The purpose of this study is to (1) evaluate pain-free efficacy of Treximet™ following treatment of menstrual migraine, (2) investigate levels of Calcitonin gene-related peptide (CGRP), estrogen, cortisol, vasoactive intestinal peptide (VIP), alpha (a)-amylase, Prostaglandin E2 (PGE2), Prostaglandin I2 (PGI2) and beta (ß)-endorphin in saliva before and after Treximet™, (3) evaluate efficacy of Treximet™ to return to baseline levels following treatment, and (4) correlate estrogen in saliva vs. urinary estradiol at mid-luteal, onset of menstrually-related migraine, and after successful treatment with Treximet™.
Subjects randomized to Group A will be provided with 1 tablet of Treximet to be taken at onset of menstrual migraine headache pain.
All subjects will be provided with 1 tablet of Treximet for treatment of persistent or recurring headache between 2 and 24 hours following treatment with study medication at headache onset.
Tablet for oral administration contains sumatriptan 85mg / naproxen sodium 500mg.
Subjects randomized to Group B will be provided with 1 tablet of placebo to be taken at onset of menstrual migraine headache pain.
A placebo tablet matching Treximet for oral administration.
Number of subjects either pain free or mild at 2 hours then pain level increases within 24 hours following treatment with Treximet versus (vs.) Placebo for 1 menstrual migraine.
0-3 pain scale with 0=No Pain, 1=Mild, 2=Moderate,and 3=Severe.
Duration of 1 menstrual migraine from time of treatment at menstrual migraine headache onset until pain free in Treximet vs. Placebo arms.
0-3 pain scale with 0=No Pain, 1=Mild, 2=Moderate, and 3=Severe.
Vasoactive Intestinal Peptide (VIP), Prostaglandin E2 (PGE2), Cortisol, Prostaglandin I2 (PGI2), Estradiol, and β-endorphin** levels collected at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment in Treximet vs. Placebo arms for 1 menstrual migraine headache * This endpoint was separated into 3 outcome measures as all biomarkers were not reported in the same units of measure. Calcitonin Gene-Related Peptide (CGRP) and α-amylase both have their own outcome measure reported individually.
**β-endorphin levels were not assayed due to limitations on saliva sample volumes.
* This endpoint was separated into 3 outcome measures as all biomarkers were not reported in the same units of measure.
VIP, PGE2, Cortisol, PGI2, Estradiol, and β-endorphin** levels collected at Menstrual Migraine Headache Onset, Migraine Headache Free and 24 Hours Migraine Headache Free in Treximet vs. Placebo arm for 1 menstrual migraine headache.
* This endpoint was separated into 3 outcome measures as all biomarkers were not reported in the same units of measure. CGRP and α-amylase both have their own outcome measure reported individually.
CGRP levels collected at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Treximet vs. Placebo arm for 1 menstrual migraine headache.
*Urine estradiol levels were not collected at migraine onset, therefore; correlations could not be completed for that time point.
Number of subjects either pain-free or mild at 2 hours then pain level increases within 24 hours following treatment in Treximet vs. Placebo arm for 1 menstrual migraine headache with Treximet vs. Placebo in responders* vs. non-responders.
*A responder is defined as those who at the time of two hours post treatment reported mild or no pain. Additionally, these subjects could not have taken a rescue medication or have a pain level increase within 24 hours post treatment.
A non-responder is one that fails to meet the responder criteria.
Duration of time from treatment at menstrual migraine headache onset until pain-free in Treximet vs. Placebo arms in responders* vs. non-responders for 1 menstrual migraine.
0-3 Pain Scale, with 0=No Pain, 1=Mild, 2=Moderate, and 3=Severe.
VIP, PGE2, Cortisol, PGI2, Estradiol, and β-endorphin** levels collected for 1 menstrual migraine headache at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment in Treximet vs. Placebo arms in responders vs. non-responders***.
*This endpoint was separated into 3 outcome measures as all biomarkers were not reported in the same unit of measure. CGRP and α-amylase both have their own outcome measure reported individually.
***A responder is defined as those who at the time of two hours post treatment reported mild or no pain. Additionally, these subjects could not have taken a rescue medication or have a pain level increase within 24 hours post treatment.
CGRP levels collected for 1 menstrual migraine headache at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post-Treatment in Responders vs Non-Responders**.
*This endpoint was separated into 3 outcome measures as all biomarkers were not reported in the same units of measure.
**A responder is defined as those who at the time of two hours post treatment reported mild or no pain. Additionally, these subjects could not have taken a rescue medication or have a pain level increase within 24 hours post treatment.
α-Amylase levels collected at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment in Responders vs Non-Responders*.
VIP, PGE2, Cortisol, PGI2, Estradiol, and β-endorphin** levels collected for 1 menstrual migraine headache at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders***.
*This endpoint was separated into 3 outcome measures as all biomarkers were not reported in the same units of measure. CGRP and α-amylase both have their own outcome measure reported individually.
***A responder is defined as those who at the time of two hours post treatment reported mild or no pain. Additionally, these subjects could not have taken a rescue medication or have a pain level increase within 24 hours post treatment. A non-responder is one that fails to meet the responder criteria.
CGRP levels collected for 1 menstrual migraine headache at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders**.
α-Amylase levels collected for 1 menstrual migraine at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders**.
Correlation of mean estrogen levels in saliva and urine estradiol at mid-luteal, menstrual migraine headache onset* and at migraine headache free following treatment in responders vs. non-responders**.
Any other methods with published data showing that the highest expected failure rate for that method is less than 1% per year.
has regular and predictable monthly menstrual cycles within a range of 22-32 days for the past 3 cycles.
has a history of serotonin syndrome.
has a recent history of regular use of opioids or barbiturates for treatment of their migraine headache and/or other non-migraine pain or any medication overuse that in the opinion of the investigator has exacerbated or contributed to the current headache pattern of the subject. Overuse is defined as an average of 10 days per month over the last 6 months.
has taken, or plans to take, a monoamine oxidase inhibitor (MAOI), including herbal preparations containing St. John's Wort (Hypericum perforatum), anytime within the 2 weeks prior to screening through 2 weeks post final study treatment.
has history of any bleeding disorder or is currently taking any anti-coagulant or any antiplatelet agent.
has evidence of alcohol or substance abuse within the last year or any concurrent medical or psychiatric condition which, in the investigator's judgment, will likely interfere with the study conduct, subject cooperation, or evaluation and interpretation of the study results, or which otherwise contraindicates participation in this clinical trial.
has participated in an investigational drug trial within the previous four weeks or plans to participate in another study at any time during this study.
Martin VT, Behbehani M. Ovarian hormones and migraine headache: understanding mechanisms and pathogenesis--part 2. Headache. 2006 Mar;46(3):365-86. Review.
Martin VT, Wernke S, Mandell K, Ramadan N, Kao L, Bean J, Liu J, Zoma W, Rebar R. Symptoms of premenstrual syndrome and their association with migraine headache. Headache. 2006 Jan;46(1):125-37.
Cady R, Dodick DW. Diagnosis and treatment of migraine. Mayo Clin Proc. 2002 Mar;77(3):255-61. Review.
Durham PL. Calcitonin gene-related peptide (CGRP) and migraine. Headache. 2006 Jun;46 Suppl 1:S3-8. Review.
Nappi RE, Sances G, Brundu B, De Taddei S, Sommacal A, Ghiotto N, Polatti F, Nappi G. Estradiol supplementation modulates neuroendocrine response to M-chlorophenylpiperazine in menstrual status migrainosus triggered by oral contraception-free interval. Hum Reprod. 2005 Dec;20(12):3423-8. Epub 2005 Aug 25.
Bellamy JL, Cady RK, Durham PL. Salivary levels of CGRP and VIP in rhinosinusitis and migraine patients. Headache. 2006 Jan;46(1):24-33.