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Single and Repeated Dose Escalation Study of GSK2838232

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02795754
Recruitment Status : Completed
First Posted : June 10, 2016
Last Update Posted : January 18, 2017
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Brief Summary:
GSK2838232 is a Human Immunodeficiency Virus (HIV) maturation inhibitor being developed for the treatment of HIV in combination with other antiretroviral therapy (ART). The primary objectives of this study are to investigate the safety, tolerability, and pharmacokinetics (PK) of single and repeat doses of GSK2838232. This study will be a double-blind, placebo-controlled, single and repeat dose escalation study. This study will be conducted in two Parts: single escalating doses (Part 1A and 1B), and repeated escalating once daily (QD) doses for 11 days (Part 2) of GSK2838232 co-dosed with RTV. During Part 1A, single doses of GSK2838232 (as of active pharmaceutical ingredient-powder in bottle [API PiB]) 50 milligrams (mg), 100mg and 200mg will be administered with RTV. Part 1B will evaluate the relative bioavailability of single doses of crystalline active pharmaceutical ingredient (API) Immediate Release Tablet (IR) tablets versus API PiB as reference, administered with RTV. In Part 2, multiple doses of GSK2838232 will be co-administered with RTV 100mg QD for 11 days as sequential dose cohorts. Maximum duration of study participation will be approximately 10 weeks.

Condition or disease Intervention/treatment Phase
Infection, Human Immunodeficiency Virus Drug: GSK2838232 PIB Drug: GSK2838232 IR1 Drug: GSK2838232 IR2 Drug: Placebo PIB Drug: Ritonavir Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 62 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Double-Blind (Sponsor Unblinded), Randomized, Placebo-Controlled, Continuation Single and Repeated Dose Escalation Study to Investigate the Safety, Tolerability and Pharmacokinetics of GSK2838232 With Ritonavir, in Healthy Subjects
Study Start Date : March 2016
Actual Primary Completion Date : December 2016
Actual Study Completion Date : December 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Experimental: GSK2838232 PIB (50 mg+100 mg+200 mg)+Placebo
During Part 1A, subjects will receive QD single dose of either GSK2838232 50 mg, 100 mg or 200 mg or placebo in each of the four visits (one treatment per visit).Subjects will also receive RTV along with all the doses and QD RTV for 48hours (2 doses) before all doses of GSK2838232 and placebo.
Drug: GSK2838232 PIB
GSK2838232 will be available as oral suspension for reconstitution, will be administered as 50, 100 and 200 mg in Part A and as 20, 50, 100 or 200 mg in Part B.

Drug: Placebo PIB
Oral suspension of hydromellulose acetate succinate will be supplied as powder-in-bottle for reconstitution.

Drug: Ritonavir
It is to be purchased by site. It will be white film-coated ovaloid tablets for oral administration.

Experimental: GSK2838232 PIB+IR1+IR2
During Part 1B, subjects will receive either GSK2838232 PIB, GSK2838232 IR1 or IR2 in each of the three visits (one treatment per visit) after at least 10 hours fasting and IR1 or IR2 after fat meal at visit 4.
Drug: GSK2838232 PIB
GSK2838232 will be available as oral suspension for reconstitution, will be administered as 50, 100 and 200 mg in Part A and as 20, 50, 100 or 200 mg in Part B.

Drug: GSK2838232 IR1
GSK2838232 will be available as film-coated tablet for oral use

Drug: GSK2838232 IR2
GSK2838232 will be available as film-coated tablet for oral use

Drug: Ritonavir
It is to be purchased by site. It will be white film-coated ovaloid tablets for oral administration.

Experimental: GSK2838232 PIB (20mg/50 mg/100 mg/200 mg)/Placebo
During Part 2, subjects will receive repeated QD doses of either GSK2838232 (20 mg, 50 mg, 100 mg or 200 mg) or placebo for 11 days. Subjects will also receive RTV along with all the doses of GSK2838232 and placebo.
Drug: GSK2838232 PIB
GSK2838232 will be available as oral suspension for reconstitution, will be administered as 50, 100 and 200 mg in Part A and as 20, 50, 100 or 200 mg in Part B.

