TreximetTM in the Prevention and Modification of Disease Progression in Migraine

Condition(s) targeted: Migraine

Intervention: sumatriptan/naproxen sodium (Drug); Naproxen sodium (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: Cady, Roger, M.D.

Official(s) and/or principal investigator(s):
Roger K Cady, MD, Principal Investigator, Affiliation: Clinvest

This study is being conducted to evaluate the hypothesis that use of pharmacological and non-pharmacological interventions may allow subjects at high risk for chronic migraine to avoid or reverse the transformation of episodic migraine to chronic migraine.

Official title: TreximetTM in the Prevention and Modification of Disease Progression in Migraine

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention

Primary outcome: Headache days

Secondary outcome:

Migraine attacks

Migraine severity

Migraine duration from onset to pain free

Migraine duration from time of treatment to pain free

Headache days

Migraine attacks

Doses of study medication

Doses of study medication

MIDAS scores

Compliance with lifestyle changes

Headache days

Detailed description: Two investigative centers will enroll 40 subjects in the United States. Subject participation in the 5 visit study will last 4 months.

At Visit 1, following informed consent, a medical, migraine, and medication history will be collected and a physical and neurological exam with vital signs will be performed. An ECG will be completed. A Lifestyle Choices for Better Migraine Management Questionnaire (Lifestyle Questionnaire) will be completed. Eligible subjects then complete a 1-month Baseline Period and treat migraine with their current preferred treatment of choice, documenting headache severity and associated symptoms in a 30-day Baseline Diary.

At Visit 2, the Baseline Diary will be reviewed and a pregnancy test will be collected from all subjects of childbearing potential. Vital signs will be collected and Adverse Events documented. Subjects continuing to meet eligibility criteria will be randomized 1: 1 to Treximet or naproxen and provided with study medication to treat on 14 or fewer days per month. Subjects will be encouraged to treat their migraine attacks within 1 hour of onset of headache pain and while the pain is still mild. Subjects will view an educational digital video disc (DVD) concerning lifestyle modification, receive a copy for home viewing, complete the Lifestyle Questionnaire, and receive 3 copies of the Lifestyle Questionnaire for weekly completion between Visits 2 and 3. The Migraine Disability Assessment questionnaire (MIDAS) will be completed and a 30-day Treatment Period Diary will be dispensed.

At Visits 3 and 4, Adverse Events will be collected, completed Diaries will be reviewed, and Drug Accountability performed. Pregnancy tests will be collected from all subjects of childbearing potential. Vital signs will be collected. Completed Lifestyle Questionnaires will be collected, a Lifestyle Questionnaire will be completed in the office, and 3 copies will be dispensed for weekly completion between visits. Study medication for the following month will be dispensed with a 30-day Diary.

At Visit 5, Adverse Events will be collected, completed Diaries will be reviewed, and Drug Accountability performed. Pregnancy tests will be collected from all subjects of childbearing potential. Vital signs will be collected. Completed Lifestyle Questionnaires will be collected and a Lifestyle Questionnaire will be completed in the office. Subjects will complete the MIDAS before exiting the study.

Minimum age: 18 Years. Maximum age: 65 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

Subject

- Is male or female, in otherwise good health, 18 to 65 years of age.

- Has history of frequent episodic migraine (6-14 migraine days per month) (with or

without aura) according to the 2nd Edition of The International Headache Classification (ICHD-2) for at least 3 months. (Stage 2-3 frequent transforming migraine)

- Had onset of migraine before age 50.

- Is able to differentiate migraine from any other headache they may experience (e. g.,

tension-type headache).

- Has stable history of headache at least 3 months prior to screening.

- Is not currently taking a migraine preventive or has been taking preventive for at

least 30 days prior to screening and agrees to not start, stop, or change medication and/or dosage during the study period.

- Has at least 50% of migraine attacks beginning at mild severity.

- If female of childbearing potential, has a negative urine pregnancy test at Visits

1-5 and uses, or agrees to use, for the duration of the study, a medically acceptable form of contraception as determined by the investigator.

1. Complete abstinence from intercourse from 2 weeks prior to administration of study drug throughout the study, and for a time interval after completion or premature discontinuation from the study to account for elimination of the study drug (a minimum of 7 days); or,

2. Surgically sterile (hysterectomy or tubal ligation or otherwise incapable of pregnancy); or,

3. Sterilization of male partner; or,

4. Intrauterine device with published data showing lowest expected failure rate is less than 1% per year; or,

5. Double barrier method (i. e., 2 physical barriers OR 1 physical barrier plus spermicide) for a least 1 month prior to Visit 1 and throughout study; or,

6. Hormonal contraceptives for at least 3 months prior to Visit 1 and throughout study.

- Had 6 or more migraine treatment days in 1 month prior to Visit 2.

Exclusion Criteria:

Subject

- Is unable to understand the study requirements, the informed consent, or complete

headache records as required per protocol.

- Is pregnant, actively trying to become pregnant, or breast-feeding.

- Has experienced the following migraine variants: basilar migraine, aura without

headache, familial hemiplegic migraine, complicated migraine, ophthalmoplegic migraine and retinal migraine.

- Has a history of Medication Overuse Headache (Appendix II) in the 3 months prior to

study enrollment or during the baseline phase

- Has history of acute migraine treatment greater than14 days per month in 3 months

prior to screening.

- Has abused, in the opinion of the Investigator, any of the following drugs, currently

or within the past 1 year:

1. opioids

2. alcohol

3. barbiturates

4. benzodiazepine

5. cocaine

- Has history of impaired hepatic or renal function that, in the investigator's

opinion, contraindicates participation in this study.

- Has an unstable neurological condition or a significantly abnormal neurological

examination with focal signs or signs of increased intracranial pressure.

- Suffers from cardiovascular disease (ischemic heart disease, including angina

pectoris, myocardial infarction, documented silent ischemia, or with Prinzmetal's angina); has symptoms of ischemic heart disease, ischemic abdominal syndromes, peripheral vascular disease or Raynaud's Syndrome; has uncontrolled hypertension (≥140/90mmHg in 2 out of 3 BP measurements at screening); has electrocardiogram (ECG) results outside normal limits for clinically stable patients as judged by the investigator.

- Has a history of asthma and nasal polyps.

- Has a history of peptic ulcer disease requiring therapeutic intervention in the year

prior to study enrollment

- Has evidence or history of any gastrointestinal (GI) surgery or GI ulceration or

perforation of the stomach or intestine in the past 6 months, gastrointestinal bleeding in the past year or evidence or history of inflammatory bowel disease or history of any other bleeding disorder, or has taken or plans to take any anti-coagulant or any antiplatelet agent within the 2 weeks prior to screening through 48 hours post final study treatment.

- Has history of non-steroidal anti-inflammatory drug induced gastritis, esophagitis,

or duodenitis.

- Suffers from a serious illness, or an unstable medical condition, one that could

require hospitalization, or could increase the risk of adverse events.

- Has in the opinion of the investigator a significant cardiovascular risk profile that

may include uncontrolled high blood pressure, post-menopausal women, male over 40 years old, hypercholesterolemia, obesity, diabetes mellitus, smoking, or a family history of cardiovascular disease in a 1st degree relative.

- Has in the opinion of the investigator a significant cerebrovascular risk profile

that may include female over the age of 35 using oral birth control, smoking, or a family history of cerebrovascular disease in a first degree relative.

- Has a psychiatric condition, in the opinion of the investigator that may affect the

interpretation of efficacy and safety data or contraindicates the subject's participation in the study.

- Has hypersensitivity, intolerance, or contraindication to the use of sumatriptan, any

of its components, or any other 5-HT1 agonist.

- Has a hypersensitivity, intolerance, or contraindication to the use of naproxen, any

of its components, or any other non-steroidal anti-inflammatory drug including aspirin and COX-2 inhibiting agents.

- Is currently taking a migraine prophylactic medication containing an ergotamine or

ergot derivative such as dihydroergotamine (DHE) or methysergide.

- Has taken, or plans to take, a monoamine oxidase inhibitor (MAOI) including herbal

preparations containing St. John's wort (Hypericum perforatum), anytime within the 2 weeks prior to screening through 2 weeks post final study treatment.

- Has taken or plans to take an angiotensin-converting enzyme (ACE) inhibitor or

angiotensin receptor blocker (ARB) anytime within the 2 weeks prior to screening through 48 hours post final study treatment.

- Has received any investigational agents within 30 days prior to Visit 1.

- Plans to participate in another clinical study at any time during this study.

Newport Beach Clinical Research Assoc., Inc., Newport Beach, California 92663, United States; Recruiting
Ricky Cortes, Phone: 949-759-8001, Ext: 203, Email: ricky@nbneuro.com
Paolo Rodriguez, Phone: 949-759-8001, Ext: 203, Email: paolo@nbneuro.com
Christopher P O'Carroll, MD, Principal Investigator
Daniel S Bandari, MD, Sub-Investigator
Sally De Castro-Tilsen, PA-C, Sub-Investigator
Ali Makki, DMD, Sub-Investigator

Clinvest, Springfield, Missouri 65807, United States; Recruiting
Stacey Richard, Phone: 417-841-3679, Email: srichard@clinvest.com
Debbie Milligan, RN, Phone: 417-841-3625, Email: dmilligan@clinvest.com
Roger K Cady, MD, Principal Investigator
John K Dexter, MD, Sub-Investigator

Related publications:

Cady RK, Goldstein J, Silberstein S, Juhász M, Ramsey K, Rodgers A, Hustad CM, Ho T. Expanding access to triptans: assessment of clinical outcome. Headache. 2009 Nov-Dec;49(10):1402-13. Epub 2009 Oct 8.

Cady RK, Martin VT, Géraud G, Rodgers A, Zhang Y, Ho AP, Hustad CM, Ho TP, Connor KM, Ramsey KE. Rizatriptan 10-mg ODT for early treatment of migraine and impact of migraine education on treatment response. Headache. 2009 May;49(5):687-96.

Bigal ME, Sheftell FD, Rapoport AM, Lipton RB, Tepper SJ. Chronic daily headache in a tertiary care population: correlation between the International Headache Society diagnostic criteria and proposed revisions of criteria for chronic daily headache. Cephalalgia. 2002 Jul;22(6):432-8.

Headache Classification Committee; Olesen J, Bousser MG, Diener HC, Dodick D, First M, Goadsby PJ, Göbel H, Lainez MJ, Lance JW, Lipton RB, Nappi G, Sakai F, Schoenen J, Silberstein SD, Steiner TJ. New appendix criteria open for a broader concept of chronic migraine. Cephalalgia. 2006 Jun;26(6):742-6.

Lipton RB, Stewart WF, Cady R, Hall C, O'Quinn S, Kuhn T, Gutterman D. 2000 Wolfe Award. Sumatriptan for the range of headaches in migraine sufferers: results of the Spectrum Study. Headache. 2000 Nov-Dec;40(10):783-91.

Newman LC, Lipton RB, Lay CL, Solomon S. A pilot study of oral sumatriptan as intermittent prophylaxis of menstruation-related migraine. Neurology. 1998 Jul;51(1):307-9.

Foley KA, Cady R, Martin V, Adelman J, Diamond M, Bell CF, Dayno JM, Hu XH. Treating early versus treating mild: timing of migraine prescription medications among patients with diagnosed migraine. Headache. 2005 May;45(5):538-45.

Rapoport AM, Bigal ME, Volcy M, Sheftell FD, Feleppa M, Tepper SJ. Naratriptan in the preventive treatment of refractory chronic migraine: a review of 27 cases. Headache. 2003 May;43(5):482-9.

Sheftell FD, Rapoport AM, Tepper SJ, Bigal ME. Naratriptan in the preventive treatment of refractory transformed migraine: a prospective pilot study. Headache. 2005 Nov-Dec;45(10):1400-6.

Starting date: December 2010
Last updated: September 19, 2011