Two Rizatriptan Prescribing Portions for Treatment of Migraine

• Sponsor: Clinvest (Other)
• Overall Status: Completed
• CT.gov ID: NCT00397254
• Collaborator: Merck Sharp & Dohme LLC (Industry)
• Enrollment: 197
• Locations: 10
• Arms: 2
• Duration (Months): 13
• Patients Per Site: 19.7
• Patients Per Site Per Month: 1.5

Study Details

Study Description

Brief Summary

The primary objective of this study is to evaluate a clinical limit (CL) of rizatriptan (9 rizatriptan 10mg Orally Disintegrating Tablet (ODT) per month) versus (vs.) a formulary limit (FL) of rizatriptan (27 rizatriptan 10mg ODT per month) as measured by the number of days of migraine per month.

Condition or Disease	Intervention/Treatment	Phase
Migraine	Drug: rizatriptan; Drug: rizatriptan	Phase 4

Detailed Description

A common clinical perception exists that less effective treatment of attacks increases the burden of disease across attacks in the form of increased attack frequency, severity, duration, and/or treatability. If this perception is true, more effective treatment decreases the burden of disease across attacks. There are multiple barriers to effective treatment. The triptan class of migraine medications is frequently dispensed in the context of health benefit plan formulary limitations. Because of limited supply, medications must be used very cautiously. Patients may hoard medication in reaction to fear of running out. Overly cautious use and hoarding may lead to greater disease burden.

The purpose of this study is to compare the effect of two allocations of rizatriptan - a more limited allocation ("Formulary Limit") vs. a less limited allocation ("Clinical Limit") on disease burden.

Study Design

• Study Type: Interventional
• Actual Enrollment: 197 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Investigator)
• Primary Purpose: Treatment
• Official Title: An Observer-Blind, Randomized, Parallel-Group Study to Compare the Efficacy of Two Rizatriptan Prescribing Portions for the Treatment of Migraine
• Study Start Date: Dec 1, 2006
• Actual Primary Completion Date: Jan 1, 2008
• Actual Study Completion Date: Jan 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Clinical Limit Eligible patients were randomized to one of two treatment regimens in a 1:1 ratio. Those randomized to receive a "clinical limit" of study medication received Rizatriptan 10mg ODT: 27 tablets per month.	Drug: rizatriptan; 10mg ODT 27 tablets; Other Names: Maxalt
Active Comparator: Formulary Limit Eligible patients were randomized to one of two treatment regimens in a 1:1 ratio. Those randomized to receive a "formulary limit" of study medication received Rizatriptan 10mg ODT: 9 tablets per month.	Drug: rizatriptan; 10mg ODT 9 tablets; Other Names: Maxalt

Outcome Measures

Primary Outcome Measures

1. Number of Days With Migraine [6 months]

Secondary Outcome Measures

1. Number of Migraine Attacks [6 months]

2. Percentage of Responders [6 months]

   Percentage of Responders (50% decrease in attack frequency) of Formulary Limit Group versus Percentage of Responders (50% decrease in attack frequency) in Clinical Limit Group

3. Average Attack Duration [6 months]

4. Headache Severity of All Attacks [6 months]

   4-Point Headache Severity Scale (0 = No Pain / 1 = Mild Pain / 2 = Moderate Pain / 3 = Severe Pain)

5. Percentage of Attacks With Symptom Elimination at 2 Hours [6 months]

   Percentage of attacks with elimination of all associated symptoms at 2 hours post-treatment in Formulary Limit Group versus percentage of attacks with elimination of all associated symptoms at 2 hours post-treatment in Clinical Limit Group

6. Percentage of Attacks With Return to Normal Ability to Perform Activities at 2 Hours Post-dose [6 months]

   Percentage of attacks with mild, moderate or severely impaired ability to perform activities pre-treatment with return to normal function at 2 hours post-dose in Formulary Limit Group versus Clinical Limit Group

7. Adverse Experiences [6 months]

   Participants with one or more Adverse Experiences (AEs) in Formulary Limit Group versus Clinical Limit Group collected from time patient provided informed consent until return at Visit 7 or through 14 days post-dosing of the last dose of study medication if serious adverse experience. Defined as any unfavorable and unintended change in structure, function, or chemistry of the body temporally associated with use of provided product whether or not considered related to use of the product. Includes any worsening of a preexisting condition temporally associated with use of provided product.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Patient is at least 18 years of age

• Patient has at least a 1-year history of migraine with or without aura by International Headache Society (IHS) criteria 1.1 and 1.2

• Patient typically has 3-8 migraine attacks/month

• Patient has less than 10 headache days/month with no evidence of IHS 8.2 Medication Overuse Headache

• Patient receives their triptan medication under a pre-determined prescribing allocation ranging from 6-12 tablets per month for the last 3 months preceding Visit

• Patient and investigator agree that multiple doses of rizatriptan described in the package circular are appropriate for non-responsive or recurring headache.

