Menstrual Migraine
Conditions
Keywords
Menstrual migraine, Menstrually-related migraine, Treximet, CGRP, calcitonin gene-related peptide
Brief summary
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™.
Detailed description
This double-blind multi-site study will be conducted to enroll 40 evaluable participants. All subjects will be medically stable at enrollment and be on a stabilized dosage of daily medications. At Visit 1 (Baseline) following Informed Consent, a physical and neurological exam, baseline electrocardiogram (ECG), and vital signs will be completed. A urine pregnancy test will be collected by all subjects of childbearing potential. Routine labs (electrolyte panel with creatinine, alanine aminotransferase (ALT) / aspartate aminotransferase (AST), a luteinizing hormone (LH) lab (for menstrual cycle staging) and a baseline saliva sample (for CGRP, estrogen, cortisol, VIP, a-amylase, PGI2, PGE2 and β-endorphin analysis) will be collected. Subjects should be headache-free at Visit 1. A medical, headache, and medication history will be collected on all subjects and eligible subjects will be randomized 1:1 to Group A or Group B. Group A will receive Treximet™ (sumatriptan succinate 85 milligrams (mg) and naproxen sodium 500 mg) 1 tablet. Group B will be provided 1 matching placebo tablet. Subjects will be instructed to not start study medication until notified by study staff that lab results were normal and they are eligible to proceed. Subjects will be instructed to treat as early as possible following the onset of a typical menstrual headache. Groups A and B will be provided with Treximet™ 1 tablet for rescue between 2 and 24 hours for persistent or recurring headache. Subjects will receive a Diary and instructions on Digital Versatile Disc (DVD) regarding documentation. Migraine associated symptoms (ie nausea, vomiting, light sensitivity, or sound sensitivity) will be collected as well as sleeplessness, difficulty thinking other bodily pain, and menstrual associated symptoms (to include intensity of menstrual cramps). Subjects will be given kits with written instructions for collection of urine and saliva samples and additional saliva instructions on DVD. All subjects will be given LH testing kits to define the time of ovulation. Diary documentation begins at the time of ovulation. They will collect baseline saliva and first morning urine samples during the mid-luteal time period for two consecutive days, which is defined as 4-7 days after the LH surge. Subjects will also be instructed to begin collection of saliva 48 hours prior to the start of menses at 8:00 am, 2:00 pm, and 8:00 pm for two days or until menstrual migraine occurs. They also will collect a first morning urine sample on the two mornings prior to menses. At the point of headache onset, subjects will be instructed to collect saliva at onset of pain, time of treatment, 2 and 24 hours following treatment, at pain free, 2 hours after pain free, and 24 hours after pain free. Subjects will also be instructed to collect a urine specimen when they are pain free following treatment with study medication. Subjects will document migraine associated symptoms, menstrual associated symptoms, and recurrence symptoms at all saliva collection time points in the provided Diary per instruction. Subjects should be instructed to phone the study coordinator at the end of the menstrual cycle to return for Visit 2 within 7 days. \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ At Visit 2 (Review) Diaries will be reviewed and frozen saliva and urine samples will be returned to the clinic. Subjects must meet the following criteria for urine and saliva analysis: * Diary review indicates that headache would have, if left untreated, at least one symptom of migraine (nausea, vomiting, phonophobia, or photophobia) . And * Headache was associated with the onset of menses And • Saliva and urine samples are returned to the clinic. Medical and medication history will be updated and adverse events collected. A urine pregnancy test will be collected by all subjects of childbearing potential. Drug accountability and compliance will be assessed.
Interventions
DRUGTreximet
Tablet for oral administration contains sumatriptan 85mg / naproxen sodium 500mg.
DRUGPlacebo
A placebo tablet matching Treximet for oral administration.
Sponsors
GlaxoSmithKline
Cady, Roger, M.D.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
Subject 1. is female between the ages of 18-45 and, if of child-bearing potential, has a negative pregnancy test (urine or serum) at screen, and agrees to one of the following: * Complete abstinence from intercourse from 2 weeks prior to administration of the investigational product, throughout the study, and for a time interval (5 days) after completion or premature discontinuation from the study, * History of bilateral tubal ligation * Sterilization of male partner; or, * Implants of levonorgestrel; or, * Injectable progestogen; or, * Oral contraceptive (combination therapy with ethinyl estradiol plus a progestin) with a placebo week every 1-3 months; or, * Any intrauterine device (IUD) with published data showing that the highest expected failure rate is less than 1% per year (not all IUDs meet this criterion); or, * Spermicide plus a mechanical barrier (e.g., spermicide plus a male condom or a female diaphragm); or, * Any other barrier methods (only if used in combination with any of the above acceptable methods); or, * Any other methods with published data showing that the highest expected failure rate for that method is less than 1% per year. 2. is formally diagnosed with International Classification of Headache Disorders (ICHD) menstrual migraine 3. has regular and predictable monthly menstrual cycles within a range of 22-32 days for the past 3 cycles. 4. has fewer than 15 headache days per month in past 3 months 5. has headache that, if left untreated, would have at least 1 symptom of migraine (nausea, vomiting, photophobia, or phonophobia) or respond to a triptan or ergotamine-containing medication with at least 50% of headaches 6. has a history of reliably predicting menstrual migraine headache onset at least 70% of the time 7. is medically stable as determined by the Investigator 8. if taking any concomitant medications, is on a stabilized dosage at the discretion of the investigator 9. is able to understand and communicate intelligibly with the study observer 10. is able to take oral medication, adhere to the medication regimens and perform study procedures 11. is able to read and comprehend written instructions and be willing to complete all procedures and assessments required by this protocol 12. is able to demonstrate the willingness to participate by signing and understanding an informed consent after full explanation of the study
Exclusion criteria
Subject 1. has a history of serotonin syndrome. 2. has any medical condition that, in the opinion of the investigator, could alter the response to study medication or confound the results of the study (ie. pathology of the salivary glands such as viral or bacterial sialadenitis or obstructive sialadenitis or Sjögren's Syndrome) 3. is of childbearing potential and not using adequate contraceptive measures 4. has history of retinal, basilar or hemiplegic migraine, cluster headache, or secondary headaches (such as due to trauma, infection, alterations of homeostasis, ear, nose and throat (ENT) or psychiatric disorders, cranial or cervical disorders or neuralgias) 5. in the investigator's opinion, is likely to have unrecognized cardiovascular or cerebrovascular disease (based on history or the presence of risk factors including but not limited to, hypertension, hypercholesterolemia, smoker, obesity, diabetes, or family history of coronary artery disease) 6. has blood pressure equal to or greater than 160/90 millimeters of mercury (mmHg) in 2 out of 3 blood pressure (BP) measurements at screening or is taking any angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker 7. has a history of significant congenital heart disease, cardiac arrhythmias requiring medication, or a history of a clinically significant electrocardiogram abnormality that, in the investigator's opinion, contraindicates participation in this study 8. has evidence or history of any ischemic vascular diseases including: ischemic heart disease, ischemic abdominal syndromes, peripheral vascular disease or Raynaud's Syndrome, or signs/symptoms consistent with any of the above 9. has evidence or history of central nervous system pathology including stroke and/or transient ischemic attacks (TIAs), epilepsy or structural brain lesions which lower the convulsive threshold; or has been treated with an antiepileptic drug for seizure control within 5 years prior to screening 10. has a history of impaired hepatic or renal function that, in the investigator's opinion, contraindicates participation in this study 11. has hypersensitivity, intolerance, or contraindication to the use of any triptan, non-steroidal anti-inflammatory drug (NSAID) or aspirin (including all sumatriptan and naproxen preparations) or has nasal polyps and asthma 12. is currently taking, or has taken in the previous three months, a migraine prophylactic medication containing methysergide; or is taking a migraine or menstrual migraine prophylactic medication that is not stabilized (eg. Perimenstrual use of triptans and estradiol patches) 13. 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. 14. 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. 15. is currently taking and plans to continue an oral steroid any time from screening through onset of menses that will be treated with study medication (at the discretion of the investigator) 16. has history of any bleeding disorder or is currently taking any anti-coagulant or any antiplatelet agent. 17. has evidence or history of any gastrointestinal surgery or gastrointestinal (GI) ulceration or perforation in the past six months, gastrointestinal bleeding in the past year; or evidence or history of inflammatory bowel disease 18. is pregnant, actively trying to become pregnant, or breast feeding 19. 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. 20. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Correlation of Mean Estrogen Levels in Saliva and Urine Estradiol at Mid Luteal and at Menstrual Migraine Headache Free. | From mid luteal phase and for the duration of 1 menstrual migraine headache and until headache free | Correlation of mean estrogen levels in saliva and urine estradiol at mid luteal, menstrual migraine headache onset\*, and at migraine headache free following treatment with Treximet vs. Placebo for 1 menstrual migraine headache \*Urine estradiol levels were not collected at migraine onset, therefore; correlations could not be completed for that time point. |
| Migraine Recurrence | From onset of a single menstrual migraine episode to 24 hours post menstrual migraine treatment. | 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. |
| Time to Pain Free | From onset of 1 menstrual migraine headache until pain free. | 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. |
| Biomarkers Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment | From Baseline until 2 hours post treatment of 1 menstrual migraine headache | 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. |
| CGRP Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment | From Baseline until 2 hours post treatment for 1 menstrual migraine headache | CGRP 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. |
| α-Amylase Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment | From Baseline until 2 hours post treatment for 1 menstrual migraine headache | α-Amylase levels collected at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment 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. |
| Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free. | From baseline to 24 hours post headache gone for 1 menstrual migraine headache. | 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. \*\*β-endorphin levels were not assayed due to limitations on saliva sample volumes. |
| CGRP Measured at Menstrual Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free. | From baseline to 24 hours post headache gone for 1 menstrual migraine headache | 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. \* This endpoint was separated into 3 outcome measures as all biomarkers were not reported in the same units of measure. |
| α-Amylase Measured at Menstrual Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free. | From baseline to 24 hours post headache gone for 1 menstrual migraine headache | α-Amylase 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Migraine Recurrence Responders vs Non-Responders | From the onset of 1 menstrual migraine until 24 hours post treatment. | 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. 0-3 Pain Scale with 0=No Pain, 1=Mild, 2=Moderate, and 3=Severe \*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. |
| Time to Pain-Free in Responders vs Non-Responders | From the onset of 1 menstrual migraine headache until pain-free. | 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. \*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. |
| Biomarkers Measured at Baseline, Menstrual Migraine Onset, and 2 Hours Post Treatment in Responders vs Non-Responders | From Baseline until 2 Hours post menstrual migraine treatment for 1 menstrual migraine headache. | 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. \*\*β-endorphin levels were not assayed due to limitations on saliva sample volumes. \*\*\*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 Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post-Treatment in Responders vs Non-Responders | From Baseline until 2 Hours post menstrual migraine treatment for 1 menstrual migraine headache. | 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. A non-responder is one that fails to meet the responder criteria. |
| α-Amylase Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment in Responders vs Non-Responders | From Baseline until 2 hours post treatment of 1 menstrual migraine headache. | α-Amylase levels collected at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment 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. |
| Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders | From Baseline for the duration of 1 menstrual migraine headache, an estimated 7 days | 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. \*\*β-endorphin levels were not assayed due to limitations on saliva sample volumes. \*\*\*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 Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders | From Baseline to 24 hours post headache gone for 1 menstrual migraine. | 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\*\*. \*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. A non-responder is one that fails to meet the responder criteria. |
| α-Amylase Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders | From Baseline from 24 hours post migraine gone for 1 menstrual migraine. | 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\*\*. \*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. A non-responder is one that fails to meet the responder criteria. |
| Correlation of Mean Estrogen Levels in Saliva and Urine Estradiol at Mid-Luteal and at Menstrual Migraine Headache Free in Responders vs Non-Responders | From mid luteal phase and for the duration of 1 menstrual migraine until headache free. | 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\*\*. \*Urine estradiol levels were not collected at migraine onset, therefore; correlations could not be completed for that time point. \*\*\*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. |
Countries
United States
Participant flow
Recruitment details
Subjects between the ages of 18 and 45 were recruited from two investigative sites. Subjects were enrolled from May 9,2011 through March 29, 2012. Last patient out June 5,2012.
Pre-assignment details
Subjects were enrolled and randomized at Visit 1. There were no significant events between enrollment and assignment.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Subjects randomized to Group B will be provided with 1 tablet of placebo 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.
Placebo : A placebo tablet matching Treximet for oral administration. | 20 |
| 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.
Treximet : Tablet for oral administration contains sumatriptan 85mg / naproxen sodium 500mg. | 21 |
| Total | 41 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Protocol Violation | 5 | 3 |
| Overall Study | Subject withdrew due to personal issues. | 3 | 2 |
Baseline characteristics
| Characteristic | Treximet | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 21 Participants | 20 Participants | 41 Participants |
| Age, Continuous | 36.71 years STANDARD_DEVIATION 6.5 | 34.35 years STANDARD_DEVIATION 8.22 | 35.56 years STANDARD_DEVIATION 7.4 |
| Region of Enrollment United States | 21 participants | 20 participants | 41 participants |
| Sex: Female, Male Female | 21 Participants | 20 Participants | 41 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 6 / 20 | 7 / 21 |
| serious Total, serious adverse events | 0 / 20 | 0 / 21 |
Outcome results
Primary
Biomarkers Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment
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.
Time frame: From Baseline until 2 hours post treatment of 1 menstrual migraine headache
Population: In Group B, one subject's sample was unable to be analyzed by the laboratory, therefore Group B has one less subject in the placebo arm (N=10) for all biomarker data. Sample size for each arm may vary at each time point and/or biomarker based on laboratory results obtained due to sample collection errors.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Biomarkers Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment | PGE2 Migraine Onset (n=10, 13) | 7.56 pg/mL | Standard Deviation 2.61 |
| Placebo | Biomarkers Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment | Cortisol 2 Hours Post Treatment (n=8, 10) | 2011.45 pg/mL | Standard Deviation 2259.76 |
| Placebo | Biomarkers Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment | VIP Migraine Onset (n=10, 13) | 1052.8 pg/mL | Standard Deviation 490.57 |
| Placebo | Biomarkers Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment | PGI2 Baseline (n=10, 14) | 109.51 pg/mL | Standard Deviation 62.9 |
| Placebo | Biomarkers Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment | PGE2 2 Hours Post Treatment (n=9, 14) | 8.29 pg/mL | Standard Deviation 4.43 |
| Placebo | Biomarkers Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment | PGI2 Migraine Onset (n=10, 13) | 108.23 pg/mL | Standard Deviation 61.25 |
| Placebo | Biomarkers Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment | PGE2 Baseline (n=10, 14) | 9.25 pg/mL | Standard Deviation 7.97 |
| Placebo | Biomarkers Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment | PGI2 2 Hours Post Treatment (n=9, 14) | 97.58 pg/mL | Standard Deviation 54.7 |
| Placebo | Biomarkers Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment | Cortisol Baseline (n=10, 13) | 1064.14 pg/mL | Standard Deviation 970.57 |
| Placebo | Biomarkers Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment | Estradiol Baseline (n=10, 13) | 63.37 pg/mL | Standard Deviation 42.24 |
| Placebo | Biomarkers Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment | VIP 2 Hours Post Treatment (n=9, 13) | 1130.44 pg/mL | Standard Deviation 600.29 |
| Placebo | Biomarkers Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment | Estradiol Migraine Onset (n=9, 13) | 41.68 pg/mL | Standard Deviation 30.43 |
| Placebo | Biomarkers Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment | Cortisol Migraine Onset (n=8, 13) | 1084.85 pg/mL | Standard Deviation 758.46 |
| Placebo | Biomarkers Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment | Estradiol 2 Hours Post Treatment (n=9,14) | 54.07 pg/mL | Standard Deviation 36.45 |
| Placebo | Biomarkers Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment | VIP Baseline (n=10, 14) | 763.6 pg/mL | Standard Deviation 341.01 |
| Treximet | Biomarkers Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment | Estradiol 2 Hours Post Treatment (n=9,14) | 41.66 pg/mL | Standard Deviation 22.19 |
| Treximet | Biomarkers Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment | VIP Baseline (n=10, 14) | 1149.5 pg/mL | Standard Deviation 532.07 |
| Treximet | Biomarkers Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment | VIP Migraine Onset (n=10, 13) | 1111.31 pg/mL | Standard Deviation 560.39 |
| Treximet | Biomarkers Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment | VIP 2 Hours Post Treatment (n=9, 13) | 933.77 pg/mL | Standard Deviation 643.38 |
| Treximet | Biomarkers Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment | PGE2 Baseline (n=10, 14) | 12.65 pg/mL | Standard Deviation 11.33 |
| Treximet | Biomarkers Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment | PGE2 Migraine Onset (n=10, 13) | 13.02 pg/mL | Standard Deviation 7.55 |
| Treximet | Biomarkers Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment | PGE2 2 Hours Post Treatment (n=9, 14) | 7.99 pg/mL | Standard Deviation 4.37 |
| Treximet | Biomarkers Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment | Cortisol Baseline (n=10, 13) | 1040.49 pg/mL | Standard Deviation 1292.8 |
| Treximet | Biomarkers Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment | Cortisol Migraine Onset (n=8, 13) | 1209.34 pg/mL | Standard Deviation 1795.19 |
| Treximet | Biomarkers Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment | Cortisol 2 Hours Post Treatment (n=8, 10) | 418.48 pg/mL | Standard Deviation 211.93 |
| Treximet | Biomarkers Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment | PGI2 Baseline (n=10, 14) | 160.27 pg/mL | Standard Deviation 100.22 |
| Treximet | Biomarkers Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment | PGI2 Migraine Onset (n=10, 13) | 158.29 pg/mL | Standard Deviation 76.74 |
| Treximet | Biomarkers Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment | PGI2 2 Hours Post Treatment (n=9, 14) | 201.60 pg/mL | Standard Deviation 115.16 |
| Treximet | Biomarkers Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment | Estradiol Baseline (n=10, 13) | 62.61 pg/mL | Standard Deviation 78.16 |
| Treximet | Biomarkers Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment | Estradiol Migraine Onset (n=9, 13) | 43.93 pg/mL | Standard Deviation 36.85 |
Primary
Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free.
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. \*\*β-endorphin levels were not assayed due to limitations on saliva sample volumes.
