A Microdose Study in Healthy Subjects to Describe Intravenous Pharmacokinetics of GSK3191607

NCT ID: NCT02737007

Last Updated: 2018-09-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-04-18
• Study Completion Date: 2016-05-12

Brief Summary

This is an open-label, single-centre, non-randomized study to investigate the pharmacokinetics of GSK3191607, administered as a single intravenous (IV) dose in healthy male subjects.

Six subjects will be administered an IV microdose of radio-labeled [14C]-GSK3191607. The study will provide an early readout on human pharmacokinetic parameters. The results of this study will be used to estimate the potential duration of anti-parasite effect in humans, define predicted clinical oral doses, and hence inform about the compound's potential safety margin.

Each subject will participate in the study for up to 8 weeks, and will have a screening visit, one treatment period, eight outpatient visits, and a follow-up visit.

Conditions

Malaria, Falciparum

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

[14C]-GSK3191607 IV Microdose

Subjects will receive a single microdose of 100 micrograms (mcg) of \[14C\]-GSK3191607 by intravenous infusion over 15 minutes on Day 1 of the study.

Group Type: EXPERIMENTAL

[14C]-GSK3191607

Intervention Type: DRUG

\[14C\]-GSK3191607 is a solution to be administered intravenously as a single dose infusion over 15 minutes. It is a radio-labeled product; 100 mcg of \[14C\]-GSK3191607 contains approximately 7.4 kilobecquerel (kBq) of \[14C\] radioactivity.

Interventions

[14C]-GSK3191607

\[14C\]-GSK3191607 is a solution to be administered intravenously as a single dose infusion over 15 minutes. It is a radio-labeled product; 100 mcg of \[14C\]-GSK3191607 contains approximately 7.4 kilobecquerel (kBq) of \[14C\] radioactivity.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Between 18 and 55 years of age inclusive, at the time of signing the informed consent.

Exclusion Criteria

• Body weight >= 50 kg and body mass index (BMI) within the range 19.0-31.0 kilograms per meter squared (kg/m^2) (inclusive).
• Male.
• Subjects with female partners of child bearing potential must use a condom from the time of first dose of study medication until follow-up.
• Capable of giving signed informed consent, which includes compliance with pre-defined requirements and restrictions.

• Alanine aminotransferase (ALT) and bilirubin >1.5 times upper limit of normal (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).
• Mean QT duration corrected for heart rate by Fridericia's formula (QTcF) > 450 milliseconds (msec).
• Any clinically relevant abnormality identified at the screening medical assessment (physical examination/medical history), clinical laboratory tests, or 12-lead electrocardiogram (ECG).
• At screening, a mean supine blood pressure (BP) that is higher (triplicate measurements at least 2 minutes apart) than 140/90 millimeters of mercury (mmHg).
• At screening, a supine mean pulse rate outside the range 40-90 beats per minute (BPM).
• Subject is mentally or legally incapacitated.
• Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) before the first dose of study medication, unless in the opinion of the investigator and GlaxoSmithKline (GSK) Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
• Smoking or use of tobacco products. Urinary cotinine levels indicative of use of tobacco products or nicotine-containing products.
• History of regular alcohol consumption within 6 months of the study, defined as an average weekly intake of >21 units. One unit is equivalent to 8 grams (g) of alcohol: a half pint (~240 milliliters [mL]) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
• History of sensitivity to any of the study medication or its components, or a history of drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates the subject's participation.
• Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test result at screening or within 3 months before first dose of study treatment.
• A positive pre-study drug/alcohol screen.
• A positive test for Human immunodeficiency virus (HIV).
• Participation in a clinical trial involving administration of 14C-labelled compound(s) within the last 12 months before dosing. A subject's previous effective dose will be reviewed by the medical investigator to ensure there is no risk of contamination/carryover into the current study.
• Subjects who have received a total body radiation dose of greater than 5.0 millisieverts (mSv) (upper limit of World Health Organization [WHO] category II) or exposure to significant radiation (for example, serial x ray or Computed Tomography (CT) scans, barium meal, etc.) in the 12 months before dosing.
• Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 90 day period.
• Unable to refrain from consumption of red wine, Seville oranges, grapefruit or grapefruit juice from 7 days before the first dose of study medication until the last study visit.
• The subject has participated in a clinical trial and has received an investigational product within the following time period before the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
• Exposure to more than four new chemical entities within 12 months before the first dosing day.
• An occupation which requires monitoring for radiation exposure, nuclear medicine procedures or excessive x-rays within the past 12 months before dosing.
• Unwillingness or inability to follow the procedures outlined in the protocol.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Hammersmith Medicines Research

OTHER

Sponsor Role: collaborator

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

London, , United Kingdom

Countries

United Kingdom

Other Identifiers

204853

Identifier Type: -

Identifier Source: org_study_id