Clinical trial NCT03984825: Effect of GSK3640254 on the Pharmacokinetics of a Combination Oral Contraceptive
Official title: The Effect of Coadministration of GSK3640254 on the Pharmacokinetics of a Combined Oral Contraceptive Containing Ethinyl Estradiol and Levonorgestrel in Healthy Female Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV Infections
Keywords: GSK3640254
ethinyl estradiol
levonorgestrel
oral contraceptive
drug-drug interaction
Lead sponsor: ViiV Healthcare
Sponsor class: INDUSTRY
First posted: 2019-06-13
Enrollment: 23
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is an open-label, single-sequence, 1-way drug-drug interaction study to investigate the effect of GSK3640254 on the pharmacokinetics of a combination oral contraceptive containing ethinyl estradiol (EE) and levonorgestrel (LNG). Effective contraception for women infected with human immunodeficiency virus (HIV) is important in the prevention of unplanned pregnancies. The study will consist of a screening period of 28 days, check-in (Day -4), a run-in period and a treatment period. During the run-in period, subjects will be administered Portia® (0.03 milligrams \[mg\] EE/0.15 mg LNG) once daily on Days -3 to -1. Subjects will then be administered Portia once daily on Days 1 to 10 of treatment period A followed by administration of Portia once daily along with GSK3640254 200 mg on Days 11 to 21 of treatment period B. The duration of the study is approximately 8 weeks, including Screening and Run-in. Portia is a registered trademark of Teva Pharmaceuticals USA.


Eligibility criteria: Inclusion Criteria:

* Subject must be 18 to 50 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 \>=45.0 kilograms (kg) (99 pounds \[lbs\]) and body mass index (BMI) within the range 18.5 to 31.0 kilograms per meter square (kg/m\^2) (inclusive).
* Contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
* Female subjects will be included.
* Subject must not be pregnant or breastfeeding.
* Subject is a woman of childbearing potential (WOCBP) with intact ovarian function, as determined by medical history. Subjects must use Portia for the duration of the run-in and treatment periods.
* WOCBP must have been on an acceptable form of contraceptive for at least 28 days prior to start of study intervention. Acceptable forms of contraception prior to study intervention include the following: Intrauterine device or intrauterine system; Combined estrogen and progestogen oral contraceptive; Contraceptive vaginal ring; Percutaneous contraceptive patches (if used, the patch must be removed during study participation); Bilateral tubal occlusion; Male partner sterilization with documentation of azoospermia prior to the female subject's entry into the study, and this male is the sole partner for that subject. The documentation on male sterility can come from the site personnel's review of subject's medical records, medical examination and/or semen analysis, or medical history interview provided by her or her partner.; Sexual abstinence.
* Subjects who have been on a stable regimen of an oral contraceptive for at least 3 consecutive months must be without evidence of breakthrough bleeding or spotting.
* Subjects who have been taking oral contraceptives should continue their current regimen until check-in to the clinic for the run-in period. Subjects not currently taking an oral contraceptive are eligible, provided all other eligibility criteria are met.
* Subjects may proceed to the treatment period provided the toxicity profile during the run-in period with Portia is acceptable in the opinion of the investigator.
* Subjects must agree to use an additional method of contraception from the following list of contraceptive methods for the run-in period, treatment period, and for 28 days after the last dose of study intervention: Non hormonal Intrauterine device; Bilateral tubal occlusion; Male partner sterilization with documentation of azoospermia prior to the female subject's entry into the study, and this male is the sole partner for that subject. The documentation on male sterility can come from the site personnel's review of subject's medical records, medical examination and/or semen analysis, or medical history interview provided by her or her partner.; Sexual abstinence. For the 28 days after study exit, women may resume oral contraceptives but double barrier methods (a combination of male condom with either cervical cap, diaphragm, or sponge with spermicide) must be used in addition.
* Women of childbearing potential must have a negative highly sensitive serum pregnancy test on Day -4 and Day -1.
