Infection, Human Immunodeficiency VirusPhase 2NCT00708110

Phase IIa Dose-ranging Study of GSK1349572 in HIV-1 Infected Adults

A Phase 2 study testing GSK1349572 in people with Infection, Human Immunodeficiency Virus, run by ViiV Healthcare at 18 sites in United States.

Completed

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

Official record

Search all trials

Trial summary

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Infection, Human Immunodeficiency Virus
What is being tested?: GSK1349572
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 35 participants
Where: 18 sitesUnited States
Study dates: Jun 2008to Aug 2008
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 18 to 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Male or female >/18 and </ 65 years of age.
A female subject is eligible to participate if she is of non-childbearing potential defined as pre-menopausal females with a documented tubal ligation, hysterectomy or bilateral oophorectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 MlU/ml and estradiol < 40 pg/ml (<140 pmol/L) is confirmatory]. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods in Section 8.1 if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method.
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 drug.
CD4+ cell count >/ 100 cells/mm3.
Documented HIV-1 infection and a screening plasma HIV-1 RNA >/ 5000 copies/mL.
No current antiretroviral therapy and have not received any in the 12 weeks prior to first dose.
Capable of giving written informed consent, which includes compliance

Who cannot join

The subject has a positive pre-study drug screen. Drugs that will be screened for include amphetamines, barbiturates, cocaine, and PCP.
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).
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.
Prior treatment with an integrase inhibitor (> 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

Show all 22Show fewer

Treatment with any vaccine within 30 days prior to receiving study medication.
Use of multivitamins or antacids within 24 hours prior to the first dose of investigational product.
History of regular alcohol consumption within 6 months of the screening visit defined as: an average weekly intake of >14 drinks/week for men or >7 drinks/week for women. One drink is equivalent to (12 g alcohol) = 5 ounces (150 ml) of wine or 12 ounces (360 ml) of beer or 1.5 ounces (45 ml) of 80 proof distilled spirits.
Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
Pregnant females as determined by positive urine/serum hCG test at screening or prior to dosing.
Lactating females.
Unwillingness or inability to follow the procedures outlined in the protocol.
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.
An active Center for Disease Control and Prevention (CDC) Category C disease [see Appendix 1], except cutaneous Kaposi's sarcoma not requiring systemic therapy during the trial.
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.
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.
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 screen 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 screen, 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.
Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 3x times the upper limit of normal. A single repeat of ALT and/or AST is allowed for eligibility determination.
Exclusion Criteria for Screening ECG (A single repeat is allowed for eligibility determination):

Trial locations and contacts

18 sites in 1 country.

City, postcode or hospital

18 sites in 1 country

United States18 sites

GSK Investigational Site
Atlanta, Georgia, 30308
GSK Investigational Site
Bakersfield, California, 93301
GSK Investigational Site
Charlotte, North Carolina, 28209
GSK Investigational Site
Dallas, Texas, 75204
GSK Investigational Site
Dallas, Texas, 75246
GSK Investigational Site
Denver, Colorado, 80220
GSK Investigational Site
Fort Lauderdale, Florida, 33306
GSK Investigational Site
Fort Lauderdale, Florida, 33316
GSK Investigational Site
Hillsborough, New Jersey, 08844
GSK Investigational Site
Long Beach, California, 90813
GSK Investigational Site
Newport Beach, California, 92663
GSK Investigational Site
Northridge, California, 91325
GSK Investigational Site
Orlando, Florida, 32803
GSK Investigational Site
San Francisco, California, 94115
GSK Investigational Site
Santa Fe, New Mexico, 87505
GSK Investigational Site
Vero Beach, Florida, 32960
GSK Investigational Site
Voorhees Township, New Jersey, 08043
GSK Investigational Site
Washington D.C., District of Columbia, 20009

Other trials in United States

About this study

Official title: A Phase 2a, Multicenter, Randomized, Parallel, Double-Blind, Dose Ranging, Placebo-Controlled Study to Compare Antiviral Effect, Safety, Tolerability and Pharmacokinetics of GSK1349572 Monotherapy Versus Placebo Over 10 Days in HIV-1 Infected Adults (ING111521)

GSK1349572 is an integrase inhibitor that will be evaluated for the treatment of HIV infection. This phase IIa, multicenter, randomized, parallel, double-blind, dose ranging, placebo-controlled 'proof of concept' study is to be conducted to compare antiviral effect, safety, tolerability, and pharmacokinetics of GSK1349572 monotherapy versus placebo over 10 days in ART-naïve and experienced, but integrase inhibitor naïve (meaning never having had an integrase inhibitor) HIV-1 infected adults who are not currently receiving antiretroviral therapy. This study consists of a screening visit, a treatment period and a follow-up evaluation. Thirty subjects will be randomized to receive one of three doses of GSK1349572 or placebo q24h over 10 days. Antiviral effect measures include viral load and CD4 cell count.

