A Study to Determine the Effect of Sumatriptan and Naproxen Sodium Combination Tablet, Sumatriptan Tablet, and Naproxen Sodium Tablet on Blood Pressure When Treating Migraine Headaches That Occur During a 6-month Period - Full Text View

Sponsor:	GlaxoSmithKline
Information provided by:	GlaxoSmithKline
ClinicalTrials.gov Identifier:	NCT00792636

Purpose

The purpose of this study is to test the effect on blood pressure of sumatriptan and naproxen sodium combination tablets, tablets containing only sumatriptan, and tablets containing only naproxen sodium when these drugs are taken to treat migraine headaches that occur during a 6-month period.

Condition	Intervention	Phase
Migraine With or Without Aura Migraine Disorders Acute Migraine Migraine Headaches	Drug: sumatriptan and naproxen sodium combination tablet Drug: sumatriptan tablet Drug: naproxen sodium tablet	Phase 4

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Assessment of the Effect of Sumatriptan and Naproxen Sodium Combination Tablet, Sumatriptan Tablet, and Naproxen Sodium Tablet Treatment on Blood Pressure When Administered Intermittently for Six Months for the Acute Treatment of Migraine Attacks, With or Without Aura, in Adults

Resource links provided by NLM:

MedlinePlus related topics: Headache Migraine

Drug Information available for: Naproxen Naproxen sodium Sumatriptan Sumatriptan succinate

U.S. FDA Resources

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:

Mean Change From Baseline in Systolic and Diastolic Blood Pressure at Month 6 for Sumatriptan/Naproxen [ Time Frame: Baseline and Month 6 ] [ Designated as safety issue: Yes ]
The calculation of baseline and post-baseline mean blood pressure (BP) (either systolic or diastolic) for each month (30-day period) is the average of all valid Telephonic Self-Measured Blood Pressure (T-SMBP) measurements. T-SMBP technology is a method that allows the participant to self-measure BP outside the clinic using a BP monitor and transfer the data from their home to a central server. Change from baseline was calculated as the Month 6 value minus the Baseline value. Least squares mean and confidence intervals were based on mixed model repeated measures analysis (MMRM).

Secondary Outcome Measures:

