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AzTrials

HIV InfectionsPhase 1NCT03984825

Effect of GSK3640254 on the Pharmacokinetics of a Combination Oral Contraceptive

A Phase 1 study testing GSK3640254 and Portia in people with HIV Infections, run by ViiV Healthcare at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 to 50 years, women onlyHealthy volunteers can take part
Conditions the study is for
HIV Infections
What is being tested?
GSK3640254 and Portia
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
23 participants
Where
1 siteUnited States
Study dates
13 Jun 2019to 16 Aug 2019
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 50 years
  • Women only
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • GSK Investigational Site

    Austin, Texas, 78744

Other trials in United States

About this study

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

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.

Conditions
HIV Infections
Being tested
GSK3640254, Portia
Keywords
GSK3640254, ethinyl estradiol, levonorgestrel, oral contraceptive, drug-drug interaction
Medical subject headings
HIV Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GSK3640254Drug

    GSK3640254 will be available as a 100 mg capsule. Subjects will be administered 200 mg GSK3640254 once daily via the oral route on Days 11 to 21.

  • PortiaDrug

    Portia will be available in the form of tablets containing 0.03 mg ethinyl estradiol and 0.15 mg levonorgestrel.

Study groups in NCT03984825
Study groupRoleWhat they receive
Portia followed by Portia co-administered with GSK3640254ExperimentalSubjects will be administered Portia (0.03 mg EE/0.15 mg LNG) once daily on Days -3 to -1 during run-in period and on Days 1 to 10 in treatment period A. Subjects will then receive Portia (0.03 mg EE/0.15 mg LNG) co-administered with GSK3640254 200 mg once daily on Days 11 to 21 in treatment period B.
Receives: Drug: GSK3640254; Drug: Portia

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Blood samples were collected at indicated time points for the analysis of AUC (0-tau) of EE. PK parameters were calculated by standard non-compartmental analysis. The PK population included all participants who underwent plasma PK sampling and had evaluable PK parameters estimated.

    Measured: Day 10: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 7, 12 hours and Day 11: 24 hours

  2. Period 2: AUC (0-tau) of EE

    Blood samples were collected at indicated time points for the analysis of AUC (0-tau) of EE. PK parameters were calculated by standard non-compartmental analysis.

    Measured: Day 21: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 7, 12 and 24 hours post dose

  3. Period 1:AUC (0-tau) of LNG

    Blood samples were collected at indicated time points for the analysis of AUC (0-tau) of LNG. PK parameters were calculated by standard non-compartmental analysis.

    Measured: Day 10: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 7, 12 hours and Day 11: 24 hours

  4. Period 2: AUC (0-tau) of LNG

    Blood samples were collected at indicated time points for the analysis of AUC (0-tau) of LNG. PK parameters were calculated by standard non-compartmental analysis.

    Measured: Day 21: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 7, 12 and 24 hours post dose

  5. Period 1: Maximum Observed Concentration (Cmax) and Plasma Concentration at the End of the Dosing Interval (Ctau) of EE

    Blood samples were collected at indicated time points for the analysis of Cmax and Ctau of EE. PK parameters were calculated by standard non-compartmental analysis.

    Measured: Day 10: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 7, 12 hours and Day 11: 24 hours

  6. Period 2: Cmax and Ctau of EE

    Blood samples were collected at indicated time points for the analysis of Cmax and Ctau of EE. PK parameters were calculated by standard non-compartmental analysis.

    Measured: Day 21: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 7, 12 and 24 hours

  7. Period 1:Cmax and Ctau of LNG

    Blood samples were collected at indicated time points for the analysis of Cmax and Ctau of LNG. PK parameters were calculated by standard non-compartmental analysis.

    Measured: Day 10: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 7, 12 hours and Day 11: 24 hours

  8. Period 2: Cmax and Ctau of LNG

    Blood samples were collected at indicated time points for the analysis of Cmax and Ctau of LNG. PK parameters were calculated by standard non-compartmental analysis.

    Measured: Day 21: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 7, 12 and 24 hours post dose

Secondary outcomes (100)

  1. Period 1: Effect of GSK3640254 on PD of EE/LNG- Serum Progesterone Level

    Serum samples were collected for the analysis of progesterone concentration levels when GSK3640254 is co-administered with EE/LNG. PD concentration Population comprised of all participants who underwent plasma PD sampling and had evaluable PD assay results.

