Combination therapy of naltrexone and acetaminophen for treating migraines

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

This study is testing a new treatment for migraines that combines naltrexone and acetaminophen to see if it works better than taking them separately or a placebo.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 300 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Allodynic Therapeutics, Inc (Industry-sponsored)
• Locations: 1 site (North Miami, Florida)
• Trial ID: NCT05685225 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates a novel combination therapy of naltrexone and acetaminophen for the acute treatment of migraines. It consists of two stages: the first stage is a factorial design where participants receive either the combination therapy, individual components, or a placebo, while the second stage focuses on determining the optimal dose of the combination. Participants will document their migraine attacks during a run-in period before receiving treatment in each stage. The study aims to assess the efficacy and safety of this new treatment approach.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 75 with a history of migraines for at least one year.

Not a fit: Patients with a BMI above 34 or those currently using opioids, marijuana, benzodiazepines, or excessive alcohol may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new effective option for patients suffering from acute migraines.

How similar studies have performed: While this approach is novel, similar studies exploring combination therapies for migraines have shown promising results.

Eligibility criteria

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.

Where this trial is running

North Miami, Florida

• Keystone Clinical Research — North Miami, Florida, United States (Recruiting)

Study contacts

• Principal investigator: Natalia Belikova, MD PhD — Keystone Clinical Research
• Study coordinator: Annette C Toledano, MD

Conditions Migraine; Naltrexone; Acetaminophen; Acute migraine; Low-dose naltrexone; Anxiety