* Additional requirements for pregnancy testing during and after study intervention as outlined in protocol.
* Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form and protocol.

Exclusion Criteria:

* History of jaundice associated with taking oral contraceptives or with pregnancy.
* History of clinically significant irregular bleeding while taking oral contraceptives.
* History of past deep venous thrombosis, pulmonary embolism, stroke, transient ischemic attack, phlebitis, or migraine headaches with prolonged aura.
* History of cerebrovascular or coronary artery disease.
* History of retinal vascular lesions.
* History of carcinoma of the breast, endometrium, or other known estrogen-dependent neoplasia.
* 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 Healthcare/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 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, 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 (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%).
* 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, etc), and ALT (described above), will exclude a subject 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 nonprescription 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 intervention and for the duration of the study (acetaminophen/paracetamol at doses of \<=2 grams/day and hydrocortisone cream 1% are permitted for use any time during 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 investigational product (whichever is longer).
* Where participation in the study would result in donation of blood or blood products in excess of 500 milliliters (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., symptomatic bradycardia, non-sustained or sustained atrial arrhythmias, non-sustained or sustained ventricular tachycardia, second-degree atrioventricular block Mobitz Type II, or third-degree atrioventricular block) which, in the opinion of the investigator or ViiV Healthcare/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-\<50 or \>100 beats per minute and QTcF-\>450 milliseconds.
* 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 g of alcohol: a half-pint (equivalent to 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 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: Period 1: Area Under the Plasma Concentration-time Curve From Time 0 to the End of the Dosing Interval at Steady State (AUC [0-tau]) of EE
timeFrame: Day 10: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 7, 12 hours and Day 11: 24 hours
measure: Period 2: AUC (0-tau) of EE
timeFrame: Day 21: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 7, 12 and 24 hours post dose
measure: Period 1:AUC (0-tau) of LNG
timeFrame: Day 10: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 7, 12 hours and Day 11: 24 hours
measure: Period 2: AUC (0-tau) of LNG
timeFrame: Day 21: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 7, 12 and 24 hours post dose
measure: Period 1: Maximum Observed Concentration (Cmax) and Plasma Concentration at the End of the Dosing Interval (Ctau) of EE
timeFrame: Day 10: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 7, 12 hours and Day 11: 24 hours
measure: Period 2: Cmax and Ctau of EE
timeFrame: Day 21: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 7, 12 and 24 hours
measure: Period 1:Cmax and Ctau of LNG
timeFrame: Day 10: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 7, 12 hours and Day 11: 24 hours
measure: Period 2: Cmax and Ctau of LNG
timeFrame: Day 21: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 7, 12 and 24 hours post dose
Secondary outcomes:
measure: Period 1: Effect of GSK3640254 on PD of EE/LNG- Serum Progesterone Level
timeFrame: At Day 1 and Day 10
measure: Period 2: Effect of GSK3640254 on PD of EE/LNG- Serum Progesterone Level
timeFrame: At Days 11, 21 and 22
measure: Period 1: Absolute Values of Effect of GSK3640254 on Luteinizing Hormone (LH) and Follicle-stimulating Hormone (FSH)
timeFrame: At Day 1 and Day 10
measure: Period 2: Absolute Values of Effect of GSK3640254 on LH and FSH
timeFrame: At Days 11, 21 and 22
measure: Period 2: AUC (0-tau) of GSK3640254
timeFrame: Day 21: Pre-dose, 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8 and 12 and 24 hours post dose
measure: Period 2: Cmax and Ctau of GSK3640254
timeFrame: Day 21: Pre-dose, 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8 and 12 and 24 hours post dose
measure: Period 2: Apparent Terminal Phase Half-life (t1/2) of GSK3640254
timeFrame: Day 21: Pre-dose, 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8 and 12 hours; Day 22: 24 hours; Day 23: 48 hours; Day 24: 72 hours and Day 25: 96 hours
measure: Period 2: Time of Maximum Observed Concentration (Tmax) of GSK3640254
timeFrame: Day 21: Pre-dose, 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8 and 12 and 24 hours post dose
measure: Period 1: t1/2 of EE
timeFrame: Day 10: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 7, 12 hours and Day 11: 24 hours
measure: Period 2: t1/2 of EE
timeFrame: Day 21: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 7, 12 hours and Day 22: 24 hours; Day 23: 48 hours and Day 24: 72 hours
measure: Period 1: Tmax of EE
timeFrame: Day 10: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 7, 12 hours and Day 11: 24 hours
measure: Period 2: Tmax of EE
timeFrame: Day 21: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 7, 12 hours and Day 22: 24 hours; Day 23: 48 hours and Day 24: 72 hours
measure: Period 1: t1/2 of LNG
timeFrame: Day 10: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 7, 12 hours and Day 11: 24 hours
measure: Period 2: t1/2 of LNG
timeFrame: Day 21: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 7, 12 hours; Day 22: 24 hours; Day 23: 48 hours and Day 24: 72 hours
measure: Period 1: Tmax of LNG
timeFrame: Day 10: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 7, 12 hours and Day 11: 24 hours
measure: Period 2: Tmax of LNG
timeFrame: Day 21: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 7, 12 hours; Day 22: 24 hours; Day 23: 48 hours and Day 24: 72 hours
measure: Number of Participants With Non-serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAE) (Treatment Period)
timeFrame: Up to Day 25
measure: Number of Participants With Non-SAEs and SAE (Run-in Period)
timeFrame: From Day -3 to Day -1
measure: Period 1: Change From Baseline in Clinical Chemistry Parameters: Glucose, Cholesterol, Triglycerides, Anion Gap, Calcium, Carbon Dioxide, Chloride, Phosphate, Potassium, Sodium and Blood Urea Nitrogen (BUN)
timeFrame: Baseline (Day 1, Pre-dose) and at Day 10
measure: Period 2: Change From Baseline in Clinical Chemistry Parameters: Glucose, Cholesterol, Triglycerides, Anion Gap, Calcium, Carbon Dioxide, Chloride, Phosphate, Potassium, Sodium and BUN
timeFrame: Baseline (Day 10) and at Days 21 and 24
measure: Period 1: Change From Baseline in Clinical Chemistry Parameters: Plasma Albumin, Globulin and Protein
timeFrame: Baseline (Day 1, Pre-dose) and at Day 10
measure: Period 2: Change From Baseline in Clinical Chemistry Parameters: Plasma Albumin, Globulin and Protein
timeFrame: Baseline (Day 10) and at Days 21 and 24
measure: Period 1: Change From Baseline in Clinical Chemistry Parameters: Plasma Amylase and Lipase
timeFrame: Baseline (Day 1, Pre-dose) and at Day 10
measure: Period 2: Change From Baseline in Clinical Chemistry Parameters: Plasma Amylase and Lipase
