Clinical trial NCT04128293: A Relative Bioavailability and Food-Effect Study of GSK3640254 Tablet and Capsule Formulations in Healthy Participants
Official title: A Randomized, Open-Label, Single Dose, Four-Period Crossover Clinical Trial to Assess the Relative Bioavailability of a Tablet Compared to a Capsule of GSK3640254 and to Assess the Effect of Food on the GSK3640254 Tablet in Healthy Participants
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: HIV Infections
Keywords: Healthy participants
GSK3640254
Human immunodeficiency virus (HIV)
Safety
Lead sponsor: ViiV Healthcare
Sponsor class: INDUSTRY
First posted: 2019-10-16
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Eligible participants will be randomly assigned to 1 of 4 treatment sequences (ABCD, BADC, CDAB, or DCBA) in each treatment period.
Primary purpose: TREATMENT

Brief summary: This is an open-label, single-dose, four-period, four sequential, and crossover study conducted to assess the relative bioavailability of GSK3640254 mesylate tablets and GSK3640254 mesylate capsules (in the presence of a moderate fat meal). This study will also evaluate the effect of food (fasted, moderate fat meal, and high fat meal) on the pharmacokinetics of GSK3640254 mesylate tablet formulation. Participants will be randomized to receive a single dose of GSK3640254 200 milligram (mg) capsules under moderate fat conditions and GSK3640254 200 mg tablets under moderate fat, fasted and high fat conditions in each treatment period. Approximately 16 participants will be enrolled and the duration of the study will be approximately 54 days.


Eligibility criteria: Inclusion Criteria

* Participant must be 18 to 55 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, laboratory tests, and cardiac monitoring (history and ECG).
* Body weight \>=50.0 kilogram (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 kg per square meter (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: Female participants: 1. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least 1 of the following conditions applies: a. not a woman of childbearing potential (WOCBP); or Is a WOCBP and using a nonhormonal contraceptive method that is highly effective, with a failure rate of \<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. 2. A WOCBP must have a negative highly sensitive serum pregnancy test at Screening and Day -1. 3. Additional requirements for pregnancy testing during and after study intervention.
* The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
* Capable of giving signed informed consent, which includes compliance with the requirements and restrictions.

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).
* A pre-existing condition interfering with normal gastrointestinal (GI) anatomy or motility (example \[e.g.\], gastroesophageal 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.
* 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 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.
* Presence of hepatitis B surface antigen at Screening or within 3 months prior to starting study intervention.
* Positive hepatitis C antibody test result at Screening or within 3 months prior to starting study intervention and positive on reflex to hepatitis C ribonucleic acid.
* Positive Human immunodeficiency virus-1 and -2 antigen/antibody immunoassay at Screening.
* ALT \>1.5 × upper limit of normal (ULN). A single repeat of ALT is allowed within a single Screening period to determine eligibility.
* Bilirubin \>1.5 x ULN (isolated bilirubin \>1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%). A single repeat of any laboratory abnormality is allowed within a single Screening period to determine eligibility.
* Any acute laboratory abnormality at Screening which, in the opinion of the investigator, should preclude participation in the study of an investigational compound.
* Any Grade 2 to 4 laboratory abnormality at Screening, with the exception of creatine phosphokinase and lipid abnormalities (e.g., total cholesterol, triglycerides), and ALT, 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 is allowed within a single Screening period to determine eligibility.
* A positive test result for drugs of abuse (including marijuana), alcohol, or cotinine (indicating active current smoking) at Screening or before the first dose of study intervention.
* Unable to refrain from the use of prescription or non-prescription drugs including vitamins, herbal and dietary supplements (including Saint John's wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study intervention and for the duration of the study.
* Treatment with any vaccine within 30 days prior to receiving study intervention.
* Unwillingness to abstain from excessive consumption of any food or drink containing grapefruit and grapefruit juice, Seville oranges, blood oranges, or pomelos or their fruit juices within 7 days prior to the first dose of study intervention(s) until the end of the study.
* Participation in another concurrent clinical study or prior clinical study (with the exception of imaging trials) prior to the first dosing day in the current study: 30 days, 5 half-lives, or twice the duration of the biological effect of the study intervention (whichever is longer).
* Where participation in the study would result in donation of blood or blood products in excess of 500 milliliter (mL) within 56 days.
* Any positive (abnormal) response confirmed by the investigator on a screening clinician- or qualified designee-administered Columbia Suicide Severity Rating Scale (C-SSRS).
* 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 Medical Monitor, will interfere with the safety for the individual participant.
* Exclusion criteria for Screening ECG (a single repeat is allowed for eligibility determination): Heart rate: male \<45 or \>100 beats per minute (bpm) and female \<50 or \>100 bpm, and QTcF interval: male \>450 millisecond (ms), female \>450 ms.
* History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of \>14 units. One unit is equivalent to 8 grams of alcohol: a half pint (\~240 mL) of beer, 1 glass (125 mL) of wine, or 1 (25 mL) measure of spirits.
* Unable to refrain from tobacco or nicotine-containing products within 3 months prior to Screening.
* History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates their participation.

Primary outcomes:
measure: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC[0-infinity]) for GSK3640254 200 mg Capsules and Tablets Under Fed Condition (Treatment A and B)
timeFrame: Pre-dose and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
measure: AUC(0-infinity) for GSK3640254 200 mg Tablets Under Fasted and High Fat Condition (Treatment C and D)
timeFrame: Pre-dose and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
measure: Area Under the Plasma Concentration-time Curve From Time Zero to Time t (AUC[0-t]) for GSK3640254 200 mg Capsules and Tablets Under Fed Condition (Treatment A and B)
timeFrame: Pre-dose and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
measure: AUC(0-t) for GSK3640254 200 mg Tablets Under Fasted and High Fat Condition (Treatment C and D)
timeFrame: Pre-dose and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
measure: Maximum Observed Concentration (Cmax) for GSK3640254 200 mg Capsules and Tablets Under Fed Condition (Treatment A and B)
timeFrame: Pre-dose and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
measure: Cmax for GSK3640254 200 mg Tablets Under Fasted and High Fat Condition (Treatment C and D)
timeFrame: Pre-dose and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
measure: Time of Cmax (Tmax) for GSK3640254 200 mg Capsules Under Fed Condition (Treatment A)
timeFrame: Pre-dose and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
measure: Time of Cmax (Tmax) for GSK3640254 200 mg Tablets Under Fed, Fasted and High Fat Condition (Treatment B, C and D)
timeFrame: Pre-dose and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
Secondary outcomes:
measure: Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Up to Day 14
measure: Absolute Values for Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet Count
timeFrame: Day 2
measure: Absolute Values for Hematology Parameter: Hemoglobin
timeFrame: Day 2
measure: Absolute Values for Hematology Parameter: Hematocrit
timeFrame: Day 2
measure: Absolute Values for Hematology Parameter: Erythrocytes
timeFrame: Day 2
measure: Absolute Values for Hematology Parameter: Erythrocytes Mean Corpuscular Volume
timeFrame: Day 2
measure: Absolute Values for Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin
timeFrame: Day 2
measure: Absolute Values for Chemistry Parameters: Glucose, Cholesterol, Triglycerides, Anion Gap, Calcium, Carbon Dioxide, Chloride, Phosphate, Potassium, Sodium, Blood Urea Nitrogen
timeFrame: Day 2
measure: Absolute Values for Chemistry Parameters: Creatine Kinase, Lactate Dehydrogenase, Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transferase
timeFrame: Day 2
measure: Absolute Values for Chemistry Parameters: Urate, Creatinine, Bilirubin, Direct Bilirubin
timeFrame: Day 2
measure: Absolute Values for Chemistry Parameters: Albumin, Globulin, Protein
timeFrame: Day 2
measure: Absolute Values for Chemistry Parameters: Amylase, Lipase
timeFrame: Day 2
measure: Absolute Values for Urine Parameter: Specific Gravity
timeFrame: Day 2
measure: Absolute Values for Urine Parameter: Urobilinogen
timeFrame: Day 2
measure: Absolute Values for Urine Parameter: Potential of Hydrogen (pH)
timeFrame: Day 2
measure: Absolute Values for Electrocardiogram (ECG) Parameters: PR Interval, QRS Duration, QT Interval, Corrected QT Interval Using Fridericia's Formula (QTcF), Corrected QT Interval Using Bazett's Formula (QTcB)
timeFrame: Day 1: 2 hours and 4 hours
measure: Absolute Values for Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
timeFrame: Days 2, 3, 4, and 5
measure: Absolute Values for Pulse Rate
timeFrame: Days 2, 3, 4, and 5
measure: Absolute Values for Respiratory Rate
timeFrame: Days 2, 3, 4, and 5
measure: Absolute Values for Body Temperature
timeFrame: Days 2, 3, 4, and 5
measure: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet Count
timeFrame: Baseline (Day -1) and at Day 2
measure: Change From Baseline in Hematology Parameter: Hemoglobin
timeFrame: Baseline (Day -1) and at Day 2
measure: Change From Baseline in Hematology Parameter: Hematocrit
timeFrame: Baseline (Day -1) and at Day 2
measure: Change From Baseline in Hematology Parameter: Erythrocytes
timeFrame: Baseline (Day -1) and at Day 2
measure: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume
timeFrame: Baseline (Day -1) and at Day 2
measure: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin
timeFrame: Baseline (Day -1) and at Day 2
measure: Change From Baseline in Chemistry Parameters: Glucose, Cholesterol, Triglycerides, Anion Gap, Calcium, Carbon Dioxide, Chloride, Phosphate, Potassium, Sodium, Blood Urea Nitrogen
timeFrame: Baseline (Day -1) and at Day 2
measure: Change From Baseline in Chemistry Parameters: Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase
timeFrame: Baseline (Day -1) and at Day 2
measure: Change From Baseline in Chemistry Parameters: Urate, Creatinine, Bilirubin, Direct Bilirubin
timeFrame: Baseline (Day -1) and at Day 2
measure: Change From Baseline in Chemistry Parameters: Albumin, Globulin, Protein
timeFrame: Baseline (Day -1) and at Day 2
measure: Change From Baseline in Chemistry Parameters: Amylase, Lipase
timeFrame: Baseline (Day -1) and at Day 2
measure: Change From Baseline in Urinalysis Parameter: Specific Gravity
timeFrame: Baseline (Day -1) and at Day 2
measure: Change From Baseline in Urinalysis Parameter: Urobilinogen
timeFrame: Baseline (Day -1) and at Day 2
measure: Change From Baseline in Urinalysis Parameter: pH
timeFrame: Baseline (Day -1) and at Day 2
measure: Change From Baseline in PR Interval, QRS Duration, QT Interval, QTcF, QTcB
timeFrame: Baseline (Day 1, Pre-dose), Day 1: 2 hours and 4 hours
measure: Change From Baseline in SBP and DBP
timeFrame: Baseline (Day 1, Pre-dose), Days 2, 3, 4, and 5
measure: Change From Baseline in Pulse Rate
timeFrame: Baseline (Day 1, Pre-dose), Days 2, 3, 4, and 5
measure: Change From Baseline in Respiratory Rate
timeFrame: Baseline (Day 1, Pre-dose), Days 2, 3, 4, and 5
measure: Change From Baseline in Body Temperature
timeFrame: Baseline (Day 1, Pre-dose), Days 2, 3, 4, and 5
measure: Lag Time for Absorption (Tlag) for GSK3640254
timeFrame: Pre-dose and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
measure: Apparent Terminal Phase Half-life (t1/2) for GSK3640254
timeFrame: Pre-dose and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
measure: Apparent Oral Clearance (CL/F) for GSK3640254
timeFrame: Pre-dose and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
measure: Apparent Volume of Distribution (Vz/F) for GSK3640254
timeFrame: Pre-dose and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
measure: Plasma Pharmacokinetic Concentration of GSK3640254
timeFrame: Pre-dose and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
Other outcomes:
Locations:
city: Austin
country: United States
facility: GSK Investigational Site
state: Texas
Study officials:
affiliation: ViiV Healthcare
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: