This study has been transitioned to CTIS with ID 2023-507096-21-00 check the CTIS register for the current data. To evaluate the safety and tolerability of treatment with atogepant 60 mg once daily when administered over 156 weeks for the prevention…
ID
Source
Brief title
Condition
- Headaches
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- Percentage of Participants with at Least 1 Treatment Emergent Adverse Event
across the 156-week treatment period
Secondary outcome
- Percentage of Participants with Clinically Significant Laboratory Values
(Chemistry, Hematology, Urinalysis) as assessed by the Investigator [Time
Frame: 156 weeks]
- Percentage of Participants with Clinically Significant Electrocardiograms
(ECGs) Findings as assessed by the Investigator [Time Frame: 156 weeks]
- Percentage of Participants with Clinically Significant Vital Sign
Measurements as assessed by the Investigator [Time Frame: 156weeks]
- Columbia-Suicide Severity Rating Scale (C-SSRS) Assessing Suicidal Ideation
and Behavior using 5-Point Scales [Time Frame: 156 weeks]
Background summary
Migraine affects 18% of women and 6% of men in the United States with peak
prevalence occurring between the ages of 25 to 55 years. Approximately
one-third of these migraineurs have 3 or more migraine headaches per month, and
over half report severe impairment or the need for bed rest. Prevalence is
similar in Europe, with migraine headache affecting on average 17.6% of women
and 8% of men. As of 2016, migraine is the second leading cause of disability
worldwide. Migraine is typically characterized by attacks of throbbing,
unilateral headache of moderate or severe pain intensity, associated with
nausea, vomiting, and/or sensitivity to light (photophobia) and sound
(phonophobia). In about 25% of individuals, the migraine headache is preceded
by focal neurological dysfunction (aura). Improving diagnosis and optimizing
treatments for migraine have been recognized as critically important to
overcoming current barriers to reduce the global burden of migraine. Because
there are no biological markers for migraine, diagnosis is based on clinical
history, exam, and the exclusion of other headache disorders. Physicians apply
clinical criteria to guide diagnoses and subsequent treatment. Episodic
migraine (EM) can be divided into low frequency (LFEM) and high frequency
episodic migraine (HFEM) depending on the headache days suffered per month (GBD
2017). Episodic migraine (EM) is a syndrome diagnosis applied to patients with
migraine (with or without aura) who have 1 to 14 headache days per month.
Chronic migraine is a specific ICHD-3diagnosis applied to a subset of patients
with >=15 headache days per month. This study will include participants with
episodic migraine who had failed 2-4 classes of prior oral prophylactic
medications. The rationale for targeting this population is 2-fold. Firstly,
patients on currently available oral prophylactic medications may experience
poor tolerability; secondly, many of these treatments have shown insufficient
efficacy (did not sufficiently reduce either severity or frequency) of migraine
for many patients. The consequences of the limitations in current oral
prophylactic migraine treatments amount to both poor adherence and reluctance
to initiate prophylactic treatment. In fact, recent studies have indicated that
approximately half of migraine patients discontinued their initial oral
migraine prophylactic treatment within 60 days, which might be explained by
poor tolerability or lack of efficacy. Moreover, in a US-based retrospective
database study it was concluded that approximately 70% of patients who begin
migraine prophylaxis with antidepressants, antiepileptics, or beta-blockers are
no longer taking these medications at 6 months. Of those patients who continue
to take a prophylactic medication, many still have substantial disease burden.
Therefore, the proposed population for Study 3101-304-002 reflects clinical
practice. There is severe unmet need in patients that have failed multiple
migraine prophylactic oral medications, and these patients are currently often
relying on ineffective treatments and many suffer from intolerability to
currently available medications
Study objective
This study has been transitioned to CTIS with ID 2023-507096-21-00 check the CTIS register for the current data.
