Meeting News

Lasmiditan impacts patients’ driving skills

PHILADELPHIA — Lasmiditan, an investigational, oral, first-in-class receptor antagonist for the acute treatment of migraine pain, hindered patients’ ability to drive even though the drivers did not think their driving was impaired, according to a discussion held during the American Headache Society Annual Scientific Meeting.

FDA guidance states that driving tests should occur when there is evidence that drugs such as Lasmiditan (Eli Lilly) can impact the patient’s central nervous system and ability to drive, Eric Pearlman, MD, PhD, a senior medical director at Eli Lilly, told attendees.

“Two of the major driving forces behind [the guidance] was one, that the FDA sees driving as an important public health issue and two, that research shows that drivers poorly judge their own driving performance,” he said.

Researchers randomly assigned 90 patients between 30 years and 40 years of age a single oral dose of 1-mg of alprazolam and either a 50-mg, 100-mg or 200-mg dose of Lasmiditan and then a placebo at 1.5 hours post-dose to replicate Lasmiditan peak concentration. Another 68 patients were randomized to receive single oral doses of either 100-mg or 200-mg of Lasmiditan as well as 50-mg of diphenhydramine 2 hours before each driving assessment.

 “These patients were asked ‘do you feel safe to drive?’ right before they performed a driving assessment. A relatively high proportion of subjects 55% to 80%, depending on dose — reported they were safe to drive, but the vast majority were impaired at 1.5 hours,” Pearlman said, adding that 1.5 hours is also the approximate time of Lasmiditan’s peak concentration. Researchers noted that about 8 hours after receiving their respective doses, drivers’ disabilities were “obsolete.”

Younger man with headache 2 
Lasmiditan, an investigational, oral, first-in-class receptor antagonist for the acute treatment of migraine pain, hindered patients’ ability to drive even though the drivers did not think their driving was impaired, according to a discussion held during the American Headache Society Annual Scientific Meeting.


Source:Adobe

Pearlman discussed future research topics.

“Like any good research [our study] raised more questions than it does provide answers. We actually know very little migraine’s about impact has on driving [and] the magnitude of driving impairment from other migraine treatments,” he concluded.

Other Lasmiditan data presented at the meeting included:

  • 30 healthy patients were randomized in a 2:1 ratio to receive a single 200-mg dose of Lasmiditan or placebo in a double-blinded manner on days 1 and 14, a titrated dose of up to 50-mg of open-label topiramate two times a day on days 3 to 13 and a 50-mg dose of topiramate coadministered with a single dose of Lasmiditan or placebo on day 14. At study’s end, participants did not demonstrate any clinically relevant effects on adverse events, vital signs, electrocardiograms and clinical laboratory data vs. either drug administered alone.
  • 39 healthy patients were randomized to receive the following four treatments on day 1 of four study periods: lasmiditan+sumatriptan; lasmiditan+placebo; sumatriptan+placebo or placebo+placebo with a washout of at least 4 days between each dose. At study’s end, there were no clinically relevant pharmacokinetics, cardiovascular or safety interactions observed in any of the cohorts.

“For patients in whom these reductions in heart rate may pose a risk, including patients taking medicines that lower heart rate, these findings may be clinically relevant,” researchers wrote.

Other findings included:

  • 775 patients who used a migraine preventive medication and received either a 50-mg, 100-mg or 200-mg dose of Lasmiditan were significantly more likely to be pain-free at 2 hours vs. placebo (P < .05).
  • 814 patients with migraine participating in a long-term study had interim safety and efficacy results that were “generally consistent” with those observed in the single-attack studies consisting of the same cohort. Researchers also noted that generally speaking, the frequency of dizziness (18.6%), somnolence (8.5%), paresthesia (6.8%), fatigue (5.5%), nausea (4.7%), and asthenia (2%) dropped as more doses were administered, and the effects of treatment were “generally consistent” over time for up to 1 year.
  • Patients assigned to take either placebo (n = 1,262) or a 50-mg (n = 654), 100-mg (n = 1,265) or a 200-mg (n = 1,258) dose of Lasmiditan within 4 hours of migraine onset experienced at least one of the following: dizziness, paresthesia, somnolence, fatigue, nausea, muscular weakness and hypoesthesia. Researchers wrote that these occurrences were mostly mild or moderate in severity, of “quick onset and self-limiting.”
  • Patients who received either a 50-mg (n = 744), 100-mg (n = 1,494) or 200-mg (n = 1,491) dose of Lasmitidan for a single migraine attack reported an earlier onset of efficacy measured by pain relief, photophobia-freedom and most bothersome symptom freedom compared to those treated with placebo (n = 1,488). Researchers added that some patients taking the higher doses experienced the improvement in pain relief within 30 minutes.

