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A Study of Rizatriptan for the Treatment of Acute Migraine in Patients on Topiramate for Migraine Prophylaxis

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ClinicalTrials.gov Identifier: NCT00812006
Recruitment Status : Completed
First Posted : December 19, 2008
Results First Posted : January 27, 2011
Last Update Posted : June 6, 2017
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Migraine
Interventions Drug: rizatriptan benzoate
Drug: Comparator: placebo
Enrollment 108
Recruitment Details

First Patient In: 26 March 2009; Last Patient Last Visit: 22 October 2009.

17 Outpatient centers worldwide (10 United States; 2 Canada; 2 Spain, 2 Italy; 1 France)

Pre-assignment Details

Participants were assessed, using the protocol inclusion and exclusion criteria, at Visit 1, and if eligible,

were randomized at the same visit.

Arm/Group Title Rizatriptan / Rizatriptan / Placebo Rizatriptan / Placebo / Rizatriptan Placebo / Rizatriptan / Rizatriptan
Hide Arm/Group Description First migraine treated with Rizatriptan 10 mg Orally Disintegrating Tablet (ODT); second migraine treated with Rizatriptan 10 mg Orally Disintegrating Tablet (ODT); third migraine treated with Placebo First migraine treated with Rizatriptan 10 mg Orally Disintegrating Tablet (ODT); second migraine treated with Placebo; third migraine treated with Rizatriptan 10 mg Orally Disintegrating Tablet (ODT) First migraine treated with Placebo; second migraine treated with Rizatriptan 10 mg Orally Disintegrating Tablet (ODT); third migraine treated with Rizatriptan 10 mg Orally Disintegrating Tablet (ODT)
Period Title: Overall Study
Started 36 36 36
Completed 30 33 30
Not Completed 6 3 6
Reason Not Completed
Lost to Follow-up             0             0             2
Physician Decision             0             0             1
Withdrawal by Subject             2             1             1
Lack of Qualifying Event             4             2             2
Arm/Group Title Rizatriptan / Rizatriptan / Placebo Rizatriptan / Placebo / Rizatriptan Placebo / Rizatriptan / Rizatriptan Total
Hide Arm/Group Description First migraine treated with Rizatriptan 10 mg Orally Disintegrating Tablet (ODT); second migraine treated with Rizatriptan 10 mg Orally Disintegrating Tablet (ODT); third migraine treated with Placebo First migraine treated with Rizatriptan 10 mg Orally Disintegrating Tablet (ODT); second migraine treated with Placebo; third migraine treated with Rizatriptan 10 mg Orally Disintegrating Tablet (ODT) First migraine treated with Placebo; second migraine treated with Rizatriptan 10 mg Orally Disintegrating Tablet (ODT); third migraine treated with Rizatriptan 10 mg Orally Disintegrating Tablet (ODT) Total of all reporting groups
Overall Number of Baseline Participants 36 36 36 108
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 36 participants 36 participants 36 participants 108 participants
48.3  (12.0) 43.9  (10.8) 40.0  (11.6) 44.0  (11.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 36 participants 36 participants 36 participants 108 participants
Female
32
  88.9%
33
  91.7%
34
  94.4%
99
  91.7%
Male
4
  11.1%
3
   8.3%
2
   5.6%
9
   8.3%
Ethnicity Origin  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 36 participants 36 participants 36 participants 108 participants
Black 0 1 0 1
White 36 35 36 107
Racial Origin  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 36 participants 36 participants 36 participants 108 participants
Hispanic or Latino 11 9 10 30
Not Hispanic or Latino 25 27 26 78
1.Primary Outcome
Title Pain Relief (PR)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set, which 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 have both a baseline severity measurement and at least one post-dose efficacy measurement at or prior to the 2-hour time point.
Arm/Group Title Rizatriptan Placebo
Hide Arm/Group Description:
Rizatriptan 10 mg. Patients who treated at least one attack, that was intended to be treated with rizatriptan 10 mg (excluding sponsor-provided rescue), were included. Although a patient may have treated twice with rizatriptan 10 mg, the patient was counted only once for the rizatriptan group.
Placebo. Patients who treated one attack, that was intended to be treated with placebo, were included. One patient who treated an attack with placebo within 48 hours of the previous attack was excluded from the placebo group.
Overall Number of Participants Analyzed 99 93
Measure Type: Number
Unit of Measure: Attacks
Resulting in PR at 2 hours post dose 105 21
Not resulting in PR at 2 hours post dose 88 72
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rizatriptan, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Generalized Linear Mixed Model
Comments An unstructured covariance matrix was used to model the correlation among repeated measurements within a patient.
2.Secondary Outcome
Title Sustained Pain Relief (SPR)
Hide Description 24-hour sustained pain relief (defined as pain relief at 2 hours post dose, with no administration of any rescue medication and with no occurrence of a moderate/severe headache during the respective period after dosing with the blinded study medication.
Time Frame 2 - 24 hours post dose
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set, which included all randomized participants who had at least one evaluable attack. To be considered an evaluable attack, the attack must have met the FAS criteria for PR at 2 hours post-dose, and from 2-24 hours the participant either answered 24-hour headache recurrence question or didn't have PR at any time or took rescue.
Arm/Group Title Rizatriptan Placebo
Hide Arm/Group Description:
Rizatriptan 10 mg. Patients who treated at least one attack, that was intended to be treated with rizatriptan 10 mg (excluding sponsor-provided rescue), were included. Although a patient may have treated twice with rizatriptan 10 mg, the patient was counted only once for the rizatriptan group.
Placebo. Patients who treated one attack, that was intended to be treated with placebo, were included. One patient who treated an attack with placebo within 48 hours of the previous attack was excluded from the placebo group.
Overall Number of Participants Analyzed 99 93
Measure Type: Number
Unit of Measure: Attacks
Resulting in SPR 2-24 hours post dose 67 12
Not resulting in SPR 2-24 hours post dose 126 81
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rizatriptan, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Nominal p-value was adjusted under Benjamini and Hochberg’s false discovery rate procedure for the multiple secondary endpoints at α=0.1 significance level.
Method Generalized Linear Mixed Model
Comments A compound-symmetry covariance matrix was used to model the correlation among repeated measurements within a patient, due to a convergence issue.
3.Secondary Outcome
Title Pain Freedom (PF)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set, which 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 have both a baseline severity measurement and at least one post-dose efficacy measurement at or prior to the 2-hour time point.
Arm/Group Title Rizatriptan Placebo
Hide Arm/Group Description:
Rizatriptan 10 mg. Patients who treated at least one attack, that was intended to be treated with rizatriptan 10 mg (excluding sponsor-provided rescue), were included. Although a patient may have treated twice with rizatriptan 10 mg, the patient was counted only once for the rizatriptan group.
Placebo. Patients who treated one attack, that was intended to be treated with placebo, were included. One patient who treated an attack with placebo within 48 hours of the previous attack was excluded from the placebo group.
Overall Number of Participants Analyzed 99 93
Measure Type: Number
Unit of Measure: Attacks
Resulting in PF 2 hours post dose 74 9
Not resulting in PF 2 hours post dose 119 84
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rizatriptan, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Nominal p-value was adjusted under Benjamini and Hochberg’s false discovery rate procedure for the multiple secondary endpoints at α=0.1 significance level.
Method Generalized Linear Mixed Model
Comments An unstructured covariance matrix was used to model the correlation among repeated measurements within a patient.
4.Secondary Outcome
Title Normal Rating of Functional Disability (NRFD)
Hide Description Level of functional disability was assessed on a paper diary by the participants. Level of functional disability was rated as: normal, mildly impaired, severely impaired, or unable to do activities, requires bedrest. Functional disability ratings was dichotomized to Normal and Not Normal (mildly impaired, severely impaired, or unable to do activities, requires bedrest) for analysis.
Time Frame 2 hours post dose
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set, which 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 have both a baseline severity measurement and at least one post-dose efficacy measurement at or prior to the 2-hour time point.
Arm/Group Title Rizatriptan Placebo
Hide Arm/Group Description:
Rizatriptan 10 mg. Patients who treated at least one attack, that was intended to be treated with rizatriptan 10 mg (excluding sponsor-provided rescue), were included. Although a patient may have treated twice with rizatriptan 10 mg, the patient was counted only once for the rizatriptan group.
Placebo. Patients who treated one attack, that was intended to be treated with placebo, were included. One patient who treated an attack with placebo within 48 hours of the previous attack was excluded from the placebo group.
Overall Number of Participants Analyzed 99 93
Measure Type: Number
Unit of Measure: Attacks
Resulting in NRFD at 2 hours post dose 85 16
Not resulting in NRFD at 2 hours post dose 108 77
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rizatriptan, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Nominal p-value was adjusted under Benjamini and Hochberg’s falsediscovery rate procedure for the multiple secondary endpoints at α=0.1 significance level.
Method Generalized Linear Mixed Model
Comments An unstructured covariance matrix was used to model the correlation among repeated measurements within a patient.
5.Secondary Outcome
Title Treatment Satisfaction (TS)
Hide Description Patient satisfaction was assessed on a paper diary by the participants. Level of satisfaction was rated as: completely satisfied, very satisfied, somewhat satisfied, neither satisfied nor dissatisfied, somewhat dissatisfied, very dissatisfied, or completely dissatisfied. The overall 24-hour assessment of study medication was dichotomized to Satisfaction (completely satisfied, very satisfied, somewhat satisfied) and Non-satisfaction (neither satisfied nor dissatisfied, somewhat dissatisfied, very dissatisfied, or completely dissatisfied) for analysis.
Time Frame 24 hours post dose
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set, which 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 have both a baseline severity measurement and post-dose satisfaction measurement at the 24-hour time point.
Arm/Group Title Rizatriptan Placebo
Hide Arm/Group Description:
Rizatriptan 10 mg. Patients who treated at least one attack, that was intended to be treated with rizatriptan 10 mg (excluding sponsor-provided rescue), were included. Although a patient may have treated twice with rizatriptan 10 mg, the patient was counted only once for the rizatriptan group.
Placebo. Patients who treated one attack, that was intended to be treated with placebo, were included. One patient who treated an attack with placebo within 48 hours of the previous attack was excluded from the placebo group.
Overall Number of Participants Analyzed 99 93
Measure Type: Number
Unit of Measure: Attacks
Resulting in TS at 24 hours post dose 117 31
Not resulting in TS at 24 hours post dose 76 62
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rizatriptan, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Nominal p-value was adjusted under Benjamini and Hochberg’s false discovery rate procedure for the multiple secondary endpoints at α=0.1 significance level.
Method Generalized Linear Mixed Model
Comments A compound-symmetry covariance matrix was used to model the correlation among repeated measurements within a patient, due to a convergence issue.
Time Frame Adverse experiences were collected up to 14 days after each qualified migraine headache attack that was treated with study medication.
Adverse Event Reporting Description

Adverse experiences were reported by the patient on a paper diary.

Adverse events occurring within 14 days of administration of rizatriptan (including sponsor-provided rescue) are attributed to rizatriptan group, even if placebo was administered more recently

 
Arm/Group Title Rizatriptan Placebo
Hide Arm/Group Description

Rizatriptan 10 mg. Patients who treated at least one attack with rizatriptan 10 mg (including sponsor-provided rescue) were included. Although a patient may have treated twice with rizatriptan 10 mg, the patient was counted only once for the rizatriptan group. Adverse events occurring within 14 days of any administration of rizatriptan (including sponsor-provided rescue) were attributed to rizatriptan group, even if placebo was administered more recently.

It is possible for one patient to be counted twice (once in each treatment group).

The number of randomized patients is 108, out of which, 101 took at least one dose of rizatriptan (including sponsor-provided rescue), and 94 took placebo.

Placebo. Patients who treated an attack with placebo were included. Adverse events occurring within 14 days of administration of placebo, but not within 14 days of any administration of rizatriptan (including sponsor-provided rescue), were attributed to placebo group.

It is possible for one patient to be counted twice (once in each treatment group).

The number of randomized patients is 108, out of which, 101 took at least one dose of rizatriptan (including sponsor-provided rescue), and 94 took placebo.

All-Cause Mortality
Rizatriptan Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Rizatriptan Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   0/101 (0.00%)   0/94 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Rizatriptan Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   16/101 (15.84%)   3/94 (3.19%) 
Gastrointestinal disorders     
Abdominal Distension * 1  1/101 (0.99%)  0/94 (0.00%) 
Abdominal pain upper * 1  2/101 (1.98%)  0/94 (0.00%) 
Diarrhoea * 1  1/101 (0.99%)  0/94 (0.00%) 
Nausea * 1  2/101 (1.98%)  1/94 (1.06%) 
General disorders     
Chest discomfort * 1  1/101 (0.99%)  0/94 (0.00%) 
Fatigue * 1  1/101 (0.99%)  1/94 (1.06%) 
Malaise * 1  0/101 (0.00%)  1/94 (1.06%) 
Temperature intolerance * 1  1/101 (0.99%)  0/94 (0.00%) 
Immune system disorders     
Seasonal Allergy * 1  1/101 (0.99%)  0/94 (0.00%) 
Infections and infestations     
Vaginal infection * 1  1/101 (0.99%)  0/94 (0.00%) 
Injury, poisoning and procedural complications     
Intentional overdose * 1  1/101 (0.99%)  0/94 (0.00%) 
Musculoskeletal and connective tissue disorders     
Arthalgia * 1  1/101 (0.99%)  0/94 (0.00%) 
Back pain * 1  1/101 (0.99%)  0/94 (0.00%) 
Pain in jaw * 1  1/101 (0.99%)  0/94 (0.00%) 
Nervous system disorders     
Allodynia * 1  1/101 (0.99%)  0/94 (0.00%) 
Dizziness * 1  2/101 (1.98%)  1/94 (1.06%) 
Hypersomnia * 1  1/101 (0.99%)  0/94 (0.00%) 
Hypoaesthesia * 1  1/101 (0.99%)  0/94 (0.00%) 
Peripheral paralysis * 1  1/101 (0.99%)  0/94 (0.00%) 
Somnolence * 1  6/101 (5.94%)  0/94 (0.00%) 
Psychiatric disorders     
Disorientation * 1  1/101 (0.99%)  0/94 (0.00%) 
Renal and urinary disorders     
Pollakiuria * 1  1/101 (0.99%)  0/94 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (12.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Name/Title: Senior Vice President, Global Clinical Development
Organization: Merck Sharp & Dohme Corp
Phone: 1-800-672-6372
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00812006     History of Changes
Other Study ID Numbers: 0462-085
2008_597
First Submitted: December 17, 2008
First Posted: December 19, 2008
Results First Submitted: September 23, 2010
Results First Posted: January 27, 2011
Last Update Posted: June 6, 2017