A Study of GSK1349572 Versus Raltegravir (RAL) With Investigator Selected Background Regimen in Antiretroviral-Experienced, Integrase Inhibitor-Naive Adults (SAILING)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Shionogi
GlaxoSmithKline
Information provided by (Responsible Party):
ViiV Healthcare
ClinicalTrials.gov Identifier:
NCT01231516
First received: October 21, 2010
Last updated: March 20, 2014
Last verified: March 2014
Results First Received: August 15, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Infection, Human Immunodeficiency Virus
Interventions: Drug: GSK1349572
Drug: Raltegravir
Drug: GSK1349572 Placebo
Drug: Raltegravir Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
1441 participants were screened; 724 were randomized. A total of 719 participants received at least 1 dose of study medication and comprised the intent-to-treat exposed (ITT-E) population. Four participants from one closed site were removed from the ITT-E population creating the modified ITT-E population with 715 participants.

Reporting Groups
  Description
DTG 50 mg OD Participants received dolutegravir (DTG) 50 milligrams (mg) once daily (OD) + matching Raltegravir (RAL) placebo twice daily (BID), one in the morning (AM dose) and one in the evening (PM dose) + investigator selected background antiretroviral (ART) therapy for 48 weeks. Participants who successfully completed 48 weeks of treatment continue to have access to DTG in the Open-Label phase of the study.
RAL 400 mg BID Participants received matching DTG placebo OD + RAL 400 mg BID as AM and PM doses + investigator selected background ART therapy for 48 weeks. Participants were discontinued from the study after completion of the Week 48 visit unless a participant successfully completed Week 48 and RAL was not approved and commercially available within the country, GSK will continue to supply RAL in the Open-Label Phase until it is commercially available.

Participant Flow for 2 periods

Period 1:   48 Week Double-blind Phase
    DTG 50 mg OD     RAL 400 mg BID  
STARTED     357     362  
COMPLETED     299     283  
NOT COMPLETED     58     79  
Adverse Event                 4                 11  
Lack of Efficacy                 20                 42  
Protocol Violation                 9                 6  
Met Protocol-Defined Stopping Criteria                 5                 3  
Lost to Follow-up                 5                 10  
Physician Decision                 1                 1  
Withdrawal by Subject                 11                 5  
Site Closed                 3                 1  

Period 2:   Open-label Phase
    DTG 50 mg OD     RAL 400 mg BID  
STARTED     295 [1]   27 [2]
Ongoing at the Time of Analysis     282     23  
COMPLETED     0     1  
NOT COMPLETED     295     26  
Lack of Efficacy                 7                 3  
Protocol Violation                 2                 0  
Lost to Follow-up                 3                 0  
Withdrawal by Subject                 1                 0  
Ongoing at the time of analysis                 282                 23  
[1] 4 participants completed the Double-blind Phase but did not enter the Open-label Phase.
[2] 256 participants completed the Double-blind Phase but did not enter the Open-label Phase.



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
DTG 50 mg OD Participants received dolutegravir (DTG) 50 milligrams (mg) once daily (OD) + matching Raltegravir (RAL) placebo twice daily (BID), one in the morning (AM dose) and one in the evening (PM dose) + investigator selected background antiretroviral (ART) therapy for 48 weeks. Participants who successfully completed 48 weeks of treatment continue to have access to DTG in the Open-Label phase of the study.
RAL 400 mg BID Participants received matching DTG placebo OD + RAL 400 mg BID as AM and PM doses + investigator selected background ART therapy for 48 weeks. Participants were discontinued from the study after completion of the Week 48 visit unless a participant successfully completed Week 48 and RAL was not approved and commercially available within the country, GSK will continue to supply RAL in the Open-Label Phase until it is commercially available.
Total Total of all reporting groups

Baseline Measures
    DTG 50 mg OD     RAL 400 mg BID     Total  
Number of Participants  
[units: participants]
  354     361     715  
Age [1]
[units: Years]
Mean ± Standard Deviation
  42.6  ± 10.45     42.5  ± 9.81     42.5  ± 10.13  
Gender [1]
[units: Participants]
     
Female     107     123     230  
Male     247     238     485  
Race/Ethnicity, Customized [1]
[units: Participants]
     
African American/African Heritage     143     160     303  
American Indian or Alaska Native     10     17     27  
Asian-Central/South Asian Heritage     2     2     4  
Asian-East Asian Heritage     6     4     10  
Asian-South East Asian Heritage     1     0     1  
Native Hawaiian or Other Pacific Islander     1     0     1  
White-Arabic/North African Heritage     3     3     6  
White-White/Caucasian/European Heritage     175     172     347  
Mixed Race     12     2     14  
Unknown     1     1     2  
[1] Baseline Characteristic data are reported for members of the modified Intent-To-Treat Exposed Population, all randomized participants who received at least one dose of IP excluding four participants at one site, which was closed due to Good Clinical Practice (GCP) non-compliance issues in another ViiV sponsored trial.



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Percentage of Participants With HIV-1 RNA <50 Copies/Milliliter (c/mL) at Week 48   [ Time Frame: Week 48 ]

2.  Secondary:   Number of Participants (Par.) With Detectable Virus That Has Genotypic or Phenotypic Evidence of Treatment-emergent INI Resistance at Time of Protocol Defined Virology Failure (PDVF)   [ Time Frame: Baseline until PDVF up to Week 48 ]

3.  Secondary:   Number of Participants With Plasma HIV-1 RNA <50 c/mL at Week 24   [ Time Frame: Week 24 ]

4.  Secondary:   Number of Participants With Plasma HIV-1 RNA <400 c/mL at Week 24 and Week 48   [ Time Frame: Week 24, Week 48 ]

5.  Secondary:   Absolute Values and Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at Weeks 4, 8, 12, 16, 24, 32, 40, and 48   [ Time Frame: Baseline; Weeks 4, 8, 12, 16, 24, 32, 40, and 48 ]

6.  Secondary:   Number of Participants With Indicated Post-Baseline HIV-associated Conditions, Excluding Recurrences, and Disease Progressions   [ Time Frame: From Baseline (Day 1) until Week 48 ]

7.  Secondary:   Number of Participants With the Indicated Post-Baseline Emergent Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs)   [ Time Frame: From Baseline until Week 48, including participants with post-treatment events occurring after Week 48 for participants not entering the post-Week 48 Open-Label phase of the study ]

8.  Secondary:   DTG PK Parameters Including Cmax, Cmin, C0, and C0_avg   [ Time Frame: Week 4, Week 24, and Week 48 ]

9.  Secondary:   DTG PK Parameters Including AUC(0-tau)   [ Time Frame: Week 4, Week 24, and Week 48 ]

10.  Other Pre-specified:   Absolute Values and Change From Baseline in Cluster of Differentiation 8+ (CD8+) Cell Counts at Weeks 4, 8, 12, 16, 24, 32, 40, and 48   [ Time Frame: Baseline; Weeks 4, 8, 12, 16, 24, 32, 40, and 48 ]


  Serious Adverse Events
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Time Frame Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the randomized treatment period (up to Week 48).
Additional Description SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who received at least one dose of investigational product. Also included are post-treatment events occurring after Week 48 for participants not entering the post-Week 48 Open-Label phase of the study.

Reporting Groups
  Description
DTG 50 mg OD Participants received dolutegravir (DTG) 50 milligrams (mg) once daily (OD) + matching Raltegravir (RAL) placebo twice daily (BID), one in the morning (AM dose) and one in the evening (PM dose) + investigator selected background antiretroviral (ART) therapy for 48 weeks. Participants who successfully completed 48 weeks of treatment continued to have access to DTG in the Open-Label phase of the study.
RAL 400 mg BID Participants received matching DTG placebo OD + RAL 400 mg BID as AM and PM doses + investigator selected background ART therapy for 48 weeks. Participants were discontinued from the study after completion of the Week 48 visit unless a participant successfully completed Week 48 and RAL was not approved and commercially available within the country, GSK continued to supply RAL in the Open-Label Phase until it was commercially available.

