Conditions: Migraine
Keywords: Migraine AXS-07 Meloxicam Rizatriptan Axsome Axsome Therapeutics MoSEIC meloxicam
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 1594
Healthy volunteers: no

Brief summary:
AXS-07 is an oral, investigational medicine consisting of MoSEIC meloxicam and rizatriptan, which is being developed for the acute treatment of migraine with or without aura in adults. AXS-07 tablets are formulated to provide an enhanced rate of absorption of meloxicam. This study is designed to evaluate the efficacy and safety of AXS-07 compared to meloxicam, rizatriptan, and placebo for the treatment of a migraine attack.

This is a randomized, double-blind, 4-arm, parallel group, single-dose, placebo-controlled trial. Subjects who successfully complete screening and continue to meet all entry criteria will be randomly assigned to take one dose of either AXS-07, meloxicam, rizatriptan, or placebo upon the occurrence of a qualifying migraine.

Detailed description:

Arms:
arm 1: Taken once upon a qualifying migraine arm 2: Taken once upon a qualifying migraine arm 3: Taken once upon a qualifying migraine arm 4: Taken once upon a qualifying migraine

Interventions: intervention 1: AXS-07 (MoSEIC meloxicam and rizatriptan) intervention 2: Meloxicam intervention 3: Rizatriptan intervention 4: Placebo
Intervention descriptions: intervention 1: AXS-07 taken once upon onset of a qualifying migraine. intervention 2: Meloxicam taken once upon onset of a qualifying migraine. intervention 3: Rizatriptan taken once upon onset of a qualifying migraine. intervention 4: Placebo taken once upon onset of a qualifying migraine.

Protocol document:
Prot_SAP_000.pdf: 
Document Type: Protocol 
Protocol Title: MOMENTUM (Maximizing Outcomes in Treating Acute Migraine): A Randomized, 
Double-blind, Single-dose, Placebo-controlled Study to Assess the Efficacy and Safety of AXS-07 
(meloxicam and rizatriptan) for the Acute Treatment of Migraine in Adults.
ClinicalTrials.gov Identifier:  NCT03896009
Document Date: January 16, 2019 
Certain information within this protocol has been redacted to protect either personally identifiable 
information (PII) or company confidential information (CCI). 
This may include, but is not limited to, redaction of the following: 
•
Named persons or organizations associated with the study.
•
Proprietary information, such as scales or coding systems, which are considered confidential 
information.
•
Other information as needed to protect the confidentiality of Axsome Therapeutics, personal 
information, or to otherwise protect the integrity of the clinical study.


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PROTOCOL 
 
COMPOUND 
NAME/NUMBER: 
 
AXS-07 
PROTOCOL NUMBER: 
 
AXS-07-301 
 
 
 
DEVELOPMENT PHASE: 
 
Phase 3 
PROTOCOL TITLE: 
MOMENTUM (Maximizing Outcomes in Treating Acute Migraine): 
A Randomized, Double-blind, Single-dose, Placebo-controlled 
Study to Assess the Efficacy and Safety of AXS-07 (meloxicam and 
rizatriptan) for the Acute Treatment of Migraine in Adults. 
 
PROTOCOL VERSION: 
 
Original 
PROTOCOL DATE: 
 
January 16, 2019 
 
 
This study will be performed in compliance with Good Clinical Practices and applicable 
regulatory requirements, including the archiving of essential documents. Information contained 
in this protocol is confidential in nature, and may not be used, divulged, published, or otherwise 
disclosed to others except to the extent necessary to obtain approval of the institutional review 
board or independent ethics committee, or as required by law. Persons to whom this information 
is disclosed should be informed that this information is confidential and may not be further 
disclosed without the express permission of Axsome Therapeutics, Inc. 
 
 


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APPROVAL SIGNATURES 
 
PROTOCOL NUMBER: 
AXS-07-301 
PROTOCOL TITLE:  
MOMENTUM (Maximizing Outcomes in Treating Acute Migraine): 
A Randomized, Double-blind, Single-dose, Placebo-controlled Study 
to Assess the Efficacy and Safety of AXS-07 (meloxicam and 
rizatriptan) for the Acute Treatment of Migraine in Adults. 
 
Protocol Version:  
Original: January 16, 2019 
 
I, the undersigned, have read this protocol and confirm that to the best of my knowledge it 
accurately describes the planned conduct of the study. 
  
 
 
 
 




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1. SYNOPSIS 
 
PRODUCT 
NAME/NUMBER 
AXS-07  
PROTOCOL NUMBER 
AXS-07-301 
DEVELOPMENT 
PHASE 
Phase 3 
PROTOCOL TITLE 
MOMENTUM (Maximizing Outcomes in Treating Acute Migraine): 
A Randomized, Double-blind, Single-dose, Placebo-controlled Study to Assess the Efficacy and 
Safety of AXS-07 (meloxicam and rizatriptan) for the Acute Treatment of Migraine in Adults with 
Inadequate Response to Prior Acute Treatments. 
INDICATION 
Acute treatment of migraine with or without aura in adults. 
OBJECTIVES 
Primary Objective: 
To evaluate the effect of AXS-07 as compared to placebo in the acute treatment of migraine 
headache in adults as evaluated by the following two co-primary efficacy variables:  1) pain freedom 
at Hour 2 and 2) absence of the most bothersome symptom (MBS; nausea, photophobia, or 
phonophobia) at Hour 2. 
Key Secondary Objectives: 
 
To assess the effect of AXS-07 on sustained headache pain freedom between Hour 2 and Hour 24. 
Secondary Objectives: 
To assess the effect of AXS-07 on: 
• 
Percentage of subjects with headache pain relief at Hour 2. 
• 
Change from baseline in headache pain relief over time. 
• 
Percentage of subjects with headache pain freedom over time. 
• 
Time to headache pain freedom. 
• 
Time to headache pain relief. 
• 
Time to sustained headache freedom through Hour 24. 
• 
Percentage of subjects able to perform normal activity over time. 
• 
Patient Global Impression of Change (PGI-C) scores at Hour 2. 
• 
Percentage of subjects with absence of MBS over time. 
• 
Percentage of subjects MBS free over time. 
• 
Percentage of subjects with headache pain freedom between Hours 2 and 48 (48-hour 
sustained pain-free).   
• 
Percentage of subjects with pain relapse, where relapse is defined as the return of headache 
within 48 hours after dosing, for subjects who were pain free at Hour 2. 
• 
Percentage of subjects using rescue medication. 
• 
Time to rescue medication. 
• 
Treatment response based on presence of allodynia, BMI, pain intensity, presence of 
depression, and use of preventive medication. 
STUDY DESIGN 
This study is a Phase 3, multicenter, randomized, double-blind, 4-arm, parallel group, single-dose, 
placebo-controlled trial to evaluate the efficacy and safety of AXS-07 in subjects with migraine 
attacks. The co-primary efficacy endpoints are the 1) percentage of subjects with headache pain 
freedom at Hour 2, with headache pain freedom defined as a reduction in headache severity from 
moderate or severe pain to no pain and 2) absence of the MBS (nausea, photophobia, or 
phonophobia) at Hour 2, with the MBS defined at the onset of migraine, prior to drug administration. 
The key secondary endpoint, which will be used to establish contribution of the individual 
components of AXS-07 to efficacy, is sustained freedom from headache pain between Hour 2 and 
24.  


