CompletedNCT02176018Updated Apr 3, 2018Results posted

Nuedexta for the Prevention and Modification of Disease Progression in Episodic Migraine

A Phase 2 interventional study of Dextromethorphan and quinidine and Placebo in Episodic Migraine, sponsored by Cady, Roger, M.D.. Completed at 5 sites in United States. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2018-04-03.

Sponsored by Cady, Roger, M.D. · Phase 2, Interventional, and Treatment

Phase: Phase 2
Study type: Interventional
Enrollment: 76
Allocation: Randomized
Ages: 18 Years to 65 Years
Sex: All

Study summary

The purpose of this study is to evaluate the efficacy and effectiveness of daily dextromethorphan/quinidine (Nuedexta) in reducing the frequency and progression of episodic migraine.

Read the detailed description

This is a double-blind, placebo-controlled, randomized, multi-center study to be conducted at the Headache Care Center in Springfield, MO and two other clinics in the United States. Approximately 45 subjects, 18 to 65 years of age, with frequent episodic migraine (6-14 days per month), with (1.2) or without aura (1.1) as defined by ICHD-3beta, will enter a 1-month baseline period to confirm the migraine diagnosis, as well as establish baseline characteristics. At Visit 1, subjects must not have a history of utilization of acute treatment greater than 14 days per month in the preceding 3 month period. Subjects must have a current history of ICHD-3beta migraine with 6-14 migraine days per month in the 3 months prior to the study enrollment. Eligible subjects will be randomly assigned to one of two groups in a 1:1 ratio. Randomization will occur using a computer-generated allocation schedule. Subjects meeting entrance criteria as determined both at screening and through the review of the baseline headache diary will be given the lowest available allocation number for that site. Migraine preventative use is permitted if the subject has been on a stable does for at least 2 months prior to screening and has not failed more than 3 migraine preventatives due to lack of efficacy. The study will consist of 5 office visits per subject: Visit 1 - screening, Visit 2 - randomization, and Visits 3 to 5 - three-month treatment period. During the baseline period, the subject will treat migraines with their current preferred acute treatment of choice.

Conditions studied

Episodic Migraine

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Keywords

Episodic Migraine
Migraine
Headache

In context

Migraine Disorders

1,528 studies on the registry are indexed under Migraine Disorders; 299 are open to participants now.

This study's enrollment of 76 is close to the median of 80 across 1,175 interventional studies indexed under Migraine Disorders.

Browse Migraine Disorders studies →

Lead sponsor

Cady, Roger, M.D. is the lead sponsor of 12 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 65 Years
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

male or female, in otherwise good health, 18 to 65 years of age.
history of frequent episodic migraine for at least 3 months as defined by 6-14 migraine days per month with or without aura according to the ICHD-3beta or a migraine treated with an ergot or triptan which resulted in relief.
onset of migraine before age 50.
stable history of headache at least 3 months prior to screening.
if using daily migraine preventive medications for migraine or for other medical conditions (e.g. propranolol being used for hypertension) and has been on a stable dose and regimen for at least 2 months prior to beginning the baseline period.
female, of childbearing potential, and agrees to maintain true abstinence or use (or have their partner use) one of the listed methods of birth control for the duration of the study: hormonal contraceptive, intrauterine device (IUD), condoms, diaphragm, and/or vasectomy. The use of barrier contraceptive (condom or diaphragm) should always be supplemented with the use of a spermicide. Note: To be considered not of childbearing potential, subject must be 6 weeks post-surgical bilateral oophorectomy, hysterectomy, or bilateral tubal ligation, or postmenopausal for at least one year.

Exclusion criteria

Exclusion Criteria:

unable to understand the study requirements, the informed consent, or complete headache records as required per protocol.
pregnant, actively trying to become pregnant, or breast-feeding.
female of childbearing potential not using adequate contraceptive measures.
experienced the following migraine variants: basilar migraine, aura without headache, familial hemiplegic migraine, complicated migraine, ophthalmoplegic migraine and retinal migraine.
history of Medication Overuse Headache (Appendix II) in the 3 months prior to study enrollment or during the baseline phase.
history of acute migraine treatment greater than 14 days per month in 3 months prior to screening.
history of 3 or more failed preventative medications due to lack of efficacy for prophylactic treatment of migraine after an adequate therapeutic trial.
received onabotulinumtoxinA injections within 3 months prior to screening and/or will receive onabotulinumtoxinA injections during the study.
abused, in the opinion of the Investigator, any of the following drugs, currently or within the past 1 year: opioids, alcohol, barbiturates, benzodiazepine, cocaine.
taken, or plans to take: a monoamine oxidase inhibitor (MAOI) including herbal preparations containing St. John's wort (Hypericum perforatum) within 14 days of Visit 1, concomitant medications and/or foods containing dextromethorphan, quinidine, quinine, mefloquine, paxil, dicyclomine, digitalis, thioridazine or pimozide (medications that prolong QT interval) anytime within the 2 weeks prior to screening through 2 weeks post final study treatment.
history of hypersensitivity to medications containing dextromethorphan.
history of hypersensitivity to medications or foods containing quinidine.
at an increased risk of developing serotonin syndrome, in the opinion of the investigator.
history of impaired hepatic or renal function that, in the investigator's opinion, contraindicates participation in this study.
unstable neurological condition or a significantly abnormal neurological examination with focal signs or signs of increased intracranial pressure.
cardiovascular disease (ischemic heart disease, including angina pectoris, myocardial infarction, documented silent ischemia, or with Prinzmetal's angina); has symptoms of ischemic heart disease, ischemic abdominal syndromes, peripheral vascular disease or Raynaud's Syndrome.
ECG results outside normal limits (> 470 msec), prolonged QT interval, congenital long QT syndrome, torsades de pointes, or complete AV block.
has uncontrolled hypertension (≥ 140/90mmHg in either the systolic or diastolic measurements in 2 out of 3 BP readings at screening).
serious illness, or an unstable medical condition, one that could require hospitalization, or could increase the risk of adverse events, in the opinion of the investigator.
any psychiatric disorder with psychotic features and any other psychiatric disorder not stable or well controlled, that would interfere in their ability to complete study activities.
received any investigational agents within 30 days prior to Visit 1.
plans to participate in another clinical study at any time during this study.

Study design

Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Triple (Participant, Care provider, Investigator)
Enrollment: 76 participants (actual)

Study arms

Active comparator
Nuedexta
One capsule will be taken (dextromethorphan HB and quinidine sulfate, 20 mg/10 mg) daily for seven days. On the eight day and for the remainder of the study 2 capsule will be taken twice a day. Medication will be taking daily for a total of 3 months.
Drug: Dextromethorphan and quinidine
Placebo comparator
Placebo
One capsule will be taken of placebo to match daily for seven days. On the eight day and for the remainder of the study 2 capsule will be taken twice a day. Medication will be taking daily for a total of 3 months.
Drug: Placebo

Interventions

DrugDextromethorphan and quinidine
Also known as: Nuedexta
DrugPlacebo

What researchers measure

Primary outcomes

Headache Days in Each Treatment Period Month
The average number of headache days at treatment period months 1, 2, and 3 (28 day periods for each month) for the Nuedexta arm and the Placebo arm. Headache days were defined as any patient reported head pain during the prior 24 hour period.
Time frame: Treatment Month 1, Treatment Month 2, and End of Treatment Period Month 3 (Day 116)

Secondary outcomes

Headache Days in Treatment Period Month 3
The average number of headache days at treatment period month 3 (28 day period) for the Nuedexta arm and the Placebo arm. Headache days were defined as any patient reported head pain during the prior 24 hour period.
Time frame: End of Treatment Period Month 3 (Day 116)
Migraine Days in Each Treatment Period Month
The average number of migraine days at treatment period months 1, 2, and 3 (28 day periods for each month) for the Nuedexta arm and the Placebo arm.
Time frame: Treatment Month 1, Month 2, and End of Treatment Period Month 3 (Day 116)
Headache Severity in Each Treatment Period Month
The average headache severity at treatment period months 1, 2, and 3 (28 day periods for each month) for the Nuedexta arm and the Placebo arm. Headache pain severity was measured on a scale from 1 = Mild, to 3 = Severe. Higher numbers indicating more severe headache pain.
Time frame: Treatment Month 1, Month 2, and End of Treatment Period Month 3 (Day 116)
Headache Duration in Each Treatment Period Month
The average headache duration (time of onset to pain free) at treatment period months 1, 2, and 3 (28 day periods for each month) for the Nuedexta arm and the Placebo arm. Headache duration was measured in hours.
Time frame: Treatment Month 1, Month 2, and End of Treatment Period Month 3 (Day 116)
50% Headache Reduction
The number of subjects with at least a 50% reduction in number of headache days comparing baseline to each visit (treatment period months 1, 2, and 3: 28 day for each month) in the Nuedexta arm vs. the placebo arm.
Time frame: Baseline (Day 0) to Treatment Period Month 3 (Day 116)
Acute Medication Use in Each Treatment Period Month
The average number of doses of acute medication taken at treatment period months 1, 2, and 3 (28 day periods for each month) for the Nuedexta arm and the Placebo arm
Time frame: Treatment Month 1, Month 2, and End of Treatment Period Month 3 (Day 116)
Migraine Disability Assessment Scale (MIDAS)
MIDAS scores at Visit 2 and Visit 5 (end of treatment period month 3). The MIDAS is a questionnaire consisting of five (5) "how many days in the last 3 months..." questions. Thus the range for the MIDAS is from, 0 to a maximum possible score 93 (31 days X 3 months). The MIDAS is scored according to the following: 0-5, MIDAS Grade I, Little or No Disability 6-10, MIDAS Grade II, Mild Disability 11-20, MIDAS Grade III, Moderate Disability 21+, MIDAS Grade IV, Severe Disability
Time frame: Visit 2 (Day 28) to Visit 5 (Day 116)
Headache Health Score
Headache Health Score at Visit 2 (Day 28), Visit 3 (Day 57), Visit 4 (Day 85), and Visit 5 (Day 116) for the Nuedexta arm and the placebo arm. The Headache Health Score is measured using a scale from 0 to 100, with higher scores indicating less headache impact on the subject's life.
Time frame: Visit 2 (Day 28), Visit 3 (Day 57), Visit 4 (Day 85), and Visit 5 (Day 116)
Adverse Events
Compare the number of adverse events in the Nuedexta arm vs. the placebo arm.
Time frame: Baseline (Day 0) to Treatment Period Month 3 (Day 116)

Results

Posted Apr 3, 2018

Participant flow

Participant flow — Overall Study
Milestone	Nuedexta	Placebo
Started	22	23
Completed	17	17
Not completed	5	6
Withdrew: Adverse event	0	2
Withdrew: Lost to follow-up	3	1
Withdrew: Protocol violation	1	1
Withdrew: Withdrawal by subject	1	2

Outcome measures

PrimaryHeadache Days in Each Treatment Period Month

The average number of headache days at treatment period months 1, 2, and 3 (28 day periods for each month) for the Nuedexta arm and the Placebo arm. Headache days were defined as any patient reported head pain during the prior 24 hour period.

Time frame:: Treatment Month 1, Treatment Month 2, and End of Treatment Period Month 3 (Day 116)
Reported as:: Mean · Number of Headache days

Headache Days in Each Treatment Period Month
Number of Headache days	Nuedexta	Placebo
Treatment Month 1	7.1 ± 3.31	10.88 ± 6.25
Treatment Month 2	7.05 ± 3.82	9.47 ± 6.15
Treatment Month 3	7.10 ± 3.8	9.77 ± 7.09

SecondaryHeadache Days in Treatment Period Month 3

The average number of headache days at treatment period month 3 (28 day period) for the Nuedexta arm and the Placebo arm. Headache days were defined as any patient reported head pain during the prior 24 hour period.

Time frame:: End of Treatment Period Month 3 (Day 116)
Reported as:: Mean · Number of headache days

Headache Days in Treatment Period Month 3
Number of headache days	Nuedexta	Placebo
Headache Days in Treatment Period Month 3	7.1 ± 3.8	9.77 ± 7.09

SecondaryMigraine Days in Each Treatment Period Month

The average number of migraine days at treatment period months 1, 2, and 3 (28 day periods for each month) for the Nuedexta arm and the Placebo arm.