Time frame: From baseline to 24 hours post headache gone for 1 menstrual migraine headache.
Population: In Group B, one subject's sample was unable to be analyzed by the laboratory, therefore Group B has one less subject in the placebo arm (N=10) for all biomarker data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free. | PGE2 Migraine Headache Free (n=10,4,6,) | 8.35 pg/mL | Standard Deviation 6.52 |
| Placebo | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free. | Cortisol 24 Hours Migraine Headache Free(n=10,6,6) | 1031.16 pg/mL | Standard Deviation 1474.05 |
| Placebo | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free. | VIP Migraine Headache Free (n=9,4,7) | 964.4 pg/mL | Standard Deviation 711.43 |
| Placebo | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free. | PGI2 Migraine Onset (n=10,7,6) | 108.23 pg/mL | Standard Deviation 61.25 |
| Placebo | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free. | PGE2 24 Hours Migraine Headache Free (n=10,7,7) | 10.46 pg/mL | Standard Deviation 11.43 |
| Placebo | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free. | PGI2 Migraine Headache Free (n=10,4,6) | 115.63 pg/mL | Standard Deviation 78.71 |
| Placebo | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free. | PGE2 Migraine Onset (n=10,7,6) | 7.56 pg/mL | Standard Deviation 2.61 |
| Placebo | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free. | PGI2 24 Hours Migraine Headache Free (n=10,7,7) | 97.69 pg/mL | Standard Deviation 63.84 |
| Placebo | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free. | Cortisol Migraine Onset (n=8,7,6) | 1084.5 pg/mL | Standard Deviation 7584.6 |
| Placebo | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free. | Estradiol Migraine Onset (n=9,7,6) | 37.05 pg/mL | Standard Deviation 31.67 |
| Placebo | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free. | VIP 24 Hours Migraine Headache Free (n=10,7,6) | 1059.9 pg/mL | Standard Deviation 564.42 |
| Placebo | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free. | Estradiol Migraine Headache Free (n=9,4,5,) | 48.83 pg/mL | Standard Deviation 48.82 |
| Placebo | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free. | Cortisol Migraine Headache Free (n=10,3,6) | 1490.92 pg/mL | Standard Deviation 2232.7 |
| Placebo | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free. | Estradiol 24 Hours Migraine Headache Free(n=6,7,5) | 21.34 pg/mL | Standard Deviation 26.35 |
| Placebo | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free. | VIP Migraine Onset (n=10,7,6) | 1052.8 pg/mL | Standard Deviation 490.57 |
| Treximet | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free. | Estradiol 24 Hours Migraine Headache Free(n=6,7,5) | 56.33 pg/mL | Standard Deviation 53.49 |
| Treximet | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free. | VIP Migraine Onset (n=10,7,6) | 1111.31 pg/mL | Standard Deviation 560.39 |
| Treximet | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free. | VIP Migraine Headache Free (n=9,4,7) | 949.7 pg/mL | Standard Deviation 536.21 |
| Treximet | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free. | VIP 24 Hours Migraine Headache Free (n=10,7,6) | 1353.04 pg/mL | Standard Deviation 629.56 |
| Treximet | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free. | PGE2 Migraine Onset (n=10,7,6) | 13.02 pg/mL | Standard Deviation 7.55 |
| Treximet | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free. | PGE2 Migraine Headache Free (n=10,4,6,) | 9.27 pg/mL | Standard Deviation 6.74 |
| Treximet | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free. | PGE2 24 Hours Migraine Headache Free (n=10,7,7) | 13.04 pg/mL | Standard Deviation 12.03 |
| Treximet | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free. | Cortisol Migraine Onset (n=8,7,6) | 1209.34 pg/mL | Standard Deviation 1795.19 |
| Treximet | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free. | Cortisol Migraine Headache Free (n=10,3,6) | 1498.92 pg/mL | Standard Deviation 1945.6 |
| Treximet | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free. | Cortisol 24 Hours Migraine Headache Free(n=10,6,6) | 1271.4 pg/mL | Standard Deviation 1606.11 |
| Treximet | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free. | PGI2 Migraine Onset (n=10,7,6) | 158.29 pg/mL | Standard Deviation 76.74 |
| Treximet | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free. | PGI2 Migraine Headache Free (n=10,4,6) | 167.48 pg/mL | Standard Deviation 94.28 |
| Treximet | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free. | PGI2 24 Hours Migraine Headache Free (n=10,7,7) | 224.58 pg/mL | Standard Deviation 160.51 |
| Treximet | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free. | Estradiol Migraine Onset (n=9,7,6) | 43.93 pg/mL | Standard Deviation 36.85 |
| Treximet | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free. | Estradiol Migraine Headache Free (n=9,4,5,) | 39.92 pg/mL | Standard Deviation 45.55 |
Primary
CGRP Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment
CGRP 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.
Time frame: From Baseline until 2 hours post treatment for 1 menstrual migraine headache
Population: In Group B, one subject's sample was unable to be analyzed by the laboratory, therefore Group B has one less subject in the placebo arm (N=10) for all biomarker data. Sample size for each arm may vary at each time point and/or biomarker based on laboratory results obtained due to sample collection errors.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | CGRP Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment | CGRP Baseline (n=10, 14) | 18.55 pmol/mg | Standard Deviation 16.98 |
| Placebo | CGRP Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment | CGRP Migraine Onset (n=10, 13) | 22.28 pmol/mg | Standard Deviation 14.45 |
| Placebo | CGRP Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment | CGRP 2 Hours Post Treatment (n=9, 14) | 14.92 pmol/mg | Standard Deviation 11.96 |
| Treximet | CGRP Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment | CGRP Baseline (n=10, 14) | 15.03 pmol/mg | Standard Deviation 11.73 |
| Treximet | CGRP Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment | CGRP Migraine Onset (n=10, 13) | 27.82 pmol/mg | Standard Deviation 36.66 |
| Treximet | CGRP Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment | CGRP 2 Hours Post Treatment (n=9, 14) | 21.38 pmol/mg | Standard Deviation 11.45 |
Primary
CGRP Measured at Menstrual Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free.
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. \* This endpoint was separated into 3 outcome measures as all biomarkers were not reported in the same units of measure.
Time frame: From baseline to 24 hours post headache gone for 1 menstrual migraine headache
Population: In Group B, one subject's sample was unable to be analyzed by the laboratory, therefore Group B has one less subject in the placebo arm (N=10) for all biomarker data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | CGRP Measured at Menstrual Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free. | CGRP Migraine Onset (n=10,7,6) | 22.28 pmol/mg | Standard Deviation 14.45 |
| Placebo | CGRP Measured at Menstrual Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free. | CGRP Migraine Headache Free (n=9,4,6) | 22.55 pmol/mg | Standard Deviation 30.87 |
| Placebo | CGRP Measured at Menstrual Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free. | CGRP 24 Hours Migraine Headache Free (n=9,7,7) | 29.37 pmol/mg | Standard Deviation 26.76 |
| Treximet | CGRP Measured at Menstrual Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free. | CGRP Migraine Onset (n=10,7,6) | 28.82 pmol/mg | Standard Deviation 36.66 |
| Treximet | CGRP Measured at Menstrual Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free. | CGRP Migraine Headache Free (n=9,4,6) | 32.26 pmol/mg | Standard Deviation 34.89 |
| Treximet | CGRP Measured at Menstrual Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free. | CGRP 24 Hours Migraine Headache Free (n=9,7,7) | 32.15 pmol/mg | Standard Deviation 27.74 |
Primary
Correlation of Mean Estrogen Levels in Saliva and Urine Estradiol at Mid Luteal and at Menstrual Migraine Headache Free.
Correlation of mean estrogen levels in saliva and urine estradiol at mid luteal, menstrual migraine headache onset\*, and at migraine headache free following treatment with Treximet vs. Placebo for 1 menstrual migraine headache \*Urine estradiol levels were not collected at migraine onset, therefore; correlations could not be completed for that time point.
Time frame: From mid luteal phase and for the duration of 1 menstrual migraine headache and until headache free
Population: Sample size for each arm may vary at each time point and/or biomarker based on laboratory results obtained due to sample collection errors.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Correlation of Mean Estrogen Levels in Saliva and Urine Estradiol at Mid Luteal and at Menstrual Migraine Headache Free. | Urine Pre-Cycle Day 1 (n=3, 6) | 2442.44 pg/mL | Standard Deviation 545.38 |
| Placebo | Correlation of Mean Estrogen Levels in Saliva and Urine Estradiol at Mid Luteal and at Menstrual Migraine Headache Free. | Urine Pre-Cycle Day 2 (n=6, 8) | 4333.92 pg/mL | Standard Deviation 2982.35 |
| Placebo | Correlation of Mean Estrogen Levels in Saliva and Urine Estradiol at Mid Luteal and at Menstrual Migraine Headache Free. | Saliva Pre-Cycle Day 2 (n=2, 6) | 63.45 pg/mL | Standard Deviation 57.6 |
| Placebo | Correlation of Mean Estrogen Levels in Saliva and Urine Estradiol at Mid Luteal and at Menstrual Migraine Headache Free. | Urine Pre-Cycle Day 3 (n=8, 6) | 3582.92 pg/mL | Standard Deviation 4121.17 |
| Placebo | Correlation of Mean Estrogen Levels in Saliva and Urine Estradiol at Mid Luteal and at Menstrual Migraine Headache Free. | Urine Pre-Cycle Day 4 (n=9, 10) | 3232.10 pg/mL | Standard Deviation 2941.52 |
| Placebo | Correlation of Mean Estrogen Levels in Saliva and Urine Estradiol at Mid Luteal and at Menstrual Migraine Headache Free. | Urine Migraine Headache Free (n=11, 13 | 2398.55 pg/mL | Standard Deviation 1872.88 |
| Placebo | Correlation of Mean Estrogen Levels in Saliva and Urine Estradiol at Mid Luteal and at Menstrual Migraine Headache Free. | Saliva Pre-Cycle Day 1 (n=1, 4) | 41.75 pg/mL | — |
| Placebo | Correlation of Mean Estrogen Levels in Saliva and Urine Estradiol at Mid Luteal and at Menstrual Migraine Headache Free. | Saliva Pre-Cycle Day 3 (n=8, 10) | 46.47 pg/mL | Standard Deviation 34.73 |
| Placebo | Correlation of Mean Estrogen Levels in Saliva and Urine Estradiol at Mid Luteal and at Menstrual Migraine Headache Free. | Saliva Pre-Cycle Day 4 (n=6, 9) | 55.86 pg/mL | Standard Deviation 50.17 |
| Placebo | Correlation of Mean Estrogen Levels in Saliva and Urine Estradiol at Mid Luteal and at Menstrual Migraine Headache Free. | Saliva Migraine Headache Free (n=8, 6) | 54.93 pg/mL | Standard Deviation 48.38 |
| Treximet | Correlation of Mean Estrogen Levels in Saliva and Urine Estradiol at Mid Luteal and at Menstrual Migraine Headache Free. | Saliva Pre-Cycle Day 3 (n=8, 10) | 73.08 pg/mL | Standard Deviation 58.17 |
| Treximet | Correlation of Mean Estrogen Levels in Saliva and Urine Estradiol at Mid Luteal and at Menstrual Migraine Headache Free. | Saliva Migraine Headache Free (n=8, 6) | 51.32 pg/mL | Standard Deviation 45.64 |
| Treximet | Correlation of Mean Estrogen Levels in Saliva and Urine Estradiol at Mid Luteal and at Menstrual Migraine Headache Free. | Urine Migraine Headache Free (n=11, 13 | 2989.72 pg/mL | Standard Deviation 3823.33 |
| Treximet | Correlation of Mean Estrogen Levels in Saliva and Urine Estradiol at Mid Luteal and at Menstrual Migraine Headache Free. | Saliva Pre-Cycle Day 1 (n=1, 4) | 43.33 pg/mL | Standard Deviation 23.19 |
| Treximet | Correlation of Mean Estrogen Levels in Saliva and Urine Estradiol at Mid Luteal and at Menstrual Migraine Headache Free. | Urine Pre-Cycle Day 1 (n=3, 6) | 3090.92 pg/mL | Standard Deviation 2306.67 |
| Treximet | Correlation of Mean Estrogen Levels in Saliva and Urine Estradiol at Mid Luteal and at Menstrual Migraine Headache Free. | Urine Pre-Cycle Day 2 (n=6, 8) | 2616.64 pg/mL | Standard Deviation 2833.28 |
| Treximet | Correlation of Mean Estrogen Levels in Saliva and Urine Estradiol at Mid Luteal and at Menstrual Migraine Headache Free. | Saliva Pre-Cycle Day 2 (n=2, 6) | 41.87 pg/mL | Standard Deviation 17.73 |
| Treximet | Correlation of Mean Estrogen Levels in Saliva and Urine Estradiol at Mid Luteal and at Menstrual Migraine Headache Free. | Urine Pre-Cycle Day 3 (n=8, 6) | 5089.63 pg/mL | Standard Deviation 5775.3 |
| Treximet | Correlation of Mean Estrogen Levels in Saliva and Urine Estradiol at Mid Luteal and at Menstrual Migraine Headache Free. | Saliva Pre-Cycle Day 4 (n=6, 9) | 41.72 pg/mL | Standard Deviation 31.69 |
| Treximet | Correlation of Mean Estrogen Levels in Saliva and Urine Estradiol at Mid Luteal and at Menstrual Migraine Headache Free. | Urine Pre-Cycle Day 4 (n=9, 10) | 3141.51 pg/mL | Standard Deviation 2237.74 |
Primary
Migraine Recurrence
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.
Time frame: From onset of a single menstrual migraine episode to 24 hours post menstrual migraine treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Migraine Recurrence | 0 participants |
| Treximet | Migraine Recurrence | 2 participants |
Primary
Time to Pain Free
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.
Time frame: From onset of 1 menstrual migraine headache until pain free.
Population: In Group B, one subject did not report when their headache resolve, therefore a duration for this subject could not be calculated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Time to Pain Free | 7.64 hours | Standard Deviation 4.06 |
| Treximet | Time to Pain Free | 3.90 hours | Standard Deviation 3.92 |
Primary
α-Amylase Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment
α-Amylase levels collected at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment 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.
Time frame: From Baseline until 2 hours post treatment for 1 menstrual migraine headache
Population: In Group B, one subject's sample was unable to be analyzed by the laboratory, therefore Group B has one less subject in the placebo arm (N=10) for all biomarker data. Sample size for each arm may vary at each time point and/or biomarker based on laboratory results obtained due to sample collection errors.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | α-Amylase Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment | α-Amylase Baseline (n=10, 14) | 109280.50 U/L | Standard Deviation 12499.73 |
| Placebo | α-Amylase Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment | α-Amylase Migraine Onset (n=10, 13) | 100956.70 U/L | Standard Deviation 13551.51 |
| Placebo | α-Amylase Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment | α-Amylase 2 Hours Post Treatment (n=9, 14) | 102449.80 U/L | Standard Deviation 4883 |
| Treximet | α-Amylase Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment | α-Amylase Baseline (n=10, 14) | 99626.61 U/L | Standard Deviation 7616.14 |
| Treximet | α-Amylase Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment | α-Amylase Migraine Onset (n=10, 13) | 98853.32 U/L | Standard Deviation 12958.58 |
| Treximet | α-Amylase Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment | α-Amylase 2 Hours Post Treatment (n=9, 14) | 103594.90 U/L | Standard Deviation 9335.72 |
Primary
α-Amylase Measured at Menstrual Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free.
α-Amylase 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.
Time frame: From baseline to 24 hours post headache gone for 1 menstrual migraine headache
Population: In Group B, one subject's sample was unable to be analyzed by the laboratory, therefore Group B has one less subject in the placebo arm (N=10) for all biomarker data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | α-Amylase Measured at Menstrual Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free. | α-Amylase 24 Hours Migraine Headache Free(n=10,7,7 | 100354.00 U/L | Standard Deviation 16608.96 |
| Placebo | α-Amylase Measured at Menstrual Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free. | α-Amylase Migraine Onset (n=10,7,6) | 100956.70 U/L | Standard Deviation 13551.51 |
| Placebo | α-Amylase Measured at Menstrual Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free. | α-Amylase Migraine Headache Free (n=10,4,6) | 102908.61 U/L | Standard Deviation 11522.83 |
| Treximet | α-Amylase Measured at Menstrual Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free. | α-Amylase Migraine Onset (n=10,7,6) | 98853.32 U/L | Standard Deviation 12958.58 |
| Treximet | α-Amylase Measured at Menstrual Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free. | α-Amylase Migraine Headache Free (n=10,4,6) | 101307.25 U/L | Standard Deviation 8347.11 |
| Treximet | α-Amylase Measured at Menstrual Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free. | α-Amylase 24 Hours Migraine Headache Free(n=10,7,7 | 102017.80 U/L | Standard Deviation 8825.01 |
Secondary
Biomarkers Measured at Baseline, Menstrual Migraine 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 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. \*\*β-endorphin levels were not assayed due to limitations on saliva sample volumes. \*\*\*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.
Time frame: From Baseline until 2 Hours post menstrual migraine treatment for 1 menstrual migraine headache.
Population: Sample size for each arm may vary at each time point and/or biomarker based on laboratory results obtained due to sample collection errors.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Biomarkers Measured at Baseline, Menstrual Migraine Onset, and 2 Hours Post Treatment in Responders vs Non-Responders | PGE2 2 Hours Post Treatment (n=9,7,7) | 8.29 pg/mL | Standard Deviation 4.43 |
| Placebo | Biomarkers Measured at Baseline, Menstrual Migraine Onset, and 2 Hours Post Treatment in Responders vs Non-Responders | VIP 2 Hours Post Treatment (n=9,7,6,) | 1130.44 pg/mL | Standard Deviation 600.29 |
| Placebo | Biomarkers Measured at Baseline, Menstrual Migraine Onset, and 2 Hours Post Treatment in Responders vs Non-Responders | PGI2 Migraine Onset (n=10,7,6) | 108.23 pg/mL | Standard Deviation 61.25 |
| Placebo | Biomarkers Measured at Baseline, Menstrual Migraine Onset, and 2 Hours Post Treatment in Responders vs Non-Responders | Cortisol Baseline (n=10,6,7) | 1064.14 pg/mL | Standard Deviation 970.57 |
| Placebo | Biomarkers Measured at Baseline, Menstrual Migraine Onset, and 2 Hours Post Treatment in Responders vs Non-Responders | VIP Migraine Onset (n=10,7,6) | 1052.8 pg/mL | Standard Deviation 490.57 |
| Placebo | Biomarkers Measured at Baseline, Menstrual Migraine Onset, and 2 Hours Post Treatment in Responders vs Non-Responders | PGI2 Baseline (n=10,7,7) | 109.51 pg/mL | Standard Deviation 62.9 |
| Placebo | Biomarkers Measured at Baseline, Menstrual Migraine Onset, and 2 Hours Post Treatment in Responders vs Non-Responders | Cortisol Migraine Onset (n=8,7,6) | 1084.5 pg/mL | Standard Deviation 758.46 |
| Placebo | Biomarkers Measured at Baseline, Menstrual Migraine Onset, and 2 Hours Post Treatment in Responders vs Non-Responders | Estradiol Baseline (n=9,7,6) | 63.37 pg/mL | Standard Deviation 42.24 |
| Placebo | Biomarkers Measured at Baseline, Menstrual Migraine Onset, and 2 Hours Post Treatment in Responders vs Non-Responders | Cortisol 2 Hours Post Treatment (n=8,6,4) | 2011.45 pg/mL | Standard Deviation 2259.76 |
| Placebo | Biomarkers Measured at Baseline, Menstrual Migraine Onset, and 2 Hours Post Treatment in Responders vs Non-Responders | PGE2 Baseline (n=10,7,7) | 9.25 pg/mL | Standard Deviation 7.97 |
| Placebo | Biomarkers Measured at Baseline, Menstrual Migraine Onset, and 2 Hours Post Treatment in Responders vs Non-Responders | Estradiol 2 Hours Post Treatment (n=8,7,7) | 54.07 pg/mL | Standard Deviation 36.45 |
| Placebo | Biomarkers Measured at Baseline, Menstrual Migraine Onset, and 2 Hours Post Treatment in Responders vs Non-Responders | VIP Baseline (n=10,7,7) | 763.6 pg/mL | Standard Deviation 341.01 |
| Placebo | Biomarkers Measured at Baseline, Menstrual Migraine Onset, and 2 Hours Post Treatment in Responders vs Non-Responders | PGE2 Migraine Onset (n=10,7,6) | 7.56 pg/mL | Standard Deviation 2.61 |
| Placebo | Biomarkers Measured at Baseline, Menstrual Migraine Onset, and 2 Hours Post Treatment in Responders vs Non-Responders | Estradiol Migraine Onset (n=8,7,6) | 37.05 pg/mL | Standard Deviation 31.67 |
| Placebo | Biomarkers Measured at Baseline, Menstrual Migraine Onset, and 2 Hours Post Treatment in Responders vs Non-Responders | PGI2 2 Hours Post Treatment (n=9,7,7) | 97.58 pg/mL | Standard Deviation 54.7 |
| Treximet | Biomarkers Measured at Baseline, Menstrual Migraine Onset, and 2 Hours Post Treatment in Responders vs Non-Responders | PGI2 2 Hours Post Treatment (n=9,7,7) | 155.56 pg/mL | Standard Deviation 63.48 |
| Treximet | Biomarkers Measured at Baseline, Menstrual Migraine Onset, and 2 Hours Post Treatment in Responders vs Non-Responders | VIP Baseline (n=10,7,7) | 1414.0 pg/mL | Standard Deviation 618.96 |
| Treximet | Biomarkers Measured at Baseline, Menstrual Migraine Onset, and 2 Hours Post Treatment in Responders vs Non-Responders | VIP Migraine Onset (n=10,7,6) | 1251.14 pg/mL | Standard Deviation 580.38 |
| Treximet | Biomarkers Measured at Baseline, Menstrual Migraine Onset, and 2 Hours Post Treatment in Responders vs Non-Responders | VIP 2 Hours Post Treatment (n=9,7,6,) | 1320.14 pg/mL | Standard Deviation 657.68 |
| Treximet | Biomarkers Measured at Baseline, Menstrual Migraine Onset, and 2 Hours Post Treatment in Responders vs Non-Responders | PGE2 Baseline (n=10,7,7) | 14.29 pg/mL | Standard Deviation 12.12 |
| Treximet | Biomarkers Measured at Baseline, Menstrual Migraine Onset, and 2 Hours Post Treatment in Responders vs Non-Responders | PGE2 Migraine Onset (n=10,7,6) | 14.13 pg/mL | Standard Deviation 9.48 |
| Treximet | Biomarkers Measured at Baseline, Menstrual Migraine Onset, and 2 Hours Post Treatment in Responders vs Non-Responders | PGE2 2 Hours Post Treatment (n=9,7,7) | 6.83 pg/mL | Standard Deviation 4.97 |
| Treximet | Biomarkers Measured at Baseline, Menstrual Migraine Onset, and 2 Hours Post Treatment in Responders vs Non-Responders | Cortisol Baseline (n=10,6,7) | 790.77 pg/mL | Standard Deviation 633.65 |
| Treximet | Biomarkers Measured at Baseline, Menstrual Migraine Onset, and 2 Hours Post Treatment in Responders vs Non-Responders | Cortisol Migraine Onset (n=8,7,6) | 952.52 pg/mL | Standard Deviation 864.35 |
| Treximet | Biomarkers Measured at Baseline, Menstrual Migraine Onset, and 2 Hours Post Treatment in Responders vs Non-Responders | Cortisol 2 Hours Post Treatment (n=8,6,4) | 482.32 pg/mL | Standard Deviation 253.59 |
| Treximet | Biomarkers Measured at Baseline, Menstrual Migraine Onset, and 2 Hours Post Treatment in Responders vs Non-Responders | PGI2 Baseline (n=10,7,7) | 142.99 pg/mL | Standard Deviation 65.71 |
| Treximet | Biomarkers Measured at Baseline, Menstrual Migraine Onset, and 2 Hours Post Treatment in Responders vs Non-Responders | PGI2 Migraine Onset (n=10,7,6) | 134.40 pg/mL | Standard Deviation 71 |
| Treximet | Biomarkers Measured at Baseline, Menstrual Migraine Onset, and 2 Hours Post Treatment in Responders vs Non-Responders | Estradiol Baseline (n=9,7,6) | 49.60 pg/mL | Standard Deviation 54.34 |
| Treximet | Biomarkers Measured at Baseline, Menstrual Migraine Onset, and 2 Hours Post Treatment in Responders vs Non-Responders | Estradiol Migraine Onset (n=8,7,6) | 44.89 pg/mL | Standard Deviation 41.81 |
| Treximet | Biomarkers Measured at Baseline, Menstrual Migraine Onset, and 2 Hours Post Treatment in Responders vs Non-Responders | Estradiol 2 Hours Post Treatment (n=8,7,7) | 36.64 pg/mL | Standard Deviation 23.2 |
| Treximet Non-Responder | Biomarkers Measured at Baseline, Menstrual Migraine Onset, and 2 Hours Post Treatment in Responders vs Non-Responders | PGE2 2 Hours Post Treatment (n=9,7,7) | 9.15 pg/mL | Standard Deviation 3.69 |
| Treximet Non-Responder | Biomarkers Measured at Baseline, Menstrual Migraine Onset, and 2 Hours Post Treatment in Responders vs Non-Responders | Estradiol Migraine Onset (n=8,7,6) | 42.81 pg/mL | Standard Deviation 34.04 |
| Treximet Non-Responder | Biomarkers Measured at Baseline, Menstrual Migraine Onset, and 2 Hours Post Treatment in Responders vs Non-Responders | PGI2 Migraine Onset (n=10,7,6) | 186.17 pg/mL | Standard Deviation 79.71 |
| Treximet Non-Responder | Biomarkers Measured at Baseline, Menstrual Migraine Onset, and 2 Hours Post Treatment in Responders vs Non-Responders | PGE2 Migraine Onset (n=10,7,6) | 11.72 pg/mL | Standard Deviation 5.02 |
| Treximet Non-Responder | Biomarkers Measured at Baseline, Menstrual Migraine Onset, and 2 Hours Post Treatment in Responders vs Non-Responders | PGE2 Baseline (n=10,7,7) | 11.01 pg/mL | Standard Deviation 11.12 |
| Treximet Non-Responder | Biomarkers Measured at Baseline, Menstrual Migraine Onset, and 2 Hours Post Treatment in Responders vs Non-Responders | PGI2 2 Hours Post Treatment (n=9,7,7) | 247.63 pg/mL | Standard Deviation 140.58 |
| Treximet Non-Responder | Biomarkers Measured at Baseline, Menstrual Migraine Onset, and 2 Hours Post Treatment in Responders vs Non-Responders | VIP 2 Hours Post Treatment (n=9,7,6,) | 414.0 pg/mL | Standard Deviation 226.53 |
| Treximet Non-Responder | Biomarkers Measured at Baseline, Menstrual Migraine Onset, and 2 Hours Post Treatment in Responders vs Non-Responders | VIP Baseline (n=10,7,7) | 885.0 pg/mL | Standard Deviation 258.91 |
| Treximet Non-Responder | Biomarkers Measured at Baseline, Menstrual Migraine Onset, and 2 Hours Post Treatment in Responders vs Non-Responders | Estradiol Baseline (n=9,7,6) | 66.68 pg/mL | Standard Deviation 98.5 |
| Treximet Non-Responder | Biomarkers Measured at Baseline, Menstrual Migraine Onset, and 2 Hours Post Treatment in Responders vs Non-Responders | Cortisol Migraine Onset (n=8,7,6) | 1508.97 pg/mL | Standard Deviation 2576.41 |
| Treximet Non-Responder | Biomarkers Measured at Baseline, Menstrual Migraine Onset, and 2 Hours Post Treatment in Responders vs Non-Responders | VIP Migraine Onset (n=10,7,6) | 948.17 pg/mL | Standard Deviation 538.67 |
| Treximet Non-Responder | Biomarkers Measured at Baseline, Menstrual Migraine Onset, and 2 Hours Post Treatment in Responders vs Non-Responders | Cortisol 2 Hours Post Treatment (n=8,6,4) | 322.72 pg/mL | Standard Deviation 84.78 |
| Treximet Non-Responder | Biomarkers Measured at Baseline, Menstrual Migraine Onset, and 2 Hours Post Treatment in Responders vs Non-Responders | Cortisol Baseline (n=10,6,7) | 1254.53 pg/mL | Standard Deviation 1700.66 |
| Treximet Non-Responder | Biomarkers Measured at Baseline, Menstrual Migraine Onset, and 2 Hours Post Treatment in Responders vs Non-Responders | Estradiol 2 Hours Post Treatment (n=8,7,7) | 46.68 pg/mL | Standard Deviation 21.67 |
| Treximet Non-Responder | Biomarkers Measured at Baseline, Menstrual Migraine Onset, and 2 Hours Post Treatment in Responders vs Non-Responders | PGI2 Baseline (n=10,7,7) | 177.54 pg/mL | Standard Deviation 129.41 |
Secondary
Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free 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. \*\*β-endorphin levels were not assayed due to limitations on saliva sample volumes. \*\*\*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.
Time frame: From Baseline for the duration of 1 menstrual migraine headache, an estimated 7 days
Population: Sample size for each arm may vary at each time point and/or biomarker based on laboratory results obtained due to sample collection errors.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders | Cortisol Migraine Headache Free (n=10,3,5) | 1490.92 pg/mL | Standard Deviation 2232.7 |
| Placebo | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders | VIP Migraine Headache Free (n=9,4,6) | 964.4 pg/mL | Standard Deviation 711.43 |
| Placebo | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders | Cortisol Migraine Onset (n=8,7,6) | 1084.5 pg/mL | Standard Deviation 758.46 |
| Placebo | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders | PGE2 24 Hours Migraine Headache Free (n=10,7,7) | 10.46 pg/mL | Standard Deviation 11.43 |
| Placebo | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders | VIP 24 Hours Migraine Headache Free (n=10,7,5) | 1059.9 pg/mL | Standard Deviation 564.42 |
| Placebo | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders | Estradiol Migraine Headache Free (n=9,5,4) | 48.83 pg/mL | Standard Deviation 48.82 |
| Placebo | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders | PGE2 Migraine Headache Free (n=10,4,6) | 8.35 pg/mL | Standard Deviation 6.52 |
| Placebo | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders | PGE2 Migraine Onset (n=10,7,6) | 7.56 pg/mL | Standard Deviation 2.61 |
| Placebo | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders | Estradiol Migraine Onset (n=9,7,6) | 37.75 pg/mL | Standard Deviation 31.67 |
| Placebo | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders | PGI2 Migraine Onset (n=10,7,6) | 108.23 pg/mL | Standard Deviation 61.25 |
| Placebo | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders | Estradiol 24 Hours Migraine Headache Free(n=6,7,6) | 21.34 pg/mL | Standard Deviation 26.35 |
| Placebo | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders | PGI2 24 Hours Migraine Headache Free (n=10,7,7) | 97.69 pg/mL | Standard Deviation 63.84 |
| Placebo | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders | Cortisol 24 Hours Migraine Headache Free(n=10,6,6) | 1031.16 pg/mL | Standard Deviation 1474.05 |
| Placebo | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders | VIP Migraine Onset (n=10,7,6) | 105.28 pg/mL | Standard Deviation 490.97 |
| Placebo | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders | PGI2 Migraine Headache Free (n=10,4,6) | 115.63 pg/mL | Standard Deviation 78.71 |
| Treximet | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders | VIP Migraine Headache Free (n=9,4,6) | 1409.75 pg/mL | Standard Deviation 567.81 |
| Treximet | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders | PGI2 Migraine Headache Free (n=10,4,6) | 154.16 pg/mL | Standard Deviation 68.28 |
| Treximet | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders | PGI2 24 Hours Migraine Headache Free (n=10,7,7) | 154.10 pg/mL | Standard Deviation 71.61 |
| Treximet | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders | Estradiol Migraine Onset (n=9,7,6) | 44.89 pg/mL | Standard Deviation 41.81 |
| Treximet | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders | Estradiol Migraine Headache Free (n=9,5,4) | 56.59 pg/mL | Standard Deviation 67.39 |
| Treximet | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders | Estradiol 24 Hours Migraine Headache Free(n=6,7,6) | 34.86 pg/mL | Standard Deviation 46.64 |
| Treximet | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders | VIP Migraine Onset (n=10,7,6) | 1251.14 pg/mL | Standard Deviation 580.38 |
| Treximet | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders | VIP 24 Hours Migraine Headache Free (n=10,7,5) | 1480.79 pg/mL | Standard Deviation 624.74 |
| Treximet | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders | PGE2 Migraine Onset (n=10,7,6) | 14.13 pg/mL | Standard Deviation 9.48 |
| Treximet | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders | PGE2 Migraine Headache Free (n=10,4,6) | 7.87 pg/mL | Standard Deviation 1.44 |
| Treximet | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders | PGE2 24 Hours Migraine Headache Free (n=10,7,7) | 13.43 pg/mL | Standard Deviation 14.38 |
| Treximet | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders | Cortisol Migraine Onset (n=8,7,6) | 952.52 pg/mL | Standard Deviation 864.35 |
| Treximet | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders | Cortisol Migraine Headache Free (n=10,3,5) | 592.35 pg/mL | Standard Deviation 316.8 |
| Treximet | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders | Cortisol 24 Hours Migraine Headache Free(n=10,6,6) | 863.09 pg/mL | Standard Deviation 687.42 |
| Treximet | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders | PGI2 Migraine Onset (n=10,7,6) | 134.40 pg/mL | Standard Deviation 71 |
| Treximet Non-Responder | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders | PGE2 24 Hours Migraine Headache Free (n=10,7,7) | 12.65 pg/mL | Standard Deviation 10.31 |
| Treximet Non-Responder | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders | PGI2 Migraine Onset (n=10,7,6) | 186.17 pg/mL | Standard Deviation 79.71 |
| Treximet Non-Responder | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders | PGI2 24 Hours Migraine Headache Free (n=10,7,7) | 295.07 pg/mL | Standard Deviation 197.73 |
| Treximet Non-Responder | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders | Cortisol Migraine Onset (n=8,7,6) | 1508.97 pg/mL | Standard Deviation 2576.41 |
| Treximet Non-Responder | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders | VIP Migraine Onset (n=10,7,6) | 948.97 pg/mL | Standard Deviation 538.67 |
| Treximet Non-Responder | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders | Estradiol Migraine Onset (n=9,7,6) | 42.81 pg/mL | Standard Deviation 34.04 |
| Treximet Non-Responder | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders | Cortisol Migraine Headache Free (n=10,3,5) | 2042.87 pg/mL | Standard Deviation 2363.89 |
| Treximet Non-Responder | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders | Estradiol 24 Hours Migraine Headache Free(n=6,7,6) | 81.38 pg/mL | Standard Deviation 53.46 |
| Treximet Non-Responder | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders | PGI2 Migraine Headache Free (n=10,4,6) | 176.37 pg/mL | Standard Deviation 113.87 |
| Treximet Non-Responder | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders | PGE2 Migraine Onset (n=10,7,6) | 11.72 pg/mL | Standard Deviation 5.02 |
| Treximet Non-Responder | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders | VIP 24 Hours Migraine Headache Free (n=10,7,5) | 1174.2 pg/mL | Standard Deviation 660.26 |
| Treximet Non-Responder | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders | Cortisol 24 Hours Migraine Headache Free(n=10,6,6) | 1621.38 pg/mL | Standard Deviation 2110.87 |
| Treximet Non-Responder | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders | PGE2 Migraine Headache Free (n=10,4,6) | 10.21 pg/mL | Standard Deviation 8.82 |
| Treximet Non-Responder | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders | VIP Migraine Headache Free (n=9,4,6) | 643.0 pg/mL | Standard Deviation 204.69 |
| Treximet Non-Responder | Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders | Estradiol Migraine Headache Free (n=9,5,4) | 26.58 pg/mL | Standard Deviation 15.6 |
Secondary
CGRP Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post-Treatment in Responders vs Non-Responders
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. A non-responder is one that fails to meet the responder criteria.
