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Austin, Texas 78744


Purpose:

This is an open-label, single-sequence, two-way drug interaction study to investigate the PK, safety and tolerability of GSK3640254 and DTG when administered alone or in combination in healthy subjects. Treatment of human immunodeficiency virus (HIV) infection frequently involves combination therapy. Data from this study will contribute to dosing recommendations when GSK3640254 and DTG are given in combination. The study will consist of a Screening period and 3 sequential treatment periods. Subjects will be administered DTG 50 milligrams (mg) once daily (QD) in Period 1 followed by GSK3640254 200 mg QD in Period 2. There will be a washout period of 4 days between Periods 1 and 2. In Period 3, subjects will be co-administered DTG 50 mg QD and GSK3640254 200 mg QD. The total duration of the study will be approximately 55 days, including Screening.


Criteria:

Inclusion Criteria: - Subject must be 18 to 55 years of age inclusive, at the time of signing the informed consent. - Subjects 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 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). - Male or female subjects can participate. A female subject is eligible to participate if she is not pregnant, not breastfeeding, and not a woman of childbearing potential (WOCBP). - Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and protocol. 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 (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 drugs or render the subject 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. Subjects 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 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 subject's ability to comply with the dosing schedule and protocol evaluations or which might compromise the safety of the subject. - Medical history of cardiac arrhythmias or cardiac disease or a family or personal history of long QT syndrome. - Presence of Hepatitis B surface antigen (HBsAg) 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 (RNA). - Positive HIV-1 and -2 antigen/antibody immunoassay at Screening. - 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). - 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 (CPK) and lipid abnormalities (e.g., total cholesterol, triglycerides), and ALT (described above), will exclude a subject from the study unless the investigator can provide a compelling explanation for the laboratory results 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 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) prior to the first dose of study medication 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, sinoatrial pauses, bundle branch block, or conduction abnormality) which, in the opinion of the investigator or ViiV Healthcare (VH)/GlaxoSmithKline (GSK) Medical Monitor, will interfere with the safety for the individual subject. - Exclusion criteria for screening ECG (a single repeat is allowed for eligibility determination): Heart rate (males: <45 or >100 beats per minute [bpm] and females: <50 or >100 bpm); PR interval (<120 or >200 milliseconds [msec]); QRS duration (<70 or >110 msec); QTcF interval (males: >450 msec and females: >470 msec). - 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 (equivalent to 240 mL) of beer, 1 glass (125 mL) of wine, or 1 (25 mL) measure of spirits. - Regular use of 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.


Study is Available At:


Original ID:

209712


NCT ID:

NCT03816696


Secondary ID:


Study Acronym:


Brief Title:

Study to Evaluate the Pharmacokinetic (PK) Interactions Between GSK3640254 and Dolutegravir (DTG)


Official Title:

An Open-Label Two-way Interaction Clinical Trial to Evaluate the Pharmacokinetic Interactions Between GSK3640254 and Dolutegravir in Healthy Subjects


Overall Status:

Completed


Study Phase:

Phase 1


Genders:

N/A


Minimum Age:

18 Years


Maximum Age:

55 Years


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

ViiV Healthcare


Oversight Authority:

There was an error processing this request


Reasons Why Stopped:


Study Type:

Interventional


Study Design:


Number of Arms:

1


Number of Groups:

0


Total Enrollment:

16


Enrollment Type:

Actual


Overall Contact Information

Official Name:GSK Clinical Trials
Study Director
ViiV Healthcare

Study Dates

Start Date:January 23, 2019
Completion Date:April 10, 2019
Completion Type:Actual
Primary Completion Date:March 30, 2019
Primary Completion Type:Actual
Verification Date:June 2019
Last Changed Date:June 27, 2019
First Received Date:January 22, 2019

