Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Darapladib (SB480848)
darapladib · 13 trials · 3 indications
Coronary heart disease (CHD) death=occurrence of a fatal myocardial infarction (MI), death caused by documented cardiac arrest, death resulting from heart failure in a participant with known CHD, death from other forms of acute/chronic CHD, unwitnessed death of unknown origin, or sudden death. Acute MI=evidence of myocardial necrosis in a clinical setting consistent with myocardial ischemia. Prior MI diagnosed post-randomization (e.g., silent MI)=the development of new pathological Q waves with/without symptoms OR imaging evidence of a region of loss of viable myocardium that is thinned and fails to contract, in the absence of a nonischemic cause (pre-event imaging data required for verification of new abnormality), OR pathological findings of a healed/healing MI. Urgent coronary revascularization (CR) for MI=ischemic discomfort at rest that prompted CR during the same hospitalization or resulted in hospital transfer for the purpose of CR.
CV death=death due to a CV cause, which included but was not limited to deaths resulting from stroke, arrhythmia, sudden death (witnessed/unwitnessed), MI, heart failure, pulmonary embolism, peripheral arterial disease, or complications of a CV procedure. Deaths not clearly attributable to non-CV causes are considered to be CV deaths. Acute MI=evidence of myocardial necrosis in a clinical setting consistent with myocardial ischemia. Prior MI diagnosed post-randomization (e.g., silent MI)=the development of new pathological Q waves with/without symptoms OR imaging evidence of a region of loss of viable myocardium that is thinned and fails to contract, in the absence of a non-ischemic cause (pre-event imaging data required for verification of new abnormality), OR pathological findings of a healed/healing MI. Stroke=presence of a new focal neurologic deficit thought to be of vascular origin, with signs/symptoms lasting \>24 hours or results in death (in \<24 hours).
Mean change from baseline in ETDRS Best Corrected Visual Acuity (BCVA) after 3 months of treatment
Mean change from baseline in SD-OCT after 3 months of treatment
To assess the effect of an 11 day course of once daily darapladib EC 160 mg on the number and phenotype (M1/M2 polarization) of macrophages isolated from blisters on subjects with type 2 diabetes mellitus (blisters induced by exposure to cantharidin for 48 hours). Biomarkers may include, but not be limited to: Cluster of differentiation (CD)11b, CD14, CD16, CD33, CD40, CD64, CD68, CD86, CD163, CD206, C-C chemokine receptor type 2 (CCR2), CX3 chemokine receptor 1 (CX3CR1)
An AE is any untoward medical occurrence in a patient or clinical investigation Subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
12-lead ECGs will be obtained at designated timepoint during the study, using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals.
Systolic and diastolic blood pressure and pulse rate
Hematology, clinical chemistry, urinalysis and additional parameters to be tested
Area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration
Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time
Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time
Accumulation ratios Cmax accumulation ratio
Accumulation ratios Cmax accumulation ratio
The physical examination will include assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen).
The effects of repeat oral dosing of darapladib (160mg enteric coated \[EC\] tablet once daily \[QD\]) on the pharmacokinetic parameters - Cmax and AUC(0-infinity\[inf\]) of a single oral dose of midazolam (5 mg) will be evaluated
The area under the concentrations-time curve (AUC0-24) from the time of administration of darapladib up to 24 h after administration.
The maximum concentration (Cmax) was obtained directly from the measured concentration-time curves.
To evaluate the single dose PK of Rosuvastatin, area under the concentration-time curve from time zero extrapolated to infinite time (AUC \[0-infinity\]) or area under the concentration-time curve from time zero to last time of quantifiable concentration (AUC \[0-t\]) will be assessed.
To evaluate the single dose PK of Rosuvastatin, maximum observed concentration (Cmax) will be assessed.
To evaluate the single dose PK of Rosuvastatin, time of occurrence of Cmax (Tmax), and terminal phase half-life (T1/2) will be assessed.
The PK parameter area under the concentration-time curve over the dosing interval (AUC (0-τ)) will be derived from the plasma concentration-time data.
The PK parameter maximum observed concentration (Cmax) will be derived from the plasma concentration-time data.
