Phase 1 Study of GSK2315698 in Healthy Japanese Subjects

NCT ID: NCT02953808

Last Updated: 2017-01-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-11-30
• Study Completion Date: 2016-12-31

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.

Conditions

Amyloidosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Cohort 1 Group A

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.

Group Type: EXPERIMENTAL

Placebo

Intervention Type: 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).

GSK2315698

Intervention Type: 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.

Cohort 1 Group B

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.

Group Type: EXPERIMENTAL

Placebo

Intervention Type: 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).

GSK2315698

Intervention Type: 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.

Cohort 1 Group C

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.

Group Type: EXPERIMENTAL

Placebo

Intervention Type: 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).

GSK2315698

Intervention Type: 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.

Cohort 2 Group D

In a single dosing session, subjects will receive GSK2315698 20 mg/hr as intravenous infusion over 15 hours.

Group Type: EXPERIMENTAL

GSK2315698

Intervention Type: 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.

Cohort 2 Group E

In a single dosing session, subjects will receive Placebo as an intravenous infusion over 15 hours.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: 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).

Interventions

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).

Intervention Type: DRUG

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Participant must be 20 to 64 years of age inclusive, at the time of signing the informed consent

Exclusion Criteria

• 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

• 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

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 64 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Tokyo, , Japan

Countries

Japan

Other Identifiers

205911

Identifier Type: -

Identifier Source: org_study_id