HIV Infections, Infection, Human Immunodeficiency Virus
Conditions
Brief summary
GSK2838232 is a novel HIV-1 maturation inhibitor (MI) that is being developed for the treatment of HIV-1 infection in combination with other antiretroviral therapy (ART). This study will be a 10-day monotherapy, open-label, adaptive, dose ranging, repeat-dose study. This study will be conducted in two Parts (Part A and Part B) consisting single daily doses of GSK2838232 and Cobicistat from Day 1 to Day 10. This proof of concept open-label study will be aimed to characterize the acute antiviral activity, pharmacokinetics (PK), the relationship between PK and antiviral activity, and safety of GSK2838232/cobi administered across a range of doses over 10 days in HIV-1 infected patients. A cohort of 10 subjects will be studied in Part I followed by interim (go/no-go) analysis of Part A data. On completion of an interim analysis of part A data, further cohorts of 8 subjects will then be studied in Part B in a parallel design in two or more cohorts (depending upon the data obtained in Part A). Approximately 34 HIV-1 infected treatment-naive subjects will be enrolled during the study. Subjects in both parts will have a screening visit within 30 days prior to first dose and a follow-up visit 7-14 days after the last dose. Maximum duration of study participation will be approximately 6 Weeks.
Interventions
DRUGGSK2838232
GSK2838232 capsules will be supplied as swedish orange, unmarked capsule (50 mg), and white, unmarked capsules (10 mg) in high-density polyethylene bottles.
DRUGCobicistat
Cobicistat tablets 150 mg will be supplied as an orange, round, biconvex, film-coated tablet in bulk containers for individualized dosing.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* Between 18 and 55 years of age inclusive, at the time of signing the informed consent. * Healthy (other than HIV infection) male or female as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring, defined as no other chronic medical conditions and taking no chronic medications. * A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or
Exclusion criteria
, outside the reference range for the population being studied may be included only if the investigator in consultation with the medical monitor agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. * A creatinine clearance \>80 mL/minute as determined by Cockcroft-Gault equation creatinine clearance CLcr (mL/minute) = (140 - age) x weight (Wt) divided by (72 x serum creatinine \[Scr\]) (times 0.85 if female) where age is in years, Wt is in kilogram (kg), and Scr is in units of mg/decilitre (dL). * Confirmed HIV positive; CD4+ cell count \>=350 cells/millimetre (mm)\^3 and plasma HIV-1 RNA \>=5000 copies/mL at screening. * No current and no prior ART. * Body weight \>=50 kg (110 pound \[lbs.\]) for men and \>=45 kg (99 lbs) for women and body mass index (BMI) within the range 18.5-31.0 kg/meter\^2 (inclusive) * A female subject of reproductive or non-reproductive potential is eligible to participate if she is not pregnant (as confirmed by a negative serum or urine human chorionic gonadotrophin (hCG) test at screening and prior to first dose), not lactating, and at least one of the following conditions applies: females of reproductive potential may only be enrolled if they are using two forms of complementary contraception, which must include one barrier method. They will be counselled on safer sex practices; there is no definitive drug-drug interaction (DDI) information with GSK2838232 and an interaction with oral contraceptives is possible, so other (barrier, inter-uterine device etc.) methods of contraception will be required; fertile females, who have an established, long-term lifestyle of sexual abstinence, or only same sex partners, require no other means of birth control. Pre-menopausal females with one of the following: documented tubal ligation; documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion; hysterectomy; documented bilateral oophorectomy; postmenopausal defined as 12 months of spontaneous amenorrhea in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) and estradiol levels consistent with menopause. Females on hormone replacement therapy (HRT) must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment. * Male subjects with female partners of child bearing potential must comply with the following contraception requirements from the time of first dose of study medication until one week after the last dose of study medication; vasectomy with documentation of azoospermia; male condom plus partner use of one of the contraceptive options as: Contraceptive sub dermal implant including a \<1 percent rate of failure per year; intrauterine device or intrauterine system including a \<1 percent rate of failure per year; oral contraceptive, either combined or progestogen alone or injectable progestogen; contraceptive vaginal ring; percutaneous contraceptive patches. These allowed methods of contraception are only effective when used consistently, correctly and in accordance with the product label. The investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception. * Capable of giving signed informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tmax for GSK2838232 Following Administration on Day 10 | Pre dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose on Day 10 | Serial plasma samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232. |
| Number of Participants Who Were Administered Concomitant Medications | Up to Day 22 | Concomitant medications (prescription and non-prescription) were administered only as medically necessary during the study. Number of participants who received any concomitant medications is presented. |
| Area Under the Plasma Concentration Time Curve From Zero (Pre-dose) to 24 Hours (AUC[0 to 24]) for GSK2838232 on Day 1 | Pre dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose on Day 1 | Serial plasma samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232. The analysis was performed on Pharmacokinetic Population which comprised of participants who received GSK2838232 and underwent plasma pharmacokinetic sampling during the study. |
| Maximum Observed Concentration (Cmax) for GSK2838232 on Day 1 | Pre dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose on Day 1 | Serial plasma samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232. |
| Time to Maximum Observed Concentration (Tmax) for GSK2838232 on Day 1 | Pre dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose on Day 1 | Serial plasma samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232. |
| Absorption Lag Time (Tlag) for GSK2838232 on Day 1 | Pre dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose on Day 1 | Serial plasma samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232. |
| Concentration of GSK2838232 at 24 Hours Post-dose on Day 1 | 24 hours post-dose on Day 1 | Serial plasma samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232. |
| Area Under the Concentration-time Curve Over the Dosing Interval (AUC [0 to Tau]) for GSK2838232 on Day 10 | Pre dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose on Day 10 | Serial plasma samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232. |
| Pre-dose Concentration (C0) of GSK2838232 on Day 10 | Pre dose on Day 10 | Serial plasma samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232. |
| Concentration at End of Dosing Interval (Ctau) for GSK2838232 on Day 10 | 24 hours post-dose on Day 10 | Serial plasma samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232. |
| Cmax for GSK2838232 on Day 10 | Pre dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose on Day 10 | Serial plasma samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232. |
| Apparent Oral Clearance of GSK2838232 Following Administration on Day 10 | Pre dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose on Day 10 | Serial plasma samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232. |
| Terminal Elimination Half-life (T1/2) of GSK2838232 Following Administration on Day 10 | Pre dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose on Day 10 | Serial plasma samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232. |
| Maximum Decline From Baseline in Plasma HIV-1 Ribonucleic Acid (RNA) | Baseline (Day 1) to Day 21 | Plasma samples were collected for quantitative analysis of plasma HIV-1 RNA. An HIV-1 RNA polymerase chain reaction (PCR) assay with a lower limit of detection (LLOD) of 50 copies/milliliter (ultrasensitive assay) was used for post-baseline assessments. Baseline value was the value at latest pre-dose assessment. The maximum decline was determined using change from Baseline in plasma HIV-RNA values at each time point. The analysis was performed on Intent To Treat (ITT) Population which comprised of all participants who met study criteria and were enrolled into the study with documented evidence of having received at least 1 dose of treatment and at least one post-Baseline HIV-1 RNA measurement. |
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Up to Day 22 | An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life threatening; requires hospitalization or prolongation of existing hospitalization; results in disability/incapacity; is a congenital anomaly/birth defect; other important medical events; is associated with liver injury and impaired liver function. Safety Population comprised of all participants who received at least one dose of study treatment. |
| Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance | Up to Day 22 | Blood samples were collected for the assessment of clinical chemistry parameters. The clinical concern range for the parameters were: carbon dioxide/bicarbonate (low: \<18 millimoles per liter \[mmol/L\] and high: \>32 mmol/L); urea (high: \>9 mmol/L); creatinine (high: change from Baseline \>44.2 micromoles per liter \[µmol/L\]), glucose (low: \<3 and high: \>9 mmol/L); potassium (low: \<3 and high: \>5.5 mmol/L); troponin I (high: \>=0.01 micrograms per liter \[µg/L\]) and sodium (low: \<130 mmol/L and high: \>150 mmol/L). Data for any visit post-Baseline is reported. |
| Number of Participants With Hematology Parameter Abnormalities of Potential Clinical Importance | Up to Day 22 | Blood samples were collected for the assessment of hematology parameters. The clinical concern range for the parameters were: hematocrit (high: \>0.54 proportion of red blood cells in blood); hemoglobin (high: \>180 grams per liter \[g/L\]), lymphocytes (low: \<0.8x10\^9 cells/L); neutrophil count (low: \<1.5x10\^9 cells/L); platelet count (low: \<100x10\^9 cells/L and high: \>550x10\^9 cells/L); white blood cells (low: \<3x10\^9 cells/L and high: \>20x10\^9cells/L). Data for any visit post-Baseline is reported. |
| Number of Participants With Liver Function Laboratory Abnormalities of Potential Clinical Importance | Up to Day 22 | Blood samples were collected for the assessment of liver function parameters. The clinical concern range for liver function parameters were: albumin (low: \<30 g/L), total protein (low: \<15 and high: \>15 g/L), alanine aminotransferase (high: \>=2 times upper limit of normal \[ULN\]); aspartate aminotransferase (high: \>=2 times ULN); alkaline phosphatase (high: \>=2 times ULN); total bilirubin (high: \>=1.5 times ULN); direct bilirubin (high: \>0.3 times ULN). |
| Number of Participants With Abnormal Urine Parameters | Up to Day 22 | Urine samples were collected for the assessment of following urine parameters by dipstick method: pH, glucose, protein, blood and ketones. The number of participants with abnormal urine parameters is presented. |
| Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Up to Day 22 | Triplicate 12-lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, and corrected QT (QTc) intervals. Number of participants with abnormal ECG findings at worst-case post Baseline is presented. |
| Number of Participants With Vital Signs Data Outside Clinical Concern Range | Day 1 (pre-dose) | Vital signs were measured in a semi-supine position after 5 minutes rest and included temperature, systolic and diastolic blood pressure and pulse rate. The clinical concern range for vital signs were: systolic blood pressure (SBP) (low: \<85 and high: \>160 millimeters of mercury \[mmHg\]) and diastolic blood pressure (DBP) (low: \<45 and high: \>100 mmHg). Number of participants with vital signs data outside clinical concern range is presented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Day 11 in log10 Plasma HIV-1 RNA Relative to Day 10 Cmax | Baseline (Day 1), Days 10 and 11 | Plasma samples were collected for quantitative analysis of HIV-1 RNA. Change from Baseline is the value at indicated time point minus Baseline value. Statistical analysis for the relationship between pharmacokinetic parameters (Cmax) and pharmacodynamic measures (change from Baseline in log10 plasma HIV-1 RNA) was explored using a frequentist three parameter Emax non-linear model. The model parameters estimated included: maximum response (Emax), pharmacokinetic parameter value that attains the 50% of the maximal effect (ED50) and s2e. |
| Change From Baseline to Day 11 in log10 Plasma HIV-1 RNA Relative to Day 10 Ctau | Baseline (Day 1), Days 10 and 11 | Plasma samples were collected for quantitative analysis of HIV-1 RNA. Change from Baseline is the value at indicated time point minus Baseline value. Statistical analysis for the relationship between pharmacokinetic parameters (Ctau) and pharmacodynamic measures (change from Baseline in log10 plasma HIV-1 RNA) was explored using a frequentist three parameter Emax non-linear model. The model parameters estimated included: maximum response (Emax), pharmacokinetic parameter value that attains the 50% of the maximal effect (ED50) and s2e. |
| Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Count to Day 11 | Baseline (Day 1) and Day 11 | CD4+ cell counts were assessed by flow cytometry. Baseline value is the latest pre-dose assessment value. Change from Baseline is calculated as the post-dose visit value minus Baseline value. |
| Change From Baseline to Day 11 in CD4+ Count Relative to Day 10 AUC (0 to Tau) | Baseline (Day 1), Days 10 and 11 | The relationship between pharmacokinetic parameters (AUC) and pharmacodynamic measures (change from Baseline CD4+ cell count) was explored using a frequentist linear model. The model parameters estimated included slope and intercept. The estimate (slope) along with 95% confidence interval is presented. |
| Change From Baseline to Day 11 in CD4+ Count Relative to Day 10 Cmax | Baseline (Day 1), Days 10 and 11 | The relationship between pharmacokinetic parameters (Cmax) and pharmacodynamic measures (change from Baseline CD4+ cell count) was explored using a frequentist linear model. The model parameters estimated included slope and intercept. The estimate (slope) along with 95% confidence interval is presented |
| Change From Baseline to Day 11 in CD4+ Count Relative to Day 10 Ctau | Baseline (Day 1), Days 10 and 11 | The relationship between pharmacokinetic parameters (Ctau) and pharmacodynamic measures (change from Baseline CD4+ cell count) was explored using a frequentist linear model. The model parameters estimated included slope and intercept. The estimate (slope) along with 95% confidence interval is presented. |
| Number of Participants With Emergent Drug Resistance Mutations | Up to Day 11 | Plasma samples were collected to evaluate treatment-emergent genotypic mutations in Gag, reverse transcriptase (RT) and protease (PR) and to assess phenotypic resistance to GSK2838232 and RT and PR drugs. Number of participants with treatment emergent RT/PR mutations, reduced susceptibility to nucleoside/nucleotide reverse transcriptase inhibitor (NRTI), non-nucleoside reverse transcriptase inhibitor (NNRTI), or protease inhibitor (PI), treatment emergent maturation inhibitor A364A/V and GSK2838232 phenotypic resistance is presented. |
| Accumulation Ratio for GSK2838232 | pre dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose on Days 1 and 10; pre-dose on Days 3, 4, 5, 8 and 9; Days 12 and 14 | Serial blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232. The accumulation ratios were calculated as R\_AUC=AUC(0-tau) Day 10/AUC(0-24) Day 1; R\_Cmax=Cmax Day 10/Cmax Day 1 and R\_Ctau=Ctau Day 10/C24 Day 1. |
| Dose Proportionality of GSK2838232 | pre dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose on Days 1 and 10 | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232. Dose proportionality was assessed using a fixed effects power model. Estimated slope and 90% confidence interval is presented. |
| Pre-morning Dose Concentrations (C0) on Day 2 Through 11 | Pre-dose on Days 2, 3, 4, 5, 8, 9, 10 and 11 | Blood samples were collected for pharmacokinetic analysis of GSK2838232. The pre-morning dose concentrations for Days 2 to 11 is presented. One participant from GSK2838232 100 mg arm was dosed with GSK2838232 50 mg on Days 1 and 2; hence, pharmacokinetic parameters for that participant were summarized with GSK2838232 50 mg for Days 1 and 2 and with GSK2838232 100 mg for Days 3 to 10. |
| Steady State Assessment of Plasma Pre-dose Concentrations by Treatment | Pre-dose on Days 8, 9 and 10 | A linear mixed model using Day, treatment and Day by treatment as fixed effects and participant as a random effect on the log-transformed pre-dose values was performed to evaluate if steady state was achieved using the Helmert transformation approach. The comparison was done as Day 8 versus the average of Days 9 and 10 values. The ratio of geometric least square mean for Day 8 versus average of Days 9 and 10 values is presented along with 95% confidence interval. |
| Change From Baseline to Day 11 in log10 Plasma HIV-1 RNA Relative to Day 10 AUC (0 to Tau) | Baseline (Day 1), Days 10 and 11 | Plasma samples were collected for quantitative analysis of HIV-1 RNA. Change from Baseline is the value at indicated time point minus Baseline value. Statistical analysis for relationship between pharmacokinetic parameters (AUC) and pharmacodynamic measures (Change from Baseline in plasma HIV-1 RNA) was explored using a frequentist three parameter Emax non-linear model. The model parameters estimated included: maximum response (Emax), pharmacokinetic parameter value that attains 50% of the maximal effect (ED50) and residual variability (s2e). Pharmacokinetic/Pharmacodynamic Population comprised of participants who met criteria for Per-Protocol (all participants who met study criteria and are enrolled into the study with documented evidence of having received all doses and all post-baseline HIV-1 RNA measurement, with exceptions of those who have at least one major protocol deviation) and Pharmacokinetic Population analysis sets and who underwent pharmacodynamic sampling during study. |
Countries
Canada, United States
Participant flow
Recruitment details
This was a dose ranging study to evaluate the antiviral effect, safety, tolerability and pharmacokinetics of cobicistat-boosted GSK2838232 monotherapy over 10 days in human immunodeficiency virus-1 (HIV-1) infected participants.
Pre-assignment details
A total of 85 participants were screened across 21 sites in the United States and Canada of which 52 participants failed screening. Thirty three participants were enrolled from 15 sites in the United States and Canada.
Participants by arm
| Arm | Count |
|---|---|
| GSK2838232 20 mg Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 20 milligrams (mg) and 150 mg cobicistat once daily with a light breakfast meal and 240 milliliters (mL) of water from Day 1 to Day 10. | 7 |
| GSK2838232 50 mg Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 50 mg and 150 mg cobicistat once daily with a light breakfast meal and 240 mL of water from Day 1 to Day 10. | 8 |
| GSK2838232 100 mg Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 100 mg and 150 mg cobicistat once daily with a light breakfast meal and 240 mL of water from Day 1 to Day 10. | 10 |
| GSK2838232 200 mg Eligible HIV-1 infected participants were administered a single oral dose of GSK2838232 200 mg and 150 mg cobicistat once daily with a light breakfast meal and 240 mL of water from Day 1 to Day 10. | 8 |
| Total | 33 |
Baseline characteristics
| Characteristic | Total | GSK2838232 200 mg | GSK2838232 100 mg | GSK2838232 50 mg | GSK2838232 20 mg |
|---|---|---|---|---|---|
| Age, Continuous | 29.8 Years STANDARD_DEVIATION 11.23 | 35.8 Years STANDARD_DEVIATION 14.87 | 31.8 Years STANDARD_DEVIATION 10.66 | 25.4 Years STANDARD_DEVIATION 9.74 | 25.4 Years STANDARD_DEVIATION 5.59 |
| Race/Ethnicity, Customized Race, customized American Indian or Alaska native | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race, customized Asian-South East Asian Heritage | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race, customized Black or African American | 8 Participants | 2 Participants | 5 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Race, customized Multiple-Black or African American and White | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Race, customized Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race, customized White-White/Caucasian/European Heritage | 20 Participants | 5 Participants | 4 Participants | 6 Participants | 5 Participants |
| Sex: Female, Male Female | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 32 Participants | 8 Participants | 9 Participants | 8 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 8 | 0 / 10 | 0 / 8 |
| other Total, other adverse events | 3 / 7 | 3 / 8 | 5 / 10 | 5 / 8 |
| serious Total, serious adverse events | 0 / 7 | 0 / 8 | 0 / 10 | 0 / 8 |
Outcome results
Primary
Absorption Lag Time (Tlag) for GSK2838232 on Day 1
Serial plasma samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232.
Time frame: Pre dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose on Day 1
Population: Pharmacokinetic Population. One participant from GSK2838232 100 mg arm was dosed with GSK2838232 50 mg on Days 1 and 2; hence, pharmacokinetic parameters for that participant were summarized with GSK2838232 50 mg for Day 1
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| GSK2838232 20 mg | Absorption Lag Time (Tlag) for GSK2838232 on Day 1 | 1.083 Hours |
| GSK2838232 50 mg | Absorption Lag Time (Tlag) for GSK2838232 on Day 1 | 1.000 Hours |
| GSK2838232 100 mg | Absorption Lag Time (Tlag) for GSK2838232 on Day 1 | 0.500 Hours |
| GSK2838232 200 mg | Absorption Lag Time (Tlag) for GSK2838232 on Day 1 | 0.500 Hours |
Primary
Apparent Oral Clearance of GSK2838232 Following Administration on Day 10
Serial plasma samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232.
