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Pharmacokinetics (PK) study
To compare the pharmacokinetic (PK) profiles of methotrexate (MTX) following a subcutaneous (SC) injection of MTX using the Vibex device to that obtained after an SC injection of MTX without using the device and to that obtained after an intramuscular (IM) injection of MTX in adult subjects with rheumatoid arthritis (RA).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 10mg Methotrexate (MTX) Group | Experimental | Treatment Arm A - SC injection with Vibex device, Treatment Arm B - SC injection without device and Treatment Arm C - IM injection |
|
| 15mg Methotrexate (MTX) Group | Experimental | Treatment Arm A - SC injection with Vibex device, Treatment Arm B - SC injection without device and Treatment Arm C - IM injection |
|
| 20mg Methotrexate (MTX) Group | Experimental | Treatment Arm A - SC injection with Vibex device, Treatment Arm B - SC injection without device and Treatment Arm C - IM injection |
|
| 25mg Methotrexate (MTX) Group | Experimental | Treatment Arm A - SC injection with Vibex device, Treatment Arm B - SC injection without device and Treatment Arm C - IM injection |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Methotrexate (MTX) | Drug | Vibex MTX Device |
|
| Measure | Description | Time Frame |
|---|---|---|
| Bioequivalence Based Upon 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 |
| Bioequivalence Based Upon Dose-Normalized AUC[0-24] for MTX | Dose-normalized area under the curve from time zero to 24 hours post-dose (AUC[0-24]/Dose) for each treatment | 24 Hour period |
| Bioequivalence Based Upon Dose-Normalized Cmax for MTX | Dose-normalized maximum observed concentration 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 |
The order of Methotrexate (MTX) treatment arms (A-SC injection with Vibex-MTX device, B-SC injection without device and C-IM Injection) were randomly assigned and dosing was separated by interval of atleast 7 days to allow for washout before the next treatment was administered.
Subjects were screened and enrolled at 2 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 patient's dose was the same for the entire study.
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| ID | Title | Description |
|---|---|---|
| FG000 | 10mg MTX Group | [administered via randomized sequence and crossover of Treatment Arm A -SC injection with Vibex MTX device, Treatment Arm B -SC injection without device and Treatment Arm C -IM Injection] |
| FG001 | 15mg MTX Group | [administered via randomized sequence and crossover of Treatment Arm A -SC injection with Vibex MTX device, Treatment Arm B -SC injection without device and Treatment Arm C -IM Injection] |
| FG002 | 20mg MTX Group | [administered via randomized sequence and crossover of Treatment Arm A -SC injection with Vibex MTX device, Treatment Arm B -SC injection without device and Treatment Arm C -IM Injection] |
| FG003 | 25mg MTX Group | [administered via randomized sequence and crossover of Treatment Arm A -SC injection with Vibex MTX device, Treatment Arm B -SC injection without device and Treatment Arm C -IM Injection] |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
38 subjects were randomized to a treatment sequence. Two subjects discontinued prior to receiving the first study drug dose. Safety Population = 36 subjects who received study drug and completed all study visits. All 36 subjects were included in Pharmacokinetic Population. No discontinuations after first study drug dose.
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| ID | Title | Description |
|---|---|---|
| BG000 | 10mg MTX Group | [Administered via randomized sequence and crossover of Treatment Arm A, Treatment Arm B and Treatment Arm C] |
| BG001 | 15mg MTX Group | [Administered via randomized sequence and crossover of Treatment Arm A, Treatment Arm B and Treatment Arm C] |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| 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 | Bioequivalence Based Upon 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 36 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, Treatment B and Treatment C] |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Maculopapular rash | Skin and subcutaneous tissue disorders | MedDRA 13.1 | Systematic Assessment | AE Occurred During Treatment A |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Jonathan Jaffe, MD; Vice President Clinical Development | Antares Pharma | 1-609-359-3020 | 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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| ID | Term |
|---|---|
| D008727 | Methotrexate |
| ID | Term |
|---|---|
| D000630 | Aminopterin |
| D011622 | Pterins |
| D011621 | Pteridines |
| D006574 | Heterocyclic Compounds, 2-Ring |
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|
| BG002 | 20mg MTX Group | [Administered via randomized sequence and crossover of Treatment Arm A, Treatment Arm B and Treatment Arm C] |
| BG003 | 25mg MTX Group | [Administered via randomized sequence and crossover of Treatment Arm A, Treatment Arm B and Treatment Arm C] |
| BG004 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG002 |
| Treatment Arm C |
Intramuscular (IM) injection of MTX |
|
|
|
| Primary | Bioequivalence Based Upon Dose-Normalized AUC[0-24] for MTX | Dose-normalized area under the curve from time zero to 24 hours post-dose (AUC[0-24]/Dose) for each treatment | Dose-normalized MTX PK parameter AUC(0-24)/Dose used for comparison | Posted | Mean | Standard Deviation | ng*hr/mL/mg | 24 Hour period |
|
|
|
|
| Primary | Bioequivalence Based Upon Dose-Normalized Cmax for MTX | Dose-normalized maximum observed concentration 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 |
| 9 |
| 1 |
| 9 |
| EG001 | 15mg MTX | [Administered via randomized sequence and crossover of Treatment A, Treatment B and Treatment C] | 0 | 9 | 0 | 9 |
| EG002 | 20mg MTX | [Administered via randomized sequence and crossover of Treatment A, Treatment B and Treatment C] | 0 | 9 | 2 | 9 |
| EG003 | 25mg MTX | [Administered via randomized sequence and crossover of Treatment A, Treatment B and Treatment C] | 0 | 9 | 1 | 9 |
|
| Nasopharyngitis | Infections and infestations | MedDRA 13.1 | Systematic Assessment | AE Occurred During Treatment A |
|
| Hypertension | Vascular disorders | MedDRA 13.1 | Systematic Assessment | AE Occurred During Treatment B |
|
| Injection site erythema | General disorders | MedDRA 13.1 | Systematic Assessment | AE Occurred During Treatment B |
|
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| D003240 |
| Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D000072471 |
| Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| Test / Reference Ratio |
| 101.14 |
| 2-Sided |
| 90 |
| 97.06 |
| 105.40 |
| Yes |
| Non-Inferiority or Equivalence |
The bioequivalence of Methotrexate following Treatment A-SC injection with the Vibex MTX device and Treatment C-IM injection was established if the 90% CI for the geometric LS Mean ratios of AUC(0-24)/Dose were within the range of 80% to 125%. |
| Test / Reference Ratio |
| 89.79 |
| 2-Sided |
| 90 |
| 81.61 |
| 98.78 |
| Yes |
| Non-Inferiority or Equivalence |
The bioequivalence of Methotrexate following Treatment A-SC injection with the Vibex MTX device and Treatment C-IM injection was established if the 90% CI for the geometric LS Mean ratios of Cmax/Dose were within the range of 80% to 125%. |