A Placebo-Controlled Adaptive Treatment Assignment Study of Intravenous COL-144 in the Acute Treatment of Migraine

• ClinicalTrials.gov Identifier: NCT00384774
• Recruitment Status: Completed
• First Posted: October 6, 2006
• Results First Posted: December 2, 2019
• Last Update Posted: December 2, 2019
• Sponsor: Eli Lilly and Company
• Collaborator: CoLucid Pharmaceuticals
• Information provided by (Responsible Party): Eli Lilly and Company

Tracking Information

• First Submitted Date: October 4, 2006
• First Posted Date: October 6, 2006
• Results First Submitted Date: November 8, 2019
• Results First Posted Date: December 2, 2019
• Last Update Posted Date: December 2, 2019
• Actual Study Start Date: November 2006
• Actual Primary Completion Date: June 2007 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 8, 2019)

Number of Participants With Headache Response at Two Hours After Initiation of Infusion of Study Drug [ Time Frame: 2 hours post dose ]

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 initiation of infusion of study drug.

• Original Primary Outcome Measures (submitted: October 5, 2006): - Headache response at two hours after initiation of infusion of study drug

Current Secondary Outcome Measures (submitted: November 8, 2019)

• Percentage of Participants With Headache Response 10 to 240 Minutes (Min) Post Dose [ Time Frame: 10, 20, 40, 60 90, 120, 180 and 240 minutes post dose ]
  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 initiation of infusion of study drug.
• Percentage of Participants Headache Free [ Time Frame: 10, 20, 40, 60 90, 120, 180 and 240 minutes post dose ]
  Headache free is defined as a reduction in headache severity from moderate or severe at baseline to no headache pain at 10 min, 20 min, 40 min, 60 min, 90 min, 120 min, 180 min, and 240 min after initiation of study drug.
• Number of Participants With Sustained Headache Response [ Time Frame: 2 to 24 hours post dose ]
  Sustained headache response at 2 hours is a binary response variable derived from the headache intensities recorded in the participant diary. Sustained headache response was defined as moderate or severe headache pain at baseline which became mild or absent (pain free) at 2 hours after initiation of study drug and which did not recur (became moderate or severe) within 24 hours of initiation of study drug. If rescue medication was taken within 24 hours, this was considered a headache recurrence, even if no headache was reported.
• Number of Participants With Sustained Pain Free [ Time Frame: 2 to 24 hours post dose ]
  Sustained pain free was defined as moderate or severe headache pain at baseline which became mild or absent (pain free) at 2 hours after initiation of study drug and which did not recur (became moderate or severe) within 24 hours of initiation of study drug. If rescue medication was taken within 24 hours, this was considered a headache recurrence, even if no headache was reported.
• Number of Participants With Absence of Nausea, Vomiting, Photophobia and Phonophobia [ Time Frame: 2 hours post dose ]
  Number of participants with absence of nausea, vomiting, photophobia and phonophobia.
• Number of Participants With Clinical Disability [ Time Frame: 2 hours post dose ]
  Clinical disability for each participant was assessed using the Clinical Disability Questionnaire (CDQ). Participants graded their disability on the following scale: 0, no disability, able to function normally; 1, performance of daily activities mildly impaired, can still do everything but with difficulty; 2, performance of daily activities moderately impaired, unable to do some things; 3, performance of daily activities severely impaired, cannot do all or most things, bed rest may be necessary.
• Percentage of Participants Using Rescue Medication [ Time Frame: 24 hours post dose ]
  Use of rescue medication up to 24 hours after initiation of study drug.
• Percentage of Participants Reporting a Score on the Patient Global Impression (PGI) [ Time Frame: 2 hours post dose ]
  PGI scale is a participant-rated instrument that measures participants own global impression of their illness severity. Participants were asked to mark the box that best describes their 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.

• Original Secondary Outcome Measures (submitted: October 5, 2006): Rates of headache response; Proportion of pts headache free; Rates of sustained response; Rates of sustained pain free; Relief of nausea, vomiting, etc.; Degree of clinical disability; Proportion of pts using rescue medication; Pt global impression
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Placebo-Controlled Adaptive Treatment Assignment Study of Intravenous COL-144 in the Acute Treatment of Migraine
• Official Title: A Placebo-Controlled, Group Sequential, Adaptive Treatment Assignment Study of Intravenous COL-144 (LY573144) in the Acute Treatment of Migraine
• Brief Summary: This study evaluates the efficacy of a range of intravenous doses of COL-144 in the treatment of migraine headache in order to select a dose range for further studies.

Detailed Description

This study is set up:

• to evaluate the efficacy (headache response at two hours) of a range of intravenous doses of COL-144 in order to select a dose range for further evaluation,
• to explore the time course and effect of a range of dose levels of COL-144 on features of the migraine including: headache response, proportion of participants pain-free, headache recurrence, nausea, photophobia, phonophobia, disability, use of rescue medication, patient global impression and vomiting
• to explore the safety and tolerability of a range of doses of COL-144 in terms of adverse events, physical exam, vital signs, laboratory evaluations, and ECGs
• to determine key PK parameters for COL-144 and to explore the relationship between the PK of COL-144 and the time course and extent of clinical response

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Migraine

Intervention

• Drug: Lasmiditan
  Administered as intravenous infusion
  Other Name: LY573144, COL-144
• Drug: Placebo
  Administered as intravenous infusion

Study Arms

• Experimental: Lasmiditan
  Participants received escalating doses of 2.5 mg, 5 mg, 10 mg, 20 mg, 30 mg and 45 mg of lasmiditan as intravenous injection.
  Intervention: Drug: Lasmiditan
• Placebo Comparator: Placebo
  Participants received intravenous infusion of placebo solution.
  Intervention: Drug: Placebo

Publications *

• Reuter U, Pilgrim A, Diener HC, Färkkilä M, Ferrari M for the European COL-144 investigators. COL-144: A Selective 5-HT1F Agonist For the Treatment of Migraine Attacks. European Headache & Migraine Trust International Congress 2008, London, England, Poster #PC.11, September 5, 2008.
• Ferrari MD, Farkkila M, Reuter U, Pilgrim A, Davis C, Krauss M, Diener HC; European COL-144 Investigators. Acute treatment of migraine with the selective 5-HT1F receptor agonist lasmiditan--a randomised proof-of-concept trial. Cephalalgia. 2010 Oct;30(10):1170-8. doi: 10.1177/0333102410375512. Epub 2010 Jun 15.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 8, 2019): 130
• Original Enrollment (submitted: October 5, 2006): 160
• Actual Study Completion Date: June 2007
• Actual Primary Completion Date: June 2007 (Final data collection date for primary outcome measure)

Eligibility Criteria

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 subjects aged 18 to 65 years
• Female patients of child-bearing potential must be using a highly effective form of contraception (eg combined oral contraceptive, IUD, abstinence, vasectomized partner)
• Able and willing to return to the clinic for treatment within 4 hours of the onset of a migraine headache
• Able and willing to give written informed consent

Exclusion Criteria:

• History of life threatening or intolerable adverse reaction to any triptan
• Use of prescription migraine prophylactic drugs
• 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)
• Sitting BP >160mmHg systolic or >90mmHg diastolic on 2 repeated measurements at screening
• 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 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
• 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Finland, Germany, Netherlands

Administrative Information

• NCT Number: NCT00384774
• Other Study ID Numbers: 16891; 2006-003903-38 ( EudraCT Number ); COL MIG-201 ( Other Identifier: Colucid ); H8H-CD-LAHM ( Other Identifier: Eli Lilly and Company )
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• 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/

• Current Responsible Party: Eli Lilly and Company
• Original Responsible Party: Not Provided
• Current Study Sponsor: Eli Lilly and Company
• Original Study Sponsor: CoLucid Pharmaceuticals
• Collaborators: CoLucid Pharmaceuticals

Investigators

• 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