Mean Change From Baseline in Systolic and Diastolic Blood Pressure at Month 6 for Sumatriptan and Naproxen [ Time Frame: Baseline and Month 6 ] [ Designated as safety issue: Yes ]
The calculation of baseline and post-baseline mean BP (either systolic or diastolic) for each month (30-day period) is the average of all valid Telephonic Self-Measured Blood Pressure (T-SMBP) measurements. T-SMBP technology is a method that allows the participant to self-measure BP outside the clinic using a BP monitor and transfer the data from their home to a central server. Change from baseline was calculated as the Month 6 value minus the Baseline value. Least squares mean and confidence intervals were based on mixed model repeated measures analysis (MMRM).
Treatment Difference in Systolic and Diastolic Blood Pressure Mean Changes From Baseline at 6 Months Between Sumatriptan/Naproxen and Sumatriptan [ Time Frame: Baseline and Month 6 ] [ Designated as safety issue: Yes ]
The calculation of baseline and post-baseline mean BP (either systolic or diastolic) for each month (30-day period) is the average of all valid Telephonic Self-Measured Blood Pressure (T-SMBP) measurements. T-SMBP technology is a method that allows the participant to self-measure BP outside the clinic using a BP monitor and transfer the data from their home to a central server. Change from baseline was calculated as the Month 6 value minus the Baseline value. Least squares mean and confidence intervals were based on mixed model repeated measures analysis (MMRM).
Treatment Difference in Systolic and Diastolic Blood Pressure Mean Changes From Baseline at 6 Months Between Sumatriptan/Naproxen and Naproxen [ Time Frame: Baseline and Month 6 ] [ Designated as safety issue: Yes ]
The calculation of baseline and post-baseline mean BP (either systolic or diastolic) for each month (30-day period) is the average of all valid Telephonic Self-Measured Blood Pressure (T-SMBP) measurements. T-SMBP technology is a method that allows the participant to self-measure BP outside the clinic using a BP monitor and transfer the data from their home to a central server. Change from baseline was calculated as the Month 6 value minus the Baseline value. Least squares mean and confidence intervals were based on mixed model repeated measures analysis (MMRM).
Mean Change From Baseline in Systolic and Diastolic Blood Pressure at Month 6 for Sumatriptan/Naproxen for the ITT Subpopulation of Participants Treating, on Average, <4 Migraines, 4-6 Migraines, >=4 Migraines, and >6 Migraines Per Month [ Time Frame: Baseline and Month 6 ] [ Designated as safety issue: Yes ]
The calculation of baseline and post-baseline mean BP (either systolic or diastolic) for each month (30-day period) is the average of all valid T-SMBP measurements. The subgrouping of the ITT population was created and examined to demonstrate the robustness of the results for the primary analysis.Descriptive statistics were calculated for baseline, month 6, and change from baseline to month 6. LSMeans and corresponding confidence intervals were based on MMRM analysis. LSMeans and corresponding confidence intervals were not calculated for > 6 migraines/month group due to lack of convergence.
Mean Change From Baseline in Systolic and Diastolic Blood Pressure at Month 6 for Sumatriptan/Naproxen for the ITT Subpopulation of Participants Treating, on Average, <1.3 Times Per Migraine, 1.3-1.7 Times Per Migraine, and >1.7 Times Per Migraine [ Time Frame: Baseline and Month 6 ] [ Designated as safety issue: Yes ]
The calculation of baseline and post-baseline mean BP (either systolic or diastolic) for each month (30-day period) is the average of all valid T-SMBP measurements. The subgrouping of the ITT population was created and examined to demonstrate the robustness of the results for the primary analysis.Descriptive statistics were calculated for baseline, month 6, and change from baseline to month 6. LSMeans and corresponding confidence intervals were based on MMRM analysis.
Mean Change From Baseline in Systolic and Diastolic Blood Pressure at Month 6 for Sumatriptan/Naproxen for the ITT Subpopulation of Participants Treating, on Average, With <6, 6-10, >=6, 10-14, and >14 Doses Per Month [ Time Frame: Baseline and Month 6 ] [ Designated as safety issue: Yes ]
The calculation of baseline and post-baseline mean BP (either systolic or diastolic) for each month (30-day period) is the average of all valid T-SMBP measurements. The subgrouping of the ITT population was created and examined to demonstrate the robustness of the results for the primary analysis. Descriptive statistics were calculated for baseline, month 6, and change from baseline to month 6. LSMeans and corresponding confidence intervals (CIs) were based on MMRM analysis. LSMeans and CIs were not calculated for the 10-14 and the >14 doses/month groups due to lack of convergence.
Mean Change From Baseline in Systolic and Diastolic Blood Pressure at Month 6 for Sumatriptan/Naproxen for the ITT Subpopulation of Participants Treating With <30 Total Doses, 30-60 Total Doses, >=30, 60-90 Total Doses, and >90 Total Doses [ Time Frame: Baseline and Month 6 ] [ Designated as safety issue: Yes ]
The calculation of baseline and post-baseline mean BP (either systolic or diastolic) for each month (30-day period) is the average of all valid T-SMBP measurements. The subgrouping of the ITT population was created and examined to demonstrate the robustness of the results for the primary analysis. Descriptive statistics were calculated for baseline, month 6, and change from baseline to month 6. LSMeans and corresponding confidence intervals (CIs) were based on MMRM analysis. LSMeans and CIs were not calculated for the 60-90 and the >90 total dose groups due to lack of convergence.
Number of Participants With an Increase of >=5 mmHg From the Baseline Systolic Blood Pressure for the Average of Any Given Two-day Consecutive Collection of Blood Pressure Measurements [ Time Frame: Baseline to End of Study (6-month study duration) ] [ Designated as safety issue: Yes ]
The number of participants with an increase of >=5 mmHg from the baseline systolic blood pressure for the average of any given two-day consecutive collection of valid blood pressure measurements during the study were summarized. Valid blood pressure measurements were defined as follows: must be taken at least 24 hours following last dose of investigational product used to treat an individual migraine, must be taken no later than 96 hours after last dose of investigational product used to treat an individual migraine, must be taken prior to the onset of a subsequent individual migraine.
Number of Participants With an Increase of >=3 mmHg From the Baseline Diastolic Blood Pressure for the Average of Any Given Two-day Consecutive Collection of Blood Pressure Measurements [ Time Frame: Baseline to End of Study (6-month study duration) ] [ Designated as safety issue: Yes ]
The number of participants with an increase of >=3 mmHg from the baseline diastolic blood pressure for the average of any given two-day consecutive collection of valid blood pressure measurements during the study were summarized. Valid blood pressure measurements were defined as follows: must be taken at least 24 hours following last dose of investigational product used to treat an individual migraine, must be taken no later than 96 hours after last dose of investigational product used to treat an individual migraine, must be taken prior to the onset of a subsequent individual migraine.
Number of Participants With a Consecutive 2-day Average Systolic Blood Pressure of >=140 mmHg During the Study [ Time Frame: Baseline to End of Study (6-month study duration) ] [ Designated as safety issue: Yes ]
The number of participants with any valid two-day consecutive average systolic blood pressure measurement of >=140 mmHg was calculated. Valid blood pressure measurements were defined as follows: must be taken at least 24 hours following last dose of investigational product used to treat an individual migraine, must be taken no later than 96 hours after last dose of investigational product used to treat an individual migraine, must be taken prior to the onset of a subsequent individual migraine.
Number of Participants With a Consecutive 2-day Average Diastolic Blood Pressure of >=90 mmHg [ Time Frame: Baseline to End of Study (6-month study duration) ] [ Designated as safety issue: Yes ]
The number of participants with any valid two-day consecutive average diastolic blood pressure measurement of >=90 mmHg was calculated. Valid blood pressure measurements were defined as follows: must be taken at least 24 hours following last dose of investigational product used to treat an individual migraine, must be taken no later than 96 hours after last dose of investigational product used to treat an individual migraine, must be taken prior to the onset of a subsequent individual migraine.
Time to the First Day With an Average Systolic Blood Pressure Increase of >=5 mmHg From the Baseline Systolic Blood Pressure [ Time Frame: Baseline to End of Study (6-month study duration) ] [ Designated as safety issue: Yes ]
Kaplan-Meier curves for the distribution of time to the first day with an average diastolic BP increase of >=3 mmHg from the baseline diastolic BP during each calendar day were calculated and graphed for each treatment group. Only valid BP measurements were included and were defined as follows: must be taken at least 24 hours following last dose of investigational product used to treat an individual migraine, must be taken no later than 96 hours after last dose of investigational product used to treat an individual migraine, must be taken prior to the onset of a subsequent individual migraine.
Time to the First Day With an Average Diastolic Blood Pressure Increase of >=3 mmHg From the Baseline Diastolic Blood Pressure [ Time Frame: Baseline to End of Study (6-month study duration) ] [ Designated as safety issue: Yes ]
Kaplan-Meier curves for the distribution of time to the first day with an average diastolic BP increase of >=3 mmHg from the baseline diastolic BP during each calendar day were calculated and graphed for each treatment group. Only valid BP measurements were included and were defined as follows: must be taken at least 24 hours following last dose of investigational product used to treat an individual migraine, must be taken no later than 96 hours after last dose of investigational product used to treat an individual migraine, must be taken prior to the onset of a subsequent individual migraine.
Number of Participants Withdrawn From the Study Due to Blood Pressure Changes [ Time Frame: Baseline to End of Study (6-month study duration) ] [ Designated as safety issue: Yes ]
The number of participants withdrawn from the study due to protocol-defined blood pressure changes were summarized for each treatment group. Defined blood pressure changes included (1) monthly average BP ≥140 mmHg systolic or >=90 mmHg diastolic and confirmed in clinic, (2) monthly average BP increase of >=30 mmHg systolic or >=20 mmHg from in-clinic screening and confirmed in clinic, and (3) systolic >=140 mmHg or diastolic >=90 mmHg on consecutive clinic visits >=2 weeks apart.