Time frame:: Treatment Month 1, Month 2, and End of Treatment Period Month 3 (Day 116)
Reported as:: Mean · Number of Migraine days

Migraine Days in Each Treatment Period Month
Number of Migraine days	Nuedexta	Placebo
Treatment Month 1	5.65 ± 3.35	7.65 ± 2.71
Treatment Month 2	5.85 ± 3.48	6.94 ± 4.05
Treatment Month 3	6.05 ± 3.63	7.29 ± 4.3

SecondaryHeadache Severity in Each Treatment Period Month

The average headache severity at treatment period months 1, 2, and 3 (28 day periods for each month) for the Nuedexta arm and the Placebo arm. Headache pain severity was measured on a scale from 1 = Mild, to 3 = Severe. Higher numbers indicating more severe headache pain.

Time frame:: Treatment Month 1, Month 2, and End of Treatment Period Month 3 (Day 116)
Reported as:: Mean · units on a scale

Headache Severity in Each Treatment Period Month
units on a scale	Nuedexta	Placebo
Treatment Month 1	1.69 ± 0.37	2.04 ± 0.43
Treatment Month 2	1.81 ± 0.52	1.96 ± 0.45
Treatment Month 3	1.74 ± 0.46	1.86 ± 0.51

SecondaryHeadache Duration in Each Treatment Period Month

The average headache duration (time of onset to pain free) at treatment period months 1, 2, and 3 (28 day periods for each month) for the Nuedexta arm and the Placebo arm. Headache duration was measured in hours.

Time frame:: Treatment Month 1, Month 2, and End of Treatment Period Month 3 (Day 116)
Reported as:: Mean · Hours

Headache Duration in Each Treatment Period Month
Hours	Nuedexta	Placebo
Treatment Month 1	5.39 ± 2.38	5.30 ± 2.25
Treatment Month 2	6.33 ± 4.06	5.75 ± 2.78
Treatment Month 3	6.60 ± 4.81	5.46 ± 2.72

Secondary50% Headache Reduction

The number of subjects with at least a 50% reduction in number of headache days comparing baseline to each visit (treatment period months 1, 2, and 3: 28 day for each month) in the Nuedexta arm vs. the placebo arm.

Time frame:: Baseline (Day 0) to Treatment Period Month 3 (Day 116)
Reported as:: Count of participants · Participants

50% Headache Reduction
Participants	Nuedexta	Placebo
Treatment Month 1	6	0
Treatment Month 2	7	2
Treatment Month 3	8	8

SecondaryAcute Medication Use in Each Treatment Period Month

The average number of doses of acute medication taken at treatment period months 1, 2, and 3 (28 day periods for each month) for the Nuedexta arm and the Placebo arm

Time frame:: Treatment Month 1, Month 2, and End of Treatment Period Month 3 (Day 116)
Reported as:: Mean · Number of medication doses

Acute Medication Use in Each Treatment Period Month
Number of medication doses	Nuedexta	Placebo
Treatment Month 1	9.45 ± 6.82	13.06 ± 12.30
Treatment Month 2	9.50 ± 7.08	11.41 ± 12.52
Treatment Month 3	11.55 ± 11.01	10.94 ± 12.95

SecondaryMigraine Disability Assessment Scale (MIDAS)

MIDAS scores at Visit 2 and Visit 5 (end of treatment period month 3). The MIDAS is a questionnaire consisting of five (5) "how many days in the last 3 months..." questions. Thus the range for the MIDAS is from, 0 to a maximum possible score 93 (31 days X 3 months). The MIDAS is scored according to the following: 0-5, MIDAS Grade I, Little or No Disability 6-10, MIDAS Grade II, Mild Disability 11-20, MIDAS Grade III, Moderate Disability 21+, MIDAS Grade IV, Severe Disability

Time frame:: Visit 2 (Day 28) to Visit 5 (Day 116)
Reported as:: Mean · units on a scale

Migraine Disability Assessment Scale (MIDAS)
units on a scale	Nuedexta	Placebo
Visit 2 (Day28)	34.95 ± 22.65	32.88 ± 29.95
Visit 5 (Day 116)	22.50 ± 17.41	30.35 ± 42.47

SecondaryHeadache Health Score

Headache Health Score at Visit 2 (Day 28), Visit 3 (Day 57), Visit 4 (Day 85), and Visit 5 (Day 116) for the Nuedexta arm and the placebo arm. The Headache Health Score is measured using a scale from 0 to 100, with higher scores indicating less headache impact on the subject's life.

Time frame:: Visit 2 (Day 28), Visit 3 (Day 57), Visit 4 (Day 85), and Visit 5 (Day 116)
Reported as:: Mean · units on a scale

Headache Health Score
units on a scale	Nuedexta	Placebo
Visit 2 (Day 28)	78.71 ± 5.25	81.07 ± 7.37
Visit 3 (Day 57)	87.62 ± 6.57	80.30 ± 10.62
Visit 4 (Day 85)	87.14 ± 8.31	82.28 ± 10.77
Visit 5 (Day 116)	87.57 ± 6.97	84.10 ± 10.76

SecondaryAdverse Events

Compare the number of adverse events in the Nuedexta arm vs. the placebo arm.

Time frame:: Baseline (Day 0) to Treatment Period Month 3 (Day 116)
Reported as:: Number · Number of Adverse Events

Adverse Events
Number of Adverse Events	Nuedexta	Placebo
Adverse Events	9	35

Adverse events

Collected over 116 days. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Nuedexta	0/22 (0%)	0/22 (0%)	4/22 (18.2%)
Placebo	0/23 (0%)	1/23 (4.3%)	9/23 (39.1%)

Most frequent serious events

Most frequent serious events
Event	Nuedexta	Placebo
Chest PainCardiac disorders	0/22	1/23

Most frequent other events

Most frequent other events
Event	Nuedexta	Placebo
NauseaGastrointestinal disorders	1/22	3/23
Abdominal discomfortGastrointestinal disorders	2/22	0/23
CoughRespiratory, thoracic and mediastinal disorders	0/22	2/23
DizzinessNervous system disorders	0/22	2/23
NasopharyngitisInfections and infestations	0/22	2/23
TachycardiaCardiac disorders	0/22	2/23
SinusitisInfections and infestations	1/22	1/23

Baseline characteristics

Age, Continuous
Age, Continuous(years)	Nuedexta	Placebo	Total
Mean	45.23 ± 9.62	44.17 ± 11.62	44.69 ± 10.58

Sex: Female, Male
Sex: Female, Male(Participants)	Nuedexta	Placebo	Total
Female	21	19	40
Male	1	4	5

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	Nuedexta	Placebo	Total
Hispanic or Latino	0	0	0
Not Hispanic or Latino	22	23	45
Unknown or Not Reported	0	0	0

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	Nuedexta	Placebo	Total
American Indian or Alaska Native	0	0	0
Asian	0	0	0
Native Hawaiian or Other Pacific Islander	0	0	0
Black or African American	1	2	3
White	21	21	42
More than one race	0	0	0
Unknown or Not Reported	0	0	0

Region of Enrollment
Region of Enrollment(participants)	Nuedexta	Placebo	Total
United States	22	23	45

Headache Days
Headache Days(Number of Headache Days)	Nuedexta	Placebo	Total
Mean	10.5 ± 2.5	10.29 ± 5.28	10.4 ± 3.96

Migraine Days
Migraine Days(Number of Migraine days)	Nuedexta	Placebo	Total
Mean	9 ± 2.15	8 ± 2.5	8.54 ± 2.34

Headache Severity
Headache Severity(units on a scale)	Nuedexta	Placebo	Total
Mean	2.02 ± 0.386	2.17 ± 0.326	2.09 ± 0.362

2 further baseline measures are reported on the registry.

Study locations

5 sites

Swedish American Neuro and Headache Center
Rockford, Illinois 61104, United States
The Headache Center
Ridgeland, Mississippi 39157, United States
StudyMetrix Research, LLC
Saint Peters, Missouri 63303, United States
Clinvest
Springfield, Missouri 65807, United States
Island Neurological Associates, PC
Plainview, New York 11803, United States

References and documents

Study documents

Statistical analysis plan · Apr 20, 2016
Study protocol · Apr 20, 2016

Documents are hosted by the registry — open the source record to download them.

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Apr 3, 2018, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT02176018
Lead sponsor: Cady, Roger, M.D.
Collaborators: Avanir Pharmaceuticals
Responsible party: Sponsor
First posted: Jun 26, 2014
Start date: Aug 2014
Primary completion: Feb 2017
Completion: Mar 2017
Results posted: Apr 3, 2018
Last update: Apr 3, 2018

Oversight

Data monitoring committee: No

View the source record on ClinicalTrials.gov ↗

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