Evaluating Mean Level and Within-Person Consistency in Migraine Pain Intensity and Migraine-Related Disability for AVP-825 vs Oral Sumatriptan: Results from the COMPASS Study, A Randomized Trial

James S. McGinley, Dawn C. Buse, Kenneth J. Shulman, R. J. Wirth, Emmanuelle Hugentobler, Richard B. Lipton

Research output: Contribution to journalArticle

Abstract

Background: Consistency of response across multiple attacks is typically measured as the proportion of study participants who achieve a categorical endpoint over a specified number of attacks (ie, 2-hour pain-free response in 2 of 3 attacks). We applied a novel analytic approach for measuring consistency of response in the acute treatment of episodic migraine using data from the COMPASS study. Methods: The COMPASS study (NCT01667679) was a multiple attack crossover study which compared AVP-825, a Breath Powered ® intranasal delivery system for low-dose sumatriptan powder (22 mg), with 100-mg oral sumatriptan tablets in the acute treatment of migraine. Participants were 18–65 years old, met ICHD-2 criteria for migraine with or without aura, and had migraine for ≥1 year prior to screening. They were instructed to treat up to 5 migraine attacks with each treatment and recorded migraine pain intensity and disability data at pre-dose and 10, 15, 30, 45, 60, 90, and 120 minutes post-dose for each attack. We explored the mean level and within-person variability (WPV; a measure of consistency) in migraine pain intensity and migraine-related disability across multiple attacks after treatment with AVP-825 (22 mg) vs oral sumatriptan (100 mg) using location scale mixed-effects models (LSMEMs). LSMEMs controlled for pre-dose pain/disability, demographics, treatment sequence, and treatment period. Results: The mean age was 40 and the sample was 84.6% women. Participants (N = 259) treated an average of 6.8 attacks each during the course of the study. Attacks treated with AVP-825 showed significantly lower mean pain intensity and mean disability from 10 to 90 minutes post-dose (effect sizes ranged from −0.09 to −0.29 and P values ranged from P <.0001 to P =.01). WPV was significantly greater at 10–15 minutes (WPV ratios ranged from 1.20 to 1.58 and P values ranged from P <.0001 to P =.04) but significantly reduced from 45 to 120 minutes for attacks treated with AVP-825 compared to oral sumatriptan (WPV ratios ranged from 0.67 to 0.81 and P values ranged from P <.0001 to P =.03). Conclusions: LSMEMs demonstrate that treatment with AVP-825 is associated with lower average migraine pain intensity and disability from 10 to 90 minutes and greater within-person consistency across multiple migraine attacks (reduced WPV) from 45 to 120 minutes post-dose compared to oral sumatriptan. These findings may reflect the more rapid and consistent absorption of sumatriptan using AVP-825. Increased WPV with AVP-825 in the first 15 minutes likely reflects the earlier onset of treatment effects with the device compared to oral sumatriptan. LSMEMs show promise as a novel approach for assessing and comparing consistency of treatment response in migraine trials.

Original languageEnglish (US)
JournalHeadache
DOIs
StatePublished - Jan 1 2019

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Sumatriptan
Migraine Disorders
Pain
Therapeutics
Migraine without Aura
Migraine with Aura
Powders
Cross-Over Studies
Tablets
Demography

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Evaluating Mean Level and Within-Person Consistency in Migraine Pain Intensity and Migraine-Related Disability for AVP-825 vs Oral Sumatriptan : Results from the COMPASS Study, A Randomized Trial. / McGinley, James S.; Buse, Dawn C.; Shulman, Kenneth J.; Wirth, R. J.; Hugentobler, Emmanuelle; Lipton, Richard B.

In: Headache, 01.01.2019.

Research output: Contribution to journalArticle

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title = "Evaluating Mean Level and Within-Person Consistency in Migraine Pain Intensity and Migraine-Related Disability for AVP-825 vs Oral Sumatriptan: Results from the COMPASS Study, A Randomized Trial",
abstract = "Background: Consistency of response across multiple attacks is typically measured as the proportion of study participants who achieve a categorical endpoint over a specified number of attacks (ie, 2-hour pain-free response in 2 of 3 attacks). We applied a novel analytic approach for measuring consistency of response in the acute treatment of episodic migraine using data from the COMPASS study. Methods: The COMPASS study (NCT01667679) was a multiple attack crossover study which compared AVP-825, a Breath Powered {\circledR} intranasal delivery system for low-dose sumatriptan powder (22 mg), with 100-mg oral sumatriptan tablets in the acute treatment of migraine. Participants were 18–65 years old, met ICHD-2 criteria for migraine with or without aura, and had migraine for ≥1 year prior to screening. They were instructed to treat up to 5 migraine attacks with each treatment and recorded migraine pain intensity and disability data at pre-dose and 10, 15, 30, 45, 60, 90, and 120 minutes post-dose for each attack. We explored the mean level and within-person variability (WPV; a measure of consistency) in migraine pain intensity and migraine-related disability across multiple attacks after treatment with AVP-825 (22 mg) vs oral sumatriptan (100 mg) using location scale mixed-effects models (LSMEMs). LSMEMs controlled for pre-dose pain/disability, demographics, treatment sequence, and treatment period. Results: The mean age was 40 and the sample was 84.6{\%} women. Participants (N = 259) treated an average of 6.8 attacks each during the course of the study. Attacks treated with AVP-825 showed significantly lower mean pain intensity and mean disability from 10 to 90 minutes post-dose (effect sizes ranged from −0.09 to −0.29 and P values ranged from P <.0001 to P =.01). WPV was significantly greater at 10–15 minutes (WPV ratios ranged from 1.20 to 1.58 and P values ranged from P <.0001 to P =.04) but significantly reduced from 45 to 120 minutes for attacks treated with AVP-825 compared to oral sumatriptan (WPV ratios ranged from 0.67 to 0.81 and P values ranged from P <.0001 to P =.03). Conclusions: LSMEMs demonstrate that treatment with AVP-825 is associated with lower average migraine pain intensity and disability from 10 to 90 minutes and greater within-person consistency across multiple migraine attacks (reduced WPV) from 45 to 120 minutes post-dose compared to oral sumatriptan. These findings may reflect the more rapid and consistent absorption of sumatriptan using AVP-825. Increased WPV with AVP-825 in the first 15 minutes likely reflects the earlier onset of treatment effects with the device compared to oral sumatriptan. LSMEMs show promise as a novel approach for assessing and comparing consistency of treatment response in migraine trials.",
author = "McGinley, {James S.} and Buse, {Dawn C.} and Shulman, {Kenneth J.} and Wirth, {R. J.} and Emmanuelle Hugentobler and Lipton, {Richard B.}",
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T2 - Results from the COMPASS Study, A Randomized Trial

AU - McGinley, James S.

AU - Buse, Dawn C.

AU - Shulman, Kenneth J.

AU - Wirth, R. J.

AU - Hugentobler, Emmanuelle

AU - Lipton, Richard B.

