A Study to Evaluate the Efficacy and Tolerability of Rizatriptan for Treatment of Acute Migraine (0462-087)

• Sponsor: Organon and Co (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00894556
• Collaborator: (none)
• Enrollment: 109
• Arms: 4
• Actual Duration (Months): 7.1

Study Details

Study Description

Brief Summary

A study to provide evidence supporting the benefit of Rizatriptan in patients who have an inadequate response to sumatriptan.

Condition or Disease	Intervention/Treatment	Phase
Acute Migraine	Drug: rizatriptan; Drug: Comparator: Placebo; Drug: Comparator: Sumatriptan	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 109 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Crossover Trial to Evaluate the Efficacy and Tolerability of Rizatriptan 10 mg for the Treatment of Acute Migraine in Sumatriptan Non-Responders
• Actual Study Start Date: Jun 10, 2009
• Actual Primary Completion Date: Jan 12, 2010
• Actual Study Completion Date: Jan 12, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment Sequence A Rizatriptan - Rizatriptan - Placebo	Drug: rizatriptan; Single dose of 10 mg orally disintegrating tablet at onset of migraine attack; Drug: Comparator: Placebo; Placebo to Rizatriptan
Experimental: Treatment Sequence B Rizatriptan - Placebo - Rizatriptan	Drug: rizatriptan; Single dose of 10 mg orally disintegrating tablet at onset of migraine attack; Drug: Comparator: Placebo; Placebo to Rizatriptan
Experimental: Treatment Sequence C Placebo - Rizatriptan - Rizatriptan	Drug: rizatriptan; Single dose of 10 mg orally disintegrating tablet at onset of migraine attack; Drug: Comparator: Placebo; Placebo to Rizatriptan
Other: Baseline Phase Sumatriptan	Drug: Comparator: Sumatriptan; single dose of generic sumatriptan 100 mg at onset of migraine attack

Outcome Measures

Primary Outcome Measures

1. Pain Relief (PR) [2 hours post dose]

   Pain severity was rated by the participants in a paper diary. Pain severity rating scale: 0 (no pain), 1 (mild pain), 2 (moderate pain), or 3 (severe pain). Pain relief (PR) is defined as a reduction in headache severity from Grade 3/2 at baseline to Grade 1/0 post dose.

Secondary Outcome Measures

1. Pain Freedom (PF) [2 hours post dose]

   Headache pain severity, relative to the administration of study medication, was rated by the participants in a paper diary. Pain severity rating scale: 0 (no pain), 1 (mild pain), 2 (moderate pain), or 3 (severe pain). Pain freedom (PF) is defined as a reduction in headache severity from Grade 3/2 at baseline to Grade 0 (no pain) post dose.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patient has a history of migraine with or without aura for 1 year or more with 2-8 moderate or severe migraine attacks per month

• Patient generally does not respond to treatment with sumatriptan

• Patient of reproductive potential agrees to remain abstinent or use one method of highly effective birth control (i.e. IUD, condoms, hormonal contraceptive, diaphragm, vasectomy) for the duration of the study

• Patient is able to complete paper diary

Exclusion Criteria:

• Patient is pregnant or breast feeding or excepts to become pregnant during the study

• Patient has history of mild migraine attacks or migraines that usually resolve spontaneously in less than 2 hours

• Patient has basilar or hemiplegic migraines

• Patient is unable to distinguish between migraine attacks from other types of headaches

• Patient has more than 15 headache-days per month

• Patient was greater than 50 years old at age of migraine onset

• Patient has failed to respond to 3 or more triptans

• Patient has a repeated history of failing to respond to or tolerate rizatriptan

• Patient uses opioids as primary migraine therapy

• Patient uses daily opioids

• Patient has a history of Cerebrovascular Accident (CVA) or other significant cardiovascular disease

• Patient has uncontrolled hypertension

• Patient has a history of neoplastic disease

• Patient is taking a serotonin reuptake inhibitor (SSRI or SNRI) where the dose has changed 3 months prior to screening

