Pharmacokinetics and Metabolism of 14 Carbon [14C]-GSK3640254

NCT ID: NCT04507321

Last Updated: 2022-01-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 5 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-24
• Study Completion Date: 2020-11-23

Brief Summary

This is an open-label, single-center, single group, non-randomized, two-period, single sequence, mass balance study which will enroll 6 healthy male participants. This study will assess the pharmacokinetics, balance/excretion, and metabolism of GSK3640254 in humans using [14C]-radiolabeled drug substance administered as an intravenous (IV) infusion and via the oral route. The study will also provide an assessment of GSK3640254 absorption, metabolism and excretion following administration of a [14C]-radiolabeled oral suspension. Each participant will be involved in the study for up to 10 weeks which will include a screening period, two treatment periods (treatment Periods 1 and 2) separated by a washout of at least 13 days between oral doses, and a follow-up visit 7-14 days after the last assessment in treatment Period 2.

Conditions

HIV Infections

Study Design

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

Study Groups

GSK3640254 tablet + [14C]-GSK3640254 IV/[14C] oral suspension

Participants will receive a single oral dose of GSK3640254 200 milligram (mg) (2×100 mg) tablets with a moderate fat meal. Participants will then be administered a 100 microgram (mcg) dose (approximately 3.7 kilobecquerel; 100 nano Curie) of \[14C\]-GSK3640254 as an IV infusion for 1 hour on Day 1 in treatment Period 1, On Day 1 in treatment Period 2, participants will receive a single oral dose of 85 mg (approximately 3.15 megabecquerel; 85 micro Curie) \[14C\]-GSK3640254 administered as an oral suspension with a moderate fat meal. A wash out period of at least 13 days will be maintained between oral doses of treatment periods.

Group Type: EXPERIMENTAL

GSK3640254 Oral tablet

Intervention Type: DRUG

GSK3640254 will be available as white film-coated round tablets to be administered via oral route with meal in the morning with 240 milliliter (mL) of water at room temperature.

[14C]-GSK3640254 intravenous infusion

Intervention Type: DRUG

\[14C\]-GSK3640254 will be available as clear, colorless solution free from visible particulates to be administered via the IV route.

[14C]-GSK3640254 powder

Intervention Type: DRUG

\[14C\]-GSK3640254 will be available as white powder to be reconstituted into a suspension with 25 mL of vehicle before dosing so as to administer 85 mg dose with meal in the morning.

Interventions

GSK3640254 Oral tablet

GSK3640254 will be available as white film-coated round tablets to be administered via oral route with meal in the morning with 240 milliliter (mL) of water at room temperature.

Intervention Type: DRUG

[14C]-GSK3640254 intravenous infusion

\[14C\]-GSK3640254 will be available as clear, colorless solution free from visible particulates to be administered via the IV route.

Intervention Type: DRUG

[14C]-GSK3640254 powder

\[14C\]-GSK3640254 will be available as white powder to be reconstituted into a suspension with 25 mL of vehicle before dosing so as to administer 85 mg dose with meal in the morning.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Participant must be 30 to 50 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, vital signs and ECG. A participant with a clinical abnormality or laboratory parameter (i.e. outside the reference range for the population being studied), which is not specifically listed in the eligibility criteria, may be included only if the investigator agrees and documents that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
• History of regular bowel movements (averaging one or more bowel movements per day).
• Non-smoker, or ex-smoker who hasn't regularly smoked for the 6 months before Screening.
• Body weight of 50 kilograms (kg) and above, and body mass index (BMI) within the range 19.0 to 31.0 kg/square meter (m^2) (inclusive).
• Male participants are eligible to participate if they agree to the following during the study, including washout periods: Refrain from donating sperm and either a) be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent or b) Agree to use a male condom when having penile-vaginal intercourse with a woman of childbearing potential unless vasectomized.
• Capable of giving signed informed consent.

Exclusion Criteria

• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). Participants with a history of cholecystectomy must be excluded.
• Significant history of or current 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 intervention; or interfering with the interpretation of data.
• Any clinically relevant abnormality identified at the Screening medical assessment (physical examination/medical history) clinical laboratory tests, or 12-lead ECG.
• Current episode, recent history, or chronic history of diarrhea.
• Lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years.
• Any history of significant underlying psychiatric disorder, including, but not limited to, schizophrenia, bipolar disorder with or without psychotic symptoms, other psychotic disorders, or schizotypal (personality) disorder.
• Any history of major depressive disorder with or without suicidal features, or anxiety disorders that required medical intervention (pharmacologic or not) such as hospitalization or other inpatient treatment and/or chronic (>6 months) outpatient treatment. Participants with other conditions such as adjustment disorder or dysthymia that have required shorter term medical therapy (<6 months) without inpatient treatment and are currently well-controlled clinically or resolved may be considered for entry after discussion and agreement with the ViiV Healthcare (VH)/GlaxoSmithKline (GSK) Medical Monitor.
• Any pre-existing physical or other psychiatric condition (including alcohol or drug abuse), which, in the opinion of the investigator (with or without psychiatric evaluation), could interfere with the participant's ability to comply with the dosing schedule and protocol.
• Regular use of known drugs of abuse or history of drug abuse or dependence within 6 months of the study.
• Regular alcohol consumption within 6 months prior to the study defined as an average weekly intake of >21 units. One unit is equivalent to 8 grams of alcohol: a glass (equivalent to [~]240 mL) of beer, 1 small glass (~100 mL) of wine or 1 (~25 mL) measure of spirits.
• History of or regular use of tobacco- or nicotine-containing products in the 3 months prior to Screening.
• Medical history of cardiac arrhythmias, prior myocardial infarction in the past 3 months, or cardiac disease or a family or personal history of long QT syndrome.
• QT duration corrected for heart rate by Fridericia's formula (QTcF) >450 milliseconds (msec).
• At Screening or prior to the first dose, a supine blood pressure (BP) that is persistently higher than 140/90 millimeters of mercury (mmHg).
• At Screening or prior to the first dose, a supine mean heart rate (HR) outside the range of 50 to 100 beats per minute (bpm). A heart rate from 100 to 110 bpm can be rechecked by ECG or vital signs within 30 minutes to verify eligibility.
• A participant with known or suspected active COVID-19 infection OR contact with an individual with known COVID-19, within 14 days of study enrollment.
• Past or intended use of over-the-counter or prescription medication, including analgesics (example [e.g], paracetamol), herbal medications, or grapefruit and Seville orange juices within 14 days prior to the first dose of study intervention until completion of the follow-up visit unless approved by the Investigator in conjunction with a VH/GSK Medical monitor.
• Treatment with any vaccine within 30 days prior to receiving study intervention.
• Current enrollment in a clinical trial; recent participation in a clinical trial and has received an investigational product within 3 months before the first dose in the current study.
• Exposure to more than 4 new chemical entities within 12 months before the first dose in the current study.
• Participation in a clinical trial involving administration of 14C-labelled compound(s) within the last 12 months. A participant's previous effective dose will be reviewed by the medical investigator to ensure there is no risk of contamination/carryover into the current study.
• Received a total body radiation dose of greater than 10.0 millisievert (mSv) (upper limit of International Commission on Radiological Protection [ICRP] category II) or exposure to significant radiation (e.g., serial x-ray or computed tomography [CT] scans, barium meal, etc.) in the 3 years before this study.
• Alanine transaminase (ALT) >=1.5 times upper limit of normal (ULN). A single repeat of ALT is allowed within a single Screening period to determine eligibility.
• Bilirubin >=1.5 times ULN (isolated bilirubin >=1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin <35 percent (%). A single repeat of any laboratory abnormality is allowed within a single Screening period to determine eligibility.
• Presence of Hepatitis B surface antigen (HBsAg) at Screening or positive Hepatitis C antibody test result at Screening or within 3 months before the first dose of study intervention and positive on reflex to hepatitis C ribonucleic acid (RNA).
• Positive HIV-1 and -2 antigen/antibody immunoassay at Screening.
• Any positive (abnormal) response confirmed by the investigator or qualified designee-administered Columbia-Suicide Severity Rating Scale (C-SSRS).
• Any Grade 2 to 4 laboratory abnormality at Screening, with the exception of creatine phosphokinase (CPK) and lipid abnormalities (e.g., total cholesterol, triglycerides), and ALT (described above), will exclude a participant from the study unless the investigator can provide a compelling explanation for the laboratory result(s) and has the assent of the sponsor. A single repeat of any laboratory abnormality (other than a viral Screening test for HIV-1/2, hepatitis B Virus [HBV], or hepatitis C Virus [HCV]) is allowed within a single Screening period to determine eligibility.
• Any significant arrhythmia or ECG finding (e.g., prior myocardial infarction in the past 3 months, symptomatic bradycardia, non-sustained or sustained atrial arrhythmias, non-sustained or sustained ventricular tachycardia, second-degree atrioventricular block Mobitz Type II, third-degree atrioventricular block, complete heart block, or conduction abnormality) which, in the opinion of the investigator or VH/GSK Medical Monitor, will interfere with the safety for the individual participant. Any acute laboratory abnormality at Screening which, in the opinion of the investigator, should preclude participation in the study of an investigational compound.
• Has had an occupation which requires monitoring for radiation exposure, nuclear medicine procedures, or excessive x-rays within the past 3 years.
• Loss of more than 400 mL blood during the 3 months before Screening, e.g., as a blood donor, or plan to donate blood or blood products in the 3 months after the end of the trial.
• Unwillingness or inability to follow the procedures outlined in the protocol, including the use of the string bile collection device.
• History of sensitivity to GSK3640254, or their components thereof, or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

ViiV Healthcare

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

ViiV Healthcare

Locations

GSK Investigational Site

London, , United Kingdom

Countries

United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2019-004444-30

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

213051

Identifier Type: -

Identifier Source: org_study_id