Approval Probability
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Also known as GSK2586184 standard formulation, GSK2586184
GSK2586184 single and repeat dose · 3 trials · 2 indications
PASI score was determined by evaluation of body surface area (BSA) covered by plaque psoriasis in 4 areas (head/neck, arms, trunk and legs with area score of 0.1, 0.2, 0.3 and 0.4 respectively). This test included combination of both degree of involvement (assessed as per the % of affected body area using a 7-point scale such that 0=0% involvement, 1=1-9%, 2=10-29%, 3=30-49%, 4=50-69%, 5=70-89% and 6=90-100%) and severity (evaluated individually using a 5-point scale that ranged as 0=No evidence of sign, 1=slight evidence, 2=moderate evidence, 3=marked evidence and 4=very marked, most severe evidence of sign) of erythema, induration and desquamation in each of the same 4 areas. PASI score ranges from 0(no psoriasis) to 72(worse psoriasis). Final PASI=(sum of severity score for each area)x(% body affected score x area score). Baseline=Day 1. Percentage of participants who achieved \>= 75% improvement from Baseline was reported with last observation carried forward (LOCF) analysis.
Blood samples will be collected to analyse PK parameters of Rosuvastatin including area under the plasma concentration-time curve from time zero to infinity \[AUC(0-inf)\], area under the plasma concentration-time curve from time zero to the last quantifiable concentration \[AUC(0-t)\] and the maximum observed plasma concentration (Cmax).
Blood samples will be collected to analyse PK parameters of Simvastatin including AUC(0-inf), AUC(0-t) and Cmax.
Blood samples will be collected to analyse PK parameters of GSK2586184 (standard and new formulation) including AUC(0-inf), area under the plasma concentration-time curve from time 0 to 24 hrs (AUC(0-24)), time to maximum observed plasma drug concentration (Tmax) and Cmax.
Blood samples will be collected to analyse PK parameters of GSK2586184 (new formulation, without-poloxamer) including AUC (0-inf), AUC(0-24), Tmax and Cmax.
Change in health of subjects
Change in clinical chemistry, hematology and urinalysis from baseline
Change in blood pressure, heart rate and body temperature outside normal range
Change in ECG parameters outside normal range
Change in plasma concentrations of GSK2586184
Change in 24h urine creatinine, albumin and PCR values outside normal range
| Arm | Type | Description |
|---|---|---|
| 100 mg GSK2586184 | EXPERIMENTAL | Subjects will be randomized to 100 mg GSK2586184 twice daily for up to 84 days |
| 200 mg GSK2586184 | EXPERIMENTAL | Subjects will be randomized to 200 mg GSK2586184 twice daily for up to 84 days |
| 400 mg GSK2586184 | EXPERIMENTAL | Subjects will be randomized to 400 mg GSK2586184 twice daily for up to 84 days |
| Placebo | PLACEBO_COMPARATOR | Subjects will be randomized to receive Placebo twice daily for up to 84 days |
| 400 mg GSK2586184 (Cohort B) | EXPERIMENTAL | Subjects will take 400 mg GSK2586184 twice daily for up to 84 days |
| Cohort A | EXPERIMENTAL | Cohort A is a single-sequence, open-label study in which each subject will receive Simvastatin 10 mg single dose oral tablet on Days 1 and 10, Rosuvastatin 10 mg single dose oral tablet on Days 3 and 12 and GSK2586184 standard formulation 400 mg twice daily oral tablet from Day 6 to Day 14 immediately after food. At Day 10 GSK2586184 and Simvastatin and at Day 12, GSK2586184 and Rosuvastatin will be co-administered. |
| Cohort B | EXPERIMENTAL | Cohort B is a three-way crossover study in which each subject will receive a single dose of GSK2586184 standard formulation 400 mg oral tablet with food and two doses of a new formulation of GSK2586184 400 mg oral tablet, once with food and once in a fasted state, on Day 1, 4 and 7 according to their treatment sequence, with a 3-day wash out between doses. |
| Cohort A fed session | OTHER | GSK2586184 800mg single dose with food |
| Cohort A fasted session | OTHER | GSK2586184 single dose without food |
| Cohort B active study medication | ACTIVE_COMPARATOR | GSK2586184 800mg single and twice daily dose for 13 days |
| Cohort B placebo | PLACEBO_COMPARATOR | Placebo-to-match single and twice daily dose for 13 days |
| Name | Type | Description |
|---|---|---|
| 100 mg GSK2586184 | DRUG | 100 mg GSK2586184 to be taken twice daily with food (as tablets) for up to 84 days. |
| 200 mg GSK2586184 | DRUG | 200 mg GSK2586184 to be taken twice daily with food (as tablets) for up to 84 days. |
