Infection, Human Immunodeficiency VirusPhase 2NCT00945282

Safety and Tolerability Study to Evaluate Lower Dose of GSK2248761 in Antiretroviral Treatment-Naive HIV-1 Infected Adults.

A Phase 2 study testing GSK2248761, Lopinavir/ritonavir and HAART in people with Infection, Human Immunodeficiency Virus, run by ViiV Healthcare at 1 site in Argentina.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

GSK has in-licensed a novel NNRTI-class candidate (GSK2248761, IDX12899) for the treatment of subjects with HIV-1 infection from Idenix Pharmaceuticals. Idenix Pharmaceuticals completed a proof-of-concept study evaluating GSK2248761 monotherapy over seven days in forty treatment-naïve subjects infected with HIV-1. Read more about this study

Who is it for?: Ages 21 to 65 years
Conditions the study is for: Infection, Human Immunodeficiency Virus
What is being tested?: GSK2248761, Lopinavir/ritonavir and HAART
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 8 participants
Where: 1 siteArgentina
Study dates: 20 Oct 2009to 28 Nov 2009
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 21 to 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Male or Female, 21 to 65 years of age.
Female of non-childbearing potential defined as: being post-menopausal, defined as 12 months of spontaneous amenorrhea and having a serum FSH level >40 MIU/ml at Screening OR have had a documented bilateral tubal ligation or hysterectomy of at least 6 months prior to study initiation, bilateral oophorectomy or bilateral tubal ligation.
Plasma HIV-1 RNA value >= 5000 copies/mL.
CD4+ count >= 200 cells/mm3.
Is antiretroviral treatment-naïve and agrees not to start antiretroviral therapy prior to clinic check-in (Day-1).
Subject agrees to start a standard HAART regimen on Day 8 of the study or Kaletra monotherapy for 28 days within 24 hours after the last dose of study medication.
Capable of giving written informed consent, which includes being willing and able to comply with the requirements and restrictions listed in the consent form.

Who cannot join

Subject is pregnant as determined by a positive urine/serum pregnancy test at Screening and Day -1.
Lactating females.
Male subjects of reproductive potential and unwilling to use double barrier method of contraception (e.g., condom plus spermicide) and continue to use an adequate method of birth control for at least 30 days after the last dose of the study drug.
Has a positive screening Hepatitis B surface antigen, positive screening Hepatitis C virus (HCV) antibody and detectable HCV ribonucleic acid (RNA) on subsequent testing. If the Hepatitis C antibody is positive but the HCV RNA is undetectable, the subject may be included in the study.
History of regular alcohol consumption within 6 months of Screening as defined as: an average weekly intake of >21 units for males or >14 units for females. One unit is equivalent to 8 g of alcohol: a half-pint (~240 ml) of beer, 1 glass (125 ml) of wine or 1 (25 ml) measure of spirits
Has a positive pre-study drug screen. Drugs that will be screened for include amphetamines, barbiturates, cocaine and PCP.

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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 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.
Note: Study drugs include GSK2248761 placebo or the follow-up HAART or Kaletra therapy.
Received an immunomodulating agent (e.g., interleukin-2) or immunotherapeutic vaccine within 30 days before Day -1.
Requires a medication that is a known substrate, inhibitor and/or inducer of CYP3A4.
Has received an investigational drug or participated in any other research trial within 30 days or 5 half-lives, or twice the duration of the biological effect of any drug (whichever is longer) prior to the first dosing day.
Has ever had an AIDS-defining illness.
Has a history of or has a currently active clinically important disease other than HIV-1 infection that, in the opinion of the Investigator, may put the subject at risk because of participation in this study (including renal and hepatic impairment, active infections including tuberculosis or opportunistic infection, malignancy and cardiac dysfunction).
Has an intestinal malabsorption (e.g., structural defects, digestive failure, enzyme deficiencies, etc).
Has a pre-existing NNRTI drug resistance based on genotyping at Screening.
Where participation in the study would result in donation of blood or blood products in excess of 500mL within a 56 day period.
Subject has any of the following laboratory parameters at Screening (a single repeat is allowed for eligibility determination): Hemoglobin <8.5 g/dL, Neutrophil count <1000 cells/mm3, Platelet count <100,000 cells/mm3, Serum creatinine > the upper limit of normal (ULN), AST or ALT <= 2.5 x ULN.
Exclusion Criteria for Screening ECG (A single repeat is allowed for eligibility determination): Exclusion Criteria for Screening ECG: Heart rate: (males) <45 and >100 bpm (females) <50 and >100 bpm, QRS duration: >120 msec, QTc interval (Bazett): > 450 msec. Non-sustained (>= 3 consecutive beats) or sustained ventricular tachycardia. Sinus Pauses >2.5 seconds. 2nd degree (Type II) or higher AV block. Evidence of previous myocardial infarction (pathologic Q waves, S-T segment changes (except early repolarization)).

Trial locations and contacts

1 site in 1 country.

Argentina1 site

GSK Investigational Site
Buenos Aires, B1602DBG

Other trials in Argentina

About this study

Official title: A Proof of Concept Study for GSK2248761 (An Extension of NV-05A-002: A Phase I/IIa Double-Blind Study to Evaluate the Safety and Tolerability, Antiretroviral Activity, Pharmacokinetics and Pharmacodynamics of IDX12899 in Antiretroviral Treatment-Naive HIV-1 Infected Subjects, Completed by Idenix)

This study will evaluate a lower dose, or doses, of GSK2248761 to better characterize the dose-response and concentration-response curves. The results from this study will be used to select doses for future clinical studies in HIV-1 infected subjects.

Conditions: Infection, Human Immunodeficiency Virus
Being tested: GSK2248761, Lopinavir/ritonavir, HAART, Placebo
Keywords: IDX12899, adaptive, monotherapy, pharmacokinetics, Treatment-naive, HIV-1, GSK2248761, NNRTI, HIV Infections, treatment naive
Medical subject headings: Infections, Acquired Immunodeficiency Syndrome, HIV Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

GSK2248761Drug
GSK2248761 30 mg capsule once a day for 7 days. GSK2248761 is an investigational (not approved by the FDA) HIV drug in the class of non-nucleoside reuptake inhibitor class.
Lopinavir/ritonavirDrug
Also called Kaletra
Lopinavir 400 mg and ritonovir 100 mg every 12 hours for 28 days. Lopinavir/ritonavir is approved by the FDA as an HIV medication in the protease inhibitor class. Kaletra is a trademark of Abbott Laboratories.
HAARTDrug
Highly Active Antiretroviral therapy of the doctor's choice.
PlaceboDrug
Placebo is a capsule with no drug in it.
GSK2248761Drug
GSK2248761 10 mg -20 mg or 40 mg - 90 mg once a day for 7 days. GSK2248761 is an investigational (not approved by the FDA) HIV drug in the class of non-nucleoside reuptake inhibitor class.

Study groups in NCT00945282
Study group	Role	What they receive
Cohort 1	Experimental	In Cohort 1 subjects will receive either GSK2248761 30 mg or placebo once a day for 7 days. On Day 8 subjects will receive either Kaletra or HAART for 28 days. The doctor will choose the most appropriate medications for HAART. Receives: Drug: GSK2248761; Drug: Lopinavir/ritonavir; Drug: HAART; Drug: Placebo
Cohort 2	Experimental	In Cohort 2 subjects will receive either GSK2248761 in the range of 10 mg - 20 mg or 40 mg - 90 mg or placebo once a day for 7 days. On Day 8 subjects will receive either Kaletra or HAART for 28 days. The doctor will choose the most appropriate medications for HAART. The dose for Cohort 2 will be determined following evaluation of results from Cohort 1. Cohort 2 may not be done. Receives: Drug: Lopinavir/ritonavir; Drug: HAART; Drug: Placebo; Drug: GSK2248761

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Participants With Serious Adverse Events (SAEs) and Adverse Events (AEs)
An AE is defined as any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect, or is an important medical events that jeopardize the participants or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition, or a drug-induced liver injury.
Measured: Up to 38 days
Change From Baseline in Hematology Paramaters- Basophils, Eosinophils, Lymphocytes, Monocytes, White Blood Cell Count
The data for hematology parameters for Basophils, eosinophils, lymphocytes, monocytes, and white blood cell count from the change from baseline was reported. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose [Screening, Day -1 or Day 1]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise.
Measured: Baseline (pre-dose at Day -1 or Day 1) and Day 2, 4 , 7 , Day 8 and Follow-up (Day 14)
Change From Baseline in Hematology Paramaters- Hemoglobin
The data for hematology parameter hemoglobin from the change from baseline was reported. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose [Screening, Day -1 or Day 1]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise.
Measured: Baseline (pre-dose at Day -1 or Day 1) and Day 2, 4 , 7 , Day 8 and Follow-up (Day 14)
Change From Baseline in Hematology Paramaters- Platelet Count
The data for hematology parameter platelet count, for the change from baseline was reported. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose [Screening, Day -1 or Day 1]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise.
Measured: Baseline (pre-dose at Day -1 or Day 1) and Day 2, 4 , 7 , Day 8 and Follow-up (Day 14)
Change From Baseline in Hematology Paramaters- Red Blood Cell Count
The data for hematology parameter red blood cell count, for the change from baseline was reported. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose [Screening, Day -1 or Day 1]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise.
Measured: Baseline (pre-dose at Day -1 or Day 1) and Day 2, 4 , 7 , Day 8 and Follow-up (Day 14)
Change From Baseline in Hematology Parameters- Total Neutrophil
The data for hematology parameter total neutrophil count, for the change from baseline was reported. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose [Screening, Day -1 or Day 1]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise.
Measured: Baseline (pre-dose at Day -1 or Day 1) and Day 2, 4 , 7 , Day 8 and Follow-up (Day 14)
Change From Baseline in Hematology Paramaters- Mean Corpuscle Hemoglobin (MCH)
The data for hematology parameter MCH, the change from baseline was reported. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose [Screening, Day -1 or Day 1]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise.
Measured: Baseline (pre-dose at Day -1 or Day 1) and Day 2, 4 , 7 , Day 8 and Follow-up (Day 14)
Change From Baseline in Hematology Paramaters- Mean Corpuscle Volume (MCV)
The change from baseline data for hematology parameter MCV, was reported. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose [Screening, Day -1 or Day 1]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise.
Measured: Baseline (pre-dose at Day -1 or Day 1) and Day 2, 4 , 7 , Day 8 and Follow-up (Day 14)
Change From Baseline in Hematology Paramaters- Hematocrit
The data for hematology parameter Hematocrit, the change from baseline was reported. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose [Screening, Day -1 or Day 1]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise.
Measured: Baseline (pre-dose at Day -1 or Day 1) and Day 2, 4 , 7 , Day 8 and Follow-up (Day 14)
Change From Baseline in Hematology Paramaters-Mean Corpuscle Hemoglobin Concentration
The data for hematology parameter Mean Corpuscle Hemoglobin concentration, the change from baseline was reported. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose [Screening, Day -1 or Day 1]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise.
Measured: Baseline (pre-dose at Day -1 or Day 1) and Day 2, 4 , 7 , Day 8 and Follow-up (Day 14)
Change From Baseline in Clinical Chemistry Paramaters- Albumin and Total Protein
The data for clinical chemistry parameters Albumin and total protein, the change from baseline was reported. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose [Screening, Day -1 or Day 1]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise.
Measured: Baseline (pre-dose at Day -1 or Day 1) and Day 2, 4 , 7 , Day 8 and Follow-up (Day 14)
Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin.
The data for clinical chemistry parameters- Blood urea nitrogen, triglycerides, glucose, creatinine, calcium, cholesterol, total bilirubin, and direct bilirubin. The change from baseline was reported. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose [Screening, Day -1 or Day 1]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise.
Measured: Baseline (pre-dose at Day -1 or Day 1) and Day 2, 4 , 7 , Day 8 and Follow-up (Day 14)
Change From Baseline in Clinical Chemistry Paramaters- Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase
The data for clinical chemistry paramaters- alkaline phosphatase, alanine amino transferase, aspartate amino transferase, the change from baseline was reported. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose [Screening, Day -1 or Day 1]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise.
Measured: Baseline (pre-dose at Day -1 or Day 1) and Day 2, 4 , 7 , Day 8 and Follow-up (Day 14)
Change From Baseline in Clinical Chemistry Paramaters-sodium, Potassium and Carbondioxide or Bicarbonate
The data for clinical chemistry parameters- sodium, potassium and carbon dioxide or bicarbonate, the change from baseline was reported. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose [Screening, Day -1 or Day 1]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise.
Measured: Baseline (pre-dose at Day -1 or Day 1) and Day 2, 4 , 7 , Day 8 and Follow-up (Day 14)
Change From Baseline in Clinical Chemistry Paramaters- Phosphorus
The data for clinical chemistry paramaters- phosphorous, the change from baseline was reported. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose [Screening, Day -1 or Day 1]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise.
Measured: Baseline (pre-dose at Day -1 or Day 1) and Day 2, 4 , 7 , Day 8 and Follow-up (Day 14)
Change From Baseline in Clinical Chemistry Paramaters- Uric Acid
The data for clinical chemistry parameters Uric acid, the change from baseline was reported. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose [Screening, Day -1 or Day 1]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise.
Measured: Baseline (pre-dose at Day -1 or Day 1) and Day 2, 4 , 7 , Day 8 and Follow-up (Day 14)
Change From Baseline in Clinical Chemistry Paramaters- Thyroxine, Free
The data for clinical chemistry parameters Thyroxine, free the change from baseline was reported. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose [Screening, Day -1 or Day 1]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise.
Measured: Baseline (pre-dose at Day -1 or Day 1) and Day 2, 4 , 7 , Day 8 and Follow-up (Day 14)
Change From Baseline in Clinical Chemistry Paramaters- Thyroxine Total, Thyroxine Binding Globulin, Total T3.
The data for clinical chemistry parameters Thyroxine total, thyroxine binding globulin, Total T3 the change from baseline was reported. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose [Screening, Day -1 or Day 1]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise.
Measured: Baseline (pre-dose at Day -1 or Day 1) and Day 2, 4 , 7 , Day 8 and Follow-up (Day 14)
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
Triplicate 12-lead ECGs were collected at different timepoints, after participants were supine for 5 minutes, during the study using an ECG machine that automatically calculated the heart rate (HR) and measures PR, QRS, QT, and QTc intervals. The three consecutive determinations were collected 5 plus or minus 2 minutes apart and all three tracings were recorded. The participants with abnormal values categorized as abnormal clinically significant (CS) and not clinically significant (NCS) were reported.
Measured: Day 1, Day 4, Day 7, Day 8 and follow-up
Change From Baseline in Vital Signs-systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Vital sign measurements for SBP and DBP after sitting for 5 minutes were measured. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose [Screening, Day -1 or Day 1]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise.
Measured: Baseline (pre-dose at Day -1 or Day 1) and Day 1, 4, 7 , Day 8 and Follow-up (Day 14)
Change From Baseline in HR
Vital sign measurements for HR after sitting for 5 minutes were measured. The average mean values were measured. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose [Screening, Day -1 or Day 1]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise.
Measured: Baseline (pre-dose at Day -1 or Day 1) and Day 1 (4-hour), Day 4 (Pre-dose and 4 hour), Day 7 (pre-dose and 4-hour), Day 8 and follow up (Day 14)
Change From Baseline Through Day 8 in Plasma HIV-1 RNA
The quantitative analysis of plasma was done to evaluate the amount of HIV-1 RNA at Day 1,2,3,4,5,6,7, 8 and End of treatment visit. The quantification was done using a Polymerase chain reactor (PCR). The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose Day 1) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise.
Measured: Baseline (pre-dose Day 1) to Day 8
Change From Baseline to Nadir in Plasma HIV-1 RNA
The quantification of plasma HIV-1 RNA, was conducted for the change from baseline to on treatment nadir (maximum change) before starting HAART or Kaletra monotherapy on Day 8. The quantification was done using a PCR. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose Day 1]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise.
Measured: Baseline (pre-dose Day 1) to Day 8
HIV-1 Rate of Decline by Treatment
The rate of decrease in the viral load of HIV-1 virus in response to individual treatment was measured. The viral load data was assumed to have a log normal prior distribution and followed linear decline with non-informative conjugate prior densities. The rate of decline (slope of the day) for each treatment was measured using a PCR from Day 1 to Day 8. The slope has been reported as mean.
Measured: Day 1 to Day 8
GSK2248761 Pharmacokinetic (PK) Parameters Following Dose Administration on Day 1: Area Under the Plasma Concentration Time Curve 0 to Infinite (AUC[0-∞]) and Area Under the Plasma Concentration Time Curve (AUC [0-24])
AUC (0-24), measured the plasma concentration of GSK2248761 against time, from time zero (pre-dose) to 24 hrs post-dose AUC (0-24) and from time zero to extrapolated infinite time AUC (0-∞). Serial blood samples were collected on Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose on Day 1 and used for analysis.
Measured: Day 1 (Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose)
GSK2248761 PK Parameters Following Dose Administration on Day 1: Maximum Observed Concentration (Cmax) and Concentration at 24 Hours Post Dose (C24)
Cmax represents the maximum concentration of GSK2248761 in the plasma. C24 is defined as the measure of plasma drug concentration of GSK2248761, 24 hours post dose, determined on Day 1. Serial blood samples were collected on Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose on Day 1 and used for analysis.Data for dose normalized Cmax and C24 was reported.
Measured: Day 1 (Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours)
GSK2248761 PK Parameters Following Dose Administration on Day 7: Predose Concentration (C0), Concentration at End of Dosing Interval (Cτ), Minimum Observed Concentration During One Dosing Interval (Cmin) and Cmax
The C0 was defined as the concentration of drug in plasma, before dose administration on Day 7. Cτ, was defined as the concentration of drug in the plasma at the end of dosing interval. The Cmin was defined as the minimum concentration of the drug in plasma during one dosing interval on Day 7. Cmax represents the maximum concentration of GSK2248761 in the plasma on Day 7. Serial blood samples were collected on Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose on Day 7 and used for analysis.
Measured: Day 7 (Pre -dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose)
GSK2248761 PK Parameters Following Dose Administration on Day 1: Time to Maximum Observed Concentration (Tmax), Terminal Half-life (t1/2), Absorption Lag Time (Tlag)
Tmax is defined as the, time of maximum measured GSK2248761 concentration in the plasma, on Day 1. The t1/2 was defined as the time measured for plasma concentration to decrease by one half. The tlag was defined as the time taken for the drug GSK2248761, to appear in the systemic circulation following administration. Serial blood samples were collected on Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose on Day 1 and used for analysis.
Measured: Day 1 (Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose)
GSK2248761 PK Parameters Following Dose Administration on Day 1: Apparent Clearance (CL/F)
The Clearance factor was defined as the volume of plasma cleared of the drug GSK2248761, per unit time. Serial blood samples were collected on Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose on Day 1 and used for analysis.
Measured: Day 1 (Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose)
GSK2248761 PK Parameters Following Dose Administration on Day 7: AUC(0-τ)
AUC(0-τ) is the AUC to the end of dosing period. For Day 7, it is the AUC measured at the end of the dosing period at Day 7. Serial blood samples were collected on Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose on Day 7 and used for analysis.
Measured: Day 7 (Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose)
GSK2248761 PK Parameters Following Dose Administration on Day 7: Tmax
Tmax is defined as the, time of maximum measured GSK2248761 concentration in the plasma, on Day 7. Serial blood samples were collected on Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose on Day 7 and used for analysis
Measured: Day 7 (Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose)
GSK2248761 PK Parameters Following Dose Administration on Day 7: t1/2
The t1/2 was defined as the time measured for plasma concentration to decrease by one half. Serial blood samples were collected on Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose on Day 7 and used for analysis
Measured: Day 7 (Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose)
Change From Baseline in CD4+ and CD8+ T-lymphocyte Cell Count at Day1 and Day 8.
Whole venous blood samples were obtained from each participant for the analysis of lymphocyte subsets by flow cytometry (total lymphocyte counts, percentage, CD4+ cell counts, and CD8+ cell counts) at Screening, Day 1 and Day 8. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values (Day 1 and Day 8). Baseline was defined as Screening.
Measured: Baseline (Screening), Day 1 and Day 8

Secondary outcomes (6)

Percent Change From Baseline in CD4+ and CD8+ T-lymphocyte Cell Count at Day 1 and Day 8
Data for CD4+ and CD8+ cells was collected at Screening, Day 1 and Day 8. The percent change from baseline was reported at Day 1 and Day 8. Baseline was defined as Screening. The percent change from baseline was calculated as post-randomization value minus the baseline value.
Measured: Baseline (Screening), Day 1 and Day 8
Accumulation Ratio for AUC , Cmax, Cτ, and Time Invariance Ratio Following Repeat Administration
The accumulation ratio is based on the parameters, Cmax, AUC(0-tau), AUC(0-24), C(tau), C24, AND AUC(0-inf). The accumulation ratio Ro was the ratio of AUC(0-tau) on Day 7 to that of AUC(0-24) on Day 1; the accumulation ratio R (Cmax) was the ratio of Cmax on Day 7 to that of Cmax on Day 1; the accumulation ratio R(Ctau) was the ratio of Ctau on Day 7 to the ratio of C24 on Day 1 and the Time Invariance Ratio Rs was defined as the ratio of AUC(0-tau) on Day 7 to that of AUC(0-inf) on Day 1. The ratio has been reported as number.
Measured: (Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose ) on Day 1 and Day 7
Change From Baseline in Reverse Transcriptase Sequences of HIV-1 at Day 8
None of the participants had non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance mutations at codons 90, 98, 100, 101, 103, 106, 108, 138, 179, 181, 188, 190, 225, or 230 at either Day 1 or Day 8. No mutation selected by GSK2248761 in vitro was observed for any participant at either Day 1 or Day 8. This data for "Change from baseline in reverse transcriptase sequences of HIV-1 at Day 8" not collected.
Measured: Baseline (Screening) and Day 8
Assessment of the Achievement of Pre-dose GSK2248761 Steady State Concentration Following Repeat Dose Administration on Day 2 Through 7
The pre-dose GSK2248761 steady state concentration, following repeated dose administration from Day 2 through Day 7 was assessed. Serial dose sampling was done on each day of Day 2, 3, 4, 5 and Day 6 and for Day 7 (Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose), before the administration of the study drug daily.
Measured: Day 7 (Pre - dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose) and Days 2, 3, 4. 5 and 6: pre-dose only
PK Data of Day 1 AUC(0-inf) and Day 7 AUC(0-tau) at Different Doses for the Assessment of Dose Proportionality
Data for IDX899 100 mg, IDX899 200 mg, IDX899 400 mg and IDX899 800 mg for Day 1 and Day 2 were taken from the Idenix NV-05A-002 study which were combined with GSK2248761 30 mg once daily data from this study, to assess the dose proportionality. The dose proportionality occurred when increase in the administered doses were accompanied by proportional increases in measure of exposure of the drug in the plasma PK parameters like AUC, Cmax, Ctau and other factors. The dose proportionality effects of IDX899 100 mg, IDX899 200 mg, IDX899 400 mg and IDX899 800 mg, following repeat dose administration on Day 7 for the PK parameter AUC(0-tau) has been reported.
Measured: (Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose ) From Day 1 to Up to Day 7
PK Data of Cmax and Ctau at Different Doses for the Assessment of Dose Proportionality
Data for IDX899 100 mg, IDX899 200 mg, IDX899 400 mg and IDX899 800 mg for Day 1 and Day 2 were taken from the Idenix NV-05A-002 study which were combined with GSK2248761 30 mg once daily data from this study, to assess the dose proportionality. The dose proportionality occurred when increase in the administered doses were accompanied by proportional increases in measure of exposure of the drug in the plasma PK parameters like AUC, Cmax, Ctau and other factors. Data for Ctau on Day 1 is presented for concentration at 24 hours post-dose on Day 1.
Measured: (Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose ) From Day 1 to Up to Day 7

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

20 Oct 200928 Nov 2009

First posted24 Jul 2009 (estimated)
Study start20 Oct 2009
Primary completion28 Nov 2009
Study completion28 Nov 2009

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Infection, Human Immunodeficiency VirusStudies of the same condition, open and under way.
More trials run by ViiV HealthcareThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 8 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00945282
Sponsor's protocol ID: 113020
Status last verified: Aug 2017
First submitted: 23 Jul 2009
Last updated: 29 Nov 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Zala C, St Clair M, Dudas K, Kim J, Lou Y, White S, Piscitelli S, Dumont E, Pietropaolo K, Zhou XJ, Mayers D. Safety and efficacy of GSK2248761, a next-generation nonnucleoside reverse transcriptase inhibitor, in treatment-naive HIV-1-infected subjects. Antimicrob Agents Chemother. 2012 May;56(5):2570-5. doi: 10.1128/AAC.05597-11. Epub 2012 Feb 6.
PubMed 22314532

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Study at a glance

From the registry record, last updated by the sponsor on 29 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Proof of Concept Study for GSK2248761 (An Extension of NV-05A-002: A Phase I/IIa Double-Blind Study to Evaluate the Safety and Tolerability, Antiretroviral Activity, Pharmacokinetics and Pharmacodynamics of IDX12899 in Antiretroviral Treatment-Naive HIV-1 Infected Subjects, Completed by Idenix)
ClinicalTrials.gov ID: NCT00945282
Acronym / sponsor ID: 113020
Conditions: Infection, Human Immunodeficiency Virus
Keywords: IDX12899, adaptive, monotherapy, pharmacokinetics, Treatment-naive, HIV-1, GSK2248761, NNRTI
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 8 participants (actual)
Lead sponsor: ViiV HealthcareIndustry (pharma, biotech, devices)
Collaborators: GlaxoSmithKline
Study start: 20 Oct 2009 (actual)
Primary completion: 28 Nov 2009 (actual)
Study completion: 28 Nov 2009 (actual)
First posted: 24 Jul 2009 (estimated)
Results: Posted 29 Nov 2018

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 2

Arm	Type	Receives
Cohort 1	Experimental	Drug: GSK2248761, Drug: Lopinavir/ritonavir, Drug: HAART, Drug: PlaceboIn Cohort 1 subjects will receive either GSK2248761 30 mg or placebo once a day for 7 days. On Day 8 subjects will receive either Kaletra or HAART for 28 days. The doctor will choose the most appropriate medications for HAART.
Cohort 2	Experimental	Drug: Lopinavir/ritonavir, Drug: HAART, Drug: Placebo, Drug: GSK2248761In Cohort 2 subjects will receive either GSK2248761 in the range of 10 mg - 20 mg or 40 mg - 90 mg or placebo once a day for 7 days. On Day 8 subjects will receive either Kaletra or HAART for 28 days. The doctor will choose the most appropriate medications for HAART. The dose for Cohort 2 will be determined following evaluation of results from Cohort 1. Cohort 2 may not be done.

Who may qualify

Ages: 21 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

Male or Female, 21 to 65 years of age.
Female of non-childbearing potential defined as: being post-menopausal, defined as 12 months of spontaneous amenorrhea and having a serum FSH level >40 MIU/ml at Screening OR have had a documented bilateral tubal ligation or hysterectomy of at least 6 months prior to study initiation, bilateral oophorectomy or bilateral tubal ligation.
Plasma HIV-1 RNA value >= 5000 copies/mL.
CD4+ count >= 200 cells/mm3.
Is antiretroviral treatment-naïve and agrees not to start antiretroviral therapy prior to clinic check-in (Day-1).

Key exclusion criteria (18 listed)

Subject is pregnant as determined by a positive urine/serum pregnancy test at Screening and Day -1.
Lactating females.
Male subjects of reproductive potential and unwilling to use double barrier method of contraception (e.g., condom plus spermicide) and continue to use an adequate method of birth control for at least 30 days after the last dose of the study drug.
Has a positive screening Hepatitis B surface antigen, positive screening Hepatitis C virus (HCV) antibody and detectable HCV ribonucleic acid (RNA) on subsequent testing. If the Hepatitis C antibody is positive but the HCV RNA is undetectable, the subject may be included in the study.
History of regular alcohol consumption within 6 months of Screening as defined as: an average weekly intake of >21 units for males or >14 units for females. One unit is equivalent to 8 g of alcohol: a half-pint (~240 ml) of beer, 1 glass (125 ml) of wine or 1 (25 ml) measure of spirits

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
GSK2248761GSK2248761 30 mg capsule once a day for 7 days. GSK2248761 is an investigational (not approved by the FDA) HIV drug in the class of non-nucleoside reuptake inhibitor class.	Drug	Cohort 1
Lopinavir/ritonavirAlso: KaletraLopinavir 400 mg and ritonovir 100 mg every 12 hours for 28 days. Lopinavir/ritonavir is approved by the FDA as an HIV medication in the protease inhibitor class. Kaletra is a trademark of Abbott Laboratories.	Drug	Cohort 1, Cohort 2
HAARTHighly Active Antiretroviral therapy of the doctor's choice.	Drug	Cohort 1, Cohort 2
PlaceboPlacebo is a capsule with no drug in it.	Drug	Cohort 1, Cohort 2
GSK2248761GSK2248761 10 mg -20 mg or 40 mg - 90 mg once a day for 7 days. GSK2248761 is an investigational (not approved by the FDA) HIV drug in the class of non-nucleoside reuptake inhibitor class.	Drug	Cohort 2

Primary outcome

Number of Participants With Serious Adverse Events (SAEs) and Adverse Events (AEs)
Time frame: Up to 38 days
An AE is defined as any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect, or is an important medical events that jeopardize the participants or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition, or a drug-induced liver injury.
Change From Baseline in Hematology Paramaters- Basophils, Eosinophils, Lymphocytes, Monocytes, White Blood Cell Count
Time frame: Baseline (pre-dose at Day -1 or Day 1) and Day 2, 4 , 7 , Day 8 and Follow-up (Day 14)
The data for hematology parameters for Basophils, eosinophils, lymphocytes, monocytes, and white blood cell count from the change from baseline was reported. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose [Screening, Day -1 or Day 1]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise.
Change From Baseline in Hematology Paramaters- Hemoglobin
Time frame: Baseline (pre-dose at Day -1 or Day 1) and Day 2, 4 , 7 , Day 8 and Follow-up (Day 14)
The data for hematology parameter hemoglobin from the change from baseline was reported. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose [Screening, Day -1 or Day 1]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise.
Change From Baseline in Hematology Paramaters- Platelet Count
Time frame: Baseline (pre-dose at Day -1 or Day 1) and Day 2, 4 , 7 , Day 8 and Follow-up (Day 14)
The data for hematology parameter platelet count, for the change from baseline was reported. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose [Screening, Day -1 or Day 1]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise.
Change From Baseline in Hematology Paramaters- Red Blood Cell Count
Time frame: Baseline (pre-dose at Day -1 or Day 1) and Day 2, 4 , 7 , Day 8 and Follow-up (Day 14)
The data for hematology parameter red blood cell count, for the change from baseline was reported. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose [Screening, Day -1 or Day 1]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise.
Change From Baseline in Hematology Parameters- Total Neutrophil
Time frame: Baseline (pre-dose at Day -1 or Day 1) and Day 2, 4 , 7 , Day 8 and Follow-up (Day 14)
The data for hematology parameter total neutrophil count, for the change from baseline was reported. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose [Screening, Day -1 or Day 1]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise.
Change From Baseline in Hematology Paramaters- Mean Corpuscle Hemoglobin (MCH)
Time frame: Baseline (pre-dose at Day -1 or Day 1) and Day 2, 4 , 7 , Day 8 and Follow-up (Day 14)
The data for hematology parameter MCH, the change from baseline was reported. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose [Screening, Day -1 or Day 1]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise.
Change From Baseline in Hematology Paramaters- Mean Corpuscle Volume (MCV)
Time frame: Baseline (pre-dose at Day -1 or Day 1) and Day 2, 4 , 7 , Day 8 and Follow-up (Day 14)
The change from baseline data for hematology parameter MCV, was reported. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose [Screening, Day -1 or Day 1]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise.
Change From Baseline in Hematology Paramaters- Hematocrit
Time frame: Baseline (pre-dose at Day -1 or Day 1) and Day 2, 4 , 7 , Day 8 and Follow-up (Day 14)
The data for hematology parameter Hematocrit, the change from baseline was reported. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose [Screening, Day -1 or Day 1]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise.
Change From Baseline in Hematology Paramaters-Mean Corpuscle Hemoglobin Concentration
Time frame: Baseline (pre-dose at Day -1 or Day 1) and Day 2, 4 , 7 , Day 8 and Follow-up (Day 14)
The data for hematology parameter Mean Corpuscle Hemoglobin concentration, the change from baseline was reported. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose [Screening, Day -1 or Day 1]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise.
Change From Baseline in Clinical Chemistry Paramaters- Albumin and Total Protein
Time frame: Baseline (pre-dose at Day -1 or Day 1) and Day 2, 4 , 7 , Day 8 and Follow-up (Day 14)
The data for clinical chemistry parameters Albumin and total protein, the change from baseline was reported. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose [Screening, Day -1 or Day 1]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise.
Change From Baseline in Clinical Chemistry Parameters- Blood Urea Nitrogen, Triglycerides, Glucose, Creatinine, Calcium, Cholesterol, Total Bilirubin, and Direct Bilirubin.
Time frame: Baseline (pre-dose at Day -1 or Day 1) and Day 2, 4 , 7 , Day 8 and Follow-up (Day 14)
The data for clinical chemistry parameters- Blood urea nitrogen, triglycerides, glucose, creatinine, calcium, cholesterol, total bilirubin, and direct bilirubin. The change from baseline was reported. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose [Screening, Day -1 or Day 1]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise.
Change From Baseline in Clinical Chemistry Paramaters- Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase
Time frame: Baseline (pre-dose at Day -1 or Day 1) and Day 2, 4 , 7 , Day 8 and Follow-up (Day 14)
The data for clinical chemistry paramaters- alkaline phosphatase, alanine amino transferase, aspartate amino transferase, the change from baseline was reported. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose [Screening, Day -1 or Day 1]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise.
Change From Baseline in Clinical Chemistry Paramaters-sodium, Potassium and Carbondioxide or Bicarbonate
Time frame: Baseline (pre-dose at Day -1 or Day 1) and Day 2, 4 , 7 , Day 8 and Follow-up (Day 14)
The data for clinical chemistry parameters- sodium, potassium and carbon dioxide or bicarbonate, the change from baseline was reported. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose [Screening, Day -1 or Day 1]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise.
Change From Baseline in Clinical Chemistry Paramaters- Phosphorus
Time frame: Baseline (pre-dose at Day -1 or Day 1) and Day 2, 4 , 7 , Day 8 and Follow-up (Day 14)
The data for clinical chemistry paramaters- phosphorous, the change from baseline was reported. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose [Screening, Day -1 or Day 1]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise.
Change From Baseline in Clinical Chemistry Paramaters- Uric Acid
Time frame: Baseline (pre-dose at Day -1 or Day 1) and Day 2, 4 , 7 , Day 8 and Follow-up (Day 14)
The data for clinical chemistry parameters Uric acid, the change from baseline was reported. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose [Screening, Day -1 or Day 1]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise.
Change From Baseline in Clinical Chemistry Paramaters- Thyroxine, Free
Time frame: Baseline (pre-dose at Day -1 or Day 1) and Day 2, 4 , 7 , Day 8 and Follow-up (Day 14)
The data for clinical chemistry parameters Thyroxine, free the change from baseline was reported. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose [Screening, Day -1 or Day 1]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise.
Change From Baseline in Clinical Chemistry Paramaters- Thyroxine Total, Thyroxine Binding Globulin, Total T3.
Time frame: Baseline (pre-dose at Day -1 or Day 1) and Day 2, 4 , 7 , Day 8 and Follow-up (Day 14)
The data for clinical chemistry parameters Thyroxine total, thyroxine binding globulin, Total T3 the change from baseline was reported. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose [Screening, Day -1 or Day 1]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise.
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
Time frame: Day 1, Day 4, Day 7, Day 8 and follow-up
Triplicate 12-lead ECGs were collected at different timepoints, after participants were supine for 5 minutes, during the study using an ECG machine that automatically calculated the heart rate (HR) and measures PR, QRS, QT, and QTc intervals. The three consecutive determinations were collected 5 plus or minus 2 minutes apart and all three tracings were recorded. The participants with abnormal values categorized as abnormal clinically significant (CS) and not clinically significant (NCS) were reported.
Change From Baseline in Vital Signs-systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Time frame: Baseline (pre-dose at Day -1 or Day 1) and Day 1, 4, 7 , Day 8 and Follow-up (Day 14)
Vital sign measurements for SBP and DBP after sitting for 5 minutes were measured. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose [Screening, Day -1 or Day 1]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise.
Change From Baseline in HR
Time frame: Baseline (pre-dose at Day -1 or Day 1) and Day 1 (4-hour), Day 4 (Pre-dose and 4 hour), Day 7 (pre-dose and 4-hour), Day 8 and follow up (Day 14)
Vital sign measurements for HR after sitting for 5 minutes were measured. The average mean values were measured. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose [Screening, Day -1 or Day 1]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise.
Change From Baseline Through Day 8 in Plasma HIV-1 RNA
Time frame: Baseline (pre-dose Day 1) to Day 8
The quantitative analysis of plasma was done to evaluate the amount of HIV-1 RNA at Day 1,2,3,4,5,6,7, 8 and End of treatment visit. The quantification was done using a Polymerase chain reactor (PCR). The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose Day 1) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise.
Change From Baseline to Nadir in Plasma HIV-1 RNA
Time frame: Baseline (pre-dose Day 1) to Day 8
The quantification of plasma HIV-1 RNA, was conducted for the change from baseline to on treatment nadir (maximum change) before starting HAART or Kaletra monotherapy on Day 8. The quantification was done using a PCR. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline (pre-dose Day 1]) was defined as last available scheduled assessment prior to time of the first dose unless it is specified otherwise.
HIV-1 Rate of Decline by Treatment
Time frame: Day 1 to Day 8
The rate of decrease in the viral load of HIV-1 virus in response to individual treatment was measured. The viral load data was assumed to have a log normal prior distribution and followed linear decline with non-informative conjugate prior densities. The rate of decline (slope of the day) for each treatment was measured using a PCR from Day 1 to Day 8. The slope has been reported as mean.
GSK2248761 Pharmacokinetic (PK) Parameters Following Dose Administration on Day 1: Area Under the Plasma Concentration Time Curve 0 to Infinite (AUC[0-∞]) and Area Under the Plasma Concentration Time Curve (AUC [0-24])
Time frame: Day 1 (Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose)
AUC (0-24), measured the plasma concentration of GSK2248761 against time, from time zero (pre-dose) to 24 hrs post-dose AUC (0-24) and from time zero to extrapolated infinite time AUC (0-∞). Serial blood samples were collected on Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose on Day 1 and used for analysis.
GSK2248761 PK Parameters Following Dose Administration on Day 1: Maximum Observed Concentration (Cmax) and Concentration at 24 Hours Post Dose (C24)
Time frame: Day 1 (Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours)
Cmax represents the maximum concentration of GSK2248761 in the plasma. C24 is defined as the measure of plasma drug concentration of GSK2248761, 24 hours post dose, determined on Day 1. Serial blood samples were collected on Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose on Day 1 and used for analysis.Data for dose normalized Cmax and C24 was reported.
GSK2248761 PK Parameters Following Dose Administration on Day 7: Predose Concentration (C0), Concentration at End of Dosing Interval (Cτ), Minimum Observed Concentration During One Dosing Interval (Cmin) and Cmax
Time frame: Day 7 (Pre -dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose)
The C0 was defined as the concentration of drug in plasma, before dose administration on Day 7. Cτ, was defined as the concentration of drug in the plasma at the end of dosing interval. The Cmin was defined as the minimum concentration of the drug in plasma during one dosing interval on Day 7. Cmax represents the maximum concentration of GSK2248761 in the plasma on Day 7. Serial blood samples were collected on Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose on Day 7 and used for analysis.
GSK2248761 PK Parameters Following Dose Administration on Day 1: Time to Maximum Observed Concentration (Tmax), Terminal Half-life (t1/2), Absorption Lag Time (Tlag)
Time frame: Day 1 (Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose)
Tmax is defined as the, time of maximum measured GSK2248761 concentration in the plasma, on Day 1. The t1/2 was defined as the time measured for plasma concentration to decrease by one half. The tlag was defined as the time taken for the drug GSK2248761, to appear in the systemic circulation following administration. Serial blood samples were collected on Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose on Day 1 and used for analysis.
GSK2248761 PK Parameters Following Dose Administration on Day 1: Apparent Clearance (CL/F)
Time frame: Day 1 (Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose)
The Clearance factor was defined as the volume of plasma cleared of the drug GSK2248761, per unit time. Serial blood samples were collected on Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose on Day 1 and used for analysis.
GSK2248761 PK Parameters Following Dose Administration on Day 7: AUC(0-τ)
Time frame: Day 7 (Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose)
AUC(0-τ) is the AUC to the end of dosing period. For Day 7, it is the AUC measured at the end of the dosing period at Day 7. Serial blood samples were collected on Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose on Day 7 and used for analysis.
GSK2248761 PK Parameters Following Dose Administration on Day 7: Tmax
Time frame: Day 7 (Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose)
Tmax is defined as the, time of maximum measured GSK2248761 concentration in the plasma, on Day 7. Serial blood samples were collected on Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose on Day 7 and used for analysis
GSK2248761 PK Parameters Following Dose Administration on Day 7: t1/2
Time frame: Day 7 (Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose)
The t1/2 was defined as the time measured for plasma concentration to decrease by one half. Serial blood samples were collected on Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose on Day 7 and used for analysis
Change From Baseline in CD4+ and CD8+ T-lymphocyte Cell Count at Day1 and Day 8.
Time frame: Baseline (Screening), Day 1 and Day 8
Whole venous blood samples were obtained from each participant for the analysis of lymphocyte subsets by flow cytometry (total lymphocyte counts, percentage, CD4+ cell counts, and CD8+ cell counts) at Screening, Day 1 and Day 8. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values (Day 1 and Day 8). Baseline was defined as Screening.

6 secondary outcomes

Percent Change From Baseline in CD4+ and CD8+ T-lymphocyte Cell Count at Day 1 and Day 8
Time frame: Baseline (Screening), Day 1 and Day 8
Accumulation Ratio for AUC , Cmax, Cτ, and Time Invariance Ratio Following Repeat Administration
Time frame: (Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose ) on Day 1 and Day 7
Change From Baseline in Reverse Transcriptase Sequences of HIV-1 at Day 8
Time frame: Baseline (Screening) and Day 8
Assessment of the Achievement of Pre-dose GSK2248761 Steady State Concentration Following Repeat Dose Administration on Day 2 Through 7
Time frame: Day 7 (Pre - dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose) and Days 2, 3, 4. 5 and 6: pre-dose only
PK Data of Day 1 AUC(0-inf) and Day 7 AUC(0-tau) at Different Doses for the Assessment of Dose Proportionality
Time frame: (Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose ) From Day 1 to Up to Day 7
PK Data of Cmax and Ctau at Different Doses for the Assessment of Dose Proportionality
Time frame: (Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose ) From Day 1 to Up to Day 7

Results and safety

Results posted to the registry on 29 Nov 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
GSK2248761 30 mg	6	6
Placebo	2	2

Primary outcome: Number of Participants With Serious Adverse Events (SAEs) and Adverse Events (AEs)

Time frame: Up to 38 days. Count of participants. Unit: Participants

Measure	GSK2248761 30 mg n = 6	Placebo n = 2
Any AE	4	1
Any SAE	0	0

Population analysed: Safety population was defined as all participants who were randomized into the study with documented evidence of receipt of at least one dose of randomized treatment.

Primary outcome: Change From Baseline in Hematology Paramaters- Basophils, Eosinophils, Lymphocytes, Monocytes, White Blood Cell Count

Time frame: Baseline (pre-dose at Day -1 or Day 1) and Day 2, 4 , 7 , Day 8 and Follow-up (Day 14). Mean (Standard Deviation). Unit: thousand cells per microliter

Measure	GSK2248761 30 mg n = 6	Placebo n = 2
Basophils, Day 2	-1.7 (4.08)	-5.0 (7.07)
Basophils, Day 4	8.3 (9.83)	5.0 (7.07)
Basophils, Day 7	1.7 (7.53)	-10.0 (14.14)
Basophils, Day 8	3.3 (8.16)	-10.0 (14.14)
Basophils, Follow-Up	-3.3 (10.33)	-15.0 (7.07)
Eosinophils, Day 2	-1.7 (35.45)	-120.0 (141.42)
Eosinophils, Day 4	-60.0 (150.33)	-20.0 (0.00)
Eosinophils, Day 7	-38.3 (106.85)	-50.0 (28.28)

Population analysed: Safety population.

Primary outcome: Change From Baseline in Hematology Paramaters- Hemoglobin

Time frame: Baseline (pre-dose at Day -1 or Day 1) and Day 2, 4 , 7 , Day 8 and Follow-up (Day 14). Mean (Standard Deviation). Unit: gram per decilitre

Measure	GSK2248761 30 mg n = 6	Placebo n = 2
Day 2	-0.40 (0.316)	-0.50 (0.283)
Day 4	-0.28 (0.794)	0.60 (1.273)
Day 7	-0.25 (0.864)	-0.45 (0.071)
Day 8	-0.48 (0.585)	-0.45 (0.354)
Follow-up	-0.93 (0.550)	-1.00 (0.424)

Population analysed: Safety population.

Primary outcome: Change From Baseline in Hematology Paramaters- Platelet Count

Time frame: Baseline (pre-dose at Day -1 or Day 1) and Day 2, 4 , 7 , Day 8 and Follow-up (Day 14). Mean (Standard Deviation). Unit: per cubic millimeter

Measure	GSK2248761 30 mg n = 6	Placebo n = 2
Day 2	-5.7 (24.86)	3.0 (9.90)
Day 4	5.0 (18.34)	-23.5 (37.48)
Day 7	18.5 (19.77)	2.5 (10.61)
Day 8	29.3 (21.04)	2.0 (2.83)
Follow-up	23.3 (6.50)	-1.0 (33.94)

Population analysed: Safety population.

6 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to 38 Days. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
GSK2248761 30 mg	0 of 6 (0%)	4 of 6 (66.7%)	0 of 6
Placebo	0 of 2 (0%)	1 of 2 (50%)	0 of 2

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 29 Nov 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 22314532Zala C, St Clair M, Dudas K, Kim J, Lou Y, White S, Piscitelli S, Dumont E, Pietropaolo K, Zhou XJ, Mayers D. Safety and efficacy of GSK2248761, a next-generation nonnucleoside reverse transcriptase inhibitor, in treatment-naive HIV-1-infected subjects. Antimicrob Agents Chemother. 2012 May;56(5):2570-5. doi: 10.1128/AAC.05597-11. Epub 2012 Feb 6.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

GSK Clinical Trials study director

ViiV Healthcare

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing GSK2248761, Lopinavir/ritonavir and HAART in people with Infection, Human Immunodeficiency Virus, run by ViiV Healthcare at 1 site in Argentina.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Argentina. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 29 Nov 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Serious Adverse Events (SAEs) and Adverse Events (AEs) (time frame: Up to 38 days). The study lists 33 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00945282, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Nov 2018.