Conditions: Infection, Human Immunodeficiency Virus
Being tested: GSK1349572, Placebo
Keywords: dose-ranging study, phase IIa, integrase inhibitor, HIV-1 infection
Medical subject headings: Infections, Acquired Immunodeficiency Syndrome

What participants receive

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

GSK1349572Drug
GSK1349572 is an experimental drug being developed for the treatment of HIV. It is in the class of integrase inhibitors.
PlaceboDrug
Placebo is a tablet with no drug in it.

Study groups in NCT00708110
Study group	Role	What they receive
Treatment A	Experimental	GSK1349572 2 mg or placebo every 24 hours for 10 days. Screening visit up to 30 days prior to first dose and follow-up for 11 days after last dose. Receives: Drug: GSK1349572; Drug: Placebo
Treatment B	Experimental	GSK1349572 10 mg or placebo every 24 hours for 10 days. Screening visit up to 30 days prior to first dose and follow-up for 11 days after last dose. Receives: Drug: GSK1349572; Drug: Placebo
Treatment C	Experimental	GSK1349572 50 mg or placebo every 24 hours for 10 days. Screening visit up to 30 days prior to first dose and follow-up for 11 days after last dose. Receives: Drug: GSK1349572; Drug: Placebo

What is being measured

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

Change From Baseline in Plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) at Day 11
Change from Baseline in Plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) was calculated as the Day 11 value minus the Baseline value. Blood samples for the measurement of HIV-1 RNA levels were obtained throughout the treatment period (Day 1 to Day 11).
Measured: Baseline (Day 1) and Day 11
Area Under the Plasma Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-inf]) and Over 24 Hours (AUC[0-24]) of GSK1349572 Following Dose Administration on Day 1
AUC is defined as the area under the GSK1349572 concentration-time curve as a measure of drug exposure. AUC(0-inf) is defined as the area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time. AUC(0-24) is defined as the area under the concentration-time curve from time zero (pre-dose) to24 hours. Blood samples for pharmacokinetic (PK) analysis of GSK1349572 were obtained on Day 1at pre-dose (within 15 minutes prior to dose) and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post GSK1349572 dose administration.
Measured: Day 1
Maximum Observed Plasma Concentration (Cmax) and Concentration at 24 Hours Post Dose (C24) of GSK1349572 Following Dose Administration on Day 1
Cmax is defined as the maximum observed plasma concentration, and C24 is defined as the concentration at 24 hours post dose. Blood samples for PK analysis of GSK1349572 were obtained on Day 1at pre-dose (within 15 minutes prior to dose) and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post GSK1349572 dose administration. From the plasma concentration-time curve, Cmax was determined by standard non-compartmental analysis using WinNonlin Pro 4.1 or higher.
Measured: Day 1
Time to Maximum Observed Concentration (Tmax) and Absorption Lag Time (Tlag) of GSK1349572 Following Dose Administration on Day 1
tmax is defined as the time to the maximum obsevered plasma concentration. Absorption lag time is defined as the time taken for a drug to appear in the systemic circulation following administration. tlag was estimated based on PK sampling times of 0 (pre-dose), 0.5, 1, 1.5, 2 3, 4, 6, 8, 12, and 24 hours post-dose. Blood samples for PK analysis of GSK1349572 were obtained on Day 1at pre-dose (within 15 minutes prior to dose) and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post GSK1349572 dose administration. From the plasma concentration-time curve, tmax was determined by standard non-compartmental analysis using WinNonlin Pro 4.1 or higher.
Measured: Day 1
Terminal Half-life (t1/2) of GSK1349572 Following Dose Administration on Day 1
The terminal half-life (t1/2) of GSK1349572 is defined as the time required for the plasma concentration of GSK1349572 to reach half of its original concentration. Blood samples for PK analysis of GSK1349572 were obtained on Day 1at pre-dose (within 15 minutes prior to dose) and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post GSK1349572 dose administration.
Measured: Day 1
Apparent Clearance (CL/F) of GSK1349572 Following Dose Administration on Day 1
The CL/F is defined as the apparent total clearance of the drug from plasma after oral administration. Blood samples for PK analysis of GSK1349572 were obtained on Day 1at pre-dose (within 15 minutes prior to dose) and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post GSK1349572 dose administration.
Measured: Day 1
Area Under the Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) of GSK1349572 Following the Last Repeat Administration on Day 10
AUC is defined as the area under the GSK1349572 concentration-time curve as a measure of drug exposure. AUC(0-tau) is defined as the area under the concentration-time curve over the dosing interval. Blood samples for PK analysis of GSK1349572 were obtained on Day 10at pre-dose (within 15 minutes prior to dose) and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post GSK1349572 dose administration.
Measured: Day 10
Pre-dose Concentration (C0), Concentration at the End of the Dosing Interval (Ctau), Minimum Observed Concentration During One Dosing Interval (Cmin), and Maximum Obsevered Plasma Concentration (Cmax) of GSK1349572 Following the Last Repeat Administration
