Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT02953808
Other study ID # 205911
Secondary ID
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
Health authority
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

Study Design


Related Conditions & MeSH terms


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
See also
  Status Clinical Trial Phase
Recruiting NCT04893889 - Substudy (NCT04456582): Noninvasive Assessment of Myocardial Stiffness by 2D-SWE Ultrasound Technique (Two-dimensional Shear Wave Elastography) in Patients With Amyloidosis and Fabry Disease. N/A
Withdrawn NCT04943302 - Isatuximab and Bendamustine in Systemic Light Chain Amyloidosis Phase 2
Active, not recruiting NCT02909036 - Study of Captisol Enabled Melphalan and Pharmacokinetics for Patients With Multiple Myeloma or Light Chain Amyloidosis That Are Receiving an Autologous Transplant. Phase 1
Completed NCT02816476 - Daratumumab Therapy for Patients With Refractory or Relapsed AL Amyloidosis Phase 2
Completed NCT01083316 - Bortezomib and Dexamethasone Followed by High-Dose Melphalan and Stem Cell Transplantation for Primary (AL) Amyloidosis Phase 2
Completed NCT01527032 - Risk-adapted Therapy for Primary Systemic (AL) Amyloidosis Phase 2
Completed NCT02545907 - A Dose Escalation Study of Carfilzomib Taken With Thalidomide and Dexamethasone in Relapsed AL Amyloidosis Phase 1/Phase 2
Recruiting NCT05263817 - A Clinical Study of CD19/BCMA CAR-T Cells in the Treatment of Refractory POEMS Syndrome, Amyloidosis, Autoimmune Hemolytic Anemia, and Vasculitis Early Phase 1
Active, not recruiting NCT03201965 - A Study to Evaluate the Efficacy and Safety of Daratumumab in Combination With Cyclophosphamide, Bortezomib and Dexamethasone (CyBorD) Compared to CyBorD Alone in Newly Diagnosed Systemic Amyloid Light-chain (AL) Amyloidosis Phase 3
Withdrawn NCT02589860 - Analysis of Oral Mucositis in Patient's Undergoing Melphalan Conditioning and Autologous Stem Cell Transplant
Recruiting NCT05635266 - Tissue Repository Providing Annotated Biospecimens for Approved Investigator-directed Biomedical Research Initiatives
Completed NCT02574676 - Quality of Life (QOL) Registry for Patients With AL Amyloidosis
Active, not recruiting NCT02260466 - Prevalence and Post-surgical Outcomes of CARdiac Wild-type TransthyrEtin amyloidoSIs in Elderly Patients With Aortic steNosis Referred for Valvular Replacement. N/A
Withdrawn NCT02462213 - Prospective Identification of Cardiac Amyloidosis by Cardiac Magnetic Resonance Imaging N/A
Recruiting NCT05577819 - Prevalence and Prediction of ATTR in Ambulatory Patients With HFpEF N/A
Completed NCT01406314 - SAP Depleter Dose Assessment Study in Patients Phase 1
Not yet recruiting NCT04985734 - Transthyretin Amyloidosis Cardiomyopathy (ATTR-CM) in Patients With Idiopathic Peripheral Neuropathy N/A
Active, not recruiting NCT03584022 - Clinical Trial to Assess the Safety of a Novel Scaffold Biomaterial N/A
Active, not recruiting NCT05199337 - Phase 1/2 Study of ZN-d5 for the Treatment of Relapsed or Refractory Light Chain (AL) Amyloidosis Phase 1/Phase 2
Active, not recruiting NCT05235269 - A Study to Evaluate Organ Level Uptake Repeatability of 124I AT-01 in Subjects With Systemic Amyloidosis Phase 2