• Patient uses a triptan as mainstay of acute therapy at Visit 1.

• Patient of childbearing potential agrees to use adequate contraception during the study. Adequate methods of contraception are to be determined by the investigator and should be consistent with contraceptive care administered in the regular clinical use of rizatriptan outside the study.

• Patient understands study procedures, alternative treatments available, and risks involved with the study, and voluntarily agrees to participate by giving written informed consent.

Exclusion Criteria:

• Patient has headache disorders beyond migraine or episodic tension-type headache IHS 2.1

• Patient is receiving prophylactic therapy for migraine

• Patient is currently taking:

Daily or nearly daily (typically >3 days out of 7 days) use of non-steroidal anti-inflammatory drugs (NSAIDs), COX-2 inhibitors, or other analgesics. Aspirin less than or equal to 325mg daily is allowed for cardioprotection.

Monoamine oxidase inhibitors (MAOIs) Propranolol Patient taking either an MAOI ro propranolol may be enrolled in the study, if in the clinical judgement of the investigator, either of these medications can be discontinued 2 weeks prior to study entry. Otherwise the use of MAOIs and propranolol are prohibited during the study.

• Patient has basilar or hemiplegic migraine headache.

• Patient has history or clinical evidence of ischemic heart disease (e.g., angina pectoris of any type, history of myocardial infarction or documented silent ischemia) or symptoms or finding consistent with ischemic heart disease, coronary artery vasospasm (including Prinzmetal's variant angina), or other significant underlying cardiovascular disease.

• Patient has uncontrolled hypertension.

• Patient has either demonstrated hypersensitivity to or experienced a serious adverse event in response to rizatriptan or any of its inactive ingredients.

• Patient is pregnant or a nursing mother.

• Patient has a history (within 1 year) or current evidence of drug or alcohol abuse.

• Patient has received treatment with an investigational device or compound within 30 days of the study (Visit 1).

• Patient had clinical evidence of significant pulmonary, renal, hepatic, endocrine, neurologic (apart from migraine), psychiatric or any other condition that, in the opinion of the investigator may confound the results of the study, pose an additional risk, or interfere with optimal participation in the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Brian Koffman, MD	Diamond Bar	California	United States	91765
2	San Francisco Clinical Research Center	San Francisco	California	United States	94109
3	Physician Associates	Oviedo	Florida	United States	32765
4	Dr. B. Abraham, PC	Snellville	Georgia	United States	33039
5	Dhiren Shah, MD	Prince Frederick	Maryland	United States	20678
6	Westside Family Medical Center	Kalamazoo	Michigan	United States	49009
7	Clinvest	Springfield	Missouri	United States	65807
8	Mercy Health Research / Ryan Headache Center	St. Louis	Missouri	United States	63141
9	PharmQuest	Greensboro	North Carolina	United States	27401
10	Thomas Jefferson University Hospital Jefferson Headache Center	Philadelphia	Pennsylvania	United States	19107

Sponsors and Collaborators

• Clinvest
• Merck Sharp & Dohme LLC

Investigators

• Principal Investigator: Roger K Cady, MD, Clinvest

Study Documents (Full-Text)

None provided.

More Information

Publications

• Brandes JL, Visser WH, Farmer MV, Schuhl AL, Malbecq W, Vrijens F, Lines CR, Reines SA; Protocol 125 study group. Montelukast for migraine prophylaxis: a randomized, double-blind, placebo-controlled study. Headache. 2004 Jun;44(6):581-6.