• Patient has a history of drug or alcohol abuse

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Organon and Co

Investigators

• Study Director: Medical Monitor, Merck Sharp & Dohme LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Organon and Co
• ClinicalTrials.gov Identifier: NCT00894556
• Other Study ID Numbers: 0462-087; 2009_587
• First Posted: May 7, 2009
• Last Update Posted: Feb 8, 2022
• Last Verified: Feb 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Organon and Co: Treatment of acute migraine with or without aura in adults
• Additional relevant MeSH terms: Migraine Disorders; Sumatriptan; Rizatriptan

Study Results

Participant Flow

Recruitment Details	Patients were recruited at 21 study centers in the United States. First Patient In: 10-Jun-2009; First Patient Treated: 26-Jun-2009 Last Patient Last Visit: 12-Jan-2010; Last Patient Treated: 25-Dec-2009
Pre-assignment Detail	Participants who met entry criteria but had evidence of suicidality or were severely depressed (based on questionnaire scores) were excluded. Within 2 months of entry, participants were to treat a moderate/ severe migraine attack with sumatriptan 100 mg and were randomized if they still had moderate or severe pain at 2 hours post-dose.

Arm/Group Title	Rizatriptan / Rizatriptan / Placebo	Rizatriptan / Placebo / Rizatriptan	Placebo / Rizatriptan / Rizatriptan	Sumatriptan 100 mg
Arm/Group Description	Each patient was randomized to receive one of 3 treatment sequences. Three qualifying migraines were then treated based on the prescribed sequence. Two migraine attacks were treated with rizatriptan and one with placebo. The first migraine was treated with Rizatriptan 10 mg Orally Disintegrating Tablet (ODT); the second migraine with Rizatriptan 10 mg ODT; the third migraine with placebo.	Each patient was randomized to receive one of 3 treatment sequences. Three qualifying migraines were then treated based on the prescribed sequence. Two migraine attacks were treated with rizatriptan and one with placebo. The first migraine was treated with Rizatriptan 10 mg ODT; the second migraine with placebo; and the third migraine with Rizatriptan 10 mg ODT.	Each patient was randomized to receive one of 3 treatment sequences. Three qualifying migraines were then treated based on the prescribed sequence. Two migraine attacks were treated with rizatriptan and one with placebo. The first migraine was treated with Placebo; the second migraine with Rizatriptan 10mg ODT; and the third migraine with Rizatriptan 10 mg ODT	Pre-Randomization Phase conducted 2 months prior to Study Randomization. Eligible participants were to treat a moderate/severe migraine attack with sumatriptan 100 mg. Those who failed to respond to sumatriptan (i.e. continued to experience moderate or severe pain at 2 hours post dose) were classified as non-responders and were entered into the double-blind treatment phase of the study.
Period Title: Baseline Phase
STARTED	0	0	0	194
COMPLETED	0	0	0	109
NOT COMPLETED	0	0	0	85
Period Title: Baseline Phase
STARTED	37	36	36	0
COMPLETED	33	32	35	0
NOT COMPLETED	4	4	1	0

Baseline Characteristics

Arm/Group Title	Rizatriptan / Rizatriptan / Placebo	Rizatriptan / Placebo / Rizatriptan	Placebo / Rizatriptan / Rizatriptan	Total
Arm/Group Description	The first migraine was treated with Rizatriptan 10 mg Orally Disintegrating Tablet (ODT); the second migraine with Rizatriptan 10 mg ODT; the third migraine with placebo.	The first migraine was treated with Rizatriptan 10 mg ODT; the second migraine with placebo; and the third migraine with Rizatriptan 10 mg ODT.	The first migraine was treated with Placebo; the second migraine with Rizatriptan 10mg ODT; and the third migraine with Rizatriptan 10 mg ODT	Total of all reporting groups
Overall Participants	37	36	36	109
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	42.2 (13.4)	43.6 (8.9)	43.5 (10.2)	43.1 (10.9)
Sex: Female, Male (Count of Participants)
Female	32 86.5%	33 91.7%	30 83.3%	95 87.2%
Male	5 13.5%	3 8.3%	6 16.7%	14 12.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 8.1%	1 2.8%	2 5.6%	6 5.5%
Not Hispanic or Latino	34 91.9%	35 97.2%	34 94.4%	103 94.5%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	1 2.8%	1 0.9%
Asian	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	4 10.8%	4 11.1%	3 8.3%	11 10.1%
White	31 83.8%	31 86.1%	30 83.3%	92 84.4%
More than one race	2 5.4%	1 2.8%	2 5.6%	5 4.6%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Pain Relief (PR)
Description	Pain severity was rated by the participants in a paper diary. Pain severity rating scale: 0 (no pain), 1 (mild pain), 2 (moderate pain), or 3 (severe pain). Pain relief (PR) is defined as a reduction in headache severity from Grade 3/2 at baseline to Grade 1/0 post dose.
Time Frame	2 hours post dose

Outcome Measure Data

Analysis Population Description

The FAS population included all randomized participants who had at least one evaluable attack. To be considered an evaluable attack the participant must have administered study treatment for this attack and must have had both a baseline severity measurement and at least one post-dose efficacy measurement prior to or including the 2-hour time point.

Arm/Group Title	Rizatriptan	Placebo
Arm/Group Description	Migraines were treated with Rizatriptan 10 mg ODT. Although a patient may have appeared twice in the rizatriptan group, the patient was counted only once for the rizatriptan group. It is possible for one patient to be counted in both the rizatriptan and placebo groups.	Migraines were treated with placebo
Measure Participants	102	99
Measure Evaluable Attacks	202	99
Resulting in PR at 2 hours post dose	102	21
Not resulting in PR at 2 hours post dose	100	78

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rizatriptan, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Generalized Linear Mixed Model (GLIMMIX)
	Comments	An unstructured covariance matrix was used to model the correlation among repeated measurements within patient.

2. Secondary Outcome

Title	Pain Freedom (PF)
Description	Headache pain severity, relative to the administration of study medication, was rated by the participants in a paper diary. Pain severity rating scale: 0 (no pain), 1 (mild pain), 2 (moderate pain), or 3 (severe pain). Pain freedom (PF) is defined as a reduction in headache severity from Grade 3/2 at baseline to Grade 0 (no pain) post dose.
Time Frame	2 hours post dose

Outcome Measure Data

Analysis Population Description

The FAS population included all randomized participants who had at least one evaluable attack. To be considered an evaluable attack the participant must have administered study treatment for this attack and must have had both a baseline severity measurement and at least one post-dose efficacy measurement prior to or including the 2-hour time point.

Arm/Group Title	Rizatriptan	Placebo
Arm/Group Description	Migraines were treated with Rizatriptan 10 mg ODT. Although a patient may have appeared twice in the rizatriptan group, the patient was counted only once for the rizatriptan group. It is possible for one patient to be counted in both the rizatriptan and placebo groups.	Migraines were treated with placebo
Measure Participants	102	99
Measure Evaluable Attacks	202	99
Resulting in PF at 2 hours post dose	46	12
Not resulting in PF at 2 hours post dose	156	87

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rizatriptan, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Generalized Linear Mixed Model (GLIMMIX)
	Comments	An unstructured covariance matrix was used to model the correlation among repeated measurements within patient.

Adverse Events

Time Frame	Adverse events were collected from the time that participants were enrolled (signed informed consent) through 14 days after the last dose of study medication.
Adverse Event Reporting Description	Participants reported adverse events in a paper diary and were collected by the site at Visits 2 and 3, and 14 days after the last dose of study medication. AEs that occurred in the Baseline Phase (prior to randomization) are reported as a separate arm. Events not applicable to a particular Study Phase are reported as (0/0).
Arm/Group Title	Rizatriptan 10 mg		Placebo		Sumatriptan 100 mg
Arm/Group Description	Patients took at least one dose of study medication. It is possible for one patient to be counted twice (once in each treatment group). Although a patient may have had two or more adverse events of the same type, the patient is counted only once for that type of adverse event. Adverse events occurring within 14 days of administration of Rizatriptan 10 mg are attributed to Rizatriptan 10 mg group even if placebo was administered more recently.		Adverse Events that occurred in the Baseline Phase (prior to taking study medication) are identified in the tables as "Baseline Phase"
All Cause Mortality
	Rizatriptan 10 mg		Placebo		Sumatriptan 100 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Rizatriptan 10 mg		Placebo		Sumatriptan 100 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/102 (0%)		0/100 (0%)		0/194 (0%)
Other (Not Including Serious) Adverse Events
	Rizatriptan 10 mg		Placebo		Sumatriptan 100 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/102 (17.6%)		3/100 (3%)		29/194 (14.9%)
Cardiac disorders
Tachycardia - Baseline Phase	0/0 (NaN)		0/0 (NaN)		1/194 (0.5%)
Ear and labyrinth disorders
Motion Sickness - Baseline Phase	0/0 (NaN)		0/0 (NaN)		1/194 (0.5%)
Eye disorders
Eyelid Pain - Baseline Phase	0/0 (NaN)		0/0 (NaN)		1/194 (0.5%)
Eyelid ptosis - Treatment Phase	0/102 (0%)		1/100 (1%)		0/0 (NaN)
Vision blurred - Treatment Phase	1/102 (1%)		0/100 (0%)		0/0 (NaN)
Gastrointestinal disorders
Abdominal pain - Baseline Phase	0/0 (NaN)		0/0 (NaN)		1/194 (0.5%)
Abdominal pain upper - Baseline Phase	0/0 (NaN)		0/0 (NaN)		2/194 (1%)
Dry mouth - Baseline Phase	0/0 (NaN)		0/0 (NaN)		2/194 (1%)
Nausea - Baseline Phase	0/0 (NaN)		0/0 (NaN)		4/194 (2.1%)
Paraesthesia oral - Baseline Phase	0/0 (NaN)		0/0 (NaN)		2/194 (1%)
Abdominal pain upper - Treatment Phase	2/102 (2%)		1/100 (1%)		0/0 (NaN)
Diarrhoea - Treatment Phase	1/102 (1%)		0/100 (0%)		0/0 (NaN)
Nausea - Treatment Phase	4/102 (3.9%)		0/100 (0%)		0/0 (NaN)
General disorders
Asthenia - Baseline Phase	0/0 (NaN)		0/0 (NaN)		1/194 (0.5%)
Chest discomfort - Baseline Phase	0/0 (NaN)		0/0 (NaN)		3/194 (1.5%)
Fatigue - Baseline Phase	0/0 (NaN)		0/0 (NaN)		2/194 (1%)
Oedema peripheral - Baseline Phase	0/0 (NaN)		0/0 (NaN)		1/194 (0.5%)
Pain - Baseline Phase	0/0 (NaN)		0/0 (NaN)		1/194 (0.5%)
Fatigue - Treatment Phase	1/102 (1%)		0/100 (0%)		0/0 (NaN)
Feeling of relaxation - Treatment Phase	1/102 (1%)		0/100 (0%)		0/0 (NaN)
Gait disturbance - Treatment Phase	0/102 (0%)		1/100 (1%)		0/0 (NaN)
Influenza like illness - Treatment Phase	1/102 (1%)		0/100 (0%)		0/0 (NaN)
Sensation of pressure - Treatment Phase	1/102 (1%)		0/100 (0%)		0/0 (NaN)
Infections and infestations
Hordeolum - Baseline Phase	0/0 (NaN)		0/0 (NaN)		1/194 (0.5%)
Nasopharyngitis - Baseline Phase	0/0 (NaN)		0/0 (NaN)		1/194 (0.5%)
Rhinitis - Baseline Phase	0/0 (NaN)		0/0 (NaN)		1/194 (0.5%)
Injury, poisoning and procedural complications
Foot fracture - Baseline Phase	0/0 (NaN)		0/0 (NaN)		1/194 (0.5%)
Facial bones fracture - Treatment Phase	1/102 (1%)		0/100 (0%)		0/0 (NaN)
Wrist fracture - Treatment Phase	1/102 (1%)		0/100 (0%)		0/0 (NaN)
Investigations
Heart rate increased - Baseline Phase	0/0 (NaN)		0/0 (NaN)		2/194 (1%)
Musculoskeletal and connective tissue disorders
Back pain - Baseline Phase	0/0 (NaN)		0/0 (NaN)		1/194 (0.5%)
Muscle spasms - Baseline Phase	0/0 (NaN)		0/0 (NaN)		1/194 (0.5%)
Muscle tightness - Baseline Phase	0/0 (NaN)		0/0 (NaN)		1/194 (0.5%)
Neck pain - Baseline Phase	0/0 (NaN)		0/0 (NaN)		1/194 (0.5%)
Myokymia - Treatment Phase	1/102 (1%)		0/100 (0%)		0/0 (NaN)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Melanocytic naevus - Treatment Phase	1/102 (1%)		0/100 (0%)		0/0 (NaN)
Nervous system disorders
Cognitive disorder - Baseline Phase	0/0 (NaN)		0/0 (NaN)		1/194 (0.5%)
Dizziness - Baseline Phase	0/0 (NaN)		0/0 (NaN)		9/194 (4.6%)
Headache - Baseline Phase	0/0 (NaN)		0/0 (NaN)		3/194 (1.5%)
Migraine - Baseline Phase	0/0 (NaN)		0/0 (NaN)		1/194 (0.5%)
Paraesthesia - Baseline Phase	0/0 (NaN)		0/0 (NaN)		3/194 (1.5%)
Sinus headache - Baseline Phase	0/0 (NaN)		0/0 (NaN)		1/194 (0.5%)
Cognitive disorder - Treatment Phase	0/102 (0%)		1/100 (1%)		0/0 (NaN)
Dizziness - Treatment Phase	4/102 (3.9%)		1/100 (1%)		0/0 (NaN)
Dysgeusia - Treatment Phase	1/102 (1%)		0/100 (0%)		0/0 (NaN)
Paraesthesia - Treatment Phase	2/102 (2%)		1/100 (1%)		0/0 (NaN)
Sinus headache - Treatment Phase	1/102 (1%)		0/100 (0%)		0/0 (NaN)
Somnolence - Treatment Phase	2/102 (2%)		0/100 (0%)		0/0 (NaN)
Syncope - Treatment Phase	1/102 (1%)		0/100 (0%)		0/0 (NaN)
Insomnia - Treatment Phase	1/102 (1%)		0/100 (0%)		0/0 (NaN)
Psychiatric disorders
Anxiety - Baseline Phase	0/0 (NaN)		0/0 (NaN)		1/194 (0.5%)
Insomnia - Baseline Phase	0/0 (NaN)		0/0 (NaN)		1/194 (0.5%)
Reproductive system and breast disorders
Metrorrhagia - Baseline Phase	0/0 (NaN)		0/0 (NaN)		1/194 (0.5%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea - Baseline Phase	0/0 (NaN)		0/0 (NaN)		1/194 (0.5%)
Throat tightness - Baseline Phase	0/0 (NaN)		0/0 (NaN)		2/194 (1%)
Vascular disorders
Hot flush - Baseline Phase	0/0 (NaN)		0/0 (NaN)		1/194 (0.5%)
Hot flush - Treatment Phase	1/102 (1%)		0/100 (0%)		0/0 (NaN)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Merck agreements may vary with individual investigators, but will not prohibit any investigator from publishing. Merck supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.