To evaluate the safety and tolerability of treatment with atogepant 60 mg once
daily when administered over 156 weeks for the prevention of migraine in
participants with Chronic Migraine (CM) or Episodic Migraine (EM).
Study design
This is a multicenter, open-label, 156-week, long-term safety extension study
conducted in all eligible participants who complete either lead-in Study
3101-303-002 (Phase 3 CM study) or Study 3101-304-002 (Phase 3 EM study). All
participants will be treated with atogepant 60 mg once daily. The study will
consist of a 156-week open-label treatment period, and a safety follow-up
period of 4 weeks.
Intervention
All participants will be treated with atogepant 60 mg once daily. The study
will consist of an open-label treatment period of 156 weeks.
Study burden and risks
The study will include a total of 18 visits and will be up to 156 weeks in
duration. Subjects are expected to undergo procedures/assessments as described
in the section 1.3 of the study protocol, which include: Physical exam, vital
signs, demographic and medical history; ECG; eDiary: reporting information on
symptoms/signs of disease, (i.e. headache duration, frequency, characteristics,
symptoms, acute medication use, etc.); Blood and urine tests (including urine
drug screening); Completion of questionnaire and answering questions from the
study team; Pregnancy tests in women of childbearing potential; Female
patients: no breastfeeding allowed. Effective methods of birth control must be
used from the time of signing the ICF, throughout the entire study; Male
patients: due to the potential risk of the effect on the sperm appropriate
method of contraception must be used starting at screening and throughout the
entire study. The following risks were the most common side effects in a study
of patients with migraine receiving atogepant or placebo (medically inactive
substance) daily for 12 weeks: nausea, common cold, constipation, urinary tract
infection, fatigue, increased creatine phosphokinase The risks involved in
taking this study medication have been carefully assessed by previous testing
done in animal and human studies. Overall, the risks are considered to be
acceptable although some risks are unforeseeable. In addition to the risks
listed above, there may be some infrequent and unforeseeable risks associated
with the use of atogepant. Atogepant is investigational, when taken alone or in
combination with other medications, so there may be other risks that are
unknown. Older drugs in this class have been associated with an increased risk
of liver problems. However, atogepant is a new drug that has been designed
specifically to minimise this risk. Based on previous studies with this drug,
no safety issues related to taking atogepant and liver problems have been
detected. Placebo Risks: If the study subject is in the group which is assigned
placebo, study subject*s symptoms of migraine may not improve or may worsen.
Even if the study subject is in the group that gets the active drug during the
study, the symptoms may not improve or may worsen. Blood Sample Risks: Subjects
may feel a slight needle prick when blood is drawn. Some participants may have
a slight bruise that will go away within a few days. Sometimes, participants
feel light headed or feel dizzy. Other rare complications associated with the
blood sample collection include: infections, nerve lesions, accidental arterial
puncture (when the needle pierces an artery instead of a vein) and bleeding,
inflammation of vein, and dizziness. Electrocardiogram (ECG) Risks: The ECG
procedure may cause minimal discomfort and skin irritation during or after the
attachment/removal of the leads (and adhesive). Allergic Reaction Risks: As
with taking any treatment, there is a risk of allergic reaction. Some symptoms
of allergic reactions are: Rash; Wheezing and difficulty breathing; Dizziness
and fainting; Swelling around the mouth, throat or eyes; A fast pulse;
Sweating. This study will include participants with episodic migraine who had
failed 2-4 classes of prior oral prophylactic medications. The rationale for
targeting this population is 2-fold. Firstly, patients on currently available
oral prophylactic medications may experience poor tolerability; secondly, many
of these treatments have shown insufficient efficacy (did not sufficiently
reduce either severity or frequency) of migraine for many patients. The
consequences of the limitations in current oral prophylactic migraine
treatments amount to both poor adherence and reluctance to initiate
prophylactic treatment. In fact, recent studies have indicated that
approximately half of migraine patients discontinued their initial oral
migraine prophylactic treatment within 60 days, which might be explained by
poor tolerability or lack of efficacy. Moreover, in a US-based retrospective
database study it was concluded that approximately 70% of patients who begin
migraine prophylaxis with antidepressants, antiepileptics, or beta-blockers are
no longer taking these medications at 6 months. Of those patients who continue
to take a prophylactic medication, many still have substantial disease burden.