Lasmiditan is the first molecule in the “-ditan” class to be evaluated by the FDA for the acute treatment of migraine in adults, according to an Eli Lilly press release.

“If approved, it could represent the first significant innovation for the acute treatment of migraine in more than 2 decades,” the press release said. – by Janel Miller

 

References:

Alaini J, et al. Efficacy and safety of Lasmiditan in patients on concomitant migraine preventive medications: Findings from SAMURAI and SPARTAN phase 3 trials.

Ashina M, et al. Onset of efficacy following oral treatment with Lasmiditan for the acute treatment of migraine.

Bodie J, et al. Effects of Lasmiditan on driving performance: results of 2 randomized, blinded, crossover simulated driving studies with placebo and active control.

Brandes J et al. Long-term safety and efficacy of Lasmiditan for acute treatment of migraine over a one-year period: Interim results of an open label phase 3 study (GLADIATOR).

Rizzoli P, et al. Safety findings from the phase 3 studies (SAMURAI, SPARTAN) of Lasmiditan for acute treatment of migraine.

Wilbrahm, D, et al. Effects of Lasmiditan on cardiovascular parameters in healthy subjects receiving oral doses of propranolol.

Wilbrahm, D, et al. Effects of Lasmiditan when coadministered with topiramate: Results of a parallel, placebo-controlled, fixed-sequence study in healthy subjects.

Wilbrahm, D et al. Effects of Lasmiditan when coadministered with sumatriptan: results of a randomized, double-blind, crossover study in healthy subjects.

All presented at: American Headache Society Annual Scientific Meeting; July 11-14, 2019; Philadelphia.

Disclosures: Healio Primary Care was unable to determine the authors’ relevant financial disclosures prior to publication.

PHILADELPHIA — Lasmiditan, an investigational, oral, first-in-class receptor antagonist for the acute treatment of migraine pain, hindered patients’ ability to drive even though the drivers did not think their driving was impaired, according to a discussion held during the American Headache Society Annual Scientific Meeting.

FDA guidance states that driving tests should occur when there is evidence that drugs such as Lasmiditan (Eli Lilly) can impact the patient’s central nervous system and ability to drive, Eric Pearlman, MD, PhD, a senior medical director at Eli Lilly, told attendees.

“Two of the major driving forces behind [the guidance] was one, that the FDA sees driving as an important public health issue and two, that research shows that drivers poorly judge their own driving performance,” he said.

Researchers randomly assigned 90 patients between 30 years and 40 years of age a single oral dose of 1-mg of alprazolam and either a 50-mg, 100-mg or 200-mg dose of Lasmiditan and then a placebo at 1.5 hours post-dose to replicate Lasmiditan peak concentration. Another 68 patients were randomized to receive single oral doses of either 100-mg or 200-mg of Lasmiditan as well as 50-mg of diphenhydramine 2 hours before each driving assessment.

 “These patients were asked ‘do you feel safe to drive?’ right before they performed a driving assessment. A relatively high proportion of subjects 55% to 80%, depending on dose — reported they were safe to drive, but the vast majority were impaired at 1.5 hours,” Pearlman said, adding that 1.5 hours is also the approximate time of Lasmiditan’s peak concentration. Researchers noted that about 8 hours after receiving their respective doses, drivers’ disabilities were “obsolete.”

Younger man with headache 2 
Lasmiditan, an investigational, oral, first-in-class receptor antagonist for the acute treatment of migraine pain, hindered patients’ ability to drive even though the drivers did not think their driving was impaired, according to a discussion held during the American Headache Society Annual Scientific Meeting.


Source:Adobe

Pearlman discussed future research topics.

“Like any good research [our study] raised more questions than it does provide answers. We actually know very little migraine’s about impact has on driving [and] the magnitude of driving impairment from other migraine treatments,” he concluded.

