MK0462 5 mg, Sumatriptan 50 mg, and Placebo Comparison Study (0462-029)

• Sponsor: Organon and Co (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00897104
• Collaborator: (none)
• Enrollment: 933
• Arms: 3
• Duration (Months): 13

Study Details

Study Description

Brief Summary

A study to compare rizatriptan (MK0462) 5 mg by mouth (p.o.) and sumatriptan 50 mg p.o. for the acute treatment of a migraine attack.

Condition or Disease	Intervention/Treatment	Phase
Migraine Headache	Drug: rizatriptan benzoate (MK0462); Drug: Comparator: sumatriptan; Drug: Comparator: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 933 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Placebo-Controlled, Parallel-Groups, Outpatient Study to Compare the Efficacy and Safety of MK0462 5 mg p.o. and Sumatriptan 50 mg p.o. for the Acute Treatment of Migraine
• Study Start Date: Aug 1, 1995
• Actual Primary Completion Date: May 1, 1996
• Actual Study Completion Date: Sep 1, 1996

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 Rizatriptan	Drug: rizatriptan benzoate (MK0462); single dose 5 mg rizatriptan p.o.; Other Names: MK0462
Experimental: 2 Sumatriptan	Drug: Comparator: sumatriptan; single dose 50 mg sumatriptan p.o.
Placebo Comparator: 3 Placebo	Drug: Comparator: Placebo; Placebo to rizatriptan or sumatriptan, single dose placebo tablet taken orally

Outcome Measures

Primary Outcome Measures

1. Pain Relief at 2 Hours After Treatment [2 hours after treatment]

   Participants reporting pain relief defined as a reduction of headache severity from grades 2 or 3 (moderate or severe pain) at baseline to grades 0 or 1 (no headache or mild pain) at 2 hours after treatment

2. Time to Relief Within 2 Hours After Treatment [within 2 hours after treatment]

   Participants reporting time to relief (defined as the first time that a participant reported grade 0 or 1 in headache severity within 2 hours after treatment (for the comparison of rizatriptan 5 mg and sumatriptan 50 mg).

Secondary Outcome Measures

1. Pain Free at 2 Hours After Treatment [2 hours after treatment]

   Participants pain free (defined as a reduction of headache severity to grade 0 [no pain]) at 2 hours after treatment. Each participant rated headache severity on a 4-grade scale (0 = no headache; 1 = mild pain; 2 = moderate pain; 3 = severe pain).

2. Lack of Functional Disability at 2 Hours After Treatment as Measured by the Level of Impairment in Daily Activities [2 hours after treatment]

   Participants with no functional disability measured by the level of impairment to daily activities at 2 hours after treatment. Each participant rated functional disability on a 4-grade scale (0 =normal; 1 = daily activities mildly impaired; 2 = daily activities severely impaired; 3 =unable to carry out daily activities, required bed rest).

3. Presence or Absence of Associated Symptoms (Photophobia, Phonophobia, Nausea, and Vomiting) at 2 Hours After Treatment [2 hours after treatment]

   Participants who recorded the presence or absence of the associated symptoms photophobia, phonophobia, nausea, and vomiting at 2 hours after treatment.

4. Participants Who Used Escape Medication 2 Hours After the Treatment Dose [2 hours after treatment]

   Escape medication is defined as rescue medication for participants who experienced lack of efficacy from the study medication.

5. Duration of Relief (Time to Recurrence From the Time of First Recorded Pain Relief [Grade = 0 or 1]) [24 hours]

   Duration of relief or the time to recurrence from the time of first recorded pain relief (grade = 0 or 1) was calculated for responders who had a headache recurrence

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Participant had at least a 6-month history of migraine, with or without aura

• Participant was male, or if female, must have been postmenopausal, surgically sterilized, or taking adequate contraceptive precautions

• Participant was judged to be in good health, apart from migraine

Exclusion Criteria:

• Participant was Pregnant or a nursing mother

• Participant had a history or current evidence of drug or alcohol abuse

• Participant had a history or clinical evidence of cardiovascular disease

• Participant had a clinically significant Electrocardiography (ECG) abnormality

• Participant had a resting systolic blood pressure of greater than 145 mm Hg or diastolic of less than 95 mm Hg at screening

• Participant had received treatment with an investigational device or compound within 30 days of the study

• Participant typically suffered from less then 1 or more than 8 attacks of migraine per month

• Participant had difficulty in distinguishing his/her migraine attacks from tension or interval headaches

• Participant was currently taking monoamine oxidase inhibitors, methysergide or lithium

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

• Ho TW, Fan X, Rodgers A, Lines CR, Winner P, Shapiro RE. Age effects on placebo response rates in clinical trials of acute agents for migraine: pooled analysis of rizatriptan trials in adults. Cephalalgia. 2009 Jul;29(7):711-8. doi: 10.1111/j.1468-2982.2008.01788.x. Epub 2009 Feb 3.

• Responsible Party: Organon and Co
• ClinicalTrials.gov Identifier: NCT00897104
• Other Study ID Numbers: 0462-029; 2009_593
• First Posted: May 12, 2009
• Last Update Posted: Feb 3, 2022
• Last Verified: Feb 1, 2022

• Additional relevant MeSH terms: Migraine Disorders; Headache; Sumatriptan; Rizatriptan

Study Results

Participant Flow

Recruitment Details	Participants were recruited at 31 sites: 6 in UK, 9 in Norway, 2 in Switzerland, and 14 in Sweden First Participant Treated: August 1995 Last Participant Treated: May 1996.
Pre-assignment Detail	Participants screened at a pretreatment visit were given allocated drug supply with instructions. If participants had not treated an attack within 2 months of being enrolled, they were required to return for a rescreen visit. If by 4 months after being enrolled participants still had not treated an attack, they were discontinued from the study.

Arm/Group Title	Rizatriptan 5 mg	Sumatriptan 5 mg	Placebo
Arm/Group Description	Rizatriptan 5 mg orally once for treatment of single migraine attack	Sumatriptan 5 mg orally once for treatment of single migraine attack	Placebo matching Rizatriptan 5 mg or Sumatriptan 5 mg orally once for treatment of single migraine attack
Period Title: Overall Study
STARTED	418	428	87
Participants Treated	355	357	80
Participants Not Treated	63	71	7
COMPLETED	354	357	79
NOT COMPLETED	64	71	8

Baseline Characteristics

Arm/Group Title	Rizatriptan 5 mg	Sumatriptan 5 mg	Placebo	Total
Arm/Group Description	Rizatriptan 5 mg orally once for treatment of single migraine attack	Sumatriptan 5 mg orally once for treatment of single migraine attack	Placebo matching Rizatriptan 5 mg or Sumatriptan 5 mg orally once for treatment of single migraine attack	Total of all reporting groups
Overall Participants	355	357	80	792
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	39.9 (10.3)	41.8 (10.1)	44.3 (10.5)	41.2 (10.3)
Sex: Female, Male (Count of Participants)
Female	291 82%	291 81.5%	70 87.5%	652 82.3%
Male	64 18%	66 18.5%	10 12.5%	140 17.7%
Race/Ethnicity, Customized (participants) [Number]
Caucasian	352 99.2%	356 99.7%	80 100%	788 99.5%
Asian	3 0.8%	1 0.3%	0 0%	4 0.5%
Baseline Headache Severity (Number) [Number]
Grades 0,1: no pain, Mild, or missing	6 1.7%	8 2.2%	0 0%	14 1.8%
Grade 2: Moderate	216 60.8%	221 61.9%	51 63.8%	488 61.6%
Grade 3: Severe	133 37.5%	128 35.9%	29 36.3%	290 36.6%

Outcome Measures

1. Primary Outcome

Title	Pain Relief at 2 Hours After Treatment
Description	Participants reporting pain relief defined as a reduction of headache severity from grades 2 or 3 (moderate or severe pain) at baseline to grades 0 or 1 (no headache or mild pain) at 2 hours after treatment
Time Frame	2 hours after treatment

Outcome Measure Data

Analysis Population Description

An "all-participants-treated" approach was used in the primary analysis, including all participants who had at least one assessment of pain severity within 2 hours after dose. Missing data were replaced by carrying forward the preceding value.

Arm/Group Title	Rizatriptan 5 mg	Sumatriptan 5 mg	Placebo
Arm/Group Description	Rizatriptan 5 mg orally once for treatment of single migraine attack	Sumatriptan 5 mg orally once for treatment of single migraine attack	Placebo matching Rizatriptan 5 mg or Sumatriptan 5 mg orally once for treatment of single migraine attack
Measure Participants	352	356	80
2-hour pain relief	223 62.8%	238 66.7%	18 22.5%
No 2-hour pain relief	129 36.3%	118 33.1%	62 77.5%

2. Primary Outcome

Title	Time to Relief Within 2 Hours After Treatment
Description	Participants reporting time to relief (defined as the first time that a participant reported grade 0 or 1 in headache severity within 2 hours after treatment (for the comparison of rizatriptan 5 mg and sumatriptan 50 mg).
Time Frame	within 2 hours after treatment

Outcome Measure Data

Analysis Population Description

An "all-participants-treated" approach was used in the primary analysis, including all participants who had at least one assessment of pain severity within 2 hours after test medication.

Arm/Group Title	Rizatriptan 5 mg	Sumatriptan 5 mg	Placebo
Arm/Group Description	Rizatriptan 5 mg orally once for treatment of single migraine attack	Sumatriptan 5 mg orally once for treatment of single migraine attack	Placebo matching Rizatriptan 5 mg or Sumatriptan 5 mg orally once for treatment of single migraine attack
Measure Participants	352	356	80
First pain relief within 2 hrs	231 65.1%	247 69.2%	24 30%
Pain relief did not occur within 2 hrs	121 34.1%	109 30.5%	56 70%

3. Secondary Outcome

Title	Pain Free at 2 Hours After Treatment
Description	Participants pain free (defined as a reduction of headache severity to grade 0 [no pain]) at 2 hours after treatment. Each participant rated headache severity on a 4-grade scale (0 = no headache; 1 = mild pain; 2 = moderate pain; 3 = severe pain).
Time Frame	2 hours after treatment

Outcome Measure Data

Analysis Population Description

An "all-participants-treated" approach was used in the secondary analysis, including all participants who had at least one assessment of pain severity within 2 hours after test medication. Missing data were replaced by carrying forward the preceding value.

Arm/Group Title	Rizatriptan 5 mg	Sumatriptan 5 mg	Placebo
Arm/Group Description	Rizatriptan 5 mg orally once for treatment of single migraine attack	Sumatriptan 5 mg orally once for treatment of single migraine attack	Placebo matching Rizatriptan 5 mg or Sumatriptan 5 mg orally once for treatment of single migraine attack
Measure Participants	352	356	80
2-hour pain freedom	95 26.8%	113 31.7%	2 2.5%
No 2-hour pain freedom	257 72.4%	243 68.1%	78 97.5%

4. Secondary Outcome

Title	Lack of Functional Disability at 2 Hours After Treatment as Measured by the Level of Impairment in Daily Activities
Description	Participants with no functional disability measured by the level of impairment to daily activities at 2 hours after treatment. Each participant rated functional disability on a 4-grade scale (0 =normal; 1 = daily activities mildly impaired; 2 = daily activities severely impaired; 3 =unable to carry out daily activities, required bed rest).
Time Frame	2 hours after treatment

Outcome Measure Data

Analysis Population Description

An "all-participants-treated" approach was used in the secondary analysis. Missing data were replaced by carrying forward the preceding value.

