TREXIMA and RELPAX Gastric Scintigraphy Inside and Outside a Migraine

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00385008
• Collaborator: (none)
• Enrollment: 20
• Location: 1
• Arms: 2
• Actual Duration (Months): 2.4
• Patients Per Site Per Month: 8.5

Study Details

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
• 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: Sep 13, 2006
• Actual Primary Completion Date: Nov 24, 2006
• Actual Study Completion Date: Nov 24, 2006

Arms and Interventions

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

Criteria

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

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

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Lexington	Kentucky	United States	40503

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

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.

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: Oct 6, 2006
• Last Update Posted: Feb 12, 2018
• Last Verified: Aug 1, 2017

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by GlaxoSmithKline: Combination product, sumatriptan succinate, naproxen sodium, absorption, pharmacokinetics, disintegration, gastric transit, gastric scintigraphy
• Additional relevant MeSH terms: Migraine Disorders; Naproxen; Sumatriptan; Eletriptan

Study Results

Participant Flow

Recruitment Details	This study was conducted at a single site in the United States during 13 September 2006 to 24 November 2006. TREXIMA® tablet was a fixed dose combination of sumatriptan succinate 119 milligrams (mg) (equivalent to 85 mg of sumatriptan) and naproxen sodium 500 mg.
Pre-assignment Detail	First ten participants enrolled received TREXIMA and the next ten enrolled received Relpax. In each group, the first 5 participants who had a migraine and who were able to attend the clinic received the extra dose of the respective treatment.

Arm/Group Title	TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg)	Relpax (Eletriptan 40 mg)
Arm/Group Description	Ten participants received single dose of radio labeled TREXIMA tablet (fixed dose combination of sumatriptan succinate 119 mg [equivalent to 85 mg of sumatriptan] and naproxen sodium 500 mg), orally, in absence of migraine. Five participants out of these participants visited clinic when they were experiencing an acute migraine attack and received TREXIMA during migraine attack at clinic. Dosing was repeated up to 2 additional times for up to 4 total doses. Each treatment administration were separated by at least 7 days. Each dose was administered with 240 milliliter (mL) of water.	Ten participants received single dose of Relpax (eletriptan hydrobromide, 40 mg) tablet, orally, in absence of migraine. Five participants out of theses participants visited clinic when they were experiencing an acute migraine attack and received single dose Relpax (eletriptan hydrobromide, 40 mg) tablet during migraine attack at clinic. Dosing was repeated up to 2 additional times for up to 4 total doses. Each treatment administration were separated by at least 7 days. Each dose was administered with 240 mL of water.
Period Title: Overall Study
STARTED	10	10
In Absence of Migraine	10	10
In Presence of Migraine	5	5
COMPLETED	10	10
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg)	Relpax (Eletriptan 40 mg)	Total
Arm/Group Description	Ten participants received single dose of radio labeled TREXIMA tablet (fixed dose combination of sumatriptan succinate 119 mg [equivalent to 85 mg of sumatriptan] and naproxen sodium 500 mg), orally, in absence of migraine. Five participants out of these participants visited clinic when they were experiencing an acute migraine attack and received TREXIMA during migraine attack at clinic. Dosing was repeated up to 2 additional times for up to 4 total doses. Each treatment administration were separated by at least 7 days. Each dose was administered with 240 mL of water.	Ten participants received single dose of Relpax (eletriptan hydrobromide, 40 mg) tablet, orally, in absence of migraine. Five participants out of theses participants visited clinic when they were experiencing an acute migraine attack and received single dose Relpax (eletriptan hydrobromide, 40 mg) tablet during migraine attack at clinic. Dosing was repeated up to 2 additional times for up to 4 total doses. Each treatment administration were separated by at least 7 days. Each dose was administered with 240 mL of water.	Total of all reporting groups
Overall Participants	10	10	20
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	30.6 (7.50)	33.3 (7.17)	32 (7.27)
Sex: Female, Male (Count of Participants)
Female	10 100%	9 90%	19 95%
Male	0 0%	1 10%	1 5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	10 100%	10 100%	20 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Time to 10%, 50%, 90% and Complete Gastric Empting of the Radioactive Markers Representing Sumatriptan, Naproxen and Eletriptan
Description	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).
Time Frame	Day 1 of each treatment administration (For 30 days)

Outcome Measure Data

Analysis Population Description

Scintigraphy Population consisted of all participants with evaluable data from the scintigraphic images.

Arm/Group Title	TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg)	Relpax (Eletriptan 40 mg)
Arm/Group Description	Ten participants received single dose of radio labeled TREXIMA tablet (fixed dose combination of sumatriptan succinate 119 mg [equivalent to 85 mg of sumatriptan] and naproxen sodium 500 mg), orally, in absence of migraine. Five participants out of these participants visited clinic when they were experiencing an acute migraine attack and received TREXIMA during migraine attack at clinic. Dosing was repeated up to 2 additional times for up to 4 total doses. Each treatment administration were separated by at least 7 days. Each dose was administered with 240 mL of water.	Ten participants received single dose of Relpax (eletriptan hydrobromide, 40 mg) tablet, orally, in absence of migraine. Five participants out of theses participants visited clinic when they were experiencing an acute migraine attack and received single dose Relpax (eletriptan hydrobromide, 40 mg) tablet during migraine attack at clinic. Dosing was repeated up to 2 additional times for up to 4 total doses. Each treatment administration were separated by at least 7 days. Each dose was administered with 240 mL of water.
Measure Participants	10	10
10% gastric emptying, Sumatriptan, Non-migraine	0.100
10% gastric emptying, Sumatriptan, Migraine	0.130
10% gastric emptying, Naproxen, Non-migraine	1.195
10% gastric emptying, Naproxen, Migraine	1.300
10% gastric emptying, Eletriptan, Non-migraine	0.400
10% gastric emptying, Eletriptan, Migraine	0.410
50% gastric emptying, Sumatriptan, Non-migraine	0.675
50% gastric emptying, Sumatriptan, Migraine	1.070
50% gastric emptying, Naproxen, Non-migraine	2.260
50% gastric emptying, Naproxen, Migraine	2.310
50% gastric emptying, Eletriptan, Non-migraine	0.590
50% gastric emptying, Eletriptan, Migraine	0.890
90% gastric emptying, Sumatriptan, Non-migraine	3.020
90% gastric emptying, Sumatriptan, Migraine	3.440
90% gastric emptying, Naproxen, Non-migraine	4.290
90% gastric emptying, Naproxen, Migraine	4.010
90% gastric emptying, Eletriptan, Non-migraine	2.590
90% gastric emptying, Eletriptan, Migraine	2.490
Complete gastric emptying,Sumatriptan,Non-migraine	4.505
Complete gastric emptying, Sumatriptan, Migraine	4.000
Complete gastric emptying, Naproxen, Non-migraine	4.760
Complete gastric emptying, Naproxen, Migraine	4.500
Complete gastric emptying, Eletriptan,Non-migraine	3.765
Complete gastric emptying, Eletriptan, Migraine	3.510

2. Primary Outcome

Title	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
Description	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.
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.

Outcome Measure Data

Analysis Population Description

PK parameter population comprised of all participants in the PK concentration population for whom PK parameters were calculated. PK concentration population comprised of all participants who had a sample obtained and analyzed. Only those participants available at the specified time points were analyzed.

Arm/Group Title	TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg)
Arm/Group Description	Ten participants received single dose of radio labeled TREXIMA tablet (fixed dose combination of sumatriptan succinate 119 mg [equivalent to 85 mg of sumatriptan] and naproxen sodium 500 mg), orally, in absence of migraine. Five participants out of these participants visited clinic when they were experiencing an acute migraine attack and received TREXIMA during migraine attack at clinic. Dosing was repeated up to 2 additional times for up to 4 total doses. Each treatment administration were separated by at least 7 days. Each dose was administered with 240 mL of water.
Measure Participants	10
AUC (0-24), Sumatriptan, Non-migraine	231.526 (25.63)
AUC (0-24), Sumatriptan, Migraine	165.707 (38.05)
AUC (0-inf), Sumatriptan, Non-migraine	231.999 (24.76)
AUC (0-inf), Sumatriptan, Migraine	158.036 (41.67)
AUC (0-2), Sumatriptan, Non-migraine	65.156 (36.18)
AUC (0-2), Sumatriptan, Migraine	54.884 (22.28)
AUC (0-24), Naproxen, Non-migraine	570.54 (15.0)
AUC (0-24), Naproxen, Migraine	627.06 (20.6)
AUC (0-inf), Naproxen, Non-migraine	901.13 (21.9)
AUC (0-inf), Naproxen, Migraine	978.39 (23.4)
AUC (0-2), Naproxen, Non-migraine	23.16 (79.3)
AUC (0-2), Naproxen, Migraine	24.38 (117.5)

3. Primary Outcome

Title	Mean AUC (0-inf) and AUC (0-2) for Eletriptan
Description	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.
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.

Outcome Measure Data

Analysis Population Description

The PK parameter Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Relpax (Eletriptan 40 mg)
Arm/Group Description	Ten participants received single dose of Relpax (eletriptan hydrobromide, 40 mg) tablet, orally, in absence of migraine. Five participants out of theses participants visited clinic when they were experiencing an acute migraine attack and received single dose Relpax (eletriptan hydrobromide, 40 mg) tablet during migraine attack at clinic. Dosing was repeated up to 2 additional times for up to 4 total doses. Each treatment administration were separated by at least 7 days. Each dose was administered with 240 mL of water.
Measure Participants	10
AUC (0-inf), Non-migraine	540.669 (78.75)
AUC (0-inf), Migraine	570.860 (94.16)
AUC (0-2), Non-migraine	70.249 (97.29)
AUC (0-2), Migraine	78.092 (120.65)

4. Primary Outcome

Title	Maximum Observed Drug Concentration (Cmax) for Sumatriptan and Naproxen
Description	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.
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.

Outcome Measure Data

Analysis Population Description

The PK parameter Population

Arm/Group Title	TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg)
Arm/Group Description	Ten participants received single dose of radio labeled TREXIMA tablet (fixed dose combination of sumatriptan succinate 119 mg [equivalent to 85 mg of sumatriptan] and naproxen sodium 500 mg), orally, in absence of migraine. Five participants out of these participants visited clinic when they were experiencing an acute migraine attack and received TREXIMA during migraine attack at clinic. Dosing was repeated up to 2 additional times for up to 4 total doses. Each treatment administration were separated by at least 7 days. Each dose was administered with 240 mL of water.
Measure Participants	10
Sumatriptan, Non-migraine	49.900 (33.00)
Sumatriptan, Migraine	45.676 (30.77)
Naproxen, Non-migraine	46.34 (25.5)
Naproxen, Migraine	56.36 (28.1)

5. Primary Outcome

Title	Cmax for Eletriptan
Description	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.
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.

Outcome Measure Data

Analysis Population Description

PK parameter Population.

Arm/Group Title	Relpax (Eletriptan 40 mg)
Arm/Group Description	Ten participants received single dose of Relpax (eletriptan hydrobromide, 40 mg) tablet, orally, in absence of migraine. Five participants out of theses participants visited clinic when they were experiencing an acute migraine attack and received single dose Relpax (eletriptan hydrobromide, 40 mg) tablet during migraine attack at clinic. Dosing was repeated up to 2 additional times for up to 4 total doses. Each treatment administration were separated by at least 7 days. Each dose was administered with 240 mL of water.
Measure Participants	10
Non-migraine	80.246 (61.19)
Migraine	91.323 (74.84)

6. Primary Outcome

Title	Time of Maximal Drug Concentration (Tmax) for Sumatriptan and Naproxen
Description	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.
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.

Outcome Measure Data

Analysis Population Description

PK parameter Population

Arm/Group Title	TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg)
Arm/Group Description	Ten participants received single dose of radio labeled TREXIMA tablet (fixed dose combination of sumatriptan succinate 119 mg [equivalent to 85 mg of sumatriptan] and naproxen sodium 500 mg), orally, in absence of migraine. Five participants out of these participants visited clinic when they were experiencing an acute migraine attack and received TREXIMA during migraine attack at clinic. Dosing was repeated up to 2 additional times for up to 4 total doses. Each treatment administration were separated by at least 7 days. Each dose was administered with 240 mL of water.
Measure Participants	10
Sumatriptan, Non-migraine	2.000
Sumatriptan, Migraine	1.500
Naproxen, Non-migraine	4.50
Naproxen, Migraine	4.00

7. Primary Outcome

Title	Tmax for Eletriptan
Description	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.
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.

Outcome Measure Data

Analysis Population Description

PK parameter Population

Arm/Group Title	Relpax (Eletriptan 40 mg)
Arm/Group Description	Ten participants received single dose of Relpax (eletriptan hydrobromide, 40 mg) tablet, orally, in absence of migraine. Five participants out of theses participants visited clinic when they were experiencing an acute migraine attack and received single dose Relpax (eletriptan hydrobromide, 40 mg) tablet during migraine attack at clinic. Dosing was repeated up to 2 additional times for up to 4 total doses. Each treatment administration were separated by at least 7 days. Each dose was administered with 240 mL of water.
Measure Participants	10
Non-migraine	2.500
Migraine	2.000

8. Primary Outcome

Title	Time to Complete Dispersion of the Sumatriptan and Naproxen Portions of the TREXIMA Tablet and of the Relpax Tablet
Description	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).
Time Frame	Day 1 of each treatment administered (For 30 days)

Outcome Measure Data

Analysis Population Description

Scintigraphy Population

Arm/Group Title	TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg)	Relpax (Eletriptan 40 mg)
Arm/Group Description	Ten participants received single dose of radio labeled TREXIMA tablet (fixed dose combination of sumatriptan succinate 119 mg [equivalent to 85 mg of sumatriptan] and naproxen sodium 500 mg), orally, in absence of migraine. Five participants out of these participants visited clinic when they were experiencing an acute migraine attack and received TREXIMA during migraine attack at clinic. Dosing was repeated up to 2 additional times for up to 4 total doses. Each treatment administration were separated by at least 7 days. Each dose was administered with 240 mL of water.	Ten participants received single dose of Relpax (eletriptan hydrobromide, 40 mg) tablet, orally, in absence of migraine. Five participants out of theses participants visited clinic when they were experiencing an acute migraine attack and received single dose Relpax (eletriptan hydrobromide, 40 mg) tablet during migraine attack at clinic. Dosing was repeated up to 2 additional times for up to 4 total doses. Each treatment administration were separated by at least 7 days. Each dose was administered with 240 mL of water.
Measure Participants	10	10
Sumatriptan, Non-migraine	0.050
Sumatriptan, Migraine	0.050
Naproxen, Non-migraine	1.125
Naproxen, Migraine	1.250
Eletriptan, Non-migraine	0.600
Eletriptan, Migraine	0.670

9. Primary Outcome

Title	Time to First Appearance of Sumatriptan, Naproxen and Eletriptan at the Proximal Small Intestine
Description	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).
Time Frame	Day 1 of each treatment administered (For 30 days)

Outcome Measure Data

Analysis Population Description

Scintigraphy Population

Arm/Group Title	TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg)	Relpax (Eletriptan 40 mg)
Arm/Group Description	Ten participants received single dose of radio labeled TREXIMA tablet (fixed dose combination of sumatriptan succinate 119 mg [equivalent to 85 mg of sumatriptan] and naproxen sodium 500 mg), orally, in absence of migraine. Five participants out of these participants visited clinic when they were experiencing an acute migraine attack and received TREXIMA during migraine attack at clinic. Dosing was repeated up to 2 additional times for up to 4 total doses. Each treatment administration were separated by at least 7 days. Each dose was administered with 240 mL of water.	Ten participants received single dose of Relpax (eletriptan hydrobromide, 40 mg) tablet, orally, in absence of migraine. Five participants out of theses participants visited clinic when they were experiencing an acute migraine attack and received single dose Relpax (eletriptan hydrobromide, 40 mg) tablet during migraine attack at clinic. Dosing was repeated up to 2 additional times for up to 4 total doses. Each treatment administration were separated by at least 7 days. Each dose was administered with 240 mL of water.
Measure Participants	10	10
Sumatriptan, Non-migraine	4.365
Sumatriptan, Migraine	4.350
Naproxen, Non-migraine	4.510
Naproxen, Migraine	4.350
Eletriptan, Non-migraine	5.530
Eletriptan, Migraine	5.810

10. Primary Outcome

Title	Small Intestine Transit and Residence (Time to 50% Through Intestine) of the Radioactive Markers Representing Sumatriptan, Naproxen and Eletriptan
Description	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).
Time Frame	Day 1 of each treatment administered (For 30 days)

Outcome Measure Data

Analysis Population Description

Scintigraphy Population

Arm/Group Title	TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg)	Relpax (Eletriptan 40 mg)
Arm/Group Description	Ten participants received single dose of radio labeled TREXIMA tablet (fixed dose combination of sumatriptan succinate 119 mg [equivalent to 85 mg of sumatriptan] and naproxen sodium 500 mg), orally, in absence of migraine. Five participants out of these participants visited clinic when they were experiencing an acute migraine attack and received TREXIMA during migraine attack at clinic. Dosing was repeated up to 2 additional times for up to 4 total doses. Each treatment administration were separated by at least 7 days. Each dose was administered with 240 mL of water.	Ten participants received single dose of Relpax (eletriptan hydrobromide, 40 mg) tablet, orally, in absence of migraine. Five participants out of theses participants visited clinic when they were experiencing an acute migraine attack and received single dose Relpax (eletriptan hydrobromide, 40 mg) tablet during migraine attack at clinic. Dosing was repeated up to 2 additional times for up to 4 total doses. Each treatment administration were separated by at least 7 days. Each dose was administered with 240 mL of water.
Measure Participants	10	10
Sumatriptan, Non-Migraine	2.895
Sumatriptan, Migraine	2.990
Naproxen, Non-Migraine	2.550
Naproxen, Migraine	2.230
Eletriptan, Non-Migraine	4.335
Eletriptan, Migraine	4.140

11. Secondary Outcome

Title	Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description	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.
Time Frame	Up to Day 30

Outcome Measure Data

Analysis Population Description

The Safety Population consisted of all participants who were randomized and received at least one dose of study medication.

Arm/Group Title	TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg)	Relpax (Eletriptan 40 mg)
Arm/Group Description	Ten participants received single dose of radio labeled TREXIMA tablet (fixed dose combination of sumatriptan succinate 119 mg [equivalent to 85 mg of sumatriptan] and naproxen sodium 500 mg), orally, in absence of migraine. Five participants out of these participants visited clinic when they were experiencing an acute migraine attack and received TREXIMA during migraine attack at clinic. Dosing was repeated up to 2 additional times for up to 4 total doses. Each treatment administration were separated by at least 7 days. Each dose was administered with 240 mL of water.	Ten participants received single dose of Relpax (eletriptan hydrobromide, 40 mg) tablet, orally, in absence of migraine. Five participants out of theses participants visited clinic when they were experiencing an acute migraine attack and received single dose Relpax (eletriptan hydrobromide, 40 mg) tablet during migraine attack at clinic. Dosing was repeated up to 2 additional times for up to 4 total doses. Each treatment administration were separated by at least 7 days. Each dose was administered with 240 mL of water.
Measure Participants	10	10
Any AEs	8 80%	3 30%
Any SAEs	0 0%	0 0%

Adverse Events

Time Frame	SAEs and nSAEs were collected from start of the study treatment up to Day 30
Adverse Event Reporting Description	On treatment SAEs and nSAEs were reported for Safety Population.
Arm/Group Title	TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg)		Relpax (Eletriptan 40 mg)
Arm/Group Description	Ten participants received single dose of radio labeled TREXIMA tablet (fixed dose combination of sumatriptan succinate 119 mg [equivalent to 85 mg of sumatriptan] and naproxen sodium 500 mg), orally, in absence of migraine. Five participants out of these participants visited clinic when they were experiencing an acute migraine attack and received TREXIMA during migraine attack at clinic. Dosing was repeated up to 2 additional times for up to 4 total doses. Each treatment administration were separated by at least 7 days. Each dose was administered with 240 mL of water.		Ten participants received single dose of Relpax (eletriptan hydrobromide, 40 mg) tablet, orally, in absence of migraine. Five participants out of theses participants visited clinic when they were experiencing an acute migraine attack and received single dose Relpax (eletriptan hydrobromide, 40 mg) tablet during migraine attack at clinic. Dosing was repeated up to 2 additional times for up to 4 total doses. Each treatment administration were separated by at least 7 days. Each dose was administered with 240 mL of water.
All Cause Mortality
	TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg)		Relpax (Eletriptan 40 mg)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/10 (0%)
Serious Adverse Events
	TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg)		Relpax (Eletriptan 40 mg)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/10 (0%)
Other (Not Including Serious) Adverse Events
	TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg)		Relpax (Eletriptan 40 mg)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/10 (80%)		3/10 (30%)
Gastrointestinal disorders
Diarrhoea	2/10 (20%)		0/10 (0%)
Nausea	2/10 (20%)		0/10 (0%)
Abdominal pain	0/10 (0%)		1/10 (10%)
Toothache	1/10 (10%)		0/10 (0%)
Infections and infestations
Pharyngitis streptococcal	1/10 (10%)		0/10 (0%)
Musculoskeletal and connective tissue disorders
Joint stiffness	3/10 (30%)		0/10 (0%)
Muscle tightness	3/10 (30%)		0/10 (0%)
Musculoskeletal pain	1/10 (10%)		1/10 (10%)
Arthralgia	1/10 (10%)		0/10 (0%)
Flank pain	1/10 (10%)		0/10 (0%)
Neck pain	1/10 (10%)		0/10 (0%)
Nervous system disorders
Paraesthesia	3/10 (30%)		0/10 (0%)
Dizziness	0/10 (0%)		1/10 (10%)
Psychiatric disorders
Dissociation	1/10 (10%)		1/10 (10%)
Renal and urinary disorders
Nephrolithiasis	1/10 (10%)		0/10 (0%)
Skin and subcutaneous tissue disorders
Swelling face	0/10 (0%)		1/10 (10%)
Vascular disorders
Flushing	1/10 (10%)		0/10 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK 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.