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A Proof of Concept Study of GSK3640254 in Human Immunodeficiency Virus-1 (HIV-1) Infected Treatment-naive Adults

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ClinicalTrials.gov Identifier: NCT03784079
Recruitment Status : Suspended (VH placed a Temporary Halt pending additional virology analysis because some participants receiving GSK3640254 developed treatment emergent MI RAMs on Day 11)
First Posted : December 21, 2018
Last Update Posted : June 20, 2019
Sponsor:
Information provided by (Responsible Party):
ViiV Healthcare

Brief Summary:
Infection with HIV-1 continues to be a serious health threat throughout the world. Chronic exposure to combination anti-retroviral therapy identified anti-retroviral associated long-term toxicities. Hence, there is a need to prevent these co-morbidities. GSK3640254 is a next-generation HIV-1 Maturation Inhibitor (MI) which may be effective for HIV-1 infection. This study will evaluate the antiviral effect, safety, tolerability and pharmacokinetics/ pharmacodynamics of GSK3640254 in HIV-1 infected treatment-naive adults. This study will consists of two parts; Part 1 and Part 2. Part 1 will evaluate two active doses of GSK3640254, 200 milligrams (mg) (Cohort 1) and 10 mg (Cohort 2) along with placebo to match GSK3640254 Mesylate salt. Part 2 will evaluate three active doses of GSK3640254. Dose level 1 of GSK3640254 that can provide at least 30 percent of the maximum effect (Cohort 1), dose level 2 of GSK3640254 that can provide at least 75 percent of the maximum effect (Cohort 2) and dose level 3 of GSK3640254 that can provide at least 90 percent of the maximum effect (Cohort 3). These doses are anticipated to be 5 mg, 40 mg and 100 mg respectively, but could be modified based on data obtained in Part 1. Subjects will also receive placebo to match GSK3640254 Mesylate salt in Part 2 of the study. All doses will be administered after a moderate fat meal. This study will consist of Screening period (up to 14 days), Treatment period (Day 1- Day 10), post-dose Follow-up (Day 11- Day 17) and final Follow-up (Day 18-24). A total of approximately 34 subjects will be enrolled, of which, 14 subjects will be randomized in Part 1 and 20 in Part 2 of the study. Six subjects will be enrolled in each of the active dose cohorts and 2 subjects will be enrolled in each of the placebo cohorts.

Condition or disease Intervention/treatment Phase
HIV Infections Drug: GSK3640254 Drug: Placebo matching GSK3640254 Mesylate salt Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 34 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Eligible subjects will be randomized to receive two active doses of GSK3640254 along with placebo in Part 1 of the study. In Part 2, subjects will receive three active doses of GSK3640254 along with placebo depending upon the data obtained in Part 1.
Masking: Double (Participant, Investigator)
Masking Description: This will be a double blind study. Subjects and investigator will be blinded.
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind (Sponsor-unblinded), Placebo-Controlled, Adaptive Trial to Investigate the Antiviral Effect, Safety, Tolerability and Pharmacokinetics of GSK3640254 in HIV-1 Infected Treatment-Naïve Adults
Actual Study Start Date : January 31, 2019
Estimated Primary Completion Date : November 22, 2019
Estimated Study Completion Date : November 22, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Experimental: Part 1 (Cohort 1): Subjects receiving GSK3640254 200 mg
Eligible subjects from Cohort 1 of Part 1 will be randomized to receive GSK3640254 two 100 mg oral capsules along with approximately 240 mL of water following ingestion of a moderate calorie and fat meal.
Drug: GSK3640254
GSK3640254 will be available with dosing strengths of 5 mg, 20 mg, and 100 mg to be administered as an oral capsule along with 240 mL of water.

Experimental: Part 1 (Cohort 2): Subjects receiving GSK3640254 10 mg
Eligible subjects from Cohort 2 of Part 1 will be randomized to receive GSK3640254 two 5 mg oral capsules along with approximately 240 mL of water following ingestion of a moderate calorie and fat meal.
Drug: GSK3640254
GSK3640254 will be available with dosing strengths of 5 mg, 20 mg, and 100 mg to be administered as an oral capsule along with 240 mL of water.