timeFrame: Baseline (Day 10) and at Days 21 and 24
measure: Period 1: Change From Baseline in Clinical Chemistry Parameters: Plasma Creatine Kinase, Lactate Dehydrogenase, Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST) and Gamma Glutamyl Transferase (GGT)
timeFrame: Baseline (Day 1, Pre-dose) and at Day 10
measure: Period 2: Change From Baseline in Clinical Chemistry Parameters: Plasma Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST and GGT
timeFrame: Baseline (Day 10) and at Days 21 and 24
measure: Period 1: Change From Baseline in Clinical Chemistry Parameters: Plasma Urate, Creatinine, Total Bilirubin and Direct Bilirubin
timeFrame: Baseline (Day 1, Pre-dose) and at Day 10
measure: Period 2: Change From Baseline in Clinical Chemistry Parameters: Plasma Urate, Creatinine, Total Bilirubin and Direct Bilirubin
timeFrame: Baseline (Day 10) and at Days 21 and 24
measure: Period 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets
timeFrame: Baseline (Day 1, Pre-dose) and at Day 10
measure: Period 2: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets
timeFrame: Baseline (Day 10) and at Days 21 and 24
measure: Period 1: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin
timeFrame: Baseline (Day 1, Pre-dose) and at Day 10
measure: Period 2: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin
timeFrame: Baseline (Day 10) and at Days 21 and 24
measure: Period 1: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume
timeFrame: Baseline (Day 1, Pre-dose) and at Day 10
measure: Period 2: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume
timeFrame: Baseline (Day 10) and at Days 21 and 24
measure: Period 1: Change From Baseline in Hematology Parameter: Erythrocytes
timeFrame: Baseline (Day 1, Pre-dose) and at Day 10
measure: Period 2: Change From Baseline in Hematology Parameter: Erythrocytes
timeFrame: Baseline (Day 10) and at Days 21 and 24
measure: Period 1: Change From Baseline in Hematology Parameter: Hematocrit
timeFrame: Baseline (Day 1, Pre-dose) and at Day 10
measure: Period 2: Change From Baseline in Hematology Parameter: Hematocrit
timeFrame: Baseline (Day 10) and at Days 21 and 24
measure: Period 1: Change From Baseline in Hematology Parameter: Hemoglobin
timeFrame: Baseline (Day 1, Pre-dose) and at Day 10
measure: Period 2: Change From Baseline in Hematology Parameter: Hemoglobin
timeFrame: Baseline (Day 10) and at Days 21 and 24
measure: Period 1: Change From Baseline in Urine Concentration: Urine Specific Gravity
timeFrame: Baseline (Day 1, Pre-dose) and at Day 10
measure: Period 2: Change From Baseline in Urine Concentration: Urine Specific Gravity
timeFrame: Baseline (Day 10) and at Days 21 and 24
measure: Period 1: Change From Baseline in Urine Concentration: Urine Urobilinogen
timeFrame: Baseline (Day 1, Pre-dose) and at Day 10
measure: Period 2: Change From Baseline in Urine Concentration: Urine Urobilinogen
timeFrame: Baseline (Day 10) and at Days 21 and 24
measure: Period 1: Change From Baseline in Urine Concentration: Urine Potential of Hydrogen (pH)
timeFrame: Baseline (Day 1, Pre-dose) and at Day 10
measure: Period 2: Change From Baseline in Urine Concentration: Urine pH
timeFrame: Baseline (Day 10) and at Days 21 and 24
measure: Period 1: Change From Baseline in Electrocardiogram (ECG) Mean Heart Rate
timeFrame: Baseline (Day 1, Pre-dose) and at Day 10
measure: Period 2: Change From Baseline in ECG Mean Heart Rate
timeFrame: Baseline (Day 11, Pre-dose) and at Day 11: 2, 4, 6 hours, Day 15: 2, 4, 6 hours, Day 21 and 24
measure: Period 1: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval, Fridericia QT Correction Formula (QTcF) Interval, and Bazett QT Correction Formula (QTcB) Interval
