Long-Term Exposure to Rizatriptan 5-mg and 10-mg Oral Tablet (Combined Extension Protocols MK-0462-022, MK-0462-025, MK-0462-029)

• Sponsor: Organon and Co (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01286207
• Collaborator: (none)
• Enrollment: 1,959
• Arms: 3
• Duration (Months): 26

Study Details

Study Description

Brief Summary

This record describes pooled data for three extension studies: MK-0462-022 (NCT00897949); MK-0462-025 (NCT00899379); and MK-0462-029 (NCT00897104). These studies examined the long-term safety and efficacy of rizatriptan used for the treatment of acute migraine and migraine recurrence.

Condition or Disease	Intervention/Treatment	Phase
Migraine Disorders	Drug: Rizatriptan 5 mg; Drug: Rizatriptan 10 mg; Drug: Standard Care	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 1959 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: Long-Term Exposure to Rizatriptan 5-mg and 10-mg Oral Tablet (Combined Protocols 022, 025, 029)
• Study Start Date: Mar 1, 1995
• Actual Primary Completion Date: May 1, 1997
• Actual Study Completion Date: May 1, 1997

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Rizatriptan 5 mg Rizatriptan 5 mg orally once for treatment of index migraine attack, followed by two additional doses within 24 hours of the initial dose for migraine recurrence(s)	Drug: Rizatriptan 5 mg; Rizatriptan 5 mg orally once for treatment of index migraine attack, followed by two additional doses within 24 hours of the initial dose for migraine recurrence(s); Other Names: MK-0462, Maxalt
Experimental: Rizatriptan 10 mg Rizatriptan 10 mg orally once for treatment of index migraine attack, followed by two additional doses within 24 hours of the initial dose for migraine recurrence(s)	Drug: Rizatriptan 10 mg; Rizatriptan 10 mg orally once for treatment of index migraine attack, followed by two additional doses within 24 hours of the initial dose for migraine recurrence(s); Other Names: MK-0462, Maxalt
Active Comparator: Standard Care Standard care at onset of migraine attack	Drug: Standard Care; Active standard care

Outcome Measures

Primary Outcome Measures

1. Percent of Patient's Headaches With Pain Relief at 2 Hours After the Initial Dose of Test Drug [2 hours after initial dose of test drug]

   Headache severity was rated on a 4-point scale (0 = no headache; 1 = mild pain; 2 = moderate pain; 3 = severe pain) immediately before initial dose and at 2 hours thereafter. Pain relief was defined as a reduction of headache severity from grades 2/3 at baseline to 0/1.

2. Number of Participants With Serious Clinical Adverse Experiences [Up to 12 months]

   Serious clinical adverse experiences (CAEs) are any adverse events (AEs) occurring at any dose that; results in death; or is life threatening; or results in a persistent or significant disability/incapacity; or results in or prolongs an existing inpatient hospitalization; or is a congenital anomaly/birth defect; or is a cancer; or is an overdose.

3. Number of Participants With Drug-related Clinical Adverse Experiences [Up to 12 months]

   Patients with drug-related (as assessed by an investigator who is a qualified physician according to his/her best clinical judgment) CAEs.

4. Number of Participants Who Discontinued Due to Clinical Adverse Experiences [Up to 12 months]

5. Number of Participants With Drug-related Lab Adverse Experiences [Up to 12 weeks]

   Patients with drug-related (as assessed by an investigator who is a qualified physician according to his/her best clinical judgment) laboratory adverse experience (LAE). A LAE is defined as any unfavorable and unintended change in the chemistry of the body temporally associated with the use of the SPONSOR'S product, whether or not considered related to the use of the product.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Participant took part in study MK-0462-022, MK-0462-025, or MK-0462-029

• History of migraine headache

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Organon and Co

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Organon and Co
• ClinicalTrials.gov Identifier: NCT01286207
• Other Study ID Numbers: 0462 Pooled 022/025/029
• First Posted: Jan 31, 2011
• Last Update Posted: Feb 3, 2022
• Last Verified: Feb 1, 2022

• Keywords provided by Organon and Co: Migraine headache
• Additional relevant MeSH terms: Migraine Disorders; Rizatriptan

Study Results

Participant Flow

Pre-assignment Detail	All participants that completed protocol MK-0462-022 (NCT00897949), MK-0462-025 (NCT00899379), or MK-0462-029 (NCT00897104) and consented to continue in the studies up to 12 months were included in this pooled extension data.

Arm/Group Title	Rizatriptan 5 mg	Rizatriptan 10 mg	Standard Care
Arm/Group Description	Rizatriptan 5 mg orally once for treatment of index migraine attack, followed by two additional doses within 24 hours of the initial dose for migraine recurrence(s)	Rizatriptan 10 mg orally once for treatment of index migraine attack, followed by two additional doses within 24 hours of the initial dose for migraine recurrence(s)	Standard care at onset of migraine attack
Period Title: Overall Study
STARTED	751	857	351
COMPLETED	453	609	261
NOT COMPLETED	298	248	90

Baseline Characteristics

Arm/Group Title	Rizatriptan 5 mg	Rizatriptan 10 mg	Standard Care	Total
Arm/Group Description	Rizatriptan 5 mg orally once for treatment of index migraine attack, followed by two additional doses within 24 hours of the initial dose for migraine recurrence(s)	Rizatriptan 10 mg orally once for treatment of index migraine attack, followed by two additional doses within 24 hours of the initial dose for migraine recurrence(s)	Standard care at onset of migraine attack	Total of all reporting groups
Overall Participants	751	857	351	1959
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	41.6	41.1	40.7	41.2
Sex: Female, Male (Count of Participants)
Female	643 85.6%	727 84.8%	300 85.5%	1670 85.2%
Male	108 14.4%	130 15.2%	51 14.5%	289 14.8%

Outcome Measures

1. Primary Outcome

Title	Percent of Patient's Headaches With Pain Relief at 2 Hours After the Initial Dose of Test Drug
Description	Headache severity was rated on a 4-point scale (0 = no headache; 1 = mild pain; 2 = moderate pain; 3 = severe pain) immediately before initial dose and at 2 hours thereafter. Pain relief was defined as a reduction of headache severity from grades 2/3 at baseline to 0/1.
Time Frame	2 hours after initial dose of test drug

Outcome Measure Data

Analysis Population Description

All patients who took study medication and filled out their diary cards were included in the analysis of efficacy. No data were imputed.

Arm/Group Title	Rizatriptan 5 mg	Rizatriptan 10 mg	Standard Care
Arm/Group Description	Rizatriptan 5 mg orally once for treatment of index migraine attack, followed by two additional doses within 24 hours of the initial dose for migraine recurrence(s)	Rizatriptan 10 mg orally once for treatment of index migraine attack, followed by two additional doses within 24 hours of the initial dose for migraine recurrence(s)	Standard care at onset of migraine attack
Measure Participants	606	815	325
Median (Inter-Quartile Range) [percent of headaches]	80	89.5	69.6

2. Primary Outcome

Title	Number of Participants With Serious Clinical Adverse Experiences
Description	Serious clinical adverse experiences (CAEs) are any adverse events (AEs) occurring at any dose that; results in death; or is life threatening; or results in a persistent or significant disability/incapacity; or results in or prolongs an existing inpatient hospitalization; or is a congenital anomaly/birth defect; or is a cancer; or is an overdose.
Time Frame	Up to 12 months

Outcome Measure Data

Analysis Population Description

All patients who took study medication were included in the analysis.

Arm/Group Title	Rizatriptan 5 mg	Rizatriptan 10 mg	Standard Care
Arm/Group Description	Rizatriptan 5 mg orally once for treatment of index migraine attack, followed by two additional doses within 24 hours of the initial dose for migraine recurrence(s)	Rizatriptan 10 mg orally once for treatment of index migraine attack, followed by two additional doses within 24 hours of the initial dose for migraine recurrence(s)	Standard care at onset of migraine attack
Measure Participants	711	834	334
With Serious CAEs	13 1.7%	17 2%	10 2.8%
Without Serious CAEs	698 92.9%	817 95.3%	324 92.3%

3. Primary Outcome

Title	Number of Participants With Drug-related Clinical Adverse Experiences
Description	Patients with drug-related (as assessed by an investigator who is a qualified physician according to his/her best clinical judgment) CAEs.
Time Frame	Up to 12 months

Outcome Measure Data

Analysis Population Description

All patients who took study medication were included in the analysis.

Arm/Group Title	Rizatriptan 5 mg	Rizatriptan 10 mg	Standard Care
Arm/Group Description	Rizatriptan 5 mg orally once for treatment of index migraine attack, followed by two additional doses within 24 hours of the initial dose for migraine recurrence(s)	Rizatriptan 10 mg orally once for treatment of index migraine attack, followed by two additional doses within 24 hours of the initial dose for migraine recurrence(s)	Standard care at onset of migraine attack
Measure Participants	711	834	334
With drug-related CAEs	288 38.3%	456 53.2%	139 39.6%
Without drug-related CAEs	423 56.3%	378 44.1%	195 55.6%

4. Primary Outcome

Title	Number of Participants Who Discontinued Due to Clinical Adverse Experiences
Time Frame	Up to 12 months

Outcome Measure Data

Analysis Population Description

All patients who took study medication were included in the analysis.