Time frame: From Baseline until 2 Hours post menstrual migraine treatment for 1 menstrual migraine headache.
Population: Sample size for each arm may vary at each time point and/or biomarker based on laboratory results obtained due to sample collection errors.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | CGRP Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post-Treatment in Responders vs Non-Responders | CGRP Migraine Onset (n=10,7,6) | 22.28 pmol/mg | Standard Deviation 14.45 |
| Placebo | CGRP Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post-Treatment in Responders vs Non-Responders | CGRP Baseline (n=10,7,7) | 18.55 pmol/mg | Standard Deviation 16.98 |
| Placebo | CGRP Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post-Treatment in Responders vs Non-Responders | CGRP 2 Hours Post Treatment (n=9,7,7) | 14.92 pmol/mg | Standard Deviation 11.96 |
| Treximet | CGRP Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post-Treatment in Responders vs Non-Responders | CGRP Migraine Onset (n=10,7,6) | 22.74 pmol/mg | Standard Deviation 11.94 |
| Treximet | CGRP Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post-Treatment in Responders vs Non-Responders | CGRP Baseline (n=10,7,7) | 12.27 pmol/mg | Standard Deviation 6.61 |
| Treximet | CGRP Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post-Treatment in Responders vs Non-Responders | CGRP 2 Hours Post Treatment (n=9,7,7) | 21.08 pmol/mg | Standard Deviation 8.02 |
| Treximet Non-Responder | CGRP Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post-Treatment in Responders vs Non-Responders | CGRP Baseline (n=10,7,7) | 17.80 pmol/mg | Standard Deviation 15.39 |
| Treximet Non-Responder | CGRP Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post-Treatment in Responders vs Non-Responders | CGRP 2 Hours Post Treatment (n=9,7,7) | 21.67 pmol/mg | Standard Deviation 14.81 |
| Treximet Non-Responder | CGRP Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post-Treatment in Responders vs Non-Responders | CGRP Migraine Onset (n=10,7,6) | 33.76 pmol/mg | Standard Deviation 54.55 |
Secondary
CGRP Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders
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\*\*. \*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. A non-responder is one that fails to meet the responder criteria.
Time frame: From Baseline to 24 hours post headache gone for 1 menstrual migraine.
Population: Sample size for each arm may vary at each time point and/or biomarker based on laboratory results obtained due to sample collection errors.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | CGRP Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders | CGRP 24 Hours Migraine Headache Free (n=9,7,7) | 29.37 pmol/mg | Standard Deviation 26.76 |
| Placebo | CGRP Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders | CGRP Migraine Onset (n=10,7,6) | 22.28 pmol/mg | Standard Deviation 14.45 |
| Placebo | CGRP Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders | CGRP Migraine Headache Free (n=9,4,6) | 22.55 pmol/mg | Standard Deviation 30.87 |
| Treximet | CGRP Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders | CGRP 24 Hours Migraine Headache Free (n=9,7,7) | 28.43 pmol/mg | Standard Deviation 25.46 |
| Treximet | CGRP Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders | CGRP Migraine Onset (n=10,7,6) | 22.74 pmol/mg | Standard Deviation 11.94 |
| Treximet | CGRP Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders | CGRP Migraine Headache Free (n=9,4,6) | 49.48 pmol/mg | Standard Deviation 49.68 |
| Treximet Non-Responder | CGRP Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders | CGRP 24 Hours Migraine Headache Free (n=9,7,7) | 35.87 pmol/mg | Standard Deviation 31.41 |
| Treximet Non-Responder | CGRP Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders | CGRP Migraine Onset (n=10,7,6) | 33.76 pmol/mg | Standard Deviation 54.55 |
| Treximet Non-Responder | CGRP Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders | CGRP Migraine Headache Free (n=9,4,6) | 20.78 pmol/mg | Standard Deviation 17.73 |
Secondary
Correlation of Mean Estrogen Levels in Saliva and Urine Estradiol at Mid-Luteal and at Menstrual 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\*\*. \*Urine estradiol levels were not collected at migraine onset, therefore; correlations could not be completed for that time point. \*\*\*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.
Time frame: From mid luteal phase and for the duration of 1 menstrual migraine until headache free.
Population: Sample size for each arm may vary at each time point and/or biomarker based on laboratory results obtained due to sample collection errors.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Correlation of Mean Estrogen Levels in Saliva and Urine Estradiol at Mid-Luteal and at Menstrual Migraine Headache Free in Responders vs Non-Responders | Urine Pre-Cycle Day 1 (n=3,2,4) | 2442.44 pg/mL | Standard Deviation 545.38 |
| Placebo | Correlation of Mean Estrogen Levels in Saliva and Urine Estradiol at Mid-Luteal and at Menstrual Migraine Headache Free in Responders vs Non-Responders | Urine Pre-Cycle Day 3 (n=8,2,5) | 3582.92 pg/mL | Standard Deviation 4121.17 |
| Placebo | Correlation of Mean Estrogen Levels in Saliva and Urine Estradiol at Mid-Luteal and at Menstrual Migraine Headache Free in Responders vs Non-Responders | Saliva Pre-Cycle Day 3 (n=8,4,7) | 46.47 pg/mL | Standard Deviation 34.73 |
| Placebo | Correlation of Mean Estrogen Levels in Saliva and Urine Estradiol at Mid-Luteal and at Menstrual Migraine Headache Free in Responders vs Non-Responders | Saliva Migraine Headache Free (n=8,3,4) | 54.93 pg/mL | Standard Deviation 48.38 |
| Placebo | Correlation of Mean Estrogen Levels in Saliva and Urine Estradiol at Mid-Luteal and at Menstrual Migraine Headache Free in Responders vs Non-Responders | Saliva Pre-Cycle Day 4 (n=8,5,4) | 55.86 pg/mL | Standard Deviation 50.17 |
| Placebo | Correlation of Mean Estrogen Levels in Saliva and Urine Estradiol at Mid-Luteal and at Menstrual Migraine Headache Free in Responders vs Non-Responders | Saliva Pre-Cycle Day 2 (n=2,2,4) | 63.45 pg/mL | Standard Deviation 57.6 |
| Placebo | Correlation of Mean Estrogen Levels in Saliva and Urine Estradiol at Mid-Luteal and at Menstrual Migraine Headache Free in Responders vs Non-Responders | Urine Migraine Headache Free (n=10,7,7) | 2398.55 pg/mL | Standard Deviation 1872.88 |
| Placebo | Correlation of Mean Estrogen Levels in Saliva and Urine Estradiol at Mid-Luteal and at Menstrual Migraine Headache Free in Responders vs Non-Responders | Urine Pre-Cycle Day 2 (n=6,3,5) | 4333.92 pg/mL | Standard Deviation 2982.35 |
| Placebo | Correlation of Mean Estrogen Levels in Saliva and Urine Estradiol at Mid-Luteal and at Menstrual Migraine Headache Free in Responders vs Non-Responders | Urine Pre-Cycle Day 4 (n=9,5,5) | 3232.10 pg/mL | Standard Deviation 2941.52 |
| Placebo | Correlation of Mean Estrogen Levels in Saliva and Urine Estradiol at Mid-Luteal and at Menstrual Migraine Headache Free in Responders vs Non-Responders | Saliva Pre-Cycle Day 1 (n=1,0,4) | 41.75 pg/mL | — |
| Treximet | Correlation of Mean Estrogen Levels in Saliva and Urine Estradiol at Mid-Luteal and at Menstrual Migraine Headache Free in Responders vs Non-Responders | Urine Pre-Cycle Day 2 (n=6,3,5) | 875.34 pg/mL | Standard Deviation 377.69 |
| Treximet | Correlation of Mean Estrogen Levels in Saliva and Urine Estradiol at Mid-Luteal and at Menstrual Migraine Headache Free in Responders vs Non-Responders | Saliva Pre-Cycle Day 2 (n=2,2,4) | 30.89 pg/mL | Standard Deviation 7.16 |
| Treximet | Correlation of Mean Estrogen Levels in Saliva and Urine Estradiol at Mid-Luteal and at Menstrual Migraine Headache Free in Responders vs Non-Responders | Urine Pre-Cycle Day 1 (n=3,2,4) | 1898.63 pg/mL | Standard Deviation 92.07 |
| Treximet | Correlation of Mean Estrogen Levels in Saliva and Urine Estradiol at Mid-Luteal and at Menstrual Migraine Headache Free in Responders vs Non-Responders | Saliva Pre-Cycle Day 3 (n=8,4,7) | 81.05 pg/mL | Standard Deviation 60.64 |
| Treximet | Correlation of Mean Estrogen Levels in Saliva and Urine Estradiol at Mid-Luteal and at Menstrual Migraine Headache Free in Responders vs Non-Responders | Saliva Pre-Cycle Day 4 (n=8,5,4) | 31.71 pg/mL | Standard Deviation 26.78 |
| Treximet | Correlation of Mean Estrogen Levels in Saliva and Urine Estradiol at Mid-Luteal and at Menstrual Migraine Headache Free in Responders vs Non-Responders | Saliva Pre-Cycle Day 1 (n=1,0,4) | NA pg/mL | — |
| Treximet | Correlation of Mean Estrogen Levels in Saliva and Urine Estradiol at Mid-Luteal and at Menstrual Migraine Headache Free in Responders vs Non-Responders | Urine Pre-Cycle Day 3 (n=8,2,5) | 3739.44 pg/mL | Standard Deviation 1536.97 |
| Treximet | Correlation of Mean Estrogen Levels in Saliva and Urine Estradiol at Mid-Luteal and at Menstrual Migraine Headache Free in Responders vs Non-Responders | Urine Pre-Cycle Day 4 (n=9,5,5) | 2016.99 pg/mL | Standard Deviation 1295.3 |
| Treximet | Correlation of Mean Estrogen Levels in Saliva and Urine Estradiol at Mid-Luteal and at Menstrual Migraine Headache Free in Responders vs Non-Responders | Saliva Migraine Headache Free (n=8,3,4) | 75.45 pg/mL | Standard Deviation 68.38 |
| Treximet | Correlation of Mean Estrogen Levels in Saliva and Urine Estradiol at Mid-Luteal and at Menstrual Migraine Headache Free in Responders vs Non-Responders | Urine Migraine Headache Free (n=10,7,7) | 2542.09 pg/mL | Standard Deviation 3152.52 |
| Treximet Non-Responder | Correlation of Mean Estrogen Levels in Saliva and Urine Estradiol at Mid-Luteal and at Menstrual Migraine Headache Free in Responders vs Non-Responders | Saliva Pre-Cycle Day 4 (n=8,5,4) | 54.22 pg/mL | Standard Deviation 36.69 |
| Treximet Non-Responder | Correlation of Mean Estrogen Levels in Saliva and Urine Estradiol at Mid-Luteal and at Menstrual Migraine Headache Free in Responders vs Non-Responders | Urine Pre-Cycle Day 2 (n=6,3,5) | 3661.52 pg/mL | Standard Deviation 3215.32 |
| Treximet Non-Responder | Correlation of Mean Estrogen Levels in Saliva and Urine Estradiol at Mid-Luteal and at Menstrual Migraine Headache Free in Responders vs Non-Responders | Saliva Migraine Headache Free (n=8,3,4) | 33.22 pg/mL | Standard Deviation 5.48 |
| Treximet Non-Responder | Correlation of Mean Estrogen Levels in Saliva and Urine Estradiol at Mid-Luteal and at Menstrual Migraine Headache Free in Responders vs Non-Responders | Urine Pre-Cycle Day 1 (n=3,2,4) | 3687.07 pg/mL | Standard Deviation 2728.27 |
| Treximet Non-Responder | Correlation of Mean Estrogen Levels in Saliva and Urine Estradiol at Mid-Luteal and at Menstrual Migraine Headache Free in Responders vs Non-Responders | Urine Pre-Cycle Day 3 (n=8,2,5) | 5629.71 pg/mL | Standard Deviation 6940.06 |
| Treximet Non-Responder | Correlation of Mean Estrogen Levels in Saliva and Urine Estradiol at Mid-Luteal and at Menstrual Migraine Headache Free in Responders vs Non-Responders | Urine Pre-Cycle Day 4 (n=9,5,5) | 4266.02 pg/mL | Standard Deviation 2535.29 |
| Treximet Non-Responder | Correlation of Mean Estrogen Levels in Saliva and Urine Estradiol at Mid-Luteal and at Menstrual Migraine Headache Free in Responders vs Non-Responders | Urine Migraine Headache Free (n=10,7,7) | 3373.40 pg/mL | Standard Deviation 4536.7 |
| Treximet Non-Responder | Correlation of Mean Estrogen Levels in Saliva and Urine Estradiol at Mid-Luteal and at Menstrual Migraine Headache Free in Responders vs Non-Responders | Saliva Pre-Cycle Day 1 (n=1,0,4) | 43.33 pg/mL | Standard Deviation 23.19 |
| Treximet Non-Responder | Correlation of Mean Estrogen Levels in Saliva and Urine Estradiol at Mid-Luteal and at Menstrual Migraine Headache Free in Responders vs Non-Responders | Saliva Pre-Cycle Day 2 (n=2,2,4) | 47.36 pg/mL | Standard Deviation 19.65 |
| Treximet Non-Responder | Correlation of Mean Estrogen Levels in Saliva and Urine Estradiol at Mid-Luteal and at Menstrual Migraine Headache Free in Responders vs Non-Responders | Saliva Pre-Cycle Day 3 (n=8,4,7) | 67.76 pg/mL | Standard Deviation 61.65 |
Secondary
Migraine Recurrence Responders vs Non-Responders
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. 0-3 Pain Scale with 0=No Pain, 1=Mild, 2=Moderate, and 3=Severe \*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.
Time frame: From the onset of 1 menstrual migraine until 24 hours post treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Migraine Recurrence Responders vs Non-Responders | 1 participants |
| Treximet | Migraine Recurrence Responders vs Non-Responders | 2 participants |
| Treximet Non-Responder | Migraine Recurrence Responders vs Non-Responders | 0 participants |
Secondary
Time to Pain-Free in Responders vs Non-Responders
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. \*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.
Time frame: From the onset of 1 menstrual migraine headache until pain-free.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Time to Pain-Free in Responders vs Non-Responders | 7.64 hours | Standard Deviation 4.06 |
| Treximet | Time to Pain-Free in Responders vs Non-Responders | 3.13 hours | Standard Deviation 4.05 |
| Treximet Non-Responder | Time to Pain-Free in Responders vs Non-Responders | 4.68 hours | Standard Deviation 3.93 |
Secondary
α-Amylase Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment in Responders vs Non-Responders
α-Amylase levels collected at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment 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.
Time frame: From Baseline until 2 hours post treatment of 1 menstrual migraine headache.
Population: Sample size for each arm may vary at each time point and/or biomarker based on laboratory results obtained due to sample collection errors.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | α-Amylase Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment in Responders vs Non-Responders | α-Amylase Migraine Onset (n=10,7,6) | 100956.7 U/L | Standard Deviation 13551.51 |
| Placebo | α-Amylase Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment in Responders vs Non-Responders | α-Amylase Baseline (n=10,7,7) | 109280.50 U/L | Standard Deviation 12499.73 |
| Placebo | α-Amylase Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment in Responders vs Non-Responders | α-Amylase 2 Hours Post Treatment (n=9,7,7) | 102449.88 U/L | Standard Deviation 4883 |
| Treximet | α-Amylase Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment in Responders vs Non-Responders | α-Amylase Migraine Onset (n=10,7,6) | 103478.94 U/L | Standard Deviation 10789.63 |
| Treximet | α-Amylase Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment in Responders vs Non-Responders | α-Amylase Baseline (n=10,7,7) | 98002.68 U/L | Standard Deviation 6613.71 |
| Treximet | α-Amylase Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment in Responders vs Non-Responders | α-Amylase 2 Hours Post Treatment (n=9,7,7) | 103527.5 U/L | Standard Deviation 12084.79 |
| Treximet Non-Responder | α-Amylase Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment in Responders vs Non-Responders | α-Amylase Baseline (n=10,7,7) | 101250.54 U/L | Standard Deviation 8705.42 |
| Treximet Non-Responder | α-Amylase Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment in Responders vs Non-Responders | α-Amylase 2 Hours Post Treatment (n=9,7,7) | 103662.4 U/L | Standard Deviation 6540.98 |
| Treximet Non-Responder | α-Amylase Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment in Responders vs Non-Responders | α-Amylase Migraine Onset (n=10,7,6) | 93456.77 U/L | Standard Deviation 14086.68 |
Secondary
α-Amylase Measured 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\*\*. \*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. A non-responder is one that fails to meet the responder criteria.
Time frame: From Baseline from 24 hours post migraine gone for 1 menstrual migraine.
Population: Sample size for each arm may vary at each time point and/or biomarker based on laboratory results obtained due to sample collection errors.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | α-Amylase Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders | α-amylase 24 Hours Migraine Headache Free(n=10,4,6 | 100354.3 U/L | Standard Deviation 16608.96 |
| Placebo | α-Amylase Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders | α-amylase Migraine Onset (n=10,7,6) | 100956.7 U/L | Standard Deviation 13551.51 |
| Placebo | α-Amylase Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders | α-amylase Migraine Headache Free (n=9,7,7) | 102908.61 U/L | Standard Deviation 11522.83 |
| Treximet | α-Amylase Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders | α-amylase 24 Hours Migraine Headache Free(n=10,4,6 | 102475.8 U/L | Standard Deviation 9769.4 |
| Treximet | α-Amylase Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders | α-amylase Migraine Onset (n=10,7,6) | 103478.94 U/L | Standard Deviation 10789.63 |
| Treximet | α-Amylase Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders | α-amylase Migraine Headache Free (n=9,7,7) | 98720.95 U/L | Standard Deviation 13045.21 |
| Treximet Non-Responder | α-Amylase Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders | α-amylase 24 Hours Migraine Headache Free(n=10,4,6 | 101559.9 U/L | Standard Deviation 8532.96 |
| Treximet Non-Responder | α-Amylase Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders | α-amylase Migraine Headache Free (n=9,7,7) | 103031.44 U/L | Standard Deviation 3793.21 |
| Treximet Non-Responder | α-Amylase Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders | α-amylase Migraine Onset (n=10,7,6) | 93456.77 U/L | Standard Deviation 14086.08 |