timeFrame: Baseline (Day 1, Pre-dose) and at Day 10
measure: Period 2: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF and QTcB Interval
timeFrame: Baseline (Day 11, Pre-dose) and at Day 11: 2, 4, 6 hours, Day 15: 2, 4, 6 hours, Day 21 and 24
measure: Period 1: Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
timeFrame: Baseline (Day 1, Pre-dose) and at Day 10
measure: Period 2: Change From Baseline in Vital Signs: SBP and DBP
timeFrame: Baseline (Day 11, Pre-dose) and at Days 15, 21 and 24
measure: Period 1: Change From Baseline in Pulse Rate
timeFrame: Baseline (Day 1, Pre-dose) and at Day 10
measure: Period 2: Change From Baseline in Pulse Rate
timeFrame: Baseline (Day 11, Pre-dose) and at Days 15, 21 and 24
measure: Period 1: Change From Baseline in Respiratory Rate
timeFrame: Baseline (Day 1, Pre-dose) and at Day 10
measure: Period 2: Change From Baseline in Respiratory Rate
timeFrame: Baseline (Day 11, Pre-dose) and at Days 15, 21 and 24
measure: Period 1: Change From Baseline in Temperature
timeFrame: Baseline (Day 1, Pre-dose) and at Day 10
measure: Period 2: Change From Baseline in Temperature
timeFrame: Baseline (Day 11, Pre-dose) and at Days 15, 21 and 24
measure: Period 1: Absolute Values of Clinical Chemistry Parameters: Glucose, Cholesterol, Triglycerides, Anion Gap, Calcium, Carbon Dioxide, Chloride, Phosphate, Potassium, Sodium and BUN
timeFrame: Baseline (Day 1, Pre-dose) and at Day 10
measure: Period 2: Absolute Values of Clinical Chemistry Parameters: Glucose, Cholesterol, Triglycerides, Anion Gap, Calcium, Carbon Dioxide, Chloride, Phosphate, Potassium, Sodium and BUN
timeFrame: Baseline (Day 10) and at Days 21 and 24
measure: Period 1: Absolute Values of Clinical Chemistry Parameters: Plasma Albumin, Globulin and Protein
timeFrame: Baseline (Day 1, Pre-dose) and at Day 10
measure: Period 2: Absolute Values of Clinical Chemistry Parameters: Plasma Albumin, Globulin and Protein
timeFrame: Baseline (Day 10) and at Days 21 and 24
measure: Period 1: Absolute Values of Clinical Chemistry Parameters: Plasma Amylase and Lipase
timeFrame: Baseline (Day 1, Pre-dose) and at Day 10
measure: Period 2: Absolute Values of Clinical Chemistry Parameters: Plasma Amylase and Lipase
timeFrame: Baseline (Day 10) and at Days 21 and 24
measure: Period 1: Absolute Values of Clinical Chemistry Parameters: Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST and GGT
timeFrame: Baseline (Day 1, Pre-dose) and at Day 10
measure: Period 2: Absolute Values of Clinical Chemistry Parameters: Plasma Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST and GGT
timeFrame: Baseline (Day 10) and at Days 21 and 24
measure: Period 1: Absolute Values of Clinical Chemistry Parameters: Urate, Creatinine, Total Bilirubin and Direct Bilirubin
timeFrame: Baseline (Day 1, Pre-dose) and at Day 10
measure: Period 2: Absolute Values of Clinical Chemistry Parameters: Plasma Urate, Creatinine, Total Bilirubin and Direct Bilirubin
timeFrame: Baseline (Day 10) and at Days 21 and 24
measure: Period 1: Absolute Values of Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets
timeFrame: Baseline (Day 1, Pre-dose) and at Day 10
measure: Period 2: Absolute Values of Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets
timeFrame: Baseline (Day 10) and at Days 21 and 24
measure: Period 1: Absolute Values of Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin
timeFrame: Baseline (Day 1, Pre-dose) and at Day 10
measure: Period 2: Absolute Values of Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin
timeFrame: Baseline (Day 10) and at Days 21 and 24
