This study has been transitioned to CTIS with ID 2023-506724-85-00 check the CTIS register for the current data. Primary- To evaluate the safety and tolerability of long-term intermittent use of lasmiditan for the acute treatment of migraine in…
ID
Source
Brief title
Condition
- Headaches
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- Nature, proportion, and severity of TEAEs by treated attack.
- Proportion of discontinuation due to AEs.
Secondary outcome
- Proportion of treated attacks with pain freedom at 2 hours after dosing for
each 3-month period.
- Proportion of treated attacks with pain relief at 2 hours after dosing for
each 3-month period.
- Proportion of treated attacks with freedom of the most bothesome symptom, at
2 hours after dosing for each 3-month period.
Background summary
Migraine is one of the most common neurological conditions in pediatrics.
Migraine attacks are characterized by intense pain and associated symptoms,
resulting in substantial negative impacts on daily life. In children and
adolescents, migraine can have a negative impact on function (including missed
school days and poorer academic performance) and quality of life.
The goal of migraine treatment in the pediatric population is quick resolution
of the headache with minimal side effects, allowing the child to resume normal
activities. There are few positive trials of acute medication for the treatment
of migraine in children, particularly in the population less than 12 years old.
High placebo response rates, as well as shorter attack length in this
population, have complicated efforts to demonstrate efficacy of treatments.
Lasmiditan is a novel therapy for the acute treatment of migraine. Lasmiditan
is a high-affinity, centrally penetrant, selective 5-HT1F receptor agonist
developed specifically for the acute treatment of migraine. Lasmiditan
selectively targets 5-HT1F receptors on neurons in the central and peripheral
trigeminal system, decreasing neuropeptide release and inhibiting pain pathways
(including the trigeminal nerve) (Nelson et al. 2010; Vila-Pueyo 2018).
Lasmiditan is structurally and mechanistically distinct from other approaches
for the acute treatment of migraine, such as triptans, and lacks the
vasoconstrictive effects of triptans that result from 5-HT1B activity. In 2
placebo-controlled, randomized, Phase 3 efficacy trials of a single migraine
attack in adults, lasmiditan low dose, medium dose, and high dose were
associated with a greater proportion of patients achieving pain freedom and
freedom from their most bothersome associated symptom at 2 hours (Kuca et al.
2018; Goadsby et al. 2019). Lasmiditan may provide therapeutic benefit to
children and adolescents from at least 6 to less than 18 years of age.
Study objective
This study has been transitioned to CTIS with ID 2023-506724-85-00 check the CTIS register for the current data.
Primary
- To evaluate the safety and tolerability of long-term intermittent use of
lasmiditan for the acute treatment of migraine in pediatric patients.
Key Secondary
- To evaluate the efficacy of intermittently dosed lasmiditan in the treatment
of multiple migraine attacks over time in pediatric patients.
Study design
This is a prospective, randomized, open-label, 12-month study in children and
adolescents with a diagnosis of migraine who previously enrolled in and
completed Study H8H-MC-LAHX (LAHX) or Study H8H-MC-LAHV (LAHV). Study
participants will be stratified by age group (6 to <12 years and 12 to <18
years based on age at time of enrollment into Study LAHX or LAHV) and
randomized in a 1:1 ratio to treatment with weight-based doses comparable to
medium dose and high dose adult exposure.
During a 12-month open-label treatment period, study participants may use
lasmiditan to treat up to 8 migraine attacks per month on an outpatient basis.
Dosing with lasmiditan, outcomes, use of concomitant medications, and adverse
events will be recorded in a paper diary. Rescue medication may be used
beginning 2 hours after lasmiditan dosing. Patients may use 1 dose of
lasmiditan in a 24-hour period. Participants may use their usual treatment in
the event they choose not to take lasmiditan for an individual attack
Intervention
Participants will be randomized in a 1:1 ratio at study entry to treatment with
weight-based doses corresponding to the medium dose- and the high dose adult
exposure (referred to throughout as lasmiditan medium dose and lasmiditan high
dose). The lasmiditan dose may be reduced 1 time during study participation in
the event of tolerability concerns, after treatment of at least 3 migraine
attacks at the randomized dose (see Section 6.6 of the Protocol). Study
participants may use lasmiditan to treat up to 8 migraine attacks per month on
an outpatient basis.
Study burden and risks
Lasmiditan may provide therapeutic benefit to children and adolescents with
migraine. Lasmiditan is approved in the United States for the acute treatment
of migraine, with or without aura, in adults. In adults with migraine with or
without aura, lasmiditan (low dose, medium dose and high dose) has been shown
to be an effective treatment based on the primary endpoints of pain freedom and
freedom from the most bothersome symptom (selected from nausea, photophobia, or
phonophobia at the beginning of the migraine attack) at 2 hours postdose (Kuca
et al. 2018; Goadsby et al. 2019). Additional evidence of efficacy was
observed on multiple secondary measures of pain relief (2 hours), sustained
pain freedom (24 hours), functioning (2 hours), and Patient Global Impression
of Change (2 hours), as well as time to onset of pain relief, pain freedom, and
freedom from associated symptoms.
In Study LAHW, pediatric patients will have the option to treat up to 8
migraine attacks a month with lasmiditan for 12 months. Patients will be
initially randomized to receive weight-based doses comparable to medium dose
and high dose exposures in adult patients. However, patients may request 1
dose adjustment for tolerability after treating at least 3 migraine attacks at
the randomized dose.
As a centrally penetrant and neurally active drug, lasmiditan use is associated
with neurologic treatment-emergent adverse events (TEAEs), with the most common
being dizziness, paresthesia, somnolence, fatigue, nausea, hypoesthesia, and
muscle weakness. Lasmiditan is generally well-tolerated, and the vast majority
of adverse events (AEs) are mild to moderate in severity and of limited
duration.