Current available data supports the efficacy of atogepant for the prevention of
episodic migraine; in addition, atogepant has been well tolerated with no
safety concerns to date. The protocol is designed to ensure that patient safety
is assessed adequately throughout the study. An independent DSMB will review
unblinded safety data throughout the trial and make recommendations to the
sponsor, including modification or early termination of the trial, if emerging
data show unexpected and clinically significant adverse effects of treatment.
Overall the assessment of benefit/risk is favorable.
Knollstrasse -
Ludwigshafen 67061
DE
Knollstrasse -
Ludwigshafen 67061
DE
Listed location countries
Age
Inclusion criteria
1. Written informed consent and participant privacy information (eg, written
authorization for use and release of health and research study information)
obtained from the participant prior to initiation of any study-specific
procedures.
2. Participants must be using a medically acceptable and effective method of
birth control during the course of the entire study, as defined in Section
4.5.2 of the protocol.
3. Eligible participants who completed the double-blind treatment period (Visit
7) and the follow-up period (Visit 8), if applicable, depending on the timing
of study initiation, of Study 3101-303-002 or Study 3101-304-002 without
significant protocol deviations (eg, noncompliance to protocol-required
procedures) and who did not experience an AE that, in the investigator*s
opinion, may indicate an unacceptable safety risk.
Exclusion criteria
1. Requirement for any medication, diet (ie, grapefruit or grapefruit juice),
or nonpharmacological treatment that is on the list of prohibited concomitant
medications or treatments (see Section 4.5.1 and Attachment 12.1 of the study
protocol) that cannot be discontinued or switched to an allowable alternative
medication or treatment.
Exception: participants from lead-in Study 3101-303-002 taking only 1 migraine
prevention medication (with demonstrated efficacy, as listed in Attachment 12.1
of the protocol) at a stable, well-tolerated dose during the lead-in study; the
medication may be continued at the same dose or discontinued.
2. Female participant is pregnant, planning to become pregnant during the
course of the study, or currently lactating. WOCBP must have a negative urine
pregnancy test at Visit 1.
3. An ECG with clinically significant abnormalities at Visit 1 as determined by
the investigator.
4. Hypertension as defined by sitting systolic BP > 160 mm Hg or sitting
diastolic BP > 100 mm Hg at Visit 1. Vital sign measurements that exceed these
limits may be repeated only once.
5. Significant risk of self-harm based on clinical interview and responses on
the C-SSRS, orof harm to others in the opinion of the investigator;
participants must be excluded if they report suicidal ideation with intent,
with or without a plan (ie, Type 4 or 5 on the C-SSRS) since the last visit.
6. Participants with clinically significant hematologic, endocrine,
cardiovascular, pulmonary, renal, hepatic, gastrointestinal, or neurologic
disease.
7. Participant has a condition or is in a situation which in the investigator's
opinion may put the participant at significant risk, may confound the study
results, or may interfere significantly with participation in the study.
8. Any medical or other reasons (eg, unlikely to adhere to the study
procedures, keep appointments, or is planning to relocate during the study)
that, in the investigator*s opinion, might indicate that the participant is
unsuitable for participation in the study.
9. History of acute hepatitis within 6 months of screening (Visit 1); or
chronic liver disease (including nonalcoholic fatty liver disease, viral
chronic hepatitis, and cirrhosis).
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2023-507096-21-00 |
| EudraCT | EUCTR2020-002470-27-NL |
| ClinicalTrials.gov | NCT04686136 |
| CCMO | NL76039.056.21 |