measure: Period 1: Absolute Values of Hematology Parameter: Erythrocytes Mean Corpuscular Volume
timeFrame: Baseline (Day 1, Pre-dose) and at Day 10
measure: Period 2: Absolute Values of Hematology Parameter: Erythrocytes Mean Corpuscular Volume
timeFrame: Baseline (Day 10) and at Days 21 and 24
measure: Period 1: Absolute Values of Hematology Parameter: Erythrocytes
timeFrame: Baseline (Day 1, Pre-dose) and at Day 10
measure: Period 2: Absolute Values of Hematology Parameter: Erythrocytes
timeFrame: Baseline (Day 10) and at Days 21 and 24
measure: Period 1: Absolute Values of Hematology Parameter: Hematocrit
timeFrame: Baseline (Day 1, Pre-dose) and at Day 10
measure: Period 2: Absolute Values of Hematology Parameter: Hematocrit
timeFrame: Baseline (Day 10) and at Days 21 and 24
measure: Period 1: Absolute Values of Hematology Parameter: Hemoglobin
timeFrame: Baseline (Day 1, Pre-dose) and at Day 10
measure: Period 2: Absolute Values of Hematology Parameter: Hemoglobin
timeFrame: Baseline (Day 10) and at Days 21 and 24
measure: Period 1: Absolute Values of Urine Concentration: Urine Specific Gravity
timeFrame: Baseline (Day 1, Pre-dose) and at Day 10
measure: Period 2: Absolute Values of Urine Concentration: Urine Specific Gravity
timeFrame: Baseline (Day 10) and at Days 21 and 24
measure: Period 1: Absolute Values of Urine Concentration: Urine Urobilinogen
timeFrame: Baseline (Day 1, Pre-dose) and at Day 10
measure: Period 2: Absolute Values of Urine Concentration: Urine Urobilinogen
timeFrame: Baseline (Day 10) and at Days 21 and 24
measure: Period 1: Absolute Values of Urine Concentration: Urine pH
timeFrame: Baseline (Day 1, Pre-dose) and at Day 10
measure: Period 2: Absolute Values of Urine Concentration: Urine pH
timeFrame: Baseline (Day 10) and at Days 21 and 24
measure: Period 1: Number of Participants With Abnormal Urinalysis Parameters Using Dipstick Method.
timeFrame: Baseline (Day 1, Pre-dose) and at Day 10
measure: Period 2: Number of Participants With Abnormal Urinalysis Parameters Using Dipstick Method.
timeFrame: Baseline (Day 10) and at Days 21 and 24
measure: Period 1: Absolute Values of ECG Mean Heart Rate
timeFrame: Baseline (Day 1, Pre-dose) and at Day 10
measure: Period 2: Absolute Values of ECG Mean Heart Rate
timeFrame: Baseline (Day 11, Pre-dose) and at Day 11: 2, 4, 6 hours, Day 15: 2, 4, 6 hours, Day 21 and 24
measure: Period 1: Absolute Values of ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF Interval, and QTcB Interval
timeFrame: Baseline (Day 1, Pre-dose) and at Day 10
measure: Period 2: Absolute Values of ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF and QTcB Interval
timeFrame: Baseline (Day 11, Pre-dose) and at Day 11- 2, 4, 6 hours, Day 15- 2, 4, 6 hours, Day 21 and 24
measure: Period 1: Absolute Values of Vital Signs: SBP and DBP
timeFrame: Baseline (Day 1, Pre-dose) and at Day 10
measure: Period 2: Absolute Values of Vital Signs: SBP and DBP
timeFrame: Baseline (Day 11, Pre-dose) and at Days 15, 21 and 24
measure: Period 1: Absolute Values of Pulse Rate
timeFrame: Baseline (Day 1, Pre-dose) and at Day 10
measure: Period 2: Absolute Values of Pulse Rate
timeFrame: Baseline (Day 11, Pre-dose) and at Days 15, 21 and 24
measure: Period 1: Absolute Values of Respiratory Rate
timeFrame: Baseline (Day 1, Pre-dose) and at Day 10
measure: Period 2: Absolute Values of Respiratory Rate
timeFrame: Baseline (Day 11, Pre-dose) and at Days 15, 21 and 24
measure: Period 1: Absolute Values of Temperature
timeFrame: Baseline (Day 1, Pre-dose) and at Day 10
measure: Period 2: Absolute Values of Temperature
timeFrame: Baseline (Day 11, Pre-dose) and at Days 15, 21 and 24
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: