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Study to Compare the Safety and Anti-HIV Effect of GSK1265744 Versus Placebo in HIV-1 Infected Adults (ITZ112929)

Primary Purpose

Infection, Human Immunodeficiency Virus

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

GSK1265744 30mg

Placebo

GSK1265744 5mg

About this trial

This is an interventional treatment trial for Infection, Human Immunodeficiency Virus focused on measuring HIV, naive, Phase II, integrase inhibitor, GSK1265744, newly diagnosed, pharmacokinetics, AIDS, integrase, HIV Infections, Treatment naive

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

A subject will be eligible for inclusion in this study only if all of the following criteria apply:

Male or female between 18 and 65 years of age inclusive, at the time of signing the informed consent.
A female subject is eligible to participate if she is of non-childbearing potential, defined as:
Pre-menopausal females with a documented bilateral oophorectomy, tubal ligation or hysterectomy; or
Postmenopausal defined as 12 months of spontaneous amenorrhea. A follicle stimulating hormone level will be performed to confirm post-menopausal status. For this study, FSH levels > 40 MlU/ml and estradiol < 40 pg/ml (<140 pmol/L) is confirmatory.
Male subjects must agree to use one of the contraception methods listed in Section 8.1. This criterion must be followed from the time of the first dose of study medication until 14 days after the last dose of study medication.
CD4+ cell count greater than or equal to 200 cells/mm3 and plasma HIV-1 RNA greater than or equal to 5000 copies/mL at Screening.
No current antiretroviral therapy and have not received any in the 12 weeks prior to first dose.
For subjects who have received antiretroviral treatment in the past, adequate treatment options to construct HAART therapy with at least 3 active antiretrovirals for Optimized Therapy, as selected by the Investigator.
Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.

Exclusion Criteria

A subject will not be eligible for inclusion in this study if any of the following criteria apply:

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.
AST and ALT > 3ULN at Screening. A single repeat is allowed for eligibility determination.
Inadequate renal function at Screening, defined as either a serum creatinine >1.5 mg/dL or a calculated creatinine clearance (CrCl) ≤ 50 mL/min. A single repeat serum creatinine is allowed to determine eligibility.
Any acute laboratory abnormality at screening which, in the opinion of the investigator, should preclude the subject's participation in the study of an investigational compound. Any grade 4 laboratory abnormality at screening, with the exception of CPK, will 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 sponsor. A single repeat is allowed for eligibility determination.
A positive drug screen at screening and baseline. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine or PCP.
History of regular alcohol consumption, defined as an average weekly intake of >14 drinks for males or >7 drinks for females, within 6 months of Screening.

Note: One drink is equivalent to 12 g of alcohol: 12 ounces (360 ml) of beer, 5 ounces (150 ml) of wine or 1.5 ounces (45 ml) of 80 proof distilled spirits.

Any condition (including alcohol or drug abuse) which, in the opinion of the investigator, could interfere with the subject's ability to comply with the dosing schedule and protocol evaluations or which might compromise the safety of the subject.
Prior treatment with an integrase inhibitor (greater than or equal to 1 dose).
Treatment with radiation therapy or cytotoxic chemotherapeutic agents within 30 days of study drug administration or anticipated need for such treatment within the study.
Treatment with immunomodulating agents (such as systemic corticosteroids, interleukins, interferons) or any agent with known anti-HIV activity (such as hydroxyurea or foscarnet) within 30 days of study drug administration.
Treatment with any vaccine within 30 days prior to receiving study medication.
An active Center for Disease Control and Prevention (CDC) Category C disease, except cutaneous Kaposi's sarcoma not requiring systemic therapy during the trial.
Pregnant females as determined by positive serum or urine hCG test at screening or prior to dosing.
Lactating females.
Use of multivitamins or antacids within 24 hours prior to the first dose of investigational product.
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 GSK Medical Monitor, 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 medications refer to GSK1265744 or placebo.

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).
Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
History of clinically relevant pancreatitis or hepatitis within the previous 6 months.
Subjects with a pre-existing condition interfering with normal gastrointestinal anatomy or motility, hepatic and/or renal function, that could interfere with the absorption, metabolism, and/or excretion of the study drugs.
Exclusion Criteria for Screening ECG (A single repeat is allowed for eligibility determination):

Exclusion Criteria for Screening ECG:

Males Females Heart rate <45 and >100 bpm <50 and >100 bpm QRS duration >120 msec >120 msec QTc interval (Bazett) > 450 msec > 450 msec Non-sustained (≥ 3 consecutive beats) or sustained ventricular tachycardia. Sinus Pauses >3 seconds. 2nd degree (Type II) or higher AV block. Evidence of previous myocardial infarction (pathologic Q waves, S-T segment changes (except early repolarization)).

Sites / Locations

GSK Investigational Site
GSK Investigational Site
GSK Investigational Site
GSK Investigational Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

GSK1265744 30 mg

Placebo

GSK1265744 5 mg

Arm Description

GSK1265744 30 mg

Placebo to match GSK1265744

GSK1265744 5 mg

Outcomes

Primary Outcome Measures

Change From Baseline in Plasma Human Immunodeficiency Virus (HIV-1) Ribonucleic Acid (RNA) to Day 11

Plasma for quantitative HIV-1 RNA was collected on Day 1, 2, 3, 4, 7, 8, 9, 10 and 11. On Days 1, 10 and 11, two samples for HIV-1 RNA was collected between 5-20 minutes apart to reduce sample variability. An HIV-1 RNA PCR assay with a lower limit of detection (LLOD) of 50 copies/milliliter (mL) (ultrasensitive assay) was used for post-baseline assessments. An HIV-1 RNA PCR assay with a LLOD of 400 copies/mL (standard assay) was used for screening and Baseline assessments and included a re-test with and ultrasensitive assay for all Baseline values below the LLOD. Baseline was defined at Day 1. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.

GSK1265744 Pharmacokinetic (PK) Parameters Following Dose Administration on Day 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration Within a Participant Across All Treatments(AUC[0-24])

Blood samples for PK analysis of AUC(0-24) of GSK1265744 was collected on Day 1 (Pre-dose [within 15 minutes prior to dosing] and at 0.5, 1, 1.5, 2, 3, 4, 6, and 8hours post-dose). Samples were collected at nominal times relative to the proposed time of GSK1265744 dosing. The actual date and time of each blood sample collection was recorded. AUC was determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations.

GSK1265744 PK Parameters Following Dose Administration on Day 1: Concentration at 24 Hours Post Dose (C24)

Blood samples for PK analysis of C24 of GSK1265744 was collected on Day 1 (Pre-dose [within 15 minutes prior to dosing] and at 0.5, 1, 1.5, 2, 3, 4, 6, and 8hours post-dose). Samples were collected at nominal times relative to the proposed time of GSK1265744 dosing. The actual date and time of each blood sample collection was recorded.

GSK1265744 PK Parameters Following Dose Administration on Day 10: Area Under the Concentration-time Curve Over the Dosing Interval (AUC[0-tau])

Blood samples for PK analysis of C24 of GSK1265744 was collected on Day 10 (Pre-dose [within 15 minutes prior to dosing] and at 0.5, 1, 1.5, 2, 3, 4, 6, and 8hours post-dose). Samples were collected at nominal times relative to the proposed time of GSK1265744 dosing. The actual date and time of each blood sample collection was recorded. AUC was determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations.

GSK1265744 PK Parameters Following Dose Administration on Day 10: Predose Concentration (C0), Concentration at End of Dosing Interval (Ctau), Minimum Observed Concentration During One Dosing Interval (Cmin)

Blood samples for PK analysis of C0, Ctau and Cmin of GSK1265744 was collected on Day 10 (Pre-dose [within 15 minutes prior to dosing] and at 0.5, 1, 1.5, 2, 3, 4, 6, and 8hours post-dose). Samples were collected at nominal times relative to the proposed time of GSK1265744 dosing. The actual date and time of each blood sample collection was recorded.

GSK1265744 PK Parameters Following Dose Administration on Day 1 and Day 10: Maximum Observed Concentration (Cmax)

Blood samples for PK analysis of Cmax of GSK1265744 was collected at pre-dose (within 15 minutes prior to dosing) and at 0.5, 1, 1.5, 2, 3, 4, 6, and 8hours post-dose on Days 1 and 10. Samples were collected at nominal times relative to the proposed time of GSK1265744 dosing. The actual date and time of each blood sample collection was recorded.

GSK1265744 PK Parameters Following Dose Administration on Day 1 and Day 10: Time to Cmax (Tmax)

Blood samples for PK analysis of tmax of GSK1265744 was collected at pre-dose (within 15 minutes prior to dosing) and at 0.5, 1, 1.5, 2, 3, 4, 6, and 8hours post-dose on Days 1 and 10. Samples were collected at nominal times relative to the proposed time of GSK1265744 dosing. The actual date and time of each blood sample collection was recorded.

GSK1265744 PK Parameters Following Dose Administration on Day 1 and Day 10: Terminal Half-life (t1/2) and Absorption Lag Time (Tlag)

PK sampling was planned to be collected up to 24 hours only on Day 1 and Day 10. The data for this outcome measure was however not collected.

GSK1265744 PK Parameters Following Last Repeat Administration on Day 10: Apparent Clearance Following Oral Dosing (CL/F)

Blood samples for PK analysis of CL/F of GSK1265744 was collected on Day 10 (Pre-dose [within 15 minutes prior to dosing] and at 0.5, 1, 1.5, 2, 3, 4, 6, and 8hours post-dose). Samples were collected at nominal times relative to the proposed time of GSK1265744 dosing. The actual date and time of each blood sample collection was recorded.

Number of Participants With Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)

An AE is any untoward medical occurrence in a 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 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, medically significant or is associated with liver injury and impaired liver function.

Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC- Absolute Neutrophil Count), White Blood Cell Count

Blood samples for assessment of hematology parameters of basophils, eosinophils, lymphocytes, monocytes, total neutrophils (ANC- absolute neutrophil count) and white blood cell count was collected at Baseline, Day 3, 7 and 10. Baseline was defined at Day 1. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.

Change From Baseline in Hematology Parameters: Hemoglobin

Blood samples for assessment of hematology parameter of hemoglobin was collected at Baseline, Day 3, 7 and 10. Baseline was defined at Day 1. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.

Change From Baseline in Hematology Parameters: Mean Corpuscle Hemoglobin

Blood samples for assessment of hematology parameter of mean corpuscle hemoglobin was collected at Baseline, Day 3, 7 and 10. Baseline was defined at Day 1. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.

Change From Baseline in Hematology Parameters: Mean Corpuscle Volume

Blood samples for assessment of hematology parameter of mean corpuscle volume was collected at Baseline, Day 3, 7 and 10. Baseline was defined at Day 1. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.

Change From Baseline in Hematology Parameters: Platelet Count

Blood samples for assessment of hematology parameter of platelet count was collected at Baseline, Day 3, 7 and 10. Baseline was defined at Day 1. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.

Change From Baseline in Hematology Parameters: Red Blood Cell Count

Blood samples for assessment of hematology parameter of red blood cell count was collected at Baseline, Day 3, 7 and 10. Baseline was defined at Day 1. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.

Change From Baseline in Hematology Parameters: Reticulocytes

Blood samples for assessment of hematology parameter of reticulocytes was collected at Baseline, Day 3, 7 and 10. Baseline was defined at Day 1. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.

Change From Baseline in Clinical Chemistry Data: Albumin, Total Protein

Blood samples for assessment of clinical chemistry parameters of albumin and total protein was collected at Baseline, Day 3, 7 and 10. Baseline was defined at Day 1. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.

Change From Baseline in Clinical Chemistry Data: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Lipase

Blood samples for assessment of clinical chemistry parameters of alkaline phosphatase, alanine amino transferase, aspartate amino transferase, creatine kinase and lipase was collected at Baseline, Day 3, 7 and 10. Baseline was defined at Day 1. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.

Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen

Blood samples for assessment of clinical chemistry parameters of direct bilirubin, total bilirubin, calcium, cholesterol, creatinine, glucose, HDL cholesterol direct, LDL cholesterol calculation, triglycerides,Urea/BUN was collected at Baseline, Day 3, 7 and 10. Baseline was defined at Day 1. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.

Change From Baseline in Clinical Chemistry Data: Chloride, Carbon Dioxide Content/Bicarbonate, Magnesium, Sodium, Potassium

Blood samples for assessment of clinical chemistry parameters of chloride, carbon dioxide content/bicarbonate, magnesium, sodium and potassium was collected at Baseline, Day 3, 7 and 10. Baseline was defined at Day 1. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.

Number of Participants With Urinalysis Data

Samples for urinalysis assessment was collected on Day 1, Day 3 and Day 10. Urinalysis parameters included urine bilirubin, urine occult blood, urine glucose, urine ketones, urine nitrite, urine pH, urine protein, urine specific gravity and urine leukocyte esterase test for detecting white blood cell.

Change From Baseline in Vital Sign: Systolic and Diastolic Blood Pressure

Systolic and diastolic blood pressure was measured at Baseline (Day 1 pre-dose), 2 hour post dose on Day 1, pre-dose on Day 4, 7, 10 and 2 hours post dose on Day 10. Baseline was defined at Day 1 pre-dose. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.

Change From Baseline in Vital Sign: Heart Rate

Heart rate was measured at Baseline (Day 1 pre-dose), 2 hour post dose on Day 1, pre-dose on Day 4, 7, 10 and 2 hours post dose on Day 10. Baseline was defined at Day 1 pre-dose. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.

Change From Baseline in Electrocardiogram (ECG) Parameters

All ECGs were obtained after a minimum 10 minute rest in a semi-supine position. The 12-lead ECGs were obtained at Baseline (Day 1 pre-dose), 2 hour post dose on Day 1, pre-dose on Day 4, 7, 10 and 2 hours post dose on Day 10 using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, and Bazett's correction (QTcB) and Fridericia correction (QTcF) intervals. Baseline was defined at Day 1 pre-dose. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.

Secondary Outcome Measures

Change From Baseline in Plasma HIV-1 RNA

Plasma for quantitative HIV-1 RNA was collected on Day 1, 2, 3, 4, 7, 8, 9, 10 and 11. On Days 1, 10 and 11, two samples for HIV-1 RNA were collected between 5-20 minutes apart to reduce sample variability. An HIV-1 RNA PCR assay with a LLOD of 50 copies/mL (ultrasensitive assay) was used for post-baseline assessments. An HIV-1 RNA PCR assay with a LLOD of 400 copies/mL (standard assay) was used for screening and Baseline assessments and included a re-test with and ultrasensitive assay for all Baseline values below the LLOD. Baseline was defined at Day 1 (pre-dose). The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.

Change From Baseline in Plasma HIV-1 RNA to Nadir Over 11 Days

Plasma for quantitative HIV-1 RNA was collected on Day 1, 2, 3, 4, 7, 8, 9, 10 and 11. On Days 1, 10 and 11, two samples for HIV-1 RNA was collected between 5-20 minutes apart to reduce sample variability. An HIV-1 RNA PCR assay with a LLOD of 50 copies/mL (ultrasensitive assay) was used for post-baseline assessments. An HIV-1 RNA PCR assay with a LLOD of 400 copies/mL (standard assay) was used for screening and Baseline assessments and included a re-test with and ultrasensitive assay for all Baseline values below the LLOD. Nadir was the maximum change from Baseline in plasma HIV-1 RNA. Baseline was defined at Day 1 (pre-dose). The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.

Plasma HIV-1 RNA Rate of Decline (Slope) Over 11 Days

Plasma for quantitative HIV-1 RNA was collected on Day 1, 2, 3, 4, 7, 8, 9, 10 and 11. On Days 1, 10 and 11, two samples for HIV-1 RNA was collected between 5-20 minutes apart to reduce sample variability. An HIV-1 RNA PCR assay with a LLOD of 50 copies/mL (ultrasensitive assay) was used for post-baseline assessments. An HIV-1 RNA PCR assay with a LLOD of 400 copies/mL (standard assay) was used for screening and Baseline assessments and included a re-test with and ultrasensitive assay for all Baseline values below the LLOD. Estimated mean rate of decline (i.e., slope of day) with corresponding 90% confidence interval was provided for each treatment.

Number of Participants With HIV-1 RNA<400 Copies/mL

Plasma for quantitative HIV-1 RNA was collected on Day 1, 2, 3, 4, 7, 8, 9, 10 and 11. On Days 1, 10 and 11, two samples for HIV-1 RNA was collected between 5-20 minutes apart to reduce sample variability. An HIV-1 RNA PCR assay with a LLOD of 50 copies/mL (ultrasensitive assay) was used for post-baseline assessments. An HIV-1 RNA PCR assay with a LLOD of 400 copies/mL (standard assay) was used for screening and Baseline assessments and included a re-test with and ultrasensitive assay for all Baseline values below the LLOD. assessments and included a re-test with and ultrasensitive assay for all Baseline values below the LLOD. Only categories with data available at the indicated time points have been presented. Categories with null values for all the arms have not been presented.

Number of Participants With HIV-1 RNA<50 Copies/mL

Plasma for quantitative HIV-1 RNA was collected on Day 1, 2, 3, 4, 7, 8, 9, 10 and 11. On Days 1, 10 and 11, two samples for HIV-1 RNA was collected between 5-20 minutes apart to reduce sample variability. An HIV-1 RNA PCR assay with a LLOD of 50 copies/mL (ultrasensitive assay) was used for post-baseline assessments. An HIV-1 RNA PCR assay with a LLOD of 400 copies/mL (standard assay) was used for screening and Baseline assessments and included a re-test with and ultrasensitive assay for all Baseline values below the LLOD. assessments and included a re-test with and ultrasensitive assay for all Baseline values below the LLOD. Only categories with data available at the indicated time points have been presented. Categories with null values for all the arms have not been presented.

Change From Baseline in CD4+ Cell Count to Day 11

Whole venous blood samples was obtained from each participant for the analysis of lymphocyte subsets by flow cytometry on Day 1 and Day 11. Baseline was defined at Day 1. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.

Pre-morning Dose Concentrations (C0) on Day 2 Through 10 to Assess the Achievement of Steady State of GSK1265744 Following Repeat Administration

Steady state is said to be reached, when the pre-dose concentration slope estimate is close to zero. The data for pre-dose concentration on Day 1 24 hours (Day 2) through Day 10 has been presented.

Accumulation Ratios for AUC, Cmax, and Ctau

The accumulation ratio was calculated as the ratio of AUC(0-τ), Cmax, and Ctau on Day 10 to AUC(0-24), Cmax, and C24 on Day 1 for each participant. The ratio of geometric least square means of each parameter on Day 10 to Day 1 was presented along with 90% confidence interval.

Day 1 AUC(0-24) at Different Doses for the Assessment of Dose Proportionality Using Power Model

Data from GSK1265744 30 mg in HIV participants (Study ITZ111451 part C HIV cohort, NCT00659191) was combined with data from this study to access dose proportionality. Dose proportionality of GSK1265744 PK parameters was assessed following single dose administration on Day 1 (AUC[0-24]) using the power model. The mean slope and corresponding 90% confidence interval has been presented.

Day 1 Cmax and C24 at Different Doses for the Assessment of Dose Proportionality Using Power Model

Data from GSK1265744 30 mg in HIV participants (Study ITZ111451 part C HIV cohort, NCT00659191) was combined with data from this study to access dose proportionality. Dose proportionality of GSK1265744 PK parameters was assessed following single dose administration on Day 1 (Cmax, and C24) using the power model. The mean slope and corresponding 90% confidence interval has been presented.

Day 10 AUC(0-tau) at Different Doses for the Assessment of Dose Proportionality Using Power Model

Data from GSK1265744 30 mg in HIV participants (Study ITZ111451 part C HIV cohort, NCT00659191) was combined with data from this study to access dose proportionality. Dose proportionality of GSK1265744 PK parameters was assessed following a repeat dose administration on Day 10 (AUC[0-tau]) using the power model. The mean slope and corresponding 90% confidence interval has been presented.

Day 10 Cmax, C0 and Ctau at Different Doses for the Assessment of Dose Proportionality Using Power Model

Data from GSK1265744 30 mg in HIV participants (Study ITZ111451 part C HIV cohort, NCT00659191) was combined with data from this study to access dose proportionality. Dose proportionality of GSK1265744 PK parameters was assessed following a repeat dose administration on Day 10 (Cmax, Ctau and C0) using the power model. The mean slope and corresponding 90% confidence interval has been presented.

Full Information

NCT ID

NCT00920426

First Posted

June 12, 2009

Last Updated

November 2, 2017

Sponsor

ViiV Healthcare

Collaborators

Shionogi, GlaxoSmithKline

1. Study Identification

Unique Protocol Identification Number

NCT00920426

Brief Title

Study to Compare the Safety and Anti-HIV Effect of GSK1265744 Versus Placebo in HIV-1 Infected Adults (ITZ112929)

Official Title

A Phase 2a Study to Compare Antiviral Effect, Safety, Tolerability and Pharmacokinetics of GSK1265744 Monotherapy Versus Placebo in HIV-1 Infected Adults (ITZ112929)

Study Type

Interventional

2. Study Status

Record Verification Date

September 2017

Overall Recruitment Status

Completed

Study Start Date

June 9, 2009 (Actual)

Primary Completion Date

August 13, 2009 (Actual)

Study Completion Date

August 13, 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

ViiV Healthcare

Collaborators

Shionogi, GlaxoSmithKline

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

The purpose of this randomized, double-blinded study is to test the safety of GSK1265744 and how well it works on reducing the amount of HIV in the blood. It will also look at how people react to and how a human body uses GSK1265744. This study will compare the effects of GSK1265744 and placebo. The study will consist of 1 or 2 parts to look at doses of GSK1265744. About 8 people will take part in Part 1 of the study receiving dose A. If additional dosing information is needed after Part 1, about 6 people will take part in Part 2 of the study receiving dose B.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Infection, Human Immunodeficiency Virus

Keywords

HIV, naive, Phase II, integrase inhibitor, GSK1265744, newly diagnosed, pharmacokinetics, AIDS, integrase, HIV Infections, Treatment naive

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

9 (Actual)

8. Arms, Groups, and Interventions

Arm Title

GSK1265744 30 mg

Arm Type

Experimental

Arm Description

GSK1265744 30 mg

Arm Title

Placebo

Arm Type

Experimental

Arm Description

Placebo to match GSK1265744

Arm Title

GSK1265744 5 mg

Arm Type

Experimental

Arm Description

GSK1265744 5 mg

Intervention Type

Drug

Intervention Name(s)

GSK1265744 30mg

Intervention Description

GSK1265744 30 mg

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo to match GSK1265744

Intervention Type

Drug

Intervention Name(s)

GSK1265744 5mg

Intervention Description

GSK1265744 5mg

Primary Outcome Measure Information:

Title

Change From Baseline in Plasma Human Immunodeficiency Virus (HIV-1) Ribonucleic Acid (RNA) to Day 11

Description

Time Frame

Baseline (Day 1) and Day 11

Title

Description

Time Frame

Day 1 (Pre-dose [within 15 minutes prior to dosing] and at 0.5, 1, 1.5, 2, 3, 4, 6, and 8hours post-dose)

Title

GSK1265744 PK Parameters Following Dose Administration on Day 1: Concentration at 24 Hours Post Dose (C24)

Description

Time Frame

Day 1 (Pre-dose [within 15 minutes prior to dosing] and at 0.5, 1, 1.5, 2, 3, 4, 6, and 8hours post-dose)

Title

GSK1265744 PK Parameters Following Dose Administration on Day 10: Area Under the Concentration-time Curve Over the Dosing Interval (AUC[0-tau])

Description

Time Frame

Day 10 (Pre-dose [within 15 minutes prior to dosing] and at 0.5, 1, 1.5, 2, 3, 4, 6, and 8hours post-dose)

Title

Description

Time Frame

Day 10 (Pre-dose [within 15 minutes prior to dosing] and at 0.5, 1, 1.5, 2, 3, 4, 6, and 8hours post-dose)

Title

GSK1265744 PK Parameters Following Dose Administration on Day 1 and Day 10: Maximum Observed Concentration (Cmax)

Description

Time Frame

Pre-dose (within 15 minutes prior to dosing) and at 0.5, 1, 1.5, 2, 3, 4, 6, and 8hours post-dose on Days 1 and 10

Title

GSK1265744 PK Parameters Following Dose Administration on Day 1 and Day 10: Time to Cmax (Tmax)

Description

Time Frame

Pre-dose (within 15 minutes prior to dosing) and at 0.5, 1, 1.5, 2, 3, 4, 6, and 8hours post-dose on Days 1 and 10

Title

GSK1265744 PK Parameters Following Dose Administration on Day 1 and Day 10: Terminal Half-life (t1/2) and Absorption Lag Time (Tlag)

Description

PK sampling was planned to be collected up to 24 hours only on Day 1 and Day 10. The data for this outcome measure was however not collected.

Time Frame

Day 1 and Day 10

Title

GSK1265744 PK Parameters Following Last Repeat Administration on Day 10: Apparent Clearance Following Oral Dosing (CL/F)

Description

Time Frame

Day 10 (Pre-dose [within 15 minutes prior to dosing] and at 0.5, 1, 1.5, 2, 3, 4, 6, and 8hours post-dose)

Title

Number of Participants With Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)

Description

Time Frame

Day 1 to Day 11

Title

Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC- Absolute Neutrophil Count), White Blood Cell Count

Description

Time Frame