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

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 theInternational 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 havenot had surgical sterilization (i.e., tubal ligation, partial or completehysterectomy) must have a negative urine pregnancy test, be non-lactating, andcommit to using two methods of adequate and reliable contraception throughout thestudy and for 28 days after taking the last dose of the study medication (e.g.,barrier with an additional spermicidal, intra- uterine device, hormonalcontraception). Male subjects must be surgically sterile (the procedure occurredgreater than 6 months before the Screening Visit) or commit to using two differentbirth control methods during the study and for 28 days after the last dose of thestudy medication.

Exclusion Criteria:

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

2. Used opioids (including methadone and buprenorphine), barbiturate-containingmedications, muscle relaxants, or benzodiazepines within 3 months prior toscreening.

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 3months or use of any pain medication for other pain syndromes for more than 10 daysper month.

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

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

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.

10. Aspartate transaminase (AST/SGOT), alanine transaminase (ALT/SGPT), or alkalinePhosphatase ≥ 1.5 x Upper Limit of Normal (ULN). creatinine ≥ 1.5 x ULN.

11. BBB or intraventricular conduction defect with a QRS duration ≥ 150 msec. ST-Twave abnormalities.

12. Hemoglobin < 10 g/dL

13. Neutrophil count ≤ 1000/μL

14. Cholesterol ≥ 300 mg/dL

15. Triglycerides ≥ 500 mg/dL Additional exclusion criteria may apply.