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This is the first study in which GSK2315698 will be administered in Japanese population. The primary objective of the study is to investigate safety and tolerability, pharmacokinetics, and pharmacodynamics after single intravenous infusion in healthy subjects. This will be a single center, double-blind, randomized, placebo-controlled, dose-ascending study.
Subjects in Cohort 1 will attend 3 dosing sessions, and will be randomized to one of the 3 groups. Each group will receive GSK2315698 and Placebo in a defined sequence. The dose levels of GSK2315698 are set to 10 milligrams (mg) per hour (hr), 20 mg/hr, and 40 mg/hr, to be administered over 1 hour. Dosing sessions 1 and 2, and dosing sessions 2 and 3, will be separated by a washout period of at least 8 and 10 days, respectively.
Subjects in Cohort 2 will attend a single dosing session, and will be randomized to receive either GSK2315698 20 mg/hr or Placebo, over a period of 15 hours.
A sufficient number of subjects will be randomized such that 18 subjects (9 in each cohort) complete the study. The duration of participation for any subject in this study will be approximately 59 days.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1 Group A | Experimental | In dosing sessions 1, 2, and 3, subjects will receive GSK2315698 10 mg/hr, GSK2315698 20 mg/hr, and Placebo, respectively, as intravenous infusion over 1 hour. |
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| Cohort 1 Group B | Experimental | In dosing sessions 1, 2, and 3, subjects will receive GSK2315698 10 mg/hr, Placebo, and GSK2315698 40 mg/hr, respectively, as intravenous infusion over 1 hour. |
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| Cohort 1 Group C | Experimental | In dosing sessions 1, 2, and 3, subjects will receive Placebo, GSK2315698 20 mg/hr, and GSK2315698 40 mg/hr, respectively, as intravenous infusion over 1 hour. |
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| Cohort 2 Group D | Experimental | In a single dosing session, subjects will receive GSK2315698 20 mg/hr as intravenous infusion over 15 hours. |
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| Cohort 2 Group E | Placebo Comparator | In a single dosing session, subjects will receive Placebo as an intravenous infusion over 15 hours. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Placebo | Drug | 0.9% weight by volume (w/v) saline solution for intravenous infusion over 1 hour (in Cohort 1) or over 15 hours (in Cohort 2). |
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| Measure | Description | Time Frame |
|---|---|---|
| Number of subjects with adverse events (AE) and serious adverse events (SAE) | Over a maximum period of approximately 29 days | |
| Number of subjects with abnormalities in clinical laboratory parameters | Abnormalities will be assessed in laboratory parameters of hematology, clinical chemistry, and routine urinalysis. | Over a maximum period of approximately 59 days |
| Number of subjects with abnormalities in vital sign parameters | Abnormalities will be assessed in the vital signs of respiratory rate, pulse rate, blood pressure, and body temperature. Vital signs will be measured in a supine position after 5 minutes of rest. | Over a maximum period of approximately 59 days |
| Number of subjects with electrocardiogram (ECG) abnormalities | Single 12-lead ECG will be obtained using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QT interval corrected for heart rate by Fridericia's formula (QTcF) intervals. | Over a maximum period of approximately 59 days |
| Plasma concentration of GSK2315698 | Whole blood samples of approximately 2 milliliters (mL) will be collected for measurement of plasma concentrations of GSK2315698. | Pre-dose and 0.25, 1, 2, 4, 6, 8, 12, 24 hours post-dose in Cohort 1; Day 1 (pre-dose and 0.25, 1, 4, 12, 15, 18, 24 hours post-dose), and Days 5, 8, 14 in Cohort 2 |
| Maximum observed plasma concentration (Cmax) of GSK2315698 | Cmax will be calculated if data permit. | Pre-dose and 0.25, 1, 2, 4, 6, 8, 12, 24 hours post-dose in Cohort 1; Day 1 (pre-dose and 0.25, 1, 4, 12, 15, 18, 24 hours post-dose), and Days 5, 8, 14 in Cohort 2 |
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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 | Tokyo | 171-0014 | Japan |
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| ID | Term |
|---|---|
| D000686 | Amyloidosis |
| D000075363 | Immunoglobulin Light-chain Amyloidosis |
| ID | Term |
|---|---|
| D057165 | Proteostasis Deficiencies |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D054219 | Neoplasms, Plasma Cell |
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| ID | Term |
|---|---|
| C000709571 | miridesap |
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| GSK2315698 | Drug | 200 mg/mL stock solution for intravenous infusion over 1 hour (in Cohort 1) or over 15 hours (in Cohort 2). The stock solution will be diluted to obtain dosage levels of 10 mg/hr, 20 mg/hr, or 40 mg/hr. |
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| Area under the concentration-time curve from pre-dose to 24 hours (AUC0-24) of GSK2315698 | AUC0-24 will be calculated if data permit. | Pre-dose and 0.25, 1, 2, 4, 6, 8, 12, 24 hours post-dose in Cohort 1; Day 1 (pre-dose and 0.25, 1, 4, 12, 15, 18, 24 hours post-dose), and Days 5, 8, 14 in Cohort 2 |
| Time to maximum observed plasma drug concentration (Tmax) of GSK2315698 | Tmax will be calculated if data permit. | Pre-dose and 0.25, 1, 2, 4, 6, 8, 12, 24 hours post-dose in Cohort 1; Day 1 (pre-dose and 0.25, 1, 4, 12, 15, 18, 24 hours post-dose), and Days 5, 8, 14 in Cohort 2 |
| Cohort 2: Plasma concentration of GSK2315698 at 15 hours (C15hr) | C15hr will be calculated if data permit. | Pre-dose and 0.25, 1, 4, 12, and 15 hours post-dose in Cohort 2 |
| Change from Baseline in blood concentration of serum amyloid P component (SAP) | Venous blood samples of approximately 2 mL will be collected for measurement of SAP. | Day 1 (pre-dose and 0.25, 1, 2, 4, 6, 8, 12, 24 hours post-dose), Day 5, and Day 8 in Cohort 1; Day 1 (pre-dose and 0.25, 1, 4, 12, 15, 18, 24 hours post-dose), and Days 5, 8, 14 in Cohort 2 |
| Minimum blood concentration (Cmin) of SAP | Cmin will be calculated if data permit. | Day 1 (pre-dose and 0.25, 1, 2, 4, 6, 8, 12, 24 hours post-dose), Day 5, and Day 8 in Cohort 1; Day 1 (pre-dose and 0.25, 1, 4, 12, 15, 18, 24 hours post-dose), and Days 5, 8, 14 in Cohort 2 |
| Time to minimum observed concentration (Tmin) of SAP | Tmin will be calculated if data permit. | Day 1 (pre-dose and 0.25, 1, 2, 4, 6, 8, 12, 24 hours post-dose), Day 5, and Day 8 in Cohort 1; Day 1 (pre-dose and 0.25, 1, 4, 12, 15, 18, 24 hours post-dose), and Days 5, 8, 14 in Cohort 2 |
| Cohort 2: Concentration of SAP at 15 hours (C15hr) | C15hr will be calculated if data permit. | Pre-dose and 0.25, 1, 4, 12, and 15 hours post-dose in Cohort 2 |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008232 | Lymphoproliferative Disorders |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D010265 | Paraproteinemias |