
| Change From Baseline in Heart Rate | Baseline through Day 14 | Change from baseline in assessment of vital signs (heart rate). |
| Change From Baseline in Systolic Blood Pressure | Baseline through Day 14 | Change from baseline in vital signs (systolic blood pressure). |
| Change From Baseline in Diastolic Blood Pressure | Baseline through Day 14 | Change from baseline in vital signs (diastolic blood pressure). |
| Percentage of Participants With Change From Baseline in Physical Examination Parameters | Baseline through Day 14 | Participants were evaluated for skin, head, ear, nose and throat, cardiovascular and musculoskeletal changes from a normal screening to an abnormal screening. Changes in the physical examination noted as non-serious AEs or SAEs, regardless of causality, are located in the Reported Adverse Events section. |
| Change From Baseline in Hematology Tests | Baseline through Day 14 | Hematology tests, including a complete blood count (CBC) measured red blood cells, white blood cells, hemoglobin, neutrophils and platelets. |
| Number of Serious Adverse Events | up to 8 weeks | A summary of non-serious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section. |
| Number of Participants Reporting a Score on the Patient Global Impression of Improvement (PGI-I) | 2 hours postdose | PGI-I requests participants to mark the box that best describes their cluster headache condition since they started taking the medicine. The options in the displayed boxes are represented on a 7-point scale, with 1 = very much better, 2 = much better, 3 = a little better, 4 = no change, 5 = a little worse, 6 = much worse, and 7 = very much worse, a lower number indicates much better and a higher number indicates worse. |
Countries
Belgium, Finland, France, Germany, Spain
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 50 mg Lasmiditan 50 mg lasmiditan administered PO within 4 hours of a migraine attack | 82 |
| 100 mg Lasmiditan 100 mg lasmiditan administered PO within 4 hours of a migraine attack | 82 |
| 200 mg Lasmiditan 200 mg lasmiditan administered PO within 4 hours of a migraine attack | 71 |
| 400 mg Lasmiditan 400 mg lasmiditan administered PO within 4 hours of a migraine attack | 70 |
| Placebo Placebo administered PO within 4 hours of a migraine attack | 86 |
| Total | 391 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Did not use study medication | 24 | 22 | 29 | 29 | 17 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | 50 mg Lasmiditan | 100 mg Lasmiditan | 200 mg Lasmiditan | 400 mg Lasmiditan | Placebo | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 41 years | 45 years | 41 years | 40 years | 41 years | 41.0 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 82 Participants | 82 Participants | 71 Participants | 69 Participants | 86 Participants | 390 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) White | 81 Participants | 81 Participants | 70 Participants | 69 Participants | 86 Participants | 387 Participants |
| Region of Enrollment Belgium | 5 participants | 5 participants | 6 participants | 4 participants | 7 participants | 27 participants |
| Region of Enrollment Finland | 26 participants | 26 participants | 23 participants | 19 participants | 30 participants | 124 participants |
| Region of Enrollment France | 9 participants | 8 participants | 5 participants | 5 participants | 9 participants | 36 participants |
| Region of Enrollment Germany | 36 participants | 34 participants | 34 participants | 37 participants | 32 participants | 173 participants |
| Region of Enrollment Spain | 6 participants | 9 participants | 3 participants | 5 participants | 8 participants | 31 participants |
| Sex: Female, Male Female | 69 Participants | 68 Participants | 65 Participants | 65 Participants | 75 Participants | 342 Participants |
| Sex: Female, Male Male | 13 Participants | 14 Participants | 6 Participants | 5 Participants | 11 Participants | 49 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 82 | 0 / 82 | 0 / 71 | 0 / 70 | 0 / 85 |
| other Total, other adverse events | 53 / 82 | 59 / 82 | 60 / 71 | 59 / 70 | 19 / 85 |
| serious Total, serious adverse events | 0 / 82 | 0 / 82 | 1 / 71 | 0 / 70 | 0 / 85 |
Outcome results
Primary
Percentage of Participants With Headache Response
Headache response is a binary response variable derived from the headache intensities recorded in the participant diary. Headache response is defined as a reduction in headache severity from moderate or severe at baseline to mild or no headache, at two hours after administration of study drug.
Time frame: 2 hours postdose
Population: All randomized participants who received at least 1 dose of study drug and had a post-baseline evaluation.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 50 mg Lasmiditan | Percentage of Participants With Headache Response | No | 57.0 percentage of participants |
| 50 mg Lasmiditan | Percentage of Participants With Headache Response | Yes | 43.0 percentage of participants |
| 100 mg Lasmiditan | Percentage of Participants With Headache Response | No | 35.8 percentage of participants |
| 100 mg Lasmiditan | Percentage of Participants With Headache Response | Yes | 64.2 percentage of participants |
| 200 mg Lasmiditan | Percentage of Participants With Headache Response | No | 49.3 percentage of participants |
| 200 mg Lasmiditan | Percentage of Participants With Headache Response | Yes | 50.7 percentage of participants |
| 400 mg Lasmiditan | Percentage of Participants With Headache Response | Yes | 64.7 percentage of participants |
| 400 mg Lasmiditan | Percentage of Participants With Headache Response | No | 35.3 percentage of participants |
| Placebo | Percentage of Participants With Headache Response | No | 74.1 percentage of participants |
| Placebo | Percentage of Participants With Headache Response | Yes | 25.9 percentage of participants |
p-value: <0.0001Cochran-Armitage test for trend
Secondary
Actual Time to Headache Relief and Time to Pain Free
The participant answered Did your migraine pain go away completely (pain free) within 24 hours of dosing and record the time. Actual time to meaningful pain relief and actual time to pain free will be censored at 24 hours if meaningful pain relief or pain free is documented to be greater than 24 hours after dosing and Did you experience meaningful relief (headache relief) from your migraine within 24 hours after dosing?.
Time frame: up to 24 hours postdose
Population: All randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 50 mg Lasmiditan | Actual Time to Headache Relief and Time to Pain Free | Pain relief | 650.87 minutes | Standard Error 77.53 |
| 50 mg Lasmiditan | Actual Time to Headache Relief and Time to Pain Free | Pain free | 871.27 minutes | Standard Error 72.74 |
| 100 mg Lasmiditan | Actual Time to Headache Relief and Time to Pain Free | Pain relief | 291.05 minutes | Standard Error 32.24 |
| 100 mg Lasmiditan | Actual Time to Headache Relief and Time to Pain Free | Pain free | 767.33 minutes | Standard Error 74.36 |
| 200 mg Lasmiditan | Actual Time to Headache Relief and Time to Pain Free | Pain relief | 407.16 minutes | Standard Error 52.48 |
| 200 mg Lasmiditan | Actual Time to Headache Relief and Time to Pain Free | Pain free | 690.89 minutes | Standard Error 59.67 |
| 400 mg Lasmiditan | Actual Time to Headache Relief and Time to Pain Free | Pain free | 437.12 minutes | Standard Error 36.05 |
| 400 mg Lasmiditan | Actual Time to Headache Relief and Time to Pain Free | Pain relief | 218.93 minutes | Standard Error 23.87 |
| Placebo | Actual Time to Headache Relief and Time to Pain Free | Pain relief | 760.15 minutes | Standard Error 71.19 |
| Placebo | Actual Time to Headache Relief and Time to Pain Free | Pain free | 1046.47 minutes | Standard Error 77.9 |
Secondary
Change From Baseline in Diastolic Blood Pressure
Change from baseline in vital signs (diastolic blood pressure).
Time frame: Baseline through Day 14
Population: Randomized participants who received at least 1 dose of study drug and had evaluable blood pressure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 50 mg Lasmiditan | Change From Baseline in Diastolic Blood Pressure | 0.0 millimeters of mercury |
| 100 mg Lasmiditan | Change From Baseline in Diastolic Blood Pressure | 0.0 millimeters of mercury |
| 200 mg Lasmiditan | Change From Baseline in Diastolic Blood Pressure | 0.0 millimeters of mercury |
| 400 mg Lasmiditan | Change From Baseline in Diastolic Blood Pressure | 0.0 millimeters of mercury |
| Placebo | Change From Baseline in Diastolic Blood Pressure | 0.0 millimeters of mercury |
Secondary
Change From Baseline in Heart Rate
Change from baseline in assessment of vital signs (heart rate).
Time frame: Baseline through Day 14
Population: Randomized participants who received at least 1 dose of study drug and had evaluable ECG parameters.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 50 mg Lasmiditan | Change From Baseline in Heart Rate | 2.0 beats per minute |
| 100 mg Lasmiditan | Change From Baseline in Heart Rate | 3.0 beats per minute |
| 200 mg Lasmiditan | Change From Baseline in Heart Rate | 1.0 beats per minute |
| 400 mg Lasmiditan | Change From Baseline in Heart Rate | 2.0 beats per minute |
| Placebo | Change From Baseline in Heart Rate | 1.0 beats per minute |
Secondary
Change From Baseline in Hematology Tests
Hematology tests, including a complete blood count (CBC) measured red blood cells, white blood cells, hemoglobin, neutrophils and platelets.