    Measured: At Day 1 and Day 10

  2. Period 2: Effect of GSK3640254 on PD of EE/LNG- Serum Progesterone Level

    Serum samples were collected for the analysis progesterone concentration levels when GSK3640254 is co-administered with EE/LNG.

    Measured: At Days 11, 21 and 22

  3. Period 1: Absolute Values of Effect of GSK3640254 on Luteinizing Hormone (LH) and Follicle-stimulating Hormone (FSH)

    Serum samples were collected for the analysis of effect of GSK3640254 on LH and FSH.

    Measured: At Day 1 and Day 10

  4. Period 2: Absolute Values of Effect of GSK3640254 on LH and FSH

    Serum samples were collected for the analysis of effect of GSK3640254 on LH and FSH.

    Measured: At Days 11, 21 and 22

  5. Period 2: AUC (0-tau) of GSK3640254

    Blood samples were collected at indicated time points for the analysis of AUC (0-tau) of GSK3640254. PK parameters were calculated by standard non-compartmental analysis.

    Measured: Day 21: Pre-dose, 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8 and 12 and 24 hours post dose

  6. Period 2: Cmax and Ctau of GSK3640254

    Blood samples were collected at indicated time points for the analysis of Cmax and Ctau of GSK3640254. PK parameters were calculated by standard non-compartmental analysis.

    Measured: Day 21: Pre-dose, 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8 and 12 and 24 hours post dose

  7. Period 2: Apparent Terminal Phase Half-life (t1/2) of GSK3640254

    Blood samples were collected at indicated time points for the analysis of t1/2 of GSK3640254. PK parameters were calculated by standard non-compartmental analysis.

    Measured: 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

  8. Period 2: Time of Maximum Observed Concentration (Tmax) of GSK3640254

    Blood samples were collected at indicated time points for the analysis of Tmax of GSK3640254. PK parameters were calculated by standard non-compartmental analysis.

    Measured: Day 21: Pre-dose, 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8 and 12 and 24 hours post dose

  9. Period 1: t1/2 of EE

    Blood samples were collected at indicated time points for the analysis of t1/2 of EE. PK parameters were calculated by standard non-compartmental analysis.

    Measured: Day 10: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 7, 12 hours and Day 11: 24 hours

  10. Period 2: t1/2 of EE

    Blood samples were collected at indicated time points for the analysis of t1/2 of EE. PK parameters were calculated by standard non-compartmental analysis.

    Measured: 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

  11. Period 1: Tmax of EE

    Blood samples were collected at indicated time points for the analysis of Tmax of EE. PK parameters were calculated by standard non-compartmental analysis.

    Measured: Day 10: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 7, 12 hours and Day 11: 24 hours

  12. Period 2: Tmax of EE

    Blood samples were collected at indicated time points for the analysis of Tmax of EE. PK parameters were calculated by standard non-compartmental analysis.

    Measured: 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

  13. Period 1: t1/2 of LNG

    Blood samples were collected at indicated time points for the analysis of t1/2 of LNG. PK parameters were calculated by standard non-compartmental analysis.

    Measured: Day 10: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 7, 12 hours and Day 11: 24 hours

  14. Period 2: t1/2 of LNG

    Blood samples were collected at indicated time points for the analysis of t1/2 of LNG. PK parameters were calculated by standard non-compartmental analysis.

    Measured: 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

  15. Period 1: Tmax of LNG

    Blood samples were collected at indicated time points for the analysis of Tmax of LNG. PK parameters were calculated by standard non-compartmental analysis.

    Measured: Day 10: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 7, 12 hours and Day 11: 24 hours

  16. Period 2: Tmax of LNG

    Blood samples were collected at indicated time points for the analysis of Tmax of LNG. PK parameters were calculated by standard non-compartmental analysis.

    Measured: 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

  17. Number of Participants With Non-serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAE) (Treatment Period)

    An adverse event (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: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect; other important medical events that may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed before. Safety Population comprised of all participants who received at least one dose of study medication.

    Measured: Up to Day 25

  18. Number of Participants With Non-SAEs and SAE (Run-in Period)

    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: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect; other important medical events that may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed before.

    Measured: From Day -3 to Day -1

  19. 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)

    Blood samples were collected at indicated time points for the analysis of clinical chemistry parameters including Glucose, cholesterol, triglycerides, anion gap, calcium, carbon dioxide, chloride, phosphate, potassium, sodium and BUN. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was defined as post-dose visit value minus Baseline value.