Drug: Placebo PIB
Oral suspension of hydromellulose acetate succinate will be supplied as powder-in-bottle for reconstitution.

Drug: Ritonavir
It is to be purchased by site. It will be white film-coated ovaloid tablets for oral administration.




Primary Outcome Measures :
  1. Number of participants with adverse events (AEs) [ Time Frame: Approximately 10 weeks ]
    An AE is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.

  2. Safety as assessed by absolute values and change from Baseline in hematology parameters -Part 1 [ Time Frame: Baseline (Day -1) and up to 10 weeks ]
    Hematology parameters includes platelet count, red blood cells (RBC) count, mean corpuscular volume (MCV), neutrophils, white blood cells (WBC) count (absolute), mean corpuscular hemoglobin (MCH), lymphocytes, reticulocyte count, mean corpuscular hemoglobin concentration (MCHC), monocytes, hemoglobin, eosinophils, hematocrit and basophils. Hematology parameters will be evaluated at Day -2, Day -1, Day 2, Day 4, Day 14 of each visit.

  3. Safety as assessed by absolute values and change from Baseline in hematology parameters - Part 2 [ Time Frame: Baseline (Day-1) and up to Day 31 for each cohort. ]
    Hematology parameters includes platelet count, RBC count, MCV, neutrophils, WBC count (absolute), MCH, lymphocytes, reticulocyte count, MCHC, monocytes, hemoglobin, eosinophils, hematocrit and basophils. Hematology parameters will be evaluated at Day -1, Day 2, Day 4, day 8, Day 11, Day 14, Day 17, Day 31 for each cohort

  4. Safety as assessed by absolute values and change from Baseline in clinical chemistry parameters -Part 1 [ Time Frame: Baseline (Day -1) and up to 10 weeks ]
    Clinical chemistry parameters includes blood urine nitrogen (BUN), potassium, aspartate aminotransferase (AST), Lipase, Creatinine, Sodium, alanine aminotransferase (ALT), total protein, glucose, chloride, alkaline phosphatase, albumin, magnesium, total carbon dioxide (CO2), total and direct bilirubin, uric acid, calcium, phosphorus and gamma-glutamyl transferase (GGT). Clinical chemistry parameters will be evaluated at Day -2, Day -1, Day 2, Day 4, Day 14 of each visit.

  5. Safety as assessed by absolute values and change from Baseline in clinical chemistry parameters- Part 2 [ Time Frame: Baseline (Day-1) and up to Day 31 for each cohort. ]
    Clinical chemistry parameters includes BUN, potassium, AST, lipase, creatinine, sodium, ALT, total protein, glucose, chloride, alkaline phosphatase, albumin, magnesium, total CO2, total and direct bilirubin, uric acid, calcium, phosphorus and GGT. Clinical chemistry parameters will be evaluated at Day -1, Day 2, Day 4, day 8, Day 11, Day 14, Day 17, Day 31 for each cohort

  6. Safety as assessed by absolute values and change from Baseline in urinalysis parameters-Part 1 [ Time Frame: Baseline (Day -1) and up to 10 weeks ]
    Urinalysis parameters includes specific gravity, pH, glucose, protein, blood and ketones by dipstick, microscopic examination. Urinalysis parameters will be evaluated at Day -2, Day -1, Day 2, Day 4, Day 14 of each visit.

  7. Safety as assessed by absolute values and change from Baseline in urinalysis parameters-Part 2 [ Time Frame: Baseline (Day-1) and up to Day 31 for each cohort. ]
    Urinalysis parameters includes specific gravity, pH, glucose, protein, blood and ketones by dipstick, microscopic examination. Urinalysis parameters will be evaluated at Day -1, Day 2, Day 4, Day 11, Day 14, Day 17, Day 31 for each cohort

  8. Safety as assessed by Blood pressure-Part 1 [ Time Frame: 10 weeks ]
    Systolic and diastolic blood pressure will be measured on Day 1, pre-dose (triplicate) and 1, 2, 4, 6, 8, 12, 24, 48, and 72hr post-dose during each visit.

  9. Safety as assessed by Heart rate -Part 1 [ Time Frame: 10 weeks ]
    Heart rate will be measured on Day 1, pre-dose (triplicate) and 1, 2, 4, 6, 8, 12, 24, 48, and 72hr post-dose during each visit.

