Clinical trial NCT04068051
Conditions: Migraine
Keywords: Axsome AXS-07 MoSEIC™ meloxicam rizatriptan
Sponsor: Axsome Therapeutics, Inc.
Start date: 2019-07-06; Completion date: 2020-09-22
Enrollment: 706 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
MOVEMENT (Multimechanistic Treatment over Time of Migraine Symptoms) is a Phase 3 study to evaluate the long-term safety of chronic intermittent use of AXS-07 and to assess the effect of AXS-07 on migraine symptoms following repeated treatment of migraine attacks.

Detailed description:
This study is a Phase 3, multicenter, open-label, trial to evaluate the long-term safety and efficacy of intermittent chronic dosing with AXS-07 in subjects with migraine attacks. Eligible subjects will take AXS-07 following the onset of a migraine. Subjects will be treated for up to 12 months.

Arms: arm 1: None
Interventions: intervention 1: AXS-07
Intervention descriptions: intervention 1: AXS-07 (MoSEIC meloxicam and rizatriptan) taken by mouth for the acute treatment of migraine.

Protocol documents:
Prot_SAP_000.pdf: 
Document Type: Protocol and Statistical Analysis Plan
Protocol Title: An Open-Label Study to Assess the Long-term Safety of AXS-07 (meloxicam 
and rizatriptan) for the Acute Treatment of Migraine in Adults. 
ClinicalTrials.gov Identifier:  NCT04068051
Document Date: October 17, 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.


Axsome Therapeutics, Inc. 
Confidential 
AXS-07-302 
Version Date: Amendment 2, Oct 17, 2019 
Page 1 
 
PROTOCOL 
COMPOUND 
NAME/NUMBER: 
AXS-07 
PROTOCOL NUMBER: 
AXS-07-302 
 
 
DEVELOPMENT PHASE: 
Phase 3 
PROTOCOL TITLE: 
An Open-Label Study to Assess the Long-term Safety of AXS-07 
(meloxicam and rizatriptan) for the Acute Treatment of Migraine in 
Adults. 
PROTOCOL VERSION: 
Amendment 2 
PROTOCOL DATE: 
October 17, 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. 






Axsome Therapeutics, Inc. 
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AXS-07-302 
Version Date: Amendment 2, Oct 17, 2019 
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1. SYNOPSIS 
 
PRODUCT 
NAME/NUMBER 
AXS-07  
PROTOCOL NUMBER 
AXS-07-302 
DEVELOPMENT 
PHASE 
Phase 3 
PROTOCOL TITLE 
An Open-Label Study to Assess the Long-term Safety of AXS-07 (meloxicam and rizatriptan) for 
the Acute Treatment of Migraine in Adults. 
INDICATION 
Acute treatment of migraine with or without aura in adults. 
OBJECTIVES 
Primary Objective: 
To evaluate the long term safety of chronic intermittent use of AXS-07. 
Secondary Objectives: 
To assess the effect of AXS-07 on migraine symptoms following repeated treatment of migraine 
attacks. 
STUDY DESIGN 
This study is a Phase 3, multicenter, open-label, trial to evaluate the long-term safety of intermittent 
chronic dosing with AXS-07 in subjects with migraine attacks. Eligible subjects will take a dose of 
AXS-07 following the onset of a migraine. Subjects will be enrolled for up to 12 months and 
encouraged to treat all migraine attacks with AXS-07.  
Subjects are eligible subjects if they have participated in a prior AXS-07 study for the acute 
treatment of migraine with no significant changes in medical history since participation. Subjects 
who meet all eligibility criteria will be enrolled at Visit 1 and will be dispensed AXS-07 for at-home 
treatment of migraine attacks.  Subjects will be instructed to treat each migraine attack with AXS-
07 and return for clinic visits at Months 1, 3, 6, 9, and 12 (5 return visits).   
 
Migraine Headache Diary 
For the first 4 migraine attacks, the subject will record their headache pain intensity (measured by a 
4-point rating scale; 0-none, 1-mild, 2-moderate, or 3-severe), in the Migraine Headache Diary 
immediately prior to taking study medication, and at the following time points after taking study 
medication: 30 minutes, and 1, 2, 8, 24, and 48 hours after dosing.   
Prior to dosing, for the first 4 migraine attacks, the subject will define their most bothersome 
symptom (nausea, photophobia, phonophobia) and assess the presence or absence of each symptom 
at the following timepoints: 1 and 2 hours after dosing.  
The subject will be instructed to report any adverse events which occur following each dose of AXS-
07.  Use of rescue medications will also be recorded. All migraines which occur during the course 
of the study, regardless of treatment with study drug or not, will be recorded in the Migraine 
Headache Log. 
 
Study Visits 
Subjects will come to the clinic for the enrollment visit (Visit 1, Day 1), Month 1, Month 3, Month 
6, Month 9, and Month 12. At each in clinic study visit, the subject will undergo the following safety 
assessments: assessment of adverse events, review of concomitant medications, vital signs, urine 
pregnancy test (if applicable), clinical laboratory tests and an electrocardiogram.  Additionally, the 
following patient-reported scales will be completed at every visit:  Headache Impact Test-6 (HIT-
6), Migraine Disability Assessment Score (MIDAS, not conducted at Month 1), and Migraine-
Specific Quality of Life Questionnaire (MSQ).  


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PLANNED NUMBER 
OF SUBJECTS 
The study will end when there are at least 300 subjects that complete the Month 6 visit and at least 
100 subjects that complete the Month 12 visit, treating a minimum of 2 migraines a month. At that 
time, all remaining uncompleted subjects (those in various interim visits of the study) will be 
scheduled to come to the site to complete the Month 12 visit procedures.  These subjects are 
considered completing the study. 
STUDY ENTRY 
CRITERIA 
Inclusion criteria: 
A subject will be eligible for study participation if the subject meets all of the following criteria: 
1. Is male or female 18 to 65 years of age inclusive. 
2. Is willing and able to provide written informed consent to participate in the study, and 
willing and able to understand and comply with the procedures and study requirements. 
3. Participated in a prior study with AXS-07 for the acute treatment of migraine. 
4. If female, is either not of childbearing potential (defined as postmenopausal for at least 1 
year or surgically sterile [bilateral tubal ligation, bilateral oophorectomy, or 
hysterectomy]); or is nonlactating and nonpregnant (has negative pregnancy test results at 
Day 1), does not plan to get pregnant during the study or for at least one month after, and 
is using a reliable method of contraception, before study drug. 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), abstinence, vasectomized partners and intrauterine devices. 
5. Is willing and able to complete the Migraine Headache Diary. 
Exclusion criteria: 
A subject will be excluded from the study if the subject meets any of the following criteria: 
1. Significant change in medical history or concomitant medications since enrolling in the 
prior AXS-07 study. 
2. Initiation of or a change in concomitant medication to reduce the frequency of migraine 
episodes since completing the prior AXS-07 study. 
3. 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 AXS-
07. 
4. Is currently receiving propranolol or has received propranolol within 2 weeks prior to 
enrollment or plans to use during the study. 
Participation in any clinical trial of an experimental drug or device since completing the 
prior AXS-07 study. 
INVESTIGATIONAL 
PRODUCT 
AXS-07 (20 mg meloxicam/10 mg rizatriptan) tablet for oral administration.  
TREATMENT 
REGIMENS 
AXS-07 is to be taken orally with water at the onset of a migraine attack. 
PRINCIPAL 
INVESTIGATOR 
Multi-center 
PLANNED STUDY 
SITES 
Up to approximately 80 study sites in North America  
CRITERIA FOR 
EVALUATION 
Primary Outcome Measures 
• The primary safety outcome is long-term safety as evaluated by the incidence, severity, 
and relatedness of AEs following dosing with AXS-07. 
Efficacy Outcome Measures 
• Proportion of subjects with headache pain freedom at Hour 2, with headache pain 
freedom defined as pain intensity = none. 
• Proportion of subjects with absence of the most bothersome symptom (MBS; nausea, 
photophobia, or phonophobia) at Hour 2, with the MBS defined at the onset of migraine, 
prior to drug administration. 


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• Proportion of subjects with headache pain relief at Hour 2 
• Sustained headache pain freedom between Hours 2 and 24, defined as having no 
headache pain at Hour 2, with no use of rescue medication and no relapse of headache 
pain through Hour 24. 
• Change from baseline in the MIDAS total score 
• Change from baseline in HIT-6 total score 
• Change from baseline in the scores of each of the three domains of the MSQ v2.1  
• Proportion of subjects with headache pain freedom at Hour 0.5, 1, 8, 24 and 48, with 
headache pain freedom defined as pain intensity = none. 
• Proportion of subjects with headache pain relief at Hour 0.5, 1, 8, 24 and 48. 
STATISTICAL 
METHODS 
Analysis Populations: 
The following analysis populations are planned for this study: 
• 
Safety Population: The Safety Population will include all subjects who take at least one 
dose study medication. 
• 
Intent-to-treat (ITT) Population:  The ITT Population will include all subjects who take 
at least one dose of study medication and report at least one efficacy measurement. 
Descriptive statistics will be used for all variables and all data over time. 
SAMPLE SIZE 
DETERMINATION 
To assess for long-term safety, this study will enroll enough subjects to ensure that 300 subjects are 
treated for at least 6 months and 100 for 12 months, treating at least 2 migraines a month.  Up to 875 
subjects may be enrolled to achieve this sample size.  
STUDY AND 
TREATMENT 
DURATION 
The duration of participation will be up to 12 months.  Subjects will be allowed to treat each migraine 
with AXS-07 for up to the 12 months following enrollment.  Up to six planned study visits will 
occur over the 12 months.