Trial Outcomes & Findings for TREXIMA and RELPAX Gastric Scintigraphy Inside and Outside a Migraine (NCT NCT00385008)

Last Updated: 2018-02-12

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

20 participants

Primary outcome timeframe

Day 1 of each treatment administration (For 30 days)

Results posted on

2018-02-12

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg) 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.	Relpax (Eletriptan 40 mg) 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.
Overall Study STARTED	10	10
Overall Study In Absence of Migraine	10	10
Overall Study In Presence of Migraine	5	5
Overall Study COMPLETED	10	10
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

TREXIMA and RELPAX Gastric Scintigraphy Inside and Outside a Migraine

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg) n=10 Participants 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.	Relpax (Eletriptan 40 mg) n=10 Participants 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 n=20 Participants Total of all reporting groups
Age, Continuous	30.6 Years STANDARD_DEVIATION 7.50 • n=5 Participants	33.3 Years STANDARD_DEVIATION 7.17 • n=7 Participants	32 Years STANDARD_DEVIATION 7.27 • n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	9 Participants n=7 Participants	19 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	10 Participants n=5 Participants	10 Participants n=7 Participants	20 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 1 of each treatment administration (For 30 days)

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

Outcome measures

Outcome measures
Measure	TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg) n=10 Participants 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.	Relpax (Eletriptan 40 mg) n=10 Participants 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.
Time to 10%, 50%, 90% and Complete Gastric Empting of the Radioactive Markers Representing Sumatriptan, Naproxen and Eletriptan 50% gastric emptying, Eletriptan, Migraine	—	0.890 hours (hr) Interval 0.02 to 2.21
Time to 10%, 50%, 90% and Complete Gastric Empting of the Radioactive Markers Representing Sumatriptan, Naproxen and Eletriptan 10% gastric emptying, Sumatriptan, Non-migraine	0.100 hours (hr) Interval 0.03 to 0.62	—
Time to 10%, 50%, 90% and Complete Gastric Empting of the Radioactive Markers Representing Sumatriptan, Naproxen and Eletriptan 10% gastric emptying, Sumatriptan, Migraine	0.130 hours (hr) Interval 0.05 to 0.69	—
Time to 10%, 50%, 90% and Complete Gastric Empting of the Radioactive Markers Representing Sumatriptan, Naproxen and Eletriptan 10% gastric emptying, Naproxen, Non-migraine	1.195 hours (hr) Interval 0.53 to 1.91	—
Time to 10%, 50%, 90% and Complete Gastric Empting of the Radioactive Markers Representing Sumatriptan, Naproxen and Eletriptan 10% gastric emptying, Naproxen, Migraine	1.300 hours (hr) Interval 0.85 to 2.73	—
Time to 10%, 50%, 90% and Complete Gastric Empting of the Radioactive Markers Representing Sumatriptan, Naproxen and Eletriptan 10% gastric emptying, Eletriptan, Non-migraine	—	0.400 hours (hr) Interval 0.0 to 0.62
Time to 10%, 50%, 90% and Complete Gastric Empting of the Radioactive Markers Representing Sumatriptan, Naproxen and Eletriptan 10% gastric emptying, Eletriptan, Migraine	—	0.410 hours (hr) Interval 0.0 to 0.69
Time to 10%, 50%, 90% and Complete Gastric Empting of the Radioactive Markers Representing Sumatriptan, Naproxen and Eletriptan 50% gastric emptying, Sumatriptan, Non-migraine	0.675 hours (hr) Interval 0.13 to 1.8	—
Time to 10%, 50%, 90% and Complete Gastric Empting of the Radioactive Markers Representing Sumatriptan, Naproxen and Eletriptan 50% gastric emptying, Sumatriptan, Migraine	1.070 hours (hr) Interval 0.15 to 1.42	—
Time to 10%, 50%, 90% and Complete Gastric Empting of the Radioactive Markers Representing Sumatriptan, Naproxen and Eletriptan 50% gastric emptying, Naproxen, Non-migraine	2.260 hours (hr) Interval 1.42 to 3.46	—
Time to 10%, 50%, 90% and Complete Gastric Empting of the Radioactive Markers Representing Sumatriptan, Naproxen and Eletriptan 50% gastric emptying, Naproxen, Migraine	2.310 hours (hr) Interval 1.39 to 4.38	—
Time to 10%, 50%, 90% and Complete Gastric Empting of the Radioactive Markers Representing Sumatriptan, Naproxen and Eletriptan 50% gastric emptying, Eletriptan, Non-migraine	—	0.590 hours (hr) Interval 0.02 to 2.57
Time to 10%, 50%, 90% and Complete Gastric Empting of the Radioactive Markers Representing Sumatriptan, Naproxen and Eletriptan 90% gastric emptying, Sumatriptan, Non-migraine	3.020 hours (hr) Interval 2.0 to 4.29	—
Time to 10%, 50%, 90% and Complete Gastric Empting of the Radioactive Markers Representing Sumatriptan, Naproxen and Eletriptan 90% gastric emptying, Sumatriptan, Migraine	3.440 hours (hr) Interval 2.26 to 4.28	—
Time to 10%, 50%, 90% and Complete Gastric Empting of the Radioactive Markers Representing Sumatriptan, Naproxen and Eletriptan 90% gastric emptying, Naproxen, Non-migraine	4.290 hours (hr) Interval 2.44 to 5.84	—
Time to 10%, 50%, 90% and Complete Gastric Empting of the Radioactive Markers Representing Sumatriptan, Naproxen and Eletriptan 90% gastric emptying, Naproxen, Migraine	4.010 hours (hr) Interval 2.81 to 8.75	—
Time to 10%, 50%, 90% and Complete Gastric Empting of the Radioactive Markers Representing Sumatriptan, Naproxen and Eletriptan 90% gastric emptying, Eletriptan, Non-migraine	—	2.590 hours (hr) Interval 0.03 to 4.48
Time to 10%, 50%, 90% and Complete Gastric Empting of the Radioactive Markers Representing Sumatriptan, Naproxen and Eletriptan 90% gastric emptying, Eletriptan, Migraine	—	2.490 hours (hr) Interval 0.05 to 4.23
Time to 10%, 50%, 90% and Complete Gastric Empting of the Radioactive Markers Representing Sumatriptan, Naproxen and Eletriptan Complete gastric emptying,Sumatriptan,Non-migraine	4.505 hours (hr) Interval 2.5 to 6.06	—
Time to 10%, 50%, 90% and Complete Gastric Empting of the Radioactive Markers Representing Sumatriptan, Naproxen and Eletriptan Complete gastric emptying, Sumatriptan, Migraine	4.000 hours (hr) Interval 3.02 to 8.0	—
Time to 10%, 50%, 90% and Complete Gastric Empting of the Radioactive Markers Representing Sumatriptan, Naproxen and Eletriptan Complete gastric emptying, Naproxen, Non-migraine	4.760 hours (hr) Interval 2.5 to 8.03	—
Time to 10%, 50%, 90% and Complete Gastric Empting of the Radioactive Markers Representing Sumatriptan, Naproxen and Eletriptan Complete gastric emptying, Naproxen, Migraine	4.500 hours (hr) Interval 3.52 to 9.97	—
Time to 10%, 50%, 90% and Complete Gastric Empting of the Radioactive Markers Representing Sumatriptan, Naproxen and Eletriptan Complete gastric emptying, Eletriptan,Non-migraine	—	3.765 hours (hr) Interval 0.2 to 10.02
Time to 10%, 50%, 90% and Complete Gastric Empting of the Radioactive Markers Representing Sumatriptan, Naproxen and Eletriptan Complete gastric emptying, Eletriptan, Migraine	—	3.510 hours (hr) Interval 0.36 to 4.53

PRIMARY outcome

Timeframe: 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.

Population: 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.

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.

Outcome measures

Outcome measures
Measure	TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg) n=10 Participants 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.	Relpax (Eletriptan 40 mg) 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.
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 AUC (0-24), Sumatriptan, Non-migraine	231.526 microgramhr per mL (µghr/mL) Geometric Coefficient of Variation 25.63	—
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 AUC (0-24), Sumatriptan, Migraine	165.707 microgramhr per mL (µghr/mL) Geometric Coefficient of Variation 38.05	—
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 AUC (0-inf), Sumatriptan, Non-migraine	231.999 microgramhr per mL (µghr/mL) Geometric Coefficient of Variation 24.76	—
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 AUC (0-inf), Sumatriptan, Migraine	158.036 microgramhr per mL (µghr/mL) Geometric Coefficient of Variation 41.67	—
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 AUC (0-2), Sumatriptan, Non-migraine	65.156 microgramhr per mL (µghr/mL) Geometric Coefficient of Variation 36.18	—
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 AUC (0-2), Sumatriptan, Migraine	54.884 microgramhr per mL (µghr/mL) Geometric Coefficient of Variation 22.28	—
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 AUC (0-24), Naproxen, Non-migraine	570.54 microgramhr per mL (µghr/mL) Geometric Coefficient of Variation 15.0	—
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 AUC (0-24), Naproxen, Migraine	627.06 microgramhr per mL (µghr/mL) Geometric Coefficient of Variation 20.6	—
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 AUC (0-inf), Naproxen, Non-migraine	901.13 microgramhr per mL (µghr/mL) Geometric Coefficient of Variation 21.9	—
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 AUC (0-inf), Naproxen, Migraine	978.39 microgramhr per mL (µghr/mL) Geometric Coefficient of Variation 23.4	—
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 AUC (0-2), Naproxen, Non-migraine	23.16 microgramhr per mL (µghr/mL) Geometric Coefficient of Variation 79.3	—
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 AUC (0-2), Naproxen, Migraine	24.38 microgramhr per mL (µghr/mL) Geometric Coefficient of Variation 117.5	—

PRIMARY outcome

Timeframe: 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.

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

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.

Outcome measures

Outcome measures
Measure	TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg) n=10 Participants 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.	Relpax (Eletriptan 40 mg) 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.
Mean AUC (0-inf) and AUC (0-2) for Eletriptan AUC (0-inf), Non-migraine	540.669 µg*hr/mL Geometric Coefficient of Variation 78.75	—
Mean AUC (0-inf) and AUC (0-2) for Eletriptan AUC (0-inf), Migraine	570.860 µg*hr/mL Geometric Coefficient of Variation 94.16	—
Mean AUC (0-inf) and AUC (0-2) for Eletriptan AUC (0-2), Non-migraine	70.249 µg*hr/mL Geometric Coefficient of Variation 97.29	—
Mean AUC (0-inf) and AUC (0-2) for Eletriptan AUC (0-2), Migraine	78.092 µg*hr/mL Geometric Coefficient of Variation 120.65	—

PRIMARY outcome

Population: The PK parameter Population

Outcome measures

Outcome measures
Measure	TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg) n=10 Participants 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.	Relpax (Eletriptan 40 mg) 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.
Maximum Observed Drug Concentration (Cmax) for Sumatriptan and Naproxen Sumatriptan, Non-migraine	49.900 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 33.00	—
Maximum Observed Drug Concentration (Cmax) for Sumatriptan and Naproxen Sumatriptan, Migraine	45.676 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 30.77	—
Maximum Observed Drug Concentration (Cmax) for Sumatriptan and Naproxen Naproxen, Non-migraine	46.34 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 25.5	—
Maximum Observed Drug Concentration (Cmax) for Sumatriptan and Naproxen Naproxen, Migraine	56.36 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 28.1	—

PRIMARY outcome

Population: PK parameter Population.

Outcome measures

Outcome measures
Measure	TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg) n=10 Participants 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.	Relpax (Eletriptan 40 mg) 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.
Cmax for Eletriptan Migraine	91.323 ng/mL Geometric Coefficient of Variation 74.84	—
Cmax for Eletriptan Non-migraine	80.246 ng/mL Geometric Coefficient of Variation 61.19	—

PRIMARY outcome

Population: PK parameter Population

Outcome measures

Outcome measures
Measure	TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg) n=10 Participants 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.	Relpax (Eletriptan 40 mg) 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.
Time of Maximal Drug Concentration (Tmax) for Sumatriptan and Naproxen Sumatriptan, Non-migraine	2.000 hr Interval 0.67 to 5.0	—
Time of Maximal Drug Concentration (Tmax) for Sumatriptan and Naproxen Sumatriptan, Migraine	1.500 hr Interval 0.33 to 4.5	—
Time of Maximal Drug Concentration (Tmax) for Sumatriptan and Naproxen Naproxen, Non-migraine	4.50 hr Interval 1.5 to 8.0	—
Time of Maximal Drug Concentration (Tmax) for Sumatriptan and Naproxen Naproxen, Migraine	4.00 hr Interval 1.5 to 10.0	—

PRIMARY outcome

Population: PK parameter Population

Outcome measures

Outcome measures
Measure	TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg) n=10 Participants 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.	Relpax (Eletriptan 40 mg) 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.
Tmax for Eletriptan Non-migraine	2.500 hr Interval 0.83 to 6.0	—
Tmax for Eletriptan Migraine	2.000 hr Interval 1.0 to 5.5	—

PRIMARY outcome

Timeframe: Day 1 of each treatment administered (For 30 days)

Population: Scintigraphy Population

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).

Outcome measures

Outcome measures
Measure	TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg) n=10 Participants 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.	Relpax (Eletriptan 40 mg) n=10 Participants 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.
Time to Complete Dispersion of the Sumatriptan and Naproxen Portions of the TREXIMA Tablet and of the Relpax Tablet Sumatriptan, Non-migraine	0.050 hr Interval 0.05 to 0.25	—
Time to Complete Dispersion of the Sumatriptan and Naproxen Portions of the TREXIMA Tablet and of the Relpax Tablet Sumatriptan, Migraine	0.050 hr Interval 0.05 to 0.2	—
Time to Complete Dispersion of the Sumatriptan and Naproxen Portions of the TREXIMA Tablet and of the Relpax Tablet Naproxen, Non-migraine	1.125 hr Interval 0.67 to 4.0	—
Time to Complete Dispersion of the Sumatriptan and Naproxen Portions of the TREXIMA Tablet and of the Relpax Tablet Naproxen, Migraine	1.250 hr Interval 1.0 to 3.0	—
Time to Complete Dispersion of the Sumatriptan and Naproxen Portions of the TREXIMA Tablet and of the Relpax Tablet Eletriptan, Non-migraine	—	0.600 hr Interval 0.05 to 0.83
Time to Complete Dispersion of the Sumatriptan and Naproxen Portions of the TREXIMA Tablet and of the Relpax Tablet Eletriptan, Migraine	—	0.670 hr Interval 0.05 to 0.83

PRIMARY outcome

Timeframe: Day 1 of each treatment administered (For 30 days)

Population: Scintigraphy Population

Outcome measures

Outcome measures
Measure	TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg) n=10 Participants 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.	Relpax (Eletriptan 40 mg) n=10 Participants 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.
Time to First Appearance of Sumatriptan, Naproxen and Eletriptan at the Proximal Small Intestine Sumatriptan, Non-migraine	4.365 hr Interval 2.46 to 7.01	—
Time to First Appearance of Sumatriptan, Naproxen and Eletriptan at the Proximal Small Intestine Sumatriptan, Migraine	4.350 hr Interval 3.15 to 5.6	—
Time to First Appearance of Sumatriptan, Naproxen and Eletriptan at the Proximal Small Intestine Naproxen, Non-migraine	4.510 hr Interval 2.42 to 7.01	—
Time to First Appearance of Sumatriptan, Naproxen and Eletriptan at the Proximal Small Intestine Naproxen, Migraine	4.350 hr Interval 4.19 to 6.4	—
Time to First Appearance of Sumatriptan, Naproxen and Eletriptan at the Proximal Small Intestine Eletriptan, Non-migraine	—	5.530 hr Interval 3.73 to 12.0
Time to First Appearance of Sumatriptan, Naproxen and Eletriptan at the Proximal Small Intestine Eletriptan, Migraine	—	5.810 hr Interval 3.5 to 6.5

PRIMARY outcome

Timeframe: Day 1 of each treatment administered (For 30 days)

Population: Scintigraphy Population

Outcome measures

Outcome measures
Measure	TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg) n=10 Participants 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.	Relpax (Eletriptan 40 mg) n=10 Participants 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.
Small Intestine Transit and Residence (Time to 50% Through Intestine) of the Radioactive Markers Representing Sumatriptan, Naproxen and Eletriptan Sumatriptan, Non-Migraine	2.895 hr Interval 1.72 to 6.24	—
Small Intestine Transit and Residence (Time to 50% Through Intestine) of the Radioactive Markers Representing Sumatriptan, Naproxen and Eletriptan Sumatriptan, Migraine	2.990 hr Interval 2.5 to 5.45	—
Small Intestine Transit and Residence (Time to 50% Through Intestine) of the Radioactive Markers Representing Sumatriptan, Naproxen and Eletriptan Naproxen, Non-Migraine	2.550 hr Interval 0.24 to 3.86	—
Small Intestine Transit and Residence (Time to 50% Through Intestine) of the Radioactive Markers Representing Sumatriptan, Naproxen and Eletriptan Naproxen, Migraine	2.230 hr Interval 1.95 to 3.4	—
Small Intestine Transit and Residence (Time to 50% Through Intestine) of the Radioactive Markers Representing Sumatriptan, Naproxen and Eletriptan Eletriptan, Non-Migraine	—	4.335 hr Interval 1.8 to 11.49
Small Intestine Transit and Residence (Time to 50% Through Intestine) of the Radioactive Markers Representing Sumatriptan, Naproxen and Eletriptan Eletriptan, Migraine	—	4.140 hr Interval 2.13 to 6.25

SECONDARY outcome

Timeframe: Up to Day 30

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

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.

Outcome measures

Outcome measures
Measure	TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg) n=10 Participants 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.	Relpax (Eletriptan 40 mg) n=10 Participants 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.
Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) Any AEs	8 Participants	3 Participants
Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) Any SAEs	0 Participants	0 Participants

Adverse Events

TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg)

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Relpax (Eletriptan 40 mg)

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER

Measure	TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg) n=10 participants at risk 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.	Relpax (Eletriptan 40 mg) n=10 participants at risk 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.
Musculoskeletal and connective tissue disorders Joint stiffness	30.0% 3/10 • SAEs and nSAEs were collected from start of the study treatment up to Day 30 On treatment SAEs and nSAEs were reported for Safety Population.	0.00% 0/10 • SAEs and nSAEs were collected from start of the study treatment up to Day 30 On treatment SAEs and nSAEs were reported for Safety Population.
Musculoskeletal and connective tissue disorders Muscle tightness	30.0% 3/10 • SAEs and nSAEs were collected from start of the study treatment up to Day 30 On treatment SAEs and nSAEs were reported for Safety Population.	0.00% 0/10 • SAEs and nSAEs were collected from start of the study treatment up to Day 30 On treatment SAEs and nSAEs were reported for Safety Population.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	10.0% 1/10 • SAEs and nSAEs were collected from start of the study treatment up to Day 30 On treatment SAEs and nSAEs were reported for Safety Population.	10.0% 1/10 • SAEs and nSAEs were collected from start of the study treatment up to Day 30 On treatment SAEs and nSAEs were reported for Safety Population.
Musculoskeletal and connective tissue disorders Arthralgia	10.0% 1/10 • SAEs and nSAEs were collected from start of the study treatment up to Day 30 On treatment SAEs and nSAEs were reported for Safety Population.	0.00% 0/10 • SAEs and nSAEs were collected from start of the study treatment up to Day 30 On treatment SAEs and nSAEs were reported for Safety Population.
Musculoskeletal and connective tissue disorders Flank pain	10.0% 1/10 • SAEs and nSAEs were collected from start of the study treatment up to Day 30 On treatment SAEs and nSAEs were reported for Safety Population.	0.00% 0/10 • SAEs and nSAEs were collected from start of the study treatment up to Day 30 On treatment SAEs and nSAEs were reported for Safety Population.
Musculoskeletal and connective tissue disorders Neck pain	10.0% 1/10 • SAEs and nSAEs were collected from start of the study treatment up to Day 30 On treatment SAEs and nSAEs were reported for Safety Population.	0.00% 0/10 • SAEs and nSAEs were collected from start of the study treatment up to Day 30 On treatment SAEs and nSAEs were reported for Safety Population.
Gastrointestinal disorders Diarrhoea	20.0% 2/10 • SAEs and nSAEs were collected from start of the study treatment up to Day 30 On treatment SAEs and nSAEs were reported for Safety Population.	0.00% 0/10 • SAEs and nSAEs were collected from start of the study treatment up to Day 30 On treatment SAEs and nSAEs were reported for Safety Population.
Gastrointestinal disorders Nausea	20.0% 2/10 • SAEs and nSAEs were collected from start of the study treatment up to Day 30 On treatment SAEs and nSAEs were reported for Safety Population.	0.00% 0/10 • SAEs and nSAEs were collected from start of the study treatment up to Day 30 On treatment SAEs and nSAEs were reported for Safety Population.
Gastrointestinal disorders Abdominal pain	0.00% 0/10 • SAEs and nSAEs were collected from start of the study treatment up to Day 30 On treatment SAEs and nSAEs were reported for Safety Population.	10.0% 1/10 • SAEs and nSAEs were collected from start of the study treatment up to Day 30 On treatment SAEs and nSAEs were reported for Safety Population.
Gastrointestinal disorders Toothache	10.0% 1/10 • SAEs and nSAEs were collected from start of the study treatment up to Day 30 On treatment SAEs and nSAEs were reported for Safety Population.	0.00% 0/10 • SAEs and nSAEs were collected from start of the study treatment up to Day 30 On treatment SAEs and nSAEs were reported for Safety Population.
Nervous system disorders Paraesthesia	30.0% 3/10 • SAEs and nSAEs were collected from start of the study treatment up to Day 30 On treatment SAEs and nSAEs were reported for Safety Population.	0.00% 0/10 • SAEs and nSAEs were collected from start of the study treatment up to Day 30 On treatment SAEs and nSAEs were reported for Safety Population.
Nervous system disorders Dizziness	0.00% 0/10 • SAEs and nSAEs were collected from start of the study treatment up to Day 30 On treatment SAEs and nSAEs were reported for Safety Population.	10.0% 1/10 • SAEs and nSAEs were collected from start of the study treatment up to Day 30 On treatment SAEs and nSAEs were reported for Safety Population.
Psychiatric disorders Dissociation	10.0% 1/10 • SAEs and nSAEs were collected from start of the study treatment up to Day 30 On treatment SAEs and nSAEs were reported for Safety Population.	10.0% 1/10 • SAEs and nSAEs were collected from start of the study treatment up to Day 30 On treatment SAEs and nSAEs were reported for Safety Population.
Infections and infestations Pharyngitis streptococcal	10.0% 1/10 • SAEs and nSAEs were collected from start of the study treatment up to Day 30 On treatment SAEs and nSAEs were reported for Safety Population.	0.00% 0/10 • SAEs and nSAEs were collected from start of the study treatment up to Day 30 On treatment SAEs and nSAEs were reported for Safety Population.
Renal and urinary disorders Nephrolithiasis	10.0% 1/10 • SAEs and nSAEs were collected from start of the study treatment up to Day 30 On treatment SAEs and nSAEs were reported for Safety Population.	0.00% 0/10 • SAEs and nSAEs were collected from start of the study treatment up to Day 30 On treatment SAEs and nSAEs were reported for Safety Population.
Skin and subcutaneous tissue disorders Swelling face	0.00% 0/10 • SAEs and nSAEs were collected from start of the study treatment up to Day 30 On treatment SAEs and nSAEs were reported for Safety Population.	10.0% 1/10 • SAEs and nSAEs were collected from start of the study treatment up to Day 30 On treatment SAEs and nSAEs were reported for Safety Population.
Vascular disorders Flushing	10.0% 1/10 • SAEs and nSAEs were collected from start of the study treatment up to Day 30 On treatment SAEs and nSAEs were reported for Safety Population.	0.00% 0/10 • SAEs and nSAEs were collected from start of the study treatment up to Day 30 On treatment SAEs and nSAEs were reported for Safety Population.