Time frame: Baseline through Day 14
Population: All randomized participants who received at least 1 dose of study drug and had evaluable blood parameters.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 50 mg Lasmiditan | Change From Baseline in Hematology Tests | White blood cells | -0.1 million cells per liter | Standard Error 1.3 |
| 50 mg Lasmiditan | Change From Baseline in Hematology Tests | Red blood cells | 0.0 million cells per liter | Standard Error 0.2 |
| 50 mg Lasmiditan | Change From Baseline in Hematology Tests | Hemoglobin | 0.0 million cells per liter | Standard Error 0.4 |
| 50 mg Lasmiditan | Change From Baseline in Hematology Tests | Platelets | -2.3 million cells per liter | Standard Error 35.2 |
| 50 mg Lasmiditan | Change From Baseline in Hematology Tests | Neutrophils | -3.2 million cells per liter | Standard Error 9.3 |
| 100 mg Lasmiditan | Change From Baseline in Hematology Tests | White blood cells | 0.3 million cells per liter | Standard Error 1.4 |
| 100 mg Lasmiditan | Change From Baseline in Hematology Tests | Hemoglobin | 0.0 million cells per liter | Standard Error 0.4 |
| 100 mg Lasmiditan | Change From Baseline in Hematology Tests | Red blood cells | 0.0 million cells per liter | Standard Error 0.2 |
| 100 mg Lasmiditan | Change From Baseline in Hematology Tests | Neutrophils | -0.3 million cells per liter | Standard Error 7.9 |
| 100 mg Lasmiditan | Change From Baseline in Hematology Tests | Platelets | -0.5 million cells per liter | Standard Error 25.9 |
| 200 mg Lasmiditan | Change From Baseline in Hematology Tests | Platelets | 4.6 million cells per liter | Standard Error 48.4 |
| 200 mg Lasmiditan | Change From Baseline in Hematology Tests | White blood cells | -0.3 million cells per liter | Standard Error 1.6 |
| 200 mg Lasmiditan | Change From Baseline in Hematology Tests | Neutrophils | -2.8 million cells per liter | Standard Error 14.7 |
| 200 mg Lasmiditan | Change From Baseline in Hematology Tests | Red blood cells | 0.0 million cells per liter | Standard Error 0.2 |
| 200 mg Lasmiditan | Change From Baseline in Hematology Tests | Hemoglobin | 0.1 million cells per liter | Standard Error 0.4 |
| 400 mg Lasmiditan | Change From Baseline in Hematology Tests | Red blood cells | 0.0 million cells per liter | Standard Error 0.2 |
| 400 mg Lasmiditan | Change From Baseline in Hematology Tests | Hemoglobin | 0.0 million cells per liter | Standard Error 0.4 |
| 400 mg Lasmiditan | Change From Baseline in Hematology Tests | White blood cells | -0.4 million cells per liter | Standard Error 1.7 |
| 400 mg Lasmiditan | Change From Baseline in Hematology Tests | Platelets | 2.9 million cells per liter | Standard Error 34.7 |
| 400 mg Lasmiditan | Change From Baseline in Hematology Tests | Neutrophils | -3.2 million cells per liter | Standard Error 14.7 |
| Placebo | Change From Baseline in Hematology Tests | Neutrophils | -3.9 million cells per liter | Standard Error 9.9 |
| Placebo | Change From Baseline in Hematology Tests | Platelets | 1.7 million cells per liter | Standard Error 34.7 |
| Placebo | Change From Baseline in Hematology Tests | White blood cells | -0.2 million cells per liter | Standard Error 1.6 |
| Placebo | Change From Baseline in Hematology Tests | Hemoglobin | 0.0 million cells per liter | Standard Error 0.4 |
| Placebo | Change From Baseline in Hematology Tests | Red blood cells | 0.0 million cells per liter | Standard Error 0.2 |
Secondary
Change From Baseline in Systolic Blood Pressure
Change from baseline in vital signs (systolic blood pressure).
Time frame: Baseline through Day 14
Population: All randomized participants who received at least 1 dose of study drug and had evaluable blood pressure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 50 mg Lasmiditan | Change From Baseline in Systolic Blood Pressure | 1.0 millimeters of mercury |
| 100 mg Lasmiditan | Change From Baseline in Systolic Blood Pressure | 0.0 millimeters of mercury |
| 200 mg Lasmiditan | Change From Baseline in Systolic Blood Pressure | -1.5 millimeters of mercury |
| 400 mg Lasmiditan | Change From Baseline in Systolic Blood Pressure | -0.5 millimeters of mercury |
| Placebo | Change From Baseline in Systolic Blood Pressure | -0.0 millimeters of mercury |
Secondary
Disability (4 Point Scale: Not at All, Mild Interference, Marked Interference, Completely - Needs Bed Rest)
The participant is asked How much is the migraine interfering with normal activities? on a 4 point scale 0-Not at all, 1-Mild interference, 2-Marked interference ,3-Completely needs bed rest, with a lower score having lower interference and higher score worse interference.
Time frame: 2 hours postdose
Population: All randomized participants who received at least 1 dose of study drug and had evaluable data.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 50 mg Lasmiditan | Disability (4 Point Scale: Not at All, Mild Interference, Marked Interference, Completely - Needs Bed Rest) | Not at all (0) | 13 Participants |
| 50 mg Lasmiditan | Disability (4 Point Scale: Not at All, Mild Interference, Marked Interference, Completely - Needs Bed Rest) | Mild interference (1) | 26 Participants |
| 50 mg Lasmiditan | Disability (4 Point Scale: Not at All, Mild Interference, Marked Interference, Completely - Needs Bed Rest) | Marked interference (2) | 24 Participants |
| 50 mg Lasmiditan | Disability (4 Point Scale: Not at All, Mild Interference, Marked Interference, Completely - Needs Bed Rest) | Completely needs bed rest (3) | 16 Participants |
| 100 mg Lasmiditan | Disability (4 Point Scale: Not at All, Mild Interference, Marked Interference, Completely - Needs Bed Rest) | Not at all (0) | 14 Participants |
| 100 mg Lasmiditan | Disability (4 Point Scale: Not at All, Mild Interference, Marked Interference, Completely - Needs Bed Rest) | Completely needs bed rest (3) | 11 Participants |
| 100 mg Lasmiditan | Disability (4 Point Scale: Not at All, Mild Interference, Marked Interference, Completely - Needs Bed Rest) | Mild interference (1) | 33 Participants |
| 100 mg Lasmiditan | Disability (4 Point Scale: Not at All, Mild Interference, Marked Interference, Completely - Needs Bed Rest) | Marked interference (2) | 20 Participants |
| 200 mg Lasmiditan | Disability (4 Point Scale: Not at All, Mild Interference, Marked Interference, Completely - Needs Bed Rest) | Completely needs bed rest (3) | 14 Participants |
| 200 mg Lasmiditan | Disability (4 Point Scale: Not at All, Mild Interference, Marked Interference, Completely - Needs Bed Rest) | Mild interference (1) | 23 Participants |
| 200 mg Lasmiditan | Disability (4 Point Scale: Not at All, Mild Interference, Marked Interference, Completely - Needs Bed Rest) | Marked interference (2) | 17 Participants |
| 200 mg Lasmiditan | Disability (4 Point Scale: Not at All, Mild Interference, Marked Interference, Completely - Needs Bed Rest) | Not at all (0) | 12 Participants |
| 400 mg Lasmiditan | Disability (4 Point Scale: Not at All, Mild Interference, Marked Interference, Completely - Needs Bed Rest) | Not at all (0) | 10 Participants |
| 400 mg Lasmiditan | Disability (4 Point Scale: Not at All, Mild Interference, Marked Interference, Completely - Needs Bed Rest) | Mild interference (1) | 26 Participants |
| 400 mg Lasmiditan | Disability (4 Point Scale: Not at All, Mild Interference, Marked Interference, Completely - Needs Bed Rest) | Completely needs bed rest (3) | 12 Participants |
| 400 mg Lasmiditan | Disability (4 Point Scale: Not at All, Mild Interference, Marked Interference, Completely - Needs Bed Rest) | Marked interference (2) | 15 Participants |
| Placebo | Disability (4 Point Scale: Not at All, Mild Interference, Marked Interference, Completely - Needs Bed Rest) | Completely needs bed rest (3) | 31 Participants |
| Placebo | Disability (4 Point Scale: Not at All, Mild Interference, Marked Interference, Completely - Needs Bed Rest) | Marked interference (2) | 21 Participants |
| Placebo | Disability (4 Point Scale: Not at All, Mild Interference, Marked Interference, Completely - Needs Bed Rest) | Mild interference (1) | 23 Participants |
| Placebo | Disability (4 Point Scale: Not at All, Mild Interference, Marked Interference, Completely - Needs Bed Rest) | Not at all (0) | 6 Participants |
Secondary
Number of Participants Reporting a Score on the Patient Global Impression of Improvement (PGI-I)
PGI-I requests participants to mark the box that best describes their cluster headache condition since they started taking the medicine. The options in the displayed boxes are represented on a 7-point scale, with 1 = very much better, 2 = much better, 3 = a little better, 4 = no change, 5 = a little worse, 6 = much worse, and 7 = very much worse, a lower number indicates much better and a higher number indicates worse.
Time frame: 2 hours postdose
Population: All randomized participants who received at least 1 dose of study drug and had a PGI-I measurement post dose.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 50 mg Lasmiditan | Number of Participants Reporting a Score on the Patient Global Impression of Improvement (PGI-I) | Very much better | 3 Participants |
| 50 mg Lasmiditan | Number of Participants Reporting a Score on the Patient Global Impression of Improvement (PGI-I) | Very much worse | 3 Participants |
| 50 mg Lasmiditan | Number of Participants Reporting a Score on the Patient Global Impression of Improvement (PGI-I) | Much worse | 5 Participants |
| 50 mg Lasmiditan | Number of Participants Reporting a Score on the Patient Global Impression of Improvement (PGI-I) | A little better | 28 Participants |
| 50 mg Lasmiditan | Number of Participants Reporting a Score on the Patient Global Impression of Improvement (PGI-I) | Much better | 15 Participants |
| 50 mg Lasmiditan | Number of Participants Reporting a Score on the Patient Global Impression of Improvement (PGI-I) | No change | 18 Participants |
| 50 mg Lasmiditan | Number of Participants Reporting a Score on the Patient Global Impression of Improvement (PGI-I) | A little worse | 7 Participants |
| 100 mg Lasmiditan | Number of Participants Reporting a Score on the Patient Global Impression of Improvement (PGI-I) | A little worse | 6 Participants |
| 100 mg Lasmiditan | Number of Participants Reporting a Score on the Patient Global Impression of Improvement (PGI-I) | No change | 11 Participants |
| 100 mg Lasmiditan | Number of Participants Reporting a Score on the Patient Global Impression of Improvement (PGI-I) | Much better | 27 Participants |
| 100 mg Lasmiditan | Number of Participants Reporting a Score on the Patient Global Impression of Improvement (PGI-I) | Very much better | 2 Participants |
| 100 mg Lasmiditan | Number of Participants Reporting a Score on the Patient Global Impression of Improvement (PGI-I) | Much worse | 4 Participants |
| 100 mg Lasmiditan | Number of Participants Reporting a Score on the Patient Global Impression of Improvement (PGI-I) | A little better | 30 Participants |
| 100 mg Lasmiditan | Number of Participants Reporting a Score on the Patient Global Impression of Improvement (PGI-I) | Very much worse | 1 Participants |
| 200 mg Lasmiditan | Number of Participants Reporting a Score on the Patient Global Impression of Improvement (PGI-I) | No change | 12 Participants |
| 200 mg Lasmiditan | Number of Participants Reporting a Score on the Patient Global Impression of Improvement (PGI-I) | Very much better | 3 Participants |
| 200 mg Lasmiditan | Number of Participants Reporting a Score on the Patient Global Impression of Improvement (PGI-I) | Much better | 16 Participants |
| 200 mg Lasmiditan | Number of Participants Reporting a Score on the Patient Global Impression of Improvement (PGI-I) | A little better | 21 Participants |
| 200 mg Lasmiditan | Number of Participants Reporting a Score on the Patient Global Impression of Improvement (PGI-I) | A little worse | 6 Participants |
| 200 mg Lasmiditan | Number of Participants Reporting a Score on the Patient Global Impression of Improvement (PGI-I) | Much worse | 3 Participants |
| 200 mg Lasmiditan | Number of Participants Reporting a Score on the Patient Global Impression of Improvement (PGI-I) | Very much worse | 8 Participants |
| 400 mg Lasmiditan | Number of Participants Reporting a Score on the Patient Global Impression of Improvement (PGI-I) | A little better | 22 Participants |
| 400 mg Lasmiditan | Number of Participants Reporting a Score on the Patient Global Impression of Improvement (PGI-I) | A little worse | 9 Participants |
| 400 mg Lasmiditan | Number of Participants Reporting a Score on the Patient Global Impression of Improvement (PGI-I) | Much better | 19 Participants |
| 400 mg Lasmiditan | Number of Participants Reporting a Score on the Patient Global Impression of Improvement (PGI-I) | Very much worse | 2 Participants |
| 400 mg Lasmiditan | Number of Participants Reporting a Score on the Patient Global Impression of Improvement (PGI-I) | Much worse | 4 Participants |
| 400 mg Lasmiditan | Number of Participants Reporting a Score on the Patient Global Impression of Improvement (PGI-I) | Very much better | 4 Participants |
| 400 mg Lasmiditan | Number of Participants Reporting a Score on the Patient Global Impression of Improvement (PGI-I) | No change | 7 Participants |
| Placebo | Number of Participants Reporting a Score on the Patient Global Impression of Improvement (PGI-I) | A little better | 18 Participants |
| Placebo | Number of Participants Reporting a Score on the Patient Global Impression of Improvement (PGI-I) | Very much worse | 6 Participants |
| Placebo | Number of Participants Reporting a Score on the Patient Global Impression of Improvement (PGI-I) | Much worse | 9 Participants |
| Placebo | Number of Participants Reporting a Score on the Patient Global Impression of Improvement (PGI-I) | A little worse | 8 Participants |
| Placebo | Number of Participants Reporting a Score on the Patient Global Impression of Improvement (PGI-I) | Much better | 10 Participants |
| Placebo | Number of Participants Reporting a Score on the Patient Global Impression of Improvement (PGI-I) | Very much better | 3 Participants |
| Placebo | Number of Participants Reporting a Score on the Patient Global Impression of Improvement (PGI-I) | No change | 27 Participants |
Secondary
Number of Serious Adverse Events
A summary of non-serious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section.
Time frame: up to 8 weeks
Population: All randomized participants who received at least 1 dose of study drug excluding one participant who was lost to follow-up and did not report adverse events.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 50 mg Lasmiditan | Number of Serious Adverse Events | 0 adverse events |
| 100 mg Lasmiditan | Number of Serious Adverse Events | 0 adverse events |
| 200 mg Lasmiditan | Number of Serious Adverse Events | 1 adverse events |
| 400 mg Lasmiditan | Number of Serious Adverse Events | 0 adverse events |
| Placebo | Number of Serious Adverse Events | 0 adverse events |
Secondary
Percentage of Participants Who Are Headache Free (Absence of Headache) After First Dose
The percentage of participants defined as mild, moderate, or severe headache pain becoming none.
Time frame: 2 hours post dose
Population: All randomized participants who received at least 1 dose of study drug, a 2 hour postdose evaluation and evaluable headache relief data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 50 mg Lasmiditan | Percentage of Participants Who Are Headache Free (Absence of Headache) After First Dose | 13.9 percentage of participants |
| 100 mg Lasmiditan | Percentage of Participants Who Are Headache Free (Absence of Headache) After First Dose | 13.6 percentage of participants |
| 200 mg Lasmiditan | Percentage of Participants Who Are Headache Free (Absence of Headache) After First Dose | 18.8 percentage of participants |
| 400 mg Lasmiditan | Percentage of Participants Who Are Headache Free (Absence of Headache) After First Dose | 27.9 percentage of participants |
| Placebo | Percentage of Participants Who Are Headache Free (Absence of Headache) After First Dose | 7.4 percentage of participants |
p-value: =0.0006Cochran-Armitage test for trend]
Secondary
Percentage of Participants Who Have Photophobia
Percentage of participants who have symptoms of photophobia two hours post treatment.
Time frame: 2 hours postdose
Population: Randomized participants who received a dose of study drug and had postdose symptom assessments.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 50 mg Lasmiditan | Percentage of Participants Who Have Photophobia | 46.84 percentage of participants |
| 100 mg Lasmiditan | Percentage of Participants Who Have Photophobia | 31.25 percentage of participants |
| 200 mg Lasmiditan | Percentage of Participants Who Have Photophobia | 41.18 percentage of participants |
| 400 mg Lasmiditan | Percentage of Participants Who Have Photophobia | 37.31 percentage of participants |
| Placebo | Percentage of Participants Who Have Photophobia | 65.43 percentage of participants |
Secondary
Percentage of Participants Who Have Symptoms of Nausea
Percentage of participants who have symptoms of nausea two hours post treatment.
Time frame: 2 hours postdose
Population: Randomized participants who received a dose of study drug and had postdose symptom assessments.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 50 mg Lasmiditan | Percentage of Participants Who Have Symptoms of Nausea | 31.65 percentage of participants |
| 100 mg Lasmiditan | Percentage of Participants Who Have Symptoms of Nausea | 25.00 percentage of participants |
| 200 mg Lasmiditan | Percentage of Participants Who Have Symptoms of Nausea | 35.29 percentage of participants |
| 400 mg Lasmiditan | Percentage of Participants Who Have Symptoms of Nausea | 26.87 percentage of participants |
| Placebo | Percentage of Participants Who Have Symptoms of Nausea | 40.74 percentage of participants |
Secondary
Percentage of Participants Who Have Symptoms Phonophobia
Percentage of participants who have symptoms of phonophobia two hours post treatment.
Time frame: 2 hours postdose
Population: Randomized participants who received a dose of study drug and had postdose symptom assessments.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 50 mg Lasmiditan | Percentage of Participants Who Have Symptoms Phonophobia | 41.77 percentage of participants |
| 100 mg Lasmiditan | Percentage of Participants Who Have Symptoms Phonophobia | 23.75 percentage of participants |
| 200 mg Lasmiditan | Percentage of Participants Who Have Symptoms Phonophobia | 39.71 percentage of participants |
| 400 mg Lasmiditan | Percentage of Participants Who Have Symptoms Phonophobia | 31.34 percentage of participants |
| Placebo | Percentage of Participants Who Have Symptoms Phonophobia | 48.15 percentage of participants |
Secondary
Percentage of Participants Who Used Rescue Medication
Rescue medication was permitted after completion of the 2 hour assessment if migraine did not respond (participant was not pain free).
Time frame: Postdose 2 through 24 hours
Population: Randomized participants who received a dose of study drug and had postdose headache severity or symptom assessments.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 50 mg Lasmiditan | Percentage of Participants Who Used Rescue Medication | 54.5 percentage of participants |
| 100 mg Lasmiditan | Percentage of Participants Who Used Rescue Medication | 51.9 percentage of participants |
| 200 mg Lasmiditan | Percentage of Participants Who Used Rescue Medication | 61.2 percentage of participants |
| 400 mg Lasmiditan | Percentage of Participants Who Used Rescue Medication | 41.8 percentage of participants |
| Placebo | Percentage of Participants Who Used Rescue Medication | 68.8 percentage of participants |
Secondary
Percentage of Participants With Change From Baseline in Physical Examination Parameters
Participants were evaluated for skin, head, ear, nose and throat, cardiovascular and musculoskeletal changes from a normal screening to an abnormal screening. Changes in the physical examination noted as non-serious AEs or SAEs, regardless of causality, are located in the Reported Adverse Events section.
Time frame: Baseline through Day 14
Population: All randomized participants who received at last 1 dose of study drug and had a physical examination.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 50 mg Lasmiditan | Percentage of Participants With Change From Baseline in Physical Examination Parameters | Skin | 1.2 percentage of participants |
| 50 mg Lasmiditan | Percentage of Participants With Change From Baseline in Physical Examination Parameters | Musculoskeletal | 0 percentage of participants |
| 50 mg Lasmiditan | Percentage of Participants With Change From Baseline in Physical Examination Parameters | Head, ears, nose, throat | 0 percentage of participants |
| 100 mg Lasmiditan | Percentage of Participants With Change From Baseline in Physical Examination Parameters | Head, ears, nose, throat | 0 percentage of participants |
| 100 mg Lasmiditan | Percentage of Participants With Change From Baseline in Physical Examination Parameters | Skin | 2.4 percentage of participants |
| 100 mg Lasmiditan | Percentage of Participants With Change From Baseline in Physical Examination Parameters | Musculoskeletal | 1.2 percentage of participants |
| 200 mg Lasmiditan | Percentage of Participants With Change From Baseline in Physical Examination Parameters | Head, ears, nose, throat | 0 percentage of participants |
| 200 mg Lasmiditan | Percentage of Participants With Change From Baseline in Physical Examination Parameters | Skin | 1.4 percentage of participants |
| 200 mg Lasmiditan | Percentage of Participants With Change From Baseline in Physical Examination Parameters | Musculoskeletal | 0 percentage of participants |
| 400 mg Lasmiditan | Percentage of Participants With Change From Baseline in Physical Examination Parameters | Skin | 0 percentage of participants |
| 400 mg Lasmiditan | Percentage of Participants With Change From Baseline in Physical Examination Parameters | Musculoskeletal | 0 percentage of participants |
| 400 mg Lasmiditan | Percentage of Participants With Change From Baseline in Physical Examination Parameters | Head, ears, nose, throat | 1.4 percentage of participants |
| Placebo | Percentage of Participants With Change From Baseline in Physical Examination Parameters | Head, ears, nose, throat | 0 percentage of participants |
| Placebo | Percentage of Participants With Change From Baseline in Physical Examination Parameters | Skin | 0 percentage of participants |
| Placebo | Percentage of Participants With Change From Baseline in Physical Examination Parameters | Musculoskeletal | 3.5 percentage of participants |
Secondary
Percentage of Participants With Headache Recurrence
Participants who received study drug and which became pain free at 2 hours postdose and worsened again upto 24 hours post-dose.
Time frame: up to 24 hours postdose
Population: Randomized participants who received a dose of study drug, were pain free at 2 hours postdose and had postdose headache severity or symptom assessments.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 50 mg Lasmiditan | Percentage of Participants With Headache Recurrence | 55.9 percentage of participants |
| 100 mg Lasmiditan | Percentage of Participants With Headache Recurrence | 57.7 percentage of participants |
| 200 mg Lasmiditan | Percentage of Participants With Headache Recurrence | 62.9 percentage of participants |
| 400 mg Lasmiditan | Percentage of Participants With Headache Recurrence | 50.0 percentage of participants |
| Placebo | Percentage of Participants With Headache Recurrence | 57.1 percentage of participants |
Secondary
Percentage of Participants With Headache Severity (4 Point Rating Scale)
Headache severity was evaluated by the participant using the International Headache Society (IHS) four point headache severity rating scale (0=no pain, 1=mild pain, 2=moderate pain, and 3=severe pain) with a lower score being less severe and a higher score being more severe.
Time frame: 2 hours postdose
Population: Randomized participants who received a dose of study drug and had postdose headache severity or symptom assessments.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 50 mg Lasmiditan | Percentage of Participants With Headache Severity (4 Point Rating Scale) | None (0) | 13.9 percentage of participants |
| 50 mg Lasmiditan | Percentage of Participants With Headache Severity (4 Point Rating Scale) | Mild(1) | 29.1 percentage of participants |
| 50 mg Lasmiditan | Percentage of Participants With Headache Severity (4 Point Rating Scale) | Moderate(2) | 27.8 percentage of participants |
| 50 mg Lasmiditan | Percentage of Participants With Headache Severity (4 Point Rating Scale) | Severe(3) | 29.1 percentage of participants |
| 100 mg Lasmiditan | Percentage of Participants With Headache Severity (4 Point Rating Scale) | None (0) | 13.6 percentage of participants |
| 100 mg Lasmiditan | Percentage of Participants With Headache Severity (4 Point Rating Scale) | Severe(3) | 11.1 percentage of participants |
| 100 mg Lasmiditan | Percentage of Participants With Headache Severity (4 Point Rating Scale) | Mild(1) | 50.6 percentage of participants |
| 100 mg Lasmiditan | Percentage of Participants With Headache Severity (4 Point Rating Scale) | Moderate(2) | 23.5 percentage of participants |
| 200 mg Lasmiditan | Percentage of Participants With Headache Severity (4 Point Rating Scale) | Severe(3) | 21.7 percentage of participants |
| 200 mg Lasmiditan | Percentage of Participants With Headache Severity (4 Point Rating Scale) | Mild(1) | 31.9 percentage of participants |
| 200 mg Lasmiditan | Percentage of Participants With Headache Severity (4 Point Rating Scale) | Moderate(2) | 26.1 percentage of participants |
| 200 mg Lasmiditan | Percentage of Participants With Headache Severity (4 Point Rating Scale) | None (0) | 18.8 percentage of participants |
| 400 mg Lasmiditan | Percentage of Participants With Headache Severity (4 Point Rating Scale) | None (0) | 27.9 percentage of participants |
| 400 mg Lasmiditan | Percentage of Participants With Headache Severity (4 Point Rating Scale) | Mild(1) | 36.8 percentage of participants |
| 400 mg Lasmiditan | Percentage of Participants With Headache Severity (4 Point Rating Scale) | Severe(3) | 13.2 percentage of participants |
| 400 mg Lasmiditan | Percentage of Participants With Headache Severity (4 Point Rating Scale) | Moderate(2) | 20.6 percentage of participants |
| Placebo | Percentage of Participants With Headache Severity (4 Point Rating Scale) | Severe(3) | 46.9 percentage of participants |
| Placebo | Percentage of Participants With Headache Severity (4 Point Rating Scale) | Moderate(2) | 27.2 percentage of participants |
| Placebo | Percentage of Participants With Headache Severity (4 Point Rating Scale) | Mild(1) | 18.5 percentage of participants |
| Placebo | Percentage of Participants With Headache Severity (4 Point Rating Scale) | None (0) | 7.4 percentage of participants |
Secondary
Percentage of Participants With Vomiting
Percentage of participants with vomiting 2 hours post treatment.
Time frame: 2 hours postdose
Population: Randomized participants who received a dose of study drug and had postdose symptom assessments.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 50 mg Lasmiditan | Percentage of Participants With Vomiting | 5.06 percentage of participants |
| 100 mg Lasmiditan | Percentage of Participants With Vomiting | 0.00 percentage of participants |
| 200 mg Lasmiditan | Percentage of Participants With Vomiting | 7.35 percentage of participants |
| 400 mg Lasmiditan | Percentage of Participants With Vomiting | 4.80 percentage of participants |
| Placebo | Percentage of Participants With Vomiting | 11.11 percentage of participants |