Other Lasmiditan data presented at the meeting included:

  • 30 healthy patients were randomized in a 2:1 ratio to receive a single 200-mg dose of Lasmiditan or placebo in a double-blinded manner on days 1 and 14, a titrated dose of up to 50-mg of open-label topiramate two times a day on days 3 to 13 and a 50-mg dose of topiramate coadministered with a single dose of Lasmiditan or placebo on day 14. At study’s end, participants did not demonstrate any clinically relevant effects on adverse events, vital signs, electrocardiograms and clinical laboratory data vs. either drug administered alone.
  • 39 healthy patients were randomized to receive the following four treatments on day 1 of four study periods: lasmiditan+sumatriptan; lasmiditan+placebo; sumatriptan+placebo or placebo+placebo with a washout of at least 4 days between each dose. At study’s end, there were no clinically relevant pharmacokinetics, cardiovascular or safety interactions observed in any of the cohorts.

“For patients in whom these reductions in heart rate may pose a risk, including patients taking medicines that lower heart rate, these findings may be clinically relevant,” researchers wrote.

Other findings included:

  • 775 patients who used a migraine preventive medication and received either a 50-mg, 100-mg or 200-mg dose of Lasmiditan were significantly more likely to be pain-free at 2 hours vs. placebo (P < .05).
  • 814 patients with migraine participating in a long-term study had interim safety and efficacy results that were “generally consistent” with those observed in the single-attack studies consisting of the same cohort. Researchers also noted that generally speaking, the frequency of dizziness (18.6%), somnolence (8.5%), paresthesia (6.8%), fatigue (5.5%), nausea (4.7%), and asthenia (2%) dropped as more doses were administered, and the effects of treatment were “generally consistent” over time for up to 1 year.
  • Patients assigned to take either placebo (n = 1,262) or a 50-mg (n = 654), 100-mg (n = 1,265) or a 200-mg (n = 1,258) dose of Lasmiditan within 4 hours of migraine onset experienced at least one of the following: dizziness, paresthesia, somnolence, fatigue, nausea, muscular weakness and hypoesthesia. Researchers wrote that these occurrences were mostly mild or moderate in severity, of “quick onset and self-limiting.”
  • Patients who received either a 50-mg (n = 744), 100-mg (n = 1,494) or 200-mg (n = 1,491) dose of Lasmitidan for a single migraine attack reported an earlier onset of efficacy measured by pain relief, photophobia-freedom and most bothersome symptom freedom compared to those treated with placebo (n = 1,488). Researchers added that some patients taking the higher doses experienced the improvement in pain relief within 30 minutes.

Lasmiditan is the first molecule in the “-ditan” class to be evaluated by the FDA for the acute treatment of migraine in adults, according to an Eli Lilly press release.

“If approved, it could represent the first significant innovation for the acute treatment of migraine in more than 2 decades,” the press release said. – by Janel Miller

 

References:

Alaini J, et al. Efficacy and safety of Lasmiditan in patients on concomitant migraine preventive medications: Findings from SAMURAI and SPARTAN phase 3 trials.

Ashina M, et al. Onset of efficacy following oral treatment with Lasmiditan for the acute treatment of migraine.

Bodie J, et al. Effects of Lasmiditan on driving performance: results of 2 randomized, blinded, crossover simulated driving studies with placebo and active control.

Brandes J et al. Long-term safety and efficacy of Lasmiditan for acute treatment of migraine over a one-year period: Interim results of an open label phase 3 study (GLADIATOR).

Rizzoli P, et al. Safety findings from the phase 3 studies (SAMURAI, SPARTAN) of Lasmiditan for acute treatment of migraine.

Wilbrahm, D, et al. Effects of Lasmiditan on cardiovascular parameters in healthy subjects receiving oral doses of propranolol.

Wilbrahm, D, et al. Effects of Lasmiditan when coadministered with topiramate: Results of a parallel, placebo-controlled, fixed-sequence study in healthy subjects.

Wilbrahm, D et al. Effects of Lasmiditan when coadministered with sumatriptan: results of a randomized, double-blind, crossover study in healthy subjects.

All presented at: American Headache Society Annual Scientific Meeting; July 11-14, 2019; Philadelphia.

Disclosures: Healio Primary Care was unable to determine the authors’ relevant financial disclosures prior to publication.

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