More information about the known and expected benefits, risks, serious adverse
events (SAEs), and reasonably anticipated AEs of lasmiditan can be found in the
Investigator*s Brochure (IB).
Island House, Eastgate Business Park, Little Island na
Cork Co.
NL
Island House, Eastgate Business Park, Little Island na
Cork Co.
NL
Listed location countries
Age
Inclusion criteria
Type of Patient and Disease Characteristics
[1] Patient is at least 6 and less than 18 years of age at Screening (Visit 1).
[2] Patient must have a minimum body weight of 15 kg.
[3] Patient has a history of migraine with or without aura as defined by
International Headache Society International Classification of Headache
Disorders, 3rd edition (ICHD-3) (ICHD-3 2018) diagnostic criteria 1.1 or
1.2.1 and meets the following criteria:
- History of migraine attacks for more than 6 months
- Reports at least 2 and no more than 8 moderate-to-severe migraine attacks per
month in the 2 months prior to Screening Visit
- Duration of a typical untreated migraine attack (excluding sleep) is greater
than or
equal to*3 hours
- Patient has not, by history, experienced satisfactory response with a previous
migraine therapy, in the opinion of the investigator.
[4] Patient must be able to swallow a tablet.
[5] For patients taking migraine preventive medication, treatment regimen is
stable and has been taken for at least 3 months prior to Visit 1.
Informed Consent and Patient Agreements
[6] The patient and patient*s parent or guardian must understand the nature of
the
study. The patient*s parent or guardian must sign an ICF, and the patient must
sign an informed assent document as required by local regulations.
[7] The patient and patient*s parent or guardian are reliable and willing to
make
themselves available for the duration of the study and are willing to follow
study procedures.
[8] Patient is male or female; if female, must agree to abide by the following
guidance:
- Females of childbearing potential (started menses, to include any duration or
amount of spotting) must agree to use a highly effective method of contraception
(that is, one with less than 1% failure rate) such as
o combination oral contraceptives
o implanted/injected contraceptives
o intrauterine devices, or
o sterile partner until 30 days after the last dose of study medication.
- Females of childbearing potential who are abstinent (if this is complete
abstinence,
as their preferred and usual lifestyle) or in a same-sex relationship (as part
of their
preferred and usual lifestyle) must agree to either remain abstinent or stay in
a
same-sex relationship without sexual relationships with males. Periodic
abstinence
(for example, calendar, ovulation, symptothermal, and postovulation methods),
declaration of abstinence just for the duration of a trial, and withdrawal are
not
acceptable methods of contraception.
[9] The patient and patient*s parent or guardian must agree not to post any
personal medical data related to the study or information related to the study
on any website or social media site until notification that the study has been
completed. Examples of these sites include
- Facebook
- Twitter
- Snapchat
- Instagram, and
- Google+.
Exclusion criteria
Medical Conditions
[10] Patient has a history or clinical evidence of congenital heart disease,
suspected
or confirmed.
[11] ECG showing abnormalities compatible with acute cardiovascular events,
serious cardiovascular disease risk, or both.
[12] Within 6 months of screening, patient had
- myocardial infarction
- unstable angina
- percutaneous coronary intervention, and
- coronary artery bypass graft.
[13] Patient has planned cardiovascular surgery or percutaneous coronary
angioplasty, or has a history of stroke.
[14] Patient has any liver tests outside the normal range at screening that are
clinically
significant. Alanine aminotransferase (ALT) greater than 2x upper limit of
normal
(ULN), or total bilirubin level (TBL) greater than 1.5x ULN, or alkaline
phosphatase
(ALP) greater than 2x ULN must be discussed and judged not clinically
significant by
Lilly Medical prior to enrollment.
NOTE: Patients with TBL at least 1.5x ULN are not excluded if they meet all of
the
following criteria for Gilbert syndrome:
*- Bilirubin is predominantly indirect (unconjugated) at Screening (direct
bilirubin within normal limits)
* - Absence of liver disease
* - ALT, aspartate aminotransferase (AST), and ALP no greater than 1x ULN at
screening, and
* Hemoglobin not significantly decreased at screening.
[15] Patient has, in the judgement of the investigator, a psychiatric disorder
as
defined by the Diagnostic and Statistical Manual of Mental Disorders, 5th
Edition, that would interfere with adherence to study requirements or safe
participation in the trial. This includes a current or historical diagnosis of a
substance use disorder.
[16] Patient is, in the judgment of the investigator, actively suicidal and
therefore
deemed to be at significant risk for suicide.
[17] At Screening:
- patient has answered *yes* to either Question 4 or Question 5 on the *Suicidal
Ideation* portion of the Columbia-Suicide Severity Rating Scale (C-SSRS) or has
answered *yes* to any of the suicide-related behaviors on the *suicidal
behavior*
portion of the C-SSRS, and
- the ideation or behavior occurred within the past month.
[18] Patient is pregnant or breastfeeding.
[19] Patient has, in the judgment of the investigator, an acute, serious, or
unstable
medical condition or a history or presence of any other medical illness that
would preclude study participation.
Prior and Concomitant Therapy/Substances of Abuse
[20] Patient has used opioids or barbiturate-containing analgesic more than 3
times
per month for the treatment of pain in more than 2 of the past 6 months.
[21] Patient has known allergies to lasmiditan, related compounds, or any
components of the formulation.
[22] Patient has a positive urine drug screen for any substances of abuse.
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 | CTIS2023-506724-85-00 |
| EudraCT | EUCTR2019-004379-38-NL |
| CCMO | NL73491.075.20 |