Study Outcomes

Outcome Type:Secondary Outcome
Measure:T1/2 of DTG
Time Frame:Period 1 (pre-dose on Days 2 to 4, pre-dose, 1, 1.5, 2, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, and 72
Safety Issues:False
Description:Blood samples will be collected at the indicated time points for pharmacokinetic analysis of DTG.
Outcome Type:Secondary Outcome
Measure:Tmax of DTG
Time Frame:Period 1 (pre-dose on Days 2 to 4, pre-dose, 1, 1.5, 2, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, and 72
Safety Issues:False
Description:Blood samples will be collected at the indicated time points for pharmacokinetic analysis of DTG.
Outcome Type:Secondary Outcome
Measure:Apparent terminal phase half-life (T1/2) of GSK3640254
Time Frame:Period 2 (pre-dose on Days 4 to 6, pre-dose, 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, and 24 hours po
Safety Issues:False
Description:Blood samples will be collected at indicated time points for the pharmacokinetic analysis of GSK3640254
Outcome Type:Secondary Outcome
Measure:Time of maximum observed concentration (Tmax) of GSK3640254
Time Frame:Period 2 (pre-dose on Days 4 to 6, pre-dose, 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, and 24 hours po
Safety Issues:False
Description:Blood samples will be collected at indicated time points for the pharmacokinetic analysis of GSK3640254
Outcome Type:Secondary Outcome
Measure:Absolute values for oral temperature
Time Frame:Up to Day 27
Safety Issues:False
Description:Temperature will be assessed in the semi-recumbent position with a completely automated device.
Outcome Type:Secondary Outcome
Measure:Change from Baseline in oral temperature
Time Frame:Baseline and up to Day 27
Safety Issues:False
Description:Temperature will be assessed in the semi-recumbent position with a completely automated device.
Outcome Type:Secondary Outcome
Measure:Absolute values of respiratory rate
Time Frame:Up to Day 27
Safety Issues:False
Description:Respiratory rate will be assessed in the semi-recumbent position after at least 5 minutes of rest for the subject.
Outcome Type:Secondary Outcome
Measure:Change from Baseline in respiratory rate
Time Frame:Baseline and up to Day 27
Safety Issues:False
Description:Respiratory rate will be assessed in the semi-recumbent position after at least 5 minutes of rest for the subject.
Outcome Type:Secondary Outcome
Measure:Absolute values for heart rate
Time Frame:Up to Day 27
Safety Issues:False
Description:Heart rate will be assessed in the semi-recumbent position with a completely automated device.
Outcome Type:Secondary Outcome
Measure:Change from Baseline in heart rate
Time Frame:Baseline and up to Day 27
Safety Issues:False
Description:Heart rate will be assessed in the semi-recumbent position with a completely automated device.
Outcome Type:Secondary Outcome
Measure:Absolute values of SBP and DBP
Time Frame:Up to Day 27
Safety Issues:False
Description:SBP and DBP will be assessed in the semi-recumbent position with a completely automated device.
Outcome Type:Secondary Outcome
Measure:Change from Baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP)
Time Frame:Baseline and up to Day 27
Safety Issues:False
Description:SBP and DBP will be assessed in the semi-recumbent position with a completely automated device.
Outcome Type:Secondary Outcome
Measure:Absolute values of ECG parameters
Time Frame:Up to Day 26
Safety Issues:False
Description:Twelve-lead ECGs will be performed with the subject in a supine or semi-supine position after a rest of at least 10 minutes using an automated ECG machine. PR, QRS, QT, and QTcF intervals will be measured.
Outcome Type:Secondary Outcome
Measure:Change from Baseline in electrocardiogram (ECG) parameters
Time Frame:Baseline and up to Day 26
Safety Issues:False
Description:Twelve-lead ECGs will be performed with the subject in a supine or semi-supine position after a rest of at least 10 minutes using an automated ECG machine. PR, QRS, QT, and QT interval corrected for heart rate using Fredericia's formula (QTcF) intervals w
Outcome Type:Secondary Outcome
Measure:Absolute values of glucose, protein, blood, ketone, nitrite bilirubin, urobilinogen, and leukocyte esterase levels in urine
Time Frame:Up to Day 26
Safety Issues:False
Description:Urine samples will be collected to detect the presence of glucose, protein, blood, ketone, nitrite bilirubin, urobilinogen, and leukocyte esterase using the dipstick method.
Outcome Type:Secondary Outcome
Measure:Absolute values of urine pH
Time Frame:Up to Day 26
Safety Issues:False
Description:Urine samples will be collected for the assessment of urine parameters.
Outcome Type:Secondary Outcome
Measure:Absolute values of specific gravity of urine
Time Frame:Up to Day 26
Safety Issues:False
Description:Urine samples will be collected for the assessment of urine parameters.
Outcome Type:Secondary Outcome
Measure:Absolute values of triglycerides
Time Frame:Up to Day 26
Safety Issues:False
Description:Blood samples will be collected for the assessment of clinical chemistry parameters.
Outcome Type:Secondary Outcome
Measure:Absolute values of total cholesterol
Time Frame:Up to Day 26
Safety Issues:False
Description:Blood samples will be collected for the assessment of clinical chemistry parameters.
Outcome Type:Secondary Outcome
Measure:Absolute values of anion gap
Time Frame:Up to Day 26
Safety Issues:False
Description:Blood samples will be collected for the assessment of clinical chemistry parameters.
Outcome Type:Secondary Outcome
Measure:Absolute values of BUN, glucose, chloride, potassium, sodium, phosphorus, carbon dioxide and calcium
Time Frame:Up to Day 26
Safety Issues:False
Description:Blood samples will be collected for the assessment of clinical chemistry parameters.
Outcome Type:Secondary Outcome
Measure:Absolute values of ALT, AST, ALP, LDH, GGT, creatine phosphokinase, amylase and lipase levels
Time Frame:Up to Day 26
Safety Issues:False
Description:Blood samples will be collected for the assessment of clinical chemistry parameters.
Outcome Type:Secondary Outcome
Measure:Absolute values of creatinine, total bilirubin, direct bilirubin and uric acid levels
Time Frame:Up to Day 26
Safety Issues:False
Description:Blood samples will be collected for the assessment of clinical chemistry parameters.
Outcome Type:Secondary Outcome
Measure:Absolute values of albumin, globulin and total protein levels
Time Frame:Up to Day 26
Safety Issues:False
Description:Blood samples will be collected for the assessment of clinical chemistry parameters.
Outcome Type:Secondary Outcome
Measure:Absolute values of MCV
Time Frame:Up to Day 26
Safety Issues:False
Description:Blood samples will be collected for the assessment of hematology parameters.
Outcome Type:Secondary Outcome
Measure:Absolute values of MCH
Time Frame:Up to Day 26
Safety Issues:False
Description:Blood samples will be collected for the assessment of hematology parameters.
Outcome Type:Secondary Outcome
Measure:Absolute values of RBC count
Time Frame:Up to Day 26
Safety Issues:False
Description:Blood samples will be collected for the assessment of hematology parameters.
Outcome Type:Secondary Outcome
Measure:Absolute values of hematocrit level
Time Frame:Up to Day 26
Safety Issues:False
Description:Blood samples will be collected for the assessment of hematology parameters.
Outcome Type:Secondary Outcome
Measure:Absolute values of hemoglobin level
Time Frame:Up to Day 26
Safety Issues:False
Description:Blood samples will be collected for the assessment of hematology parameters.
Outcome Type:Secondary Outcome
Measure:Absolute values of absolute neutrophil count
Time Frame:Up to Day 26
Safety Issues:False
Description:Blood samples will be collected for the assessment of hematology parameters.
Outcome Type:Secondary Outcome
Measure:Absolute values of neutrophil, lymphocyte, monocyte, eosinophil, basophil and platelet count
Time Frame:Up to Day 26
Safety Issues:False
Description:Blood samples will be collected for the assessment of hematology parameters.
Outcome Type:Secondary Outcome