Placebo Comparator: Part 1: Subjects receiving placebo
Eligible subjects from Part 1 will be randomized to receive two oral capsules of placebo to match GSK3640254 Mesylate salt along with approximately 240 mL of water following ingestion of a moderate calorie and fat meal.
Drug: Placebo matching GSK3640254 Mesylate salt
Placebo to match GSK3640254 Mesylate salt will be given as an oral capsule along with 240 mL of water

Experimental: Part 2 (Cohort 1): Subjects receiving GSK3640254 5 mg
Eligible subjects from Cohort 1 of Part 2 will be randomized to receive GSK3640254, 5 mg oral capsule to provide approximately 30 percent of maximum effect, along with approximately 240 mL of water following ingestion of a moderate calorie and fat meal.
Drug: GSK3640254
GSK3640254 will be available with dosing strengths of 5 mg, 20 mg, and 100 mg to be administered as an oral capsule along with 240 mL of water.

Experimental: Part 2 (Cohort 2): Subjects receiving GSK3640254 40 mg
Eligible subjects from Cohort 2 of Part 2 will be randomized to receive GSK3640254, two 20 mg oral capsules to provide approximately 75 percent of maximum effect, along with approximately 240 mL of water following ingestion of a moderate calorie and fat meal.
Drug: GSK3640254
GSK3640254 will be available with dosing strengths of 5 mg, 20 mg, and 100 mg to be administered as an oral capsule along with 240 mL of water.

Experimental: Part 2 (Cohort 3): Subjects receiving GSK3640254 100 mg
Eligible subjects from Cohort 3 of Part 2 will be randomized to receive GSK3640254, 100 mg oral capsule to provide approximately 90 percent of maximum effect, along with approximately 240 mL of water following ingestion of a moderate calorie and fat meal.
Drug: GSK3640254
GSK3640254 will be available with dosing strengths of 5 mg, 20 mg, and 100 mg to be administered as an oral capsule along with 240 mL of water.

Placebo Comparator: Part 2: Subjects receiving placebo
Eligible subjects from Part 2 will be randomized to receive oral capsule of placebo to match GSK3640254 Mesylate salt along with approximately 240 mL of water following ingestion of a moderate calorie and fat meal.
Drug: Placebo matching GSK3640254 Mesylate salt
Placebo to match GSK3640254 Mesylate salt will be given as an oral capsule along with 240 mL of water




Primary Outcome Measures :
  1. Part 1: Maximum change from Baseline in plasma HIV-1 ribonucleic acid (RNA) [ Time Frame: Baseline (Day 1) and up to Day 24 ]
    The antiviral activity of GSK3640254 in HIV-1-infected subjects will be assessed.

  2. Part 2: Maximum Change from Baseline in plasma HIV-1 RNA [ Time Frame: Baseline (Day 1) and up to Day 24 ]
    The antiviral activity of GSK3640254 in HIV-1-infected subjects will be assessed.


Secondary Outcome Measures :
  1. Part 1: Number of subjects with adverse events and serious adverse events [ Time Frame: Up to Day 24 ]
    An adverse event is any untoward medical occurrence in a clinical study subject, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Serious adverse event is defined as any untoward medical occurrence that, at any dose that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or other situations as per Medical or scientific judgment.

  2. Part 2: Number of subjects with adverse events and serious adverse events [ Time Frame: Up to Day 24 ]
    An adverse event is any untoward medical occurrence in a clinical study subject, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Serious adverse event is defined as any untoward medical occurrence that, at any dose that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or other situations as per Medical or scientific judgment.

  3. Part 1: Number of subjects with abnormal findings for hematology parameters [ Time Frame: Up to Day 24 ]
    Blood samples will be collected from subjects for analysis of hematology parameters including platelet count, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), percent reticulocytes, white blood cells (WBC) count, neutrophils, lymphocytes, monocytes, eosinophils, basophils, red blood cells (RBC) count, hemoglobin and hematocrit.

  4. Part 2: Number of subjects with abnormal findings for hematology parameters [ Time Frame: Up to Day 24 ]
    Blood samples will be collected from subjects for analysis of hematology parameters including platelet count, MCV, MCH, percent reticulocytes, WBC count, neutrophils, lymphocytes, monocytes, eosinophils, basophils, RBC count, hemoglobin and hematocrit.

  5. Part 1: Number of subjects with abnormal findings for clinical chemistry parameters [ Time Frame: Up to Day 24 ]
    Blood samples will be collected from subjects for analysis of clinical chemistry parameters including blood urea nitrogen (BUN), potassium, aspartate aminotransferase (AST), total bilirubin, direct bilirubin, creatinine sodium bicarbonate, chloride, alanine aminotransferase (ALT), total protein, glucose (nonfasting), calcium, magnesium, phosphate, alkaline phosphatase, cholesterol, triglycerides, high density lipoprotein (HDL), low density lipoprotein (LDL) Amylase and Lipase .