C0 is defined as the pre-dose concentration. Ctau is defined as the concentration at the end of the dosing interval. Cmin is defined as the minimum observed concentration during one dosing interval. Cmax is defined as the maximum obsevered plasma concentration. Blood samples for PK analysis of GSK1349572 were obtained on Day 10 at pre-dose (within 15 minutes prior to dose) and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post GSK1349572 dose administration.
Measured: Day 10
Time to the Maximum Observed Concentration (Tmax) of GSK1349572 Following the Last Repeat Administration on Day 10
tmax is defined as the time to the maximum obsevered plasma concentration. Blood samples for PK analysis of GSK1349572 were obtained on Day 10 at pre-dose (within 15 minutes prior to dose) and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post GSK1349572 dose administration. From the plasma concentration-time curve, tmax was determined by standard non-compartmental analysis using WinNonlin Pro 4.1 or higher.
Measured: Day 10
Terminal Half-life (t1/2) of GSK1349572 Following the Last Repeat Administration on Day 10
The terminal half-life (t1/2) of GSK1349572 is defined as the time required for the plasma concentration of GSK1349572 to reach half of its original concentration. Blood samples for PK analysis of GSK1349572 were obtained on Day 10 at pre-dose (within 15 minutes prior to dose) and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post GSK1349572 dose administration.
Measured: Day 10
Apparent Clearance (CL/F) of GSK1349572 Following Dose Administration on Day 10
The CL/F is defined as the apparent total clearance of the drug from plasma after oral administration. Blood samples for PK analysis of GSK1349572 were obtained on Day 10 at pre-dose (within 15 minutes prior to dose) and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post GSK1349572 dose administration.
Measured: Day 10
Number of Participants With Any Non-serious Adverse Event (AE) or Serious Adverse Event (SAE)
An AE is defined as 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, is a congenital anomaly/birth defect, or is an event of possible drug-induced liver injury. Refer to the general Adverse AE/SAE module for a complete list of AEs and SAEs.
Measured: From Baseline (Day 1) until Follow-up (average of 3 study weeks)
Number of Participants Who Received the Indicated Concomitant Medications During the Study Period
Concomitant medications received during the study period are presented by generic term. Only those concomitant medications that were received by at least two participants are presented. "Multiple ingredient" is the term used in the statistical package for items that contain more than one active ingredient.
Measured: From Baseline (Day 1) until Follow-up (average of 3 study weeks)
Change From Baseline in Mean Blood Pressure at Days 1, 4, 7, and 10
Blood pressure measurement included systolic blood pressure (SBP) and diastolic BP (DBP). Change in the mean blood pressure from Baseline was calculated as the post-Baseline value minus the Baseline value. Data are presented for change from Baseline at Day 1 (2 hours post dose [hrs]), Day 4 (1 hr pre-dose), Day 7 (1 hr pre-dose), and Day 10 (1 hr pre-dose and 2 hrs post dose).
Measured: Baseline and Days 1, 4, 7, and 10
Change From Baseline in Mean Heart Rate at Days 1, 4, 7, and 10
Heart rate is the measure of heart beats per minute (bpm). Change in the mean heart rate from Baseline was calculated as the post-Baseline value minus the Baseline value. Data are presented for change from Baseline at Day 1 (2 hours post dose [hrs]), Day 4 (1 hr pre-dose), Day 7 (1 hr pre-dose), and Day 10 (1 hr pre-dose and 2 hrs post dose).
Measured: Baseline and Days 1, 4, 7, and 10
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
A 12-lead electrocardiogram (ECG) was performed by qualified personnel at the site after the participant had rested for at least 5 minutes in a semi-recumbent or supine position. If a QTc measurement of >=500 milliseconds (msec) was noted on a scheduled or unscheduled ECG, two additional ECGs were to be obtained within 5 minutes to confirm the abnormality. The number of participants with abnormal clinically significant (CS) and not clinically significant (NCS) ECG findings are presented here. The site determined if an ECG finding is significant or not. ECGs were obtained at Screening, Day 1 (pre-dose [twice] and then 1.0, 1.5, and 2.0 hours [hrs] post dose), Day 4 (pre-dose), Day 7 (pre-dose), Day 10 (pre-dose and then 1.0, 1.5, and 2.0 hrs post dose), Day 11 (prior to the 24 hr PK sample [pre lab]), and Follow-up.
Measured: Screening; Days 1, 7, 10, 11; and Follow-up (up to Study Day 21)
Number of Participants With the Indicated Grade 3 and Grade 4 Laboratory Abnormalities
Clinical laboratory toxicities were graded according to the National Institutes of Allergy and Infectious Diseases (NIAID), Division of Acquired Immunodeficiency Syndrome (DAIDS). Grade 1, Mild; Grade 2, Moderate; Grade 3 (G3), Severe; Grade 4 (G4), Life-threatening or disabling; Grade 5, Death. Data are presented only for Grade 3 and Grade 4 laboratory abnormalities. Clinical laboratory abnormalities included: increased glucose, lipase, decreased platelets, and triglycerides.
Measured: Screening; Days 1, 3, 7, and 10; and Follow-up (up to Study Day 21)

Secondary outcomes (8)

Mean Change From Baseline in Plasma HIV-1 RNA to Nadir (Maximum Change) at Day 11
Plasma HIV-1 RNA change from Baseline to the on-treatment nadir (maximum change) was calculated as the post-Baseline value minus the Baseline value.
Measured: Baseline and Day 11
Median Change From Baseline in Plasma HIV-1 RNA to Nadir (Maximum Change) at Day 11
Plasma HIV-1 RNA change from Baseline to the on-treatment nadir (maximum change) was calculated as the post-Baseline value minus the Baseline value.
Measured: Baseline and Day 11
Plasma HIV-1 RNA Rate of Decline Over 10 Days
The rate of decline of plasma HIV-1 RNA levels from Day 1 to Day 11 was measured.
Measured: Day 1 to Day 11
Number of Participants With HIV-1 RNA <400 Copies/mL and <50 Copies/mL
The number of participants who achieved plasma HIV-1 RNA levels <400 copies/mL and <50 copies/mL through Day 11 was measured.
Measured: Day 11
Median Change From Baseline in Plasma HIV-1 RNA Levels During the Follow-up Period (Days 11 to 21)
Change from Baseline in Plasma HIV-1 RNA levels was calculated as the value during the Follow-up period minus the Basline value.
Measured: Baseline and Follow-up period (Days 11 to 21)
Mean Change From Baseline in Plasma HIV-1 RNA Levels During the Follow-up Period (Days 11 to 21)
Change from Baseline in Plasma HIV-1 RNA levels was calculated as the value during the Follow-up period minus the Basline value.
Measured: Baseline and Follow-up period (Days 11 to 21)
Median Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Count at Day 11
Median change from Baseline in CD4+ cell count was calculated as the Day 11 value minus the Baseline value.
Measured: Baseline and Day 11
Number of Participants With the Emergence of Drug Resistance Mutations
The number of participants with the emergence (from Baseline) of drug resistance mutations at Day 11 was measured.
Measured: Baseline and Day 11

Timeline

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

Jun 2008Aug 2008

First posted2 Jul 2008 (estimated)
Study startJun 2008
Primary completionAug 2008
Study completionAug 2008

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: 35 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00708110
Sponsor's protocol ID: 111521
Status last verified: Aug 2013
First submitted: 30 Jun 2008
Last updated: 5 Dec 2013
Results posted: Yes, on ClinicalTrials.gov

Publications

Min S, Sloan L, DeJesus E, Hawkins T, McCurdy L, Song I, Stroder R, Chen S, Underwood M, Fujiwara T, Piscitelli S, Lalezari J. Antiviral activity, safety, and pharmacokinetics/pharmacodynamics of dolutegravir as 10-day monotherapy in HIV-1-infected adults. AIDS. 2011 Sep 10;25(14):1737-45. doi: 10.1097/QAD.0b013e32834a1dd9.
PubMed 21716073

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Not yet recruiting
HealthMpowerment Korea: Pilot Testing the Cultural Adaptation of a Digital HIV Intervention for Men Who Have Sex With Men in South Korea
HIV Infections, HIV Prevention and Care
Not yet recruiting
Prescribe to Prevent HIV: A Hybrid Trial Helping Addiction Clinics Prevent HIV & Infections Through Safer Drug Use Support
People Who Use Opioids/People With Opioid Use Disorder (OUD)
Enrolling by invitation
Promoting Aging and Thriving With HIV
HIV (Human Immunodeficiency Virus), Geriatric
RecruitingObservational study
Cohort of Women Living With HIV-1 and Receiving Bictegravir/Emtricitabine/Tenofovir Alafenamide
HIV (Human Immunodeficiency Virus), Pregnancy
Not yet recruiting
HIV/STI/HCV Testing and Overdose Prevention Among Survivors of Sex Trafficking
HIV Testing, STI

All Infection, Human Immunodeficiency Virus trials

Study at a glance

From the registry record, last updated by the sponsor on 5 Dec 2013. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 2a, Multicenter, Randomized, Parallel, Double-Blind, Dose Ranging, Placebo-Controlled Study to Compare Antiviral Effect, Safety, Tolerability and Pharmacokinetics of GSK1349572 Monotherapy Versus Placebo Over 10 Days in HIV-1 Infected Adults (ING111521)
ClinicalTrials.gov ID: NCT00708110
Acronym / sponsor ID: 111521
Conditions: Infection, Human Immunodeficiency Virus
Keywords: dose-ranging study, phase IIa, integrase inhibitor, HIV-1 infection
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 35 participants (actual)
Lead sponsor: ViiV HealthcareIndustry (pharma, biotech, devices)
Collaborators: Shionogi, GlaxoSmithKline
Study start: Jun 2008
Primary completion: Aug 2008 (actual)
Study completion: Aug 2008 (actual)
First posted: 2 Jul 2008 (estimated)
Results: Posted 30 Oct 2013

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: 3

Arm	Type	Receives
Treatment A	Experimental	Drug: GSK1349572, Drug: PlaceboGSK1349572 2 mg or placebo every 24 hours for 10 days. Screening visit up to 30 days prior to first dose and follow-up for 11 days after last dose.
Treatment B	Experimental	Drug: GSK1349572, Drug: PlaceboGSK1349572 10 mg or placebo every 24 hours for 10 days. Screening visit up to 30 days prior to first dose and follow-up for 11 days after last dose.
Treatment C	Experimental	Drug: GSK1349572, Drug: PlaceboGSK1349572 50 mg or placebo every 24 hours for 10 days. Screening visit up to 30 days prior to first dose and follow-up for 11 days after last dose.

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

Male or female >/18 and </ 65 years of age.
A female subject is eligible to participate if she is of non-childbearing potential defined as pre-menopausal females with a documented tubal ligation, hysterectomy or bilateral oophorectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 MlU/ml and estradiol < 40 pg/ml (<140 pmol/L) is confirmatory]. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods in Section 8.1 if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method.
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 drug.
CD4+ cell count >/ 100 cells/mm3.
Documented HIV-1 infection and a screening plasma HIV-1 RNA >/ 5000 copies/mL.

Key exclusion criteria (22 listed)

The subject has a positive pre-study drug screen. Drugs that will be screened for include amphetamines, barbiturates, cocaine, and PCP.
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).
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.
Prior treatment with an integrase inhibitor (> 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.

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
GSK1349572GSK1349572 is an experimental drug being developed for the treatment of HIV. It is in the class of integrase inhibitors.	Drug	Treatment A, Treatment B, Treatment C
PlaceboPlacebo is a tablet with no drug in it.	Drug	Treatment A, Treatment B, Treatment C

Primary outcome

Change From Baseline in Plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) at Day 11
Time frame: Baseline (Day 1) and Day 11
Change from Baseline in Plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) was calculated as the Day 11 value minus the Baseline value. Blood samples for the measurement of HIV-1 RNA levels were obtained throughout the treatment period (Day 1 to Day 11).
Area Under the Plasma Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-inf]) and Over 24 Hours (AUC[0-24]) of GSK1349572 Following Dose Administration on Day 1
Time frame: Day 1
AUC is defined as the area under the GSK1349572 concentration-time curve as a measure of drug exposure. AUC(0-inf) is defined as the area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time. AUC(0-24) is defined as the area under the concentration-time curve from time zero (pre-dose) to24 hours. Blood samples for pharmacokinetic (PK) analysis of GSK1349572 were obtained on Day 1at pre-dose (within 15 minutes prior to dose) and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post GSK1349572 dose administration.
Maximum Observed Plasma Concentration (Cmax) and Concentration at 24 Hours Post Dose (C24) of GSK1349572 Following Dose Administration on Day 1
Time frame: Day 1
Cmax is defined as the maximum observed plasma concentration, and C24 is defined as the concentration at 24 hours post dose. Blood samples for PK analysis of GSK1349572 were obtained on Day 1at pre-dose (within 15 minutes prior to dose) and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post GSK1349572 dose administration. From the plasma concentration-time curve, Cmax was determined by standard non-compartmental analysis using WinNonlin Pro 4.1 or higher.
Time to Maximum Observed Concentration (Tmax) and Absorption Lag Time (Tlag) of GSK1349572 Following Dose Administration on Day 1
Time frame: Day 1
tmax is defined as the time to the maximum obsevered plasma concentration. Absorption lag time is defined as the time taken for a drug to appear in the systemic circulation following administration. tlag was estimated based on PK sampling times of 0 (pre-dose), 0.5, 1, 1.5, 2 3, 4, 6, 8, 12, and 24 hours post-dose. Blood samples for PK analysis of GSK1349572 were obtained on Day 1at pre-dose (within 15 minutes prior to dose) and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post GSK1349572 dose administration. From the plasma concentration-time curve, tmax was determined by standard non-compartmental analysis using WinNonlin Pro 4.1 or higher.
Terminal Half-life (t1/2) of GSK1349572 Following Dose Administration on Day 1
Time frame: Day 1
The terminal half-life (t1/2) of GSK1349572 is defined as the time required for the plasma concentration of GSK1349572 to reach half of its original concentration. Blood samples for PK analysis of GSK1349572 were obtained on Day 1at pre-dose (within 15 minutes prior to dose) and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post GSK1349572 dose administration.
Apparent Clearance (CL/F) of GSK1349572 Following Dose Administration on Day 1
Time frame: Day 1
The CL/F is defined as the apparent total clearance of the drug from plasma after oral administration. Blood samples for PK analysis of GSK1349572 were obtained on Day 1at pre-dose (within 15 minutes prior to dose) and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post GSK1349572 dose administration.
Area Under the Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) of GSK1349572 Following the Last Repeat Administration on Day 10
Time frame: Day 10
AUC is defined as the area under the GSK1349572 concentration-time curve as a measure of drug exposure. AUC(0-tau) is defined as the area under the concentration-time curve over the dosing interval. Blood samples for PK analysis of GSK1349572 were obtained on Day 10at pre-dose (within 15 minutes prior to dose) and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post GSK1349572 dose administration.
Pre-dose Concentration (C0), Concentration at the End of the Dosing Interval (Ctau), Minimum Observed Concentration During One Dosing Interval (Cmin), and Maximum Obsevered Plasma Concentration (Cmax) of GSK1349572 Following the Last Repeat Administration
Time frame: Day 10
C0 is defined as the pre-dose concentration. Ctau is defined as the concentration at the end of the dosing interval. Cmin is defined as the minimum observed concentration during one dosing interval. Cmax is defined as the maximum obsevered plasma concentration. Blood samples for PK analysis of GSK1349572 were obtained on Day 10 at pre-dose (within 15 minutes prior to dose) and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post GSK1349572 dose administration.
Time to the Maximum Observed Concentration (Tmax) of GSK1349572 Following the Last Repeat Administration on Day 10
Time frame: Day 10
tmax is defined as the time to the maximum obsevered plasma concentration. Blood samples for PK analysis of GSK1349572 were obtained on Day 10 at pre-dose (within 15 minutes prior to dose) and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post GSK1349572 dose administration. From the plasma concentration-time curve, tmax was determined by standard non-compartmental analysis using WinNonlin Pro 4.1 or higher.
Terminal Half-life (t1/2) of GSK1349572 Following the Last Repeat Administration on Day 10
Time frame: Day 10
The terminal half-life (t1/2) of GSK1349572 is defined as the time required for the plasma concentration of GSK1349572 to reach half of its original concentration. Blood samples for PK analysis of GSK1349572 were obtained on Day 10 at pre-dose (within 15 minutes prior to dose) and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post GSK1349572 dose administration.
Apparent Clearance (CL/F) of GSK1349572 Following Dose Administration on Day 10
Time frame: Day 10
The CL/F is defined as the apparent total clearance of the drug from plasma after oral administration. Blood samples for PK analysis of GSK1349572 were obtained on Day 10 at pre-dose (within 15 minutes prior to dose) and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post GSK1349572 dose administration.
Number of Participants With Any Non-serious Adverse Event (AE) or Serious Adverse Event (SAE)
Time frame: From Baseline (Day 1) until Follow-up (average of 3 study weeks)
An AE is defined as 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, is a congenital anomaly/birth defect, or is an event of possible drug-induced liver injury. Refer to the general Adverse AE/SAE module for a complete list of AEs and SAEs.
Number of Participants Who Received the Indicated Concomitant Medications During the Study Period
Time frame: From Baseline (Day 1) until Follow-up (average of 3 study weeks)
Concomitant medications received during the study period are presented by generic term. Only those concomitant medications that were received by at least two participants are presented. "Multiple ingredient" is the term used in the statistical package for items that contain more than one active ingredient.
Change From Baseline in Mean Blood Pressure at Days 1, 4, 7, and 10
Time frame: Baseline and Days 1, 4, 7, and 10
Blood pressure measurement included systolic blood pressure (SBP) and diastolic BP (DBP). Change in the mean blood pressure from Baseline was calculated as the post-Baseline value minus the Baseline value. Data are presented for change from Baseline at Day 1 (2 hours post dose [hrs]), Day 4 (1 hr pre-dose), Day 7 (1 hr pre-dose), and Day 10 (1 hr pre-dose and 2 hrs post dose).
Change From Baseline in Mean Heart Rate at Days 1, 4, 7, and 10
Time frame: Baseline and Days 1, 4, 7, and 10
Heart rate is the measure of heart beats per minute (bpm). Change in the mean heart rate from Baseline was calculated as the post-Baseline value minus the Baseline value. Data are presented for change from Baseline at Day 1 (2 hours post dose [hrs]), Day 4 (1 hr pre-dose), Day 7 (1 hr pre-dose), and Day 10 (1 hr pre-dose and 2 hrs post dose).
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
Time frame: Screening; Days 1, 7, 10, 11; and Follow-up (up to Study Day 21)
A 12-lead electrocardiogram (ECG) was performed by qualified personnel at the site after the participant had rested for at least 5 minutes in a semi-recumbent or supine position. If a QTc measurement of >=500 milliseconds (msec) was noted on a scheduled or unscheduled ECG, two additional ECGs were to be obtained within 5 minutes to confirm the abnormality. The number of participants with abnormal clinically significant (CS) and not clinically significant (NCS) ECG findings are presented here. The site determined if an ECG finding is significant or not. ECGs were obtained at Screening, Day 1 (pre-dose [twice] and then 1.0, 1.5, and 2.0 hours [hrs] post dose), Day 4 (pre-dose), Day 7 (pre-dose), Day 10 (pre-dose and then 1.0, 1.5, and 2.0 hrs post dose), Day 11 (prior to the 24 hr PK sample [pre lab]), and Follow-up.
Number of Participants With the Indicated Grade 3 and Grade 4 Laboratory Abnormalities
Time frame: Screening; Days 1, 3, 7, and 10; and Follow-up (up to Study Day 21)
Clinical laboratory toxicities were graded according to the National Institutes of Allergy and Infectious Diseases (NIAID), Division of Acquired Immunodeficiency Syndrome (DAIDS). Grade 1, Mild; Grade 2, Moderate; Grade 3 (G3), Severe; Grade 4 (G4), Life-threatening or disabling; Grade 5, Death. Data are presented only for Grade 3 and Grade 4 laboratory abnormalities. Clinical laboratory abnormalities included: increased glucose, lipase, decreased platelets, and triglycerides.

8 secondary outcomes

Mean Change From Baseline in Plasma HIV-1 RNA to Nadir (Maximum Change) at Day 11
Time frame: Baseline and Day 11
Median Change From Baseline in Plasma HIV-1 RNA to Nadir (Maximum Change) at Day 11
Time frame: Baseline and Day 11
Plasma HIV-1 RNA Rate of Decline Over 10 Days
Time frame: Day 1 to Day 11
Number of Participants With HIV-1 RNA <400 Copies/mL and <50 Copies/mL
Time frame: Day 11
Median Change From Baseline in Plasma HIV-1 RNA Levels During the Follow-up Period (Days 11 to 21)
Time frame: Baseline and Follow-up period (Days 11 to 21)
Mean Change From Baseline in Plasma HIV-1 RNA Levels During the Follow-up Period (Days 11 to 21)
Time frame: Baseline and Follow-up period (Days 11 to 21)
Median Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Count at Day 11
Time frame: Baseline and Day 11
Number of Participants With the Emergence of Drug Resistance Mutations
Time frame: Baseline and Day 11

Results and safety

Results posted to the registry on 30 Oct 2013, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Placebo	7	7
GSK1349572 2 mg QD	9	9
GSK1349572 10 mg QD	9	9
GSK1349572 50 mg QD	10	10

Primary outcome: Change From Baseline in Plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) at Day 11

Time frame: Baseline (Day 1) and Day 11. Mean (Standard Deviation). Unit: Log10 copies/milliliter (log10 copies/mL

Measure	Placebo n = 7	GSK1349572 2 mg QD n = 9	GSK1349572 10 mg QD n = 9	GSK1349572 50 mg QD n = 10
Value	0.05 (0.26)	-1.51 (0.58)	-2.03 (0.49)	-2.46 (0.35)

Placebo vs GSK1349572 2 mg QD: Mean Difference (Final Values): -1.54 (95% CI -2.00 to -1.07), p <0.001, ANCOVA
Placebo vs GSK1349572 10 mg QD: Mean Difference (Final Values): -2.04 (95% CI -2.52 to -1.55), p <0.001, ANCOVA
Placebo vs GSK1349572 50 mg QD: Mean Difference (Final Values): -2.48 (95% CI -2.94 to -2.02), p <0.001, ANCOVA

Population analysed: Intent to Treat Exposed (ITT\[E\]) Population: all participants who met study criteria and were randomized into the study with documented evidence of having received at least one dose of randomized treatment and at least one post-baseline HIV-1 RNA measurement

Primary outcome: Area Under the Plasma Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-inf]) and Over 24 Hours (AUC[0-24]) of GSK1349572 Following Dose Administration on Day 1

Time frame: Day 1. Geometric mean (Geometric Coefficient of Variation). Unit: Micrograms*hour per milliliter (µg*hr/mL

Measure	Placebo n = 0	GSK1349572 2 mg QD n = 9	GSK1349572 10 mg QD n = 7	GSK1349572 50 mg QD n = 10
AUC(0-inf)	–	2.63 (39)	10.1 (26)	40.5 (33)
AUC(0-24)	–	2.05 (33)	7.41 (27)	30.34 (33)

Population analysed: Pharmacokinetic Summary (PKS) Population: participants (par.) with an evaluable profile of GSK1349572 on Day 10. Par. were excluded if they vomited within 2 hours of dosing on Day 10, missed more than one dose 2 days prior to Day 10, and took prohibited concomitant medication during the treatment period. No par. were analyzed in the placebo group.

Primary outcome: Maximum Observed Plasma Concentration (Cmax) and Concentration at 24 Hours Post Dose (C24) of GSK1349572 Following Dose Administration on Day 1

Time frame: Day 1. Geometric mean (Geometric Coefficient of Variation). Unit: Micrograms per milliliter (µg/mL)

Measure	Placebo n = 0	GSK1349572 2 mg QD n = 9	GSK1349572 10 mg QD n = 7	GSK1349572 50 mg QD n = 10
Cmax	–	0.18 (35)	0.57 (28)	2.46 (32)
C24	–	0.03 (49)	0.15 (30)	0.59 (31)

Population analysed: PKS Population. No participants were analyzed in the placebo group.

Primary outcome: Time to Maximum Observed Concentration (Tmax) and Absorption Lag Time (Tlag) of GSK1349572 Following Dose Administration on Day 1

Time frame: Day 1. Median (Full Range). Unit: Hours

Measure	Placebo n = 0	GSK1349572 2 mg QD n = 9	GSK1349572 10 mg QD n = 7	GSK1349572 50 mg QD n = 10
tmax	–	1.50 (0.50 to 3.00)	2.00 (1.02 to 6.00)	2.09 (1.00 to 3.97)
tlag	–	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)

Population analysed: PKS Population. No participants were analyzed for the placebo group.

8 secondary outcomes are reported in the full results.

Adverse events

Time frame: Serious adverse events (SAEs) and non-serious AEs were collected from Baseline (Day 1) until Follow-up (average of 3 study weeks).. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo	0 of 7 (0%)	5 of 7 (71.4%)	Not reported
GSK1349572 2 mg QD	0 of 9 (0%)	4 of 9 (44.4%)	Not reported
GSK1349572 10 mg QD	0 of 9 (0%)	7 of 9 (77.8%)	Not reported
GSK1349572 50 mg QD	0 of 10 (0%)	7 of 10 (70%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 Dec 2013.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 21716073Min S, Sloan L, DeJesus E, Hawkins T, McCurdy L, Song I, Stroder R, Chen S, Underwood M, Fujiwara T, Piscitelli S, Lalezari J. Antiviral activity, safety, and pharmacokinetics/pharmacodynamics of dolutegravir as 10-day monotherapy in HIV-1-infected adults. AIDS. 2011 Sep 10;25(14):1737-45. doi: 10.1097/QAD.0b013e32834a1dd9.

Related trials for Infection, Human Immunodeficiency Virus

Not yet recruiting
HealthMpowerment Korea: Pilot Testing the Cultural Adaptation of a Digital HIV Intervention for Men Who Have Sex With Men in South Korea
HIV Infections, HIV Prevention and Care
Not yet recruiting
Prescribe to Prevent HIV: A Hybrid Trial Helping Addiction Clinics Prevent HIV & Infections Through Safer Drug Use Support
People Who Use Opioids/People With Opioid Use Disorder (OUD)
Enrolling by invitation
Promoting Aging and Thriving With HIV
HIV (Human Immunodeficiency Virus), Geriatric
RecruitingObservational study
Cohort of Women Living With HIV-1 and Receiving Bictegravir/Emtricitabine/Tenofovir Alafenamide
HIV (Human Immunodeficiency Virus), Pregnancy
Not yet recruiting
HIV/STI/HCV Testing and Overdose Prevention Among Survivors of Sex Trafficking
HIV Testing, STI

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

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

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing GSK1349572 in people with Infection, Human Immunodeficiency Virus, run by ViiV Healthcare at 18 sites in United States.

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 22 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 5 Dec 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 18 sites in United States. 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 30 Oct 2013). 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?

Change From Baseline in Plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) at Day 11 (time frame: Baseline (Day 1) and Day 11). The study lists 17 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 NCT00708110, 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 5 Dec 2013.