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

NCT02737007 | Completed Phase 1

• 1 other identifier: 204853
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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

Keywords

Malaria; Microdose; GSK3191607

Outcome Measures

Primary Outcomes (13)

• Maximum observed concentration (Cmax) of GSK3191607 in plasma following a single intravenous (IV) microdose

  Pre-dose; and 0.25, 0.75, 1.5, 3, 6, 8, 12, 16, 24, 48, 72, 96, 120, 168, 216, 264, 312, and 336 hours following start of infusion

• Terminal phase half life (t1/2) of GSK3191607 following a single IV microdose

  Pre-dose; and 0.25, 0.75, 1.5, 3, 6, 8, 12, 16, 24, 48, 72, 96, 120, 168, 216, 264, 312, and 336 hours following start of infusion

• Time of occurrence of Cmax (tmax) of GSK3191607 following a single IV microdose

  Pre-dose; and 0.25, 0.75, 1.5, 3, 6, 8, 12, 16, 24, 48, 72, 96, 120, 168, 216, 264, 312, and 336 hours following start of infusion

• AUC(0-t) of GSK3191607 following a single IV microdose

  AUC(0-t) is the area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration.

  Pre-dose; and 0.25, 0.75, 1.5, 3, 6, 8, 12, 16, 24, 48, 72, 96, 120, 168, 216, 264, 312, and 336 hours following start of infusion

• AUC(0-infinity) of GSK3191607 following a single IV microdose

  AUC(0-infinity) is the area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time.

  Pre-dose; and 0.25, 0.75, 1.5, 3, 6, 8, 12, 16, 24, 48, 72, 96, 120, 168, 216, 264, 312, and 336 hours following start of infusion

• Systemic clearance (CL) of GSK3191607 following a single IV microdose

  Pre-dose; and 0.25, 0.75, 1.5, 3, 6, 8, 12, 16, 24, 48, 72, 96, 120, 168, 216, 264, 312, and 336 hours following start of infusion

• GSK3191607 volume of distribution at steady state (Vss)

  Pre-dose; and 0.25, 0.75, 1.5, 3, 6, 8, 12, 16, 24, 48, 72, 96, 120, 168, 216, 264, 312, and 336 hours following start of infusion

• Cmax of radioactive drug-related material (RDM) in plasma following a single IV microdose of [14C]-GSK3191607

  RDM is a measure of total radioactivity. Cmax of RDM will be compared with that of the parent drug (GSK3191607).

  Pre-dose; and 0.25, 0.75, 1.5, 3, 6, 8, 12, 16, 24, 48, 72, 96, 120, 168, 216, 264, 312, and 336 hours following start of infusion

• T1/2 of RDM following a single IV microdose of [14C]-GSK3191607

  T1/2 of RDM will be compared with that of the parent drug.

  Pre-dose; and 0.25, 0.75, 1.5, 3, 6, 8, 12, 16, 24, 48, 72, 96, 120, 168, 216, 264, 312, and 336 hours following start of infusion

• Tmax of RDM following a single IV microdose of [14C]-GSK3191607

  Tmax of RDM will be compared with that of the parent drug.

  Pre-dose; and 0.25, 0.75, 1.5, 3, 6, 8, 12, 16, 24, 48, 72, 96, 120, 168, 216, 264, 312, and 336 hours following start of infusion

• AUC(0-t) of RDM following a single IV microdose of [14C]-GSK3191607

  AUC(0-t) of RDM will be compared with that of the parent drug.

  Pre-dose; and 0.25, 0.75, 1.5, 3, 6, 8, 12, 16, 24, 48, 72, 96, 120, 168, 216, 264, 312, and 336 hours following start of infusion

• AUC(0-infinity) of RDM following a single IV microdose of [14C]-GSK3191607

  AUC(0-infinity) of RDM will be compared with that of the parent drug.

  Pre-dose; and 0.25, 0.75, 1.5, 3, 6, 8, 12, 16, 24, 48, 72, 96, 120, 168, 216, 264, 312, and 336 hours following start of infusion

• Amount of RDM excreted in urine (Ae) following a single IV microdose of [14C]-GSK3191607

  Subjects will be asked to void their bladders before study treatment administration. A blank urine sample will be collected pre-dose.

  Pre-dose; and 0-24 hours and 24-48 hours after the start of infusion

Secondary Outcomes (9)

• Whole-Blood:Plasma ratio of Cmax of RDM following a single IV microdose of [14C]-GSK3191607

  Pre-dose; and 0.25, 0.75, 1.5, 3, 6, 8, 12, 16, 24, 48, 72, 96, 120, 168, 216, 264, 312, and 336 hours following start of infusion

• Whole-Blood:Plasma ratio of tmax of RDM following a single IV microdose of [14C]-GSK3191607

  Pre-dose; and 0.25, 0.75, 1.5, 3, 6, 8, 12, 16, 24, 48, 72, 96, 120, 168, 216, 264, 312, and 336 hours following start of infusion

• Whole-Blood:Plasma ratio of t1/2 of RDM following a single IV microdose of [14C]-GSK3191607

  Pre-dose; and 0.25, 0.75, 1.5, 3, 6, 8, 12, 16, 24, 48, 72, 96, 120, 168, 216, 264, 312, and 336 hours following start of infusion

• Whole-Blood:Plasma ratio of AUC(0-t) of RDM following a single IV microdose of [14C]-GSK3191607

  Pre-dose; and 0.25, 0.75, 1.5, 3, 6, 8, 12, 16, 24, 48, 72, 96, 120, 168, 216, 264, 312, and 336 hours following start of infusion

• Whole-Blood:Plasma ratio of AUC(0-infinity) of RDM following a single IV microdose of [14C]-GSK3191607

  Pre-dose; and 0.25, 0.75, 1.5, 3, 6, 8, 12, 16, 24, 48, 72, 96, 120, 168, 216, 264, 312, and 336 hours following start of infusion

Study Arms (1)

[14C]-GSK3191607 IV Microdose

EXPERIMENTAL

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.

Drug: [14C]-GSK3191607

Interventions

[14C]-GSK3191607 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.

[14C]-GSK3191607 IV Microdose

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead
• Hammersmith Medicines Research: collaborator

Study Sites (1)

GSK Investigational Site

London, NW10 7EW, United Kingdom

Location

Related Links

• Results for study 204853 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Malaria, Falciparum; Malaria

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 31, 2016
• First Posted: April 13, 2016
• Study Start: April 18, 2016
• Primary Completion: May 12, 2016
• Study Completion: May 12, 2016
• Last Updated: September 13, 2018

Record last verified: 2018-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

GB (1)