Safety and Efficacy Study of GSK2838232 in Human Immunodeficiency Virus (HIV)-1 Infected Adults

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03045861
• Collaborator: (none)
• Enrollment: 33
• Locations: 14
• Arms: 4
• Actual Duration (Months): 13.2
• Patients Per Site: 2.4
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Infection, Human Immunodeficiency Virus; HIV Infections	Drug: GSK2838232; Drug: Cobicistat	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 33 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2a, Multicenter, Randomized, Adaptive, Open-label, Dose Ranging Study to Evaluate the Antiviral Effect, Safety, Tolerability and Pharmacokinetics of Cobicistat-boosted GSK2838232 Monotherapy Over 10 Days in HIV-1 Infected Treatment-naive Adults
• Actual Study Start Date: Mar 17, 2017
• Actual Primary Completion Date: Apr 23, 2018
• Actual Study Completion Date: Apr 23, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1-GSK2838232 100 mg + Cobicistat 150 mg in Part A During Part A (Cohort 1), subjects will receive a single dose of GSK2838232 100 mg and Cobicistat 150 mg once daily each morning with a light breakfast meal and 240 mL of water from Day 1 to Day 10. Subjects will be followed up to Day 22.	Drug: GSK2838232; GSK2838232 capsules will be supplied as swedish orange, unmarked capsule (50 mg), and white, unmarked capsules (10 mg) in high-density polyethylene bottles.; Drug: Cobicistat; Cobicistat tablets 150 mg will be supplied as an orange, round, biconvex, film-coated tablet in bulk containers for individualized dosing.
Experimental: Cohort 2-GSK2838232 200 mg + Cobicistat 150 mg in Part B During Part B (Cohort 2), subjects will receive a single dose of GSK2838232 200 mg and Cobicistat 150 mg once daily each morning with a light breakfast meal and 240 mL of water from Day 1 to Day 10. Subjects will be followed up to Day 22.	Drug: GSK2838232; GSK2838232 capsules will be supplied as swedish orange, unmarked capsule (50 mg), and white, unmarked capsules (10 mg) in high-density polyethylene bottles.; Drug: Cobicistat; Cobicistat tablets 150 mg will be supplied as an orange, round, biconvex, film-coated tablet in bulk containers for individualized dosing.
Experimental: Cohort 3-GSK2838232 50 mg + Cobicistat 150 mg in Part B During Part B (Cohort 3), subjects will receive a single dose of GSK2838232 50 mg and Cobicistat 150 mg once daily each morning with a light breakfast meal and 240 mL of water from Day 1 to Day 10. Subjects will be followed up to Day 22.	Drug: GSK2838232; GSK2838232 capsules will be supplied as swedish orange, unmarked capsule (50 mg), and white, unmarked capsules (10 mg) in high-density polyethylene bottles.; Drug: Cobicistat; Cobicistat tablets 150 mg will be supplied as an orange, round, biconvex, film-coated tablet in bulk containers for individualized dosing.
Experimental: Cohort 4-GSK2838232 20 mg + Cobicistat 150 mg in Part B During Part B (Cohort 4), subjects will receive a single dose of GSK2838232 20 mg and Cobicistat 150 mg once daily each morning with a light breakfast meal and 240 mL of water from Day 1 to Day 10. Subjects will be followed up to Day 22.	Drug: GSK2838232; GSK2838232 capsules will be supplied as swedish orange, unmarked capsule (50 mg), and white, unmarked capsules (10 mg) in high-density polyethylene bottles.; Drug: Cobicistat; Cobicistat tablets 150 mg will be supplied as an orange, round, biconvex, film-coated tablet in bulk containers for individualized dosing.

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

5. 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).

6. 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.

7. 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.

8. 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.

9. 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.

10. 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.

11. 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.

12. 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.

13. 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.

14. 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.

15. 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.

16. 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.

17. 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.

18. 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.

19. 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.

20. 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.

21. 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.

Secondary Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. 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

7. 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.

8. 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.

9. 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.

10. 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.

11. 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.

12. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: Male
• Accepts 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.

Exclusion Criteria:

• Alanine aminotransferase (ALT) and bilirubin (BIL) >1.5 x upper limit of normal (ULN), isolated BIL >1.5xULN is acceptable if BIL is fractionated and direct BIL <35 percent.

• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones); hepatitis B virus (HBV) and/or hepatitis C virus (HCV) positive.

• Subjects who have any other chronic medical condition, including cardiovascular (CV), respiratory, neurologic, psychiatric, renal, gastrointestinal (GI), oncologic, rheumatologic, or dermatologic.

• Medical history of cardiac arrhythmias or cardiac disease or a family or personal history of long QT syndrome.

• Unable to refrain from the use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and GSK medical monitor the medication will not interfere with the study procedures or compromise subject safety.

• History of regular alcohol consumption within 6 months of the study defined as: an average weekly intake of >14 drinks for males or >7 drinks for females. One drink is equivalent to 12 grams (g) of alcohol: 12 ounces (360 mL) of beer, 5 ounces (150 mL) of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits.

• Smoking is an exclusion criteria for this study. Subject having urinary cotinine levels indicative of smoking at screening.

• Chronic marijuana or use of other elicit medications (cocaine, heroin) is an exclusion criteria.

• 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.

• Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment.

• Screening or Baseline cardiac troponin I greater than the 99 percent cutoff (>0.045 nanogram [ng]/mL by the Dimension Vista cardiac troponin [CTN] I assay).

• A positive pre-study drug/alcohol screen.

• Prior history of receiving an HIV maturation inhibitor

• Where participation in the study would result in donation of blood or blood products in excess of 500 mL within 56 days.

• The subject has participated in a clinical trial and has received an investigational product within the following time period 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).

• Exposure to more than four new chemical entities within 12 months prior to the first dosing day.

• Treatment with radiation therapy or cytotoxic chemotherapeutic agents within 30 days of study drug administration or anticipated need for such treatment within the study.

• Treatment with immunomodulating agents (such as systemic corticosteroids, interleukins, interferons) or any agent with known anti-HIV activity (such as hydroxyurea or foscarnet) within 30 days of study drug administration.

• An active Center for Disease Control and Prevention (CDC) category C disease except cutaneous Kaposi's sarcoma not requiring systemic therapy during the trial.

• Treatment with any vaccine within 30 days prior to receiving study medication.

• Exclusion criteria for 24-hour screening holter: any symptomatic arrhythmia (except isolated extra systoles); sustained cardiac arrhythmias (such as atrial fibrillation, flutter or supraventricular tachycardia [>=10 seconds]); non-sustained or sustained ventricular tachycardia (defined as >=3 consecutive ventricular ectopic beats); any conduction abnormality including but not specific to left or complete bundle branch block, atrioventricular (AV) block, high grade or complete heart block Wolff-Parkinson-White (WPW) syndrome etc.; sinus pauses >3 seconds.

• Exclusion criteria for screening ECG (a single repeat is allowed for eligibility determination): heart rate <45 and >100 beats per minute (bpm) for males, and <50 and

100 bpm for females; PR Interval <120 and >220 milliseconds (msec); QRS duration <70 and >120 msec; corrected QT (QTc) interval >450 msec; Evidence of previous myocardial infarction (Does not include ST segment changes associated with repolarization); any conduction abnormality (including but not specific to left or right complete bundle branch block, AV block [2nd degree or higher], WPW syndrome); sinus pauses >3 seconds; any significant arrhythmia which, in the opinion of the principal investigator or GSK medical monitor, will interfere with the safety for the individual subject; non-sustained or sustained ventricular tachycardia (>=3 consecutive ventricular ectopic beats).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Birmingham	Alabama	United States	35226
2	GSK Investigational Site	Bakersfield	California	United States	93301
3	GSK Investigational Site	Los Angeles	California	United States	90027
4	GSK Investigational Site	Los Angeles	California	United States	90069
5	GSK Investigational Site	Fort Pierce	Florida	United States	34982
6	GSK Investigational Site	Miami	Florida	United States	33133
7	GSK Investigational Site	Orlando	Florida	United States	32803
8	GSK Investigational Site	Springfield	Massachusetts	United States	01107
9	GSK Investigational Site	Berkley	Michigan	United States	48072
10	GSK Investigational Site	Newark	New Jersey	United States	07102
11	GSK Investigational Site	Dallas	Texas	United States	75246
12	GSK Investigational Site	Longview	Texas	United States	75602
13	GSK Investigational Site	Toronto	Ontario	Canada	M5G 2C4
14	GSK Investigational Site	Montreal	Quebec	Canada	H2L 4P9

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

• Study Protocol - Jun 15, 2017
• Statistical Analysis Plan - May 11, 2018

More Information

Publications

• DeJesus E, Harward S, Jewell RC, Johnson M, Dumont E, Wilches V, Halliday F, Talarico CL, Jeffrey J, Gan J, Xu J, Felizarta F, Scribner A, Ramgopal M, Benson P, Johns BA. A Phase IIa Study Evaluating Safety, Pharmacokinetics, and Antiviral Activity of GSK2838232, a Novel, Second-generation Maturation Inhibitor, in Participants With Human Immunodeficiency Virus Type 1 Infection. Clin Infect Dis. 2020 Aug 22;71(5):1255-1262. doi: 10.1093/cid/ciz938.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT03045861
• Other Study ID Numbers: 200911
• First Posted: Feb 8, 2017
• Last Update Posted: Mar 11, 2020
• Last Verified: Mar 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Infections; Communicable Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Immunologic Deficiency Syndromes; Cobicistat; GSK-2838232

Study Results

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 Detail	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.

Arm/Group Title	GSK2838232 20 mg	GSK2838232 50 mg	GSK2838232 100 mg	GSK2838232 200 mg
Arm/Group Description	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.	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.	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.	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.
Period Title: Part A (Up to 10 Days)
STARTED	0	0	10	0
COMPLETED	0	0	10	0
NOT COMPLETED	0	0	0	0
Period Title: Part A (Up to 10 Days)
STARTED	7	8	0	8
COMPLETED	7	8	0	8
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	GSK2838232 20 mg	GSK2838232 50 mg	GSK2838232 100 mg	GSK2838232 200 mg	Total
Arm/Group Description	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.	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.	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.	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.	Total of all reporting groups
Overall Participants	7	8	10	8	33
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	25.4 (5.59)	25.4 (9.74)	31.8 (10.66)	35.8 (14.87)	29.8 (11.23)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	1 10%	0 0%	1 3%
Male	7 100%	8 100%	9 90%	8 100%	32 97%
Race/Ethnicity, Customized (Count of Participants)
American Indian or Alaska native	1 14.3%	0 0%	1 10%	0 0%	2 6.1%
Asian-South East Asian Heritage	1 14.3%	0 0%	0 0%	0 0%	1 3%
Black or African American	0 0%	1 12.5%	5 50%	2 25%	8 24.2%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	1 12.5%	1 3%
White-White/Caucasian/European Heritage	5 71.4%	6 75%	4 40%	5 62.5%	20 60.6%
Multiple-Black or African American and White	0 0%	1 12.5%	0 0%	0 0%	1 3%

Outcome Measures

1. Primary Outcome

Title	Maximum Decline From Baseline in Plasma HIV-1 Ribonucleic Acid (RNA)
Description	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

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	GSK2838232 20 mg	GSK2838232 50 mg	GSK2838232 100 mg	GSK2838232 200 mg
Arm/Group Description	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.	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.	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.	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.
Measure Participants	7	8	10	8
Mean (Standard Deviation) [Copies per milliliter]	-42095.14 (37575.520)	-49065.88 (71339.743)	-32947.50 (54291.492)	-33149.13 (31785.663)

2. Primary Outcome

Title	Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description	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

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	GSK2838232 20 mg	GSK2838232 50 mg	GSK2838232 100 mg	GSK2838232 200 mg
Arm/Group Description	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.	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.	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.	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.
Measure Participants	7	8	10	8
Any AEs	3 42.9%	3 37.5%	5 50%	5 62.5%
Any SAEs	0 0%	0 0%	0 0%	0 0%

3. Primary Outcome

Title	Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance
Description	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

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	GSK2838232 20 mg	GSK2838232 50 mg	GSK2838232 100 mg	GSK2838232 200 mg
Arm/Group Description	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.	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.	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.	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.
Measure Participants	7	8	10	8
Carbon dioxide/bicarbonate; >32 mmol/L	0 0%	0 0%	0 0%	0 0%
Carbon dioxide/bicarbonate; <18 mmol/L	0 0%	0 0%	3 30%	0 0%
Urea; >9 mmol/L	1 14.3%	0 0%	0 0%	0 0%
Creatinine; Change >44.2 mmol/L	0 0%	0 0%	0 0%	0 0%
Glucose; >9 mmol/L	0 0%	0 0%	0 0%	0 0%
Glucose; <3 mmol/L	0 0%	0 0%	0 0%	0 0%
Potassium; >5.5 mmol/L	0 0%	0 0%	0 0%	2 25%
Potassium; <3 mmol/L	0 0%	0 0%	0 0%	0 0%
Sodium; >150 mmol/L	0 0%	0 0%	0 0%	0 0%
Sodium; <130 mmol/L	0 0%	0 0%	0 0%	0 0%
Troponin I; >=0.01 µg/L	7 100%	8 100%	10 100%	8 100%

4. Primary Outcome

Title	Number of Participants With Hematology Parameter Abnormalities of Potential Clinical Importance
Description	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

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	GSK2838232 20 mg	GSK2838232 50 mg	GSK2838232 100 mg	GSK2838232 200 mg
Arm/Group Description	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.	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.	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.	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.
Measure Participants	7	8	10	8
Hematocrit; >0.54	0 0%	0 0%	1 10%	1 12.5%
Hematocrit; decline from Baseline >0.075	1 14.3%	1 12.5%	3 30%	0 0%
Hemoglobin; >180	0 0%	0 0%	0 0%	0 0%
Hemoglobin; decline from Baseline >25	0 0%	0 0%	1 10%	0 0%
Lymphocytes; <0.8	0 0%	0 0%	0 0%	0 0%
Neutrophils; <1.5	1 14.3%	0 0%	3 30%	1 12.5%
Platelets; >550	0 0%	0 0%	0 0%	0 0%
Platelets; <100	0 0%	0 0%	1 10%	0 0%
White blood cells; >20	0 0%	0 0%	0 0%	0 0%
White blood cells; <3	0 0%	0 0%	0 0%	1 12.5%

5. Primary Outcome

Title	Number of Participants With Liver Function Laboratory Abnormalities of Potential Clinical Importance
Description	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

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	GSK2838232 20 mg	GSK2838232 50 mg	GSK2838232 100 mg	GSK2838232 200 mg
Arm/Group Description	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.	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.	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.	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.
Measure Participants	7	8	10	8
Albumin; <30	0 0%	0 0%	0 0%	0 0%
Total Protein; ULN+15	0 0%	0 0%	0 0%	0 0%
Total Protein; lower limit of normal (LLN)-15	0 0%	0 0%	0 0%	0 0%
ALT; >=2 times ULN	0 0%	0 0%	0 0%	0 0%
AST; >=2 times ULN	0 0%	1 12.5%	0 0%	0 0%
ALP; >=2 times ULN	0 0%	0 0%	0 0%	0 0%
Total bilirubin; >=1.5 times ULN	0 0%	0 0%	1 10%	0 0%
Direct bilirubin; >=0.3 times ULN	0 0%	0 0%	0 0%	0 0%

6. Primary Outcome

Title	Number of Participants With Abnormal Urine Parameters
Description	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

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	GSK2838232 20 mg	GSK2838232 50 mg	GSK2838232 100 mg	GSK2838232 200 mg
Arm/Group Description	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.	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.	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.	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.
Measure Participants	7	8	10	8
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 0%

7. Primary Outcome

Title	Number of Participants With Abnormal Electrocardiogram (ECG) Findings
Description	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

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	GSK2838232 20 mg	GSK2838232 50 mg	GSK2838232 100 mg	GSK2838232 200 mg
Arm/Group Description	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.	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.	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.	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.
Measure Participants	7	8	10	8
Abnormal-not clinically significant	5 71.4%	6 75%	8 80%	4 50%
Abnormal-clinically significant	0 0%	0 0%	0 0%	0 0%

8. Primary Outcome

Title	Number of Participants With Vital Signs Data Outside Clinical Concern Range
Description	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)

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	GSK2838232 20 mg	GSK2838232 50 mg	GSK2838232 100 mg	GSK2838232 200 mg
Arm/Group Description	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.	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.	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.	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.
Measure Participants	7	8	10	8
SBP; >Clinical concern range	0 0%	0 0%	1 10%	0 0%
SBP; <Clinical concern range	0 0%	0 0%	0 0%	0 0%
DBP; >Clinical concern range	0 0%	0 0%	1 10%	0 0%
DBP; <Clinical concern range	0 0%	0 0%	0 0%	0 0%

9. Primary Outcome

Title	Number of Participants Who Were Administered Concomitant Medications
Description	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

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	GSK2838232 20 mg	GSK2838232 50 mg	GSK2838232 100 mg	GSK2838232 200 mg
Arm/Group Description	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.	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.	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.	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.
Measure Participants	7	8	10	8
Count of Participants [Participants]	2 28.6%	3 37.5%	3 30%	3 37.5%

10. Primary Outcome

Title	Area Under the Plasma Concentration Time Curve From Zero (Pre-dose) to 24 Hours (AUC[0 to 24]) for GSK2838232 on Day 1
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	GSK2838232 20 mg	GSK2838232 50 mg	GSK2838232 100 mg	GSK2838232 200 mg
Arm/Group Description	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.	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.	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.	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.
Measure Participants	7	9	9	8
Geometric Mean (Geometric Coefficient of Variation) [Hours*nanograms per milliliter]	187 (35.5)	453 (60.4)	966 (67.4)	2752 (51.7)

11. Primary Outcome

Title	Maximum Observed Concentration (Cmax) for GSK2838232 on Day 1
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	GSK2838232 20 mg	GSK2838232 50 mg	GSK2838232 100 mg	GSK2838232 200 mg
Arm/Group Description	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.	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.	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.	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.
Measure Participants	7	9	9	8
Geometric Mean (Geometric Coefficient of Variation) [Nanograms per milliliter]	12.65 (36.4)	32.39 (61.0)	65.62 (76.7)	190.0 (44.3)

12. Primary Outcome

Title	Time to Maximum Observed Concentration (Tmax) for GSK2838232 on Day 1
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	GSK2838232 20 mg	GSK2838232 50 mg	GSK2838232 100 mg	GSK2838232 200 mg
Arm/Group Description	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.	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.	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.	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.
Measure Participants	7	9	9	8
Median (Full Range) [Hours]	4.033	3.250	6.000	4.000

13. Primary Outcome

Title	Absorption Lag Time (Tlag) for GSK2838232 on Day 1
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	GSK2838232 20 mg	GSK2838232 50 mg	GSK2838232 100 mg	GSK2838232 200 mg
Arm/Group Description	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.	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.	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.	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.
Measure Participants	7	9	9	8
Median (Full Range) [Hours]	1.083	1.000	0.500	0.500

14. Primary Outcome

Title	Concentration of GSK2838232 at 24 Hours Post-dose on Day 1
Description	Serial plasma samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232.
Time Frame	24 hours post-dose on Day 1

Outcome Measure Data

Analysis Population Description

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/Group Title	GSK2838232 20 mg	GSK2838232 50 mg	GSK2838232 100 mg	GSK2838232 200 mg
Arm/Group Description	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.	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.	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.	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.
Measure Participants	7	9	9	8
Geometric Mean (Geometric Coefficient of Variation) [Nanograms per milliliter]	5.890 (27.6)	13.45 (87.3)	30.72 (58.3)	87.33 (54.6)

15. Primary Outcome

Title	Area Under the Concentration-time Curve Over the Dosing Interval (AUC [0 to Tau]) for GSK2838232 on Day 10
Description	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

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Population. Only those participants with data available at the specified time point were analyzed.

Arm/Group Title	GSK2838232 20 mg	GSK2838232 50 mg	GSK2838232 100 mg	GSK2838232 200 mg
Arm/Group Description	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.	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.	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.	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.
Measure Participants	7	7	10	7
Geometric Mean (Geometric Coefficient of Variation) [Hours*nanograms per milliliter]	590 (33.4)	1024 (40.8)	2727 (53.1)	5664 (67.1)

16. Primary Outcome

Title	Pre-dose Concentration (C0) of GSK2838232 on Day 10
Description	Serial plasma samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232.
Time Frame	Pre dose on Day 10

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Population. Only those participants with data available at the specified time point were analyzed.

Arm/Group Title	GSK2838232 20 mg	GSK2838232 50 mg	GSK2838232 100 mg	GSK2838232 200 mg
Arm/Group Description	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.	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.	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.	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.
Measure Participants	7	7	10	7
Geometric Mean (Geometric Coefficient of Variation) [Nanograms per milliliter]	20.02 (28.8)	36.66 (39.8)	75.31 (57.0)	155.5 (64.5)

17. Primary Outcome

Title	Concentration at End of Dosing Interval (Ctau) for GSK2838232 on Day 10
Description	Serial plasma samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232.
Time Frame	24 hours post-dose on Day 10

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Population. Only those participants with data available at the specified time point were analyzed.

Arm/Group Title	GSK2838232 20 mg	GSK2838232 50 mg	GSK2838232 100 mg	GSK2838232 200 mg
Arm/Group Description	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.	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.	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.	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.
Measure Participants	7	7	10	7
Geometric Mean (Geometric Coefficient of Variation) [Nanograms per milliliter]	19.24 (33.7)	31.76 (53.8)	78.98 (58.3)	180.3 (79.8)

18. Primary Outcome

Title	Cmax for GSK2838232 on Day 10
Description	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

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Population. Only those participants with data available at the specified time point were analyzed.

Arm/Group Title	GSK2838232 20 mg	GSK2838232 50 mg	GSK2838232 100 mg	GSK2838232 200 mg
Arm/Group Description	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.	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.	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.	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.
Measure Participants	7	7	10	7
Geometric Mean (Geometric Coefficient of Variation) [Nanograms per milliliter]	32.65 (30.8)	56.40 (33.0)	157.9 (54.0)	306.5 (59.2)

19. Primary Outcome

Title	Apparent Oral Clearance of GSK2838232 Following Administration on Day 10
Description	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

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Population. Only those participants with data available at the specified time point were analyzed.

Arm/Group Title	GSK2838232 20 mg	GSK2838232 50 mg	GSK2838232 100 mg	GSK2838232 200 mg
Arm/Group Description	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.	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.	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.	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.
Measure Participants	7	7	10	7
Geometric Mean (Geometric Coefficient of Variation) [Liters per hour]	33.91 (33.4)	48.84 (40.8)	36.67 (53.1)	35.31 (67.1)

20. Primary Outcome

Title	Terminal Elimination Half-life (T1/2) of GSK2838232 Following Administration on Day 10
Description	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

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Population. Only those participants with data available at the specified time point were analyzed.

Arm/Group Title	GSK2838232 20 mg	GSK2838232 50 mg	GSK2838232 100 mg	GSK2838232 200 mg
Arm/Group Description	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.	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.	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.	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.
Measure Participants	4	5	10	7
Geometric Mean (Geometric Coefficient of Variation) [Hours]	19.221 (17.1)	16.298 (24.0)	18.113 (18.3)	16.351 (8.8)

21. Primary Outcome

Title	Tmax for GSK2838232 Following Administration on Day 10
Description	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

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Population. Only those participants with data available at the specified time point were analyzed.

Arm/Group Title	GSK2838232 20 mg	GSK2838232 50 mg	GSK2838232 100 mg	GSK2838232 200 mg
Arm/Group Description	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.	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.	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.	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.
Measure Participants	7	7	10	7
Median (Full Range) [Hours]	6.000	4.000	6.000	4.083

22. Secondary Outcome

Title	Change From Baseline to Day 11 in log10 Plasma HIV-1 RNA Relative to Day 10 AUC (0 to Tau)
Description	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

Outcome Measure Data

Analysis Population Description

Pharmacokinetic/Pharmacodynamic Population

Arm/Group Title	GSK2838232 20 mg	GSK2838232 50 mg	GSK2838232 100 mg	GSK2838232 200 mg
Arm/Group Description	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.	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.	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.	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.
Measure Participants	7	7	10	8
Mean (Standard Deviation) [log10 copies per milliliter]	-0.4979 (0.44873)	-1.1671 (0.51996)	-1.1745 (0.45005)	-1.5994 (0.32718)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GSK2838232 20 mg, GSK2838232 50 mg, GSK2838232 100 mg, GSK2838232 200 mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Emax
	Estimated Value	-1.822
	Confidence Interval	(2-Sided) 95%; -2.333 to 1.310
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	GSK2838232 20 mg, GSK2838232 50 mg, GSK2838232 100 mg, GSK2838232 200 mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	ED50
	Estimated Value	1020.755
	Confidence Interval	(2-Sided) 95%; 100.786 to 1940.724
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	GSK2838232 20 mg, GSK2838232 50 mg, GSK2838232 100 mg, GSK2838232 200 mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	s2e
	Estimated Value	0.200
	Confidence Interval	(2-Sided) 95%; 0.095 to 0.306
	Parameter Dispersion	Type: Value:
	Estimation Comments

23. Secondary Outcome

Title	Change From Baseline to Day 11 in log10 Plasma HIV-1 RNA Relative to Day 10 Cmax
Description	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

Outcome Measure Data

Analysis Population Description

Pharmacokinetic/Pharmacodynamic Population.

Arm/Group Title	GSK2838232 20 mg	GSK2838232 50 mg	GSK2838232 100 mg	GSK2838232 200 mg
Arm/Group Description	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.	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.	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.	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.
Measure Participants	7	7	10	8
Mean (Standard Deviation) [log10 copies per milliliter]	-0.4979 (0.44873)	-1.1671 (0.51996)	-1.1745 (0.45005)	-1.5994 (0.32718)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GSK2838232 20 mg, GSK2838232 50 mg, GSK2838232 100 mg, GSK2838232 200 mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Emax
	Estimated Value	-1.801
	Confidence Interval	(2-Sided) 95%; -2.319 to -1.283
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	GSK2838232 20 mg, GSK2838232 50 mg, GSK2838232 100 mg, GSK2838232 200 mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	ED50
	Estimated Value	55.572
	Confidence Interval	(2-Sided) 95%; 3.565 to 107.579
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	GSK2838232 20 mg, GSK2838232 50 mg, GSK2838232 100 mg, GSK2838232 200 mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	s2e
	Estimated Value	0.206
	Confidence Interval	(2-Sided) 95%; 0.097 to 0.314
	Parameter Dispersion	Type: Value:
	Estimation Comments

24. Secondary Outcome

Title	Change From Baseline to Day 11 in log10 Plasma HIV-1 RNA Relative to Day 10 Ctau
Description	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

Outcome Measure Data

Analysis Population Description

Pharmacokinetic/Pharmacodynamic Population.

Arm/Group Title	GSK2838232 20 mg	GSK2838232 50 mg	GSK2838232 100 mg	GSK2838232 200 mg
Arm/Group Description	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.	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.	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.	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.
Measure Participants	7	7	10	8
Mean (Standard Deviation) [log10 copies per milliliter]	-0.4979 (0.44873)	-1.1671 (0.51996)	-1.1745 (0.45005)	-1.5994 (0.32718)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GSK2838232 20 mg, GSK2838232 50 mg, GSK2838232 100 mg, GSK2838232 200 mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Emax
	Estimated Value	-1.846
	Confidence Interval	(2-Sided) 95%; -2.352 to -1.340
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	GSK2838232 20 mg, GSK2838232 50 mg, GSK2838232 100 mg, GSK2838232 200 mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	ED50
	Estimated Value	32.415
	Confidence Interval	(2-Sided) 95%; 4.687 to 60.143
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	GSK2838232 20 mg, GSK2838232 50 mg, GSK2838232 100 mg, GSK2838232 200 mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	s2e
	Estimated Value	0.200
	Confidence Interval	(2-Sided) 95%; 0.094 to 0.305
	Parameter Dispersion	Type: Value:
	Estimation Comments

25. Secondary Outcome

Title	Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Count to Day 11
Description	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

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants with data available at the specified time points were analyzed.

Arm/Group Title	GSK2838232 20 mg	GSK2838232 50 mg	GSK2838232 100 mg	GSK2838232 200 mg
Arm/Group Description	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.	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.	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.	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.
Measure Participants	7	7	10	8
Mean (Standard Deviation) [Cells per microliter]	-1.4 (95.26)	52.0 (145.36)	40.7 (94.47)	11.1 (75.15)

26. Secondary Outcome

Title	Change From Baseline to Day 11 in CD4+ Count Relative to Day 10 AUC (0 to Tau)
Description	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

Outcome Measure Data

Analysis Population Description

Pharmacokinetic/Pharmacodynamic Population

Arm/Group Title	Participants Receiving GSK2838232
Arm/Group Description	Participants who received GSK2838232 at doses of 20 mg, 50 mg, 100 mg and 200 mg were included.
Measure Participants	31
Number (95% Confidence Interval) [cells/microliter/ng*h/mL]	-0.003

27. Secondary Outcome

Title	Change From Baseline to Day 11 in CD4+ Count Relative to Day 10 Cmax
Description	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

Outcome Measure Data

Analysis Population Description

Pharmacokinetic/Pharmacodynamic Population

Arm/Group Title	Participants Receiving GSK2838232
Arm/Group Description	Participants who received GSK2838232 at doses of 20 mg, 50 mg, 100 mg and 200 mg were included.
Measure Participants	31
Number (95% Confidence Interval) [cells/microliter/nanograms/milliliter]	-0.067

28. Secondary Outcome

Title	Change From Baseline to Day 11 in CD4+ Count Relative to Day 10 Ctau
Description	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

Outcome Measure Data

Analysis Population Description

Pharmacokinetic/Pharmacodynamic Population

Arm/Group Title	Participants Receiving GSK2838232
Arm/Group Description	Participants who received GSK2838232 at doses of 20 mg, 50 mg, 100 mg and 200 mg were included.
Measure Participants	31
Number (95% Confidence Interval) [cells/microliter/nanograms/milliliter]	-0.079

29. Secondary Outcome

Title	Number of Participants With Emergent Drug Resistance Mutations
Description	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

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	GSK2838232 20 mg	GSK2838232 50 mg	GSK2838232 100 mg	GSK2838232 200 mg
Arm/Group Description	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.	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.	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.	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.
Measure Participants	7	8	10	8
RT/PR mutations	0 0%	0 0%	0 0%	0 0%
Reduced susceptibility to NRTIs, NNRTIs, PIs	0 0%	0 0%	0 0%	0 0%
GSK2838232 phenotypic resistance	0 0%	1 12.5%	0 0%	0 0%
Treatment emergent A364A/V	0 0%	1 12.5%	1 10%	0 0%

30. Secondary Outcome

Title	Accumulation Ratio for GSK2838232
Description	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

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Population. Only participants with data available at the specified time points were analyzed.

Arm/Group Title	GSK2838232 20 mg	GSK2838232 50 mg	GSK2838232 100 mg	GSK2838232 200 mg
Arm/Group Description	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.	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.	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.	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.
Measure Participants	7	7	10	7
R_AUC	3.149 (42.2)	2.004 (34.4)	3.229 (46.1)	2.211 (27.2)
R_Cmax	2.580 (45.1)	1.498 (40.0)	2.753 (43.4)	1.668 (26.5)
R_Ctau	3.267 (41.2)	2.118 (43.9)	3.038 (64.8)	2.210 (45.1)

31. Secondary Outcome

Title	Dose Proportionality of GSK2838232
Description	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

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category )

Arm/Group Title	Participants Receiving GSK2838232
Arm/Group Description	Participants who received GSK2838232 at doses of 20 mg, 50 mg, 100 mg and 200 mg were included.
Measure Participants	33
AUC(0-24); Day 1	1.157
Cmax; Day 1	1.158
C24; Day 1	1.170
AUC (0 to tau); Day 10	1.012
Cmax; Day 10	1.013
Ctau; Day 10	0.988

32. Secondary Outcome

Title	Pre-morning Dose Concentrations (C0) on Day 2 Through 11
Description	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

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles)

Arm/Group Title	GSK2838232 20 mg	GSK2838232 50 mg	GSK2838232 100 mg	GSK2838232 200 mg
Arm/Group Description	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.	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.	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.	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.
Measure Participants	7	9	10	8
Day 2; n=7, 9, 9, 8	6.08 (1.695)	16.39 (9.002)	34.17 (13.990)	96.94 (44.319)
Day 3; n=7, 8, 10, 8	13.99 (5.576)	29.03 (11.870)	51.27 (25.971)	163.98 (91.368)
Day 4; n=7, 7, 10, 8	14.66 (5.771)	31.80 (13.319)	64.49 (26.710)	176.28 (96.684)
Day 5; n=4, 6, 10, 7	15.03 (3.308)	34.35 (15.626)	76.14 (35.179)	206.29 (69.533)
Day 8; n=7, 8, 10, 8	19.72 (7.139)	43.14 (16.664)	86.39 (43.382)	187.16 (110.304)
Day 9; n=7, 6, 10, 8	20.53 (6.760)	43.83 (18.691)	89.32 (40.407)	206.75 (124.166)
Day 10; n=7, 7, 10, 8	20.76 (6.426)	39.19 (16.502)	84.52 (39.940)	189.05 (107.636)
Day 11; n=7, 7, 10, 8	20.16 (6.828)	35.09 (16.038)	89.87 (49.195)	219.23 (133.552)

33. Secondary Outcome

Title	Steady State Assessment of Plasma Pre-dose Concentrations by Treatment
Description	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

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Population

Arm/Group Title	GSK2838232 20 mg	GSK2838232 50 mg	GSK2838232 100 mg	GSK2838232 200 mg
Arm/Group Description	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.	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.	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.	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.
Measure Participants	7	8	10	8
Number (95% Confidence Interval) [Ratio]	0.924	0.999	0.958	0.961

Adverse Events

Time Frame	SAEs and non-serious AEs were collected from the start of study treatment until Day 22
Adverse Event Reporting Description	SAEs and non-serious AEs were collected in the Safety Population
Arm/Group Title	GSK2838232 20 mg		GSK2838232 50 mg		GSK2838232 100 mg		GSK2838232 200 mg
Arm/Group Description	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.		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.		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.		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.
All Cause Mortality
	GSK2838232 20 mg		GSK2838232 50 mg		GSK2838232 100 mg		GSK2838232 200 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/7 (0%)		0/8 (0%)		0/10 (0%)		0/8 (0%)
Serious Adverse Events
	GSK2838232 20 mg		GSK2838232 50 mg		GSK2838232 100 mg		GSK2838232 200 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/7 (0%)		0/8 (0%)		0/10 (0%)		0/8 (0%)
Other (Not Including Serious) Adverse Events
	GSK2838232 20 mg		GSK2838232 50 mg		GSK2838232 100 mg		GSK2838232 200 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/7 (42.9%)		3/8 (37.5%)		5/10 (50%)		5/8 (62.5%)
Blood and lymphatic system disorders
Lymphadenopathy	0/7 (0%)	0	0/8 (0%)	0	1/10 (10%)	1	0/8 (0%)	0
Gastrointestinal disorders
Diarrhoea	1/7 (14.3%)	1	0/8 (0%)	0	0/10 (0%)	0	0/8 (0%)	0
Toothache	0/7 (0%)	0	0/8 (0%)	0	1/10 (10%)	1	0/8 (0%)	0
General disorders
Fatigue	1/7 (14.3%)	1	0/8 (0%)	0	0/10 (0%)	0	0/8 (0%)	0
Medical device site dermatitis	0/7 (0%)	0	1/8 (12.5%)	1	0/10 (0%)	0	0/8 (0%)	0
Medical device site reaction	1/7 (14.3%)	1	0/8 (0%)	0	0/10 (0%)	0	0/8 (0%)	0
Infections and infestations
Upper respiratory tract infection	0/7 (0%)	0	1/8 (12.5%)	1	0/10 (0%)	0	0/8 (0%)	0
Urinary tract infection	0/7 (0%)	0	0/8 (0%)	0	0/10 (0%)	0	1/8 (12.5%)	1
Viral upper respiratory tract infection	1/7 (14.3%)	1	0/8 (0%)	0	0/10 (0%)	0	0/8 (0%)	0
Musculoskeletal and connective tissue disorders
Musculoskeletal pain	1/7 (14.3%)	1	0/8 (0%)	0	0/10 (0%)	0	0/8 (0%)	0
Myalgia	1/7 (14.3%)	1	0/8 (0%)	0	0/10 (0%)	0	0/8 (0%)	0
Pain in extremity	0/7 (0%)	0	1/8 (12.5%)	1	0/10 (0%)	0	0/8 (0%)	0
Nervous system disorders
Headache	0/7 (0%)	0	0/8 (0%)	0	2/10 (20%)	2	0/8 (0%)	0
Dizziness	0/7 (0%)	0	0/8 (0%)	0	0/10 (0%)	0	1/8 (12.5%)	1
Head discomfort	0/7 (0%)	0	0/8 (0%)	0	0/10 (0%)	0	1/8 (12.5%)	1
Presyncope	0/7 (0%)	0	0/8 (0%)	0	0/10 (0%)	0	1/8 (12.5%)	1
Somnolence	0/7 (0%)	0	0/8 (0%)	0	1/10 (10%)	1	0/8 (0%)	0
Psychiatric disorders
Abnormal dreams	1/7 (14.3%)	1	0/8 (0%)	0	0/10 (0%)	0	0/8 (0%)	0
Anxiety	1/7 (14.3%)	1	0/8 (0%)	0	0/10 (0%)	0	0/8 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	0/7 (0%)	0	0/8 (0%)	0	1/10 (10%)	1	0/8 (0%)	0
Nasal congestion	0/7 (0%)	0	0/8 (0%)	0	0/10 (0%)	0	1/8 (12.5%)	1
Skin and subcutaneous tissue disorders
Acne	0/7 (0%)	0	1/8 (12.5%)	1	0/10 (0%)	0	0/8 (0%)	0
Night sweats	0/7 (0%)	0	1/8 (12.5%)	1	0/10 (0%)	0	0/8 (0%)	0
Pruritus	1/7 (14.3%)	1	0/8 (0%)	0	0/10 (0%)	0	0/8 (0%)	0
Rash	0/7 (0%)	0	0/8 (0%)	0	1/10 (10%)	1	0/8 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.