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Relative Bioavailability Comparison study
A Phase 2, Open-Label, Randomized, 3-Way Crossover Study to Compare the Relative Bioavailability of Oral Methotrexate and the VIBEX™ MTX Device in Adult Subjects With Rheumatoid Arthritis
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 10 mg Methotrexate (MTX) | Experimental | MTX dose group was assigned based on the subject's current therapeutic regimen of MTX and rheumatoid arthritis disease status. The sequence of treatments A, B and C was randomly assigned. |
|
| 15 mg MTX | Experimental | MTX dose group was assigned based on the subject's current therapeutic regimen of MTX and rheumatoid arthritis disease status. The sequence of treatments A, B and C was randomly assigned. |
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| 20 mg MTX | Experimental | MTX dose group was assigned based on the subject's current therapeutic regimen of MTX and rheumatoid arthritis disease status. The sequence of treatments A, B and C was randomly assigned. |
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| 25 mg MTX | Experimental | MTX dose group was assigned based on the subject's current therapeutic regimen of MTX and rheumatoid arthritis disease status. The sequence of treatments A, B and C was randomly assigned. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MTX | Drug |
|
| Measure | Description | Time Frame |
|---|---|---|
| Dose-Normalized AUC[0-Inf] for MTX | Dose-normalized area under the curve from time zero to infinity (AUC[0-inf]/Dose) for each treatment | 24 Hour period |
| Dose-Normalized AUC[0-24] for MTX | Dose-normalized area under the curve from time zero to 24 hours (AUC[0-24]/Dose) for each treatment | 24 Hour period |
| Dose-Normalized Cmax for MTX | Dose-normalized maximum observed concentration (Cmax) for each treatment | 24 Hour period |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Alan J Kivitz, MD;CPI | Altoona Center for Clinical Research | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Altoona Center for Clinical Research | Duncansville | Pennsylvania | 16635 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24728329 | Derived | Schiff MH, Jaffe JS, Freundlich B. Head-to-head, randomised, crossover study of oral versus subcutaneous methotrexate in patients with rheumatoid arthritis: drug-exposure limitations of oral methotrexate at doses >/=15 mg may be overcome with subcutaneous administration. Ann Rheum Dis. 2014 Aug;73(8):1549-51. doi: 10.1136/annrheumdis-2014-205228. Epub 2014 Apr 12. |
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MTX was administered via randomized sequence and crossover of Treatment A, Treatment B and Treatment C within the same dose group. Treatments were administered at a 7 day interval (On study days 1, 8 and 15)
Subjects were screened and enrolled at 4 sites in the US. Approximately equal number of subjects on 10 mg, 15 mg, 20 mg and 25 mg doses were recruited. The dose group was determined by the Investigator based on subject's current therapeutic regimen of MTX and disease status. The subject's dose was the same for the entire study
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| ID | Title | Description |
|---|---|---|
| FG000 | 10mg MTX | [administered via randomized sequence and crossover of Treatment A - Oral Methotrexate (MTX) Tablets, Treatment B - SC injection of Vibex MTX into the Abdomen and Treatment C - SC injection of Vibex MTX into the Thigh] |
| FG001 | 15mg MTX | [administered via randomized sequence and crossover of Treatment A - Oral Methotrexate (MTX) Tablets, Treatment B - SC injection of Vibex MTX into the Abdomen and Treatment C - SC injection of Vibex MTX into the Thigh] |
| FG002 | 20mg MTX | [administered via randomized sequence and crossover of Treatment A - Oral Methotrexate (MTX) Tablets, Treatment B - SC injection of Vibex MTX into the Abdomen and Treatment C - SC injection of Vibex MTX into the Thigh] |
| FG003 | 25mg MTX | [administered via randomized sequence and crossover of Treatment A - Oral Methotrexate (MTX) Tablets, Treatment B - SC injection of Vibex MTX into the Abdomen and Treatment C - SC injection of Vibex MTX into the Thigh] |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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In total, 50 subjects were randomized, of which 49 were included in the safety population. Of 49, 47 completed the study and 2 discontinued from the study after first dose.
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| ID | Title | Description |
|---|---|---|
| BG000 | 10mg MTX | [administered via randomized sequence and crossover of Treatment A - Oral Methotrexate (MTX) Tablets, Treatment B - SC injection of Vibex MTX into the Abdomen and Treatment C - SC injection of Vibex MTX into the Thigh] |
| BG001 | 15mg MTX |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Dose-Normalized AUC[0-Inf] for MTX | Dose-normalized area under the curve from time zero to infinity (AUC[0-inf]/Dose) for each treatment | The Population was defined as all randomized subjects who received at least 1 dose of study drug and who had at least 1 valid post-dose plasma concentration value. | Posted | Mean | Standard Deviation | ng*hr/mL/mg | 24 Hour period |
|
The Safety Population was defined as all randomized subjects who received at least 1 dose of study drug. The Safety Population included 49 subjects.
Adverse events were classified by treatment at onset. Any adverse event that occurred on Day 1 (after check-in) for a given treatment period was assigned to the treatment for that period.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 10mg MTX | [administered via randomized sequence and crossover of Treatment A - Oral Methotrexate (MTX) Tablets, Treatment B - SC injection of Vibex MTX into the Abdomen and Treatment C - SC injection of Vibex MTX into the Thigh] |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Sick Sinus Syndrome (15 mg Vibex MTX SC Thigh) | Cardiac disorders | MedDRA 13.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea (20 mg MTX Oral) | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Jonathan Jaffe, MD; Vice President Clinical Development | Antares Pharma Inc. | 609-359-3020 | 324 | jjaffe@antarespharma.com |
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| ID | Term |
|---|---|
| D001172 | Arthritis, Rheumatoid |
| ID | Term |
|---|---|
| D001168 | Arthritis |
| D007592 | Joint Diseases |
| D009140 | Musculoskeletal Diseases |
| D012216 | Rheumatic Diseases |
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| Death |
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[administered via randomized sequence and crossover of Treatment A - Oral Methotrexate (MTX) Tablets, Treatment B - SC injection of Vibex MTX into the Abdomen and Treatment C - SC injection of Vibex MTX into the Thigh] |
| BG002 | 20mg MTX | [administered via randomized sequence and crossover of Treatment A - Oral Methotrexate (MTX) Tablets, Treatment B - SC injection of Vibex MTX into the Abdomen and Treatment C - SC injection of Vibex MTX into the Thigh] |
| BG003 | 25mg MTX | [administered via randomized sequence and crossover of Treatment A - Oral Methotrexate (MTX) Tablets, Treatment B - SC injection of Vibex MTX into the Abdomen and Treatment C - SC injection of Vibex MTX into the Thigh] |
| BG004 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Number | participants |
|
| Region of Enrollment | Number | participants |
|
| Treatment C |
SC injection of Vibex MTX into the Thigh |
|
|
|
| Primary | Dose-Normalized AUC[0-24] for MTX | Dose-normalized area under the curve from time zero to 24 hours (AUC[0-24]/Dose) for each treatment | The Population was defined as all randomized subjects who received at least 1 dose of study drug and who had at least 1 valid post-dose plasma concentration value. | Posted | Mean | Standard Deviation | ng*hr/mL/mg | 24 Hour period |
|
|
|
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| Primary | Dose-Normalized Cmax for MTX | Dose-normalized maximum observed concentration (Cmax) for each treatment | The Population was defined as all randomized subjects who received at least 1 dose of study drug and who had at least 1 valid post-dose plasma concentration value. | Posted | Mean | Standard Deviation | ng/mL/mg | 24 Hour period |
|
|
|
|
| 0 |
| 13 |
| 2 |
| 13 |
| EG001 | 15mg MTX | [administered via randomized sequence and crossover of Treatment A - Oral Methotrexate (MTX) Tablets, Treatment B - SC injection of Vibex MTX into the Abdomen and Treatment C - SC injection of Vibex MTX into the Thigh] | 1 | 12 | 0 | 12 |
| EG002 | 20mg MTX | [administered via randomized sequence and crossover of Treatment A - Oral Methotrexate (MTX) Tablets, Treatment B - SC injection of Vibex MTX into the Abdomen and Treatment C - SC injection of Vibex MTX into the Thigh] | 0 | 12 | 1 | 12 |
| EG003 | 25mg MTX | [administered via randomized sequence and crossover of Treatment A - Oral Methotrexate (MTX) Tablets, Treatment B - SC injection of Vibex MTX into the Abdomen and Treatment C - SC injection of Vibex MTX into the Thigh] | 1 | 12 | 0 | 12 |
| Myocardial Infarction (25 mg Vibex MTX SC Abdomen) | Cardiac disorders | MedDRA 13.1 | Systematic Assessment |
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| Fatigue (10 mg Vibex MTX SC Thigh) | General disorders | MedDRA 13.1 | Systematic Assessment |
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| Rheumatoid Arthritis (10 mg Vibex MTX SC Abdomen) | Musculoskeletal and connective tissue disorders | MedDRA 13.1 | Systematic Assessment |
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| D003240 |
| Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| To compare the relative bioavailability of methotrexate (MTX) following oral administration to that obtained after subcutaneous (SC) injection into the thigh using the VIBEX MTX device by measuring the area under the curve from time zero to the 24 hour concentration AUC(0-24) | Test / Reference ratio | 125.20 | 2-Sided | 90 | 119.16 | 131.55 | Yes | Non-Inferiority or Equivalence | Bioavailability comparisons were performed at each dose level. |
| To compare the relative bioavailability of MTX following SC injection into the abdomen to that obtained after SC injection into the thigh using the VIBEX MTX device by measuring the area under the curve from time zero to the 24 hour concentration AUC(0-24) | Test / Reference Ratio | 101.82 | 2-Sided | 90 | 99.39 | 104.31 | Yes | Non-Inferiority or Equivalence | Test of bioequivalence was performed at each dose level. |
|
To compare the relative bioavailability of methotrexate (MTX) following oral administration to that obtained after subcutaneous (SC) injection into the thigh using the VIBEX MTX device by measuring the maximum observed concentration (Cmax) |
| Test / Reference Ratio |
| 82.12 |
| 2-Sided |
| 90 |
| 76.16 |
| 88.55 |
| Yes |
| Non-Inferiority or Equivalence |
Bioavailability comparisons were performed at each dose level. |
| To compare the relative bioavailability of MTX following SC injection into the abdomen to that obtained after SC injection into the thigh using the VIBEX MTX device by measuring the maximum observed concentration (Cmax) | Test / Reference Ratio | 115.63 | 2-Sided | 90 | 108.83 | 122.86 | Yes | Non-Inferiority or Equivalence | Test of bioequivalence was performed at each dose level. |