    Measured: Baseline (Day 1, Pre-dose) and at Day 10

  20. Period 2: Change From Baseline in Clinical Chemistry Parameters: Glucose, Cholesterol, Triglycerides, Anion Gap, Calcium, Carbon Dioxide, Chloride, Phosphate, Potassium, Sodium and BUN

    Blood samples were collected at indicated time points for the analysis of clinical chemistry parameters including Glucose, cholesterol, triglycerides, anion gap, calcium, carbon dioxide, chloride, phosphate, potassium, sodium and BUN. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was defined as post-dose visit value minus Baseline value.

    Measured: Baseline (Day 10) and at Days 21 and 24

  21. Period 1: Change From Baseline in Clinical Chemistry Parameters: Plasma Albumin, Globulin and Protein

    Blood samples were collected at indicated time points for the analysis of clinical chemistry parameters including plasma albumin, globulin and protein. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was defined as post-dose visit value minus Baseline value.

    Measured: Baseline (Day 1, Pre-dose) and at Day 10

  22. Period 2: Change From Baseline in Clinical Chemistry Parameters: Plasma Albumin, Globulin and Protein

    Blood samples were collected at indicated time points for the analysis of clinical chemistry parameters including plasma albumin, globulin and protein. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was defined as post-dose visit value minus Baseline value.

    Measured: Baseline (Day 10) and at Days 21 and 24

  23. Period 1: Change From Baseline in Clinical Chemistry Parameters: Plasma Amylase and Lipase

    Blood samples were collected at indicated time points for the analysis of clinical chemistry parameters including plasma amylase and lipase. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was defined as post-dose visit value minus Baseline value.

    Measured: Baseline (Day 1, Pre-dose) and at Day 10

  24. Period 2: Change From Baseline in Clinical Chemistry Parameters: Plasma Amylase and Lipase

    Blood samples were collected at indicated time points for the analysis of clinical chemistry parameters including plasma amylase and lipase. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was defined as post-dose visit value minus Baseline value.

    Measured: Baseline (Day 10) and at Days 21 and 24

  25. 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)

    Blood samples were collected at indicated time points for the analysis of clinical chemistry parameters including Plasma creatine kinase, lactate dehydrogenase, ALT, ALP, AST and GGT. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was defined as post-dose visit value minus Baseline value.

    Measured: Baseline (Day 1, Pre-dose) and at Day 10

  26. Period 2: Change From Baseline in Clinical Chemistry Parameters: Plasma Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST and GGT

    Blood samples were collected at indicated time points for the analysis of clinical chemistry parameters including Plasma creatine kinase, lactate dehydrogenase, ALT, ALP, AST and GGT. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was defined as post-dose visit value minus Baseline value.

    Measured: Baseline (Day 10) and at Days 21 and 24

  27. Period 1: Change From Baseline in Clinical Chemistry Parameters: Plasma Urate, Creatinine, Total Bilirubin and Direct Bilirubin

    Blood samples were collected at indicated time points for the analysis of clinical chemistry parameters including Plasma urate, creatinine, total bilirubin and direct bilirubin. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was defined as post-dose visit value minus Baseline value.

    Measured: Baseline (Day 1, Pre-dose) and at Day 10

  28. Period 2: Change From Baseline in Clinical Chemistry Parameters: Plasma Urate, Creatinine, Total Bilirubin and Direct Bilirubin

    Blood samples were collected at indicated time points for the analysis of clinical chemistry parameters including Plasma urate, creatinine, total bilirubin and direct bilirubin. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was defined as post-dose visit value minus Baseline value.

    Measured: Baseline (Day 10) and at Days 21 and 24

  29. Period 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets

    Blood samples were collected at indicated time points for the analysis of hematology parameters including Basophils, eosinophils, leukocytes, lymphocytes, monocytes, neutrophils and platelets. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was defined as post-dose visit value minus Baseline value.

    Measured: Baseline (Day 1, Pre-dose) and at Day 10

  30. Period 2: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets

    Blood samples were collected at indicated time points for the analysis of hematology parameters including Basophils, eosinophils, leukocytes, lymphocytes, monocytes, neutrophils and platelets. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was defined as post-dose visit value minus Baseline value.

    Measured: Baseline (Day 10) and at Days 21 and 24

  31. Period 1: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin

    Blood samples were collected at indicated time points for the analysis of hematology parameter erythrocytes mean corpuscular hemoglobin. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was defined as post-dose visit value minus Baseline value.

