Phase 1 Study of GSK2315698 in Healthy Japanese Subjects

Amyloidosis Clinical Trial

Official title:

A Single Centre, Double-blind, Randomised, Placebo-controlled, and Single Dose-ascending Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics, of Single Intravenous Doses of GSK2315698 in Healthy Japanese Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02953808
• Other study ID #: 205911
• Status: Completed
• Phase: Phase 1
• First received: November 1, 2016
• Last updated: January 18, 2017
• Start date: November 2016
• Est. completion date: December 2016

Study information

• Verified date: January 2017
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: December 2016
• Est. primary completion date: December 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 20 Years to 64 Years

Eligibility

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

Exclusion Criteria:

• History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study treatment; or interfering with the interpretation of data

• Clinically abnormal hypotonia or hyperpiesia as determined by the investigator

• Previous surgical procedures on the upper digestive tract including cholecystectomy (gallbladder removal), and/or cholelithotomy (gallstone removal)

• Alanine Aminotransferase (ALT) >1.5 multiplied by upper limit of normal (ULN)

• Bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%)

• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)

• QTcF >450 millisecond (msec) QTcF is either machine-read or manually over-read. The specific formula that will be used to determine eligibility and discontinuation for an individual subject should be determined prior to initiation of the study. In other words, several different formulae cannot be used to calculate the corrected QT interval (QTc) for an individual subject and then the lowest QTc value used to include or discontinue the subject from the trial. For purposes of data analysis, QTcF, another QT correction formula, or a composite of available values of QTc will be used

• Past or intended use of over-the-counter or prescription medication including herbal medications within 14 days prior to dosing. Specific study-defined medications may be allowed

• History of donation of blood or blood products >=400 mL within 3 months or >=200 mL within 1 month prior to screening

• Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day

• Current enrollment or past participation within the last 3 months, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer) before signing of consent in this or any other clinical study involving an investigational study treatment or any other type of medical research

• The subject is positive for Serological test for syphilis (Rapid plasma reagin test [RPR] and Treponema pallidum Latex Agglutination [TPLA]), Human immunodeficiency virus (HIV) antigen/antibody, Hepatitis B surface antigen (HbsAg), Hepatitis C virus (HCV) antibody, or Human T-cell lymphotropic virus type 1 (HTLV-1) antibody at screening

• Positive pre-study drug screen

• Regular use of known drugs of abuse

• Regular alcohol consumption within 6 months prior to the study defined as an average weekly intake of >14 units for males. One unit is equivalent to 350 mL of beer, 150 mL of wine or 45 mL of 80 proof distilled spirits

• Smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening; Sensitivity to any of the study treatments, or components thereof, or drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates participation in the study

Related Conditions & MeSH terms

• Amyloidosis

Intervention

Drug:
• Placebo
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).
• GSK2315698
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.

Locations

Country	Name	City	State
Japan	GSK Investigational Site	Tokyo

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of subjects with adverse events (AE) and serious adverse events (SAE)		Over a maximum period of approximately 29 days
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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