Enrollment:	407
Study Start Date:	November 2008
Study Completion Date:	November 2009
Primary Completion Date:	November 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: sumatriptan and naproxen sodium combination	Drug: sumatriptan and naproxen sodium combination tablet sumatriptan 85mg and naproxen sodium 500mg
Active Comparator: sumatriptan	Drug: sumatriptan tablet sumatriptan 85mg
Active Comparator: naproxen sodium	Drug: naproxen sodium tablet Naproxen sodium 500mg

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Subjects eligible for enrollment in the study must meet all of the following criteria:

Male and female outpatients 18 to 65 years of age. Female subjects are eligible for participation in the study if they are:
- Females of non-childbearing potential
- Females of childbearing potential and who have a negative urine pregnancy test at Screening and agree to use one of the GlaxoSmithKline specified highly effective methods for avoiding pregnancy. Subjects taking oral contraceptives must be on a stable regimen for at least two months prior to Screening.
Subject with migraines, with or without aura (ICHD-II criteria, 1.2.1 or 1.1) [International Headache Society, 2004]. Subject must have a history of two to eight attacks per month, on average, for the six months prior to the Screening Visit. Additionally the subject is to have experienced at least two, but no more than eight, migraine attacks per month for the three months prior to Screening Visit.
Subject is able to distinguish migraine attacks from other headaches (i.e. tension-type headaches).
Subject is willing and able to provide written informed consent, to comprehend and perform the requirements of the protocol.

Exclusion criteria:

Subjects meeting any of the following criteria must not be enrolled in the study:

Subject has ≥10 migraine attacks or ≥15 headache days per month in total (including migraine, probable migraine or tension-type headache).
Subject has retinal (ICHD-II 1.4), basilar (ICHD-II 1.2.6), or hemiplegic migraine (ICHD-II 1.2.4), or secondary headaches [International Headache Society, 2004].
Subject has a history of controlled or uncontrolled hypertension or is currently taking any angiotension-converting enzyme (ACE) inhibitor or angiotension receptor blocker.
Subject has an in-clinic screening blood pressure of ≥ 130/85 mmHg in two out of three blood pressure measurements.
Subject is taking any anti-hypertensive medication for any reason including for migraine prophylaxis.
Subject has a glycosylated hemoglobin ≥ 8.0
Subject has a chronic condition (i.e. osteoarthritis, rheumatoid arthritis,fibromyalgia) which requires chronic daily administration of non-steroidal anti-inflammatory drugs (NSAIDS) (including acetaminophen) or opioids or opioid combination products.
Subject, in the investigator's opinion, is likely to have unrecognized cardiovascular or cerebrovascular disease.
Subject has a history of congenital heart disease, cardiac arrhythmias requiring medication, or a history of a clinically significant electrocardiogram abnormality that, in the investigator's opinion, contraindicates participation in the study.
Subject has evidence or history of any ischemic vascular diseases including: ischemic heart disease, ischemic abdominal syndromes, peripheral vascular disease or Raynaud's Syndrome, or any signs or symptoms consistent with any of the above.
Subject has evidence or history of central nervous system pathology including stroke and/or transient ischemic attacks (TIAs), epilepsy or structural brain lesions which lower the convulsive threshold, or has been treated with an antiepileptic drug for seizure control within five years prior to Screening.
Subject has a history of impaired hepatic or renal function that, in the investigator's opinion, contraindicates participation in the study.
Subject has hypersensitivity, allergy, intolerance or contraindication to the use of any triptan, NSAID, or aspirin (including all sumatriptan and naproxen preparations) or has nasal polyps and asthma.
Subject is currently taking, or has used, an ergot or ergot-derived medication in the previous three months for migraine prophylaxis or is taking a medication that is not stabilized (i.e. change of a dose within the past two months) for chronic or intermittent migraine prophylaxis or for a co-morbid condition that is not stabilized.
Subject has a recent history of regular use of opioids or barbiturates for the treatment of their migraine headache and/or other non-migraine pain. Regular use is defined as an average of four days per month over the last six months.
Subject has taken or plans to take a monoamine oxidase inhibitor (MAOI), including herbal preparations containing St. John's Wort (Hypericum perforatum) or a CNS stimulant medication (such as atomoxetine, dextroamphetamine and amephetamine products, dexmethlyphenidate, lisdexamdetamine dimesylate and methylphenidate) anytime within two weeks prior to Screening through two-weeks post-treatment.
Subject has a history of any bleeding disorder or is currently taking any anticoagulant or any anti-platelet agent. (except low-dose aspirin <=325mg/day for cardioprotective reasons).
Subject has evidence or history of any gastrointestinal surgery, gastrointestinal ulceration or perforation in the past six months, gastrointestinal bleeding in the past year, or evidence or history of inflammatory bowel disease.
Subject is pregnant, actively trying to become pregnant, or breast feeding or subject is not willing to have pregnancy tests performed as required.
Subject tests positive for illicit substances on toxicology screen or has evidence of alcohol or substance abuse within the last year, or any concurrent medical or psychiatric condition which, in the investigator's judgment, will likely interfere with the study conduct, subject cooperation, or evaluation and interpretation of the study results, or which otherwise contraindicates participation in this clinical trial.
Subject has participated in an investigational drug trial within the previous four weeks or plans to participate in another study at any time during the study.

Responsible Party:	Cheri Hudson; Clinical Disclosure Advisor, GSK Clinical Disclosure
ClinicalTrials.gov Identifier:	NCT00792636 History of Changes
Other Study ID Numbers:	110948
Study First Received:	November 17, 2008
Results First Received:	October 7, 2010
Last Updated:	March 17, 2011
Health Authority:	United States: Food and Drug Administration