    Measured: Baseline (Day 1, Pre-dose) and at Day 10

  32. Period 2: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin

    Blood samples were collected at indicated time points for the analysis of hematology parameter erythrocytes mean corpuscular hemoglobin. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was defined as post-dose visit value minus Baseline value.

    Measured: Baseline (Day 10) and at Days 21 and 24

  33. Period 1: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume

    Blood samples were collected at indicated time points for the analysis of hematology parameter erythrocytes mean corpuscular volume. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was defined as post-dose visit value minus Baseline value.

    Measured: Baseline (Day 1, Pre-dose) and at Day 10

  34. Period 2: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume

    Blood samples were collected at indicated time points for the analysis of hematology parameter erythrocytes mean corpuscular volume. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was defined as post-dose visit value minus Baseline value.

    Measured: Baseline (Day 10) and at Days 21 and 24

  35. Period 1: Change From Baseline in Hematology Parameter: Erythrocytes

    Blood samples were collected at indicated time points for the analysis of hematology parameter erythrocytes. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was defined as post-dose visit value minus Baseline value.

    Measured: Baseline (Day 1, Pre-dose) and at Day 10

  36. Period 2: Change From Baseline in Hematology Parameter: Erythrocytes

    Blood samples were collected at indicated time points for the analysis of hematology parameter erythrocytes. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was defined as post-dose visit value minus Baseline value.

    Measured: Baseline (Day 10) and at Days 21 and 24

  37. Period 1: Change From Baseline in Hematology Parameter: Hematocrit

    Blood samples were collected at indicated time points for the analysis of hematology parameter hematocrit. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was defined as post-dose visit value minus Baseline value.

    Measured: Baseline (Day 1, Pre-dose) and at Day 10

  38. Period 2: Change From Baseline in Hematology Parameter: Hematocrit

    Blood samples were collected at indicated time points for the analysis of hematology parameter hematocrit. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was defined as post-dose visit value minus Baseline value.

    Measured: Baseline (Day 10) and at Days 21 and 24

  39. Period 1: Change From Baseline in Hematology Parameter: Hemoglobin

    Blood samples were collected at indicated time points for the analysis of hematology parameter hemoglobin. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was defined as post-dose visit value minus Baseline value.

    Measured: Baseline (Day 1, Pre-dose) and at Day 10

  40. Period 2: Change From Baseline in Hematology Parameter: Hemoglobin

    Blood samples were collected at indicated time points for the analysis of hematology parameter hemoglobin. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was defined as post-dose visit value minus Baseline value.

    Measured: Baseline (Day 10) and at Days 21 and 24

  41. Period 1: Change From Baseline in Urine Concentration: Urine Specific Gravity

    Urine samples were collected at indicated time points for the assessment of 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. The concentration of the excreted molecules determines the urine's specific gravity. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was defined as post-dose visit value minus Baseline value.

    Measured: Baseline (Day 1, Pre-dose) and at Day 10

  42. Period 2: Change From Baseline in Urine Concentration: Urine Specific Gravity

    Urine samples were collected at indicated time points for the assessment of 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. The concentration of the excreted molecules determines the urine's specific gravity. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was defined as post-dose visit value minus Baseline value.

    Measured: Baseline (Day 10) and at Days 21 and 24

  43. Period 1: Change From Baseline in Urine Concentration: Urine Urobilinogen

    Urine samples were collected at indicated time points for the assessment of urine urobilinogen. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was defined as post-dose visit value minus Baseline value.

    Measured: Baseline (Day 1, Pre-dose) and at Day 10

  44. Period 2: Change From Baseline in Urine Concentration: Urine Urobilinogen

    Urine samples were collected at indicated time points for the assessment of urine urobilinogen. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was defined as post-dose visit value minus Baseline value.

    Measured: Baseline (Day 10) and at Days 21 and 24

  45. Period 1: Change From Baseline in Urine Concentration: Urine Potential of Hydrogen (pH)

    Urine samples were collected at indicated time points for the assessment of Urinary pH. 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 acid pH (5.0 - 6.0). Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was defined as post-dose visit value minus Baseline value.

    Measured: Baseline (Day 1, Pre-dose) and at Day 10

  46. Period 2: Change From Baseline in Urine Concentration: Urine pH

    Urine samples were collected at indicated time points for the assessment of Urinary pH. 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 acid pH (5.0 - 6.0). Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was defined as post-dose visit value minus Baseline value.

