The Preventive Treatment of Migraine With Low-Dose Naltrexone and Acetaminophen Combination

Inclusion Criteria

• The patient is a male or a female 18 years of age or older.
• History of migraine with or without aura according to the International Classification of Headache Disorders (ICHD)-3rd edition (beta version) for at least one-year with onset of migraine prior to 50 years of age.
• Migraine-associated nausea with ≥half of migraine attacks.
• 5-8 migraine/probable migraine headache days on average per month in the three months prior to Visit 1 and during the Baseline Period.
• The patient agrees to refrain from taking opiate medications from Visit 1 to 7 days after the last dose of the study drug.
• The patient is able to complete study questionnaires, comply with the study requirements and restrictions, and willing to provide written informed consent and authorize HIPAA.
• The patient has been taking a stable dose of a medication with migraine prevention potential for at least 3 month prior to the screening visit and agrees to not start, stop, or change dosage of any medication with migraine prevention potential during the study period. (E.g., beta-blockers, calcium channel blockers, tricyclic antidepressants, anticonvulsants, selective serotonin re-uptake inhibitors (SSRIs), serotonin-norepinephrine re-uptake inhibitors (SNRIs), magnesium or riboflavin supplements at high doses, herbal preparations (e.g. feverfew or St. john's wort)), Botulinum toxin must be discontinued one year prior to Visit 1.
• The patient agrees to forgo any elective surgery for the duration of the study.
• The female patient who is premenopausal or postmenopausal less than 1 year, or have not had surgical sterilization (i.e., tubal ligation, partial or complete hysterectomy) must have a negative urine pregnancy test, be non-lactating, and commit to using 2 methods of adequate and reliable contraception throughout the study and for 28 days after taking the last dose of the study drug (e.g., barrier with additional spermicidal, intra-uterine device, hormonal contraception). Male patients must be surgically sterile or commit to the use of 2 different methods of birth control during the study and for 28 days after the study.

Exclusion Criteria

• Usage of acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs) ≥15 days/month, or ergotamine and triptans >10 days/month, or opioids and barbiturates >2 days/month in the 3 months prior to Visit 1 or during the Baseline Period.
• Tension-type-like, and/or migraine-like headache on ≥15 days per month in the 3 months prior to Visit 1 or during the Baseline Period. Diagnosis of chronic migraine, cluster headache or neurologically complicated migraine (hemiplegic, basilar, retinal, ophthalmoplegic migraine).
• Regular use of the following medications for any reason: acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDs), antipsychotic drugs, monoamine oxidase inhibitors, benzodiazepines, sleep medications, muscle relaxants, anti-emetic medications, blood thinning medications (e.g., warfarin or heparin), cannabinoids, or botulinum toxin to head and neck regions. Low-dose aspirin for cardiovascular disease prophylaxis is permitted.
• Confounding painful conditions, (e.g. fibromyalgia, chronic low back pain, complex regional pain syndrome, etc.).
• Diagnosis of any concurrent medical or psychiatric condition; this includes, chronic unstable debilitating diseases such as Parkinson's disease, multiple sclerosis, cancer, significant renal impairment, significant hepatic impairment, etc.
• The patient has a history or diagnosis of moderate-to-severe hepatic or renal impairment (>2 × the upper limit of normal [ULN] for alanine transaminase or aspartate transaminase. ≥1.5 × ULN for alkaline Phosphatase, bilirubin, BUN, or creatinine). (Patients with elevated bilirubin level due to Gilbert's syndrome are allowed).
• The patient has a history within the previous 5 years of abuse of any drug, prescription, illicit, or alcohol.
• The Female patient is pregnant, actively trying