Lack of hemodynamic interaction between CGRP-receptor antagonist telcagepant (MK-0974) and sumatriptan

Results from a randomized study in patients with migraine

M. Depré, C. Macleod, J. Palcza, M. O. Behm, I. De Lepeleire, T. Han, D. Panebianco, William Smith, R. Blanchard, J. A. Chodakewitz, M. G. Murphy, J. N. De Hoon

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Objective: The objective of this article is to assess the effects of sumatriptan monotherapy, telcagepant monotherapy, and their combination on blood pressure (BP) in migraine patients during a headache-free period. Methods: A double-blind, placebo-controlled, four-period, single-dose, randomized crossover study in 24 migraine patients was conducted. In each period, patients received a single oral dose of sumatriptan 100 mg alone, telcagepant 600 mg alone, sumatriptan 100 mg coadministered with telcagepant 600 mg, or placebo. Semi-recumbent BP was measured pre-dose and at seven post-dose timepoints over a period of six hours. Individual time-weighted averages in mean arterial pressure (MAP) were evaluated using a linear mixed-effects model. The pharmacokinetics of sumatriptan alone and in the presence of telcagepant were also evaluated using limited sampling times. Results: The mean difference in time-weighted (02.5 h) MAP (90% confidence interval) was 1.2 mmHg (-0.2, 2.7) between telcagepant and placebo, 4.0mmHg (2.5, 5.5) between sumatriptan and placebo, and 1.5mmHg (0.0, 3.0) between telcagepant with sumatriptan vs sumatriptan alone. When coadministered with telcagepant, the AUC06h and Cmax of sumatriptan were increased by 23% and 24%, respectively. The small MAP increases observed after coadministration could possibly be associated with the slight elevations in sumatriptan levels. Conclusion: Telcagepant does not elevate mean MAP, and coadministration of telcagepant with sumatriptan results in elevations in MAP similar to those observed following administration of sumatriptan alone in migraineurs during the interictal period. When coadministered, telcagepant slightly increases the plasma levels of sumatriptan, but without an apparent clinically meaningful effect.

Original languageEnglish (US)
Pages (from-to)1292-1301
Number of pages10
JournalCephalalgia
Volume33
Issue number16
DOIs
StatePublished - Dec 1 2013

Fingerprint

Calcitonin Gene-Related Peptide Receptors
Sumatriptan
Migraine Disorders
Hemodynamics
Arterial Pressure
Placebos
telcagepant
Blood Pressure
Double-Blind Method
Cross-Over Studies
Headache

All Science Journal Classification (ASJC) codes

  • Clinical Neurology

Cite this

Lack of hemodynamic interaction between CGRP-receptor antagonist telcagepant (MK-0974) and sumatriptan : Results from a randomized study in patients with migraine. / Depré, M.; Macleod, C.; Palcza, J.; Behm, M. O.; De Lepeleire, I.; Han, T.; Panebianco, D.; Smith, William; Blanchard, R.; Chodakewitz, J. A.; Murphy, M. G.; De Hoon, J. N.

In: Cephalalgia, Vol. 33, No. 16, 01.12.2013, p. 1292-1301.

Research output: Contribution to journalArticle

Depré, M, Macleod, C, Palcza, J, Behm, MO, De Lepeleire, I, Han, T, Panebianco, D, Smith, W, Blanchard, R, Chodakewitz, JA, Murphy, MG & De Hoon, JN 2013, 'Lack of hemodynamic interaction between CGRP-receptor antagonist telcagepant (MK-0974) and sumatriptan: Results from a randomized study in patients with migraine', Cephalalgia, vol. 33, no. 16, pp. 1292-1301. https://doi.org/10.1177/0333102413494272
Depré, M. ; Macleod, C. ; Palcza, J. ; Behm, M. O. ; De Lepeleire, I. ; Han, T. ; Panebianco, D. ; Smith, William ; Blanchard, R. ; Chodakewitz, J. A. ; Murphy, M. G. ; De Hoon, J. N. / Lack of hemodynamic interaction between CGRP-receptor antagonist telcagepant (MK-0974) and sumatriptan : Results from a randomized study in patients with migraine. In: Cephalalgia. 2013 ; Vol. 33, No. 16. pp. 1292-1301.
@article{6f8cbcda1c42483bace4767915d04e06,
title = "Lack of hemodynamic interaction between CGRP-receptor antagonist telcagepant (MK-0974) and sumatriptan: Results from a randomized study in patients with migraine",
abstract = "Objective: The objective of this article is to assess the effects of sumatriptan monotherapy, telcagepant monotherapy, and their combination on blood pressure (BP) in migraine patients during a headache-free period. Methods: A double-blind, placebo-controlled, four-period, single-dose, randomized crossover study in 24 migraine patients was conducted. In each period, patients received a single oral dose of sumatriptan 100 mg alone, telcagepant 600 mg alone, sumatriptan 100 mg coadministered with telcagepant 600 mg, or placebo. Semi-recumbent BP was measured pre-dose and at seven post-dose timepoints over a period of six hours. Individual time-weighted averages in mean arterial pressure (MAP) were evaluated using a linear mixed-effects model. The pharmacokinetics of sumatriptan alone and in the presence of telcagepant were also evaluated using limited sampling times. Results: The mean difference in time-weighted (02.5 h) MAP (90{\%} confidence interval) was 1.2 mmHg (-0.2, 2.7) between telcagepant and placebo, 4.0mmHg (2.5, 5.5) between sumatriptan and placebo, and 1.5mmHg (0.0, 3.0) between telcagepant with sumatriptan vs sumatriptan alone. When coadministered with telcagepant, the AUC06h and Cmax of sumatriptan were increased by 23{\%} and 24{\%}, respectively. The small MAP increases observed after coadministration could possibly be associated with the slight elevations in sumatriptan levels. Conclusion: Telcagepant does not elevate mean MAP, and coadministration of telcagepant with sumatriptan results in elevations in MAP similar to those observed following administration of sumatriptan alone in migraineurs during the interictal period. When coadministered, telcagepant slightly increases the plasma levels of sumatriptan, but without an apparent clinically meaningful effect.",
author = "M. Depr{\'e} and C. Macleod and J. Palcza and Behm, {M. O.} and {De Lepeleire}, I. and T. Han and D. Panebianco and William Smith and R. Blanchard and Chodakewitz, {J. A.} and Murphy, {M. G.} and {De Hoon}, {J. N.}",
year = "2013",
month = "12",
day = "1",
doi = "10.1177/0333102413494272",
language = "English (US)",
volume = "33",
pages = "1292--1301",
journal = "Cephalalgia",
issn = "0333-1024",
publisher = "SAGE Publications Ltd",
number = "16",

