Naltrexone and Acetaminophen Combination and Its Components in Adult Acute Migraine (AT-06)

Sponsor

Allodynic Therapeutics, LLC (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05685225

Collaborator

(none)

300

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

This study compares the efficacy of naltrexone/acetaminophen combination and each component versus placebo in the treatment of acute migraine and co-morbid anxiety in adults

Condition or Disease	Intervention/Treatment	Phase
Migraine	Drug: Naltrexone/Acetaminophen Drug: Naltrexone Drug: Acetaminophen Drug: Placebo	Phase 2

Detailed Description

This study consists of the following events:

Screening Visit (Day 1)
30-day Run-In (Days 1-30)
Randomization Visit (Days 31-37)
Treatment (Days 31-97): up to 60 days to treat one migraine attack at home
Follow-up (Days 34 -104): 3 to 7 days after taking the study medication

Study Design

Study Type:

Interventional

Anticipated Enrollment :

300 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Full-FactorialRandomized, Double-Blind, Placebo-Controlled, Parallel-Group, Full-Factorial

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Full-Factorial, Safety and Efficacy Study of Immediate Release Naltrexone and Acetaminophen Combination in Acute Migraine and Co-Morbid Anxiety in Adults

Anticipated Study Start Date :

May 1, 2023

Anticipated Primary Completion Date :

May 1, 2024

Anticipated Study Completion Date :

May 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Naltrexone/Acetaminophen A single dose for a Qualifying Migraine	Drug: Naltrexone/Acetaminophen Combination
Active Comparator: Naltrexone A single dose for a Qualifying Migraine	Drug: Naltrexone Naltrexone alone
Active Comparator: Acetaminophen A single dose for a Qualifying Migraine	Drug: Acetaminophen Acetaminophen alone
Placebo Comparator: Placebo A single dose for a Qualifying Migraine	Drug: Placebo Matching Placebo

Outcome Measures

Primary Outcome Measures

The proportion of acute migraine subjects achieving a statistical significance of 0.05 for freedom from pain for naltrexone/acetaminophen versus placebo [2 hours after dosing]
Freedom from pain is defined as headache pain absence from moderate or severe pain at baseline, without prior rescue medication. Pain is measured on a 4-point scale (0=none, 1=mild, 2=moderate, 3=severe)
The proportion of acute migraine subjects achieving a statistical significance of 0.05 for freedom from MBS for naltrexone/acetaminophen versus placebo [2 hours after dosing]
Definition of freedom from MBS: Absence of the prospectively identified Most Bothersome Symptom (MBS). The MBS (nausea, photophobia or phonophobia) is measured on a binary scale (absent, present).

Secondary Outcome Measures

Pain relief [2 hours after dosing]
Definition of pain relief: Headache pain severity reduction from moderate or severe to mild or no headache pain.
Freedom from photophobia [2 hours after dosing]
Definition of freedom from photophobia: photophobia absence
Freedom from phonophobia [2 hours after dosing]
Definition of freedom from phonophobia: phonophobia absence
Freedom from nausea [2 hours after dosing]
Definition of freedom from nausea: nausea absence
Sustained pain relief [2 to 24 hours]
Definition of sustained pain relief: No occurrence of headache pain of moderate or severe intensity with no use of rescue medication.
Sustained freedom from pain [2 to 24 hours]
Definition of sustained freedom from pain: No occurrence of headache pain of any intensity with no use of rescue medication.
Functional disability [2 hours after dosing]
Definition of functional disability: ability to work or function was measured as (0=normal 1=mildly impaired, 2=moderately impaired, 3=Severely impaired, requires bedrest). Freedom from functional disability was defined as normal function.
Functional disability [24 hours after dosing]
Definition of functional disability: ability to work or function was measured as (0=normal 1=mildly impaired, 2=moderately impaired, 3=Severely impaired, requires bedrest). Freedom from functional disability was defined as normal function.
Rescue medications use [within 24 hours]
Definition of rescue medication use: The use of an additional medication for treating the current migraine.
Pain relapse [within 48 hours]
Definition of pain relapse: The return of headache pain of any severity when the subject had freedom from pain at 2 hours.

Other Outcome Measures

Change in the Hamilton Anxiety Rating Scale score [Baseline (Randomization Visit) to 2 hours after dosing]
The Hamilton Anxiety Rating Scale (HAM-A) is a psychological questionnaire used by clinicians to rate the severity of a patient's anxiety. 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.
Change in "hurt feelings" score [2 hours after dosing]
Self-reported "Hurt feelings: (0=Not at all, 1=Slightly, 2=Moderate, 3=Extremely)
Change in "tense or wound-up feelings" score [2 hours after dosing]
Self-reported "Tense or wound-up feelings": (0=Not at all, 1=Slightly, 2=Moderate, 3=Extremely)
Change in "overall sense of wellbeing" [2 hours after dosing]
Self-reported "overall sense of wellbeing" (physical and emotional) is 0=Poor, 1=Okay 2=Good, 3=Superb. "Overall sense of wellbeing (physical and emotional)" [reflecting lack of physical pain, presence of positive emotions (such as good mood, alertness, confidence, high life satisfaction, and ability to manage stress), and the absence of negative emotions (depression and anxiety)].
Sustained freedom from pain for naltrexone/acetaminophen versus naltrexone [2 to 24 hours]
Definition of sustained freedom from pain: No occurrence of headache pain of any intensity with no use of rescue medication.
Sustained freedom from pain for naltrexone/acetaminophen versus Acetaminophen [2 to 24 hours]
Definition of sustained freedom from pain: No occurrence of headache pain of any intensity with no use of rescue medication.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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
Able to refrain from using any opioid medications (including methadone and buprenorphine) during the study and 7 days after taking the study medication

Exclusion Criteria:

A woman who is pregnant, nursing, or planning a pregnancy
Using medications to treat headaches or any other pain syndrome ≥10 days per month in any of the 3 months prior to screening (including acetaminophen, NSAIDs, triptans, ergotamine, opioids, or combination analgesics)
Using any opioids, barbiturate-containing medications, muscle relaxants, benzodiazepines, or marijuana within 6 months prior to screening
Symptoms consistent with chronic migraine, hemiplegic migraine, retinal migraine, trigeminal autonomic cephalgia, cranial neuropathy, or new persistent daily headache
Body mass index > 37 kg/m2
A history of cardiovascular or cerebrovascular disease including the following: ischemic heart disease, unstable angina, myocardial infarction, transient ischemic attack, Percutaneous Coronary Intervention (PCI), cardiac surgery, stroke, or transient ischemic attack (TIA), heart failure class III or IV; atrial fibrillation, 2nd, or 3rd-degree atrioventricular block within 6 months prior to screening
Uncontrolled hypertension or diabetes. Major depression, schizophrenia, dementia, epilepsy, major neurological disorders, or pain syndromes
A history of gastric or small intestinal surgery (including gastric bypass, gastric banding, gastric sleeve, gastric balloon, etc.) or a disease that causes malabsorption. Hepatic disease or suspected infection, (hepatitis B or C, or cancer). Also, any current use of prescription anti-coagulant (Pradaxa, Coumadin, Eliquis, Xarelto)
Significant hematologic, endocrine, pulmonary, renal, hepatic, or gastrointestinal disease; history of malignancy
A history of alcohol or drug abuse within the previous 12 months, current cannabis use, or a positive urine drug test at the Screening Visit
Clinically significant ECG abnormalities