Arm/Group Title	Rizatriptan 5 mg	Rizatriptan 10 mg	Standard Care
Arm/Group Description	Rizatriptan 5 mg orally once for treatment of index migraine attack, followed by two additional doses within 24 hours of the initial dose for migraine recurrence(s)	Rizatriptan 10 mg orally once for treatment of index migraine attack, followed by two additional doses within 24 hours of the initial dose for migraine recurrence(s)	Standard care at onset of migraine attack
Measure Participants	711	834	334
Discontinued due to CAEs	26 3.5%	37 4.3%	7 2%
Not discontinued due to CAEs	685 91.2%	797 93%	327 93.2%

5. Primary Outcome

Title	Number of Participants With Drug-related Lab Adverse Experiences
Description	Patients with drug-related (as assessed by an investigator who is a qualified physician according to his/her best clinical judgment) laboratory adverse experience (LAE). A LAE is defined as any unfavorable and unintended change in the chemistry of the body temporally associated with the use of the SPONSOR'S product, whether or not considered related to the use of the product.
Time Frame	Up to 12 weeks

Outcome Measure Data

Analysis Population Description

All patients who took study medication and had lab test(s)were included in the analysis.

Arm/Group Title	Rizatriptan 5 mg	Rizatriptan 10 mg	Standard Care
Arm/Group Description	Rizatriptan 5 mg orally once for treatment of index migraine attack, followed by two additional doses within 24 hours of the initial dose for migraine recurrence(s)	Rizatriptan 10 mg orally once for treatment of index migraine attack, followed by two additional doses within 24 hours of the initial dose for migraine recurrence(s)	Standard care at onset of migraine attack
Measure Participants	709	827	333
Number [participants]	15 2%	23 2.7%	4 1.1%

