Trial Outcomes & Findings for The Preventive Treatment of Migraine With Low-Dose Naltrexone and Acetaminophen Combination (NCT NCT03194555)
NCT ID: NCT03194555
Last Updated: 2024-04-10
Results Overview
Migraine with or without aura is defined according to the International Classification of Headache Disorders (ICHD)-3rd edition (beta version). Migraine headaches must be moderate or severe and lasting ≥30 minutes. When the patient falls asleep during migraine and wakes up without it, duration of the attack is reckoned until the time of awakening).
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
12 participants
Primary outcome timeframe
From the 28-day baseline period to the last 28 days of the 84-days double-blinded treatment period.
Results posted on
2024-04-10
Participant Flow
Patient recruitment was conducted in a single site in Miami, Florida.
Participant milestones
| Measure |
Low-Dose Naltrexone and Acetaminophen Combination
Low-Dose Naltrexone and Acetaminophen Combination: Twice daily
|
Placebo
Placebo: Twice daily
|
|---|---|---|
|
Overall Study
STARTED
|
6
|
6
|
|
Overall Study
COMPLETED
|
6
|
6
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
The Preventive Treatment of Migraine With Low-Dose Naltrexone and Acetaminophen Combination
Baseline characteristics by cohort
| Measure |
Low-Dose Naltrexone and Acetaminophen Combination
n=6 Participants
Low-Dose Naltrexone and Acetaminophen Combination: Twice daily
|
Placebo
n=6 Participants
Placebo: Twice daily
|
Total
n=12 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
6 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
41.5 years
STANDARD_DEVIATION 14.3 • n=5 Participants
|
39 years
STANDARD_DEVIATION 10.4 • n=7 Participants
|
40 years
STANDARD_DEVIATION 12 • n=5 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
4 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
6 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
African American
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
6 participants
n=5 Participants
|
6 participants
n=7 Participants
|
12 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: From the 28-day baseline period to the last 28 days of the 84-days double-blinded treatment period.Population: Modified intent to treat (mITT) participants included all randomized participants who took study drug.
Migraine with or without aura is defined according to the International Classification of Headache Disorders (ICHD)-3rd edition (beta version). Migraine headaches must be moderate or severe and lasting ≥30 minutes. When the patient falls asleep during migraine and wakes up without it, duration of the attack is reckoned until the time of awakening).
Outcome measures
| Measure |
Low-Dose Naltrexone and Acetaminophen Combination
n=6 Participants
Low-Dose Naltrexone and Acetaminophen Combination: Twice daily
|
Placebo
n=6 Participants
Placebo: Twice daily
|
|---|---|---|
|
Change in Monthly Migraine Days (MMD) From Baseline to the Last 28 Days of Treatment Period.
|
-5.67 days
Standard Deviation 3.2
|
-3.5 days
Standard Deviation 5.56
|
SECONDARY outcome
Timeframe: From the 28-day baseline period to the last 28 days of the 84-days double-blinded treatment period.Population: Modified intent to treat (mITT) participants included all randomized participants who took study drug.
MMD stands for change in Monthly Migraine Days from 28-day baseline to the last 28 days of the double-blind treatment period
Outcome measures
| Measure |
Low-Dose Naltrexone and Acetaminophen Combination
n=6 Participants
Low-Dose Naltrexone and Acetaminophen Combination: Twice daily
|
Placebo
n=6 Participants
Placebo: Twice daily
|
|---|---|---|
|
The Number of Participants With More Than 50% Improvement in the Mean Monthly Migraine Days (MMDs)
|
4 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: From the28-day baseline period to the last 28 days of the 84-day treatment period.Population: Modified intent to treat (mITT) participants included all randomized participants who took study drug.
Outcome measures
| Measure |
Low-Dose Naltrexone and Acetaminophen Combination
n=6 Participants
Low-Dose Naltrexone and Acetaminophen Combination: Twice daily
|
Placebo
n=6 Participants
Placebo: Twice daily
|
|---|---|---|
|
The Number of Participants With More Than 75% Improvement in the Mean Monthly Migraine Days (MMDs)
|
4 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: From the 28-day baseline period to the last 28 days of the 84-day treatment period.Population: Modified intent to treat (mITT) participants included all randomized participants who took study drug.
Outcome measures
| Measure |
Low-Dose Naltrexone and Acetaminophen Combination
n=6 Participants
Low-Dose Naltrexone and Acetaminophen Combination: Twice daily
|
Placebo
n=6 Participants
Placebo: Twice daily
|
|---|---|---|
|
The Number of Participants With 100% Improvement in Mean MMD in the Last 28 Days Double-blinded Treatment Period.
|
3 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: From the 28-day baseline period to the last 28 days of the 84-day treatment period.Population: Modified intent to treat (mITT) participants included all randomized participants who took study drug.
Outcome measures
| Measure |
Low-Dose Naltrexone and Acetaminophen Combination
n=6 Participants
Low-Dose Naltrexone and Acetaminophen Combination: Twice daily
|
Placebo
n=6 Participants
Placebo: Twice daily
|
|---|---|---|
|
Mean Monthly Acute Migraine Medication Treatment Days Change From Baseline to Last 28 Days of Treatment
Baseline acute number of migraine medication treatment days
|
7.67 days
Standard Deviation 2.07
|
8.67 days
Standard Deviation 3.5
|
|
Mean Monthly Acute Migraine Medication Treatment Days Change From Baseline to Last 28 Days of Treatment
Acute migraine medication treatment days in last 28 days of treatment period
|
2.67 days
Standard Deviation 4.32
|
5.5 days
Standard Deviation 3.27
|
|
Mean Monthly Acute Migraine Medication Treatment Days Change From Baseline to Last 28 Days of Treatment
change in monthly acute migraine medication treatment days baseline to last 28 days of treatment
|
-5 days
Standard Deviation 5.37
|
-3.17 days
Standard Deviation 5.49
|
SECONDARY outcome
Timeframe: From the 28-day baseline period to the last 28 days of the 84-day treatment period.Population: Modified intent to treat (mITT) participants included all randomized participants who took study drug.
HIT-6 - headache impact test - was designed to provide a global measure of adverse headache impact. Score range is 36-78, Score ≥ 60 - a very severe impact on life, scored ≤ 49 little to no impact on life. The percent responders were calculated as follows: the change from baseline score divided by the score at the baseline minus 36.
Outcome measures
| Measure |
Low-Dose Naltrexone and Acetaminophen Combination
n=6 Participants
Low-Dose Naltrexone and Acetaminophen Combination: Twice daily
|
Placebo
n=6 Participants
Placebo: Twice daily
|
|---|---|---|
|
The Change in HIT-6 From Baseline to Last 28 Days of Treatment
Baseline (Randomization visit) mean HIT-6, score
|
68.5 score
Standard Deviation 5.68
|
68.83 score
Standard Deviation 5.27
|
|
The Change in HIT-6 From Baseline to Last 28 Days of Treatment
HIT-6 in last 28 days of treatment, score
|
47.83 score
Standard Deviation 17.69
|
58 score
Standard Deviation 12.08
|
|
The Change in HIT-6 From Baseline to Last 28 Days of Treatment
The change in HIT-6 from baseline to last 28 days of treatment, score
|
-20.67 score
Standard Deviation 19.08
|
-10.83 score
Standard Deviation 12.98
|
OTHER_PRE_SPECIFIED outcome
Timeframe: From baseline to month 3 of the treatment period.Population: Modified intent to treat (mITT) participants included all randomized participants who took study drug,
Average of PIRS-20, (0-60 = higher with difficulty with sleep)
Outcome measures
| Measure |
Low-Dose Naltrexone and Acetaminophen Combination
n=6 Participants
Low-Dose Naltrexone and Acetaminophen Combination: Twice daily
|
Placebo
n=6 Participants
Placebo: Twice daily
|
|---|---|---|
|
The Change in Mean PIRS-20 From Baseline to Last 7 Days of Treatment.
Baseline (Randomization visit) mean PIRS-20, score
|
32.67 score
Standard Deviation 16.97
|
31.83 score
Standard Deviation 7.03
|
|
The Change in Mean PIRS-20 From Baseline to Last 7 Days of Treatment.
PIRS-20 in last week of treatment period, score
|
10 score
Standard Deviation 19.32
|
20.83 score
Standard Deviation 14.39
|
|
The Change in Mean PIRS-20 From Baseline to Last 7 Days of Treatment.
The change in PIRS-20 from baseline to last week of treatment, score
|
-22.67 score
Standard Deviation 22.64
|
-11 score
Standard Deviation 8.92
|
OTHER_PRE_SPECIFIED outcome
Timeframe: From baseline to month 3 of the treatment period.Population: Modified intent to treat (mITT) participants included all randomized participants who took study drug.
Outcome measures
| Measure |
Low-Dose Naltrexone and Acetaminophen Combination
n=6 Participants
Low-Dose Naltrexone and Acetaminophen Combination: Twice daily
|
Placebo
n=6 Participants
Placebo: Twice daily
|
|---|---|---|
|
The Number of Participants Who Had an Improvement in Patient Global Impression of Change (PGIC) at End of Treatment
PGIC, Change≥2 points, (%)
|
4 Participants
|
2 Participants
|
|
The Number of Participants Who Had an Improvement in Patient Global Impression of Change (PGIC) at End of Treatment
PGIC, Change=3 points, (%)
|
4 Participants
|
2 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: From baseline to month 3 of the treatment period.Population: Modified intent to treat (mITT) participants included all randomized participants who took study drug.
Outcome measures
| Measure |
Low-Dose Naltrexone and Acetaminophen Combination
n=6 Participants
Low-Dose Naltrexone and Acetaminophen Combination: Twice daily
|
Placebo
n=6 Participants
Placebo: Twice daily
|
|---|---|---|
|
The Number of Participants Reporting Patients' Satisfaction Level
Satisfied or very satisfied (level 2 or 3)
|
4 Participants
|
2 Participants
|
|
The Number of Participants Reporting Patients' Satisfaction Level
Very satisfied (level 3)
|
4 Participants
|
2 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: From baseline to month 3 of the treatment period.Outcome measures
| Measure |
Low-Dose Naltrexone and Acetaminophen Combination
n=6 Participants
Low-Dose Naltrexone and Acetaminophen Combination: Twice daily
|
Placebo
n=6 Participants
Placebo: Twice daily
|
|---|---|---|
|
Mean Monthly Migraine Hours Change From Baseline to Last 28 Days of Treatment
Baseline, hours
|
70.78 Hours
Standard Deviation 47.6
|
54.44 Hours
Standard Deviation 36.21
|
|
Mean Monthly Migraine Hours Change From Baseline to Last 28 Days of Treatment
Monthly migraine hours in last 28 days of treatment, hours
|
24.65 Hours
Standard Deviation 35.23
|
37.07 Hours
Standard Deviation 38.05
|
|
Mean Monthly Migraine Hours Change From Baseline to Last 28 Days of Treatment
The change in monthly migraine hours from baseline to last 28 days of treatment, hours
|
-46.13 Hours
Standard Deviation 59.44
|
-17.37 Hours
Standard Deviation 41.11
|
OTHER_PRE_SPECIFIED outcome
Timeframe: From baseline to month 3 of the treatment periodPopulation: Modified intent to treat (mITT) participants included all randomized participants who took study drug.
Outcome measures
| Measure |
Low-Dose Naltrexone and Acetaminophen Combination
n=6 Participants
Low-Dose Naltrexone and Acetaminophen Combination: Twice daily
|
Placebo
n=6 Participants
Placebo: Twice daily
|
|---|---|---|
|
Change in at Least Moderate Migraine Days in Treatment
Mean monthly at least moderate Headaches days at baseline
|
8.33 days
Standard Deviation 2.73
|
9 days
Standard Deviation 2.45
|
|
Change in at Least Moderate Migraine Days in Treatment
Mean at least moderate migraine days in the last 28 days of the treatment period
|
3.67 days
Standard Deviation 5.57
|
6.17 days
Standard Deviation 4.54
|
|
Change in at Least Moderate Migraine Days in Treatment
The change in at least moderate migraine days from baseline to the last 28 days of treatment period
|
-4.78 days
Standard Deviation 4.42
|
-2.83 days
Standard Deviation 5.74
|
OTHER_PRE_SPECIFIED outcome
Timeframe: From baseline to month 3 of the treatment period.Population: Modified intent to treat (mITT) participants included all randomized participants who took study drug.
Outcome measures
| Measure |
Low-Dose Naltrexone and Acetaminophen Combination
n=6 Participants
Low-Dose Naltrexone and Acetaminophen Combination: Twice daily
|
Placebo
n=6 Participants
Placebo: Twice daily
|
|---|---|---|
|
The Number of Participants Who Achieved the Percentage of Response in at Least Moderate Migraine Days Baseline to Last 28 Days of Treatment
≥50%
|
4 Participants
|
2 Participants
|
|
The Number of Participants Who Achieved the Percentage of Response in at Least Moderate Migraine Days Baseline to Last 28 Days of Treatment
≥75%
|
4 Participants
|
1 Participants
|
|
The Number of Participants Who Achieved the Percentage of Response in at Least Moderate Migraine Days Baseline to Last 28 Days of Treatment
≥90%
|
3 Participants
|
1 Participants
|
|
The Number of Participants Who Achieved the Percentage of Response in at Least Moderate Migraine Days Baseline to Last 28 Days of Treatment
100%
|
3 Participants
|
1 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: From baseline to month 3 of the treatment period.Population: Modified intent to treat (mITT) participants included all randomized participants who took study drug.
Outcome measures
| Measure |
Low-Dose Naltrexone and Acetaminophen Combination
n=6 Participants
Low-Dose Naltrexone and Acetaminophen Combination: Twice daily
|
Placebo
n=6 Participants
Placebo: Twice daily
|
|---|---|---|
|
Mean Severe Headache Days Change From Baseline to Last 28 Days of Treatment
Mean monthly severe headaches days at baseline
|
4.83 days
Standard Deviation 1.72
|
4.33 days
Standard Deviation 2.88
|
|
Mean Severe Headache Days Change From Baseline to Last 28 Days of Treatment
Mean severe headache days in the last 28 days of the treatment period
|
2.67 days
Standard Deviation 3.93
|
2.5 days
Standard Deviation 3.02
|
|
Mean Severe Headache Days Change From Baseline to Last 28 Days of Treatment
The change in severe headache days from baseline to the last 28 days of the treatment period
|
-2.17 days
Standard Deviation 2.79
|
-1.83 days
Standard Deviation 3.87
|
Adverse Events
Low-Dose Naltrexone and Acetaminophen Combination
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Low-Dose Naltrexone and Acetaminophen Combination
n=6 participants at risk
Low-Dose Naltrexone and Acetaminophen Combination: Twice daily
|
Placebo
n=6 participants at risk
Placebo: Twice daily
|
|---|---|---|
|
General disorders
Dry Mouth
|
16.7%
1/6 • One month follow-up after 3 months of treatment
The safety population included all the 12 randomized patients who took the study drug (ITT).
|
0.00%
0/6 • One month follow-up after 3 months of treatment
The safety population included all the 12 randomized patients who took the study drug (ITT).
|
|
General disorders
Fatigue
|
16.7%
1/6 • One month follow-up after 3 months of treatment
The safety population included all the 12 randomized patients who took the study drug (ITT).
|
16.7%
1/6 • One month follow-up after 3 months of treatment
The safety population included all the 12 randomized patients who took the study drug (ITT).
|
|
Gastrointestinal disorders
Gastroesophageal Reflux
|
16.7%
1/6 • One month follow-up after 3 months of treatment
The safety population included all the 12 randomized patients who took the study drug (ITT).
|
0.00%
0/6 • One month follow-up after 3 months of treatment
The safety population included all the 12 randomized patients who took the study drug (ITT).
|
|
General disorders
Heavy Breathing
|
16.7%
1/6 • One month follow-up after 3 months of treatment
The safety population included all the 12 randomized patients who took the study drug (ITT).
|
16.7%
1/6 • One month follow-up after 3 months of treatment
The safety population included all the 12 randomized patients who took the study drug (ITT).
|
|
General disorders
Nausea
|
16.7%
1/6 • One month follow-up after 3 months of treatment
The safety population included all the 12 randomized patients who took the study drug (ITT).
|
0.00%
0/6 • One month follow-up after 3 months of treatment
The safety population included all the 12 randomized patients who took the study drug (ITT).
|
|
General disorders
Palpitations
|
16.7%
1/6 • One month follow-up after 3 months of treatment
The safety population included all the 12 randomized patients who took the study drug (ITT).
|
0.00%
0/6 • One month follow-up after 3 months of treatment
The safety population included all the 12 randomized patients who took the study drug (ITT).
|
|
General disorders
Somnolence
|
16.7%
1/6 • One month follow-up after 3 months of treatment
The safety population included all the 12 randomized patients who took the study drug (ITT).
|
16.7%
1/6 • One month follow-up after 3 months of treatment
The safety population included all the 12 randomized patients who took the study drug (ITT).
|
|
General disorders
Vomiting
|
16.7%
1/6 • One month follow-up after 3 months of treatment
The safety population included all the 12 randomized patients who took the study drug (ITT).
|
0.00%
0/6 • One month follow-up after 3 months of treatment
The safety population included all the 12 randomized patients who took the study drug (ITT).
|
Additional Information
Dr. Annette Toledano, Sponsor-Investigator
Allodynic Therapeutics, Inc.
Phone: +13058956808
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place