Back to resultsA Phase 2 Study Evaluating Naltrexone-Acetaminophen in Acute Migraine and Co-Occurring Anxiety in Adults
Primary Purpose
Migraine, Episodic Migraine, Migraine, Classic
Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Naltrexone-Acetaminophen
Naltrexone
Acetaminophen
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Migraine focused on measuring Naltrexone, Acetaminophen, Acute migraine, Low-dose naltrexone, Anxiety
Eligibility Criteria
Inclusion Criteria: Male or female ages 18 to 75 years, inclusive At least 1-year of history of migraine with or without aura as defined by the International Classification of Headache Disorders 3rd edition (ICHD-3) Migraine onset before age 50 years No use of opioids (including methadone and buprenorphine) from 6 months before the study, during the study, and for 7 days after taking the study medication No use barbiturate-containing medications, muscle relaxants, benzodiazepines, or marijuana from 6 months before the study and during the study, BMI equal to or lower than 36 kg/m2. Exclusion Criteria: Pregnant or nursing women or those planning a pregnancy. Use of opioids in the past 6 months. Use of medications to treat headaches more than 10 days per month in any of the past 3 months. Use of barbiturate-containing medications, muscle relaxants, benzodiazepines, or marijuana in the past 6 months. Positive results for cocaine, marijuana, opiates, methamphetamines, and oxycodone in a urine drug screen. Symptoms consistent with chronic migraine, cranial neuropathy, and other pain syndromes. Headaches lasting more than 2 days in the past 3 months. More than one emergency care treatment for migraine in the past 12 months. BMI equal to or greater than 37 kg/m2. Uncontrolled cardiovascular or cerebrovascular disease or a recent history of heart failure, atrial fibrillation, or myocardial infarction. Uncontrolled hypertension or diabetes. Current diagnosis of major depression, schizophrenia, dementia, significant neurological disorders, or other pain syndromes. Gastric or small intestinal surgery or malabsorption and hepatic disease. Significant hematologic, endocrine, pulmonary, renal, or gastrointestinal disease or history of malignancy in the past 5 years. History of alcohol or drug abuse or current cannabis use in the past 12 months. Known allergy to naltrexone or acetaminophen. Participation in another clinical trial. Immediate family members or same household members participating in the study. Site personnel, their friends, and family. Paid referral fees are not allowed. Abnormal laboratory or ECG results such as bundle branch block, liver or kidney function tests, hemoglobin level, neutrophil count, cholesterol, or triglycerides.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Active Comparator
Active Comparator
Placebo Comparator
Arm Label
Naltrexone-Acetaminophen
Naltrexone
Acetaminophen
Placebo
Arm Description
Subjects take a single dose for a Qualifying Migraine
Subjects take a single dose for a Qualifying Migraine
Subjects take a single dose for a Qualifying Migraine
Subjects take a single dose for a Qualifying Migraine
Outcomes
Primary Outcome Measures
The proportion of subjects with acute migraine who achieved freedom from pain 2 hours after dosing with naltrexone-acetaminophen compared to the placebo.
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.
The proportion of subjects with acute migraine who achieved freedom from migraine's Most Bothersome Symptoms (MBS) 2 hours after dosing with naltrexone-acetaminophen compared to the placebo
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
The proportion of subjects with acute migraine who achieved pain relief compared to placebo
Pain relief is defined as a reduction in headache pain severity from moderate or severe to mild or no headache pain.
The proportion of subjects with acute migraine who achieved freedom from photophobia
Freedom from photophobia is defined as absence of photophobia
The proportion of subjects with acute migraine who achieved freedom from phonophobia
Freedom from phonophobia is defined as absence of phonophobia
The proportion of subjects with acute migraine who achieved freedom from nausea
Freedom from nausea is defined as absence of nausea
The proportion of subjects with acute migraine who achieved sustained pain relief from 2 to 24 hours
Sustained pain relief is defined as the absence of headache pain of moderate or severe intensity without the use of rescue medication.
The proportion of subjects with acute migraine who achieved sustained pain freedom from 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
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
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
Rescue medication use refers to the use of an additional medication to treat the current migraine.
Pain relapse 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.
Full Information
NCT ID
NCT05685225
First Posted
December 27, 2022
Last Updated
July 20, 2023
Sponsor
Allodynic Therapeutics, LLC
1. Study Identification
Unique Protocol Identification Number
NCT05685225
Brief Title
A Phase 2 Study Evaluating Naltrexone-Acetaminophen in Acute Migraine and Co-Occurring Anxiety in Adults
Official Title
A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Full-Factorial Study to Evaluate Naltrexone-Acetaminophen Combination in Treating Acute Migraine and Co-Occurring Anxiety in Adults
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
January 1, 2024 (Anticipated)
Primary Completion Date
September 1, 2024 (Anticipated)
Study Completion Date
November 1, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Allodynic Therapeutics, LLC
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Naltrexone has a dual function as an opioid receptor antagonist and a Toll-Like Receptor-4 (TLR4) antagonist. While primarily approved in a 50 mg tablet for treating opioid and alcohol addiction by blocking opioid receptors, naltrexone's TLR4-blocking effect is also significant. This action reduces the levels of pro-inflammatory cytokines responsible for pain generation, primarily in the trigeminal ganglion and dorsal root ganglia. These sites play a key role in the effectiveness of naltrexone as a pain-alleviating agent. Acetaminophen is the active ingredient in Tylenol, an over-the-counter non-opioid analgesic and antipyretic agent.
Both naltrexone and acetaminophen have demonstrated effectiveness in the treatment of acute migraine, physical pain, and emotional pain. However, while naltrexone has demonstrated potential in animal and human studies, confirmatory clinical trials for pain treatment in humans are still lacking.
Additionally, it is important to note that around 50% of migraine patients experience co-occurring anxiety. Therefore, this study aims to assess the effectiveness of naltrexone-acetaminophen in treating migraine and co-occurring anxiety compared to each drug alone and placebo. The sponsor has conducted four clinical studies showing promising results of naltrexone-acetaminophen in treating migraine, chronic low-back pain, and emotional pain.
Detailed Description
This study evaluating naltrexone-acetaminophen in acute migraine and co-occurring anxiety in adults lasts between 1.2 to 3.5 months (depending on when a migraine attack is treated during the treatment period). The study includes the following key events:
Screening Visit (Day 1).
30-day Run-In Period (Days 1-30).
Randomization Visit (Days 31-37).
Treatment Period (Days 31-97): up to 60 days to treat a migraine at home.
End-of-Study Visit (Days 36 -106): 3 to 7 days after treatment.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Migraine, Episodic Migraine, Migraine, Classic, Migraine With Aura, Migraine Without Aura
Keywords
Naltrexone, Acetaminophen, Acute migraine, Low-dose naltrexone, Anxiety
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Full-Factorial
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
300 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Naltrexone-Acetaminophen
Arm Type
Experimental
Arm Description
Subjects take a single dose for a Qualifying Migraine
Arm Title
Naltrexone
Arm Type
Active Comparator
Arm Description
Subjects take a single dose for a Qualifying Migraine
Arm Title
Acetaminophen
Arm Type
Active Comparator
Arm Description
Subjects take a single dose for a Qualifying Migraine
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Subjects take a single dose for a Qualifying Migraine
Intervention Type
Drug
Intervention Name(s)
Naltrexone-Acetaminophen
Other Intervention Name(s)
ALLOD-2
Intervention Description
Combination
Intervention Type
Drug
Intervention Name(s)
Naltrexone
Intervention Description
Naltrexone alone
Intervention Type
Drug
Intervention Name(s)
Acetaminophen
Intervention Description
Acetaminophen alone
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matching placebo
Primary Outcome Measure Information:
Title
The proportion of subjects with acute migraine who achieved freedom from pain 2 hours after dosing with naltrexone-acetaminophen compared to the placebo.
Description
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.
Time Frame
2 hours after dosing
Title
The proportion of subjects with acute migraine who achieved freedom from migraine's Most Bothersome Symptoms (MBS) 2 hours after dosing with naltrexone-acetaminophen compared to the placebo
Description
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.
Time Frame
2 hours after dosing
Secondary Outcome Measure Information:
Title
The proportion of subjects with acute migraine who achieved pain relief compared to placebo
Description
Pain relief is defined as a reduction in headache pain severity from moderate or severe to mild or no headache pain.
Time Frame
2 hours after dosing
Title
The proportion of subjects with acute migraine who achieved freedom from photophobia
Description
Freedom from photophobia is defined as absence of photophobia
Time Frame
2 hours after dosing
Title
The proportion of subjects with acute migraine who achieved freedom from phonophobia
Description
Freedom from phonophobia is defined as absence of phonophobia
Time Frame
2 hours after dosing
Title
The proportion of subjects with acute migraine who achieved freedom from nausea
Description
Freedom from nausea is defined as absence of nausea
Time Frame
2 hours after dosing
Title
The proportion of subjects with acute migraine who achieved sustained pain relief from 2 to 24 hours
Description
Sustained pain relief is defined as the absence of headache pain of moderate or severe intensity without the use of rescue medication.
Time Frame
2 to 24 hours
Title
The proportion of subjects with acute migraine who achieved sustained pain freedom from 2 to 24 hours
Description
Sustained pain freedom is defined as the absence of any headache pain of any intensity without the use of rescue medication.
Time Frame
2 to 24 hours
Title
Functional disability at 2 hours
Description
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.
Time Frame
2 hours after dosing
Title
Functional disability at 24 hours
Description
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.
Time Frame
24 hours after dosing
Title
Use of rescue medications within 24 hours
Description
Rescue medication use refers to the use of an additional medication to treat the current migraine.
Time Frame
within 24 hours
Title
Pain relapse within 48 hours
Description
Pain relapse refers to the reappearance of headache pain of any severity when the subject had been free of pain 2 hours after dosing.
Time Frame
within 48 hours
Other Pre-specified Outcome Measures:
Title
Hamilton Anxiety Rating Scale score
Description
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.
Time Frame
Baseline (Randomization Visit) to 2 hours after dosing
Title
Self-reported hurt feelings score
Description
Self-reported hurt feelings on a 4-point scale: (0=Not at all, 1=Slightly, 2=Moderate, 3=Extremely).
Time Frame
2 hours after dosing
Title
Self-reported tense feelings score
Description
Self-reported tense feelings on a 4-point scale: (0=Not at all, 1=Slightly, 2=Moderate, 3=Extremely).
Time Frame
2 hours after dosing
Title
Self-reported overall sense of wellbeing
Description
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.
Time Frame
2 hours after dosing
Title
Sustained pain freedom for naltrexone-acetaminophen versus naltrexone
Description
Sustained pain freedom is defined as the absence of any headache pain of any intensity without the use of rescue medication.
Time Frame
2 to 24 hours
Title
Sustained pain freedom for naltrexone-acetaminophen versus Acetaminophen
Description
Sustained pain freedom is defined as the absence of any headache pain of any intensity without the use of rescue medication.
Time Frame
2 to 24 hours
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or female ages 18 to 75 years, inclusive
At least 1-year of history of migraine with or without aura as defined by the International Classification of Headache Disorders 3rd edition (ICHD-3)
Migraine onset before age 50 years
No use of opioids (including methadone and buprenorphine) from 6 months before the study, during the study, and for 7 days after taking the study medication
No use barbiturate-containing medications, muscle relaxants, benzodiazepines, or marijuana from 6 months before the study and during the study,
BMI equal to or lower than 36 kg/m2.
Exclusion Criteria:
Pregnant or nursing women or those planning a pregnancy.
Use of opioids in the past 6 months.
Use of medications to treat headaches more than 10 days per month in any of the past 3 months.
Use of barbiturate-containing medications, muscle relaxants, benzodiazepines, or marijuana in the past 6 months.
Positive results for cocaine, marijuana, opiates, methamphetamines, and oxycodone in a urine drug screen.
Symptoms consistent with chronic migraine, cranial neuropathy, and other pain syndromes.
Headaches lasting more than 2 days in the past 3 months.
More than one emergency care treatment for migraine in the past 12 months.
BMI equal to or greater than 37 kg/m2.
Uncontrolled cardiovascular or cerebrovascular disease or a recent history of heart failure, atrial fibrillation, or myocardial infarction.
Uncontrolled hypertension or diabetes.
Current diagnosis of major depression, schizophrenia, dementia, significant neurological disorders, or other pain syndromes.
Gastric or small intestinal surgery or malabsorption and hepatic disease.
Significant hematologic, endocrine, pulmonary, renal, or gastrointestinal disease or history of malignancy in the past 5 years.
History of alcohol or drug abuse or current cannabis use in the past 12 months.
Known allergy to naltrexone or acetaminophen.
Participation in another clinical trial.
Immediate family members or same household members participating in the study.
Site personnel, their friends, and family. Paid referral fees are not allowed.
Abnormal laboratory or ECG results such as bundle branch block, liver or kidney function tests, hemoglobin level, neutrophil count, cholesterol, or triglycerides.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Annette C Toledano, MD
Phone
3058956808
Email
ctg@allodynic.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Annette C Toledano, MD
Organizational Affiliation
Allodynic Therapeutics, LLC
Official's Role
Study Director
12. IPD Sharing Statement
Plan to Share IPD
No
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A Phase 2 Study Evaluating Naltrexone-Acetaminophen in Acute Migraine and Co-Occurring Anxiety in Adults
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