  10. Safety as assessed by Blood pressure-Part 2 [ Time Frame: 31 days in each cohort ]
    Systolic and diastolic blood pressure will be measured on Day -1, Day 1 at pre dose (triplicate), and 1hr, 4hr, 24hr, 48hr and 72hr post dose, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11 at pre dose (triplicate), and 1hr, 4hr, 24hr, 48hr and 72hr post dose and at follow up during each cohort.

  11. Safety as assessed by Heart rate -Part 2 [ Time Frame: 31 days in each cohort ]
    Heart rate will be measured on Day -1, Day 1 at pre dose (triplicate), and 1hr, 4hr, 24hr, 48hr and 72hr post dose, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11 at pre dose (triplicate), and 1hr, 4hr, 24hr, 48hr and 72hr post dose and at follow up during each cohort.

  12. Safety as assessed by Electrocardiogram (ECG) parameters-Part 1 [ Time Frame: Up to 10 weeks ]
    12-lead ECG will be conducted pre-dose on Day 1 (triplicate), and 1, 2, 4, 6, 8, 12, 24, 48 72 hour post dose.

  13. Safety as assessed by ECG parameters-Part 2 [ Time Frame: 31 days in for each cohort ]
    A single 12-Lead ECG will be conducted at screening and Day -1, Day 1 at pre dose (triplicate), and 1 hour, 12 hour, 24hour, 48 hour and 72 hour post dose, Day 5, Day 8 and Day 11 at pre dose (triplicate), and 1 hr, 12 hour, 24 hour, 48 hour, and 72 hour post dose and at follow up during each cohort.

  14. Area under the concentration-time curve from time zero (pre-dose) to 24 hours (AUC[0-24]), Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC [0-inf]) in Part 1 [ Time Frame: Plasma samples will be collected pre-dose (within 15 minutes prior to dosing) and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose at each study visit ]
  15. Apparent oral clearance (CL/F) for single dose GSK2838232 in Part 1A [ Time Frame: Plasma samples will be collected pre-dose (within 15 minutes [min]prior to dosing) and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose at each study visit during Part 1A. ]
  16. Area under the concentration-time curve over the dosing interval (AUC[0 tau]) for repeated dose GSK2838232 in Part 2 [ Time Frame: Day 1; pre-dose (within 15 min prior to dosing) and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12 and 24 hr post dose.On Day 11; pre-dose (within 15 min prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120 and 144 hr post dose ]
  17. Apparent oral clearance (CL/F) for repeated dose GSK2838232 in Part 2 [ Time Frame: Plasma samples will be collected on Day 11; pre-dose (within 15 minutes prior to dosing) and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120 and 144 hours post dose. ]
  18. Tmax for repeated dose GSK2838232 in Part 2 [ Time Frame: Day 1; pre-dose (within 15 min prior to dosing) and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12 and 24 hr post dose. On Day 11; pre-dose (within 15 min prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96,120 and 144 hr post dose ]
  19. Tlag for repeated dose GSK2838232 in Part 2 [ Time Frame: Day 1; pre-dose (within 15 min prior to dosing) and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12 and 24 hr post dose. On Day 11; pre-dose (within 15 min prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96,120 and 144 hr post dose ]
  20. T1/2 for repeated dose GSK2838232 in Part 2 [ Time Frame: Day 1; pre-dose (within 15 min prior to dosing) and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12 and 24 hr post dose. On Day 11; pre-dose (within 15 min prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96,120 and 144 hr post dose ]
  21. Tlast for repeated dose GSK2838232 in Part 2 [ Time Frame: Day 1; pre-dose (within 15 min prior to dosing) and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12 and 24 hr post dose. On Day 11; pre-dose (within 15 min prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96,120 and 144 hr post dose ]
  22. Maximum observed concentration (Cmax) in Part 1 [ Time Frame: Plasma samples will be collected pre-dose (within 15 minutes prior to dosing) and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose at each study visit ]
  23. Concentration at 24 hours post dose (C24) in Part 1 [ Time Frame: Plasma samples will be collected pre-dose (within 15 minutes prior to dosing) and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose at each study visit ]
  24. Last measurable concentration (Clast) in Part 1 [ Time Frame: Plasma samples will be collected pre-dose (within 15 minutes prior to dosing) and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose at each study visit ]
  25. Time of occurence of Cmac (tmax) in Part 1 [ Time Frame: Plasma samples will be collected pre-dose (within 15 minutes prior to dosing) and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose at each study visit ]
  26. Lag time before observation of drug concentrations in sampled matrix (tlag) in Part 1 [ Time Frame: Plasma samples will be collected pre-dose (within 15 minutes prior to dosing) and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose at each study visit ]
  27. Terminal phase half life (t1/2) in Part 1 [ Time Frame: Plasma samples will be collected pre-dose (within 15 minutes prior to dosing) and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose at each study visit ]
  28. Time of last observed quantifiable concentration (t-last) in Part 1 [ Time Frame: Plasma samples will be collected pre-dose (within 15 minutes prior to dosing) and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose at each study visit ]
  29. Cmax of GSK2826232 in Part 2 [ Time Frame: Day 1; pre-dose (within 15 min prior to dosing) and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12 and 24 hr post dose.On Day 11; pre-dose (within 15 min prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120 and 144 hr post dose ]
  30. Clast of GSK2826232 in Part 2 [ Time Frame: Day 1; pre-dose (within 15 min prior to dosing) and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12 and 24 hr post dose.On Day 11; pre-dose (within 15 min prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120 and 144 hr post dose ]
  31. Concentration-time curve over the dosing interval (Ctau) of GSK2838232 in Part 2 [ Time Frame: Day 1; pre-dose (within 15 min prior to dosing) and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12 and 24 hr post dose.On Day 11; pre-dose (within 15 min prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120 and 144 hr post dose ]

