Single-Site Study of Naltrexone/Acetaminophen for the Acute Treatment of Migraine: A Phase 2 Randomized Trial (AT-06)

December 2, 2025 updated by: Allodynic Therapeutics, Inc

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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

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

Study Type

Interventional

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Florida
      • North Miami, Florida, United States, 33181
        • Keystone Clinical Research

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Stage 1: Naltrexone/Acetaminophen
One dose for a Qualifying Migraine Attack
Drug: Stage 1: Naltrexone/Acetaminophen
Combination
Other Names:
  • ALLOD-2
Active Comparator: Stage 1: Naltrexone
One dose for a Qualifying Migraine Attack
Drug: Stage 1: Naltrexone
Naltrexone alone
Active Comparator: Satge 1: Acetaminophen
One dose for a Qualifying Migraine Attack
Drug: Stage 1: Acetaminophen
Acetaminophen alone
Placebo Comparator: Stage 1: Placebo
One dose for a Qualifying Migraine Attack
Drug: Stage1: Placebo
Matching placebo
Experimental: Stage 2: Naltrexone/Acetaminophen-high dose
One dose for a qualifying migraine attack
Drug: Stage 2: Naltrxone/Acetaminophen high dose
Combination high dose
Other Names:
  • ALLOD-2
Experimental: Stage 2: Naltrexone/Acetaminophen-medium dose
One dose for a qualifying migraine attack
Drug: Stage 2: Naltrexone/Acetaminophen medium dose
Combination medium dose
Other Names:
  • ALLOD-2
Experimental: Stage 2: Naltrexone/Acetaminophen-low dose
One dose for a qualifying migraine attack
Drug: Stage 2: Naltrxone/Acetaminophen low dose
Combination low dose
Other Names:
  • ALLOD-2
Placebo Comparator: Stage 2: Placebo
One dose for a qualifying migraine attack
Drug: Stage 2: Placebo
Matching Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of subjects with acute migraine who achieved freedom from pain after dosing
Time Frame: 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.
2 hours after dosing
Proportion of subjects with acute migraine who achieved freedom from migraine's Most Bothersome Symptoms (MBS) after dosing
Time Frame: 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.
2 hours after dosing

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Functional disability at 2 hours
Time Frame: 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.
2 hours after dosing
Functional disability at 24 hours
Time Frame: 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.
24 hours after dosing
Use of rescue medications within 24 hours
Time Frame: within 24 hours
Rescue medication use refers to the use of an additional medication to treat the current migraine.
within 24 hours
Pain relapse within 48 hours
Time Frame: 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.
within 48 hours
The proportion of subjects with acute migraine who achieved sustained pain freedom from 2 to 24 hours
Time Frame: 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.
2 to 24 hours
Proportion of subjects with acute migraine who achieved pain relief
Time Frame: 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.
2 hours after dosing
Proportion of subjects with acute migraine who achieved freedom from photophobia
Time Frame: 2 hours after dosing
Freedom from photophobia is defined as absence of photophobia
2 hours after dosing
Proportion of subjects with acute migraine who achieved freedom from phonophobia
Time Frame: 2 hours after dosing
Freedom from phonophobia is defined as absence of phonophobia
2 hours after dosing
Proportion of subjects with acute migraine who achieved freedom from nausea
Time Frame: 2 hours after dosing
Freedom from nausea is defined as absence of nausea
2 hours after dosing
Proportion of subjects with acute migraine who achieved sustained pain relief from 2 to 24 hours
Time Frame: 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.
2 to 24 hours

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Hamilton Anxiety Rating Scale score
Time Frame: Baseline (Randomization Visit) to 2 hours after dosing
The Hamilton Anxiety Rating Scale is a validated assessment tool for measuring anxiety symptoms. The scale consists of fourteen items designed to assess the severity of anxiety on a scale of zero to four, with four being the most severe.
Baseline (Randomization Visit) to 2 hours after dosing
Self-reported hurt feelings score
Time Frame: 2 hours after dosing
Self-reported hurt feelings on a 4-point scale: (0=Not at all, 1=Slightly, 2=Moderate, 3=Extremely).
2 hours after dosing
Self-reported tense feelings score
Time Frame: 2 hours after dosing
Self-reported tense feelings on a 4-point scale: (0=Not at all, 1=Slightly, 2=Moderate, 3=Extremely).
2 hours after dosing
Self-reported overall sense of wellbeing
Time Frame: 2 hours after dosing
Self-reported overall sense of wellbeing (physical and emotional) is a subjective measurement that reflects an individual's perception of their physical and emotional health. It is typically assessed on a 4-point scale, ranging from 0 (Poor) to 3 (Superb), with 1 (Okay) and 2 (Good) representing intermediate levels of wellbeing. This measurement considers factors such as physical pain, positive emotions, life satisfaction, stress management, and the absence of negative emotions like depression and anxiety.
2 hours after dosing
Hamilton Anxiety Rating Scale score
Time Frame: Baseline (Randomization Visit) to 24 hours after dosing
The Hamilton Anxiety Rating Scale is a validated assessment tool for measuring anxiety symptoms. The scale consists of fourteen items designed to assess the severity of anxiety on a scale of zero to four, with four being the most severe.
Baseline (Randomization Visit) to 24 hours after dosing

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Allodynic Therapeutics, Inc

Investigators

  • Study Director: Annette C Toledano, MD, Allodynic Therapeutics, Inc
  • Principal Investigator: Natalia Belikova, MD PhD, Keystone Clinical Research

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 31, 2025

Primary Completion (Actual)

December 2, 2025

Study Completion (Actual)

December 2, 2025

Study Registration Dates

First Submitted

December 27, 2022

First Submitted That Met QC Criteria

January 13, 2023

First Posted (Actual)

January 17, 2023

Study Record Updates

Last Update Posted (Actual)

December 8, 2025

Last Update Submitted That Met QC Criteria

December 2, 2025

Last Verified

December 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AT-06

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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