• ClinicalTrials.gov Identifier: NCT00397254
• Other Study ID Numbers: 078-00
• First Posted: Nov 9, 2006
• Last Update Posted: Jun 8, 2010
• Last Verified: Sep 1, 2009

• Keywords provided by , ,: Migraine; rizatriptan
• Additional relevant MeSH terms: Migraine Disorders; Rizatriptan

Study Results

Participant Flow

Pre-assignment Detail	3-month Baseline Period occurred prior to randomization to Clinical Limit or Formulary Limit groups. 42 subjects discontinued from total enrollment of 197: (2) Adverse Event (AE), (10) Lost to Follow Up (LFU), (11) Withdrew consent, (1) Pregnancy, (16) Failed to meet Inclusion/Exclusion at Visit 4 Randomization, (2) Other

Arm/Group Title	Rizatriptan 27 Tablets - Clinical Limit	Rizatriptan 9 Tablets - Formulary Limit
Arm/Group Description	Eligible patients were randomized to one of two treatment regimens in a 1:1 ratio. Those randomized to receive a "clinical limit" of study medication received Rizatriptan 10mg orally disintegrating tablet (ODT): 27 tablets per month.	Eligible patients were randomized to one of two treatment regimens in a 1:1 ratio. Those randomized to receive a "formulary limit" of study medication received Rizatriptan 10mg orally disintegrating tablet (ODT): 9 tablets per month.
Period Title: Overall Study
STARTED	79	76
COMPLETED	77	74
NOT COMPLETED	2	2

Baseline Characteristics

Arm/Group Title	Baseline Period - Rizatriptan 9 Tablets
Arm/Group Description	Prior to randomization at Visit 2 (to rizatriptan 9 tablets or rizatriptan 27 tablets), all subjects in Baseline were provided with 9 tablets of rizatriptan.
Overall Participants	197
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	197 100%
>=65 years	0 0%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	42
Sex: Female, Male (Count of Participants)
Female	173 87.8%
Male	24 12.2%
Region of Enrollment (participants) [Number]
United States	197 100%

Outcome Measures

1. Primary Outcome

Title	Number of Days With Migraine
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

197 enrolled in Baseline(BL). Analysis of BL Characteristics on 197. 42 discontinued (2 Adverse Event(AE),10 Lost to followup(LFU),11 Withdrew consent,1 Pregnant,16 Failed randomization criteria,2 Other). 155 randomized. 4/155 LFU. 151 in analysis(77 Clinical Limit/74 Formulary Limit). 143 completed all visits(74 Clinical Limit/69 Formulary Limit).

Arm/Group Title	Rizatriptan 27 Tablets - Clinical Limit	Rizatriptan 9 Tablets - Formulary Limit
Arm/Group Description	Eligible patients were randomized to one of two treatment regimens in a 1:1 ratio. Those randomized to receive a "clinical limit" of study medication received Rizatriptan 10mg orally disintegrating tablet (ODT): 27 tablets per month.	Eligible patients were randomized to one of two treatment regimens in a 1:1 ratio. Those randomized to receive a "formulary limit" of study medication received Rizatriptan 10mg orally disintegrating tablet (ODT): 9 tablets per month.
Measure Participants	77	74
Mean (Standard Deviation) [Days]	2.666 (1.297)	2.738 (1.313)

2. Secondary Outcome

Title	Number of Migraine Attacks
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

197 enrolled in Baseline(BL). Analysis of BL Characteristics on 197. 42 discontinued (2 Adverse Event(AE),10 Lost to followup(LFU),11 Withdrew consent,1 Pregnant,16 Failed randomization criteria,2 Other). 155 randomized. 4/155 LFU. 151 in analysis(77 Clinical Limit/74 Formulary Limit). 143 completed all visits(74 Clinical Limit/69 Formulary Limit).

Arm/Group Title	Rizatriptan 27 Tablets - Clinical Limit	Rizatriptan 9 Tablets - Formulary Limit
Arm/Group Description	Eligible patients were randomized to one of two treatment regimens in a 1:1 ratio. Those randomized to receive a "clinical limit" of study medication received Rizatriptan 10mg orally disintegrating tablet (ODT): 27 tablets per month.	Eligible patients were randomized to one of two treatment regimens in a 1:1 ratio. Those randomized to receive a "formulary limit" of study medication received Rizatriptan 10mg orally disintegrating tablet (ODT): 9 tablets per month.
Measure Participants	77	74
Mean (Standard Deviation) [Migraine attacks]	4.855 (2.093)	4.399 (1.548)

3. Secondary Outcome

Title	Percentage of Responders
Description	Percentage of Responders (50% decrease in attack frequency) of Formulary Limit Group versus Percentage of Responders (50% decrease in attack frequency) in Clinical Limit Group
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

197 enrolled in Baseline(BL). Analysis of BL Characteristics on 197. 42 discontinued (2 Adverse Event(AE),10 Lost to followup(LFU),11 Withdrew consent,1 Pregnant,16 Failed randomization criteria,2 Other). 155 randomized. 4/155 LFU. 151 in analysis(77 Clinical Limit/74 Formulary Limit). 143 completed all visits(74 Clinical Limit/69 Formulary Limit).

Arm/Group Title	Rizatriptan 27 Tablets - Clinical Limit	Rizatriptan 9 Tablets - Formulary Limit
Arm/Group Description	Eligible patients were randomized to one of two treatment regimens in a 1:1 ratio. Those randomized to receive a "clinical limit" of study medication received Rizatriptan 10mg orally disintegrating tablet (ODT): 27 tablets per month.	Eligible patients were randomized to one of two treatment regimens in a 1:1 ratio. Those randomized to receive a "formulary limit" of study medication received Rizatriptan 10mg orally disintegrating tablet (ODT): 9 tablets per month.
Measure Participants	77	74
Number [Percentage of Participants]	7.79 4%	2.70 NaN

4. Secondary Outcome

Title	Average Attack Duration
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

197 enrolled in Baseline(BL). Analysis of BL Characteristics on 197. 42 discontinued (2 Adverse Event(AE),10 Lost to followup(LFU),11 Withdrew consent,1 Pregnant,16 Failed randomization criteria,2 Other). 155 randomized. 4/155 LFU. 151 in analysis(77 Clinical Limit/74 Formulary Limit). 143 completed all visits(74 Clinical Limit/69 Formulary Limit).

Arm/Group Title	Rizatriptan 27 Tablets - Clinical Limit	Rizatriptan 9 Tablets - Formulary Limit
Arm/Group Description	Eligible patients were randomized to one of two treatment regimens in a 1:1 ratio. Those randomized to receive a "clinical limit" of study medication received Rizatriptan 10mg orally disintegrating tablet (ODT): 27 tablets per month.	Eligible patients were randomized to one of two treatment regimens in a 1:1 ratio. Those randomized to receive a "formulary limit" of study medication received Rizatriptan 10mg orally disintegrating tablet (ODT): 9 tablets per month.
Measure Participants	77	74
Mean (Standard Deviation) [Hours]	11.569 (8.188)	12.930 (9.192)

5. Secondary Outcome

Title	Headache Severity of All Attacks
Description	4-Point Headache Severity Scale (0 = No Pain / 1 = Mild Pain / 2 = Moderate Pain / 3 = Severe Pain)
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

197 enrolled in Baseline(BL). Analysis of BL Characteristics on 197. 42 discontinued (2 Adverse Event(AE),10 Lost to followup(LFU),11 Withdrew consent,1 Pregnant,16 Failed randomization criteria,2 Other). 155 randomized. 4/155 LFU. 151 in analysis(77 Clinical Limit/74 Formulary Limit). 143 completed all visits(74 Clinical Limit/69 Formulary Limit).

Arm/Group Title	Rizatriptan 27 Tablets - Clinical Limit	Rizatriptan 9 Tablets - Formulary Limit
Arm/Group Description	Eligible patients were randomized to one of two treatment regimens in a 1:1 ratio. Those randomized to receive a "clinical limit" of study medication received Rizatriptan 10mg orally disintegrating tablet (ODT): 27 tablets per month.	Eligible patients were randomized to one of two treatment regimens in a 1:1 ratio. Those randomized to receive a "formulary limit" of study medication received Rizatriptan 10mg orally disintegrating tablet (ODT): 9 tablets per month.
Measure Participants	77	74
Median (Full Range) [Units on a scale]	1.50	1.59

6. Secondary Outcome

Title	Percentage of Attacks With Symptom Elimination at 2 Hours
Description	Percentage of attacks with elimination of all associated symptoms at 2 hours post-treatment in Formulary Limit Group versus percentage of attacks with elimination of all associated symptoms at 2 hours post-treatment in Clinical Limit Group
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

197 enrolled in Baseline(BL). Analysis of BL Characteristics on 197. 42 discontinued (2 Adverse Event(AE),10 Lost to followup(LFU),11 Withdrew consent,1 Pregnant,16 Failed randomization criteria,2 Other). 155 randomized. 4/155 LFU. 151 in analysis(77 Clinical Limit/74 Formulary Limit). 143 completed all visits(74 Clinical Limit/69 Formulary Limit).

Arm/Group Title	Rizatriptan 27 Tablets - Clinical Limit	Rizatriptan 9 Tablets - Formulary Limit
Arm/Group Description	Eligible patients were randomized to one of two treatment regimens in a 1:1 ratio. Those randomized to receive a "clinical limit" of study medication received Rizatriptan 10mg orally disintegrating tablet (ODT): 27 tablets per month.	Eligible patients were randomized to one of two treatment regimens in a 1:1 ratio. Those randomized to receive a "formulary limit" of study medication received Rizatriptan 10mg orally disintegrating tablet (ODT): 9 tablets per month.
Measure Participants	77	74
Number [Percentage of attacks]	58.35	56.60

7. Secondary Outcome

Title	Percentage of Attacks With Return to Normal Ability to Perform Activities at 2 Hours Post-dose
Description	Percentage of attacks with mild, moderate or severely impaired ability to perform activities pre-treatment with return to normal function at 2 hours post-dose in Formulary Limit Group versus Clinical Limit Group
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

197 enrolled in Baseline(BL). Analysis of BL Characteristics on 197. 42 discontinued (2 Adverse Event(AE),10 Lost to followup(LFU),11 Withdrew consent,1 Pregnant,16 Failed randomization criteria,2 Other). 155 randomized. 4/155 LFU. 151 in analysis(77 Clinical Limit/74 Formulary Limit). 143 completed all visits(74 Clinical Limit/69 Formulary Limit).

Arm/Group Title	Rizatriptan 27 Tablets - Clinical Limit	Rizatriptan 9 Tablets - Formulary Limit
Arm/Group Description	Eligible patients were randomized to one of two treatment regimens in a 1:1 ratio. Those randomized to receive a "clinical limit" of study medication received Rizatriptan 10mg orally disintegrating tablet (ODT): 27 tablets per month.	Eligible patients were randomized to one of two treatment regimens in a 1:1 ratio. Those randomized to receive a "formulary limit" of study medication received Rizatriptan 10mg orally disintegrating tablet (ODT): 9 tablets per month.
Measure Participants	77	74
Number [Percentage of attacks]	50.74	48.67

8. Secondary Outcome

Title	Adverse Experiences
Description	Participants with one or more Adverse Experiences (AEs) in Formulary Limit Group versus Clinical Limit Group collected from time patient provided informed consent until return at Visit 7 or through 14 days post-dosing of the last dose of study medication if serious adverse experience. Defined as any unfavorable and unintended change in structure, function, or chemistry of the body temporally associated with use of provided product whether or not considered related to use of the product. Includes any worsening of a preexisting condition temporally associated with use of provided product.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

197 enrolled in Baseline(BL). Analysis of BL Characteristics on 197. 42 discontinued (2 Adverse Event(AE),10 Lost to followup(LFU),11 Withdrew consent,1 Pregnant,16 Failed randomization criteria,2 Other). 155 randomized. 4/155 LFU. 151 in analysis(77 Clinical Limit/74 Formulary Limit). 143 completed all visits(74 Clinical Limit/69 Formulary Limit).

Arm/Group Title	Rizatriptan 27 Tablets - Clinical Limit	Rizatriptan 9 Tablets - Formulary Limit
Arm/Group Description	Eligible patients were randomized to one of two treatment regimens in a 1:1 ratio. Those randomized to receive a "clinical limit" of study medication received Rizatriptan 10mg orally disintegrating tablet (ODT): 27 tablets per month.	Eligible patients were randomized to one of two treatment regimens in a 1:1 ratio. Those randomized to receive a "formulary limit" of study medication received Rizatriptan 10mg orally disintegrating tablet (ODT): 9 tablets per month.
Measure Participants	77	74
Number [Participants]	18 9.1%	24 NaN

Adverse Events

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Investigator is free to publish results of it's part of the study in collaboration with the other investigators subsequent to the multicenter publication issued by Clinvest. Principal Investigator (PI) may publish results of it's data with copy of any manuscript for review to Clinvest 60 days prior to submission for publication.