HIV-1 infected antiretroviral therapy naive adult subjects MedDRA version: 12.1 Level: LLT Classification code 10008922 Term: Chronic infection with HIV
Conditions
Sponsors
ViiV Healthcare UK Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) HIV-1 infected adults =18 years of age. A female is eligible to enter and participate in the study if she falls into one of the following categories: a. Non-childbearing potential; or, b. Child-bearing potential, with a negative pregnancy test at screen and Day 1 and agrees to one of the methods of contraception listed below. Premenarchal females who develop child-bearing potential while on study will also be expected to follow one of the methods of contraception listed below: -Complete abstinence from intercourse from 2 weeks prior to administration of IP, throughout the study, and for at least 2 weeks after discontinuation of all study medications. Should a subject of child-bearing potential decide to become sexually active during the course of the study, she must be counseled and be willing to use one of the other contraception methods listed below: -Double barrier method (male condom/spermicide, male condom/diaphragm, diaphragm/spermicide). -Any intrauterine device (IUD) with published data showing that the expected failure rate is =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1)Any pre-existing physical or mental condition (including substance abuse disorder) which, may interfere with the subject’s ability to comply with the study requirements or which may compromise the safety of the subject 2)Any condition which, in the opinion of the Investigator, may interfere with the absorption, distribution, metabolism or excretion of the drug or render the subject unable to take oral medication 3)Women who are currently breastfeeding 4)Any evidence of an active Centers for Disease and Prevention Control (CDC) Category C disease, except cutaneous Kaposi’s sarcoma not requiring systemic therapy 5)History of ongoing or clinically relevant hepatitis within the previous 6 months, including chronic hepatitis B virus (HBV) infection (HBsAg positive). Asymptomatic individuals with chronic hepatitis C virus (HCV) infection will not be excluded 6)History of liver cirrhosis with or without hepatitis viral co-infection; 7)Ongoing or clinically relevant pancreatitis 8)History of the following cardiac diseases: myocardial infarction, congestive heart failure, documented hypertrophic cardiomyopathy, sustained ventricular tachycardia; 9)Personal or known family history of prolonged QT syndrome 10)History or presence of allergy or intolerance to the study drugs or their components, or a history of drug or other allergy that, in the opinion of the Principal Investigator, contraindicates their participation. In addition, if heparin is used during PK sampling, subjects with a history of sensitivity to heparin or heparin-induced thrombocytopenia should not be enrolled Exclusionary genotypes: 11)Evidence of viral resistance to any antiviral drug indicative of primary transmitted resistance in a screening or historical resistance test result Exclusionary lab values at screening: 12)Any acute laboratory abnormality at screening, which, in the opinion of the Investigator, would preclude the subject’s participation in the study of an investigational compound. Any verified Grade 4 laboratory abnormality at screening would exclude a subject from study participation unless the Investigator can provide a compelling explanation for the laboratory result(s) and has the assent of the medical monitor 13)Any of the following laboratory values at screening: •Creatinine clearance 2xULN but 35% direct bilirubin); 14)Any clinically significant finding on screening electrocardiograph (ECG), specifically (a single repeat is allowed to determine eligibility): •Heart rate 100bpm (males), 100bpm (females); Note: A heart rate from 100 to 110 BPM can be rechecked within 30 minutes to verify eligibility. •QRS duration >120msec; •QTc interval > 450msec; •Non-sustained (= 3 consecutive beats) or sustained ventricular tachycardia; •Sinus pauses >2.5 seconds; •2nd degree (Type II) or higher AV (Atrioventricular) block; •Evidence of WPW (Wolff-Parkinson-White) syndrome (ventricular preexcitation); •Pathologic Q waves (defined as Q wave > 40msec OR depth >0.4 mV); •Any other abnormality which in the opinion of the investigator would interfere with the safety of the subject Exclusionary tr
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To select a once daily dose of GSK2248761 for further evaluation in Phase 3 based on a comparison of the Week 16 antiviral activity and tolerability of two oral doses of GSK2248761 in HIV-1 infected therapy-naïve adult subjects;Primary end point(s): The proportion of subjects with HIV-1 RNA <50copies/mL through Week 16. Dose selection will be based primarily on antiviral activity and tolerability in conjunction with immunologic, safety, virologic resistance and PK measures. Data from the Week 24 analysis will be used to confirm dose selection.;Secondary Objective: To evaluate the effect of GSK2248761 on virologic and immunologic markers of HIV infection through week 96 To evaluate safety and tolerability of GSK2248761 through week 4 and 96 To collect GSK2248761 limited and intensive PK samples for population modelling approach to characterize GSK2248761 PK and identify potential covariates that influence the PK To confirm the optimal GSK2248761 dose at Week 24 based on antiviral activity in conjunction with immunologic, safety and PK measures To explore exposure-response relationships of GSK2248761 and predict clinical PK and PD outcome to assist with dose selection for Phase 3 trials To assess the development of viral resistance in subjects experiencing protocol-defined virologic failure To evaluate the effect of subject characteristics on exposure-response parameters of GSK2248761 To evaluate the antiviral activity, safety, tolerability and development of viral resistance of the selected dose of GSK2248761 relative to EFV | — |
Countries
Germany, Spain
Outcome results
None listed