    Measured: Baseline (Day 10) and at Days 21 and 24

  47. Period 1: Change From Baseline in Electrocardiogram (ECG) Mean Heart Rate

    Twelve-lead ECGs were performed with the participant in a supine or semi-supine position after a rest of at least 10 minutes using an automated ECG machine to measure heart rate. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was defined as post-dose visit value minus Baseline value.

    Measured: Baseline (Day 1, Pre-dose) and at Day 10

  48. Period 2: Change From Baseline in ECG Mean Heart Rate

    Twelve-lead ECGs were performed with the participant in a supine or semi-supine position after a rest of at least 10 minutes using an automated ECG machine to measure heart rate. Baseline is defined as the average of the triplicate predose assessments on Day 11. Change from Baseline was defined as post-dose visit value minus Baseline value.

    Measured: Baseline (Day 11, Pre-dose) and at Day 11: 2, 4, 6 hours, Day 15: 2, 4, 6 hours, Day 21 and 24

  49. 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

    Twelve-lead ECGs were performed with the participant in a supine or semi-supine position after a rest of at least 10 minutes using an automated ECG machine to measure PR interval, QRS duration, QT Interval, QTcF Interval and QTcB interval. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was defined as post-dose visit value minus Baseline value.

    Measured: Baseline (Day 1, Pre-dose) and at Day 10

  50. Period 2: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF and QTcB Interval

    Twelve-lead ECGs were performed with the participant in a supine or semi-supine position after a rest of at least 10 minutes using an automated ECG machine to measure heart rate. Baseline is defined as the average of the triplicate predose assessments on Day 11. Change from Baseline was defined as post-dose visit value minus Baseline value.

    Measured: Baseline (Day 11, Pre-dose) and at Day 11: 2, 4, 6 hours, Day 15: 2, 4, 6 hours, Day 21 and 24

  51. Period 1: Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)

    SBP and DBP were assessed in the semi-recumbent position with a completely automated device at indicated time-points. Baseline is defined as the average of the triplicate pre-dose assessments. Change from Baseline was defined as post-dose visit value minus Baseline value.

    Measured: Baseline (Day 1, Pre-dose) and at Day 10

  52. Period 2: Change From Baseline in Vital Signs: SBP and DBP

    SBP and DBP were assessed in the semi-recumbent position with a completely automated device at indicated time-points. Baseline is defined as as the average of the triplicate pre-dose assessments. Change from Baseline was defined as post-dose visit value minus Baseline value.

    Measured: Baseline (Day 11, Pre-dose) and at Days 15, 21 and 24

  53. Period 1: Change From Baseline in Pulse Rate

    Pulse rate was assessed in the semi-recumbent position with a completely automated device at indicated time-points. Baseline is defined as the average of the triplicate predose assessments. Change from Baseline was defined as post-dose visit value minus Baseline value.

    Measured: Baseline (Day 1, Pre-dose) and at Day 10

  54. Period 2: Change From Baseline in Pulse Rate

    Pulse rate was assessed in the semi-recumbent position with a completely automated device at indicated time-points. Baseline is defined as the average of the triplicate predose assessments. Change from Baseline was defined as post-dose visit value minus Baseline value.

    Measured: Baseline (Day 11, Pre-dose) and at Days 15, 21 and 24

  55. Period 1: Change From Baseline in Respiratory Rate

    Respiratory rate was assessed at indicated time-points. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was defined as post-dose visit value minus Baseline value.

    Measured: Baseline (Day 1, Pre-dose) and at Day 10

  56. Period 2: Change From Baseline in Respiratory Rate

    Respiratory rate was assessed at indicated time-points. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was defined as post-dose visit value minus Baseline value.

    Measured: Baseline (Day 11, Pre-dose) and at Days 15, 21 and 24

  57. Period 1: Change From Baseline in Temperature

    Temperature was assessed at indicated time-points. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was defined as post-dose visit value minus Baseline value.

    Measured: Baseline (Day 1, Pre-dose) and at Day 10

  58. Period 2: Change From Baseline in Temperature

    Temperature was assessed at indicated time-points. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was defined as post-dose visit value minus Baseline value.

    Measured: Baseline (Day 11, Pre-dose) and at Days 15, 21 and 24

  59. Period 1: Absolute Values of Clinical Chemistry Parameters: Glucose, Cholesterol, Triglycerides, Anion Gap, Calcium, Carbon Dioxide, Chloride, Phosphate, Potassium, Sodium and BUN

    Blood samples were collected at indicated time points for the analysis of clinical chemistry parameters including Glucose, cholesterol, triglycerides, anion gap, calcium, carbon dioxide, chloride, phosphate, potassium, sodium and BUN. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment.

