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

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ClinicalTrials.gov Identifier: NCT03045861
Recruitment Status : Completed
First Posted : February 8, 2017
Last Update Posted : June 12, 2018
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

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 Drug: GSK2838232 Drug: Cobicistat Phase 2

Study Type : Interventional  (Clinical Trial)
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 : March 17, 2017
Actual Primary Completion Date : April 23, 2018
Actual Study Completion Date : April 23, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS
Drug Information available for: Cobicistat

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.




Primary Outcome Measures :
  1. Maximum decline from Baseline (Day 1) in plasma HIV-1 ribonucleic acid (RNA) [ Time Frame: Baseline (Day 1) and up to Day 11 ]
    Blood samples for the measurement of HIV-1 RNA levels will be obtained for HIV-1 RNA analysis.

  2. Number of subjects with any adverse event (AE) and any serious adverse event (SAE) [ Time Frame: Up to 3 Weeks ]
    An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other situations judged by physician, is associated with liver injury and impaired liver function.

  3. Safety as assessed by concurrent medications during the treatment period [ Time Frame: Up to 3 Weeks ]
    Concurrent medications (permitted as per study protocol) received during the treatment period will be documented in case report forms.

  4. Number of subjects with abnormal hematology laboratory tests [ Time Frame: Up to 3 Weeks ]
    Hematology values will be assessed.

  5. Number of subjects with abnormal clinical chemistry laboratory tests [ Time Frame: Up to 3 Weeks ]
    Clinical chemistry values will be assessed.

  6. Number of subjects with abnormal routine urinalysis laboratory tests [ Time Frame: Up to 3 Weeks ]
    Routine urinalysis parameters will be assessed.

  7. Number of subjects with abnormal electrocardiogram (ECG) findings [ Time Frame: Up to 3 Weeks ]
    Triplicate 12-lead ECGs will be obtained at indicated time point during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QT corrected (QTc) intervals. On Day 1, ECGs (x2) will be performed pre dose , and then 1, 1.5, 2, 3, 4 and 6 hours post dose. On Days 4, 5 and 8, ECGs will be obtained prior to morning dosing and at 2, 4 and 6 hours post dose. On Day 10, ECGs (x2) will be performed pre dose, and then 1, 1.5, 2, 3, 4 and 6 hours post dose. On Day 11, an ECG will be obtained prior to the 24-hour PK sample.

  8. Systolic and diastolic blood pressure (BP) as a measure of safety [ Time Frame: Up to 3 Weeks ]
    Systolic and diastolic BP will be measured in semi-supine position after 5 minutes rest. Three readings of blood pressure will be taken of which first reading will be rejected. Second and third readings will be averaged to give the measurement. Systolic and diastolic BP will be obtained at Screening (x1) and Day 1 pre dose (x2); on Day 1 at 2 hours post-morning dose and on Days 4, 5 and 8 pre dose; on Day 10 at pre dose and 2 hours post-morning dose, and at Follow-up.

  9. Pulse rate as a measure of safety [ Time Frame: Up to 3 Weeks ]
    Pulse rate will be measured in semi-supine position after 5 minutes rest. Three readings of pulse rate will be taken of which first reading will be rejected. Second and third readings will be averaged to give the measurement. Pulse rate will be obtained at Screening (x1) and Day 1 pre dose (x2); on Day 1 at 2 hours post-morning dose and on Days 4, 5 and 8 pre dose; on Day 10 at pre dose and 2 hours post-morning dose, and at Follow-up.

  10. Body temperature as a measure of safety [ Time Frame: Up to 3 Weeks ]
    Body temperature will be measured in semi-supine position after 5 minutes rest. Body temperature will be obtained at Screening (x1) and Day 1 pre dose (x2).

  11. Area under the plasma concentration-time curve (AUC) from time zero (Pre-dose) to over 24 hours time (AUC[0-24]) of GSK2838232 following dose administration on Day 1 [ Time Frame: PK samples will be taken at pre dose and post dose at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours on Day 1 ]
    2 milliliter (mL) of blood samples will be collected at indicated time points for PK analysis.

  12. Maximum observed plasma concentration (Cmax) and concentration at 24 hours post dose (C24) of GSK2838232 on Day 1 [ Time Frame: PK samples will be taken at pre dose and post dose at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours on Day 1. ]
    Cmax is defined as the maximum observed plasma concentration. 2 mL of blood samples will be collected at indicated time points for PK analysis.

  13. Time to maximum observed concentration (Tmax) of GSK2838232 on Day 1 [ Time Frame: PK samples will be taken at pre dose and post dose at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours on Day 1 ]
    2 mL of blood samples will be collected at indicated time points for PK analysis.

  14. Absorption lag time (Tlag) of GSK2838232 on Day 1 [ Time Frame: PK samples will be taken at pre dose and post dose at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours on Day 1 ]
    Absorption lag time is defined as the time taken for a drug to appear in the systemic circulation following administration. 2 mL of blood samples will be collected at indicated time points for PK analysis.

  15. Area under the concentration-time curve over the dosing interval (AUC[0-tau]) of GSK2838232 on Day 10 [ Time Frame: PK samples will be taken at pre dose and post dose at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours on Day 1 and Day 10. Pre dose PK samples will be taken on Days 3, 4, 5, 8 and 9 and a single sample will be taken on Days 12 and 14. ]
    AUC (0-tau) is defined as the area under the concentration-time curve over the dosing interval. 2 mL of blood samples will be collected at indicated time points for PK analysis.

  16. Pre dose concentration (C0) of GSK2838232 on Day 10 [ Time Frame: PK samples will be taken at pre dose and post dose at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours on Day 1 and Day 10. Pre dose PK samples will be taken on Days 3, 4, 5, 8 and 9 and a single sample will be taken on Days 12 and 14. ]
    C0 is defined as the pre-dose concentration. 2 mL of blood samples will be collected at indicated time points for PK analysis.

  17. Concentration at the end of the dosing interval (Ctau) of GSK2838232 on Day 10 [ Time Frame: PK samples will be taken at pre dose and post dose at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours on Day 1 and Day 10. Pre dose PK samples will be taken on Days 3, 4, 5, 8 and 9 and a single sample will be taken on Days 12 and 14. ]
    Ctau is defined as the concentration at the end of the dosing interval. 2 mL of blood samples will be collected at indicated time points for PK analysis.

  18. Cmax of GSK2838232 on Day 10 [ Time Frame: PK samples will be taken at pre dose and post dose at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours on Day 1 and Day 10. Pre dose PK samples will be taken on Days 3, 4, 5, 8 and 9 and a single sample will be taken on Days 12 and 14. ]
    Cmax is defined as the maximum observed plasma concentration. 2 mL of blood samples will be collected at indicated time points for PK analysis.

  19. Tmax of GSK2838232 on Day 10 [ Time Frame: PK samples will be taken at pre dose and post dose at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours on Day 1 and Day 10. Pre dose PK samples will be taken on Days 3, 4, 5, 8 and 9 and a single sample will be taken on Days 12 and 14. ]
    Tmax is defined as the time to the maximum observed plasma concentration. 2 mL of blood samples will be collected at indicated time points for PK analysis

  20. Terminal half-life (t1/2) of GSK2838232 on Day 10 [ Time Frame: PK samples will be taken at pre dose and post dose at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours on Day 1 and Day 10. Pre dose PK samples will be taken on Days 3, 4, 5, 8 and 9 and a single sample will be taken on Days 12 and 14. ]
    T1/2 of GSK2838232 is defined as the time required for the plasma concentration of GSK2838232 to reach half of its original concentration. 2 mL of blood samples will be collected at indicated time points for PK analysis.

  21. Apparent oral clearance (CL/F) of GSK2838232 on Day 10 [ Time Frame: PK samples will be taken at pre dose and post dose at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours on Day 1 and Day 10. Pre dose PK samples will be taken on Days 3, 4, 5, 8 and 9 and a single sample will be taken on Days 12 and 14. ]
    The CL/F is defined as the apparent total clearance of the drug from plasma after oral administration. 2 mL of blood samples will be collected at indicated time points for PK analysis


Secondary Outcome Measures :
  1. Relationship of GSK2838232 PK parameter AUC(0-tau) (Day 10) with respect to change from baseline in HIV-1 RNA (Day 11) [ Time Frame: Up to 3 weeks ]
    Relationships between various PK parameters and PD measures will be explored using various models.

  2. Relationship of GSK2838232 PK parameters Cmax (Day 10) with respect to change from baseline in HIV-1 RNA (Day 11) [ Time Frame: Up to 3 weeks ]
    Relationships between various PK parameters and PD measures will be explored using various models.

  3. Relationship of GSK2838232 PK parameter Ctau (Day 10) with respect to change from baseline in HIV-1 RNA (Day 11) [ Time Frame: Up to 3 weeks ]
    Relationships between various PK parameters and PD measures will be explored using various models)

  4. Change from baseline in cluster of differentiation 4+ (CD4+) cell count [ Time Frame: Up to Day 11 ]
    Change from Baseline in CD4+ cell count will be calculated as the Day 11 value minus the Baseline value.

  5. Relationship of GSK2838232 PK parameter Cmax (Day 10) with respect to change from baseline in CD4+ cell count [ Time Frame: PD: Baseline (Day 1) and Day 11; PK: pre dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post- am dose on Day 1 and Day 10; pre dose on the mornings of Days 3, 4, 5, 8 and 9 and a single sample on Days 12 and 14. ]
    Relationships between various PK parameters and PD measures will be explored using various models.

  6. Relationship of GSK2838232 PK parameter Ctau (Day 10) with respect to change from baseline in CD4+ cell count [ Time Frame: PD: Baseline (Day 1) and Day 11; PK: pre dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post- am dose on Day 1 and Day 10; pre dose on the mornings of Days 3, 4, 5, 8 and 9 and a single sample on Days 12 and 14. ]
    Relationships between various PK parameters and PD measures will be explored using various models.

  7. Number of participants with the emergence of drug resistance mutations [ Time Frame: Baseline (Day 1) and Day 11 ]
    The number of participants with the emergence (from Baseline) of drug resistance mutations at Day 11 was measured

  8. GSK2838232 Day 10 AUC(0-tau) compared to Day 1 AUC(0-24) to estimate accumulation ratio (R) [ Time Frame: PK samples will be taken pre dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-am dose on Day 1 and Day 10. Pre dose PK samples will be taken on the mornings of Days 3, 4, 5, 8 and 9 and a single sample will be taken on Days 12 and 14. ]
    Comparisons of Day 10 with Day 1 PK for each dose will be used for the accumulation ratio (R) evaluation.

  9. GSK2838232 Day 10 Cmax and Ctau compared to Day 1 Cmax and C24 to estimate accumulation ratio (R), respectively [ Time Frame: PK samples will be taken pre dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-am dose on Day 1 and Day 10. Pre dose PK samples will be taken on the mornings of Days 3, 4, 5, 8 and 9 and a single sample will be taken on Days 12 and 14. ]
    Comparisons of Day 10 with Day 1 PK for each dose will be used for the accumulation ratio (R) evaluation.

  10. Pre-morning dose concentrations (C0) of GSK2838232 from Day 2 to Day 11 [ Time Frame: Pre dose on Days 1, 3, 4, 5, 8, 9 and 10 ]
    2 mL of blood samples will be collected at indicated time points for PK analysis.

  11. Day 1 AUC(0-24) and at different doses levels (20, 50, 100 and 200 milligram [mg]) for the assessment of dose proportionality [ Time Frame: PK samples will be taken at pre dose and post dose at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours on Day 1 and Day 10. Pre dose PK samples will be taken on Days 3, 4, 5, 8 and 9 and a single sample will be taken on Days 12 and 14. ]
    Dose proportionality of plasma GSK2838232 PK parameters from Day 1 and Day 10 will be assessed using a power model for all doses (20, 50, 100 and 200 mg)

  12. Day 10 AUC(0-tau) at different doses levels (20, 50, 100 and 200 milligram [mg]) for the assessment of dose proportionality [ Time Frame: PK samples will be taken at pre dose and post dose at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours on Day 1 and Day 10. Pre dose PK samples will be taken on Days 3, 4, 5, 8 and 9 and a single sample will be taken on Days 12 and 14. ]
    Dose proportionality of plasma GSK2838232 PK parameters from Day 1 and Day 10 will be assessed using a power model for all doses (20, 50, 100 and 200 mg).

  13. Day 1 and Day 10 Cmax [ Time Frame: PK samples will be taken at pre dose and post dose at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours on Day 1 and Day 10. Pre dose PK samples will be taken on Days 3, 4, 5, 8 and 9 and a single sample will be taken on Days 12 and 14. ]
    Dose proportionality of plasma GSK2838232 PK parameters from Day 1 and Day 10 will be assessed using a power model if multiple dose levels are assessed.

  14. Day 1 C24 [ Time Frame: PK samples will be taken at pre dose and post dose at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours on Day 1 and Day 10. Pre dose PK samples will be taken on Days 3, 4, 5, 8 and 9 and a single sample will be taken on Days 12 and 14. ]
    Dose proportionality of plasma GSK2838232 PK parameters from Day 1 and Day 10 will be assessed using a power model if multiple dose levels are assessed.

  15. Day 10 Ctau [ Time Frame: PK samples will be taken at pre dose and post dose at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours on Day 1 and Day 10. Pre dose PK samples will be taken on Days 3, 4, 5, 8 and 9 and a single sample will be taken on Days 12 and 14. ]
    Dose proportionality of plasma GSK2838232 PK parameters from Day 1 and Day 10 will be assessed using a power model if multiple dose levels are assessed.



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.


Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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).

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): NCT03045861


Locations
United States, Alabama
GSK Investigational Site
Birmingham, Alabama, United States, 35226
United States, California
GSK Investigational Site
Bakersfield, California, United States, 93301
GSK Investigational Site
Long Beach, California, United States, 90813
GSK Investigational Site
Los Angeles, California, United States, 90027
GSK Investigational Site
Los Angeles, California, United States, 90069
GSK Investigational Site
San Francisco, California, United States, 94109
United States, District of Columbia
GSK Investigational Site
Washington, District of Columbia, United States, 20009
United States, Florida
GSK Investigational Site
Fort Lauderdale, Florida, United States, 33316
GSK Investigational Site
Fort Pierce, Florida, United States, 34982
GSK Investigational Site
Miami, Florida, United States, 33133
GSK Investigational Site
Orlando, Florida, United States, 32803
GSK Investigational Site
Pensacola, Florida, United States, 32503
GSK Investigational Site
West Palm Beach, Florida, United States, 33401
United States, Georgia
GSK Investigational Site
Macon, Georgia, United States, 31201
United States, Illinois
GSK Investigational Site
Chicago, Illinois, United States, 60613
United States, Massachusetts
GSK Investigational Site
Springfield, Massachusetts, United States, 01107
United States, Michigan
GSK Investigational Site
Berkley, Michigan, United States, 48072
United States, New Jersey
GSK Investigational Site
Newark, New Jersey, United States, 07102
United States, Texas
GSK Investigational Site
Bellaire, Texas, United States, 77401
GSK Investigational Site
Dallas, Texas, United States, 75246
GSK Investigational Site
Longview, Texas, United States, 75602
Canada, Ontario
GSK Investigational Site
Ottawa, Ontario, Canada, K1H 8L6
GSK Investigational Site
Toronto, Ontario, Canada, M5G 2C4
Canada, Quebec
GSK Investigational Site
Montreal, Quebec, Canada, H2L 4P9
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT03045861     History of Changes
Other Study ID Numbers: 200911
First Posted: February 8, 2017    Key Record Dates
Last Update Posted: June 12, 2018
Last Verified: June 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Immunologic Deficiency Syndromes
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Cobicistat
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action