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The potential for a drug interaction between Darapladib and Rosuvastatin is felt to be low and it would be helpful to quantify this risk in man in order to guide prescribing physicians. The primary aims of this study are to estimate the potential effects of repeat doses of Darapladib on the PK of Rosuvastatin as well as evaluating safety and tolerability. Two part approaches are planned for this study. Part A of the study will examine the effects of repeat doses Darapladib on the PK of Rosuvastatin in healthy volunteers of Caucasian descent. Based on whether a significant increase in Rosuvastatin exposure is observed in Caucasians in Part A, a decision will be made regarding whether to proceed with a conditional Part B to examine this effect in healthy volunteers of Far-East Asian descent.
In both parts, subjects will receive Rosuvastatin 10 milligrams (mg) once daily (QD) for 1 day during the first treatment period (Treatment Period 1), followed by a 4 day PK sampling period/wash-out. Subjects will then receive darapladib 160 mg QD for the next 10 days with 24-hour PK sampling on the last day (Day 14 of the study). Immediately following this, all subjects will then receive the combination of Darapladib 160 mg and Rosuvastatin 10 mg for 1 day and continued Darapladib dosing of 160 mg QD for additional 3 days (Treatment Period 2) while blood samples are collected to assess Rosuvastatin PK. Plasma samples collected on Day 15 will be analyzed for both Rosuvastatin and Darapladib concentrations.
Subjects will be required to return to the unit approximately 10 to 14 days following the last dose of study medication for a clinic visit for assessments and then will return again at 35 ±7 days following the last dose for the final follow-up visit of the study. The duration of each subject's participation in the study from screening to follow-up will be approximately three months.
Approximately 18 evaluable subjects will be enrolled in Part A and another 18 subjects will be enrolled in Part B (if conducted) to complete dosing and all assessments.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part A | Experimental | All subjects will be of Caucasian descent and will receive single dose of Rosuvastatin 10 mg for 1 day (Day 1) during treatment period 1, then will receive Darapladib 160 mg once daily (QD) for 10 days (Day 5 to 14) in treatment period 2. Immediately following this, all subjects will receive the combination of Darapladib 160 mg and Rosuvastatin 10 mg for 1 day (Day 15) and continued Darapladib dosing of 160 mg QD for additional 3 days (Days 16 to 18) in treatment period 2. |
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| Part B | Experimental | The decision to initiate Part B will be made by the GSK study team based on an evaluation of data from Part A. Part B will consist of a cohort of healthy subjects of Far-East Asian descent and will be conducted similar to Part A. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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). |
|
| Measure | Description | Time Frame |
|---|---|---|
| Single dose PK of Rosuvastatin assessed by AUC (0-infinity) or AUC (0-t) when co-administered with darapladib and when administered alone. | 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. | 09 days. Blood samples will be collected on Day 1 to 5 (pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 hours [hrs] post dose) and on Day 15 to 18 (pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, and 24, 36, 48, 72, and 96 hrs post dose). |
| Single dose PK of Rosuvastatin assessed by Cmax when co-administered with darapladib and when administered alone. | To evaluate the single dose PK of Rosuvastatin, maximum observed concentration (Cmax) will be assessed. | 09 days. Blood samples will be collected on Day 1 to 5 (pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 hours [hrs] post dose) and on Day 15 to 18 (pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, and 24, 36, 48, 72, and 96 hrs post dose). |
| Single dose PK of Rosuvastatin assessed by Tmax and T1/2 (as data permit) when co-administered with darapladib and when administered alone. | To evaluate the single dose PK of Rosuvastatin, time of occurrence of Cmax (Tmax), and terminal phase half-life (T1/2) will be assessed. | 09 days. Blood samples will be collected on Day 1 to 5 (pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 hours [hrs] post dose) and on Day 15 to 18 (pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, and 24, 36, 48, 72, and 96 hrs post dose). |
| Measure | Description | Time Frame |
|---|---|---|
| Single dose Rosuvastatin PK compared between Caucasian subjects (Part A) and if performed, Asian subjects (Part B). | Single dose Rosuvastatin PK will be assessed by comparison of AUC (0-infinity), or AUC (0-t), Cmax, Tmax and T1/2 as data permit. | 05 days. Blood samples will be collected on Day 1 to Day 5 (pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours [hrs] post dose). |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Glendale | California | 91206 | United States |
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| Label | URL |
|---|---|
| Results for study 115677 can be found on the GSK Clinical Study Register. | View source |
| Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research. | View source |
| ID | Type | URL | Comment |
|---|---|---|---|
| 115677 | Clinical Study Report | View IPD |
Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
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|
| Darapladib 160 mg | Drug | Enteric coated tablet will be administered orally as once daily for 14 days in Treatment Period 2 only (Day 5 to Day 18). |
|
| Rosuvastatin PK when co-administered with repeat doses of Darapladib compared between Caucasian subjects (Part A) and if performed, Asian subjects (Part B). | Rosuvastatin PK when co-administered with repeat doses of Darapladib will be assessed by comparison of AUC (0-infinity), or AUC (0-t), Cmax, Tmax and T1/2 as data permit. | 01 day. Blood samples will be collected on Day 15 (pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, and 24 hrs post dose) of each part. |
| Repeat doses PK of Darapladib compared between Caucasian subjects (Part A) and if performed, Asian subjects (Part B). | Repeat doses PK of Darapladib assessed by comparison of area under the concentration-time curve over the dosing interval (AUC [0-tau]), Cmax, Tmax and T1/2 as data permit | 02 days. Blood samples will be collected on Day 13 (pre-dose), and Day 14 (pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12 and 24 hrs post-dose) of each part. |
| Repeat doses PK of Darapladib assessed by AUC (0-tau) when co-administered with single dose of Rosuvastatin and when administered alone. | To evaluate the repeat doses PK of Darapladib, AUC (0-tau), will be assessed when repeat doses of Darapladib given with single dose of Rosuvastatin and when given alone. | 03 days. Blood samples will be collected on Day 13 (pre-dose), Day 14 (pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12 and 24 hrs post-dose) and Day 15 (0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, and 24 hrs post dose). |
| Repeat doses PK of Darapladib assessed by Cmax when co-administered with single dose Rosuvastatin and when administered alone | To evaluate the repeat doses PK of Darapladib, Cmax will be assessed when repeat doses of Darapladib given with single dose of Rosuvastatin and when given alone. | 03 days. Blood samples will be collected on Day 13 (pre-dose), Day 14 (pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12 and 24 hrs post-dose) and Day 15 (0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, and 24 hrs post dose). |
| Repeat doses PK of Darapladib assessed by Tmax, and T1/2 (as data permit) when co-administered with Rosuvastatin and when administered alone | To evaluate the repeat doses PK of Darapladib, Tmax, and T1/2 will be assessed when repeat doses of Darapladib given with single dose of Rosuvastatin and when given alone. | 03 days. Blood samples will be collected on Day 13 (pre-dose), Day 14 (pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12 and 24 hrs post-dose) and Day 15 (0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, and 24 hrs post dose). |
| Safety and tolerability of darapladib when co-administered with Rosuvastatin assessed by incidence and severity of adverse events | Adverse events (AEs) will be collected from the start of study treatment and until the follow-up contact. Intensity of AEs will be categorized as mild, moderate or severe | Up to 60 days |
| Safety and tolerability of darapladib when co-administered with Rosuvastatin assessed by vital signs | Vital signs measurement will include systolic and diastolic blood pressure and pulse rate. | Up to 60 days |
| Safety and tolerability of darapladib when co-administered with Rosuvastatin assessed by clinical laboratory data | Clinical laboratory tests include hematology, clinical chemistry, urinalysis and additional parameters. | Up to 60 days |
For additional information about this study please refer to the GSK Clinical Study Register |
| 115677 | Annotated Case Report Form | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 115677 | Individual Participant Data Set | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 115677 | Dataset Specification | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 115677 | Informed Consent Form | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 115677 | Study Protocol | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 115677 | Statistical Analysis Plan | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| ID | Term |
|---|---|
| D050197 | Atherosclerosis |
| ID | Term |
|---|---|
| D001161 | Arteriosclerosis |
| D001157 | Arterial Occlusive Diseases |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D000068718 | Rosuvastatin Calcium |
| C529040 | darapladib |
| ID | Term |
|---|---|
| D013449 | Sulfonamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D005464 | Fluorobenzenes |
| D006845 | Hydrocarbons, Fluorinated |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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