Time frame: Pre dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose on Day 10
Population: Pharmacokinetic Population. Only those participants with data available at the specified time point were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| GSK2838232 20 mg | Apparent Oral Clearance of GSK2838232 Following Administration on Day 10 | 33.91 Liters per hour | Geometric Coefficient of Variation 33.4 |
| GSK2838232 50 mg | Apparent Oral Clearance of GSK2838232 Following Administration on Day 10 | 48.84 Liters per hour | Geometric Coefficient of Variation 40.8 |
| GSK2838232 100 mg | Apparent Oral Clearance of GSK2838232 Following Administration on Day 10 | 36.67 Liters per hour | Geometric Coefficient of Variation 53.1 |
| GSK2838232 200 mg | Apparent Oral Clearance of GSK2838232 Following Administration on Day 10 | 35.31 Liters per hour | Geometric Coefficient of Variation 67.1 |
Primary
Area Under the Concentration-time Curve Over the Dosing Interval (AUC [0 to Tau]) for GSK2838232 on Day 10
Serial plasma samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232.
Time frame: Pre dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose on Day 10
Population: Pharmacokinetic Population. Only those participants with data available at the specified time point were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| GSK2838232 20 mg | Area Under the Concentration-time Curve Over the Dosing Interval (AUC [0 to Tau]) for GSK2838232 on Day 10 | 590 Hours*nanograms per milliliter | Geometric Coefficient of Variation 33.4 |
| GSK2838232 50 mg | Area Under the Concentration-time Curve Over the Dosing Interval (AUC [0 to Tau]) for GSK2838232 on Day 10 | 1024 Hours*nanograms per milliliter | Geometric Coefficient of Variation 40.8 |
| GSK2838232 100 mg | Area Under the Concentration-time Curve Over the Dosing Interval (AUC [0 to Tau]) for GSK2838232 on Day 10 | 2727 Hours*nanograms per milliliter | Geometric Coefficient of Variation 53.1 |
| GSK2838232 200 mg | Area Under the Concentration-time Curve Over the Dosing Interval (AUC [0 to Tau]) for GSK2838232 on Day 10 | 5664 Hours*nanograms per milliliter | Geometric Coefficient of Variation 67.1 |
Primary
Area Under the Plasma Concentration Time Curve From Zero (Pre-dose) to 24 Hours (AUC[0 to 24]) for GSK2838232 on Day 1
Serial plasma samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232. The analysis was performed on Pharmacokinetic Population which comprised of participants who received GSK2838232 and underwent plasma pharmacokinetic sampling during the study.
Time frame: Pre dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose on Day 1
Population: Pharmacokinetic Population. One participant from GSK2838232 100 mg arm was dosed with GSK2838232 50 mg on Days 1 and 2; hence, pharmacokinetic parameters for that participant were summarized with GSK2838232 50 mg for Day 1
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| GSK2838232 20 mg | Area Under the Plasma Concentration Time Curve From Zero (Pre-dose) to 24 Hours (AUC[0 to 24]) for GSK2838232 on Day 1 | 187 Hours*nanograms per milliliter | Geometric Coefficient of Variation 35.5 |
| GSK2838232 50 mg | Area Under the Plasma Concentration Time Curve From Zero (Pre-dose) to 24 Hours (AUC[0 to 24]) for GSK2838232 on Day 1 | 453 Hours*nanograms per milliliter | Geometric Coefficient of Variation 60.4 |
| GSK2838232 100 mg | Area Under the Plasma Concentration Time Curve From Zero (Pre-dose) to 24 Hours (AUC[0 to 24]) for GSK2838232 on Day 1 | 966 Hours*nanograms per milliliter | Geometric Coefficient of Variation 67.4 |
| GSK2838232 200 mg | Area Under the Plasma Concentration Time Curve From Zero (Pre-dose) to 24 Hours (AUC[0 to 24]) for GSK2838232 on Day 1 | 2752 Hours*nanograms per milliliter | Geometric Coefficient of Variation 51.7 |
Primary
Cmax for GSK2838232 on Day 10
Serial plasma samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232.
Time frame: Pre dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose on Day 10
Population: Pharmacokinetic Population. Only those participants with data available at the specified time point were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| GSK2838232 20 mg | Cmax for GSK2838232 on Day 10 | 32.65 Nanograms per milliliter | Geometric Coefficient of Variation 30.8 |
| GSK2838232 50 mg | Cmax for GSK2838232 on Day 10 | 56.40 Nanograms per milliliter | Geometric Coefficient of Variation 33 |
| GSK2838232 100 mg | Cmax for GSK2838232 on Day 10 | 157.9 Nanograms per milliliter | Geometric Coefficient of Variation 54 |
| GSK2838232 200 mg | Cmax for GSK2838232 on Day 10 | 306.5 Nanograms per milliliter | Geometric Coefficient of Variation 59.2 |
Primary
Concentration at End of Dosing Interval (Ctau) for GSK2838232 on Day 10
Serial plasma samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232.
Time frame: 24 hours post-dose on Day 10
Population: Pharmacokinetic Population. Only those participants with data available at the specified time point were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| GSK2838232 20 mg | Concentration at End of Dosing Interval (Ctau) for GSK2838232 on Day 10 | 19.24 Nanograms per milliliter | Geometric Coefficient of Variation 33.7 |
| GSK2838232 50 mg | Concentration at End of Dosing Interval (Ctau) for GSK2838232 on Day 10 | 31.76 Nanograms per milliliter | Geometric Coefficient of Variation 53.8 |
| GSK2838232 100 mg | Concentration at End of Dosing Interval (Ctau) for GSK2838232 on Day 10 | 78.98 Nanograms per milliliter | Geometric Coefficient of Variation 58.3 |
| GSK2838232 200 mg | Concentration at End of Dosing Interval (Ctau) for GSK2838232 on Day 10 | 180.3 Nanograms per milliliter | Geometric Coefficient of Variation 79.8 |
Primary
Concentration of GSK2838232 at 24 Hours Post-dose on Day 1
Serial plasma samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232.
Time frame: 24 hours post-dose on Day 1
Population: Pharmacokinetic Population. One participant from GSK2838232 100 mg arm was dosed with GSK2838232 50 mg on Days 1 and 2; hence, pharmacokinetic parameters for that participant were summarized with GSK2838232 50 mg for Day 1
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| GSK2838232 20 mg | Concentration of GSK2838232 at 24 Hours Post-dose on Day 1 | 5.890 Nanograms per milliliter | Geometric Coefficient of Variation 27.6 |
| GSK2838232 50 mg | Concentration of GSK2838232 at 24 Hours Post-dose on Day 1 | 13.45 Nanograms per milliliter | Geometric Coefficient of Variation 87.3 |
| GSK2838232 100 mg | Concentration of GSK2838232 at 24 Hours Post-dose on Day 1 | 30.72 Nanograms per milliliter | Geometric Coefficient of Variation 58.3 |
| GSK2838232 200 mg | Concentration of GSK2838232 at 24 Hours Post-dose on Day 1 | 87.33 Nanograms per milliliter | Geometric Coefficient of Variation 54.6 |
Primary
Maximum Decline From Baseline in Plasma HIV-1 Ribonucleic Acid (RNA)
Plasma samples were collected for quantitative analysis of plasma HIV-1 RNA. An HIV-1 RNA polymerase chain reaction (PCR) assay with a lower limit of detection (LLOD) of 50 copies/milliliter (ultrasensitive assay) was used for post-baseline assessments. Baseline value was the value at latest pre-dose assessment. The maximum decline was determined using change from Baseline in plasma HIV-RNA values at each time point. The analysis was performed on Intent To Treat (ITT) Population which comprised of all participants who met study criteria and were enrolled into the study with documented evidence of having received at least 1 dose of treatment and at least one post-Baseline HIV-1 RNA measurement.
Time frame: Baseline (Day 1) to Day 21
Population: ITT Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GSK2838232 20 mg | Maximum Decline From Baseline in Plasma HIV-1 Ribonucleic Acid (RNA) | -42095.14 Copies per milliliter | Standard Deviation 37575.52 |
| GSK2838232 50 mg | Maximum Decline From Baseline in Plasma HIV-1 Ribonucleic Acid (RNA) | -49065.88 Copies per milliliter | Standard Deviation 71339.743 |
| GSK2838232 100 mg | Maximum Decline From Baseline in Plasma HIV-1 Ribonucleic Acid (RNA) | -32947.50 Copies per milliliter | Standard Deviation 54291.492 |
| GSK2838232 200 mg | Maximum Decline From Baseline in Plasma HIV-1 Ribonucleic Acid (RNA) | -33149.13 Copies per milliliter | Standard Deviation 31785.663 |
Primary
Maximum Observed Concentration (Cmax) for GSK2838232 on Day 1
Serial plasma samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232.
Time frame: Pre dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose on Day 1
Population: Pharmacokinetic Population. One participant from GSK2838232 100 mg arm was dosed with GSK2838232 50 mg on Days 1 and 2; hence, pharmacokinetic parameters for that participant were summarized with GSK2838232 50 mg for Day 1
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| GSK2838232 20 mg | Maximum Observed Concentration (Cmax) for GSK2838232 on Day 1 | 12.65 Nanograms per milliliter | Geometric Coefficient of Variation 36.4 |
| GSK2838232 50 mg | Maximum Observed Concentration (Cmax) for GSK2838232 on Day 1 | 32.39 Nanograms per milliliter | Geometric Coefficient of Variation 61 |
| GSK2838232 100 mg | Maximum Observed Concentration (Cmax) for GSK2838232 on Day 1 | 65.62 Nanograms per milliliter | Geometric Coefficient of Variation 76.7 |
| GSK2838232 200 mg | Maximum Observed Concentration (Cmax) for GSK2838232 on Day 1 | 190.0 Nanograms per milliliter | Geometric Coefficient of Variation 44.3 |
Primary
Number of Participants Who Were Administered Concomitant Medications
Concomitant medications (prescription and non-prescription) were administered only as medically necessary during the study. Number of participants who received any concomitant medications is presented.
Time frame: Up to Day 22
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GSK2838232 20 mg | Number of Participants Who Were Administered Concomitant Medications | 2 Participants |
| GSK2838232 50 mg | Number of Participants Who Were Administered Concomitant Medications | 3 Participants |
| GSK2838232 100 mg | Number of Participants Who Were Administered Concomitant Medications | 3 Participants |
| GSK2838232 200 mg | Number of Participants Who Were Administered Concomitant Medications | 3 Participants |
Primary
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
Triplicate 12-lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, and corrected QT (QTc) intervals. Number of participants with abnormal ECG findings at worst-case post Baseline is presented.