Measure:Change from Baseline in glucose, protein, blood, ketone, nitrite bilirubin, urobilinogen, and leukocyte esterase levels in urine
Time Frame:Baseline and up to Day 26
Safety Issues:False
Description:Urine samples will be collected to detect the presence of glucose, protein, blood, ketone, nitrite bilirubin, urobilinogen, and leukocyte esterase using the dipstick method.
Outcome Type:Secondary Outcome
Measure:Change from Baseline in potential of hydrogen (pH) of urine
Time Frame:Baseline and up to Day 26
Safety Issues:False
Description:Urine samples will be collected for the assessment of urine parameters.
Outcome Type:Secondary Outcome
Measure:Change from Baseline in specific gravity of urine
Time Frame:Baseline and up to Day 26
Safety Issues:False
Description:Urine samples will be collected for the assessment of urine parameters.
Outcome Type:Secondary Outcome
Measure:Change from Baseline in triglyceride
Time Frame:Baseline and up to Day 26
Safety Issues:False
Description:Blood samples will be collected for the assessment of clinical chemistry parameters.
Outcome Type:Secondary Outcome
Measure:Change from Baseline in total cholesterol
Time Frame:Baseline and up to Day 26
Safety Issues:False
Description:Blood samples will be collected for the assessment of clinical chemistry parameters.
Outcome Type:Secondary Outcome
Measure:Change from Baseline in anion gap
Time Frame:Baseline and up to Day 26
Safety Issues:False
Description:Blood samples will be collected for the assessment of clinical chemistry parameters.
Outcome Type:Secondary Outcome
Measure:Change from Baseline in blood urea nitrogen (BUN), glucose, chloride, potassium, sodium, phosphorus, carbon dioxide and calcium
Time Frame:Baseline and up to Day 26
Safety Issues:False
Description:Blood samples will be collected for the assessment of clinical chemistry parameters.
Outcome Type:Secondary Outcome
Measure:Change from Baseline in alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP), lactate dehydrogenase (LDH), gamma-glutamyl transferase(GGT), creatine phosphokinase, amylase and lipase levels
Time Frame:Baseline and up to Day 26
Safety Issues:False
Description:Blood samples will be collected for the assessment of clinical chemistry parameters.
Outcome Type:Secondary Outcome
Measure:Change from Baseline in creatinine, total bilirubin, direct bilirubin and uric acid levels
Time Frame:Baseline and up to Day 26
Safety Issues:False
Description:Blood samples will be collected for the assessment of clinical chemistry parameters.
Outcome Type:Secondary Outcome
Measure:Change from Baseline in albumin, globulin and total protein levels
Time Frame:Baseline and up to Day 26
Safety Issues:False
Description:Blood samples will be collected for the assessment of clinical chemistry parameters.
Outcome Type:Secondary Outcome
Measure:Change from Baseline in mean corpuscular volume (MCV)
Time Frame:Baseline and up to Day 26
Safety Issues:False
Description:Blood samples will be collected for the assessment of hematology parameters.
Outcome Type:Secondary Outcome
Measure:Change from Baseline in mean corpuscular hemoglobin (MCH)
Time Frame:Baseline and up to Day 26
Safety Issues:False
Description:Blood samples will be collected for the assessment of hematology parameters.
Outcome Type:Secondary Outcome
Measure:Change from Baseline in red blood cell (RBC) count
Time Frame:Baseline and up to Day 26
Safety Issues:False
Description:Blood samples will be collected for the assessment of hematology parameters.
Outcome Type:Secondary Outcome
Measure:Change from Baseline in hematocrit level
Time Frame:Baseline and up to Day 26
Safety Issues:False
Description:Blood samples will be collected for the assessment of hematology parameters.
Outcome Type:Secondary Outcome
Measure:Change from Baseline in hemoglobin level
Time Frame:Baseline and up to Day 26
Safety Issues:False
Description:Blood samples will be collected for the assessment of hematology parameters.
Outcome Type:Secondary Outcome
Measure:Change from Baseline in absolute neutrophil count
Time Frame:Baseline and up to Day 26
Safety Issues:False
Description:Blood samples will be collected for the assessment of hematology parameters.
Outcome Type:Secondary Outcome
Measure:Change from Baseline in neutrophil, lymphocyte, monocyte, eosinophil, basophil and platelet count
Time Frame:Baseline and up to Day 26
Safety Issues:False
Description:Blood samples will be collected for the assessment of hematology parameters.
Outcome Type:Secondary Outcome
Measure:Number of subjects with adverse events and serious adverse events (SAE)
Time Frame:Up to Day 27
Safety Issues:False
Description:An adverse event is any untoward medical occurrence in a clinical study subject, 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
Outcome Type:Primary Outcome
Measure:Ctau for GSK3640254
Time Frame:Period 2 (pre-dose on Days 4 to 6, pre-dose, 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, and 24 hours po
Safety Issues:False
Description:Blood samples will be collected at the indicated time points for pharmacokinetic analysis of GSK3640254.
Outcome Type:Primary Outcome
Measure:Cmax for GSK3640254
Time Frame:Period 2 (pre-dose on Days 4 to 6, pre-dose, 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, and 24 hours po
Safety Issues:False
Description:Blood samples will be collected at the indicated time points for pharmacokinetic analysis of GSK3640254.
Outcome Type:Primary Outcome
Measure:AUC(0 to tau) for GSK3640254
Time Frame:Period 2 (pre-dose on Days 4 to 6, pre-dose, 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, and 24 hours po
Safety Issues:False
Description:Blood samples will be collected at the indicated time points for pharmacokinetic analysis of GSK3640254.
Outcome Type:Primary Outcome
Measure:Plasma concentration at the end of the dosing interval (Ctau) for DTG
Time Frame:Period 1 (pre-dose on Days 2 to 4, pre-dose, 1, 1.5, 2, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, and 72
Safety Issues:False
Description:Blood samples will be collected at the indicated time points for pharmacokinetic analysis of DTG.
Outcome Type:Primary Outcome
Measure:Maximum observed concentration (Cmax) for DTG
Time Frame:Period 1 (pre-dose on Days 2 to 4, pre-dose, 1, 1.5, 2, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, and 72
Safety Issues:False
Description:Blood samples will be collected at the indicated time points for pharmacokinetic analysis of DTG.
Outcome Type:Primary Outcome
Measure:Area under the plasma concentration-time curve from time 0 to the end of the dosing (AUC[0 to tau]) for DTG
Time Frame:Period 1 (pre-dose on Days 2 to 4, pre-dose, 1, 1.5, 2, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, and 72
Safety Issues:False
Description:Blood samples will be collected at the indicated time points for pharmacokinetic analysis of DTG.

Study Interventions

Intervention Type:Drug
Name:GSK3640254
Description:GSK3640254 will be available as 100 mg capsules. Subjects will be administered GSK3640254 200 mg QD via the oral route.
Arm Name:DTG followed by GSK3640254 followed by DTG+GSK3640
Intervention Type:Drug
Name:DTG
Description:DTG will be available as 50 mg tablets. Subjects will be administered DTG 50 mg QD via the oral route.
Arm Name:DTG followed by GSK3640254 followed by DTG+GSK3640

Study Arms

Study Arm Type:Experimental
Arm Name:DTG followed by GSK3640254 followed by DTG+GSK3640254
Description:Subjects will receive DTG 50 mg QD on Days 1 through 5 in Period 1 followed by a wash-out period of 4 days. Subjects will then receive GSK3640254 200 mg QD on Days 1 through 7 in Period 2 followed by co-administration of DTG 50 mg QD with GSK3640254 200 mg QD on Days 1 through 7 in Period 3.

Study Agencies

Agency Class:Industry
Agency Type:Lead Sponsor
Agency Name:ViiV Healthcare

Sample and Retention Information

There are no available Sample and Retention Information

Study References

There are no available Study References

Data Source: ClinicalTrials.gov

Date Processed: January 21, 2020

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