The objective of this study is to test the safety of the research study drug, MK-0462 (rizatriptan) and to test the ability of study drug to relieve or reduce migraine for the study population.
ID
Source
Brief title
Condition
- Headaches
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To evaluate the safety and tolerability of rizatriptan in the long term
treatment of acute migraine in pediatric patients age 12-17 years.
Secondary outcome
To estimate the efficacy of rizatriptan as measured by pain freedom at 2 hours
post dose in the long term treatment of acute migraine in pediatric patients
age 12-17 years.
Background summary
Migraine is a common neurological disorder afflicting children, adolescents and
adults. It contributes significantly to school absence, work loss, medication
use, impaired quality of life, and health care visits. Rizatriptan
(manufactured and marketed as MAXALT by Merck & Co, Inc., Whitehouse Station,
NJ) is a 5-HT1B/1D agonist approved at a therapeutic dose of 10 or 5 mg (up to
2 - 3 doses/24 hours depending on local product label; interdose interval of 2
hours or more) for the acute treatment of migraine in adults. Triptans are
prescribed for and used by pediatric migraineurs with very limited
systematically collected data supporting their safety and efficacy in this
population. Two well-controlled trials performed with rizatriptan 5 mg in
adolescents aged 12 to 17 failed to demonstrate a statistically significant
difference between treatments on the primary endpoint (pain freedom at hour 2
post dose). However, a response trend was observed in the rizatriptan group in
the lower age stratum (12-14 years) compared to the higher age stratum (15-17
years), as well as by weight, in that heavier children trended toward
poorer outcomes. These findings suggest that the older and heavier children may
have had insufficient exposures based on weight. A third controlled trial
conducted by Ahonen et al. applied a weight-based dosing strategy for pediatric
migraineurs age 6 to 17, wherein patients weighing < 40 kg received rizatriptan
5 mg or placebo and patients weighing * 40 kg received rizatriptan 10 mg or
placebo. This study demonstrated a significant treatment effect for both doses
of rizatriptan compared to placebo [1]. Data from a recently completed
pharmacokinetic study (P083) demonstrated that exposures following single dose
administration of 5 mg rizatriptan ODT to pediatric
migraineurs weighing 20-39 kg or 10 mg rizatriptan orally disintegrating tablet
(ODT) to pediatric migraineurs weighing * 40 kg were similar to those observed
following single dose administration of 10 mg rizatriptan ODT to adults. This
study plans to use a similar weight-based dosing strategy to further assess the
long term safety and tolerability of rizatriptan in pediatric migraineurs. Two
oral formulations of rizatriptan are currently available: solid tablet and ODT.
The ODT formulation accounts for slightly more than half of the prescriptions
in pediatric patients.
Study objective
The objective of this study is to test the safety of the research study drug,
MK-0462 (rizatriptan) and to test the ability of study drug to relieve or
reduce migraine for the study population.
Study design
This is an open label study. All patients will receive rizatriptan for up to 12
months. Study medication will be dosed based on the patient*s body weight at
screening (Visit 1). Patients weighing < 40 kg will receive 5 mg, whereas
patients weighing 40 kg or more will receive 10 mg. Patients will be provided
with sufficient medication to treat up to 8 migraine attacks per month during
the study.
Intervention
Rizatriptan ODT (5 mg and 10 mg) will be provided by the SPONSOR and dosed
according to screening body weight as follows: patients weighing < 40 kg will
receive rizatriptan 5 mg; and patients weighing * 40 kg will receive
rizatriptan 10 mg. Patients will be provided with sufficient medication to
treatment up to 8 migraine attacks per month.
Study burden and risks
Reported side effects for MK-0462 (rizatriptan) are:
Numbness, pain and/or pressure (chest, neck, throat and/or jaw region and
general), dry, mouth, nausea, dizziness, headache, sleepiness,
weakness/tiredness, seizures, anaphylactic reaction (a potentially
life-threatening allergic reaction that requires immediate medical attention)
In addition, an uncommon but potentially life-threatening condition called
serotonin syndrome can occur with rizatriptan or other medications in the
triptan class particularly when taken together with certain types of
antidepressant and mood disorder medications called selective serotonin
reuptake inhibitors (SSRIs), such as fluoxetine, paroxetine, sertraline,
olanzapine/fluoxetine, citalopram hydrobromide, escitalopram oxalate, and
selective serotonin/norepinephrine reuptake inhibitors (SNRIs), such as
venlafaxine, and duloxetine.
UG4C-54, P.O. Box 1000
PA 19454-2505 Upper Gwynedd
US
UG4C-54, P.O. Box 1000
PA 19454-2505 Upper Gwynedd
US
Listed location countries
Age
Inclusion criteria
1. Patient is between 12 and 17 years of age at screening visit 1, inclusive.
2. Patient weighs * 20 kg.
3. Patient is either:
a. of reproductive potential and agrees to maintain true abstinence* or use (or have
their partner use) one of the listed highly effective methods of birth control within
the projected duration of the study: hormonal contraceptives, intrauterine device
(IUD), condoms, diaphragm, and/or vasectomy. The use of barrier contraceptive
(condom or diaphragm) should always be supplemented with the use of a
spermicide. Complete details regarding contraceptive requirements are specified
in protocol Section 3.2.3.2.
b. not of reproductive potential. For the purposes of this protocol, the following
definitions apply:
A female patient who is not of reproductive potential is defined as:
one who 1) has not reached menarche, or 2) is 6 weeks post surgical bilateral
oophorectomy, hysterectomy, or bilateral tubal ligation.
A male patient who is not of reproductive potential is defined as:
one who has undergone a successful vasectomy. A successful vasectomy is
defined as: 1) microscopic documentation of azoospermia, or 2) a vasectomy
more than 2 years ago with no resultant pregnancy despite sexual activity post
vasectomy.
* If abstinence is not a locally acceptable method of contraception, then another highly
effective birth control method must be used.
4. Patient has a history of migraine defined by International Headache Society [IHS]
migraine definitions, and meets the following criteria:
a. Unilateral or bilateral migraine headache, with or without aura;
b. History of migraine attacks for > 6 months; and
c. Reports * 1 to * 8 mild, moderate or severe migraine attacks per month in the
2 months prior to screening Visit 1.
5. Patient is able to complete the migraine diary and is cooperative with completing the
prestudy assessments. Patients who require help to read should be assisted by an
adult; however, the patient will provide the actual responses to the pain scale
questions in the migraine diary.
6. The parent or guardian and patient agree to the patient*s participation in the study as
indicated by parental/guardian signature on the consent form and patient assent.
7. For patients taking migraine prophylactic medication, treatment regimen has been
stable for at least 3 months prior to Visit 1.
Exclusion criteria
1. Patient is pregnant (positive serum *-hCG test at screening) or breast-feeding, or is a
female expecting to conceive within the projected duration of study participation.
2. Patient has a history of predominantly mild migraine attacks or migraines usually
resolved spontaneously in less than 2 hours.
3. Patient has basilar or hemiplegic migraine headaches (see Appendix 6.2 for
diagnostic guidance for basilar type migraines).
4. Patient has >15 headache-days per month OR has taken medication for acute
headache on more than 10 days per month in any of the 3 months prior to screening.
5. Patient has clinical, laboratory, or ECG evidence of uncontrolled hypertension,
uncontrolled diabetes, HIV disease, any neoplastic disease, or other significant
pulmonary, renal, hepatic, endocrine, neurological, or other systemic disease in the
opinion of the investigator (e.g., epilepsy; systemic lupus erythematosus; Kawasaki
disease; homozygous sickle cell anemia; recurrent syncope).
6. Patient has a history or clinical evidence of any of the following: congenital heart
disease suspected or confirmed; atherosclerotic disease; history of cerebrovascular
pathology including stroke; Prinzmetal*s angina; cardiac arrhythmias requiring
medication; and hypertension for age.
7. Patient has a history or current evidence of any clinically significant disease that,
according to the investigator, might confound the results of the study [e.g., chronic
pain syndromes (i.e., condition requiring daily use of opiates), major psychiatric
diagnoses such as schizophrenia, bipolar disorder, or major depression], that
complicate the interpretation of the study results, that might interfere with the
patient*s participation for the full duration of the study, or pose an additional undue
risk to the patient.
8. Patient has either demonstrated hypersensitivity to or experienced a serious adverse
event in response to rizatriptan.
9. Patient has demonstrated hypersensitivity to or experienced a serious adverse event in
response to 3 or more pharmacologic classes of drugs (prescription and over-thecounter).
10. Patient did not experience satisfactory relief from migraine pain with treatment of 2
or more adequate courses of 5HT1 agonists, in the opinion of the investigator.
11. Patient has a recent history (within the past year) or current evidence of drug or
alcohol abuse or is a "recreatinoal user' of illicit drugs
12. Patient is currently taking monoamine oxidase inhibitors, methysergide, or
propranolol, and is unable to tolerate withdrawal of these medications for the
intervals required.
13. Patient is currently participating or has participated in a study with an investigational
compound or device within 30 days of screening. (This includes studies using
commercially available compounds or devices for investigational purposes, e.g., new
indications). Note: Patients who participated in the acute efficacy study (rizatriptan may enter into this study within 30 days of completion of the acute
study.
14. Patient has abnormal screening laboratory values as per the guidelines listed below or
other clinically significant, unexplained laboratory abnormality, according to the
investigator:
a. AST > 1.5 x upper limit of normal
b. ALT > 1.5 x upper limit of normal
c. Total bilirubin > 1.5 x upper limit of normal
d. Serum creatinine > 1.5 x upper limit of normal
15. Patient is legally or mentally incapacitated.
16. Patient has undergone major surgery (in the opinion of the investigator) within 30
days of screening or has donated blood products or has had phlebotomy of > 300 ml
within 8 weeks of signing informed consent, or intends to donate blood products or
receive blood products within 30 days of screening and throughout the study.
17. Patient is unlikely to adhere to study procedures, keep appointments, or is planning to
relocate during the study.
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 |
---|---|
EudraCT | EUCTR2009-016375-30-NL |
ClinicalTrials.gov | NCT01004263 |
CCMO | NL30631.075.09 |