Amyloidosis
Conditions
Keywords
GSK2315698, Dose-ascending, Systemic amyloidosis
Brief summary
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.
Interventions
DRUGPlacebo
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).
DRUGGSK2315698
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.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
20 Years to 64 Years
Healthy volunteers
Yes
Inclusion criteria
* Participant must be 20 to 64 years of age inclusive, at the time of signing the informed consent * Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring. A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or
Exclusion criteria
, outside the reference range for the population being studied may be included only if the investigator in consultation with the Medical Monitor if required agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures * Peripheral veins suitable for venous blood sampling and cannulation * Body weight \>=50 kilograms (kg) and body mass index (BMI) within the range 18.5-24.9 kg per meter (m) squared (inclusive) * Male: A Japanese male participant must agree to use contraception during the treatment period and until follow up visit * Capable of giving signed informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Over a maximum period of approximately 59 days | Abnormalities will be assessed in laboratory parameters of hematology, clinical chemistry, and routine urinalysis. |
| Number of subjects with abnormalities in vital sign parameters | Over a maximum period of approximately 59 days | 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. |
| Number of subjects with electrocardiogram (ECG) abnormalities | Over a maximum period of approximately 59 days | 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. |
| Plasma concentration 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 | Whole blood samples of approximately 2 milliliters (mL) will be collected for measurement of plasma concentrations of GSK2315698. |
| Maximum observed plasma concentration (Cmax) 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 | Cmax will be calculated if data permit. |
| Area under the concentration-time curve from pre-dose to 24 hours (AUC0-24) 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 | AUC0-24 will be calculated if data permit. |
| Time to maximum observed plasma drug concentration (Tmax) 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 | Tmax will be calculated if data permit. |
| Cohort 2: Plasma concentration of GSK2315698 at 15 hours (C15hr) | Pre-dose and 0.25, 1, 4, 12, and 15 hours post-dose in Cohort 2 | C15hr will be calculated if data permit. |
| Change from Baseline in blood concentration of serum amyloid P component (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 | Venous blood samples of approximately 2 mL will be collected for measurement of SAP. |
| Minimum blood concentration (Cmin) 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 | Cmin will be calculated if data permit. |
| Time to minimum observed concentration (Tmin) 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 | Tmin will be calculated if data permit. |
| Cohort 2: Concentration of SAP at 15 hours (C15hr) | Pre-dose and 0.25, 1, 4, 12, and 15 hours post-dose in Cohort 2 | C15hr will be calculated if data permit. |
Countries
Japan
Outcome results
None listed