}

TY - JOUR

T1 - Lack of hemodynamic interaction between CGRP-receptor antagonist telcagepant (MK-0974) and sumatriptan

T2 - Results from a randomized study in patients with migraine

AU - Depré, M.

AU - Macleod, C.

AU - Palcza, J.

AU - Behm, M. O.

AU - De Lepeleire, I.

AU - Han, T.

AU - Panebianco, D.

AU - Smith, William

AU - Blanchard, R.

AU - Chodakewitz, J. A.

AU - Murphy, M. G.

AU - De Hoon, J. N.

PY - 2013/12/1

Y1 - 2013/12/1

N2 - Objective: The objective of this article is to assess the effects of sumatriptan monotherapy, telcagepant monotherapy, and their combination on blood pressure (BP) in migraine patients during a headache-free period. Methods: A double-blind, placebo-controlled, four-period, single-dose, randomized crossover study in 24 migraine patients was conducted. In each period, patients received a single oral dose of sumatriptan 100 mg alone, telcagepant 600 mg alone, sumatriptan 100 mg coadministered with telcagepant 600 mg, or placebo. Semi-recumbent BP was measured pre-dose and at seven post-dose timepoints over a period of six hours. Individual time-weighted averages in mean arterial pressure (MAP) were evaluated using a linear mixed-effects model. The pharmacokinetics of sumatriptan alone and in the presence of telcagepant were also evaluated using limited sampling times. Results: The mean difference in time-weighted (02.5 h) MAP (90% confidence interval) was 1.2 mmHg (-0.2, 2.7) between telcagepant and placebo, 4.0mmHg (2.5, 5.5) between sumatriptan and placebo, and 1.5mmHg (0.0, 3.0) between telcagepant with sumatriptan vs sumatriptan alone. When coadministered with telcagepant, the AUC06h and Cmax of sumatriptan were increased by 23% and 24%, respectively. The small MAP increases observed after coadministration could possibly be associated with the slight elevations in sumatriptan levels. Conclusion: Telcagepant does not elevate mean MAP, and coadministration of telcagepant with sumatriptan results in elevations in MAP similar to those observed following administration of sumatriptan alone in migraineurs during the interictal period. When coadministered, telcagepant slightly increases the plasma levels of sumatriptan, but without an apparent clinically meaningful effect.

AB - Objective: The objective of this article is to assess the effects of sumatriptan monotherapy, telcagepant monotherapy, and their combination on blood pressure (BP) in migraine patients during a headache-free period. Methods: A double-blind, placebo-controlled, four-period, single-dose, randomized crossover study in 24 migraine patients was conducted. In each period, patients received a single oral dose of sumatriptan 100 mg alone, telcagepant 600 mg alone, sumatriptan 100 mg coadministered with telcagepant 600 mg, or placebo. Semi-recumbent BP was measured pre-dose and at seven post-dose timepoints over a period of six hours. Individual time-weighted averages in mean arterial pressure (MAP) were evaluated using a linear mixed-effects model. The pharmacokinetics of sumatriptan alone and in the presence of telcagepant were also evaluated using limited sampling times. Results: The mean difference in time-weighted (02.5 h) MAP (90% confidence interval) was 1.2 mmHg (-0.2, 2.7) between telcagepant and placebo, 4.0mmHg (2.5, 5.5) between sumatriptan and placebo, and 1.5mmHg (0.0, 3.0) between telcagepant with sumatriptan vs sumatriptan alone. When coadministered with telcagepant, the AUC06h and Cmax of sumatriptan were increased by 23% and 24%, respectively. The small MAP increases observed after coadministration could possibly be associated with the slight elevations in sumatriptan levels. Conclusion: Telcagepant does not elevate mean MAP, and coadministration of telcagepant with sumatriptan results in elevations in MAP similar to those observed following administration of sumatriptan alone in migraineurs during the interictal period. When coadministered, telcagepant slightly increases the plasma levels of sumatriptan, but without an apparent clinically meaningful effect.

UR - http://www.scopus.com/inward/record.url?scp=84887847827&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84887847827&partnerID=8YFLogxK

U2 - 10.1177/0333102413494272

DO - 10.1177/0333102413494272

M3 - Article

VL - 33

SP - 1292

EP - 1301

JO - Cephalalgia

JF - Cephalalgia

SN - 0333-1024

IS - 16

ER -