Secondary Outcome Measures :
  1. AUC (0-inf) in Part 1 [ Time Frame: Plasma samples will be collected pre-dose (within 15 minutes prior to dosing) and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose at each study visit ]
  2. Cmax in Part 1 [ Time Frame: Plasma samples will be collected pre-dose (within 15 minutes prior to dosing) and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose at each study visit ]
  3. AUC(0-tau) in Part 2 [ Time Frame: Day 1 pre-dose; 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24 hr post dose. Days 3-10 pre-dose; Day 11; pre-dose and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120 and 144 hr post dose; all pre-dose within 15 min prior to dosing ]
  4. Cmax in Part 2 [ Time Frame: Day 1 pre-dose; 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24 hr post dose. Days 3-10 pre-dose; Day 11; pre-dose and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120 and 144 hr post dose; all pre-dose within 15 min prior to dosing ]
  5. Ctau in Part 2 [ Time Frame: Day 1 pre-dose; 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24 hr post dose. Days 3-10 pre-dose; Day 11; pre-dose and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120 and 144 hr post dose; all pre-dose within 15 min prior to dosing ]
  6. Pre-dose GSK2838232 plasma concentrations on Day 2-11 in Part 2 [ Time Frame: Up to Day 11 ]
  7. Accumulation ratios (Ro) for AUC (0-tau) [ Time Frame: Day 1 pre-dose; 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24 hr post dose. Days 3-10 pre-dose; Day 11; pre-dose and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120 and 144 hr post dose; all pre-dose within 15 min prior to dosing ]
  8. Accumulation ratios (Ro) for Cmax [ Time Frame: Day 1 pre-dose; 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24 hr post dose. Days 3-10 pre-dose; Day 11; pre-dose and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120 and 144 hr post dose; all pre-dose within 15 min prior to dosing ]
  9. Accumulation ratios (Ro) for Ctau (where tau is 24 hours) [ Time Frame: Day 1 pre-dose; 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24 hr post dose. Days 3-10 pre-dose; Day 11; pre-dose and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120 and 144 hr post dose; all pre-dose within 15 min prior to dosing ]


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 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Age: Between 18 and 55 years of age inclusive, at the time of signing the informed consent.
  • Healthy as determined by the Investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring.
  • A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, and outside the reference range for the population being studied, may be included only if the Investigator in consultation with the Medical Monitor, if required, agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures
  • A creatinine clearance (CLcr) >80milliliter/minute (mL/min) as determined by Cockcroft-Gault equation CLcr (mL/min) = (140 - age) * weight (Wt) / (72 * serum creatinine [Scr]) (times 0.85 if female) where age is in years, Wt is in kilogram (kg), and Scr is in units of milligram / decilitre (mg/dL);.
  • Body weight >= 50.0 kg (110 pounds [lbs.]) for men and >= 45.0kg (99lbs) for women and body mass index (BMI)
  • Male or females of non-reproductive potential:

A female subject is eligible to participate if she is not pregnant [as confirmed by a negative serum human chorionic gonadotrophin (hCG) test], not lactating, and of non-reproductive potential which is defined as:

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 Post menopausal 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 (refer to laboratory reference ranges for confirmatory levels)]. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they 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, or Male condom plus partner use of one of the contraceptive options following: Contraceptive subdermal implant that meets the standard operating procedure (SOP) effectiveness criteria including a <1% rate of failure per year, as stated in the product label; Intrauterine device or intrauterine system that meets the SOP effectiveness criteria including a <1% rate of failure per year, as stated in the product label; Oral Contraceptive, either combined or progestogen alone. 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 as described in Study protocol which includes compliance with the requirements and restrictions listed in the consent form and in protocol.

Exclusion Criteria:

  • Alanine aminotransferase and bilirubin >1.0* upper limit of normal (ULN).
  • Current or chronic history of liver disease, or known hepatic or biliary abnormalities.
  • Subjects who have asthma or a history of asthma.
  • Medical history of cardiac arrhythmias or cardiac disease or a family and 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 GlaxoSmithKline (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: For US sites: 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 (150mL) of wine or 1.5 ounces (45mL) of 80 proof distilled spirits.
  • Regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
  • History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the Investigator or Medical Monitor, contraindicates their participation
  • Presence of hepatitis B surface antigen (HBsAg), or 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% cut-off (>.045 nanograms/mL by the Dimension Vista Cardiac troponin assay) for a given assay.
  • A positive pre-study drug/alcohol screen.
  • A positive test for HIV antibody.
  • Where participation in the study would result in donation of blood or blood products in excess of 500mL 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.
  • Exclusion Criteria for 48-Hour Screening Holter:

Any symptomatic arrhythmia (except isolated extra systoles). Sustained cardiac arrhythmias (such as atrial fibrillation or flutter, supraventricular tachycardia (>=10 consecutive beats), complete heart block).

Non-sustained or sustained ventricular tachycardia (defined as >= 3 consecutive ventricular ectopic beats).

Any conduction abnormality (including but not specific to left or right incomplete or complete bundle branch block, atrioventricular (AV) block [2nd degree or higher], Wolf Parkinson White (WPW) syndrome etc.).

Sinus Pauses > 3 seconds. 300 or more supraventricular ectopic beats in 24 hours. 250 or more ventricular ectopic beats in 24 hours.

  • Any clinically significant abnormal echocardiogram finding. Abnormal echocardiogram findings should be discussed with the Medical Monitor prior to enrolment.
  • Exclusion criteria for screening ECG (a single repeat is allowed for eligibility determination):

Heart rate for Males <45 and >100 beats per minute (bpm), for females <50 and >100bpm PR Interval <120 and >220 millisecond (msec) QRS duration <70 and >120msec QT interval corrected (Fridericia's) >450msec


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): NCT02795754


Locations
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United States, Maryland
GSK Investigational Site
Baltimore, Maryland, United States, 21225
Sponsors and Collaborators
GlaxoSmithKline
Investigators
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Study Director: GSK Clinical Trials GlaxoSmithKline
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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT02795754    
Other Study ID Numbers: 204953
First Posted: June 10, 2016    Key Record Dates
Last Update Posted: January 18, 2017
Last Verified: January 2017
Keywords provided by GlaxoSmithKline:
GSK2838232
HIV
repeated dose escalation
immediate release tablet
single dose escalation
Additional relevant MeSH terms:
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Acquired Immunodeficiency Syndrome
HIV Infections
Immunologic Deficiency Syndromes
Immune System Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Ritonavir
GSK2838232
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors