TREXIMA and RELPAX Gastric Scintigraphy Inside and Outside a Migraine

• ClinicalTrials.gov Identifier: NCT00385008
• Recruitment Status: Completed
• First Posted: October 6, 2006
• Results First Posted: February 12, 2018
• Last Update Posted: February 12, 2018
• Sponsor: GlaxoSmithKline
• Information provided by (Responsible Party): GlaxoSmithKline

Study Description

Brief Summary:

An evaluation of tablet disintegration and absorption and gastric transit of sumatriptan and naproxen sodium from a TREXIMA tablet and eletriptan from a RELPAX 40mg tablet.

Condition or disease	Intervention/treatment	Phase
Migraine Disorders	Drug: Combination Product (sumatriptan succinate / naproxen sodium); Drug: RELPAX(eletriptan) 40mg Tablet	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open Label, Single Dose, Parallel Group Study to Evaluate Absorption and Transit Characteristics of TREXIMA and RELPAX in Patients Inside and Outside of an Acute Migraine Attack.
• Actual Study Start Date: September 13, 2006
• Actual Primary Completion Date: November 24, 2006
• Actual Study Completion Date: November 24, 2006

Arms and Interventions

Arm	Intervention/treatment
Arm 1; open-label active drug	Drug: Combination Product (sumatriptan succinate / naproxen sodium); sumatriptan/naproxen sodium
Arm 2; open-label active drug	Drug: RELPAX(eletriptan) 40mg Tablet; eletriptan tablets; Other Name: Combination Product (sumatriptan succinate / naproxen sodium)

Outcome Measures

Primary Outcome Measures :

1. Time to 10%, 50%, 90% and Complete Gastric Empting of the Radioactive Markers Representing Sumatriptan, Naproxen and Eletriptan [ Time Frame: Day 1 of each treatment administration (For 30 days) ]
   Scintigraphic images were analyzed in a time-lapse format and regions of interest were drawn to include the stomach and small intestine. Images were recorded in a supine position and a series of 3 to 60 consecutive anterior scintigraphic images, each 1 minute in duration, were recorded using a clinical grade gamma camera. After this initial continuous imaging sequence, additional images were recorded to coincide with pharmacokinetic (PK) blood sampling times as necessary to monitor the tablet disintegration and transit time through the intestines. Prior to ingesting the radiolabeled dosage forms, two external markers (2-3 microcuries of indium-111 or technetium-99m) were placed on each participant to facilitate consistent positioning underneath the gamma camera. The first marker was placed on the right side of the participant's chest (approximately at the fifth intercostal rib) and a second marker was placed on the hip bone (approximately the left anterior superior ileac spine).
2. Mean Area Under the Drug Concentration Time Curve (AUC) From Time of Dosing Through 2 Hour Post-dose [AUC (0-2)], Through 24 Hour [AUC (0-24)] and AUC From Time of Dosing Extrapolated to Infinity [AUC (0-inf)] for Sumatriptan and Naproxen [ Time Frame: Pre-dose and then at 5 minute intervals through 60 minutes, at 75 minutes, every 30 minutes from 90 minutes through 6 hours, and at 8, 10, 12, 24, 48 and 72 hours post-dose for each treatment administered. ]
   Following TREXIMA administration, 6 mL blood sample was collected at pre-dose and then at 5, 10 , 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, and 75 minutes. Then at 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6 hour and at 8, 10, 12, 24, 48, 72 hour post-dose for each treatment administered. All available plasma supernatant was withdrawn from the precipitated blood fraction.
3. Mean AUC (0-inf) and AUC (0-2) for Eletriptan [ Time Frame: Pre-dose and then at 5 minute intervals through 60 minutes, at 75 minutes, every 30 minutes from 90 minutes through 6 hours, and at 8, 10, 12 hours post-dose for each treatment administered. ]
   Following Relpax administration, 8 mL blood sample was collected at pre-dose and then at 5, 10 , 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, and 75 minutes. Then at 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6 hour and at 8, 10, 12 hour post-dose for each treatment administered. All available plasma supernatant was withdrawn from the precipitated blood fraction.
4. Maximum Observed Drug Concentration (Cmax) for Sumatriptan and Naproxen [ Time Frame: Pre-dose and then at 5 minute intervals through 60 minutes, at 75 minutes, every 30 minutes from 90 minutes through 6 hours, and at 8, 10, 12, 24, 48 and 72 hours post-dose for each treatment administered. ]
   Following TREXIMA administration, 6 mL blood sample was collected at pre-dose and then at 5, 10 , 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, and 75 minutes. Then at 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6 hour and at 8, 10, 12, 24, 48, 72 hour post-dose for each treatment administered. All available plasma supernatant was withdrawn from the precipitated blood fraction.
5. Cmax for Eletriptan [ Time Frame: Pre-dose and then at 5 minute intervals through 60 minutes, at 75 minutes, every 30 minutes from 90 minutes through 6 hours, and at 8, 10, 12 hours post-dose for each treatment administered. ]
   Following Relpax administration, 8 mL blood sample was collected at pre-dose and then at 5, 10 , 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, and 75 minutes. Then at 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6 hour and at 8, 10, 12 hour post-dose for each treatment administered. All available plasma supernatant was withdrawn from the precipitated blood fraction.
6. Time of Maximal Drug Concentration (Tmax) for Sumatriptan and Naproxen [ Time Frame: Pre-dose and then at 5 minute intervals through 60 minutes, at 75 minutes, every 30 minutes from 90 minutes through 6 hours, and at 8, 10, 12, 24, 48 and 72 hours post-dose for each treatment administered. ]
   Following TREXIMA administration, 6 mL blood sample was collected at pre-dose and then at 5, 10 , 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, and 75 minutes. Then at 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6 hour and at 8, 10, 12, 24, 48, 72 hour post-dose for each treatment administered. All available plasma supernatant was withdrawn from the precipitated blood fraction.
7. Tmax for Eletriptan [ Time Frame: Pre-dose and then at 5 minute intervals through 60 minutes, at 75 minutes, every 30 minutes from 90 minutes through 6 hours, and at 8, 10, 12 hours post-dose for each treatment administered. ]
   Following Relpax administration, 8 mL blood sample was collected at pre-dose and then at 5, 10 , 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, and 75 minutes. Then at 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6 hour and at 8, 10, 12 hour post-dose for each treatment administered. All available plasma supernatant was withdrawn from the precipitated blood fraction.
8. Time to Complete Dispersion of the Sumatriptan and Naproxen Portions of the TREXIMA Tablet and of the Relpax Tablet [ Time Frame: Day 1 of each treatment administered (For 30 days) ]
   Scintigraphic images were analyzed in a time-lapse format and regions of interest were to be drawn to include the stomach and small intestine. Images were recorded in a supine position and a series of 3 to 60 consecutive anterior scintigraphic images, each 1 minute in duration, were recorded using a clinical grade gamma camera. After this initial continuous imaging sequence, additional images were recorded to coincide with PK blood sampling times as necessary to monitor the tablet disintegration and transit time through the intestines. Prior to ingesting the radiolabeled dosage forms, two external markers (2-3 microcuries of indium-111 or technetium-99m) were placed on each participant to facilitate consistent positioning underneath the gamma camera. The first marker was placed on the right side of the participant's chest (approximately at the fifth intercostal rib) and a second marker was placed on the hip bone (approximately the left anterior superior ileac spine).
9. Time to First Appearance of Sumatriptan, Naproxen and Eletriptan at the Proximal Small Intestine [ Time Frame: Day 1 of each treatment administered (For 30 days) ]
   Scintigraphic images were analyzed in a time-lapse format and regions of interest were to be drawn to include the stomach and small intestine. Images were recorded in a supine position and a series of 3 to 60 consecutive anterior scintigraphic images, each 1 minute in duration, were recorded using a clinical grade gamma camera. After this initial continuous imaging sequence, additional images were recorded to coincide with PK blood sampling times as necessary to monitor the tablet disintegration and transit time through the intestines. Prior to ingesting the radiolabeled dosage forms, two external markers (2-3 microcuries of indium-111 or technetium-99m) were placed on each participant to facilitate consistent positioning underneath the gamma camera. The first marker was placed on the right side of the participant's chest (approximately at the fifth intercostal rib) and a second marker was placed on the hip bone (approximately the left anterior superior ileac spine).
10. Small Intestine Transit and Residence (Time to 50% Through Intestine) of the Radioactive Markers Representing Sumatriptan, Naproxen and Eletriptan [ Time Frame: Day 1 of each treatment administered (For 30 days) ]
    Scintigraphic images were analyzed in a time-lapse format and regions of interest were to be drawn to include the stomach and small intestine. Images were recorded in a supine position and a series of 3 to 60 consecutive anterior scintigraphic images, each 1 minute in duration, were recorded using a clinical grade gamma camera. After this initial continuous imaging sequence, additional images were recorded to coincide with PK blood sampling times as necessary to monitor the tablet disintegration and transit time through the intestines. Prior to ingesting the radiolabeled dosage forms, two external markers (2-3 microcuries of indium-111 or technetium-99m) were placed on each participant to facilitate consistent positioning underneath the gamma camera. The first marker was placed on the right side of the participant's chest (approximately at the fifth intercostal rib) and a second marker was placed on the hip bone (approximately the left anterior superior ileac spine).

Secondary Outcome Measures :

1. Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to Day 30 ]
   AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Consented males and nonpregnant females using adequate contraception, between 18 and 55 years of age, with at least 1-6 migraines per month for past 6 months. Subjects will be excluded for confirmed or suspected ischemic heart disease, uncontrolled hypertension at screening; a history of epilepsy or structural brain lesions which lowered the convulsive threshold; confirmed or suspected cardiovascular, cerebrovascular, peripheral vascular, congenital heart disease, or ischemic bowel disease; impaired hepatic or renal function; basilar or hemiplegic migraine. Other exclusion criteria included use of a monoamine oxidase inhibitor within 2 weeks before screening; ergot prophylactics in past 3 months; anticoagulants; smoking more than 10 cigarettes/day, evidence of alcohol or substance abuse; GI bleeding disorders, inflammatory bowel disease; or any concurrent medical or psychiatric condition that in the investigator's opinion could affect interpretation of efficacy or safety information or which otherwise contraindicated participation in the study.

Contacts and Locations

Locations

United States, Kentucky

GSK Investigational Site

Lexington, Kentucky, United States, 40503

Sponsors and Collaborators

GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials; GlaxoSmithKline

More Information

Additional Information:

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 Data/Documents: Individual Participant Data Set 

Identifier: TRX105848
For additional information about this study please refer to the GSK Clinical Study Register

Statistical Analysis Plan 

Identifier: TRX105848
For additional information about this study please refer to the GSK Clinical Study Register

Study Protocol 

Identifier: TRX105848
For additional information about this study please refer to the GSK Clinical Study Register

Dataset Specification 

Identifier: TRX105848
For additional information about this study please refer to the GSK Clinical Study Register

Clinical Study Report 

Identifier: TRX105848
For additional information about this study please refer to the GSK Clinical Study Register

Informed Consent Form 

Identifier: TRX105848
For additional information about this study please refer to the GSK Clinical Study Register

Annotated Case Report Form 

Identifier: TRX105848
For additional information about this study please refer to the GSK Clinical Study Register

Publications:

Kori S, Byrd S, Doll W, Page R, and Sandefer E. Gastric Emptying and Absorption of a Sumatriptan with RT Technology 85mg and Naproxen Sodium 500mg Tablet. Cephalalgia 2007; Vol 27; 649.

Kori S, Byrd S, Doll W, Page R, and Sandefer E. Gastroscintigraphic Evaluation of Gastric Emptying and Absorption of Another Conventionally Formulated Triptan. Cephalalgia 2007; Vol 27; 730.

Kori S, Byrd SC, Doll WJ, Page RC, and Sandefer EP. Gastric Transit and Absorption of Sumatriptan and Naproxen from a Fixed Single-Tablet Sumatriptan RT Technology 85mg and Naproxen Sodium 500mg in Migraineurs both During and Outside a Migraine Attack: Evaluation by Gastric Scintigraphy. Headache 2007; 47(5):751.

Kori S, Doll WJ, Page RC, Byrd SC, Sandefer EP. Gastric Transit and Absorption of Eletriptan, another Conventionally Formulated Triptan, in Migraineurs both During and Outside a Migraine Attack: Evaluation by Gastric Scintigraphy. Headache 2007; 47(5):752.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT00385008
• Other Study ID Numbers: TRX105848
• First Posted: October 6, 2006
• Results First Posted: February 12, 2018
• Last Update Posted: February 12, 2018
• Last Verified: August 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• 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.

Keywords provided by GlaxoSmithKline:

Combination product, sumatriptan succinate, naproxen sodium, absorption, pharmacokinetics, disintegration, gastric transit, gastric scintigraphy

Additional relevant MeSH terms:

Migraine Disorders; Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Naproxen; Sumatriptan; Eletriptan; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antirheumatic Agents; Gout Suppressants; Cyclooxygenase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Vasoconstrictor Agents; Serotonin 5-HT1 Receptor Agonists; Serotonin Receptor Agonists; Serotonin Agents; Neurotransmitter Agents