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
1. To evaluate the efficacy of rizatriptan compared to placebo in the treatment
of acute migraine as measured by pain freedom at 2 hours in pediatric
migraineurs between 12 and 17 years of age who have not, historically, achieved
satisfactory response to
treatment with NSAIDS or APAP.
2. To evaluate the safety and tolerability of rizatriptan in pediatric
migraineurs between 12 and 17 years of age who have not, historically, achieved
a satisfactory response to treatment with NSAIDS or APAP.
Secondary outcome
1. To evaluate the efficacy of rizatriptan compared to placebo in the treatment
of acute migraine as measured by pain relief at 2 hours in pediatric
migraineurs between 12 and 17 years of age who have not, historically, achieved
a satisfactory response to
treatment with NSAIDS or APAP.
2. To evaluate the efficacy of rizatriptan compared to placebo in the treatment
of acute migraine as measured by pain freedom at 2 hours in pediatric
migraineurs between 6 and 17 years of age who have not, historically, achieved
a satisfactory response to treatment with NSAIDS or APAP.
3. To evaluate the efficacy of rizatriptan compared to placebo in the treatment
of acute migraine as measured by pain relief at 2 hours in pediatric
migraineurs between 6 and 17 years of age who have not, historically, achieved
a satisfactory response to treatment with NSAIDS or APAP.
4. To evaluate the safety and tolerability of rizatriptan in pediatric
migraineurs between 6 and 17 years of age who have not, historically, achieved
a satisfactory response to treatment with NSAIDS or APAP.
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 MAXALTby 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 or more hours) for the acute treatment
of migraine in adults. 5-HT1B/1D agonists (triptans) are prescribed for and
used by pediatric migraineurs with very limited systematically collected data
on their safety and efficacy in this population. Two well-controlled trials
conducted with rizatriptan 5 mg in adolescents aged 12 to 17 failed to
demonstrate a statistically significant difference between the treatments on
the primary endpoint (pain freedom at 2 hours 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 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 efficacy and safety of rizatriptan in
pediatric migraineurs age 6 to 17 years. Two oral formulations of rizatriptan
are currently available: solid tablet and orally disintegrating tablet (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 a randomized, double-blind (with in-house blinding),
placebo-controlled, parallelgroup study. Patients will treat a single migraine
attack in two stages, with Stage 1 to identify placebo non-responders who will
then enter into Stage 2. In Stage 1, patients will be randomized in a 20:1
ratio to placebo or rizatriptan, with randomization stratified based on age (6
to 11 years old vs. 12 to 17 years old). Patients will administer study
medication within 30 minutes of onset of a qualifying migraine attack. After 15
minutes, patients will call into the Interactive Voice Response (IVR) system to
report their pain intensity level. Patients who report mild pain or no pain
(i.e., responders) will be instructed to take no further study medication.
Patients who report moderate or severe pain (i.e., non-responders) will be
instructed to take study medication in Stage 2. Nonresponders to placebo in
Stage 1 will be randomized in a 1:1 ratio to rizatriptan or placebo, with
randomization stratified based on age (6 to 11 years old vs. 12 to 17 years
old) and migraine intensity reported at 15 minutes post Stage 1 dose (moderate
versus severe). The migraine intensity reported at 15 minutes post Stage 1 dose
will be used as the Stage 2 baseline pain severity. Non-responders to
rizatriptan in Stage 1 will be allocated to receive placebo in Stage 2.
A qualifying migraine is defined as a migraine of moderate or severe intensity
and treatment with study medication is limited to settings where the study
procedures may be followed (Please see section 3.2.3.6.1 Qualifying Migraine
for further details). Patients will complete a paper migraine diary at
prespecified time points to evaluate efficacy and tolerability.
Intervention
The study has two stages:
Stage 1 treatment is to be administered within 30 minutes following the onset
of a qualifying migraine.
Stage 2 treatment is to be administered immediately after IVRS confirmation for
Stage 2 (occurring just after the 15-minute post dose response for Stage 1).
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 6 and 17 years of age inclusive at screening Visit 1.
2. Patient weighs * 20 kg.
3. Patient has a history of migraine as defined by International Headache Society [IHSAppendix
6.1, 6.3] migraine definitions and meets the following criteria:
a. Unilateral or bilateral migraine headache, with or without aura;
b. History of migraine attacks for more than 6 months;
c. Reports * 1 to * 8 moderate or severe migraine attacks per month in the 2 months
prior to screening Visit 1. This also includes attacks which were treated early,
while pain was mild, but which, in the patient*s judgment, would have progressed
to moderate or severe if untreated.
d. Duration of a typical untreated migraine attack (excluding sleep) is * 3 hours.
4. Patient has had a history of migraine with or without aura for more than 6 months
5. 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, 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.
OR
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.
6. Patient is willing to stay awake for at least 2 hours after administration of the first
dose of study medication.
7. Patient has not experienced satisfactory relief from migraine pain with NSAIDs or
APAP treatment, in the opinion of the investigator.
8. 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 written responses to the pain scale
questions in the migraine diary.
9. 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.
10. For patients taking migraine prophylactic medication, treatment regimen is stable and
has been taken 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 (For diagnostic criteria for
basilar migraine, see Appendix 6.2)
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 congenital heart disease suspected or
confirmed; atherosclerotic disease; history of cerebrovascular pathology including
stroke; Prinzmetal*s angina; cardiac arrhythmias requiring medication; or
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
0462, Protocol 082-00 Issue Date: 01-Sep-2009 17
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, 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 (over-the-counter and
prescription).
10. Patient did not experience satisfactory relief from migraine pain to prior treatment
with 2 or more adequate courses of 5HT1 agonists.
11. Patient has a recent history (within the past year) or current evidence of drug or
alcohol abuse or is a
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).
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.
0462, Protocol 082-00 Issue Date: 01-Sep-2009 18
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 | EUCTR2009-016374-32-NL |
| ClinicalTrials.gov | NCT01001234 |
| CCMO | NL30596.075.09 |