PY - 2019/1/1

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N2 - Background: Consistency of response across multiple attacks is typically measured as the proportion of study participants who achieve a categorical endpoint over a specified number of attacks (ie, 2-hour pain-free response in 2 of 3 attacks). We applied a novel analytic approach for measuring consistency of response in the acute treatment of episodic migraine using data from the COMPASS study. Methods: The COMPASS study (NCT01667679) was a multiple attack crossover study which compared AVP-825, a Breath Powered ® intranasal delivery system for low-dose sumatriptan powder (22 mg), with 100-mg oral sumatriptan tablets in the acute treatment of migraine. Participants were 18–65 years old, met ICHD-2 criteria for migraine with or without aura, and had migraine for ≥1 year prior to screening. They were instructed to treat up to 5 migraine attacks with each treatment and recorded migraine pain intensity and disability data at pre-dose and 10, 15, 30, 45, 60, 90, and 120 minutes post-dose for each attack. We explored the mean level and within-person variability (WPV; a measure of consistency) in migraine pain intensity and migraine-related disability across multiple attacks after treatment with AVP-825 (22 mg) vs oral sumatriptan (100 mg) using location scale mixed-effects models (LSMEMs). LSMEMs controlled for pre-dose pain/disability, demographics, treatment sequence, and treatment period. Results: The mean age was 40 and the sample was 84.6% women. Participants (N = 259) treated an average of 6.8 attacks each during the course of the study. Attacks treated with AVP-825 showed significantly lower mean pain intensity and mean disability from 10 to 90 minutes post-dose (effect sizes ranged from −0.09 to −0.29 and P values ranged from P <.0001 to P =.01). WPV was significantly greater at 10–15 minutes (WPV ratios ranged from 1.20 to 1.58 and P values ranged from P <.0001 to P =.04) but significantly reduced from 45 to 120 minutes for attacks treated with AVP-825 compared to oral sumatriptan (WPV ratios ranged from 0.67 to 0.81 and P values ranged from P <.0001 to P =.03). Conclusions: LSMEMs demonstrate that treatment with AVP-825 is associated with lower average migraine pain intensity and disability from 10 to 90 minutes and greater within-person consistency across multiple migraine attacks (reduced WPV) from 45 to 120 minutes post-dose compared to oral sumatriptan. These findings may reflect the more rapid and consistent absorption of sumatriptan using AVP-825. Increased WPV with AVP-825 in the first 15 minutes likely reflects the earlier onset of treatment effects with the device compared to oral sumatriptan. LSMEMs show promise as a novel approach for assessing and comparing consistency of treatment response in migraine trials.

AB - Background: Consistency of response across multiple attacks is typically measured as the proportion of study participants who achieve a categorical endpoint over a specified number of attacks (ie, 2-hour pain-free response in 2 of 3 attacks). We applied a novel analytic approach for measuring consistency of response in the acute treatment of episodic migraine using data from the COMPASS study. Methods: The COMPASS study (NCT01667679) was a multiple attack crossover study which compared AVP-825, a Breath Powered ® intranasal delivery system for low-dose sumatriptan powder (22 mg), with 100-mg oral sumatriptan tablets in the acute treatment of migraine. Participants were 18–65 years old, met ICHD-2 criteria for migraine with or without aura, and had migraine for ≥1 year prior to screening. They were instructed to treat up to 5 migraine attacks with each treatment and recorded migraine pain intensity and disability data at pre-dose and 10, 15, 30, 45, 60, 90, and 120 minutes post-dose for each attack. We explored the mean level and within-person variability (WPV; a measure of consistency) in migraine pain intensity and migraine-related disability across multiple attacks after treatment with AVP-825 (22 mg) vs oral sumatriptan (100 mg) using location scale mixed-effects models (LSMEMs). LSMEMs controlled for pre-dose pain/disability, demographics, treatment sequence, and treatment period. Results: The mean age was 40 and the sample was 84.6% women. Participants (N = 259) treated an average of 6.8 attacks each during the course of the study. Attacks treated with AVP-825 showed significantly lower mean pain intensity and mean disability from 10 to 90 minutes post-dose (effect sizes ranged from −0.09 to −0.29 and P values ranged from P <.0001 to P =.01). WPV was significantly greater at 10–15 minutes (WPV ratios ranged from 1.20 to 1.58 and P values ranged from P <.0001 to P =.04) but significantly reduced from 45 to 120 minutes for attacks treated with AVP-825 compared to oral sumatriptan (WPV ratios ranged from 0.67 to 0.81 and P values ranged from P <.0001 to P =.03). Conclusions: LSMEMs demonstrate that treatment with AVP-825 is associated with lower average migraine pain intensity and disability from 10 to 90 minutes and greater within-person consistency across multiple migraine attacks (reduced WPV) from 45 to 120 minutes post-dose compared to oral sumatriptan. These findings may reflect the more rapid and consistent absorption of sumatriptan using AVP-825. Increased WPV with AVP-825 in the first 15 minutes likely reflects the earlier onset of treatment effects with the device compared to oral sumatriptan. LSMEMs show promise as a novel approach for assessing and comparing consistency of treatment response in migraine trials.

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