    Measured: Baseline (Day 1, Pre-dose) and at Day 10

  60. Period 2: Absolute Values of Clinical Chemistry Parameters: Glucose, Cholesterol, Triglycerides, Anion Gap, Calcium, Carbon Dioxide, Chloride, Phosphate, Potassium, Sodium and BUN

    Blood samples were collected at indicated time points for the analysis of clinical chemistry parameters including Glucose, cholesterol, triglycerides, anion gap, calcium, carbon dioxide, chloride, phosphate, potassium, sodium and BUN. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment.

    Measured: Baseline (Day 10) and at Days 21 and 24

  61. Period 1: Absolute Values of Clinical Chemistry Parameters: Plasma Albumin, Globulin and Protein

    Blood samples were collected at indicated time points for the analysis of clinical chemistry parameters including plasma albumin, globulin and protein. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment.

    Measured: Baseline (Day 1, Pre-dose) and at Day 10

  62. Period 2: Absolute Values of Clinical Chemistry Parameters: Plasma Albumin, Globulin and Protein

    Blood samples were collected at indicated time points for the analysis of clinical chemistry parameters including plasma albumin, globulin and protein. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment.

    Measured: Baseline (Day 10) and at Days 21 and 24

  63. Period 1: Absolute Values of Clinical Chemistry Parameters: Plasma Amylase and Lipase

    Blood samples were collected at indicated time points for the analysis of clinical chemistry parameters including plasma amylase and lipase. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment.

    Measured: Baseline (Day 1, Pre-dose) and at Day 10

  64. Period 2: Absolute Values of Clinical Chemistry Parameters: Plasma Amylase and Lipase

    Blood samples were collected at indicated time points for the analysis of clinical chemistry parameters including plasma amylase and lipase. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment.

    Measured: Baseline (Day 10) and at Days 21 and 24

  65. Period 1: Absolute Values of Clinical Chemistry Parameters: Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST and GGT

    Blood samples were collected at indicated time points for the analysis of clinical chemistry parameters including creatine kinase, lactate dehydrogenase, ALT, ALP, AST and GGT. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment.

    Measured: Baseline (Day 1, Pre-dose) and at Day 10

  66. Period 2: Absolute Values of Clinical Chemistry Parameters: Plasma Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST and GGT

    Blood samples were collected at indicated time points for the analysis of clinical chemistry parameters including Plasma creatine kinase, lactate dehydrogenase, ALT, ALP, AST and GGT. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment.

    Measured: Baseline (Day 10) and at Days 21 and 24

  67. Period 1: Absolute Values of Clinical Chemistry Parameters: Urate, Creatinine, Total Bilirubin and Direct Bilirubin

    Blood samples were collected at indicated time points for the analysis of clinical chemistry parameters including Plasma urate, creatinine, total bilirubin and direct bilirubin. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment.

    Measured: Baseline (Day 1, Pre-dose) and at Day 10

  68. Period 2: Absolute Values of Clinical Chemistry Parameters: Plasma Urate, Creatinine, Total Bilirubin and Direct Bilirubin

    Blood samples were collected at indicated time points for the analysis of clinical chemistry parameters including Plasma urate, creatinine, total bilirubin and direct bilirubin. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment.

    Measured: Baseline (Day 10) and at Days 21 and 24

  69. Period 1: Absolute Values of Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets

    Blood samples were collected at indicated time points for the analysis of hematology parameters including Basophils, eosinophils, leukocytes, lymphocytes, monocytes, neutrophils and platelets. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment.

    Measured: Baseline (Day 1, Pre-dose) and at Day 10

  70. Period 2: Absolute Values of Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets

    Blood samples were collected at indicated time points for the analysis of hematology parameters including Basophils, eosinophils, leukocytes, lymphocytes, monocytes, neutrophils and platelets. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment.

    Measured: Baseline (Day 10) and at Days 21 and 24

  71. Period 1: Absolute Values of Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin

    Blood samples were collected at indicated time points for the analysis of hematology parameter erythrocytes mean corpuscular hemoglobin. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment.

    Measured: Baseline (Day 1, Pre-dose) and at Day 10

  72. Period 2: Absolute Values of Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin

    Blood samples were collected at indicated time points for the analysis of hematology parameter erythrocytes mean corpuscular hemoglobin. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment.

    Measured: Baseline (Day 10) and at Days 21 and 24

  73. Period 1: Absolute Values of Hematology Parameter: Erythrocytes Mean Corpuscular Volume

    Blood samples were collected at indicated time points for the analysis of hematology parameter erythrocytes mean corpuscular volume. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment.

    Measured: Baseline (Day 1, Pre-dose) and at Day 10

  74. Period 2: Absolute Values of Hematology Parameter: Erythrocytes Mean Corpuscular Volume

    Blood samples were collected at indicated time points for the analysis of hematology parameter erythrocytes mean corpuscular volume. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment.

    Measured: Baseline (Day 10) and at Days 21 and 24

  75. Period 1: Absolute Values of Hematology Parameter: Erythrocytes

    Blood samples were collected at indicated time points for the analysis of hematology parameter erythrocytes. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment.

    Measured: Baseline (Day 1, Pre-dose) and at Day 10

  76. Period 2: Absolute Values of Hematology Parameter: Erythrocytes

    Blood samples were collected at indicated time points for the analysis of hematology parameter erythrocytes. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment.

    Measured: Baseline (Day 10) and at Days 21 and 24

  77. Period 1: Absolute Values of Hematology Parameter: Hematocrit

    Blood samples were collected at indicated time points for the analysis of hematology parameter hematocrit. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment.

    Measured: Baseline (Day 1, Pre-dose) and at Day 10

  78. Period 2: Absolute Values of Hematology Parameter: Hematocrit

    Blood samples were collected at indicated time points for the analysis of hematology parameter hematocrit. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment.

    Measured: Baseline (Day 10) and at Days 21 and 24

  79. Period 1: Absolute Values of Hematology Parameter: Hemoglobin

    Blood samples were collected at indicated time points for the analysis of hematology parameter hemoglobin. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment.

    Measured: Baseline (Day 1, Pre-dose) and at Day 10

  80. Period 2: Absolute Values of Hematology Parameter: Hemoglobin

    Blood samples were collected at indicated time points for the analysis of hematology parameter hemoglobin. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment.

    Measured: Baseline (Day 10) and at Days 21 and 24

  81. Period 1: Absolute Values of Urine Concentration: Urine Specific Gravity

    Urine samples were collected at indicated time points for the assessment of 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. The concentration of the excreted molecules determines the urine's specific gravity. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment.

    Measured: Baseline (Day 1, Pre-dose) and at Day 10

  82. Period 2: Absolute Values of Urine Concentration: Urine Specific Gravity

    Urine samples were collected at indicated time points for the assessment of 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. The concentration of the excreted molecules determines the urine's specific gravity. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment.

    Measured: Baseline (Day 10) and at Days 21 and 24

  83. Period 1: Absolute Values of Urine Concentration: Urine Urobilinogen

    Urine samples were collected at indicated time points for the assessment of urine urobilinogen. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment.

    Measured: Baseline (Day 1, Pre-dose) and at Day 10

  84. Period 2: Absolute Values of Urine Concentration: Urine Urobilinogen

    Urine samples were collected at indicated time points for the assessment of urine urobilinogen. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment.

    Measured: Baseline (Day 10) and at Days 21 and 24

  85. Period 1: Absolute Values of Urine Concentration: Urine pH

    Urine samples were collected at indicated time points for the assessment of Urinary pH. 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 acid pH (5.0 - 6.0). Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment.

    Measured: Baseline (Day 1, Pre-dose) and at Day 10

  86. Period 2: Absolute Values of Urine Concentration: Urine pH

    Urine samples were collected at indicated time points for the assessment of Urinary pH. 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 acid pH (5.0 - 6.0). Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment.

    Measured: Baseline (Day 10) and at Days 21 and 24

  87. Period 1: Number of Participants With Abnormal Urinalysis Parameters Using Dipstick Method.

    The dipstick test gives results in a semi-quantitative manner and results for urinalysis parameters (ketones, glucose, bilirubin, occult blood, nitrite and blood protein) can be read as positive, trace, 1+, 2+, 3+ and 4+ indicating proportional concentrations in the urine sample. Only participants with abnormal findings for urinalysis at any visit has been presented.

    Measured: Baseline (Day 1, Pre-dose) and at Day 10

  88. Period 2: Number of Participants With Abnormal Urinalysis Parameters Using Dipstick Method.

    The dipstick test gives results in a semi-quantitative manner and results for urinalysis parameters (ketones, glucose, bilirubin, occult blood, nitrite and blood protein) can be read as positive, trace, 1+, 2+, 3+ and 4+ indicating proportional concentrations in the urine sample. Only participants with abnormal findings for urinalysis at any visit has been presented.

    Measured: Baseline (Day 10) and at Days 21 and 24

  89. Period 1: Absolute Values of ECG Mean Heart Rate

    Twelve-lead ECGs were performed with the participant in a supine or semi-supine position after a rest of at least 10 minutes using an automated ECG machine to measure heart rate. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment.

    Measured: Baseline (Day 1, Pre-dose) and at Day 10

  90. Period 2: Absolute Values of ECG Mean Heart Rate

    Twelve-lead ECGs were performed with the participant in a supine or semi-supine position after a rest of at least 10 minutes using an automated ECG machine to measure heart rate. Baseline is defined as the average of the triplicate predose assessments on Day 11.

    Measured: Baseline (Day 11, Pre-dose) and at Day 11: 2, 4, 6 hours, Day 15: 2, 4, 6 hours, Day 21 and 24

  91. Period 1: Absolute Values of ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF Interval, and QTcB Interval

    Twelve-lead ECGs were performed with the participant in a supine or semi-supine position after a rest of at least 10 minutes using an automated ECG machine to measure PR interval, QRS duration, QT Interval, QTcF Interval and QTcB interval. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment.

    Measured: Baseline (Day 1, Pre-dose) and at Day 10

  92. Period 2: Absolute Values of ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF and QTcB Interval

    Twelve-lead ECGs were performed with the participant in a supine or semi-supine position after a rest of at least 10 minutes using an automated ECG machine to measure PR Interval, QRS Duration, QT Interval, QTcF and QTcB Interval. Baseline is defined as the average of the triplicate predose assessments on Day 11.

    Measured: Baseline (Day 11, Pre-dose) and at Day 11- 2, 4, 6 hours, Day 15- 2, 4, 6 hours, Day 21 and 24

  93. Period 1: Absolute Values of Vital Signs: SBP and DBP

    SBP and DBP were assessed in the semi-recumbent position with a completely automated device at indicated time-points. Baseline is defined as the average of the triplicate predose assessments on Day 11.

    Measured: Baseline (Day 1, Pre-dose) and at Day 10

  94. Period 2: Absolute Values of Vital Signs: SBP and DBP

    SBP and DBP were assessed in the semi-recumbent position with a completely automated device at indicated time-points. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment.

    Measured: Baseline (Day 11, Pre-dose) and at Days 15, 21 and 24

  95. Period 1: Absolute Values of Pulse Rate

    Pulse rate was assessed in the semi-recumbent position with a completely automated device at indicated time-points. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment.

    Measured: Baseline (Day 1, Pre-dose) and at Day 10

  96. Period 2: Absolute Values of Pulse Rate

    Pulse rate was assessed in the semi-recumbent position with a completely automated device at indicated time-points. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment.

    Measured: Baseline (Day 11, Pre-dose) and at Days 15, 21 and 24

  97. Period 1: Absolute Values of Respiratory Rate

    Respiratory rate was assessed indicated time-points. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment.

    Measured: Baseline (Day 1, Pre-dose) and at Day 10

  98. Period 2: Absolute Values of Respiratory Rate

    Respiratory rate was assessed indicated time-points. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment.

    Measured: Baseline (Day 11, Pre-dose) and at Days 15, 21 and 24

  99. Period 1: Absolute Values of Temperature

    Temperature was assessed at indicated time-points. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment.

    Measured: Baseline (Day 1, Pre-dose) and at Day 10

  100. Period 2: Absolute Values of Temperature

    Temperature was assessed at indicated time-points. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment.

    Measured: Baseline (Day 11, Pre-dose) and at Days 15, 21 and 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Jun 2019
  2. Study start13 Jun 2019
  3. Primary completion16 Aug 2019
  4. Study completion16 Aug 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
23 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03984825
Sponsor's protocol ID
208135
Status last verified
Aug 2020
First submitted
10 Jun 2019
Last updated
27 Aug 2020
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: IPD for this study will be made available via the Clinical Study Data Request site.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing GSK3640254 and Portia in people with HIV Infections, run by ViiV Healthcare at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Aug 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome 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 (time frame: Day 10: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 7, 12 hours and Day 11: 24 hours). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03984825.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Aug 2020.

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