  6. Part 2: Number of subjects with abnormal findings for clinical chemistry parameters [ Time Frame: Up to Day 24 ]
    Blood samples will be collected from subjects for analysis of clinical chemistry parameters including BUN, potassium, AST, total bilirubin, direct bilirubin, creatinine sodium bicarbonate, chloride, ALT, total protein, glucose (nonfasting), calcium, magnesium, phosphate, alkaline phosphatase, cholesterol, triglycerides, HDL, LDL, Amylase and Lipase .

  7. Part 1: Number of subjects with abnormal findings for urinalysis parameters [ Time Frame: Up to Day 24 ]
    Urine samples will be collected from subjects for analysis of specific gravity, potential of hydrogen (pH) of urine, presence of glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, and leukocyte esterase in urine by dipstick test. Microscopic examination will be performed if blood or protein is abnormal.

  8. Part 2: Number of subjects with abnormal findings for urinalysis parameters [ Time Frame: Up to Day 24 ]
    Urine samples will be collected from subjects for analysis of specific gravity, pH of urine, presence of glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, and leukocyte esterase in urine by dipstick test. Microscopic examination will be performed if blood or protein is abnormal.

  9. Part 1: Number of subjects with abnormal values for blood pressure [ Time Frame: Up to Day 24 ]
    Systolic and diastolic blood pressure of subjects will be measured in a semi-supine position after at least 5 minutes of rest.

  10. Part 2: Number of subjects with abnormal values for blood pressure [ Time Frame: Up to Day 24 ]
    Systolic and diastolic blood pressure of subjects will be measured in a semi-supine position after at least 5 minutes of rest.

  11. Part 1: Number of subjects with abnormal values for respiratory rate [ Time Frame: Up to Day 24 ]
    Respiratory rate of subjects will be measured in a semi-supine position after at least 5 minutes of rest.

  12. Part 2: Number of subjects with abnormal values for respiratory rate [ Time Frame: Up to Day 24 ]
    Respiratory rate of subjects will be measured in a semi-supine position after at least 5 minutes of rest.

  13. Part 1: Number of subjects with abnormal values for pulse rate [ Time Frame: Up to Day 24 ]
    Pulse rate of subjects will be measured in a semi-supine or supine position after at least 5 minutes of rest.

  14. Part 2: Number of subjects with abnormal values for pulse rate [ Time Frame: Up to Day 24 ]
    Pulse rate of subjects will be measured in a semi-supine or supine position after at least 5 minutes of rest.

  15. Part 1: Number of subjects with abnormal values for electrocardiogram parameters [ Time Frame: Up to Day 24 ]
    Single 12-lead electrocardiogram will be obtained using an electrocardiogram machine.

  16. Part 2: Number of subjects with abnormal values for electrocardiogram parameters [ Time Frame: Up to Day 24 ]
    Single 12-lead electrocardiogram will be obtained using an electrocardiogram machine.

  17. Part 1: Area under the plasma concentration time curve from zero to 24 (AUC [0-24]) following administration of GSK3640254 on Day 1 [ Time Frame: Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose ]
    Blood samples will be collected for pharmacokinetic analysis of GSK3640254.

  18. Part 2: AUC (0-24) following administration of GSK3640254 on Day 1 [ Time Frame: Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose ]
    Blood samples will be collected for pharmacokinetic analysis of GSK3640254.

  19. Part 1: Maximum observed concentration (Cmax) following administration of GSK3640254 on Day 1 [ Time Frame: Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose ]
    Blood samples will be collected for pharmacokinetic analysis of GSK3640254.

  20. Part 2: Cmax following administration of GSK3640254 on Day 1 [ Time Frame: Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose ]
    Blood samples will be collected for pharmacokinetic analysis of GSK3640254.

  21. Part 1: Time to maximum observed concentration (Tmax) following administration of GSK3640254 on Day 1 [ Time Frame: Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose ]
    Blood samples will be collected for pharmacokinetic analysis of GSK3640254.

  22. Part 2: Tmax following administration of GSK3640254 on Day 1 [ Time Frame: Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose ]
    Blood samples will be collected for pharmacokinetic analysis of GSK3640254.

  23. Part 1: Concentration at 24 hours post-dose (C24) following administration of GSK3640254 on Day 1 [ Time Frame: 24 hours post-dose on Day 1 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK3640254.

  24. Part 2: C24 following administration of GSK3640254 on Day 1 [ Time Frame: 24 hours post-dose on Day 1 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK3640254.

  25. Part 1: Absorption lag time (Tlag) following administration of GSK3640254 on Day 1 [ Time Frame: Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose ]
    Blood samples will be collected for pharmacokinetic analysis of GSK3640254.

  26. Part 2: Tlag following administration of GSK3640254 on Day 1 [ Time Frame: Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose ]
    Blood samples will be collected for pharmacokinetic analysis of GSK3640254.

  27. Part 1: Area under the plasma drug concentration-time curve from pre-dose to the end of the dosing interval at steady state (AUC [0-tau]) following repeat dose administration of GSK3640254 [ Time Frame: Day 1: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose; Day 3 or 4, Day 5 or 6 or 7: Pre-dose; Day 11, Day 12, Day 13 or 14 or 15 or 16 or 17; Day 8 or 9 or 10: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose ]
    Blood samples will be collected for pharmacokinetic analysis of GSK3640254.

  28. Part 2: AUC (0-tau) following repeat dose administration of GSK3640254 [ Time Frame: Day 1: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose; Day 3 or 4, Day 5 or 6 or 7: Pre-dose; Day 11, Day 12, Day 13 or 14 or 15 or 16 or 17; Day 8 or 9 or 10: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose ]
    Blood samples will be collected for pharmacokinetic analysis of GSK3640254.

  29. Part 1: Cmax following repeat dose administration of GSK3640254 [ Time Frame: Day 1: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose; Day 3 or 4, Day 5 or 6 or 7: Pre-dose; Day 11, Day 12, Day 13 or 14 or 15 or 16 or 17; Day 8 or 9 or 10: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose ]
    Blood samples will be collected for pharmacokinetic analysis of GSK3640254.

  30. Part 2: Cmax following repeat dose administration of GSK3640254 [ Time Frame: Day 1: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose; Day 3 or 4, Day 5 or 6 or 7: Pre-dose; Day 11, Day 12, Day 13 or 14 or 15 or 16 or 17; Day 8 or 9 or 10: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose ]
    Blood samples will be collected for pharmacokinetic analysis of GSK3640254.

  31. Part 1: Tmax following repeat dose administration of GSK3640254 [ Time Frame: Day 1: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose; Day 3 or 4, Day 5 or 6 or 7: Pre-dose; Day 11, Day 12, Day 13 or 14 or 15 or 16 or 17; Day 8 or 9 or 10: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose ]
    Blood samples will be collected for pharmacokinetic analysis of GSK3640254.

  32. Part 2: Tmax following repeat dose administration of GSK3640254 [ Time Frame: Day 1: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose; Day 3 or 4, Day 5 or 6 or 7: Pre-dose; Day 11, Day 12, Day 13 or 14 or 15 or 16 or 17; Day 8 or 9 or 10: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose ]
    Blood samples will be collected for pharmacokinetic analysis of GSK3640254.

  33. Part 1: Concentration (C0) following repeat dose administration of GSK3640254 [ Time Frame: Pre-dose on Day 1, Day 3 or 4, Day 5 or 6 or 7; Day 11, Day 12, Day 13 or 14 or 15 or 16 or 17 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK3640254.

  34. Part 2: C0 following repeat dose administration of GSK3640254 [ Time Frame: Pre-dose on Day 1, Day 3 or 4, Day 5 or 6 or 7; Day 11, Day 12, Day 13 or 14 or 15 or 16 or 17 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK3640254.

  35. Part 1: Concentration at end of dosing interval (Ctau) following repeat dose administration of GSK3640254 [ Time Frame: Day 1: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose; Day 3 or 4, Day 5 or 6 or 7: Pre-dose; Day 11, Day 12, Day 13 or 14 or 15 or 16 or 17; Day 8 or 9 or 10: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose ]
    Blood samples will be collected for pharmacokinetic analysis of GSK3640254.

  36. Part 2: Ctau following repeat dose administration of GSK3640254 [ Time Frame: Day 1: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose; Day 3 or 4, Day 5 or 6 or 7: Pre-dose; Day 11, Day 12, Day 13 or 14 or 15 or 16 or 17; Day 8 or 9 or 10: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose ]
    Blood samples will be collected for pharmacokinetic analysis of GSK3640254.

  37. Part 1: Apparent terminal phase half-life (t1/2) following repeat dose administration of GSK3640254 [ Time Frame: Day 1: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose; Day 3 or 4, Day 5 or 6 or 7: Pre-dose; Day 11, Day 12, Day 13 or 14 or 15 or 16 or 17; Day 8 or 9 or 10: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose ]
    Blood samples will be collected for pharmacokinetic analysis of GSK3640254.

  38. Part 2: T1/2 following repeat dose administration of GSK3640254 [ Time Frame: Day 1: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose; Day 3 or 4, Day 5 or 6 or 7: Pre-dose; Day 11, Day 12, Day 13 or 14 or 15 or 16 or 17; Day 8 or 9 or 10: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose ]
    Blood samples will be collected for pharmacokinetic analysis of GSK3640254.

  39. Part 1: Apparent oral clearance (CL/F) following repeat dose administration of GSK3640254 [ Time Frame: Day 1: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose; Day 3 or 4, Day 5 or 6 or 7: Pre-dose; Day 11, Day 12, Day 13 or 14 or 15 or 16 or 17; Day 8 or 9 or 10: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose ]
    Blood samples will be collected for pharmacokinetic analysis of GSK3640254.

  40. Part 2: CL/F following repeat dose administration of GSK3640254 [ Time Frame: Day 1: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose; Day 3 or 4, Day 5 or 6 or 7: Pre-dose; Day 11, Day 12, Day 13 or 14 or 15 or 16 or 17; Day 8 or 9 or 10: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose ]
    Blood samples will be collected for pharmacokinetic analysis of GSK3640254.

  41. Part 1: AUC (0-tau) of GSK3640254 with respect to change from Baseline in HIV-1 RNA [ Time Frame: Day 1: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose; Day 3 or 4, Day 5 or 6 or 7: Pre-dose; Day 11, Day 12, Day 13 or 14 or 15 or 16 or 17; Day 8 or 9 or 10: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose ]
    Relationships between pharmacokinetic and pharmacodynamics parameters will be explored following administration of GSK3640254

  42. Part 2: AUC (0-tau) of GSK3640254 with respect to change from Baseline in HIV-1 RNA [ Time Frame: Day 1: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose; Day 3 or 4, Day 5 or 6 or 7: Pre-dose; Day 11, Day 12, Day 13 or 14 or 15 or 16 or 17; Day 8 or 9 or 10: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose ]
    Relationships between pharmacokinetic and pharmacodynamics parameters will be explored following administration of GSK3640254.

  43. Part 1:Cmax of GSK3640254 with respect to change from Baseline in HIV-1 RNA [ Time Frame: Day 1: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose; Day 3 or 4, Day 5 or 6 or 7: Pre-dose; Day 11, Day 12, Day 13 or 14 or 15 or 16 or 17; Day 8 or 9 or 10: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose ]
    Relationships between pharmacokinetic and pharmacodynamics parameters will be explored following administration of GSK3640254.

  44. Part 2: Cmax of GSK3640254 with respect to change from Baseline in HIV-1 RNA [ Time Frame: Day 1: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose; Day 3 or 4, Day 5 or 6 or 7: Pre-dose; Day 11, Day 12, Day 13 or 14 or 15 or 16 or 17; Day 8 or 9 or 10: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose ]
    Relationships between pharmacokinetic and pharmacodynamics parameters will be explored following administration of GSK3640254.

  45. Part 1: Ctau of GSK3640254 with respect to change from Baseline IN HIV-1 RNA [ Time Frame: Day 1: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose; Day 3 or 4, Day 5 or 6 or 7: Pre-dose; Day 11, Day 12, Day 13 or 14 or 15 or 16 or 17; Day 8 or 9 or 10: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose ]
    Relationships between pharmacokinetic and pharmacodynamics parameters will be explored following administration of GSK3640254.

  46. Part 2:Ctau of GSK3640254 with respect to change from Baseline in HIV-1 RNA [ Time Frame: Day 1: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose; Day 3 or 4, Day 5 or 6 or 7: Pre-dose; Day 11, Day 12, Day 13 or 14 or 15 or 16 or 17; Day 8 or 9 or 10: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose ]
    Relationships between pharmacokinetic and pharmacodynamics parameters will be explored following administration of GSK3640254.

  47. Part 1:Accumulation ratio of GSK3640254 following repeat dose by AUC (0-tau) [ Time Frame: Day 1: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose; Day 3 or 4, Day 5 or 6 or 7: Pre-dose; Day 11, Day 12, Day 13 or 14 or 15 or 16 or 17; Day 8 or 9 or 10: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose ]
    Accumulation ratio will be estimated from the ratio of AUC (0-tau) following repeat dose/AUC (0-24) following dosing on Day 1.

  48. Part 2:Accumulation ratio of GSK3640254 following repeat dose by AUC (0-tau) [ Time Frame: Day 1: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose; Day 3 or 4, Day 5 or 6 or 7: Pre-dose; Day 11, Day 12, Day 13 or 14 or 15 or 16 or 17; Day 8 or 9 or 10: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose ]
    Accumulation ratio will be estimated from the ratio of AUC (0-tau) following repeat dose/AUC (0-24) following dosing on Day 1.

  49. Part 1: Accumulation ratio of GSK3640254 following repeat dose by Cmax [ Time Frame: Day 1: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose; Day 3 or 4, Day 5 or 6 or 7: Pre-dose; Day 11, Day 12, Day 13 or 14 or 15 or 16 or 17; Day 8 or 9 or 10: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose ]
    Accumulation ratio will be estimated from the ratio of Cmax following repeat dose/Cmax following dosing on Day 1.

  50. Part 2: Accumulation ratio of GSK3640254 following repeat dose by Cmax [ Time Frame: Day 1: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose; Day 3 or 4, Day 5 or 6 or 7: Pre-dose; Day 11, Day 12, Day 13 or 14 or 15 or 16 or 17; Day 8 or 9 or 10: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose ]
    Accumulation ratio will be estimated from the ratio of Cmax following repeat dose/Cmax following dosing on Day 1.

  51. Part 1: Accumulation ratio of GSK3640254 following repeat dose by Ctau [ Time Frame: Day 1: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose; Day 3 or 4, Day 5 or 6 or 7: Pre-dose; Day 11, Day 12, Day 13 or 14 or 15 or 16 or 17; Day 8 or 9 or 10: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose ]
    Accumulation ratio will be estimated from the ratio of Ctau following repeat dose/C24 following dosing on Day 1.

  52. Part 2: Accumulation ratio of GSK3640254 following repeat dose by Ctau [ Time Frame: Day 1: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose; Day 3 or 4, Day 5 or 6 or 7: Pre-dose; Day 11, Day 12, Day 13 or 14 or 15 or 16 or 17; Day 8 or 9 or 10: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose ]
    Accumulation ratio will be estimated from the ratio of Ctau following repeat dose/C24 following dosing on Day 1.

  53. Part 1: Dose proportionality of GSK3640254 administered on Day 1 based on AUC (0-24) [ Time Frame: Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose ]
    Dose proportionality will be assessed from the AUC (0-24) following administration of GSK3640254 on Day 1.

  54. Part 2: Dose proportionality of GSK3640254 administered on Day 1 based on AUC (0-24) [ Time Frame: Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose ]
    Dose proportionality will be assessed from the AUC (0-24) following administration of GSK3640254 on Day 1.

  55. Part 1: Dose proportionality of GSK3640254 administered on Day 1 based on Cmax [ Time Frame: Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose ]
    Dose proportionality will be assessed from the Cmax following administration of GSK3640254 on Day 1.

  56. Part 2: Dose proportionality of GSK3640254 administered on Day 1 based on Cmax [ Time Frame: Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose ]
    Dose proportionality will be assessed from the Cmax following administration of GSK3640254 on Day 1.

  57. Part 1: Dose proportionality of GSK3640254 administered on Day 1 based on C24 [ Time Frame: Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose ]
    Dose proportionality will be assessed from the C24 following administration of GSK3640254 on Day 1.

  58. Part 2: Dose proportionality of GSK3640254 administered on Day 1 based on C24 [ Time Frame: Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose ]
    Dose proportionality will be assessed from the C24 following administration of GSK3640254 on Day 1.

  59. Part 1: Dose proportionality of GSK3640254 following repeat dose administration based on AUC (0-tau) [ Time Frame: Day 1: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose; Day 3 or 4, Day 5 or 6 or 7: Pre-dose; Day 11, Day 12, Day 13 or 14 or 15 or 16 or 17; Day 8 or 9 or 10: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose ]
    Dose proportionality will be assessed from the AUC (0-tau) following repeat dose administration of GSK3640254.

  60. Part 2: Dose proportionality of GSK3640254 following repeat dose administration based on AUC (0-tau) [ Time Frame: Day 1: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose; Day 3 or 4, Day 5 or 6 or 7: Pre-dose; Day 11, Day 12, Day 13 or 14 or 15 or 16 or 17; Day 8 or 9 or 10: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose ]
    Dose proportionality will be assessed from the AUC (0-tau) following repeat dose administration of GSK3640254.

  61. Part 1: Dose proportionality of GSK3640254 following repeat dose administration based on Cmax [ Time Frame: Day 1: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose; Day 3 or 4, Day 5 or 6 or 7: Pre-dose; Day 11, Day 12, Day 13 or 14 or 15 or 16 or 17; Day 8 or 9 or 10: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose ]
    Dose proportionality will be assessed from the Cmax following repeat dose administration of GSK3640254.

  62. Part 2: Dose proportionality of GSK3640254 following repeat dose administration based on Cmax [ Time Frame: Day 1: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose; Day 3 or 4, Day 5 or 6 or 7: Pre-dose; Day 11, Day 12, Day 13 or 14 or 15 or 16 or 17; Day 8 or 9 or 10: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose ]
    Dose proportionality will be assessed from the Cmax following repeat dose administration of GSK3640254.

  63. Part 1: Dose proportionality of GSK3640254 following repeat dose administration based on Ctau [ Time Frame: Day 1: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose; Day 3 or 4, Day 5 or 6 or 7: Pre-dose; Day 11, Day 12, Day 13 or 14 or 15 or 16 or 17; Day 8 or 9 or 10: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose ]
    Dose proportionality will be assessed from the Ctau following repeat dose administration of GSK3640254.

  64. Part 2: Dose proportionality of GSK3640254 following repeat dose administration based on Ctau [ Time Frame: Day 1: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose; Day 3 or 4, Day 5 or 6 or 7: Pre-dose; Day 11, Day 12, Day 13 or 14 or 15 or 16 or 17; Day 8 or 9 or 10: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose ]
    Dose proportionality will be assessed from the Ctau following repeat dose administration of GSK3640254.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subject must be 18 to 65 years of age inclusive, at the time of signing the informed consent.
  • Subjects who are healthy (other than HIV infection) as determined by the Investigator or medically qualified designee based on a medical evaluation including medical history, laboratory tests, and cardiac monitoring.
  • Screening Cluster of designation 4 positive (CD4+) T-cell count >=350 cells per millimeter cube (cells/mm^3).
  • Documented HIV infection and Screening plasma HIV-1 RNA >=5000 copies/milliliter (mL). A single repeat of this test is allowed within a single Screening period to determine eligibility.
  • Treatment-naive: No anti-retrovirals (in combination or monotherapy) received after the diagnosis of HIV-1 infection.
  • Body weight >=50.0 kilograms (kg) (110 Pounds) for men and >=45.0 kg (99 pounds) for women and body mass index (BMI) within the range 18.5-31.0 kg/meter square (kg/m^2) (inclusive).
  • A female subject is eligible to participate if she is not pregnant, not breastfeeding, and not a woman of childbearing potential (WOCBP).
  • Capable of giving signed informed consent.
  • For subjects enrolled in France: a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.

Exclusion Criteria:

  • Presence of Hepatitis B surface antigen (HBsAg) at screening or within 3 months prior to starting study treatment.
  • Positive Hepatitis C antibody test result at screening or within 3 months prior to starting study treatment and positive on reflex to Hepatitis C RNA.
  • ALT >2 times upper limit of normal (ULN). A single repeat of ALT is allowed within a single Screening period to determine eligibility.
  • Bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin <35 percent).
  • Subjects with primary HIV infection, evidenced by acute retroviral syndrome (example given [e.g.], fever, malaise, fatigue, etc) and/or evidence of recent (within 3 months) documented viremia without antibody production and/or evidence of recent (within 3 months) documented seroconversion.
  • Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones);
  • A pre-existing condition interfering with normal gastrointestinal anatomy or motility (e.g., gastroesophageal reflux disease [GERD], gastric ulcers, gastritis), hepatic and/or renal function, that could interfere with the absorption, metabolism, and/or excretion of the study drugs or render the subject unable to take oral study treatment.
  • Any acute laboratory abnormality at screen which, in the opinion of the investigator, should preclude participation in the study of an investigational compound.
  • Any Grade 2-4 laboratory abnormality at screen, with the exception of creatine phosphokinase (CPK) and lipid abnormalities (e.g., total cholesterol, triglycerides, etc), and ALT (described above), will exclude a subject from the study unless the investigator can provide a compelling explanation for the laboratory result(s) and has the assent of the sponsor. A single repeat of any lab abnormality is allowed within a single screening period to determine eligibility.
  • Any history of significant underlying psychiatric disorder, including but not limited to schizophrenia, bipolar disorder with or without psychotic symptoms, other psychotic disorders, or schizotypal (personality) disorder.
  • Any history of major depressive disorder with or without suicidal features, or anxiety disorders, that required medical intervention (pharmacologic or not) such as hospitalization or other inpatient treatment and/or chronic (>6 months) outpatient treatment. Subjects with other conditions such as adjustment disorder or dysthymia that have required shorter term medical therapy (<6 months) without inpatient treatment and are currently well-controlled clinically or resolved may be considered for entry after discussion and agreement with the ViiV Medical Monitor.
  • Any pre-existing physical or other psychiatric condition (including alcohol or drug abuse), which, in the opinion of the investigator (with or without psychiatric evaluation), could interfere with the subject's ability to comply with the dosing schedule and protocol evaluations or which might compromise the safety of the subject.
  • Medical history of cardiac arrhythmias or cardiac disease or a family or personal history of long QT syndrome.
  • 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.
  • The subject has participated in a clinical trial and has received an investigational product within the 30 days prior to the first dosing day in the current study.
  • Any positive (abnormal) response confirmed by the investigator on a Screening clinician- (or qualified designee-) administered Columbia Suicide Severity Rating Scale (CSSRS).
  • Any positive result for illicit drug use (e.g., cocaine, heroin) at Screening. A positive screen for marijuana is not exclusionary, though if positive for delta-9-tetrahydrocannabinol (THC).
  • Where participation in the study would result in donation of blood or blood products in excess of 500 mL within 56 days.
  • Exposure to more than four new investigational drugs or vaccines 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.
  • Ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous cell carcinoma, or cervical, anal or penile intraepithelial neoplasia; or other localized malignancies require agreement between the investigator and the study medical monitor for inclusion of the subject prior to randomization.
  • 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 screening electrocardiogram (a single repeat is allowed for eligibility determination): Heart rate of <45 or >100 beats per minute (bpm) for males and <50 or >100 bpm for females; PR Interval of <120 or >200 milliseconds (msec) for both males and females; QRS duration of <70 or >110 msec for both males and females; QT interval corrected (QTc) for heart rate according to Fridericia's formula (QTcF) of >450 msec for males and >470 msec for females. A heart rate from 100 to 110 bpm can be rechecked by electrocardiogram or vitals within 30 minutes to verify eligibility. QTcF is either machine read or manually over-read.
  • Any significant arrhythmia or electrocardiogram finding (e.g., prior myocardial infarction, sinoatrial pauses, bundle branch block, or conduction abnormality) which, in the opinion of the Investigator OR ViiV Medical Monitor, will interfere with the safety for the individual subject.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03784079


Locations
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United States, California
GSK Investigational Site
Bakersfield, California, United States, 93301
United States, Florida
GSK Investigational Site
Orlando, Florida, United States, 32803
United States, Texas
GSK Investigational Site
Longview, Texas, United States, 75605
France
GSK Investigational Site
Marseille, France, 13003
GSK Investigational Site
Paris, France, 75018
GSK Investigational Site
Tourcoing cedex, France, 59208
Germany
GSK Investigational Site
Muenchen, Bayern, Germany, 81675
GSK Investigational Site
Frankfurt am Main, Hessen, Germany, 60590
GSK Investigational Site
Frankfurt, Hessen, Germany, 60596
GSK Investigational Site
Berlin, Germany, 12157
GSK Investigational Site
Hamburg, Germany, 20246
Italy
GSK Investigational Site
Roma, Lazio, Italy, 00149
GSK Investigational Site
Milano, Lombardia, Italy, 20127
GSK Investigational Site
Milano, Lombardia, Italy, 20157
South Africa
GSK Investigational Site
Bloemfontein, South Africa, 9301
GSK Investigational Site
Durban, South Africa, 4001
GSK Investigational Site
Johannesburg, South Africa, 2113
Spain
GSK Investigational Site
Alicante, Spain, 03010
GSK Investigational Site
Badalona, Spain, 08916
GSK Investigational Site
Barcelona, Spain, 08025
GSK Investigational Site
Barcelona, Spain, 08035
GSK Investigational Site
Barcelona, Spain, 08907
GSK Investigational Site
Madrid, Spain, 28006
GSK Investigational Site
Madrid, Spain, 28034
GSK Investigational Site
Madrid, Spain, 28040
GSK Investigational Site
Madrid, Spain, 28046
GSK Investigational Site
Sevilla, Spain, 41013
Sponsors and Collaborators
ViiV Healthcare
Investigators
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Study Director: GSK Clinical Trials ViiV Healthcare

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Responsible Party: ViiV Healthcare
ClinicalTrials.gov Identifier: NCT03784079     History of Changes
Other Study ID Numbers: 208132
First Posted: December 21, 2018    Key Record Dates
Last Update Posted: June 20, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints of the study.
Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
URL: http://clinicalstudydatarequest.com

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by ViiV Healthcare:
HIV-1, Antiviral Effect, GSK3640254, Proof of Concept
Additional relevant MeSH terms:
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HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Antiviral Agents
Anti-Infective Agents