An Open-label, Randomized, 3-period Crossover Study to Evaluate Sumatriptan Pharmacokinetics for a TREXIMA™ (Sumatriptan Succinate / Naproxen Sodium) Tablet Followed by IMITREX® (Sumatriptan Succinate)

An Open-label, Randomized, 3-period Crossover Study to Evaluate Sumatriptan Pharmacokinetics for a TREXIMA™ (Sumatriptan Succinate / Naproxen Sodium) Tablet Followed by IMITREX® (Sumatriptan Succinate) Injection 4mg Administered Using the IMITREX STATdose System® and a TREXIMA Tablet Followed by IMI

This study will evaluate the exposure of sumatriptan after administration of TREXIMA (sumatriptan 85mg/naproxen sodium 500mg) followed by a subcutaneous IMITREX injection (4mg or 6mg) 2 hours later compared to administration of a IMITREX 100mg tablet followed by a IMITREX 100mg tablet 2 hours later.

Study Overview

• Status: Completed
• Conditions: Migraine Disorders
• Intervention / Treatment: Drug: TREXIMA™; Drug: IMITREX® (4mg); Drug: IMITREX® (6mg); Drug: IMITREX Tablet 100mg

Detailed Description

An open-label, randomized, 3-period crossover study to evaluate sumatriptan pharmacokinetics for a TREXIMA™ (sumatriptan succinate / naproxen sodium) Tablet followed by IMITREX® (sumatriptan succinate) Injection 4mg administered using the IMITREX STATdose System® and a TREXIMA tablet followed by IMITREX® (sumatriptan succinate) Injection 6mg administered using the IMITREX STATdose System® compared with an IMITREX Tablet 100mg followed by an IMITREX Tablet 100mg.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Washington
    • Tacoma, Washington, United States, 98418
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 51 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy adult males and females between 18 and 55 years of age, inclusive. Healthy subjects are defined as individuals who are free from clinically significant illness or disease as determined by their medical history, physical examination, laboratory studies and other tests.
• Female subjects of non-childbearing potential
• Any subject taking oral contraceptives has been on a stable regimen for at least 2 months prior to screening.
• BMI: 20-30 kg/m2, inclusive.
• Subject is willing and able to provide written informed consent.

Exclusion Criteria:

• Subjects who suffer from migraine attacks.
• Subject has confirmed or suspected ischemic heart disease; angina pectoris, history of myocardial infarction, documented silent ischemia, Prinzmetal's angina-coronary vasospasm, signs, or symptoms consistent with any of the above.
• Subject has evidence or history of ischemic abdominal syndromes, peripheral vascular disease or Raynaud's syndrome.
• Subject has cardiac arrhythmias requiring medication or a history of a clinically significant electrocardiogram abnormality that, in the investigator's opinion, contraindicates participation in this study.
• Subject has a history of cerebrovascular pathology including stroke and/or transient ischemic attacks.
• Subject has a history of congenital heart disease.
• Subject has hypertension at screening.
• Subject, in the investigator's opinion, is likely to have unrecognized cardiovascular or cerebrovascular disease.
• Subject has a history of epilepsy or structural brain lesions which lower the convulsive threshold or treated with an antiepileptic drug for seizure control within 5 years prior to screening.
• History of impaired hepatic or renal function.
• Subject is currently taking or has taken in the previous 4 weeks, herbal preparations containing St. John's Wort.
• Use of other prescription or non-prescription drugs, vitamins, herbal and dietary supplements, within 7 days prior to the first dose of study medication.

Note: Excluded from this list are: acetaminophen at doses of less than or equal to 2 grams per day and contraceptives.

• Subject has a hypersensitivity, intolerance, or contraindication to the use of sumatriptan or naproxen sodium or any of their components or any other 5-HT1 receptor agonist.
• Subject has a history of any gastrointestinal surgery that specifically indicates a past history of bleeding, ulceration or perforation.
• Subject has a history of gastric bypass or stapling surgery.
• Subject has a history of GI ulceration in the past six months or gastrointestinal bleeding in the past year.
• Subject has a history of inflammatory bowel disease.
• Treatment with an investigational drug within 30 preceding the first dose of study medication.
• Positive serum beta-human chorionic gonadotropin test -females.
• Pregnant, actively trying to become pregnant or breast-feeding.
• Subjects with a history of drug or alcohol abuse.
• History of regular alcohol consumption exceeding 7 drinks per week for females or 14 drinks per week for men within 6 months of screening.
• Positive urine drug screen including alcohol at screening.
• Donation of blood in excess of 500 mL within 56 days prior to first dose of study medication.
• Subjects who smoke more than 10 cigarettes per day.
• History of sensitivity to heparin, heparin-induced thrombocytopenia or sensitivity to any of the study medications or components thereof.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TREXIMA tablet followed by IMITREX injection (4mg); TREXIMA™ (sumatriptan succinate / naproxen sodium) Tablet followed by IMITREX® (sumatriptan succinate) Injection 4mg administered using the IMITREX STATdose System®	Drug: TREXIMA™; sumatriptan succinate / naproxen sodium tablet; Drug: IMITREX® (4mg); sumatriptan succinate injection (4mg) administered using the IMITREX STATdose System®
Experimental: TREXIMA tablet followed by IMITREX injection (6mg); TREXIMA tablet followed by IMITREX® (sumatriptan succinate) Injection 6mg administered using the IMITREX STATdose System®	Drug: TREXIMA™; sumatriptan succinate / naproxen sodium tablet; Drug: IMITREX® (6mg); sumatriptan succinate injection (6mg) administered using the IMITREX STATdose System®
Active Comparator: IMITREX tablet (100mg); IMITREX 100mg tablet followed 2 hours later by a second IMITREX 100mg tablet	Drug: IMITREX Tablet 100mg; IMITREX 100mg tablet followed 2 hours later by a second IMITREX 100mg tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The maximum plasma concentration (Cmax) after the second dose and total exposure (measured by AUC(0-∞) calculated as pooled exposure from both the initial and second dose).	ten weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Incidence and severity of adverse events, blood pressure, pulse, ECGs and clinical laboratory tests.	ten weeks

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Berges A, Walls C, Lener SE, McDonald SA. Pharmacokinetics and tolerability of sumatriptan after single-dose administration of a fixed-dose combination tablet of sumatriptan/naproxen sodium 85/500 mg followed two hours later by subcutaneous sumatriptan 4- or 6-mg injection: a randomized, open-label, three-period crossover study in healthy volunteers. Clin Ther. 2010 Jun;32(6):1165-77. doi: 10.1016/j.clinthera.2010.06.014.

Helpful Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Study record dates

Study Major Dates

• Study Start (Actual): May 6, 2008
• Primary Completion (Actual): June 14, 2008
• Study Completion (Actual): June 14, 2008

Study Registration Dates

• First Submitted: March 26, 2009
• First Submitted That Met QC Criteria: April 2, 2009
• First Posted (Estimate): April 3, 2009

Study Record Updates

• Last Update Posted (Actual): August 4, 2017
• Last Update Submitted That Met QC Criteria: August 3, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: Sumatriptan exposure
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Migraine Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Serotonin Agents; Serotonin 5-HT1 Receptor Agonists; Serotonin Receptor Agonists; Vasoconstrictor Agents; Sumatriptan
• Other Study ID Numbers: 103629

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

1. Dataset Specification
   Information identifier: 103629
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Study Protocol
   Information identifier: 103629
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Annotated Case Report Form
   Information identifier: 103629
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Individual Participant Data Set
   Information identifier: 103629
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Clinical Study Report
   Information identifier: 103629
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Informed Consent Form
   Information identifier: 103629
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Statistical Analysis Plan
   Information identifier: 103629
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register