Time frame: Up to Day 22
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GSK2838232 20 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Abnormal-not clinically significant | 5 Participants |
| GSK2838232 20 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Abnormal-clinically significant | 0 Participants |
| GSK2838232 50 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Abnormal-clinically significant | 0 Participants |
| GSK2838232 50 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Abnormal-not clinically significant | 6 Participants |
| GSK2838232 100 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Abnormal-clinically significant | 0 Participants |
| GSK2838232 100 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Abnormal-not clinically significant | 8 Participants |
| GSK2838232 200 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Abnormal-clinically significant | 0 Participants |
| GSK2838232 200 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Abnormal-not clinically significant | 4 Participants |
Primary
Number of Participants With Abnormal Urine Parameters
Urine samples were collected for the assessment of following urine parameters by dipstick method: pH, glucose, protein, blood and ketones. The number of participants with abnormal urine parameters is presented.
Time frame: Up to Day 22
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GSK2838232 20 mg | Number of Participants With Abnormal Urine Parameters | 0 Participants |
| GSK2838232 50 mg | Number of Participants With Abnormal Urine Parameters | 0 Participants |
| GSK2838232 100 mg | Number of Participants With Abnormal Urine Parameters | 0 Participants |
| GSK2838232 200 mg | Number of Participants With Abnormal Urine Parameters | 0 Participants |
Primary
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life threatening; requires hospitalization or prolongation of existing hospitalization; results in disability/incapacity; is a congenital anomaly/birth defect; other important medical events; is associated with liver injury and impaired liver function. Safety Population comprised of all participants who received at least one dose of study treatment.
Time frame: Up to Day 22
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GSK2838232 20 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any AEs | 3 Participants |
| GSK2838232 20 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any SAEs | 0 Participants |
| GSK2838232 50 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any SAEs | 0 Participants |
| GSK2838232 50 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any AEs | 3 Participants |
| GSK2838232 100 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any AEs | 5 Participants |
| GSK2838232 100 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any SAEs | 0 Participants |
| GSK2838232 200 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any AEs | 5 Participants |
| GSK2838232 200 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any SAEs | 0 Participants |
Primary
Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance
Blood samples were collected for the assessment of clinical chemistry parameters. The clinical concern range for the parameters were: carbon dioxide/bicarbonate (low: \<18 millimoles per liter \[mmol/L\] and high: \>32 mmol/L); urea (high: \>9 mmol/L); creatinine (high: change from Baseline \>44.2 micromoles per liter \[µmol/L\]), glucose (low: \<3 and high: \>9 mmol/L); potassium (low: \<3 and high: \>5.5 mmol/L); troponin I (high: \>=0.01 micrograms per liter \[µg/L\]) and sodium (low: \<130 mmol/L and high: \>150 mmol/L). Data for any visit post-Baseline is reported.
Time frame: Up to Day 22
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GSK2838232 20 mg | Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance | Carbon dioxide/bicarbonate; >32 mmol/L | 0 Participants |
| GSK2838232 20 mg | Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance | Creatinine; Change >44.2 mmol/L | 0 Participants |
| GSK2838232 20 mg | Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance | Potassium; <3 mmol/L | 0 Participants |
| GSK2838232 20 mg | Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance | Carbon dioxide/bicarbonate; <18 mmol/L | 0 Participants |
| GSK2838232 20 mg | Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance | Potassium; >5.5 mmol/L | 0 Participants |
| GSK2838232 20 mg | Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance | Glucose; >9 mmol/L | 0 Participants |
| GSK2838232 20 mg | Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance | Urea; >9 mmol/L | 1 Participants |
| GSK2838232 20 mg | Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance | Troponin I; >=0.01 µg/L | 7 Participants |
| GSK2838232 20 mg | Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance | Sodium; <130 mmol/L | 0 Participants |
| GSK2838232 20 mg | Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance | Glucose; <3 mmol/L | 0 Participants |
| GSK2838232 20 mg | Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance | Sodium; >150 mmol/L | 0 Participants |
| GSK2838232 50 mg | Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance | Glucose; <3 mmol/L | 0 Participants |
| GSK2838232 50 mg | Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance | Sodium; >150 mmol/L | 0 Participants |
| GSK2838232 50 mg | Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance | Potassium; >5.5 mmol/L | 0 Participants |
| GSK2838232 50 mg | Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance | Potassium; <3 mmol/L | 0 Participants |
| GSK2838232 50 mg | Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance | Urea; >9 mmol/L | 0 Participants |
| GSK2838232 50 mg | Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance | Troponin I; >=0.01 µg/L | 8 Participants |
| GSK2838232 50 mg | Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance | Creatinine; Change >44.2 mmol/L | 0 Participants |
| GSK2838232 50 mg | Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance | Sodium; <130 mmol/L | 0 Participants |
| GSK2838232 50 mg | Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance | Glucose; >9 mmol/L | 0 Participants |
| GSK2838232 50 mg | Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance | Carbon dioxide/bicarbonate; <18 mmol/L | 0 Participants |
| GSK2838232 50 mg | Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance | Carbon dioxide/bicarbonate; >32 mmol/L | 0 Participants |
| GSK2838232 100 mg | Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance | Sodium; <130 mmol/L | 0 Participants |
| GSK2838232 100 mg | Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance | Carbon dioxide/bicarbonate; >32 mmol/L | 0 Participants |
| GSK2838232 100 mg | Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance | Carbon dioxide/bicarbonate; <18 mmol/L | 3 Participants |
| GSK2838232 100 mg | Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance | Urea; >9 mmol/L | 0 Participants |
| GSK2838232 100 mg | Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance | Creatinine; Change >44.2 mmol/L | 0 Participants |
| GSK2838232 100 mg | Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance | Glucose; >9 mmol/L | 0 Participants |
| GSK2838232 100 mg | Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance | Glucose; <3 mmol/L | 0 Participants |
| GSK2838232 100 mg | Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance | Potassium; >5.5 mmol/L | 0 Participants |
| GSK2838232 100 mg | Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance | Potassium; <3 mmol/L | 0 Participants |
| GSK2838232 100 mg | Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance | Sodium; >150 mmol/L | 0 Participants |
| GSK2838232 100 mg | Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance | Troponin I; >=0.01 µg/L | 10 Participants |
| GSK2838232 200 mg | Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance | Glucose; <3 mmol/L | 0 Participants |
| GSK2838232 200 mg | Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance | Troponin I; >=0.01 µg/L | 8 Participants |
| GSK2838232 200 mg | Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance | Sodium; >150 mmol/L | 0 Participants |
| GSK2838232 200 mg | Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance | Glucose; >9 mmol/L | 0 Participants |
| GSK2838232 200 mg | Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance | Creatinine; Change >44.2 mmol/L | 0 Participants |
| GSK2838232 200 mg | Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance | Urea; >9 mmol/L | 0 Participants |
| GSK2838232 200 mg | Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance | Sodium; <130 mmol/L | 0 Participants |
| GSK2838232 200 mg | Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance | Carbon dioxide/bicarbonate; <18 mmol/L | 0 Participants |
| GSK2838232 200 mg | Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance | Carbon dioxide/bicarbonate; >32 mmol/L | 0 Participants |
| GSK2838232 200 mg | Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance | Potassium; <3 mmol/L | 0 Participants |
| GSK2838232 200 mg | Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance | Potassium; >5.5 mmol/L | 2 Participants |
Primary
Number of Participants With Hematology Parameter Abnormalities of Potential Clinical Importance
Blood samples were collected for the assessment of hematology parameters. The clinical concern range for the parameters were: hematocrit (high: \>0.54 proportion of red blood cells in blood); hemoglobin (high: \>180 grams per liter \[g/L\]), lymphocytes (low: \<0.8x10\^9 cells/L); neutrophil count (low: \<1.5x10\^9 cells/L); platelet count (low: \<100x10\^9 cells/L and high: \>550x10\^9 cells/L); white blood cells (low: \<3x10\^9 cells/L and high: \>20x10\^9cells/L). Data for any visit post-Baseline is reported.
Time frame: Up to Day 22
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GSK2838232 20 mg | Number of Participants With Hematology Parameter Abnormalities of Potential Clinical Importance | Hematocrit; >0.54 | 0 Participants |
| GSK2838232 20 mg | Number of Participants With Hematology Parameter Abnormalities of Potential Clinical Importance | Hematocrit; decline from Baseline >0.075 | 1 Participants |
| GSK2838232 20 mg | Number of Participants With Hematology Parameter Abnormalities of Potential Clinical Importance | Hemoglobin; >180 | 0 Participants |
| GSK2838232 20 mg | Number of Participants With Hematology Parameter Abnormalities of Potential Clinical Importance | Hemoglobin; decline from Baseline >25 | 0 Participants |
| GSK2838232 20 mg | Number of Participants With Hematology Parameter Abnormalities of Potential Clinical Importance | Lymphocytes; <0.8 | 0 Participants |
| GSK2838232 20 mg | Number of Participants With Hematology Parameter Abnormalities of Potential Clinical Importance | Neutrophils; <1.5 | 1 Participants |
| GSK2838232 20 mg | Number of Participants With Hematology Parameter Abnormalities of Potential Clinical Importance | Platelets; >550 | 0 Participants |
| GSK2838232 20 mg | Number of Participants With Hematology Parameter Abnormalities of Potential Clinical Importance | Platelets; <100 | 0 Participants |
| GSK2838232 20 mg | Number of Participants With Hematology Parameter Abnormalities of Potential Clinical Importance | White blood cells; >20 | 0 Participants |
| GSK2838232 20 mg | Number of Participants With Hematology Parameter Abnormalities of Potential Clinical Importance | White blood cells; <3 | 0 Participants |
| GSK2838232 50 mg | Number of Participants With Hematology Parameter Abnormalities of Potential Clinical Importance | Hemoglobin; >180 | 0 Participants |
| GSK2838232 50 mg | Number of Participants With Hematology Parameter Abnormalities of Potential Clinical Importance | White blood cells; >20 | 0 Participants |
| GSK2838232 50 mg | Number of Participants With Hematology Parameter Abnormalities of Potential Clinical Importance | Hemoglobin; decline from Baseline >25 | 0 Participants |
| GSK2838232 50 mg | Number of Participants With Hematology Parameter Abnormalities of Potential Clinical Importance | Lymphocytes; <0.8 | 0 Participants |
| GSK2838232 50 mg | Number of Participants With Hematology Parameter Abnormalities of Potential Clinical Importance | Neutrophils; <1.5 | 0 Participants |
| GSK2838232 50 mg | Number of Participants With Hematology Parameter Abnormalities of Potential Clinical Importance | Platelets; >550 | 0 Participants |
| GSK2838232 50 mg | Number of Participants With Hematology Parameter Abnormalities of Potential Clinical Importance | White blood cells; <3 | 0 Participants |
| GSK2838232 50 mg | Number of Participants With Hematology Parameter Abnormalities of Potential Clinical Importance | Platelets; <100 | 0 Participants |
| GSK2838232 50 mg | Number of Participants With Hematology Parameter Abnormalities of Potential Clinical Importance | Hematocrit; >0.54 | 0 Participants |
| GSK2838232 50 mg | Number of Participants With Hematology Parameter Abnormalities of Potential Clinical Importance | Hematocrit; decline from Baseline >0.075 | 1 Participants |
| GSK2838232 100 mg | Number of Participants With Hematology Parameter Abnormalities of Potential Clinical Importance | Platelets; <100 | 1 Participants |
| GSK2838232 100 mg | Number of Participants With Hematology Parameter Abnormalities of Potential Clinical Importance | Platelets; >550 | 0 Participants |
| GSK2838232 100 mg | Number of Participants With Hematology Parameter Abnormalities of Potential Clinical Importance | White blood cells; <3 | 0 Participants |
| GSK2838232 100 mg | Number of Participants With Hematology Parameter Abnormalities of Potential Clinical Importance | Hematocrit; >0.54 | 1 Participants |
| GSK2838232 100 mg | Number of Participants With Hematology Parameter Abnormalities of Potential Clinical Importance | Hemoglobin; decline from Baseline >25 | 1 Participants |
| GSK2838232 100 mg | Number of Participants With Hematology Parameter Abnormalities of Potential Clinical Importance | Neutrophils; <1.5 | 3 Participants |
| GSK2838232 100 mg | Number of Participants With Hematology Parameter Abnormalities of Potential Clinical Importance | White blood cells; >20 | 0 Participants |
| GSK2838232 100 mg | Number of Participants With Hematology Parameter Abnormalities of Potential Clinical Importance | Hematocrit; decline from Baseline >0.075 | 3 Participants |
| GSK2838232 100 mg | Number of Participants With Hematology Parameter Abnormalities of Potential Clinical Importance | Lymphocytes; <0.8 | 0 Participants |
| GSK2838232 100 mg | Number of Participants With Hematology Parameter Abnormalities of Potential Clinical Importance | Hemoglobin; >180 | 0 Participants |
| GSK2838232 200 mg | Number of Participants With Hematology Parameter Abnormalities of Potential Clinical Importance | Lymphocytes; <0.8 | 0 Participants |
| GSK2838232 200 mg | Number of Participants With Hematology Parameter Abnormalities of Potential Clinical Importance | Platelets; <100 | 0 Participants |
| GSK2838232 200 mg | Number of Participants With Hematology Parameter Abnormalities of Potential Clinical Importance | Neutrophils; <1.5 | 1 Participants |
| GSK2838232 200 mg | Number of Participants With Hematology Parameter Abnormalities of Potential Clinical Importance | White blood cells; <3 | 1 Participants |
| GSK2838232 200 mg | Number of Participants With Hematology Parameter Abnormalities of Potential Clinical Importance | Platelets; >550 | 0 Participants |
| GSK2838232 200 mg | Number of Participants With Hematology Parameter Abnormalities of Potential Clinical Importance | Hematocrit; decline from Baseline >0.075 | 0 Participants |
| GSK2838232 200 mg | Number of Participants With Hematology Parameter Abnormalities of Potential Clinical Importance | Hemoglobin; >180 | 0 Participants |
| GSK2838232 200 mg | Number of Participants With Hematology Parameter Abnormalities of Potential Clinical Importance | Hemoglobin; decline from Baseline >25 | 0 Participants |
| GSK2838232 200 mg | Number of Participants With Hematology Parameter Abnormalities of Potential Clinical Importance | Hematocrit; >0.54 | 1 Participants |
| GSK2838232 200 mg | Number of Participants With Hematology Parameter Abnormalities of Potential Clinical Importance | White blood cells; >20 | 0 Participants |
Primary
Number of Participants With Liver Function Laboratory Abnormalities of Potential Clinical Importance
Blood samples were collected for the assessment of liver function parameters. The clinical concern range for liver function parameters were: albumin (low: \<30 g/L), total protein (low: \<15 and high: \>15 g/L), alanine aminotransferase (high: \>=2 times upper limit of normal \[ULN\]); aspartate aminotransferase (high: \>=2 times ULN); alkaline phosphatase (high: \>=2 times ULN); total bilirubin (high: \>=1.5 times ULN); direct bilirubin (high: \>0.3 times ULN).
Time frame: Up to Day 22
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GSK2838232 20 mg | Number of Participants With Liver Function Laboratory Abnormalities of Potential Clinical Importance | Albumin; <30 | 0 Participants |
| GSK2838232 20 mg | Number of Participants With Liver Function Laboratory Abnormalities of Potential Clinical Importance | Total Protein; ULN+15 | 0 Participants |
| GSK2838232 20 mg | Number of Participants With Liver Function Laboratory Abnormalities of Potential Clinical Importance | Total Protein; lower limit of normal (LLN)-15 | 0 Participants |
| GSK2838232 20 mg | Number of Participants With Liver Function Laboratory Abnormalities of Potential Clinical Importance | ALT; >=2 times ULN | 0 Participants |
| GSK2838232 20 mg | Number of Participants With Liver Function Laboratory Abnormalities of Potential Clinical Importance | AST; >=2 times ULN | 0 Participants |
| GSK2838232 20 mg | Number of Participants With Liver Function Laboratory Abnormalities of Potential Clinical Importance | ALP; >=2 times ULN | 0 Participants |
| GSK2838232 20 mg | Number of Participants With Liver Function Laboratory Abnormalities of Potential Clinical Importance | Total bilirubin; >=1.5 times ULN | 0 Participants |
| GSK2838232 20 mg | Number of Participants With Liver Function Laboratory Abnormalities of Potential Clinical Importance | Direct bilirubin; >=0.3 times ULN | 0 Participants |
| GSK2838232 50 mg | Number of Participants With Liver Function Laboratory Abnormalities of Potential Clinical Importance | ALP; >=2 times ULN | 0 Participants |
| GSK2838232 50 mg | Number of Participants With Liver Function Laboratory Abnormalities of Potential Clinical Importance | AST; >=2 times ULN | 1 Participants |
| GSK2838232 50 mg | Number of Participants With Liver Function Laboratory Abnormalities of Potential Clinical Importance | Total Protein; ULN+15 | 0 Participants |
| GSK2838232 50 mg | Number of Participants With Liver Function Laboratory Abnormalities of Potential Clinical Importance | Direct bilirubin; >=0.3 times ULN | 0 Participants |
| GSK2838232 50 mg | Number of Participants With Liver Function Laboratory Abnormalities of Potential Clinical Importance | Total bilirubin; >=1.5 times ULN | 0 Participants |
| GSK2838232 50 mg | Number of Participants With Liver Function Laboratory Abnormalities of Potential Clinical Importance | ALT; >=2 times ULN | 0 Participants |
| GSK2838232 50 mg | Number of Participants With Liver Function Laboratory Abnormalities of Potential Clinical Importance | Total Protein; lower limit of normal (LLN)-15 | 0 Participants |
| GSK2838232 50 mg | Number of Participants With Liver Function Laboratory Abnormalities of Potential Clinical Importance | Albumin; <30 | 0 Participants |
| GSK2838232 100 mg | Number of Participants With Liver Function Laboratory Abnormalities of Potential Clinical Importance | Total bilirubin; >=1.5 times ULN | 1 Participants |
| GSK2838232 100 mg | Number of Participants With Liver Function Laboratory Abnormalities of Potential Clinical Importance | Total Protein; lower limit of normal (LLN)-15 | 0 Participants |
| GSK2838232 100 mg | Number of Participants With Liver Function Laboratory Abnormalities of Potential Clinical Importance | ALT; >=2 times ULN | 0 Participants |
| GSK2838232 100 mg | Number of Participants With Liver Function Laboratory Abnormalities of Potential Clinical Importance | AST; >=2 times ULN | 0 Participants |
| GSK2838232 100 mg | Number of Participants With Liver Function Laboratory Abnormalities of Potential Clinical Importance | ALP; >=2 times ULN | 0 Participants |
| GSK2838232 100 mg | Number of Participants With Liver Function Laboratory Abnormalities of Potential Clinical Importance | Direct bilirubin; >=0.3 times ULN | 0 Participants |
| GSK2838232 100 mg | Number of Participants With Liver Function Laboratory Abnormalities of Potential Clinical Importance | Albumin; <30 | 0 Participants |
| GSK2838232 100 mg | Number of Participants With Liver Function Laboratory Abnormalities of Potential Clinical Importance | Total Protein; ULN+15 | 0 Participants |
| GSK2838232 200 mg | Number of Participants With Liver Function Laboratory Abnormalities of Potential Clinical Importance | Total Protein; lower limit of normal (LLN)-15 | 0 Participants |
| GSK2838232 200 mg | Number of Participants With Liver Function Laboratory Abnormalities of Potential Clinical Importance | ALT; >=2 times ULN | 0 Participants |
| GSK2838232 200 mg | Number of Participants With Liver Function Laboratory Abnormalities of Potential Clinical Importance | Total Protein; ULN+15 | 0 Participants |
| GSK2838232 200 mg | Number of Participants With Liver Function Laboratory Abnormalities of Potential Clinical Importance | Albumin; <30 | 0 Participants |
| GSK2838232 200 mg | Number of Participants With Liver Function Laboratory Abnormalities of Potential Clinical Importance | AST; >=2 times ULN | 0 Participants |
| GSK2838232 200 mg | Number of Participants With Liver Function Laboratory Abnormalities of Potential Clinical Importance | Direct bilirubin; >=0.3 times ULN | 0 Participants |
| GSK2838232 200 mg | Number of Participants With Liver Function Laboratory Abnormalities of Potential Clinical Importance | Total bilirubin; >=1.5 times ULN | 0 Participants |
| GSK2838232 200 mg | Number of Participants With Liver Function Laboratory Abnormalities of Potential Clinical Importance | ALP; >=2 times ULN | 0 Participants |
Primary
Number of Participants With Vital Signs Data Outside Clinical Concern Range
Vital signs were measured in a semi-supine position after 5 minutes rest and included temperature, systolic and diastolic blood pressure and pulse rate. The clinical concern range for vital signs were: systolic blood pressure (SBP) (low: \<85 and high: \>160 millimeters of mercury \[mmHg\]) and diastolic blood pressure (DBP) (low: \<45 and high: \>100 mmHg). Number of participants with vital signs data outside clinical concern range is presented.
Time frame: Day 1 (pre-dose)
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GSK2838232 20 mg | Number of Participants With Vital Signs Data Outside Clinical Concern Range | SBP; >Clinical concern range | 0 Participants |
| GSK2838232 20 mg | Number of Participants With Vital Signs Data Outside Clinical Concern Range | SBP; <Clinical concern range | 0 Participants |
| GSK2838232 20 mg | Number of Participants With Vital Signs Data Outside Clinical Concern Range | DBP; >Clinical concern range | 0 Participants |
| GSK2838232 20 mg | Number of Participants With Vital Signs Data Outside Clinical Concern Range | DBP; <Clinical concern range | 0 Participants |
| GSK2838232 50 mg | Number of Participants With Vital Signs Data Outside Clinical Concern Range | SBP; <Clinical concern range | 0 Participants |
| GSK2838232 50 mg | Number of Participants With Vital Signs Data Outside Clinical Concern Range | DBP; >Clinical concern range | 0 Participants |
| GSK2838232 50 mg | Number of Participants With Vital Signs Data Outside Clinical Concern Range | DBP; <Clinical concern range | 0 Participants |
| GSK2838232 50 mg | Number of Participants With Vital Signs Data Outside Clinical Concern Range | SBP; >Clinical concern range | 0 Participants |
| GSK2838232 100 mg | Number of Participants With Vital Signs Data Outside Clinical Concern Range | DBP; >Clinical concern range | 1 Participants |
| GSK2838232 100 mg | Number of Participants With Vital Signs Data Outside Clinical Concern Range | SBP; <Clinical concern range | 0 Participants |
| GSK2838232 100 mg | Number of Participants With Vital Signs Data Outside Clinical Concern Range | DBP; <Clinical concern range | 0 Participants |
| GSK2838232 100 mg | Number of Participants With Vital Signs Data Outside Clinical Concern Range | SBP; >Clinical concern range | 1 Participants |
| GSK2838232 200 mg | Number of Participants With Vital Signs Data Outside Clinical Concern Range | DBP; <Clinical concern range | 0 Participants |
| GSK2838232 200 mg | Number of Participants With Vital Signs Data Outside Clinical Concern Range | SBP; <Clinical concern range | 0 Participants |
| GSK2838232 200 mg | Number of Participants With Vital Signs Data Outside Clinical Concern Range | SBP; >Clinical concern range | 0 Participants |
| GSK2838232 200 mg | Number of Participants With Vital Signs Data Outside Clinical Concern Range | DBP; >Clinical concern range | 0 Participants |
Primary
Pre-dose Concentration (C0) of GSK2838232 on Day 10
Serial plasma samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232.
Time frame: Pre dose on Day 10
Population: Pharmacokinetic Population. Only those participants with data available at the specified time point were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| GSK2838232 20 mg | Pre-dose Concentration (C0) of GSK2838232 on Day 10 | 20.02 Nanograms per milliliter | Geometric Coefficient of Variation 28.8 |
| GSK2838232 50 mg | Pre-dose Concentration (C0) of GSK2838232 on Day 10 | 36.66 Nanograms per milliliter | Geometric Coefficient of Variation 39.8 |
| GSK2838232 100 mg | Pre-dose Concentration (C0) of GSK2838232 on Day 10 | 75.31 Nanograms per milliliter | Geometric Coefficient of Variation 57 |
| GSK2838232 200 mg | Pre-dose Concentration (C0) of GSK2838232 on Day 10 | 155.5 Nanograms per milliliter | Geometric Coefficient of Variation 64.5 |
Primary
Terminal Elimination Half-life (T1/2) of GSK2838232 Following Administration on Day 10
Serial plasma samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232.
Time frame: Pre dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose on Day 10
Population: Pharmacokinetic Population. Only those participants with data available at the specified time point were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| GSK2838232 20 mg | Terminal Elimination Half-life (T1/2) of GSK2838232 Following Administration on Day 10 | 19.221 Hours | Geometric Coefficient of Variation 17.1 |
| GSK2838232 50 mg | Terminal Elimination Half-life (T1/2) of GSK2838232 Following Administration on Day 10 | 16.298 Hours | Geometric Coefficient of Variation 24 |
| GSK2838232 100 mg | Terminal Elimination Half-life (T1/2) of GSK2838232 Following Administration on Day 10 | 18.113 Hours | Geometric Coefficient of Variation 18.3 |
| GSK2838232 200 mg | Terminal Elimination Half-life (T1/2) of GSK2838232 Following Administration on Day 10 | 16.351 Hours | Geometric Coefficient of Variation 8.8 |
Primary
Time to Maximum Observed Concentration (Tmax) for GSK2838232 on Day 1
Serial plasma samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232.
Time frame: Pre dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose on Day 1
Population: Pharmacokinetic Population. One participant from GSK2838232 100 mg arm was dosed with GSK2838232 50 mg on Days 1 and 2; hence, pharmacokinetic parameters for that participant were summarized with GSK2838232 50 mg for Day 1
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| GSK2838232 20 mg | Time to Maximum Observed Concentration (Tmax) for GSK2838232 on Day 1 | 4.033 Hours |
| GSK2838232 50 mg | Time to Maximum Observed Concentration (Tmax) for GSK2838232 on Day 1 | 3.250 Hours |
| GSK2838232 100 mg | Time to Maximum Observed Concentration (Tmax) for GSK2838232 on Day 1 | 6.000 Hours |
| GSK2838232 200 mg | Time to Maximum Observed Concentration (Tmax) for GSK2838232 on Day 1 | 4.000 Hours |
Primary
Tmax for GSK2838232 Following Administration on Day 10
Serial plasma samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232.
Time frame: Pre dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose on Day 10
Population: Pharmacokinetic Population. Only those participants with data available at the specified time point were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| GSK2838232 20 mg | Tmax for GSK2838232 Following Administration on Day 10 | 6.000 Hours |
| GSK2838232 50 mg | Tmax for GSK2838232 Following Administration on Day 10 | 4.000 Hours |
| GSK2838232 100 mg | Tmax for GSK2838232 Following Administration on Day 10 | 6.000 Hours |
| GSK2838232 200 mg | Tmax for GSK2838232 Following Administration on Day 10 | 4.083 Hours |
Secondary
Accumulation Ratio for GSK2838232
Serial blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232. The accumulation ratios were calculated as R\_AUC=AUC(0-tau) Day 10/AUC(0-24) Day 1; R\_Cmax=Cmax Day 10/Cmax Day 1 and R\_Ctau=Ctau Day 10/C24 Day 1.
Time frame: pre dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose on Days 1 and 10; pre-dose on Days 3, 4, 5, 8 and 9; Days 12 and 14
Population: Pharmacokinetic Population. Only participants with data available at the specified time points were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| GSK2838232 20 mg | Accumulation Ratio for GSK2838232 | R_AUC | 3.149 Ratio | Geometric Coefficient of Variation 42.2 |
| GSK2838232 20 mg | Accumulation Ratio for GSK2838232 | R_Ctau | 3.267 Ratio | Geometric Coefficient of Variation 41.2 |
| GSK2838232 20 mg | Accumulation Ratio for GSK2838232 | R_Cmax | 2.580 Ratio | Geometric Coefficient of Variation 45.1 |
| GSK2838232 50 mg | Accumulation Ratio for GSK2838232 | R_AUC | 2.004 Ratio | Geometric Coefficient of Variation 34.4 |
| GSK2838232 50 mg | Accumulation Ratio for GSK2838232 | R_Ctau | 2.118 Ratio | Geometric Coefficient of Variation 43.9 |
| GSK2838232 50 mg | Accumulation Ratio for GSK2838232 | R_Cmax | 1.498 Ratio | Geometric Coefficient of Variation 40 |
| GSK2838232 100 mg | Accumulation Ratio for GSK2838232 | R_Cmax | 2.753 Ratio | Geometric Coefficient of Variation 43.4 |
| GSK2838232 100 mg | Accumulation Ratio for GSK2838232 | R_AUC | 3.229 Ratio | Geometric Coefficient of Variation 46.1 |
| GSK2838232 100 mg | Accumulation Ratio for GSK2838232 | R_Ctau | 3.038 Ratio | Geometric Coefficient of Variation 64.8 |
| GSK2838232 200 mg | Accumulation Ratio for GSK2838232 | R_AUC | 2.211 Ratio | Geometric Coefficient of Variation 27.2 |
| GSK2838232 200 mg | Accumulation Ratio for GSK2838232 | R_Ctau | 2.210 Ratio | Geometric Coefficient of Variation 45.1 |
| GSK2838232 200 mg | Accumulation Ratio for GSK2838232 | R_Cmax | 1.668 Ratio | Geometric Coefficient of Variation 26.5 |
Secondary
Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Count to Day 11
CD4+ cell counts were assessed by flow cytometry. Baseline value is the latest pre-dose assessment value. Change from Baseline is calculated as the post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1) and Day 11
Population: ITT Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GSK2838232 20 mg | Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Count to Day 11 | -1.4 Cells per microliter | Standard Deviation 95.26 |
| GSK2838232 50 mg | Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Count to Day 11 | 52.0 Cells per microliter | Standard Deviation 145.36 |
| GSK2838232 100 mg | Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Count to Day 11 | 40.7 Cells per microliter | Standard Deviation 94.47 |
| GSK2838232 200 mg | Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Count to Day 11 | 11.1 Cells per microliter | Standard Deviation 75.15 |
Secondary
Change From Baseline to Day 11 in CD4+ Count Relative to Day 10 AUC (0 to Tau)
The relationship between pharmacokinetic parameters (AUC) and pharmacodynamic measures (change from Baseline CD4+ cell count) was explored using a frequentist linear model. The model parameters estimated included slope and intercept. The estimate (slope) along with 95% confidence interval is presented.
Time frame: Baseline (Day 1), Days 10 and 11
Population: Pharmacokinetic/Pharmacodynamic Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GSK2838232 20 mg | Change From Baseline to Day 11 in CD4+ Count Relative to Day 10 AUC (0 to Tau) | -0.003 cells/microliter/ng*h/mL |
Secondary
Change From Baseline to Day 11 in CD4+ Count Relative to Day 10 Cmax
The relationship between pharmacokinetic parameters (Cmax) and pharmacodynamic measures (change from Baseline CD4+ cell count) was explored using a frequentist linear model. The model parameters estimated included slope and intercept. The estimate (slope) along with 95% confidence interval is presented
Time frame: Baseline (Day 1), Days 10 and 11
Population: Pharmacokinetic/Pharmacodynamic Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GSK2838232 20 mg | Change From Baseline to Day 11 in CD4+ Count Relative to Day 10 Cmax | -0.067 cells/microliter/nanograms/milliliter |
Secondary
Change From Baseline to Day 11 in CD4+ Count Relative to Day 10 Ctau
The relationship between pharmacokinetic parameters (Ctau) and pharmacodynamic measures (change from Baseline CD4+ cell count) was explored using a frequentist linear model. The model parameters estimated included slope and intercept. The estimate (slope) along with 95% confidence interval is presented.
Time frame: Baseline (Day 1), Days 10 and 11
Population: Pharmacokinetic/Pharmacodynamic Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GSK2838232 20 mg | Change From Baseline to Day 11 in CD4+ Count Relative to Day 10 Ctau | -0.079 cells/microliter/nanograms/milliliter |
Secondary
Change From Baseline to Day 11 in log10 Plasma HIV-1 RNA Relative to Day 10 AUC (0 to Tau)
Plasma samples were collected for quantitative analysis of HIV-1 RNA. Change from Baseline is the value at indicated time point minus Baseline value. Statistical analysis for relationship between pharmacokinetic parameters (AUC) and pharmacodynamic measures (Change from Baseline in plasma HIV-1 RNA) was explored using a frequentist three parameter Emax non-linear model. The model parameters estimated included: maximum response (Emax), pharmacokinetic parameter value that attains 50% of the maximal effect (ED50) and residual variability (s2e). Pharmacokinetic/Pharmacodynamic Population comprised of participants who met criteria for Per-Protocol (all participants who met study criteria and are enrolled into the study with documented evidence of having received all doses and all post-baseline HIV-1 RNA measurement, with exceptions of those who have at least one major protocol deviation) and Pharmacokinetic Population analysis sets and who underwent pharmacodynamic sampling during study.
Time frame: Baseline (Day 1), Days 10 and 11
Population: Pharmacokinetic/Pharmacodynamic Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GSK2838232 20 mg | Change From Baseline to Day 11 in log10 Plasma HIV-1 RNA Relative to Day 10 AUC (0 to Tau) | -0.4979 log10 copies per milliliter | Standard Deviation 0.44873 |
| GSK2838232 50 mg | Change From Baseline to Day 11 in log10 Plasma HIV-1 RNA Relative to Day 10 AUC (0 to Tau) | -1.1671 log10 copies per milliliter | Standard Deviation 0.51996 |
| GSK2838232 100 mg | Change From Baseline to Day 11 in log10 Plasma HIV-1 RNA Relative to Day 10 AUC (0 to Tau) | -1.1745 log10 copies per milliliter | Standard Deviation 0.45005 |
| GSK2838232 200 mg | Change From Baseline to Day 11 in log10 Plasma HIV-1 RNA Relative to Day 10 AUC (0 to Tau) | -1.5994 log10 copies per milliliter | Standard Deviation 0.32718 |
95% CI: [-2.333, 1.31]
95% CI: [100.786, 1940.724]
95% CI: [0.095, 0.306]
Secondary
Change From Baseline to Day 11 in log10 Plasma HIV-1 RNA Relative to Day 10 Cmax
Plasma samples were collected for quantitative analysis of HIV-1 RNA. Change from Baseline is the value at indicated time point minus Baseline value. Statistical analysis for the relationship between pharmacokinetic parameters (Cmax) and pharmacodynamic measures (change from Baseline in log10 plasma HIV-1 RNA) was explored using a frequentist three parameter Emax non-linear model. The model parameters estimated included: maximum response (Emax), pharmacokinetic parameter value that attains the 50% of the maximal effect (ED50) and s2e.
Time frame: Baseline (Day 1), Days 10 and 11
Population: Pharmacokinetic/Pharmacodynamic Population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GSK2838232 20 mg | Change From Baseline to Day 11 in log10 Plasma HIV-1 RNA Relative to Day 10 Cmax | -0.4979 log10 copies per milliliter | Standard Deviation 0.44873 |
| GSK2838232 50 mg | Change From Baseline to Day 11 in log10 Plasma HIV-1 RNA Relative to Day 10 Cmax | -1.1671 log10 copies per milliliter | Standard Deviation 0.51996 |
| GSK2838232 100 mg | Change From Baseline to Day 11 in log10 Plasma HIV-1 RNA Relative to Day 10 Cmax | -1.1745 log10 copies per milliliter | Standard Deviation 0.45005 |
| GSK2838232 200 mg | Change From Baseline to Day 11 in log10 Plasma HIV-1 RNA Relative to Day 10 Cmax | -1.5994 log10 copies per milliliter | Standard Deviation 0.32718 |
95% CI: [-2.319, -1.283]
95% CI: [3.565, 107.579]
95% CI: [0.097, 0.314]
Secondary
Change From Baseline to Day 11 in log10 Plasma HIV-1 RNA Relative to Day 10 Ctau
Plasma samples were collected for quantitative analysis of HIV-1 RNA. Change from Baseline is the value at indicated time point minus Baseline value. Statistical analysis for the relationship between pharmacokinetic parameters (Ctau) and pharmacodynamic measures (change from Baseline in log10 plasma HIV-1 RNA) was explored using a frequentist three parameter Emax non-linear model. The model parameters estimated included: maximum response (Emax), pharmacokinetic parameter value that attains the 50% of the maximal effect (ED50) and s2e.
Time frame: Baseline (Day 1), Days 10 and 11
Population: Pharmacokinetic/Pharmacodynamic Population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GSK2838232 20 mg | Change From Baseline to Day 11 in log10 Plasma HIV-1 RNA Relative to Day 10 Ctau | -0.4979 log10 copies per milliliter | Standard Deviation 0.44873 |
| GSK2838232 50 mg | Change From Baseline to Day 11 in log10 Plasma HIV-1 RNA Relative to Day 10 Ctau | -1.1671 log10 copies per milliliter | Standard Deviation 0.51996 |
| GSK2838232 100 mg | Change From Baseline to Day 11 in log10 Plasma HIV-1 RNA Relative to Day 10 Ctau | -1.1745 log10 copies per milliliter | Standard Deviation 0.45005 |
| GSK2838232 200 mg | Change From Baseline to Day 11 in log10 Plasma HIV-1 RNA Relative to Day 10 Ctau | -1.5994 log10 copies per milliliter | Standard Deviation 0.32718 |
95% CI: [-2.352, -1.34]
95% CI: [4.687, 60.143]
95% CI: [0.094, 0.305]
Secondary
Dose Proportionality of GSK2838232
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232. Dose proportionality was assessed using a fixed effects power model. Estimated slope and 90% confidence interval is presented.
Time frame: pre dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose on Days 1 and 10
Population: Pharmacokinetic Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category )
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GSK2838232 20 mg | Dose Proportionality of GSK2838232 | AUC(0-24); Day 1 | 1.157 slope of log dose |
| GSK2838232 20 mg | Dose Proportionality of GSK2838232 | Cmax; Day 1 | 1.158 slope of log dose |
| GSK2838232 20 mg | Dose Proportionality of GSK2838232 | C24; Day 1 | 1.170 slope of log dose |
| GSK2838232 20 mg | Dose Proportionality of GSK2838232 | AUC (0 to tau); Day 10 | 1.012 slope of log dose |
| GSK2838232 20 mg | Dose Proportionality of GSK2838232 | Cmax; Day 10 | 1.013 slope of log dose |
| GSK2838232 20 mg | Dose Proportionality of GSK2838232 | Ctau; Day 10 | 0.988 slope of log dose |
Secondary
Number of Participants With Emergent Drug Resistance Mutations
Plasma samples were collected to evaluate treatment-emergent genotypic mutations in Gag, reverse transcriptase (RT) and protease (PR) and to assess phenotypic resistance to GSK2838232 and RT and PR drugs. Number of participants with treatment emergent RT/PR mutations, reduced susceptibility to nucleoside/nucleotide reverse transcriptase inhibitor (NRTI), non-nucleoside reverse transcriptase inhibitor (NNRTI), or protease inhibitor (PI), treatment emergent maturation inhibitor A364A/V and GSK2838232 phenotypic resistance is presented.
Time frame: Up to Day 11
Population: ITT Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GSK2838232 20 mg | Number of Participants With Emergent Drug Resistance Mutations | RT/PR mutations | 0 Participants |
| GSK2838232 20 mg | Number of Participants With Emergent Drug Resistance Mutations | Reduced susceptibility to NRTIs, NNRTIs, PIs | 0 Participants |
| GSK2838232 20 mg | Number of Participants With Emergent Drug Resistance Mutations | GSK2838232 phenotypic resistance | 0 Participants |
| GSK2838232 20 mg | Number of Participants With Emergent Drug Resistance Mutations | Treatment emergent A364A/V | 0 Participants |
| GSK2838232 50 mg | Number of Participants With Emergent Drug Resistance Mutations | Reduced susceptibility to NRTIs, NNRTIs, PIs | 0 Participants |
| GSK2838232 50 mg | Number of Participants With Emergent Drug Resistance Mutations | GSK2838232 phenotypic resistance | 1 Participants |
| GSK2838232 50 mg | Number of Participants With Emergent Drug Resistance Mutations | Treatment emergent A364A/V | 1 Participants |
| GSK2838232 50 mg | Number of Participants With Emergent Drug Resistance Mutations | RT/PR mutations | 0 Participants |
| GSK2838232 100 mg | Number of Participants With Emergent Drug Resistance Mutations | GSK2838232 phenotypic resistance | 0 Participants |
| GSK2838232 100 mg | Number of Participants With Emergent Drug Resistance Mutations | Reduced susceptibility to NRTIs, NNRTIs, PIs | 0 Participants |
| GSK2838232 100 mg | Number of Participants With Emergent Drug Resistance Mutations | Treatment emergent A364A/V | 1 Participants |
| GSK2838232 100 mg | Number of Participants With Emergent Drug Resistance Mutations | RT/PR mutations | 0 Participants |
| GSK2838232 200 mg | Number of Participants With Emergent Drug Resistance Mutations | Treatment emergent A364A/V | 0 Participants |
| GSK2838232 200 mg | Number of Participants With Emergent Drug Resistance Mutations | Reduced susceptibility to NRTIs, NNRTIs, PIs | 0 Participants |
| GSK2838232 200 mg | Number of Participants With Emergent Drug Resistance Mutations | RT/PR mutations | 0 Participants |
| GSK2838232 200 mg | Number of Participants With Emergent Drug Resistance Mutations | GSK2838232 phenotypic resistance | 0 Participants |
Secondary
Pre-morning Dose Concentrations (C0) on Day 2 Through 11
Blood samples were collected for pharmacokinetic analysis of GSK2838232. The pre-morning dose concentrations for Days 2 to 11 is presented. One participant from GSK2838232 100 mg arm was dosed with GSK2838232 50 mg on Days 1 and 2; hence, pharmacokinetic parameters for that participant were summarized with GSK2838232 50 mg for Days 1 and 2 and with GSK2838232 100 mg for Days 3 to 10.
Time frame: Pre-dose on Days 2, 3, 4, 5, 8, 9, 10 and 11
Population: Pharmacokinetic Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK2838232 20 mg | Pre-morning Dose Concentrations (C0) on Day 2 Through 11 | Day 2; n=7, 9, 9, 8 | 6.08 Nanograms per milliliter | Standard Deviation 1.695 |
| GSK2838232 20 mg | Pre-morning Dose Concentrations (C0) on Day 2 Through 11 | Day 3; n=7, 8, 10, 8 | 13.99 Nanograms per milliliter | Standard Deviation 5.576 |
| GSK2838232 20 mg | Pre-morning Dose Concentrations (C0) on Day 2 Through 11 | Day 4; n=7, 7, 10, 8 | 14.66 Nanograms per milliliter | Standard Deviation 5.771 |
| GSK2838232 20 mg | Pre-morning Dose Concentrations (C0) on Day 2 Through 11 | Day 5; n=4, 6, 10, 7 | 15.03 Nanograms per milliliter | Standard Deviation 3.308 |
| GSK2838232 20 mg | Pre-morning Dose Concentrations (C0) on Day 2 Through 11 | Day 8; n=7, 8, 10, 8 | 19.72 Nanograms per milliliter | Standard Deviation 7.139 |
| GSK2838232 20 mg | Pre-morning Dose Concentrations (C0) on Day 2 Through 11 | Day 9; n=7, 6, 10, 8 | 20.53 Nanograms per milliliter | Standard Deviation 6.76 |
| GSK2838232 20 mg | Pre-morning Dose Concentrations (C0) on Day 2 Through 11 | Day 10; n=7, 7, 10, 8 | 20.76 Nanograms per milliliter | Standard Deviation 6.426 |
| GSK2838232 20 mg | Pre-morning Dose Concentrations (C0) on Day 2 Through 11 | Day 11; n=7, 7, 10, 8 | 20.16 Nanograms per milliliter | Standard Deviation 6.828 |
| GSK2838232 50 mg | Pre-morning Dose Concentrations (C0) on Day 2 Through 11 | Day 9; n=7, 6, 10, 8 | 43.83 Nanograms per milliliter | Standard Deviation 18.691 |
| GSK2838232 50 mg | Pre-morning Dose Concentrations (C0) on Day 2 Through 11 | Day 8; n=7, 8, 10, 8 | 43.14 Nanograms per milliliter | Standard Deviation 16.664 |
| GSK2838232 50 mg | Pre-morning Dose Concentrations (C0) on Day 2 Through 11 | Day 3; n=7, 8, 10, 8 | 29.03 Nanograms per milliliter | Standard Deviation 11.87 |
| GSK2838232 50 mg | Pre-morning Dose Concentrations (C0) on Day 2 Through 11 | Day 11; n=7, 7, 10, 8 | 35.09 Nanograms per milliliter | Standard Deviation 16.038 |
| GSK2838232 50 mg | Pre-morning Dose Concentrations (C0) on Day 2 Through 11 | Day 10; n=7, 7, 10, 8 | 39.19 Nanograms per milliliter | Standard Deviation 16.502 |
| GSK2838232 50 mg | Pre-morning Dose Concentrations (C0) on Day 2 Through 11 | Day 5; n=4, 6, 10, 7 | 34.35 Nanograms per milliliter | Standard Deviation 15.626 |
| GSK2838232 50 mg | Pre-morning Dose Concentrations (C0) on Day 2 Through 11 | Day 4; n=7, 7, 10, 8 | 31.80 Nanograms per milliliter | Standard Deviation 13.319 |
| GSK2838232 50 mg | Pre-morning Dose Concentrations (C0) on Day 2 Through 11 | Day 2; n=7, 9, 9, 8 | 16.39 Nanograms per milliliter | Standard Deviation 9.002 |
| GSK2838232 100 mg | Pre-morning Dose Concentrations (C0) on Day 2 Through 11 | Day 10; n=7, 7, 10, 8 | 84.52 Nanograms per milliliter | Standard Deviation 39.94 |
| GSK2838232 100 mg | Pre-morning Dose Concentrations (C0) on Day 2 Through 11 | Day 4; n=7, 7, 10, 8 | 64.49 Nanograms per milliliter | Standard Deviation 26.71 |
| GSK2838232 100 mg | Pre-morning Dose Concentrations (C0) on Day 2 Through 11 | Day 5; n=4, 6, 10, 7 | 76.14 Nanograms per milliliter | Standard Deviation 35.179 |
| GSK2838232 100 mg | Pre-morning Dose Concentrations (C0) on Day 2 Through 11 | Day 8; n=7, 8, 10, 8 | 86.39 Nanograms per milliliter | Standard Deviation 43.382 |
| GSK2838232 100 mg | Pre-morning Dose Concentrations (C0) on Day 2 Through 11 | Day 9; n=7, 6, 10, 8 | 89.32 Nanograms per milliliter | Standard Deviation 40.407 |
| GSK2838232 100 mg | Pre-morning Dose Concentrations (C0) on Day 2 Through 11 | Day 11; n=7, 7, 10, 8 | 89.87 Nanograms per milliliter | Standard Deviation 49.195 |
| GSK2838232 100 mg | Pre-morning Dose Concentrations (C0) on Day 2 Through 11 | Day 2; n=7, 9, 9, 8 | 34.17 Nanograms per milliliter | Standard Deviation 13.99 |
| GSK2838232 100 mg | Pre-morning Dose Concentrations (C0) on Day 2 Through 11 | Day 3; n=7, 8, 10, 8 | 51.27 Nanograms per milliliter | Standard Deviation 25.971 |
| GSK2838232 200 mg | Pre-morning Dose Concentrations (C0) on Day 2 Through 11 | Day 4; n=7, 7, 10, 8 | 176.28 Nanograms per milliliter | Standard Deviation 96.684 |
| GSK2838232 200 mg | Pre-morning Dose Concentrations (C0) on Day 2 Through 11 | Day 5; n=4, 6, 10, 7 | 206.29 Nanograms per milliliter | Standard Deviation 69.533 |
| GSK2838232 200 mg | Pre-morning Dose Concentrations (C0) on Day 2 Through 11 | Day 3; n=7, 8, 10, 8 | 163.98 Nanograms per milliliter | Standard Deviation 91.368 |
| GSK2838232 200 mg | Pre-morning Dose Concentrations (C0) on Day 2 Through 11 | Day 2; n=7, 9, 9, 8 | 96.94 Nanograms per milliliter | Standard Deviation 44.319 |
| GSK2838232 200 mg | Pre-morning Dose Concentrations (C0) on Day 2 Through 11 | Day 8; n=7, 8, 10, 8 | 187.16 Nanograms per milliliter | Standard Deviation 110.304 |
| GSK2838232 200 mg | Pre-morning Dose Concentrations (C0) on Day 2 Through 11 | Day 11; n=7, 7, 10, 8 | 219.23 Nanograms per milliliter | Standard Deviation 133.552 |
| GSK2838232 200 mg | Pre-morning Dose Concentrations (C0) on Day 2 Through 11 | Day 10; n=7, 7, 10, 8 | 189.05 Nanograms per milliliter | Standard Deviation 107.636 |
| GSK2838232 200 mg | Pre-morning Dose Concentrations (C0) on Day 2 Through 11 | Day 9; n=7, 6, 10, 8 | 206.75 Nanograms per milliliter | Standard Deviation 124.166 |
Secondary
Steady State Assessment of Plasma Pre-dose Concentrations by Treatment
A linear mixed model using Day, treatment and Day by treatment as fixed effects and participant as a random effect on the log-transformed pre-dose values was performed to evaluate if steady state was achieved using the Helmert transformation approach. The comparison was done as Day 8 versus the average of Days 9 and 10 values. The ratio of geometric least square mean for Day 8 versus average of Days 9 and 10 values is presented along with 95% confidence interval.
Time frame: Pre-dose on Days 8, 9 and 10
Population: Pharmacokinetic Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GSK2838232 20 mg | Steady State Assessment of Plasma Pre-dose Concentrations by Treatment | 0.924 Ratio |
| GSK2838232 50 mg | Steady State Assessment of Plasma Pre-dose Concentrations by Treatment | 0.999 Ratio |
| GSK2838232 100 mg | Steady State Assessment of Plasma Pre-dose Concentrations by Treatment | 0.958 Ratio |
| GSK2838232 200 mg | Steady State Assessment of Plasma Pre-dose Concentrations by Treatment | 0.961 Ratio |