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Dose-ranging Study of Oral COL-144 in Acute Migraine Treatment

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ClinicalTrials.gov Identifier: NCT00883051
Recruitment Status : Completed
First Posted : April 17, 2009
Results First Posted : December 23, 2019
Last Update Posted : December 23, 2019
Sponsor:
Collaborator:
CoLucid Pharmaceuticals
Information provided by (Responsible Party):
Eli Lilly and Company

Tracking Information
First Submitted Date  ICMJE April 16, 2009
First Posted Date  ICMJE April 17, 2009
Results First Submitted Date  ICMJE November 8, 2019
Results First Posted Date  ICMJE December 23, 2019
Last Update Posted Date December 23, 2019
Study Start Date  ICMJE July 2009
Actual Primary Completion Date February 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 20, 2019)
Percentage of Participants With Headache Response [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: April 16, 2009)
Headache response, defined as a reduction in headache severity from moderate or severe at baseline to mild or no headache two hours after intake of study drug. [ Time Frame: Two hours after intake of study drug ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 20, 2019)
  • Percentage of Participants Who Are Headache Free (Absence of Headache) After First Dose [ Time Frame: 2 hours post dose ]
    The percentage of participants defined as mild, moderate, or severe headache pain becoming none.
  • Percentage of Participants With Headache Recurrence [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 2 hours postdose ]
    Percentage of participants who have symptoms of nausea two hours post treatment.
  • Percentage of Participants Who Have Symptoms Phonophobia [ Time Frame: 2 hours postdose ]
    Percentage of participants who have symptoms of phonophobia two hours post treatment.
  • Percentage of Participants Who Have Photophobia [ Time Frame: 2 hours postdose ]
    Percentage of participants who have symptoms of photophobia two hours post treatment.
  • Percentage of Participants With Vomiting [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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).
  • Number of Participants Reporting a Score on the Patient Global Impression of Improvement (PGI-I) [ Time Frame: 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.
  • Actual Time to Headache Relief and Time to Pain Free [ Time Frame: 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 [ Time Frame: Baseline through Day 14 ]
    Change from baseline in assessment of vital signs (heart rate).
  • Change From Baseline in Systolic Blood Pressure [ Time Frame: Baseline through Day 14 ]
    Change from baseline in vital signs (systolic blood pressure).
  • Change From Baseline in Diastolic Blood Pressure [ Time Frame: Baseline through Day 14 ]
    Change from baseline in vital signs (diastolic blood pressure).
  • Percentage of Participants With Change From Baseline in Physical Examination Parameters [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 16, 2009)
  • Headache free (absence of headache) [ Time Frame: Two hours after intake of study drug ]
  • Headache severity (4 point scale: none, mild, moderate, severe) [ Time Frame: From time immediately before intake of study drug until 2 hours after after intake of study drug ]
  • Headache recurrence [ Time Frame: Within 24 hours hours after after intake of study drug ]
  • Presence or absence of nausea, phonophobia, photophobia, vomiting [ Time Frame: From time immediately before intake of study drug until 2 hours after intake of study drug ]
  • Disability (4 Point Scale: Not at All, Mild Interference, Marked Interference, Completely - Needs Bed Rest) [ Time Frame: From time immediately before intake of study drug until 2 hours after intake of study drug ]
  • Requirement for rescue medication (yes or no) [ Time Frame: Between 2 and 24 hours after intake of study drug ]
  • Patient global impression (7 point scale) [ Time Frame: Between 2 hours after intake of study drug ]
  • Time to headache relief and time to pain free [ Time Frame: Within 24 hours after intake of study drug ]
  • Adverse events (spontaneously reported) [ Time Frame: Throughout the whole study duration ]
  • 12-Lead electrocardiograms (ECGs) [ Time Frame: Baseline and within 14 days after treatment ]
  • Vital signs [ Time Frame: Baseline and within 14 days after treatment ]
  • Clinical laboratory parameters [ Time Frame: Baseline and within 14 days after treatment ]
  • Physical examination [ Time Frame: Baseline and within 14 days after treatment ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Dose-ranging Study of Oral COL-144 in Acute Migraine Treatment
Official Title  ICMJE A Double Blind Randomized Placebo-Controlled Parallel Group Dose-Ranging Study of Oral COL-144 in the Acute Treatment of 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Migraine Disorders
Intervention  ICMJE
  • Drug: Lasmiditan
    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.
    Other Name: LY573144
  • Drug: Placebo
    Placebo
Study Arms  ICMJE
  • Experimental: 50 mg Lasmiditan
    50 mg lasmiditan administered orally (PO)
    Intervention: Drug: Lasmiditan
  • Experimental: 100 mg Lasmiditan
    100 mg lasmiditan administered orally (PO)
    Intervention: Drug: Lasmiditan
  • Experimental: 200 mg Lasmiditan
    200 mg lasmiditan administered orally (PO)
    Intervention: Drug: Lasmiditan
  • Experimental: 400 mg Lasmiditan
    400 mg lasmiditan administered orally (PO)
    Intervention: Drug: Lasmiditan
  • Placebo Comparator: Placebo
    Placebo administered orally (PO)
    Intervention: Drug: Placebo
Publications * Färkkilä M, Diener HC, Géraud G, Láinez M, Schoenen J, Harner N, Pilgrim A, Reuter U; COL MIG-202 study group. Efficacy and tolerability of lasmiditan, an oral 5-HT(1F) receptor agonist, for the acute treatment of migraine: a phase 2 randomised, placebo-controlled, parallel-group, dose-ranging study. Lancet Neurol. 2012 May;11(5):405-13. doi: 10.1016/S1474-4422(12)70047-9. Epub 2012 Mar 28.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 20, 2019)
512
Original Estimated Enrollment  ICMJE
 (submitted: April 16, 2009)
450
Actual Study Completion Date  ICMJE February 2010
Actual Primary Completion Date February 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   Finland,   France,   Germany,   Spain
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00883051
Other Study ID Numbers  ICMJE 16892
H8H-CD-LAHO ( Other Identifier: Eli Lilly and Company )
2008-005010-43 ( EudraCT Number )
COL MIG-202 ( Other Identifier: Colucid )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
URL: https://vivli.org/
Responsible Party Eli Lilly and Company
Study Sponsor  ICMJE Eli Lilly and Company
Collaborators  ICMJE CoLucid Pharmaceuticals
Investigators  ICMJE
Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) Eli Lilly and Company
PRS Account Eli Lilly and Company
Verification Date January 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP