Low-Dose Naltrexone and Acetaminophen Combination and Its Components in the Acute Treatment of Migraine

Study Overview
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Brief Summary
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The study consists of a screening visit, out-patient treatment of a moderate or severe migraine attack with a single dose of the study medication within 8 weeks, and End-of-Study Visit 2-7 days after dosing.

Official Title
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A Clinical Trial to Assess a Single Dose of Low-Dose Naltrexone and Acetaminophen Combination and Its Components in the Acute Treatment of Migraine

Conditions
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Migraine With or Without Aura

Intervention / Treatment
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* Drug: Naltrexone and Acetaminophen
* Drug: Naltrexone and Acetaminophen-High Dose
* Drug: Naltrexone Alone (regular dose)
* Drug: Acetaminophen Alone
* Drug: Matching Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or 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 first migraine prior to age 50. Migraine-associated nausea with ≥half of migraine attacks. 2 - 8 migraines per month in each of the previous 3 months. 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 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 adequate and reliable contraception throughout the study (e.g., barrier with additional spermicidal, intra-uterine device, hormonal contraception). The male patient must be surgically sterile or commit to the use of 2 different methods of birth control during the study and for 28 days after taking the study drug. Exclusion Criteria: The patient in the opinion of the investigator, may have medication-overuse headache pain (as defined by ICHD - 3 beta criteria for medication-overuse headache), (analgesic, opioid, ergotamine or triptan overuse) during the 3 months preceding screening. The patient in the opinion of the investigator has chronic migraine (as defined by ICHD - 3 beta criteria for chronic migraine). History of cluster headache or neurologically complicated migraine (hemiplegic, basilar, retinal, ophthalmoplegic migraine). Initiation or change in medications with possible migraine prophylactic effects during 3 months before inclusion into the trial (E.g., calcium channel blockers, tricyclic antidepressants, beta-blockers, selective serotonin re-uptake inhibitors (SSRIs), serotonin-norepinephrine re-uptake inhibitors (SNRIs), or Botox). Any concurrent medical or psychiatric condition, this includes, but is not limited to chronic unstable debilitating diseases, significant renal or hepatic impairment. A history within the previous 3 years of abuse of any drug, prescription, illicit, or alcohol. The Female patient is pregnant or breast-feeding. The Male patient is not practicing 2 different methods of birth control with their partner during the study, and for 28 days after the investigational drug last dose or will not remain abstinent during the study, and for 28 days after the last dose. Use of opiates or barbiturates more than 3 days per month. Known-hypersensitivity reaction to any of the components of the investigational drug. Consumption of analgesic medication for other conditions on a regular basis, (nonsteroidal anti-inflammatory drugs, or acetaminophen, or muscle relaxants). Use of emergency care treatment more than 3 times in the previous 6 months. Participation in another study with an investigational drug within 30 days prior to randomization and/or a plan to participate during the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Naltrexone and Acetaminophen<br>Patients take one capsule containing naltrexone and one capsule containing acetaminophen together for a qualifying migraine | Drug: Naltrexone and Acetaminophen<br>* Naltrexone plus acetaminophen<br>|
| Experimental: Naltrexon/Acetaminophen-High Capsules<br>Patient take one capsule containing naltrexone (high dose) and one capsule containing acetaminophen together for a qualifying migraine | Drug: Naltrexone and Acetaminophen-High Dose<br>* Naltrexon (high dose) plus acetaminophen<br>|
| Active Comparator: Naltrexone Alone Capsules<br>Patient take one capsule containing naltrexone and one capsule containing placebo together for a qualifying migraine | Drug: Naltrexone Alone (regular dose)<br>* Naltrexone Alone plus Placebo<br>|
| Active Comparator: Acetaminophen Alone Capsules<br>Patient take one capsule containing naltrexone and one capsule containing placebo together for a qualifying migraine | Drug: Acetaminophen Alone<br>* Acetaminophen Alone plus Placebo<br>|
| Placebo Comparator: Placebo Capsules<br>Patient take two capsule containing placebo together for a qualifying migraine | Drug: Matching Placebo<br>* Two Placebo capsules<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| % of patients reporting no headache pain. | Self-reported headache pain on a four-point Likert scale. | 2 hours post-dose | 
| % of patients having absence of most bothersome migraine-associated symptom (MBS). | MBS was prospectively identified at baseline. Self-reported MBS as present or absent. | 2 hours post-dose | 
| % of patients who have sustained pain freedom | Defined as having no headache pain at 2 hours after dose, with no use of rescue medication and no relapse of headache pain within 24 hours after administration of the investigational drug. | 24-hour post-dose. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| % of patients having absence of nausea, photophobia, phonophobia, and neck/shoulder pain | Self-reported the current status of their associated symptom as present or absent. | 24-hour post-dose. | 
| % of patients who used rescue medications |  | 2-24 hours | 
| % of patients who had headache pain relapse. | Defined as the return of headache of any severity within 48 hours after administration of the investigational drug, when the patient was pain-free at 2 hours after the administration of the investigational drug. | 2-48 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Migraine Disorders, Headache Disorders, Migraine with Aura, Migraine without Aura