Single-Site Study of Naltrexone/Acetaminophen for the Acute Treatment of Migraine: A Phase 2 Randomized Trial

Safety and Efficacy of Naltrexone/Acetaminophen for the Acute Treatment of Migraine: A Single-Site, Phase 2 Randomized Trial

• This two-stage clinical trial will assess a novel combination therapy for acute migraine. In Stage 1 (factorial), participants will receive the combination, each individual component, or placebo. In Stage 2 (dose-finding), they will test three doses of the combination. Before both stages, participants will complete a run-in period, documenting a migraine attack without study medication. They will then treat one migraine attack in each stage.
• 4 visits
• Requirements: Migraine Diagnosis. BMI below 34. Read, write, and speak English. No opioids, marijuana, benzodiazepines, or excessive alcohol.

This study evaluating naltrexone-acetaminophen in the acute treatment of migraine.

Inclusion Criteria:

1. Ages 18 to 75 years, inclusive.
2. At least 1-year of history of migraine with or without aura as defined by the International Classification of Headache Disorders 3rd edition 17 (ICHD-3).
3. Migraine onset before age 50 years.
4. Read, write, and speak English
5. BMI Higher than 20 and Lower than 34
6. The female subject who is premenopausal or postmenopausal less than one 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 two methods of adequate and reliable contraception throughout the study and for 28 days after taking the last dose of the study medication (e.g., barrier with an additional spermicidal, intra- uterine device, hormonal contraception). Male subjects must be surgically sterile (the procedure occurred greater than 6 months before the Screening Visit) or commit to using two different birth control methods during the study and for 28 days after the last dose of the study medication.

Exclusion Criteria:

1. Pregnant or nursing women or those planning a pregnancy.

2. Used opioids (including methadone and buprenorphine), barbiturate-containing medications, muscle relaxants, or benzodiazepines within 3 months prior to screening.

3. Used any recreational drugs in the past 3 months.

4. Use of medications to treat headaches more than 10 days per month in the past 3 months or use of any pain medication for other pain syndromes for more than 10 days per month.

5. Uncontrolled cardiovascular or cerebrovascular disease or a history of heart failure, atrial fibrillation, or myocardial infarction.

6. Uncontrolled hypertension (systolic/diastolic blood pressure ˃ 140/90 mmHg) or diabetes.

7. Immediate family members or same household members participating in the study.

8. Site personnel, their friends, and family.

9. Abnormal laboratory or ECG results.

   1. Aspartate transaminase (AST/SGOT), alanine transaminase (ALT/SGPT), or alkaline Phosphatase ≥ 1.5 x Upper Limit of Normal (ULN). creatinine ≥ 1.5 x ULN.
   2. BBB or intraventricular conduction defect with a QRS duration ≥ 150 msec. ST-T wave abnormalities.
   3. Hemoglobin < 10 g/dL
   4. Neutrophil count ≤ 1000/μL
   5. Cholesterol ≥ 300 mg/dL
   6. Triglycerides ≥ 500 mg/dL Additional exclusion criteria may apply.