A Phase 2b study to select a once daily oral dose of GSK2248761 in HIV-1 infected antiretroviral therapy experienced adults with non-nucleoside reverse transcriptaseinhibitor (NNRTI) resistance

• Conditions: HIV-1 infected antiretroviral therapy experienced adult subjects; MedDRA version: 12.1Level: LLTClassification code 10008922Term: Chronic infection with HIV

• Registration Number: EUCTR2010-018532-40-BE
• Lead Sponsor: ViiV Healthcare UK Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-09-02
• Last Update Posted: 18 August 2014

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 150

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 <1% per year (not all IUDs meet this criterion).
- Any other method with published data showing that the lowest expected
failure rate for that method is <1% per year.
Note: Since no data is currently available on interactions between hormonal
contraceptives and GSK2248761, hormonal contraceptives are excluded medications in this study unless supportive drug interaction data becomes available.
Note:Non-child-bearing potential is defined as pre-menopausal with a documented tubal ligation, hysterectomy or bilateral oophorectomy; or post-menopausal defined as 24 months of spontaneous amenorrhea.
Any contraception method must be used consistently and in accordance with the
approved product label.
All study subjects should be counseled on the practice of safer sexual practices including
the use of effective barrier methods (e.g. male condom/spermicide).
2) HIV-1 infection with a screening plasma HIV-1 RNA =400copies/mL;
3) Previously received or current treatment with antiretroviral therapy (HAART) for
HIV-1 infection (patient may be off ART at time of screening);
4) HIV-1 harboring NNRTI resistance by screening genotype (defined as the presence
of =1 NNRTI resistance-associated mutations
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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;
11.HIV-1 genotype results with any of the following will be excluded:
•Any screening genotype with virus showing a Y181 mutation in combination with any other NNRTI resistance-associated mutations;
•Any screening genotype with virus showing a Y181I or Y188L alone or in combination with any other NNRTI resistance-associated mutations;
12.HIV-1 phenotype results with any of the following will be excluded:
•Any screening phenotype with virus showing etravirine fold change >10;
•Any screening phenotype with virus showing darunavir fold change >20;
•Any screening phenotype with virus showing raltegravir fold change >1.5;
13.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;
14.Any of the following laboratory values at screening:
•Creatinine clearance <50 mL/min via Cockroft-Gault method;
•Alanine aminotransferase (ALT) =5 times ULN. Subjects with ALT > 2xULN but <5xULN may participate in the study, if in the opinion of the Investigator and GSK medical monitor the lab abnormality will not interfere with the study procedures or compromise subject safety;
•Alanine aminotransferase (ALT) =?3xULN and bilirubin =?1.5xULN (with >35% direct bilirubin);
15.Any clinically significant finding on screening electrocardiograph (ECG), specifically (a single repeat is allowed to determine eligibility):
•Heart rate <45 and >100bpm (males), <50 and >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 >

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified