Effect of Therapeutic and Supratherapeutic Oral Doses of GSK3640254 on Cardiac Conduction Compared to Placebo and a Single Oral Dose of Moxifloxacin

NCT04563845 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 213053
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

This study will aim to evaluate the effect of therapeutic and supratherapeutic oral doses of GSK3640254 on cardiac conduction compared to placebo and a single oral dose of Moxifloxacin in healthy adult participants. The study has 2 parts: Part 1 will determine the supratherapeutic dose for Part 2, which will be the main corrected QT interval (QTc) study. Part 1 will evaluate once daily (QD) dosing of GSK3640254 or placebo and Part 2 will investigate the safety, tolerability and Pharmacokinetics (PK) of GSK3640254 doses on cardiac conduction as compared to placebo and a single oral dose of Moxifloxacin in healthy adult participants. Moxifloxacin will be included as a positive control.

Conditions

HIV Infections

Keywords

GSK3640254; Moxifloxacin; Electrocardiogram; Cardiac Conduction; Supratherapeutic dose

Outcome Measures

Primary Outcomes (41)

• Part 1: Area Under the Plasma Concentration-time Curve From Time Zero to Time t (AUC[0-t]) of GSK3640254

  Blood samples were collected at indicated time points. Pharmacokinetic (PK) analysis was conducted using standard non-compartmental methods.

  Pre-dose and 30 minutes, 1 Hour, 2 Hours, 3 Hours, 3 Hours 30 minutes, 4 Hours, 4 Hours 30 minutes, 5 Hours, 6 Hours, 12 Hours, 24 Hours, 48 Hours post-dose on Day 7

• Part 1: AUC From Time Zero to the End of the Dosing Interval at Steady State (AUC[0-tau]) of GSK3640254

  Blood samples were collected at indicated time points. PK analysis was conducted using standard non-compartmental methods.

  Pre-dose and 30 minutes, 1 Hour, 2 Hours, 3 Hours, 3 Hours 30 minutes, 4 Hours, 4 Hours 30 minutes, 5 Hours, 6 Hours, 12 Hours, 24 Hours, 48 Hours post-dose on Day 7

• Part 1: Maximum Observed Concentration (Cmax) of GSK3640254

  Blood samples were collected at indicated time points. PK analysis was conducted using standard non-compartmental methods.

  Pre-dose and 30 minutes, 1 Hour, 2 Hours, 3 Hours, 3 Hours 30 minutes, 4 Hours, 4 Hours 30 minutes, 5 Hours, 6 Hours, 12 Hours, 24 Hours, 48 Hours post-dose on Day 7

• Part 1: Plasma Concentration at the End of the Dosing Interval (Ctau) of GSK3640254

  Blood samples were collected at indicated time points. PK analysis was conducted using standard non-compartmental methods

  Pre-dose and 30 minutes, 1 Hour, 2 Hours, 3 Hours, 3 Hours 30 minutes, 4 Hours, 4 Hours 30 minutes, 5 Hours, 6 Hours, 12 Hours, 24 Hours, 48 Hours post-dose on Day 7

• Part 1: Time of Maximum Observed Concentration (Tmax) of GSK3640254

  Blood samples were collected at indicated time points. PK analysis was conducted using standard non-compartmental methods.

  Pre-dose and 30 minutes, 1 Hour, 2 Hours, 3 Hours, 3 Hours 30 minutes, 4 Hours, 4 Hours 30 minutes, 5 Hours, 6 Hours, 12 Hours, 24 Hours, 48 Hours post-dose on Day 7

• Part 1: Plasma Concentration of GSK3640254

  Blood samples were collected at indicated time points to analyze the plasma concentration of GSK3640254.

  Pre-dose and 30 minutes, 1 Hour, 2 Hour, 3 Hours, 3 Hours 30 minutes, 4 Hours, 4 Hours 30 minutes, 5 Hours, 6 Hours, 12 Hours, 24 Hours, 48 Hours post-dose on Day 7

• Part 1: Plasma Concentration of Major Metabolites of GSK3640254

  Blood samples were to be collected at indicated time points to analyze the plasma concentration of major metabolites of GSK3640254.

  Pre-dose and 30 minutes, 1 Hour, 2 Hour, 3 Hours, 3 Hours 30 minutes, 4 Hours, 4 Hours 30 minutes, 5 Hours, 6 Hours, 12 Hours, 24 Hours, 48 Hours post-dose on Day 7

• Part 1: Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs

  An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any untoward medical occurrence that, at any dose that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect as per medical and scientific judgment. Adverse events which were not Serious Adverse Events were considered as Non-Serious adverse events.

  Up to Day 9

• Part 1: Absolute Values for Hematology Parameter: Hemoglobin

  Blood samples were collected at indicated time points to analyze hemoglobin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  Baseline (Day -2), Day 3, Day 7, and Day 9

• Part 1: Absolute Values for Hematology Parameter: Hematocrit

  Blood samples were collected at indicated time points to analyze hematocrit. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  Baseline (Day -2), Day 3, Day 7, and Day 9

• Part 1: Absolute Values for Hematology Parameter: Erythrocytes Mean Corpuscular Volume

  Blood samples were collected at indicated time points to analyze erythrocytes mean corpuscular volume. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  Baseline (Day -2), Day 3, Day 7, and Day 9

• Part 1: Absolute Values for Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin

  Blood samples were collected at indicated time points to analyze erythrocytes mean corpuscular hemoglobin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  Baseline (Day -2), Day 3, Day 7, and Day 9

• Part 1: Absolute Values for Hematology Parameter: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes

  Blood samples were collected at indicated time points to analyze basophils, eosinophils, lymphocytes, monocytes, neutrophils, platelets and leukocytes. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. .

  Baseline (Day -2), Day 3, Day 7, and Day 9

• Part 1: Absolute Values for Hematology Parameter: Erythrocytes

  Blood samples were collected at indicated time points to analyze erythrocytes. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  Baseline (Day -2), Day 3, Day 7, and Day 9

• Part 1: Change From Baseline in Hematology Parameter: Hemoglobin

  Blood samples were collected at indicated time points to analyze hemoglobin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  Baseline (Day -2), Day 3, Day 7, and Day 9

• Part 1: Change From Baseline in Hematology Parameter: Hematocrit

  Blood samples were collected at indicated timepoints to analyze hemotocrit. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  Baseline (Day -2), Day 3, Day 7, and Day 9

• Part 1: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume

  Blood samples were collected at indicated time points to analyze erythrocytes mean corpuscular volume. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  Baseline (Day -2), Day 3, Day 7, and Day 9

• Part 1: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin

  Blood samples were collected at idicated time points to analyze erythrocytes mean corpuscular hemoglobin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  Baseline (Day -2), Day 3, Day 7, and Day 9

• Part 1: Change From Baseline in Hematology Parameter: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes

  Blood samples were collected at indicated time points to analyze basophils, eosinophils, lymphocytes, monocytes, neutrophils, platelets and leukocytes. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  Baseline (Day -2), Day 3, Day 7, and Day 9

• Part 1: Change From Baseline in Hematology Parameter: Erythrocytes

  Blood samples were collected at indicated time points to analyze the hematology parameter: Erythrocytes. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  Baseline (Day -2), Day 3, Day 7, and Day 9

• Part 1: Absolute Values for Chemistry Parameters: Glucose, Cholesterol, Magnesium, Triglycerides, Anion Gap, Calcium, Carbon Dioxide, Chloride, Phosphate, Potassium, Sodium, and Blood Urea Nitrogen

  Blood samples were collected at indicated time points to analyze glucose, cholesterol, magnesium, triglycerides, anion gap, calcium, carbon dioxide, chloride, phosphate, potassium, sodium, and blood urea nitrogen. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  Baseline (Day -2), Day 3, Day 7, and Day 9

• Part 1: Absolute Values for Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transferase (GGT), Creatine Kinase, and Lactate Dehydrogenase

  Blood samples were collected at indicated time points to analyze ALT, ALP, AST, GGT, creatine kinase, and lactate dehydrogenase. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  Baseline (Day -2), Day 3, Day 7, and Day 9

• Part 1: Absolute Values for Chemistry Parameters: Creatinine, Urate, Total Bilirubin, and Direct Bilirubin

  Blood samples were collected at indicated timepoints to analyze creatinine, urate, total bilirubin, and direct bilirubin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  Baseline (Day -2), Day 3, Day 7, Day 9

• Part 1: Absolute Values for Chemistry Parameters: Albumin, Globulin, and Total Protein

  Blood samples were collected at indicated timepoints to analyze albumin, globulin, and total protein. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  Baseline (Day -2), Day 3, Day 7, Day 9

• Part 1: Absolute Values for Chemistry Parameters: Amylase and Lipase

  Blood samples were collected at indicated timepoints to analyze amylase and lipase. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  Baseline (Day -2), Day 3, Day 7, and Day 9

• Part 1: Change From Baseline in Chemistry Parameters: Glucose, Cholesterol, Magnesium, Triglycerides, Anion Gap, Calcium, Carbon Dioxide, Chloride, Phosphate, Potassium, Sodium, Blood Urea Nitrogen

  Blood samples were collected at indicated time points to analyze glucose, cholesterol, magnesium, triglycerides, anion gap, calcium, carbon dioxide, chloride, phosphate, potassium, sodium, and blood urea nitrogen. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  Baseline (Day -2), Day 3, Day 7, and Day 9

• Part 1: Change From Baseline in Chemistry Parameters: ALT, ALP, AST, GGT, Creatine Kinase, Lactate Dehydrogenase

  Blood samples were collected at indicated time points to analyze ALT, ALP, AST, GGT, creatine kinase, and lactate dehydrogenase. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  Baseline (Day -2), Day 3, Day 7, and Day 9

• Part 1: Change From Baseline in Chemistry Parameters: Creatinine, Urate, Total Bilirubin, Direct Bilirubin

  Blood samples were collected at indicated timepoints to analyze creatinine, urate, total bilirubin, and direct bilirubin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  Baseline (Day -2), Day 3, Day 7, and Day 9

• Part 1: Change From Baseline in Chemistry Parameters: Albumin, Globulin, and Total Protein

  Blood samples were collected at indicated timepoints to analyze albumin, globulin, and total protein. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value

  Baseline (Day -2), Day 3, Day 7, and Day 9

• Part 1: Change From Baseline in Chemistry Parameters: Amylase and Lipase

  Blood samples were collected at indicated timepoints to analyze amylase and lipase. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  Baseline (Day -2), Day 3, Day 7, and Day 9

• Part 1: Absolute Values for Urinalysis Parameter: Specific Gravity

  Urine samples were collected at indicated time points to analyze the urine specific gravity. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  Baseline (Day -2), Day 3, Day 7, and Day 9

• Part 1: Absolute Values for Urinalysis Parameter: Potential of Hydrogen (pH)

  Urine samples were collected at indicated time points to analyze the urine pH by dipstick test. The dipstick test gives results in a semi-quantitative manner indicating proportional concentrations in the urine sample. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acidic pH (5.0 - 6.0). Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  Baseline (Day -2), Day 3, Day 7, and Day 9

• Part 1: Change From Baseline in Urinalysis Parameter: Specific Gravity

  Urine samples were collected at indicated time points to analyze the urine specific gravity. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  Baseline (Day -2), Day 3, Day 7, and Day 9

• Part 1: Change From Baseline in Urinalysis Parameter: pH

  Urine samples were collected at indicated time points to analyze the urine pH by dipstick test. The dipstick test gives results in a semi-quantitative manner indicating proportional concentrations in the urine sample. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acidic pH (5.0 - 6.0). Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  Baseline (Day -2), Day 3, Day 7, and Day 9

• Part 1: Number of Participants With Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) Findings

  A 12-lead ECG was recorded with the participant in a supine position. 12-lead ECGs were obtained by using an automated ECG machine. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Data for number of participants with clinically significant abnormal 12-Lead ECG findings has reported

  Baseline(Day-2), Day1: 2 Hours, 4 Hours, 6 Hours; Day 4: 2 Hours, 4 Hours, 6 Hours, Day 7: 2 Hours, 4 Hours, 6 Hours and Day 9

• Part 1: Absolute Values for Vital Parameters: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)

  SBP and DBP were measured in the semi-recumbent or supine position with a completely automated device after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  Baseline (Pre-dose, Day 1), Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8 and Day 9

• Part 1: Absolute Values for Vital Parameter: Pulse Rate

  Pulse rate was measured in the semi-recumbent or supine position with a completely automated device after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  Baseline (Pre-dose, Day 1), Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8 and Day 9

• Part 1: Absolute Values for Vital Parameter: Temperature

  Temperature was measured in the semi-recumbent or supine position with a completely automated device after at least 5 minutes of rest for the participant in a quiet setting without distractions.Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  Baseline (Pre-dose, Day 1), Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8 and Day 9

• Part 2: Placebo-corrected Change From Baseline in QT Interval Corrected for Heart Rate Using Fridericia's Formula (QTcF) Following Administration of GSK3640254 100 mg and GSK3640254 500 mg Using Concentration-QTc (C-QTc) Analysis

  Twelve-lead ECGs were recorded in participant using automated ECG machine \& performed with participant in supine position after a rest of at least 10 minutes.Baseline was defined as the latest pre-dose assessment with a non-missing value for each visit. Change from Baseline was calculated by subtracting Baseline value from post dose value. Placebo-corrected change from Baseline in QT interval corrected for heart rate using Fridericia's formula (QTcF) was calculated as difference in model-predicted mean change from Baseline in QTcF between treatment groups using C-QTc analysis. A linear mixed-effects model with change from Baseline in QTcF as the dependent variable, time-matched GSK3640254 plasma concentration as a fixed effect, centered Baseline as additional covariate,treatment \&time as categorical factors, \& a random intercept \& slope per participant. In all calculations, concentrations in participants who received placebo were set to 0.

  Baseline (Pre-dose, Day 1) and up to Day 7

• Part 2: Plasma Concentration of GSK3640254

  Blood samples were collected at indicated time points to analyze the plasma concentration of GSK3640254.

  Pre-dose and 30 minutes, 1 Hour, 2 Hour, 3 Hours, 3 Hours 30 minutes, 4 Hours, 4 Hours 30 minutes, 5 Hours, 6 Hours, 8 Hours, 10 Hours, 12 Hours, 24 Hours post-dose on Day 7 in each treatment period

• Part 2: Plasma Concentration of Major Metabolites of GSK3640254

  Blood samples were to be collected at indicated time points to analyze the plasma concentration of major metabolites of GSK3640254.

  Pre-dose and 30 minutes, 1 Hour, 2 Hour, 3 Hours, 3 Hours 30 minutes, 4 Hours, 4 Hours 30 minutes, 5 Hours, 6 Hours, 8 Hours, 10 Hours, 12 Hours, 24 Hours post-dose on Day 7 in each treatment period

Secondary Outcomes (49)

• Part 2: Change From Baseline in Heart Rate (HR) - For GSK3640254 100 mg, GSK3640254 500 mg and Placebo Arms

  Baseline (Pre-dose, Day 1), Day 7 : Predose and 0.5, 1, 2, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 24 Hours post dose

• Part 2: Change From Baseline in QT Interval Corrected for Heart Rate Using Fridericia's Formula (QTcF) - For GSK3640254 100 mg, GSK3640254 500 mg and Placebo Arms

  Baseline (Pre-dose, Day 1), Day 7: Predose and 0.5, 1, 2, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 24 Hours post dose

• Part 2: Change From Baseline in PR Interval - For GSK3640254 100 mg, GSK3640254 500 mg and Placebo Arms

  Baseline (Pre-dose, Day 1), Day 7: Predose and 0.5, 1, 2, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 24 Hours post dose

• Part 2: Change From Baseline in QRS Interval - For GSK3640254 100 mg, GSK3640254 500 mg and Placebo Arms

  Baseline (Pre-dose, Day 1), Day 7 : Predose and 0.5, 1, 2, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 24 Hours post dose

• Part 2: Placebo-corrected Change From Baseline in QT Interval Corrected for Heart Rate Using Fridericia's Formula (QTcF) Following Administration of GSK3640254 100 mg and GSK3640254 500 mg By-time Point Analysis

  Baseline (Pre-dose, Day 1), Day 7 : Predose and 0.5, 1, 2, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 24 Hours post dose

Other Outcomes (1)

• Part 2: Change From Baseline in QTcF - For Placebo and Moxifloxacin Arm

  Baseline (Pre-dose, Day 1), Day 7: Predose and 0.5, 1, 2, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 24 Hours post dose

Study Arms (3)

Part 1: Participants receiving placebo

PLACEBO COMPARATOR

Participants will receive a single dose of placebo once daily for 7 days following ingestion of a moderate fat meal.

Drug: GSK3640254; Drug: Placebo

Part 1: Participants receiving GSK3640254 500 milligrams (mg)

EXPERIMENTAL

Participants will receive a single dose of GSK3640254 500 mg once daily for 7 days following ingestion of a moderate fat meal.

Drug: GSK3640254

Part 2: Main QTc Study

EXPERIMENTAL

Participants will be randomized to 1:1:1:1 ratio to receive Treatment T- Therapeutic dose of GSK3640254 (100 mg QD) on Days 1 through 7 or Treatment ST- Supratherapeutic dose of GSK3640254 (to be determined from Part 1) on Days 1 through 7 or Treatment P- Placebo for GSK3640254 on Days 1 through 7 or Treatment M- Moxifloxacin (GSK3640254 placebo Days 1 through 6 and a single dose of Moxifloxacin \[400 mg\] on Day 7 in 4 treatment periods. There will be at least 7 days wash out period between each period.

Drug: GSK3640254; Drug: Placebo; Drug: Moxifloxacin

Interventions

GSK3640254 DRUG

GSK3640254 will be administered.

Part 1: Participants receiving GSK3640254 500 milligrams (mg); Part 1: Participants receiving placebo; Part 2: Main QTc Study

Placebo DRUG

Placebo will be administered.

Part 1: Participants receiving placebo; Part 2: Main QTc Study

Moxifloxacin DRUG

Moxifloxacin will be administered.

Part 2: Main QTc Study

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Participant must be 18 to 50 years of age inclusive, at the time of signing the informed consent.
• Participants who are healthy as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination (including cardiopulmonary examination), laboratory tests, and cardiac monitoring (history and ECG).
• Body weight more than or equal to (\>=)50.0 kilograms (kg) (110 pounds \[lbs\]) for men and \>=45.0 kg (99 lbs) for women and body mass index within the range 18.5 to 31.0 kilograms per square meter (kg/m\^2) (inclusive).
• Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• Male or female participants:
• Male participants should not engage in intercourse while confined in the clinic. There is no need for an extended period of double barrier use or prolonged abstinence after study discharge.
• Female participants:
• (i) A female participant is eligible to participate if she is not pregnant, planning to become pregnant within the next 6 months, or breastfeeding, and at least 1 of the following conditions applies: Is not a woman of childbearing potential (WOCBP) OR Is a WOCBP and using a non-hormonal contraceptive method that is highly effective, with a failure rate of less than (\<)1 percent (%) for 28 days before intervention, during the intervention period, and for at least 28 days after the last dose of study intervention. The investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention.
• (ii) A WOCBP must have a negative highly sensitive serum pregnancy test at Screening and Check-in.
• Capable of giving signed informed, which includes compliance with the requirements and restrictions listed in the Informed Consent Form (ICF) and in this protocol.

You may not qualify if:

• Participants with current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• A pre-existing condition interfering with normal Gastrointestinal (GI) anatomy or motility (for example \[e.g.\], gastro-esophageal reflux disease, gastric ulcers, gastritis), hepatic and/or renal function, that could interfere with the absorption, metabolism, and/or excretion of the study intervention or render the participant unable to take oral study intervention.
• Prior cholecystectomy (prior appendectomy is acceptable).
• Clinically significant illness, including viral syndromes, within 3 weeks of dosing.
• A participant with known or suspected active Coronavirus Disease-2019 (COVID-19) infection OR contact with an individual with known COVID-19, within 14 days of study enrollment (World Health Organization \[WHO\] definitions).
• 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 (more than \[\>\]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/GlaxoSmithKline (VH/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 evaluations or which might compromise the safety of the participant.
• 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.
• History indicative of an increased risk of a cardiac arrhythmia or cardiac disease, including the following:
• History of symptomatic cardiac arrhythmias or palpitations associated with pre-syncope or syncope, or history of unexplained syncope.
• History of cardiac arrest.
• History of clinically relevant cardiac disease including symptomatic or asymptomatic arrhythmias (including but not limited to ventricular fibrillation, ventricular tachycardia, any degree of atrioventricular block, Brugada syndrome, Wolff-Parkinson-White Syndrome, and sinus bradycardia, defined as HR less than 50 bpm based on vital signs or ECG), presyncope or syncopal episodes, or additional risk factors for torsades de pointes (e.g., heart failure).
• History of clinically relevant structural cardiac disease including hypertrophic obstructive cardiomyopathy.
• History of hypokalemia.

Sponsors & Collaborators

• ViiV Healthcare: lead

Study Sites (1)

GSK Investigational Site

Austin, Texas, 78744, United States

Location

Related Publications (1)

• Zhang Y, Bush M, Yazdani P, Zhan J, Wen B, Bainbridge V, Wynne BR, Joshi S, Lataillade M. Effects of the HIV-1 maturation inhibitor GSK3640254 on QT interval in healthy participants. Pharmacol Res Perspect. 2023 Dec;11(6):e01151. doi: 10.1002/prp2.1151.

  PMID: 37961928 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

GSK3640254; Moxifloxacin

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: GSK Response Center
• Organization: ViiV Healthcare

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  ViiV Healthcare

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 18, 2020
• First Posted: September 25, 2020
• Study Start: November 9, 2020
• Primary Completion: October 30, 2021
• Study Completion: October 30, 2021
• Last Updated: December 6, 2023
• Results First Posted: December 6, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
• 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

US (1)