Clinical trial NCT05685225: Single-Site Study of Naltrexone/Acetaminophen for the Acute Treatment of Migraine: A Phase 2 Randomized Trial
Official title: Safety and Efficacy of Naltrexone/Acetaminophen for the Acute Treatment of Migraine: A Single-Site, Phase 2 Randomized Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Migraine
Keywords: Naltrexone
Acetaminophen
Acute migraine
Low-dose naltrexone
Anxiety
Lead sponsor: Allodynic Therapeutics, Inc
Sponsor class: INDUSTRY
First posted: 2023-01-17
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, Double-Blind, Placebo-Controlled, Parallel-Group
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Proportion of subjects with acute migraine who achieved freedom from pain after dosing
timeFrame: 2 hours after dosing
measure: Proportion of subjects with acute migraine who achieved freedom from migraine's Most Bothersome Symptoms (MBS) after dosing
timeFrame: 2 hours after dosing
Secondary outcomes:
measure: Proportion of subjects with acute migraine who achieved pain relief
timeFrame: 2 hours after dosing
measure: Proportion of subjects with acute migraine who achieved freedom from photophobia
timeFrame: 2 hours after dosing
measure: Proportion of subjects with acute migraine who achieved freedom from phonophobia
timeFrame: 2 hours after dosing
measure: Proportion of subjects with acute migraine who achieved freedom from nausea
timeFrame: 2 hours after dosing
measure: Proportion of subjects with acute migraine who achieved sustained pain relief from 2 to 24 hours
timeFrame: 2 to 24 hours
measure: The proportion of subjects with acute migraine who achieved sustained pain freedom from 2 to 24 hours
timeFrame: 2 to 24 hours
measure: Functional disability at 2 hours
timeFrame: 2 hours after dosing
measure: Functional disability at 24 hours
timeFrame: 24 hours after dosing
measure: Use of rescue medications within 24 hours
timeFrame: within 24 hours
measure: Pain relapse within 48 hours
timeFrame: within 48 hours
Other outcomes:
measure: Hamilton Anxiety Rating Scale score
timeFrame: Baseline (Randomization Visit) to 2 hours after dosing
measure: Hamilton Anxiety Rating Scale score
timeFrame: Baseline (Randomization Visit) to 24 hours after dosing
measure: Self-reported overall sense of wellbeing
timeFrame: 2 hours after dosing
measure: Self-reported hurt feelings score
timeFrame: 2 hours after dosing
measure: Self-reported tense feelings score
timeFrame: 2 hours after dosing
Locations:
city: North Miami
country: United States
facility: Keystone Clinical Research
state: Florida
Study officials:
affiliation: Allodynic Therapeutics, Inc
name: Annette C Toledano, MD
role: STUDY_DIRECTOR
affiliation: Keystone Clinical Research
name: Natalia Belikova, MD PhD
role: PRINCIPAL_INVESTIGATOR
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