Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
This will be an exploratory, open-label, single sequence, two part study (Part A and an optional Part B). The aim of this study will be to assess whether systemic inhibition of Lipoprotein associated phospholipase A2 (Lp-PLA2) in humans, effected by 11 days of once daily dosing to steady state with 160 milligrams (mg) of enteric coated (EC) darapladib, will specifically reduce the number of macrophages and/or result in a higher proportion of M2 macrophages in skin blisters induced by cantharidin (a chemical agent that causes blisters). In Part A of the study, a cohort of 8 subjects with type 2 diabetes mellitus will be recruited. In Part B of the study, a cohort of 8 additional healthy subjects with matching age (+/- 24 months) and gender to Part A may be recruited.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Darapladib | Drug | EC tablet with a unit dose strength of 160 mg administered once daily orally for 11 days. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Macrophage cell count and surface expression of markers of M1 and M2 polarization in blister fluid | 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) | Up to 6 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Number of monocytes and surface expression of markers of M1 or M2 polarization in peripheral blood | To assess the effect of an 11 day course of once daily darapladib EC 160 mg on the number and phenotype of monocytes (M1/M2 ratio) isolated from peripheral blood of subjects with type 2 diabetes mellitus. Biomarkers may include, but not be limited to: CD11b, CD14, CD16, CD40, CD64, CD68, CD163, CD206 |
Not provided
Inclusion Criteria:
Additional Criteria for Diabetic Subjects
Exclusion Criteria for all subjects:
Additional Criteria for Diabetic Subjects:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Cambridge | CB2 0GG | United Kingdom |
Not provided
| Label | URL |
|---|---|
| Results for study 200934 can be found on the GSK Clinical Study Register. | View source |
Not provided
Not provided
| ID | Term |
|---|---|
| D050197 | Atherosclerosis |
| D003924 | Diabetes Mellitus, Type 2 |
| ID | Term |
|---|---|
| D001161 | Arteriosclerosis |
| D001157 | Arterial Occlusive Diseases |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C529040 | darapladib |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Up to 6 weeks |
| Enzymatic activity of Lp-PLA2 in blister fluid | Blood samples will be taken for assessments of enzymatic activity of Lp-PLA2 (measured by hydrolysis of radio-labeled platelet-activating factor [PAF]) | Up to 6 weeks |
| Total cell count, lymphocyte count, neutrophil count and macrophage count in blister fluid | Blister fluids will be collected to assess the differences in blister phenotype (volume, appearance, cellularity) between subjects | Up to 6 weeks |
| Concentrations of soluble mediators of macrophage polarization | Soluble mediators will be measured in blister fluid assessed by a multiplex platform (Meso scale delivery or Luminex) and may include but not be restricted to matrix metalloproteinase 9 (MMP9), interleukin (IL)-12, IL-23, IL-10, interferon-gamma, tumor necrosis factor-alpha, IL-1 beta, IL-6, IL-8, IL-4, IL-13, transforming growth factor-beta, monocyte chemotactic protein-1 and C-reactive protein | Up to 6 weeks |
| Time to healing of cantharidin-induced blisters | Blisters will be considered to be healed when the blister cover has fallen off and the blister area becomes dry | Up to 8 weeks |
| D003920 |
| Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |