This study has been transitioned to CTIS with ID 2023-506253-38-00 check the CTIS register for the current data. Primary- To test the hypothesis that lasmiditan high dose is superior to placebo in the acute treatment of a migraine attack in…
ID
Source
Brief title
Condition
- Headaches
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary
- Proportion of patients >=6 to <18 years of age with pain freedom at 2 hours
after dosing
Secondary outcome
Key Secondary
- Proportion of patients >=6 to <18 years of age with pain freedom at 2 hours
after dosing
- Proportion of patients >=6 to <18 years of age with pain freedom at 2 hours
after dosing
Secondary
- Proportion of patients with pain freedom at 2 hours after dosing in the
subgroup of patients >=6 to <12 years of age and in the subgroup of patients 12
to <18 years of age
- Proportion of patients >=6 to <18 years of age with pain relief at 2 hours
after dosing
- Proportion of patients >=6 to <18 years of age MBS-free at 2 hours after dosing
- In patients >=6 to <18 years of age:
* Proportion of patients nausea-free at 2 hours after dosing
* Proportion of patients photophobia-free at 2 hours after dosing
* Proportion of patients phonophobia-free at 2 hours after dosing
- Proportion of patients >=6 to <18 years of age with sustained pain freedom at
24 and 48 hours
- In patients >=6 to <18 years of age:
* Proportion of patients using additional medication for migraine within 24 and
48 hours
* Time to use of additional migraine medication
- In patients >=6 to <18 years of age:
* Proportion of patients with pain freedom at 30 minutes, 1, 1.5, and 2 hours
after dosing
* Proportion of patients with pain relief at 30 minutes, 1, 1.5, and 2 hours
after dosing
* Proportion of patients MBS-free at 30 minutes, 1, 1.5, and 2 hours after
dosing
* Proportion of patients nausea-free at 30 minutes, 1, 1.5, and 2 hours after
dosing
* Proportion of patients photophobia-free at 30 minutes, 1, 1.5, and 2 hours
after dosing
* Proportion of patients phonophobia-free at 30 minutes, 1, 1.5, and 2 hours
after dosing
- Proportion of patients >=6 to <18 years of age with PGIC rating of *a lot
better,* *better,* *no different,* *worse,* and *a lot worse* at 2 hours
- Proportion of patients >=6 to <18 years of age with a rating of 0 (*not at
all*), 1 (*a little*), 2 (*a lot*), or 3 (*completely*) at 2 hours
Acceptability of the Formulation
- Proportion of patients >=6 to <18 years of age with a rating of *very easy,*
*easy,* *neither easy nor hard,* *hard,* or *very hard* at 24 hours after
dosing
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 2023-506253-38-00 check the CTIS register for the current data.
Primary
- To test the hypothesis that lasmiditan high dose is superior to placebo in
the acute treatment of a migraine attack in pediatric patients >=6 to <18 years
of age
Key Secondary
- To test the hypothesis that lasmiditan medium dose is superior to placebo in
the acute treatment of a migraine attack in pediatric patients >=6 to <18 years
of age
- To test the hypothesis that lasmiditan low dose is superior to placebo in the
acute treatment of a migraine attack in pediatric patients >=6 to <18 years of
age
Secondary
- To evaluate the efficacy of lasmiditan (low dose, medium dose, and high dose)
compared with placebo with respect to pain freedom in age subgroups
- To evaluate the efficacy of lasmiditan (low dose, medium dose, and high dose)
compared with placebo with respect to pain relief
- To evaluate the efficacy of lasmiditan (low dose, medium dose, and high dose)
compared with placebo with respect to resolution of the MBS
- To evaluate the efficacy of lasmiditan (low dose, medium dose, and high dose)
compared with placebo with respect to absence of individual associated symptoms
of migraine
- To evaluate the efficacy of lasmiditan (low dose, medium dose, and high dose)
compared with placebo with respect to sustained pain freedom
- To evaluate the efficacy of lasmiditan (low dose, medium dose, and high dose)
compared with placebo with respect to use of additional medication within 24
and 48 hours
- To evaluate the efficacy of lasmiditan (low dose, medium dose, and high dose)
compared with placebo with respect to time of onset of outcomes of pain
freedom, pain relief, and freedom from associated symptoms of migraine,
including the MBS
- To evaluate the efficacy of lasmiditan (low dose, medium dose, and high dose)
compared with placebo with respect to patient-reported global measure of change
- To evaluate the efficacy of lasmiditan (low dose, medium dose, and high dose)
compared with placebo with respect to the degree of migraine interference in
normal activities
Acceptability of the Formulation
- To evaluate the acceptability of lasmiditan tablets (low dose, medium dose,
and high dose) with respect to ease of swallowing of the tablets
Study design
Study LAHV is a multi-country, randomized, double-blind, parallel-group,
placebo-controlled trial in patients of at least 6 to less than 18 years of age
who meet International Classification of Headache Disorders criteria for a
diagnosis of migraine. Study LAHV will assess the efficacy, safety, and
tolerability of lasmiditan low dose, medium dose, and high dose compared to
placebo in the treatment of a single migraine attack. Patients will treat a
single migraine attack in 2 stages: a double-blind placebo challenge (Stage 1)
prior to randomization in the efficacy analysis period (Stage 2). Patients will
record characteristics of treated migraine and outcomes in an electronic diary
prior to dosing and at specified intervals after dosing. Patients will record
any AEs and concomitant use of medication throughout the Treatment Period in a
paper diary. An End-of-Study Visit will be conducted within 28 days of dosing
of study medication or after 12 weeks if no migraine attack is treated with
study drug.
Intervention
This study involves a comparison of lasmiditan film-coated tablets with
placebo. The study medication will be administered by mouth. To maintain the
blind, each dose will require 3 tablets. The proposed lasmiditan dose,
definitions of weight thresholds for this study, or both may be
amended prior to the first enrollment, based on the PK and safety data from
Study LAHX. The selected dose for each weight cohort is intended to reflect
exposures comparable to the low, medium and high doses of lasmiditan in adults.
Study burden and risks
Migraine is a disabling and prevalent disorder that impacts children. There are
few approved treatments for migraine in children and adolescents in the US,
with only 1 approved treatment (rizatriptan) available for children aged at
least 6 to less than 12 years. Current treatments are not sufficiently meeting
the needs of all patients (El-Chammas et al. 2013). Lasmiditan is a highly
selective 5-HT1F agonist that is being developed for the acute treatment of
migraine attacks. Lasmiditan demonstrated efficacy and safety in 2
placebo-controlled, randomized, Phase 3 efficacy trials in adults (Kuca et al.
2018; Goadsby et al. 2019). If approved in a pediatric population, lasmiditan
would provide another acute treatment option for children and adolescents with
migraine. As a centrally penetrant 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.
It is generally well-tolerated, and the vast majority of events in adults are
mild to moderate and of limited duration. Further information can be found in
the Investigator*s Brochure. Patients who complete Visits 1, 2, 3, and 801 in
Study LAHV may be eligible to participate in an open-label, 12-month, long-term
safety study, Study LAHW. Treatment of a qualifying migraine during during the
12-week treatment period is not required to qualify for Study LAHW. In Study
LAHW, patients will have the opportunity to treat multiple migraine attacks
with lasmiditan.
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 | CTIS2023-506253-38-00 |
| EudraCT | EUCTR2019-004378-24-NL |
| CCMO | NL73301.075.20 |