Migraine Disorders
Conditions
Keywords
Combination product, sumatriptan succinate, naproxen sodium, absorption, pharmacokinetics, disintegration, gastric transit, gastric scintigraphy
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.
Interventions
sumatriptan/naproxen sodium
DRUGRELPAX(eletriptan) 40mg Tablet
eletriptan tablets
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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). |
| 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). |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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). |
| 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
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 details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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 mL of water. | 10 |
| 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. | 10 |
| Total | 20 |
Baseline characteristics
| Characteristic | Relpax (Eletriptan 40 mg) | Total | TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg) |
|---|---|---|---|
| Age, Continuous | 33.3 Years STANDARD_DEVIATION 7.17 | 32 Years STANDARD_DEVIATION 7.27 | 30.6 Years STANDARD_DEVIATION 7.5 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 10 Participants | 20 Participants | 10 Participants |
| Sex: Female, Male Female | 9 Participants | 19 Participants | 10 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 10 |
| other Total, other adverse events | 8 / 10 | 3 / 10 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 |
Outcome results
Primary
Cmax for Eletriptan
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.
Population: PK parameter Population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg) | Cmax for Eletriptan | Migraine | 91.323 ng/mL | Geometric Coefficient of Variation 74.84 |
| TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg) | Cmax for Eletriptan | Non-migraine | 80.246 ng/mL | Geometric Coefficient of Variation 61.19 |
Primary
Maximum Observed Drug Concentration (Cmax) for Sumatriptan and Naproxen
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.
Population: The PK parameter Population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg) | Maximum Observed Drug Concentration (Cmax) for Sumatriptan and Naproxen | Sumatriptan, Non-migraine | 49.900 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 33 |
| TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg) | Maximum Observed Drug Concentration (Cmax) for Sumatriptan and Naproxen | Sumatriptan, Migraine | 45.676 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 30.77 |
| TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg) | 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 |
| TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg) | 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
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
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.
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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg) | 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 microgram*hr per mL (µg*hr/mL) | Geometric Coefficient of Variation 25.63 |
| TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg) | 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 microgram*hr per mL (µg*hr/mL) | Geometric Coefficient of Variation 38.05 |
| TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg) | 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 microgram*hr per mL (µg*hr/mL) | Geometric Coefficient of Variation 24.76 |
| TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg) | 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 microgram*hr per mL (µg*hr/mL) | Geometric Coefficient of Variation 41.67 |
| TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg) | 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 microgram*hr per mL (µg*hr/mL) | Geometric Coefficient of Variation 36.18 |
| TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg) | 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 microgram*hr per mL (µg*hr/mL) | Geometric Coefficient of Variation 22.28 |
| TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg) | 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 microgram*hr per mL (µg*hr/mL) | Geometric Coefficient of Variation 15 |
| TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg) | 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 microgram*hr per mL (µg*hr/mL) | Geometric Coefficient of Variation 20.6 |
| TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg) | 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 microgram*hr per mL (µg*hr/mL) | Geometric Coefficient of Variation 21.9 |
| TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg) | 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 microgram*hr per mL (µg*hr/mL) | Geometric Coefficient of Variation 23.4 |
| TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg) | 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 microgram*hr per mL (µg*hr/mL) | Geometric Coefficient of Variation 79.3 |
| TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg) | 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 microgram*hr per mL (µg*hr/mL) | Geometric Coefficient of Variation 117.5 |
Primary
Mean AUC (0-inf) and AUC (0-2) for Eletriptan
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.
Population: The PK parameter Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg) | 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 |
| TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg) | 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 |
| TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg) | 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 |
| TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg) | 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
Small Intestine Transit and Residence (Time to 50% Through Intestine) of the Radioactive Markers Representing Sumatriptan, Naproxen and Eletriptan
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)
Population: Scintigraphy Population
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg) | 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 |
| TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg) | Small Intestine Transit and Residence (Time to 50% Through Intestine) of the Radioactive Markers Representing Sumatriptan, Naproxen and Eletriptan | Sumatriptan, Migraine | 2.990 hr |
| TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg) | 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 |
| TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg) | Small Intestine Transit and Residence (Time to 50% Through Intestine) of the Radioactive Markers Representing Sumatriptan, Naproxen and Eletriptan | Naproxen, Migraine | 2.230 hr |
| Relpax (Eletriptan 40 mg) | 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 |
| Relpax (Eletriptan 40 mg) | Small Intestine Transit and Residence (Time to 50% Through Intestine) of the Radioactive Markers Representing Sumatriptan, Naproxen and Eletriptan | Eletriptan, Migraine | 4.140 hr |
Primary
Time of Maximal Drug Concentration (Tmax) for Sumatriptan and Naproxen
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.
Population: PK parameter Population
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg) | Time of Maximal Drug Concentration (Tmax) for Sumatriptan and Naproxen | Sumatriptan, Non-migraine | 2.000 hr |
| TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg) | Time of Maximal Drug Concentration (Tmax) for Sumatriptan and Naproxen | Sumatriptan, Migraine | 1.500 hr |
| TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg) | Time of Maximal Drug Concentration (Tmax) for Sumatriptan and Naproxen | Naproxen, Non-migraine | 4.50 hr |
| TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg) | Time of Maximal Drug Concentration (Tmax) for Sumatriptan and Naproxen | Naproxen, Migraine | 4.00 hr |
Primary
Time to 10%, 50%, 90% and Complete Gastric Empting of the Radioactive Markers Representing Sumatriptan, Naproxen and Eletriptan
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)
Population: Scintigraphy Population consisted of all participants with evaluable data from the scintigraphic images.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg) | 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) |
| TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg) | 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) |
| TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg) | 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) |
| TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg) | 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) |
| TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg) | 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) |
| TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg) | 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) |
| TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg) | 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) |
| TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg) | 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) |
| TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg) | 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) |
| TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg) | 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) |
| TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg) | 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) |
| TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg) | 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) |
| TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg) | 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) |
| TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg) | 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) |
| TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg) | 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) |
| TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg) | 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) |
| Relpax (Eletriptan 40 mg) | 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) |
| Relpax (Eletriptan 40 mg) | 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) |
| Relpax (Eletriptan 40 mg) | 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) |
| Relpax (Eletriptan 40 mg) | 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) |
| Relpax (Eletriptan 40 mg) | 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) |
| Relpax (Eletriptan 40 mg) | 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) |
| Relpax (Eletriptan 40 mg) | 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) |
| Relpax (Eletriptan 40 mg) | 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) |
Primary
Time to Complete Dispersion of the Sumatriptan and Naproxen Portions of the TREXIMA Tablet and of the Relpax Tablet
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)
Population: Scintigraphy Population
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg) | 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 |
| TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg) | Time to Complete Dispersion of the Sumatriptan and Naproxen Portions of the TREXIMA Tablet and of the Relpax Tablet | Sumatriptan, Migraine | 0.050 hr |
| TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg) | 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 |
| TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg) | Time to Complete Dispersion of the Sumatriptan and Naproxen Portions of the TREXIMA Tablet and of the Relpax Tablet | Naproxen, Migraine | 1.250 hr |
| Relpax (Eletriptan 40 mg) | 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 |
| Relpax (Eletriptan 40 mg) | Time to Complete Dispersion of the Sumatriptan and Naproxen Portions of the TREXIMA Tablet and of the Relpax Tablet | Eletriptan, Migraine | 0.670 hr |
Primary
Time to First Appearance of Sumatriptan, Naproxen and Eletriptan at the Proximal Small Intestine
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)
Population: Scintigraphy Population
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg) | Time to First Appearance of Sumatriptan, Naproxen and Eletriptan at the Proximal Small Intestine | Sumatriptan, Non-migraine | 4.365 hr |
| TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg) | Time to First Appearance of Sumatriptan, Naproxen and Eletriptan at the Proximal Small Intestine | Sumatriptan, Migraine | 4.350 hr |
| TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg) | Time to First Appearance of Sumatriptan, Naproxen and Eletriptan at the Proximal Small Intestine | Naproxen, Non-migraine | 4.510 hr |
| TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg) | Time to First Appearance of Sumatriptan, Naproxen and Eletriptan at the Proximal Small Intestine | Naproxen, Migraine | 4.350 hr |
| Relpax (Eletriptan 40 mg) | Time to First Appearance of Sumatriptan, Naproxen and Eletriptan at the Proximal Small Intestine | Eletriptan, Non-migraine | 5.530 hr |
| Relpax (Eletriptan 40 mg) | Time to First Appearance of Sumatriptan, Naproxen and Eletriptan at the Proximal Small Intestine | Eletriptan, Migraine | 5.810 hr |
Primary
Tmax for Eletriptan
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.
Population: PK parameter Population
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg) | Tmax for Eletriptan | Non-migraine | 2.500 hr |
| TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg) | Tmax for Eletriptan | Migraine | 2.000 hr |
Secondary
Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs)
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
Population: The Safety Population consisted of all participants who were randomized and received at least one dose of study medication.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg) | Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any AEs | 8 Participants |
| TREXIMA (Sumatriptan 85 mg + Naproxen 500 mg) | Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any SAEs | 0 Participants |
| Relpax (Eletriptan 40 mg) | Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any AEs | 3 Participants |
| Relpax (Eletriptan 40 mg) | Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any SAEs | 0 Participants |