| 400 mg GSK2586184 | DRUG | 400 mg GSK2586184 to be taken twice daily with food (as tablets) for up to 84 days. |
| Placebo | DRUG | Placebo tablets to be taken twice daily with food for up to 84 days. |
| GSK2586184 standard formulation | DRUG | GSK2586184 standard formulation is a white film coated round biconvex 200 mg oral tablet. For cohort A, it is to be administered at 400 mg (200 mg x 2 tablets) twice daily from Day 6 to Day 14. For cohort B, it is to be administered at 400 mg (200 mg x 2 tablets) single dose after standard breakfast either on Day 1, 4 and 7 according to the treatment sequence, each separated by a 3-day wash out period. |
| Simvastatin | DRUG | Simvastatin 10 mg oral tablet is peach-coloured, oval-shaped tablets. It is to be administered orally as a single dose of 10 mg tablet on the mornings of Day 1 and Day 10. |
| Rosuvastatin | DRUG | GSK2586184 new formulation without poloxamer is a white film coated round biconvex 200 mg oral tablet. In cohort B, it is to be administered at 400 mg (200 mg x 2 tablets) single dose once after standard breakfast and once after overnight fasting, either on Day 1, 4 and 7 according to the treatment sequence, each separated by a 3-day washout period. |
| GSK2586184 new formulation | DRUG | GSK2586184 new formulation without poloxamer is a white film coated round biconvex 200 mg oral tablet. In cohort B, it is to be administered at 400 mg (200 mg x 2 tablets) single dose once after standard breakfast and once after overnight fasting, either on Day 1, 4 and 7 according to the treatment sequence, each separated by a 3-day washout period. |
| GSK2586184 800mg single and repeat dose | DRUG | GSK2586184 800mg single dose and then twice daily dosing for 13 days |
| Placebo-to-match GSK2586184 | DRUG | Placebo-to-match GSK2586184 |
| GSK2586184 single dose taken with food | OTHER | GSK2586184 single dose taken with FDA approved high fat, high calorie breakfast |
| GSK2586184 single dose taken without food | OTHER | GSK2586184 single dose taken in a fasted state |
Inclusion Criteria: * Otherwise healthy subjects with a diagnosis of moderate to severe plaque psoriasis defined by the following criteria: * Diagnosed for at least 12 months before the first dose of study medication * Psoriasis plaques cover \>=10% of body surface area. * PASI score of \>=12, and ...
Top 12 of 13 competitors
| Company | Ticker | Trials | Lead Phase | Drugs |
|---|---|---|---|---|
| Johnson & Johnson | JNJ | 11 | PHASE3 | JNJ-77242113, Ustekinumab, Guselkumab |
| Bristol-Myers Squibb Company | BMY | 14 | PHASE3 | Deucravacitinib |
| AbbVie, Inc. | ABBV | 5 | PHASE3 | Risankizumab |
| Takeda Pharmaceutical Co. Ltd. Sponsored ADR | TAK | 3 | PHASE3 | Zasocitinib |
| Alumis Inc. | ALMS | 2 | PHASE3 | Envudeucitinib |
| Oruka Therapeutics, Inc. | ORKA | 4 | PHASE2 | ORKA-002, ORKA-001 |
| Can-Fite Biopharma Ltd | CANF | 1 | PHASE3 | Piclidenoson |
| Organon & Co. | OGN | 1 | PHASE3 | Tapinarof |
| Vanda Pharmaceuticals Inc. | VNDA | 1 | PHASE3 | Ponesimod |
| Novartis AG Sponsored ADR | NVS | 4 | - | Secukinumab |
| Bausch Health Companies Inc. | BHC | 2 | - | Brodalumab |
| Merck & Co., Inc. | MRK | 1 | PHASE1 | MK-8644 |
GSK2586184 was studied for the treatment of chronic plaque psoriasis and systemic lupus erythematosus. It is an investigational small molecule developed by GSK plc and has been evaluated in placebo-controlled clinical trials in both indications. It is not described as an approved therapy for either condition.
GSK2586184 is developed by GSK plc, which trades under the ticker GSK. The compound was advanced by GSK through Phase 1 and Phase 2 clinical testing in immunology and dermatology indications before those studies were completed.
GSK2586184 reached Phase 2 clinical development. Its dose-ranging Phase 2 study in chronic plaque psoriasis was completed, and two Phase 1 studies in systemic lupus erythematosus were also completed. No active trials are ongoing, and the drug is investigational rather than approved.
GSK2586184 has been studied in completed trials including NCT01782664, a Phase 2 dose-ranging study in chronic plaque psoriasis enrolling 68 patients in Germany and the United Kingdom, and NCT01953835 and NCT01687309, Phase 1 pharmacokinetic studies in systemic lupus erythematosus conducted in the United States and Belgium.
GSK2586184 was evaluated in a randomized, double-blind, placebo-controlled Phase 2 dose-ranging study in patients with chronic plaque psoriasis. That trial, NCT01782664, enrolled 68 adults across sites in Germany and the United Kingdom and has been completed.