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

Phase 2

Recruiting

• Conditions: Migraine
• Interventions: Drug: Acetaminophen; Drug: Naltrexone-Acetaminophen; Drug: Placebo; Drug: Naltrexone

• Registration Number: NCT05685225
• Lead Sponsor: Allodynic Therapeutics, Inc

Brief Summary

* 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.

Detailed Description

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

Study Timeline

• Study First Submitted: 2022-12-27
• Study First Submitted QC: 2023-01-13
• Study First Posted: 2023-01-17
• Status Verified: 2025-01
• Study Start: 2025-01-31
• Last Update Submitted: 2025-03-20
• Last Update Posted: 2025-03-24
• Primary Completion: 2026-12-31
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 300

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Acetaminophen	Acetaminophen	Subjects take a single dose for a Qualifying Migraine
Naltrexone-Acetaminophen	Naltrexone-Acetaminophen	Subjects take a single dose for a Qualifying Migraine
Placebo	Placebo	Subjects take a single dose for a Qualifying Migraine
Naltrexone	Naltrexone	Subjects take a single dose for a Qualifying Migraine

Primary Outcome Measures

Name	Time	Method
Proportion of subjects with acute migraine who achieved freedom from pain after dosing	2 hours after dosing	Freedom from pain is defined as the absence of headache pain from moderate or severe pain at baseline, without the use of rescue medication. The pain is measured on a 4-point scale, with 0 indicating no pain, 1 for mild pain, 2 for moderate pain, and 3 for severe pain.
Proportion of subjects with acute migraine who achieved freedom from migraine's Most Bothersome Symptoms (MBS) after dosing	2 hours after dosing	MBS freedom is defined as the absence of the identified Most Bothersome Symptom (MBS), which can be nausea, photophobia, or phonophobia. The MBS is measured on a binary scale, either absent or present.

Secondary Outcome Measures

Name	Time	Method
Proportion of subjects with acute migraine who achieved pain relief	2 hours after dosing	Pain relief is defined as a reduction in headache pain severity from moderate or severe to mild or no headache pain.
Proportion of subjects with acute migraine who achieved freedom from photophobia	2 hours after dosing	Freedom from photophobia is defined as absence of photophobia
Proportion of subjects with acute migraine who achieved freedom from phonophobia	2 hours after dosing	Freedom from phonophobia is defined as absence of phonophobia
Proportion of subjects with acute migraine who achieved freedom from nausea	2 hours after dosing	Freedom from nausea is defined as absence of nausea
Proportion of subjects with acute migraine who achieved sustained pain relief from 2 to 24 hours	2 to 24 hours	Sustained pain relief is defined as the reduction of headache pain severity from moderate or severe intensity to mild without the use of rescue medication.
The proportion of subjects with acute migraine who achieved sustained pain freedom from 2 to 24 hours	2 to 24 hours	Sustained pain freedom is defined as the absence of any headache pain of any intensity without the use of rescue medication.
Functional disability at 2 hours	2 hours after dosing	Functional disability refers to the inability to perform activities of daily living or work tasks to a normal level due to physical, mental, or sensory impairments. It is measured on a scale of 0 to 3, where 0 indicates normal function and 3 indicates the need for bedrest due to severe impairment.
Functional disability at 24 hours	24 hours after dosing	Functional disability refers to the inability to perform activities of daily living or work tasks to a normal level due to physical, mental, or sensory impairments. It is measured on a scale of 0 to 3, where 0 indicates normal function and 3 indicates the need for bedrest due to severe impairment.
Use of rescue medications within 24 hours	within 24 hours	Rescue medication use refers to the use of an additional medication to treat the current migraine.
Pain relapse within 48 hours	within 48 hours	Pain relapse refers to the reappearance of headache pain of any severity when the subject had been free of pain 2 hours after dosing.

Trial Locations

Locations (1)

Keystone Clinical Research; 🇺🇸 North Miami, Florida, United States