Arm/Group Title	Rizatriptan 5 mg	Sumatriptan 5 mg	Placebo
Arm/Group Description	Rizatriptan 5 mg orally once for treatment of single migraine attack	Sumatriptan 5 mg orally once for treatment of single migraine attack	Placebo matching Rizatriptan 5 mg or Sumatriptan 5 mg orally once for treatment of single migraine attack
Measure Participants	350	355	80
Normal	108 30.4%	116 32.5%	4 5%
Mildly Impaired	152 42.8%	148 41.5%	28 35%
Severely Impaired	38 10.7%	42 11.8%	18 22.5%
Required Bed Rest	52 14.6%	49 13.7%	30 37.5%

5. Secondary Outcome

Title	Presence or Absence of Associated Symptoms (Photophobia, Phonophobia, Nausea, and Vomiting) at 2 Hours After Treatment
Description	Participants who recorded the presence or absence of the associated symptoms photophobia, phonophobia, nausea, and vomiting at 2 hours after treatment.
Time Frame	2 hours after treatment

Outcome Measure Data

Analysis Population Description

"All-participants-treated" approach was used. Missing data were replaced by carrying forward the preceding value. Participants Analyzed For Nausea: Rizatriptan 348; Sumatriptan 352; Placebo 78. Participants Analyzed for Vomiting: Rizatriptan 342; Sumatriptan 342; Placebo 73. Number of participants analyzed is correct for the other categories.

Arm/Group Title	Rizatriptan 5 mg	Sumatriptan 5 mg	Placebo
Arm/Group Description	Rizatriptan 5 mg orally once for treatment of single migraine attack	Sumatriptan 5 mg orally once for treatment of single migraine attack	Placebo matching Rizatriptan 5 mg or Sumatriptan 5 mg orally once for treatment of single migraine attack
Measure Participants	350	354	80
2-hour Photophobia	161 45.4%	153 42.9%	66 82.5%
No 2-hour Photophobia	189 53.2%	201 56.3%	14 17.5%
2-hour Phonophobia	126 35.5%	125 35%	47 58.8%
No 2-hour Phonophobia	224 63.1%	229 64.1%	33 41.3%
2-hour Nausea	105 29.6%	131 36.7%	48 60%
No 2-hour Nausea	243 68.5%	221 61.9%	30 37.5%
Not Analyzed for Nausea	2 0.6%	2 0.6%	2 2.5%
2-hour Vomiting	12 3.4%	12 3.4%	6 7.5%
No 2-hour Vomiting	330 93%	330 92.4%	67 83.8%
Not Analyzed for Vomiting	8 2.3%	12 3.4%	7 8.8%

6. Secondary Outcome

Title	Participants Who Used Escape Medication 2 Hours After the Treatment Dose
Description	Escape medication is defined as rescue medication for participants who experienced lack of efficacy from the study medication.
Time Frame	2 hours after treatment

Outcome Measure Data

Analysis Population Description

An "all-participants-treated" approach was used in the secondary analysis. Missing data were replaced by carrying forward the preceding value.

Arm/Group Title	Rizatriptan 5 mg	Sumatriptan 5 mg	Placebo
Arm/Group Description	Rizatriptan 5 mg orally once for treatment of single migraine attack	Sumatriptan 5 mg orally once for treatment of single migraine attack	Placebo matching Rizatriptan 5 mg or Sumatriptan 5 mg orally once for treatment of single migraine attack
Measure Participants	355	357	80
Used Escape Medication	73 20.6%	55 15.4%	33 41.3%
Did not Use Escape Medication	282 79.4%	302 84.6%	47 58.8%

7. Secondary Outcome

Title	Duration of Relief (Time to Recurrence From the Time of First Recorded Pain Relief [Grade = 0 or 1])
Description	Duration of relief or the time to recurrence from the time of first recorded pain relief (grade = 0 or 1) was calculated for responders who had a headache recurrence
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

The duration of relief, or the time to recurrence from the time of first recorded pain relief (grade = 0 or 1), was calculated for responders who had a headache recurrence.

Arm/Group Title	Rizatriptan 5 mg	Sumatriptan 5 mg	Placebo
Arm/Group Description	Rizatriptan 5 mg orally once for treatment of single migraine attack	Sumatriptan 5 mg orally once for treatment of single migraine attack	Placebo matching Rizatriptan 5 mg or Sumatriptan 5 mg orally once for treatment of single migraine attack
Measure Participants	84	80	6
Mean (Standard Deviation) [Hours]	11.07 (6.56)	11.58 (5.86)	14.38 (5.00)

Adverse Events

Time Frame	During the 24 hours treatment period, and up to and including 7 days after the last dose of study therapy.
Adverse Event Reporting Description	Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories. The At Risk population are the participants that received study treatment.
Arm/Group Title	Rizatriptan 5 mg		Sumatriptan 5 mg		Placebo
Arm/Group Description	Rizatriptan 5 mg orally once for treatment of single migraine attack		Sumatriptan 5 mg orally once for treatment of single migraine attack		Placebo matching Rizatriptan 5 mg or Sumatriptan 5 mg orally once for treatment of single migraine attack
All Cause Mortality
	Rizatriptan 5 mg		Sumatriptan 5 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Rizatriptan 5 mg		Sumatriptan 5 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/355 (0%)		0/357 (0%)		0/80 (0%)
Other (Not Including Serious) Adverse Events
	Rizatriptan 5 mg		Sumatriptan 5 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	92/355 (25.9%)		108/357 (30.3%)		16/80 (20%)
Cardiac disorders
Palpitation	2/355 (0.6%)		6/357 (1.7%)		0/80 (0%)
Tachycardia	2/355 (0.6%)		2/357 (0.6%)		1/80 (1.3%)
Gastrointestinal disorders
Dry Mouth	10/355 (2.8%)		9/357 (2.5%)		0/80 (0%)
Dyspepsia	1/355 (0.3%)		1/357 (0.3%)		2/80 (2.5%)
Nausea	13/355 (3.7%)		21/357 (5.9%)		2/80 (2.5%)
Pain, Mouth	0/355 (0%)		0/357 (0%)		1/80 (1.3%)
Vomiting	2/355 (0.6%)		5/357 (1.4%)		0/80 (0%)
General disorders
Asthenia/Fatigue	25/355 (7%)		18/357 (5%)		1/80 (1.3%)
Fever	1/355 (0.3%)		1/357 (0.3%)		1/80 (1.3%)
Pain, Abdominal	4/355 (1.1%)		5/357 (1.4%)		0/80 (0%)
Pain, Chest	8/355 (2.3%)		16/357 (4.5%)		0/80 (0%)
Warm Sensation	4/355 (1.1%)		3/357 (0.8%)		1/80 (1.3%)
Musculoskeletal and connective tissue disorders
Heaviness, Regional	3/355 (0.8%)		4/357 (1.1%)		0/80 (0%)
Pain, Back	0/355 (0%)		4/357 (1.1%)		0/80 (0%)
Pain, Neck	2/355 (0.6%)		7/357 (2%)		2/80 (2.5%)
Stiffness	1/355 (0.3%)		5/357 (1.4%)		0/80 (0%)
Strain	0/355 (0%)		0/357 (0%)		1/80 (1.3%)
Nervous system disorders
Dizziness	13/355 (3.7%)		17/357 (4.8%)		4/80 (5%)
Headache	7/355 (2%)		6/357 (1.7%)		0/80 (0%)
Hypesthesia	4/355 (1.1%)		6/357 (1.7%)		3/80 (3.8%)
Mental Acuity Decreased	3/355 (0.8%)		5/357 (1.4%)		1/80 (1.3%)
Paresthesia	11/355 (3.1%)		12/357 (3.4%)		2/80 (2.5%)
Vertigo	6/355 (1.7%)		3/357 (0.8%)		1/80 (1.3%)
Psychiatric disorders
Apathy	1/355 (0.3%)		1/357 (0.3%)		1/80 (1.3%)
Dream Abnormality	0/355 (0%)		2/357 (0.6%)		1/80 (1.3%)
Somnolence	13/355 (3.7%)		17/357 (4.8%)		0/80 (0%)
Respiratory, thoracic and mediastinal disorders
Discomfort, Pharyngeal	5/355 (1.4%)		5/357 (1.4%)		0/80 (0%)
Dyspnea	0/355 (0%)		2/357 (0.6%)		1/80 (1.3%)

Limitations/Caveats

No limitations were encountered in this study.

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.