Adverse Events

Adverse Event Reporting Description	The 'total # participants affected' w/ Other AEs DOES include subjects w/ any AE (including SAEs) >1 event. The true overall # of subjects affected w/ only any NonSerious AE >5% is less than the # reported, but unable to be determined for this pooled extension period. Specific Other AEs reported DO NOT include SAEs and DO NOT include events <5%
Arm/Group Title	Rizatriptan 5 mg		Rizatriptan 10 mg		Standard Care
Arm/Group Description	Rizatriptan 5 mg orally once for treatment of index migraine attack, followed by two additional doses within 24 hours of the initial dose for migraine recurrence(s)		Rizatriptan 10 mg orally once for treatment of index migraine attack, followed by two additional doses within 24 hours of the initial dose for migraine recurrence(s)		Standard care at onset of migraine attack
All Cause Mortality
	Rizatriptan 5 mg		Rizatriptan 10 mg		Standard Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Rizatriptan 5 mg		Rizatriptan 10 mg		Standard Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/711 (1.8%)		17/834 (2%)		10/334 (3%)
Blood and lymphatic system disorders
Agranulocytosis	0/711 (0%)		1/834 (0.1%)		0/334 (0%)
Thrombocytopenia	0/711 (0%)		1/834 (0.1%)		0/334 (0%)
Cardiac disorders
Embolism/infarction, pulmonary	0/711 (0%)		1/834 (0.1%)		0/334 (0%)
Endocrine disorders
Neoplasm, thyroid, malignant	1/711 (0.1%)		0/834 (0%)		0/334 (0%)
Gastrointestinal disorders
Appendicitis	0/711 (0%)		1/834 (0.1%)		0/334 (0%)
Cholelithiasis	0/711 (0%)		1/834 (0.1%)		1/334 (0.3%)
Gastroenteritis	1/711 (0.1%)		0/834 (0%)		0/334 (0%)
Hemorrhage, anal/rectal	0/711 (0%)		1/834 (0.1%)		0/334 (0%)
Rectocele	1/711 (0.1%)		0/834 (0%)		0/334 (0%)
Vomiting	0/711 (0%)		1/834 (0.1%)		0/334 (0%)
General disorders
Hernia, inguinal	0/711 (0%)		0/834 (0%)		1/334 (0.3%)
Melanoma	1/711 (0.1%)		0/834 (0%)		0/334 (0%)
Pain, abdominal	0/711 (0%)		1/834 (0.1%)		2/334 (0.6%)
Pain, chest	0/711 (0%)		1/834 (0.1%)		0/334 (0%)
Septicimea	0/711 (0%)		0/834 (0%)		1/334 (0.3%)
Surgery, abdominal	0/711 (0%)		0/834 (0%)		1/334 (0.3%)
Trauma	1/711 (0.1%)		0/834 (0%)		0/334 (0%)
Metabolism and nutrition disorders
Anaphylaxis	0/711 (0%)		1/834 (0.1%)		0/334 (0%)
Dehydration	0/711 (0%)		1/834 (0.1%)		0/334 (0%)
Musculoskeletal and connective tissue disorders
Fracture, elbow, right	0/711 (0%)		1/834 (0.1%)		0/334 (0%)
Fracture, hip, right	1/711 (0.1%)		0/834 (0%)		0/334 (0%)
Pain, back	0/711 (0%)		1/834 (0.1%)		0/334 (0%)
Pain, knee	1/711 (0.1%)		0/834 (0%)		0/334 (0%)
Pain, neck	1/711 (0.1%)		1/834 (0.1%)		0/334 (0%)
Trauma, cartilage	1/711 (0.1%)		0/834 (0%)		0/334 (0%)
Nervous system disorders
Anxiety	1/711 (0.1%)		0/834 (0%)		0/334 (0%)
Depression	1/711 (0.1%)		0/834 (0%)		1/334 (0.3%)
Headache	0/711 (0%)		1/834 (0.1%)		0/334 (0%)
Meningitis	0/711 (0%)		0/834 (0%)		1/334 (0.3%)
Migraine	1/711 (0.1%)		3/834 (0.4%)		3/334 (0.9%)
Reproductive system and breast disorders
Abortion	0/711 (0%)		1/834 (0.1%)		0/334 (0%)
Cystocele	0/711 (0%)		0/834 (0%)		1/334 (0.3%)
Hypertrophy, uterine	0/711 (0%)		1/834 (0.1%)		0/334 (0%)
Neoplasm, breast, malignant	1/711 (0.1%)		0/834 (0%)		0/334 (0%)
Neoplasm, uterine, benign	1/711 (0.1%)		0/834 (0%)		0/334 (0%)
Pregnancy	0/711 (0%)		1/834 (0.1%)		0/334 (0%)
Prostatitis	0/711 (0%)		1/834 (0.1%)		0/334 (0%)
Respiratory, thoracic and mediastinal disorders
Asthma	0/711 (0%)		1/834 (0.1%)		0/334 (0%)
Wheezing	0/711 (0%)		1/834 (0.1%)		0/334 (0%)
Skin and subcutaneous tissue disorders
Neoplasm, skin, malignant	0/711 (0%)		2/834 (0.2%)		0/334 (0%)
Other (Not Including Serious) Adverse Events
	Rizatriptan 5 mg		Rizatriptan 10 mg		Standard Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	492/711 (69.2%)		679/834 (81.4%)		267/334 (79.9%)
Gastrointestinal disorders
Diarrhea	21/711 (3%)		32/834 (3.8%)		18/334 (5.4%)
Nausea	117/711 (16.5%)		178/834 (21.3%)		86/334 (25.7%)
Vomiting	51/711 (7.2%)		72/834 (8.6%)		29/334 (8.7%)
General disorders
Asthenia/fatigue	70/711 (9.8%)		111/834 (13.3%)		44/334 (13.2%)
Pain, abdominal	24/711 (3.4%)		27/834 (3.2%)		18/334 (5.4%)
Pain, chest	34/711 (4.8%)		61/834 (7.3%)		28/334 (8.4%)
Musculoskeletal and connective tissue disorders
Pain, back	30/711 (4.2%)		48/834 (5.8%)		18/334 (5.4%)
Nervous system disorders
Dizziness	69/711 (9.7%)		135/834 (16.2%)		35/334 (10.5%)
Headache	62/711 (8.7%)		100/834 (12%)		42/334 (12.6%)
Insomnia	21/711 (3%)		31/834 (3.7%)		17/334 (5.1%)
Paresthesia	34/711 (4.8%)		63/834 (7.6%)		24/334 (7.2%)
Somnolence	50/711 (7%)		127/834 (15.2%)		30/334 (9%)
Respiratory, thoracic and mediastinal disorders
Infection, respiratory, upper	78/711 (11%)		114/834 (13.7%)		46/334 (13.8%)
Influenza	46/711 (6.5%)		52/834 (6.2%)		25/334 (7.5%)
Pharyngitis	21/711 (3%)		47/834 (5.6%)		22/334 (6.6%)
Sinusitis	37/711 (5.2%)		72/834 (8.6%)		26/334 (7.8%)

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.