Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
fostamatinib · 17 trials · 16 indications
ACR20: American College of Rheumatology 20% response criteria, based on count of swollen and tender joints (out of 28 joints), blood test measures of inflammation (such as CRP) and the physician and patient's own assessments of disease activity, pain and physical function. Non-responder imputation has been applied by carrying the baseline observation forward. BID=twice daily, CRP=C-reactive protein, DMARD=disease-modifying anti-rheumatic drug, PO=orally, QD=once a day.
mTSS: modified total Sharp score, a measure of structural progression based upon X-rays. Hand and foot joints are scored for erosions and joint space narrowing and the results summed to give a value between 0 and 448. A higher value represents more serious progression of the disease. After disregarding ineligible records, patients with 2 or more non-missing values have had missing data imputed via linear extrapolation/interpolation methods. Patients with only 1 result have been excluded from the analysis. ANCOVA=analysis of covariance, BID=twice daily, DMARD=disease-modifying anti-rheumatic drug, IP=investigational product, PO=orally, QD=once a day.
ACR20: American College of Rheumatology 20% response criteria, based on count of swollen and tender joints (out of 28 joints), blood test measures of inflammation (such as C-Reactive Protein) and the physician and patient's own assessments of disease activity, pain and physical function. BID = twice daily, DMARD = disease-modifying anti-rheumatic drug, PO = orally, QD = once daily.
ACR20: American College of Rheumatology 20% response criteria, based on count of swollen and tender joints (out of 28 joints), blood test measures of inflammation (such as CRP) and the physician and patient's own assessments of disease activity, pain and physical function. BID = twice daily, CRP = C-reactive protein, DMARD = disease-modifying anti-rheumatic drug, PO = orally, QD = once a day.
ANCOVA=analysis of covariance, BID=twice daily, FAS=full analysis set, IP=investigational product, SBP=systolic blood pressure.
Patients were assessed using the revised response criteria for malignant lymphoma (Cheson). Patients were assessed for response, with CT and FDG-PET scans at 8 weeks, then every 12 weeks until radiological progression by clinical CT. Complete response (CR) was defined as disappearance of all target and non-target lesions in the liver and spleen and all lymph node masses regressed to normal size. Partial response (PR) was defined as ≥50% reduction in sum of the product of the diameters (SPD) for measured lymph nodes, splenic and liver lesions separately compared to baseline SPD. Objective response rate (CR + PR) analysis, exact binomial test, primary analysis.
AUC - area under the plasma concentration time curve from zero to infinity ; tmax - time to max plasma concentration; t1/2 - terminal elimination half life; Rac - accumulation ratio
AUC-Area under the plasma concentration time curve; AUC(0-t)-Area under plasma concentration time curve from zero to time of the last measurable concentration; Cmax - max plasma concentration; t½ λz-Terminal half-life; MRT- Mean residence time; CL - Total body clearance; Vz - Volume of distribution during the terminal phase
PK Parameters: AUC, AUC (0-t), Cmax, t½ λz and MRT
Assessments will include but is not limited to: plasma R406 AUC, Cmax
Assessments will include but is not limited to: plasma R406 AUC, Cmax )
* Pharmacokinetics of warfarin measured by AUC * Pharmacokinetics of warfarin measured Cmax
Parameters include: AUC, Cmax
| Arm | Type | Description |
|---|---|---|
| Dosing Regimen A | EXPERIMENTAL | Oral Treatment |
| Dosing Regimen B | EXPERIMENTAL | Oral Treatment |
| Dosing Regimen C | PLACEBO_COMPARATOR | Oral Treatment |
| Fostamatinib 200 | EXPERIMENTAL | 200mg fostamatinib bid n=60 |
| Rosuvastatin | EXPERIMENTAL | Single, oral dose of rosuvastatin 20mg in first period and in second period (after wash out) fostamatinib 100 mg twice daily, then single oral dose of rosuvastatin 20 mg plus continued oral dosing of fostamatinib 100 mg twice daily, then continue fostamatinib 100 mg twice daily |
| Simvastatin | EXPERIMENTAL | Single, oral dose of simvastatin 40 mg in first period and in second period (after wash out) fostamatinib 100 mg twice daily, then single oral dose of simvastatin 40 mg plus continued oral dosing of fostamatinib 100 mg twice daily, then continue fostamatinib 100 mg twice daily |
| Fostamatinib 100mg | EXPERIMENTAL | Up to two cohorts of Japanese subjects are planned to receive fostamatinib 100mg single and multiple twice daily doses |
| Fostamatinib 200mg | EXPERIMENTAL | Up to two cohorts of Japanese subjects are planned to receive fostamatinib 200mg single and multiple twice daily doses |
| Fostamatinib 50 mg tablet | EXPERIMENTAL | - |
| Fostamatinib 100 μg [14C] R406 intravenous micro tracer dose | EXPERIMENTAL | - |
| A | EXPERIMENTAL | Fostamatinib 50 mg tablet x 2 (Phase 3 batch) |
| B | SHAM_COMPARATOR | Fostamatinib 50 mg tablet x 3 (Phase 3 batch) |
| C | EXPERIMENTAL | Fostamatinib 100 mg tablet (new formulation) |
| D | EXPERIMENTAL | Fostamatinib 150 mg tablet (new formulation) |
| E | EXPERIMENTAL | Fostamatinib 50 mg tablet x 2 (Phase 3 batch) |
| 1 | EXPERIMENTAL | Digoxin |
| 2 | EXPERIMENTAL | Fostamatinib |
| warfarin | EXPERIMENTAL | - |
| warfarin and fostamatinib | EXPERIMENTAL | - |
| pioglitazone | EXPERIMENTAL | - |
| pioglitazone and fostamatinib | EXPERIMENTAL | - |
| Treatment A | PLACEBO_COMPARATOR | Monophasic oral contraceptive (Microgynon® 30) with placebo tablets |
| Treatment B | EXPERIMENTAL | Monophasic oral contraceptive (Microgynon® 30) and fostamatinib |
| 3 | EXPERIMENTAL | Moderate renal impairment (Stage 2) |
| 4 | EXPERIMENTAL | Severe renal impairment (Stage 2) |
| 5 | EXPERIMENTAL | End stage renal disease (Stage 1) |
| Name | Type | Description |
|---|---|---|
| fostamatinib | DRUG | fostamatinib 100 mg twice daily |
| placebo, fostamatinib | DRUG | Placebo for 24 weeks followed by fostamatinib 100 mg twice daily |
| placebo | DRUG | Placebo twice daily |
| Rosuvastatin | DRUG | 20-mg tablet |
| Simvastatin | DRUG | 40-mg tablet |
| Fostamatinib 100mg | DRUG | oral tablet |
| Fostamatinib 200mg | DRUG | oral tablet |
| Digoxin | DRUG | oral tablets, 0.25mg bd on Day 1 and 0.25 Once daily from Day 2 to 15 |
| rifampicin | DRUG | oral tablets, 600mg (2 X 300mg) 8 doses over 8 days |
| warfarin | DRUG | 2 single 25 mg doses of Warfarin (5 x 5 mg tablets) administered 14 days apart |
| pioglitazone | DRUG | oral tablets, 30mg single dose per period |
| Microgynon® 30 (Oral contraceptive) | DRUG | Oral tablets, repeated doses |
Inclusion Criteria: * Active rheumatoid arthritis (RA) diagnosed after the age of 16 * Currently taking methotrexate * 6 or more swollen joints and 6 or more tender/painful joints (from 28 joint count) and either Erythrocyte Sedimentation Rate (ESR) blood result of 28mm/h or more, or C-Reactive Pro...
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Fostamatinib is an investigational small molecule being studied in hepatic impairment, healthy volunteers, healthy Japanese volunteers, rheumatoid arthritis, and diffuse large B-cell lymphoma. It has completed nine Phase 1 clinical trials with a total enrollment of 2,536 participants.
Fostamatinib is being developed by AstraZeneca PLC, which trades under the ticker AZN. The company has sponsored nine clinical trials of the drug, all of which are completed.
Fostamatinib is in Phase 1 clinical development. All nine of its trials are completed, with none currently active. The drug remains investigational and has not been approved for any use.
Fostamatinib has completed nine Phase 1 trials, including NCT01208155, a bioavailability study in healthy males; NCT01222455, a study in subjects with hepatic impairment; NCT01276262, a drug-drug interaction study with an oral contraceptive; and NCT01355354, a study with digoxin in healthy subjects.
Fostamatinib is a prodrug that is converted to R406 in the body. One clinical trial, NCT01222455, measured the amount of R406 in blood after fostamatinib administration, indicating R406 is the active metabolite.