| Arm | Type | Description |
|---|---|---|
| Darapladib 160 mg | EXPERIMENTAL | Single daily oral tablet |
| Placebo | PLACEBO_COMPARATOR | Single daily oral tablet |
| Darapladib | EXPERIMENTAL | Single daily oral tablet |
| Part A | EXPERIMENTAL | Part A will consist of 2 sessions. In Session 1, 3 blisters will be induced by a challenging agent (cantharidin solution 0.2 %, with 5 microliter administered topically) in T2DM subjects on Day 1. Blisters will be harvested 48 (+/-2) hour (hr) post induction. In Session 2, the same subjects will be administered darapladib EC tablet 160 mg orally, once daily for 11 days. On Day 10, 3 blisters will be induced by cantharidin. Blisters will be harvested 48 (+/-2) hr post induction. |
| Part B | EXPERIMENTAL | In Part B, healthy subjects will be enrolled and will follow the same dosing procedure as in Part A. The decision to initiate Part B will be made by the GSK study team based on an evaluation of data from Part A. |
| darapladib 160mg | EXPERIMENTAL | drug |
| Darapladib+Diltizem Arm | EXPERIMENTAL | Each subject will receive darapladib EC tablet 160 mg once daily for 10 days followed by darapladib EC tablet 160 mg once daily + diltiazem 240mg once daily for 14 days and then diltiazem 240mg once daily alone for three days |
| Renal Impaired Group | EXPERIMENTAL | Subjects with renal impairment received darapladip 160 mg daily for 10 consecutive days. |
| Healthy Control Group | EXPERIMENTAL | Healthy volunteers matching with renal impairment subjects for gender, age and BMI; received darapladip 160 mg daily for 10 consecutive days. |
| moderate hepatic impaired subjects | EXPERIMENTAL | Male and female subjects with moderate hepatic impairment defined by a Child-Pugh score of 7-9 will be included. The subjects will be administered 40 mg oral doses of darapladib (SB-480848) enteric-coated tablets daily for 10 consecutive days. |
| normal healthy volunteers | EXPERIMENTAL | Healthy male and female subjects will be included and will be matched as closely as possible to the group of moderate hepatic impairment subjects for gender, age and body mass index. Each subject will receive daily 40 mg oral doses of darapladib (SB-480848) enteric-coated tablets for 10 consecutive days. |
| Single dose | EXPERIMENTAL | single oral dose |
| Repeat Dose | EXPERIMENTAL | 28 day repeat dose |
| Name | Type | Description |
|---|---|---|
| Darapladib 160 mg | DRUG | Lp-PLA2 inhibitor |
| Placebo | DRUG | Placebo administered |
| Standard Therapy | OTHER | Guideline mandated therapy for individual's condition |
| Darapladib | DRUG | Lp-PLA2 inhibitor administered in addition to standard therapy |
| darapladib 160mg | DRUG | drug |
| Midazolam | DRUG | The subjects will receive a single oral dose of midazolam 5 mg on Day 1, 3 and14. It is provided as syrup. Each mL of syrup contains midazolam hydrochloride equivalent to 2 mg midazolam |
| Diltiazem | DRUG | Extended release, Blue capsule imprinted with cardizem CD and 240mg on one end, 240 mg, Oral/repeat dose/17 days |
| Rosuvastatin 10 mg | DRUG | Enteric coated tablet will be administered orally as a single dose once in Treatment Period 1 (Day 1) and Treatment Period 2 (Day 15). |
| Darapladib (SB480848) | DRUG | - |
Inclusion Criteria: * Signed written informed consent. * Men or women at least 18 years old (in Taiwan, at least 20 years old). Women must be post-menopausal or using a highly effective method for avoidance of pregnancy. * Hospitalization for acute coronary syndrome (ACS) within 30 days prior to st...
Darapladib is an investigational small molecule drug developed by GSK plc for cardiovascular conditions. It was studied in acute coronary syndrome, atherosclerosis, and diabetic retinopathy. It is a PLA2G7 inhibitor that has completed Phase 3 clinical development but is not approved for any indication.
Darapladib was studied for acute coronary syndrome, atherosclerosis, and diabetic retinopathy. It is an investigational therapy and has not been approved for any use. All clinical trials of darapladib have been completed, and no active trials are ongoing.
Darapladib targets PLA2G7, also known as lipoprotein-associated phospholipase A2. It acts as an inhibitor of this enzyme. By inhibiting PLA2G7, darapladib was designed to reduce inflammation associated with atherosclerotic plaque, though its clinical development has been completed.
Darapladib is developed by GSK plc, which trades under the ticker GSK. GSK sponsored the clinical development program for darapladib, including Phase 3 trials in cardiovascular indications.
Darapladib has completed Phase 3 clinical development. It is an investigational drug and is not approved by the FDA or any regulatory agency. All 11 clinical trials of darapladib are completed, with no active trials currently recruiting.
Darapladib has been evaluated in 11 completed clinical trials, including NCT02058641, NCT02000804, NCT01873339, and NCT01852565. These trials studied darapladib in atherosclerosis and included pharmacokinetic assessments and a study of inflammatory blisters in type 2 diabetes.
Yes, darapladib is also known as SB480848. Other names used in research and clinical settings include darapladib 160 mg and darapladib 160mg, which refer to the 160 milligram dose studied in trials. All these names refer to the same investigational compound.