Rheumatoid Arthritis (RA)
Conditions
Brief summary
Relative Bioavailability Comparison study
Detailed description
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
Interventions
DRUGMTX
* Treatment A - 1 dose (4, 6, 8 or 10 tablets respectively to make up 10 mg, 15 mg, 20 mg or 25 mg MTX - per subject's dose group) * Treatment B - SC injection using VIBEX MTX device into abdomen (VIBEX MTX device pre-filled with 10 mg, 15 mg, 20 mg or 25 mg MTX) * Treatment C - SC injection using VIBEX MTX device into thigh (VIBEX MTX device pre-filled with 10 mg, 15 mg, 20 mg or 25 mg MTX)
Sponsors
Antares Pharma Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female patients ≥18 years of age, diagnosed with Rheumatoid Arthritis
Exclusion criteria
* Pregnant females * Any other clinically significant disease or disorder which, in the opinion of the investigator might put the subject at risk
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose-Normalized AUC[0-Inf] for MTX | 24 Hour period | Dose-normalized area under the curve from time zero to infinity (AUC\[0-inf\]/Dose) for each treatment |
| Dose-Normalized AUC[0-24] for MTX | 24 Hour period | Dose-normalized area under the curve from time zero to 24 hours (AUC\[0-24\]/Dose) for each treatment |
| Dose-Normalized Cmax for MTX | 24 Hour period | Dose-normalized maximum observed concentration (Cmax) for each treatment |
Countries
United States
Participant flow
Recruitment details
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
Pre-assignment details
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)
Participants by arm
| Arm | Count |
|---|---|
| 10mg MTX \[administered via randomized sequence and crossover of Treatment A - Oral Methotrexate (MTX) Tablets, Treatment B - SC injection of Vibex MTX into the Abdomen and Treatment C - SC injection of Vibex MTX into the Thigh\] | 13 |
| 15mg MTX \[administered via randomized sequence and crossover of Treatment A - Oral Methotrexate (MTX) Tablets, Treatment B - SC injection of Vibex MTX into the Abdomen and Treatment C - SC injection of Vibex MTX into the Thigh\] | 12 |
| 20mg MTX \[administered via randomized sequence and crossover of Treatment A - Oral Methotrexate (MTX) Tablets, Treatment B - SC injection of Vibex MTX into the Abdomen and Treatment C - SC injection of Vibex MTX into the Thigh\] | 12 |
| 25mg MTX \[administered via randomized sequence and crossover of Treatment A - Oral Methotrexate (MTX) Tablets, Treatment B - SC injection of Vibex MTX into the Abdomen and Treatment C - SC injection of Vibex MTX into the Thigh\] | 12 |
| Total | 49 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 | 0 |
| Overall Study | Death | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | 10mg MTX | 15mg MTX | 20mg MTX | 25mg MTX | Total |
|---|---|---|---|---|---|
| Age, Continuous | 62.9 years STANDARD_DEVIATION 12.51 | 63.4 years STANDARD_DEVIATION 7.49 | 60.0 years STANDARD_DEVIATION 10.4 | 59.0 years STANDARD_DEVIATION 11.53 | 61.4 years STANDARD_DEVIATION 10.53 |
| Race/Ethnicity, Customized African American | 1 participants | 1 participants | 2 participants | 1 participants | 5 participants |
| Race/Ethnicity, Customized White | 12 participants | 11 participants | 10 participants | 11 participants | 44 participants |
| Region of Enrollment United States | 13 participants | 12 participants | 12 participants | 12 participants | 49 participants |
| Sex: Female, Male Female | 11 Participants | 5 Participants | 8 Participants | 7 Participants | 31 Participants |
| Sex: Female, Male Male | 2 Participants | 7 Participants | 4 Participants | 5 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 13 | 0 / 12 | 1 / 12 | 0 / 12 |
| serious Total, serious adverse events | 0 / 13 | 1 / 12 | 0 / 12 | 1 / 12 |
Outcome results
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
Time frame: 24 Hour period
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Dose-Normalized AUC[0-24] for MTX | 107.64 ng*hr/mL/mg | Standard Deviation 37.732 |
| Treatment B | Dose-Normalized AUC[0-24] for MTX | 137.88 ng*hr/mL/mg | Standard Deviation 44.513 |
| Treatment C | Dose-Normalized AUC[0-24] for MTX | 133.78 ng*hr/mL/mg | Standard Deviation 44.406 |
Comparison: To compare the relative bioavailability of methotrexate (MTX) following oral administration to that obtained after subcutaneous (SC) injection into the abdomen using the VIBEX MTX device by measuring the area under the curve from time zero to the 24 hour concentration AUC(0-24)90% CI: [121.28, 134.36]
Comparison: 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)90% CI: [119.16, 131.55]
Comparison: 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)90% CI: [99.39, 104.31]
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
Time frame: 24 Hour period
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Dose-Normalized AUC[0-Inf] for MTX | 109.47 ng*hr/mL/mg | Standard Deviation 39.19 |
| Treatment B | Dose-Normalized AUC[0-Inf] for MTX | 140.84 ng*hr/mL/mg | Standard Deviation 46.66 |
| Treatment C | Dose-Normalized AUC[0-Inf] for MTX | 136.45 ng*hr/mL/mg | Standard Deviation 46.675 |
Comparison: To compare the relative bioavailability of methotrexate (MTX) following oral administration to that obtained after subcutaneous (SC) injection into the abdomen using the VIBEX MTX device by measuring the area under the curve from time zero to the last measurable concentration AUC(0-inf).90% CI: [121.61, 134.7]
Comparison: To compare the relative bioavailability of MTX following oral administration to that obtained after SC injection into the thigh using the VIBEX MTX device by measuring the AUC(0-Inf).90% CI: [119.43, 131.84]
Comparison: 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 AUC(0-inf)90% CI: [99.41, 104.36]
Primary
Dose-Normalized Cmax for MTX
Dose-normalized maximum observed concentration (Cmax) for each treatment
Time frame: 24 Hour period
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Dose-Normalized Cmax for MTX | 22.697 ng/mL/mg | Standard Deviation 7.496 |
| Treatment B | Dose-Normalized Cmax for MTX | 21.935 ng/mL/mg | Standard Deviation 8.243 |
| Treatment C | Dose-Normalized Cmax for MTX | 18.436 ng/mL/mg | Standard Deviation 5.321 |
Comparison: To compare the relative bioavailability of methotrexate (MTX) following oral administration to that obtained after subcutaneous (SC) injection into the abdomen using the VIBEX MTX device by measuring the maximum observed concentration (Cmax)90% CI: [86.42, 104.06]
Comparison: 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)90% CI: [76.16, 88.55]
Comparison: 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)90% CI: [108.83, 122.86]