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To qualify for the study, subjects must be 18 to 65 years of age, have an established diagnosis of 
migraine (history indicating the presence of migraine for at least 1 year) with or without aura as 
defined by the International Classification of Headache Disorder, 3rd Edition (ICHD-3), experience 
an average of 2 to 8 moderate or severe migraine attacks per month (no more than 10 migraine days 
per month) over the past 3 months, and have a history of inadequate response to prior acute migraine 
treatments. An inadequate response is defined as a score of ≤7 on the Migraine Treatment 
Optimization Questionnaire (m-TOQ-4), corresponding to moderate or worse response to prior 
treatments over the preceding 4 weeks. 
Subjects who successfully complete the Screening visit (Visit 1) and continue to meet all entry 
criteria, will be randomly assigned at Visit 2 (randomization) to receive, in a 2:2:2:1 ratio, AXS-07, 
rizatriptan 10 mg, meloxicam 20 mg, or placebo, dispensed for at-home treatment of a single 
migraine attack. Subjects will have approximately 12 weeks to complete the study, which consists 
of a 14-day screening period followed by 10 weeks to complete treatment. A follow-up visit (Visit 
3) will occur after treating one attack (to be scheduled as soon as possible but within 1 week after 
dosing), or within 10 weeks after randomization (Visit 2) if the study medication is not used. 
Treatment and Assessments:  
After randomization, upon the occurrence of the next qualifying migraine attack (defined as the 
onset of moderate or severe pain intensity) subjects will take the study medication (one tablet). The 
study medication is to be taken orally with water. 
Headache Diary 
Headache pain intensity (measured by a 4-point rating scale; none, mild, moderate, or severe), will 
be recorded by subjects in the Headache Diary immediately prior to taking study medication, and at 
the following time points after taking study medication: 15, 30 and 45 minutes, and 1, 1.5, 2, 4, 12, 
16, 24, and 48 hours after dosing.   
Prior to dosing, the subject will define their most bothersome symptom (nausea, photophobia, 
phonophobia) and assess the presence or absence of each symptom at the following timepoints: 30 
minutes and 1, 2, and 4 hours after dosing. In addition, functional disability with regard to daily 
activities (on a 4-point scale) will be recorded pre-dose and at 30 minutes, 1, 2, 4, 12, and 24 hours 
after dosing. Subjects will assess PGI-C 2 hours after dosing. 
Subjects will be instructed to follow restrictions regarding use of other medications, including rescue 
medications, and must not sleep or nap for at least 2 hours after taking study drug. 
A physical examination will be performed at Screening. Samples for clinical laboratory testing 
(hematology and chemistry) will be collected at Screening. A urine pregnancy test will be performed 
at Screening and randomization (Visit 2). At each visit, vital signs will be assessed and concomitant 
medications will be reviewed.  Adverse events will be assessed following dosing with study drug. 




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administration and for the duration of the trial. Reliable methods of contraception include 
hormonal, double-barrier methods (e.g., condom and diaphragm, condom and foam, 
condom and sponge, each with spermicidal jellies or cream) and intrauterine devices. 
12. Is willing and able to complete the Headache Diary. 
Exclusion criteria: 
A subject will be excluded from the study if the subject meets any of the following criteria: 
1. Has a known history of allergic reaction, hypersensitivity, or clinically significant 
intolerance to rizatriptan or another triptan, acetaminophen, aspirin, or any NSAIDs, 
including meloxicam; history of NSAID-induced bronchospasm (subjects with the triad of 
asthma, nasal polyps, and chronic rhinitis are at greater risk for bronchospasm and should 
be considered carefully); or hypersensitivity, allergy, or significant reaction to any 
ingredients of the study drug. 
2. Has experienced > 8 migraine attacks monthly during either of the 2 months before 
screening. 
3. Is suffering from cluster headaches (every day or every other day), or other types of 
migraine. 
4. Has experienced chronic daily headache (≥ 15 days per month of non-migraine headaches 
during each of the 3 months before screening). 
5. Has a history of brain stem aura, ophthalmoplegic or hemiplegic migraine headache, or any 
potentially serious neurological condition that is associated with headache. 
6. Has confirmed or suspected cardiovascular or cerebrovascular disease. 
7. Has history, symptoms, or significant risk factors for ischemic heart (e.g., silent ischemia, 
angina, myocardial infarction); coronary artery vasospasm; arrhythmia (e.g., atrial 
fibrillation or flutter, frequent premature ventricular contractions, atrioventricular block); 
clinically significant findings on ECG; cardiac accessory conduction pathway disorder 
(e.g., Wolff-Parkinson-White syndrome); or other cardiovascular disease. 
8. Has history of stroke, transient ischemic attack or other cerebrovascular syndrome; 
peripheral vascular disease; or ischemic bowel disease. 
9. Has uncontrolled hypertension (diastolic blood pressure > 95 mm Hg or systolic blood 
pressure > 160 mm Hg). 
10. Is a female subject and is taking estrogenic contraceptives who, in addition, smokes and 
has experienced migraine attack with aura. 
11. Has a concurrent medical condition(s) that requires the chronic use of analgesics, narcotic 
analgesics, steroidal or non-steroidal anti-inflammatory agents, tranquilizers, sedatives-
hypnotics, antipsychotics, or nitrates or their use for prevention of migraine attacks. 
12. Clinically significant abnormalities indicated from the medical history, physical exam, 
clinical chemistry, hematology, urine drug screen. 
13. Had a diagnosis or suspicion of drug induced or chronic daily headaches within 1 year. 
14. Has used MAO inhibitor, lithium, methylergonovine, or cimetidine in the 2 weeks before 
randomization, 
15. Has a history or current diagnosis of any clinically significant cardiac, pulmonary, 
neurological, immunological, hematological, gastrointestinal, hepatic, renal, or endocrine 
disease or any other condition which, in the opinion of the investigator, could compromise 
the subject’s welfare, ability to communicate with the study staff, or otherwise 
contraindicate study participation. 
16. Has a history or current diagnosis of schizophrenia, or another significant psychiatric 
disorder which, in the opinion of the investigator, would affect the subject’s ability to 
comply with the study requirements. Stable bipolar disease and stable major depressive 
disorder is allowed.  


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17. Is receiving systemic chemotherapy, has an active malignancy of any type, or has been 
diagnosed with cancer within 5 years before Screening (excluding squamous or basal cell 
carcinoma of the skin). 
18. Has a known or suspected history of alcoholism or drug abuse or misuse within 1 year 
before Screening or evidence of tolerance or physical dependence before study drug 
administration. 
19. Has, or has had within 1 year, any clinically significant gastrointestinal (GI) disorder, 
including peptic or gastric ulcers or GI bleeding. 
20. Has a medical or surgical condition of the GI system (including motility dysfunction) or 
renal system that might significantly alter the absorption, distribution, or excretion of any 
drug substance. 
21. Is considered by the investigator, for any reason (including, but not limited to, the risks 
described as precautions, warnings, and contraindications in the current version of the 
investigator’s brochure for AXS-07 tablets), to be an unsuitable candidate to receive the 
study drug. 
22. Is using or expects to use concurrent analgesic, NSAIDs (except aspirin at a dose of 
≤ 325 mg daily for cardiovascular prophylaxis) during the trial. 
23. Is currently receiving or expects to use anticoagulants (e.g., heparin, warfarin, nutritional 
supplements having anticoagulant properties); or has bleeding problems, coagulation 
abnormalities, active blood dyscrasia, hemorrhagic disease, anemia, porphyria, 
phenylketonuria, bone marrow suppression, or immunosuppression. 
24. Is currently receiving propanol or has received propranolol within 2 weeks prior to 
randomization.  
25. Has been treated with agents that could affect the analgesic response (such as central alpha 
agents adrenergic [clonidine and tizanidine]) within 2 weeks before randomization or 
expects to use such agents during the treatment period. 
26. Has tested positive for drugs of abuse (including medical marijuana) on the urine drug 
screen at randomization (Visit 2). Subjects who test positive at Screening and can produce 
a prescription for the medication from their physician may be considered for study 
enrollment at the discretion of the investigator. 
27. Has clinically significant abnormalities indicated from the medical history, physical exam, 
and laboratory findings at Screening that in the investigator’s opinion contraindicates study 
participation. 
28. Is HIV positive. 
29. Has previously participated in another clinical study of AXS-07 or received any 
investigational drug or device or investigational therapy within 30 days before Screening. 
30. Has significant difficulty swallowing tablets or is unable to tolerate oral medication. 
INVESTIGATIONAL 
PRODUCT 
AXS-07 (20 mg meloxicam/10 mg rizatriptan) tablet for oral administration.  
REFERENCE 
PRODUCT 
Matching meloxicam, rizatriptan, and placebo tablets for oral administration. 
TREATMENT 
REGIMENS 
The study drug (AXS-07, meloxicam, rizatriptan, or placebo) is to be taken orally with water within 
30 minutes of onset of a migraine attack of moderate to severe pain intensity.  
PRINCIPAL 
INVESTIGATOR 
Multi-center 
PLANNED STUDY 
SITES 
Up to 100 study sites in North America  




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STUDY AND 
TREATMENT 
DURATION 
The duration of participation will be up to 12 weeks as follows: 
Screening Period: 14 days. 
Treatment Period: up to 10 weeks.