Serious Adverse Events
    DTG 50 mg OD     RAL 400 mg BID  
Total, serious adverse events      
# participants affected / at risk     33/357 (9.24%)     42/362 (11.60%)  
Blood and lymphatic system disorders      
Anaemia † 1    
# participants affected / at risk     0/357 (0.00%)     2/362 (0.55%)  
Coagulation factor deficiency † 1    
# participants affected / at risk     0/357 (0.00%)     1/362 (0.28%)  
Disseminated intravascular coagulation † 1    
# participants affected / at risk     1/357 (0.28%)     0/362 (0.00%)  
Methaemoglobinaemia † 1    
# participants affected / at risk     1/357 (0.28%)     0/362 (0.00%)  
Cardiac disorders      
Angina pectoris † 1    
# participants affected / at risk     1/357 (0.28%)     0/362 (0.00%)  
Cardiomyopathy † 1    
# participants affected / at risk     0/357 (0.00%)     1/362 (0.28%)  
Coronary artery disease † 1    
# participants affected / at risk     0/357 (0.00%)     1/362 (0.28%)  
Eye disorders      
Iridocyclitis † 1    
# participants affected / at risk     0/357 (0.00%)     1/362 (0.28%)  
Gastrointestinal disorders      
Pancreatitis † 1    
# participants affected / at risk     2/357 (0.56%)     1/362 (0.28%)  
Abdominal pain † 1    
# participants affected / at risk     1/357 (0.28%)     0/362 (0.00%)  
Anal ulcer † 1    
# participants affected / at risk     0/357 (0.00%)     1/362 (0.28%)  
Intestinal obstruction † 1    
# participants affected / at risk     0/357 (0.00%)     1/362 (0.28%)  
Oral mucosal blistering † 1    
# participants affected / at risk     0/357 (0.00%)     1/362 (0.28%)  
Pancreatitis acute † 1    
# participants affected / at risk     0/357 (0.00%)     1/362 (0.28%)  
Pancreatitis relapsing † 1    
# participants affected / at risk     1/357 (0.28%)     0/362 (0.00%)  
Rectal haemorrhage † 1    
# participants affected / at risk     1/357 (0.28%)     0/362 (0.00%)  
Small intestine obstruction † 1    
# participants affected / at risk     0/357 (0.00%)     1/362 (0.28%)  
General disorders      
Non-cardiac chest pain † 1    
# participants affected / at risk     0/357 (0.00%)     1/362 (0.28%)  
Pyrexia † 1    
# participants affected / at risk     1/357 (0.28%)     0/362 (0.00%)  
Hepatobiliary disorders      
Hepatitis † 1    
# participants affected / at risk     2/357 (0.56%)     1/362 (0.28%)  
Hepatotoxicity † 1    
# participants affected / at risk     1/357 (0.28%)     1/362 (0.28%)  
Acute hepatic failure † 1    
# participants affected / at risk     0/357 (0.00%)     1/362 (0.28%)  
Liver disorder † 1    
# participants affected / at risk     1/357 (0.28%)     0/362 (0.00%)  
Immune system disorders      
Immune reconstitution inflammatory syndrome † 1    
# participants affected / at risk     1/357 (0.28%)     0/362 (0.00%)  
Sarcoidosis † 1    
# participants affected / at risk     0/357 (0.00%)     1/362 (0.28%)  
Infections and infestations      
Pneumonia † 1    
# participants affected / at risk     2/357 (0.56%)     4/362 (1.10%)  
Gastroenteritis † 1    
# participants affected / at risk     1/357 (0.28%)     1/362 (0.28%)  
Postoperative wound infection † 1    
# participants affected / at risk     0/357 (0.00%)     2/362 (0.55%)  
Anal abscess † 1    
# participants affected / at risk     0/357 (0.00%)     1/362 (0.28%)  
Bronchitis † 1    
# participants affected / at risk     1/357 (0.28%)     0/362 (0.00%)  
Bronchopneumonia † 1    
# participants affected / at risk     0/357 (0.00%)     1/362 (0.28%)  
Cellulitis † 1    
# participants affected / at risk     0/357 (0.00%)     1/362 (0.28%)  
Cytomegalovirus oesophagitis † 1    
# participants affected / at risk     0/357 (0.00%)     1/362 (0.28%)  
Disseminated tuberculosis † 1    
# participants affected / at risk     0/357 (0.00%)     1/362 (0.28%)  
Extrapulmonary tuberculosis † 1    
# participants affected / at risk     0/357 (0.00%)     1/362 (0.28%)  
Gangrene † 1    
# participants affected / at risk     0/357 (0.00%)     1/362 (0.28%)  
Gas gangrene † 1    
# participants affected / at risk     0/357 (0.00%)     1/362 (0.28%)  
Gastroenteritis viral † 1    
# participants affected / at risk     1/357 (0.28%)     0/362 (0.00%)  
Genital herpes † 1    
# participants affected / at risk     0/357 (0.00%)     1/362 (0.28%)  
Histoplasmosis disseminated † 1    
# participants affected / at risk     1/357 (0.28%)     0/362 (0.00%)  
Infection † 1    
# participants affected / at risk     0/357 (0.00%)     1/362 (0.28%)  
Infective myositis † 1    
# participants affected / at risk     0/357 (0.00%)     1/362 (0.28%)  
Intervertebral discitis † 1    
# participants affected / at risk     0/357 (0.00%)     1/362 (0.28%)  
Joint abscess † 1    
# participants affected / at risk     1/357 (0.28%)     0/362 (0.00%)  
Legionella infection † 1    
# participants affected / at risk     1/357 (0.28%)     0/362 (0.00%)  
Lower respiratory tract infection † 1    
# participants affected / at risk     1/357 (0.28%)     0/362 (0.00%)  
Orchitis † 1    
# participants affected / at risk     0/357 (0.00%)     1/362 (0.28%)  
Parvovirus infection † 1    
# participants affected / at risk     1/357 (0.28%)     0/362 (0.00%)  
Pneumonia staphylococcal † 1    
# participants affected / at risk     0/357 (0.00%)     1/362 (0.28%)  
Pneumonia viral † 1    
# participants affected / at risk     1/357 (0.28%)     0/362 (0.00%)  
Progressive multifocal leukoencephalopathy † 1    
# participants affected / at risk     0/357 (0.00%)     1/362 (0.28%)  
Subcutaneous abscess † 1    
# participants affected / at risk     0/357 (0.00%)     1/362 (0.28%)  
Toxoplasmosis † 1    
# participants affected / at risk     1/357 (0.28%)     0/362 (0.00%)  
Tuberculosis liver † 1    
# participants affected / at risk     1/357 (0.28%)     0/362 (0.00%)  
Wound infection † 1    
# participants affected / at risk     0/357 (0.00%)     1/362 (0.28%)  
Wound infection staphylococcal † 1    
# participants affected / at risk     0/357 (0.00%)     1/362 (0.28%)  
Injury, poisoning and procedural complications      
Alcohol poisoning † 1    
# participants affected / at risk     1/357 (0.28%)     0/362 (0.00%)  
Fibula fracture † 1    
# participants affected / at risk     1/357 (0.28%)     0/362 (0.00%)  
Overdose † 1    
# participants affected / at risk     1/357 (0.28%)     0/362 (0.00%)  
Upper limb fracture † 1    
# participants affected / at risk     1/357 (0.28%)     0/362 (0.00%)  
Investigations      
Blood alkaline phosphatase increased † 1    
# participants affected / at risk     0/357 (0.00%)     1/362 (0.28%)  
Metabolism and nutrition disorders      
Dehydration † 1    
# participants affected / at risk     0/357 (0.00%)     2/362 (0.55%)  
Hyperglycaemia † 1    
# participants affected / at risk     0/357 (0.00%)     1/362 (0.28%)  
Hyperkalaemia † 1    
# participants affected / at risk     1/357 (0.28%)     0/362 (0.00%)  
Lactic acidosis † 1    
# participants affected / at risk     0/357 (0.00%)     1/362 (0.28%)  
Musculoskeletal and connective tissue disorders      
Rhabdomyolysis † 1    
# participants affected / at risk     2/357 (0.56%)     0/362 (0.00%)  
Arthritis † 1    
# participants affected / at risk     0/357 (0.00%)     1/362 (0.28%)  
Back pain † 1    
# participants affected / at risk     1/357 (0.28%)     0/362 (0.00%)  
Intervertebral disc protrusion † 1    
# participants affected / at risk     0/357 (0.00%)     1/362 (0.28%)  
Myositis † 1    
# participants affected / at risk     1/357 (0.28%)     0/362 (0.00%)  
Neoplasms benign, malignant and unspecified (incl cysts and polyps)      
Adenocarcinoma † 1    
# participants affected / at risk     0/357 (0.00%)     1/362 (0.28%)  
Cervix carcinoma † 1    
# participants affected / at risk     0/357 (0.00%)     1/362 (0.28%)  
Immunoblastic lymphoma † 1    
# participants affected / at risk     0/357 (0.00%)     1/362 (0.28%)  
Metastatic neoplasm † 1    
# participants affected / at risk     1/357 (0.28%)     0/362 (0.00%)  
Vulval neoplasm † 1    
# participants affected / at risk     0/357 (0.00%)     1/362 (0.28%)  
Nervous system disorders      
Cerebrovascular accident † 1    
# participants affected / at risk     0/357 (0.00%)     2/362 (0.55%)  
Cerebrovascular disorder † 1    
# participants affected / at risk     1/357 (0.28%)     0/362 (0.00%)  
Headache † 1    
# participants affected / at risk     0/357 (0.00%)     1/362 (0.28%)  
Psychiatric disorders      
Suicidal ideation † 1    
# participants affected / at risk     4/357 (1.12%)     1/362 (0.28%)  
Alcohol withdrawal syndrome † 1    
# participants affected / at risk     2/357 (0.56%)     0/362 (0.00%)  
Depression † 1    
# participants affected / at risk     2/357 (0.56%)     0/362 (0.00%)  
Mental status changes † 1    
# participants affected / at risk     1/357 (0.28%)     1/362 (0.28%)  
Suicide attempt † 1    
# participants affected / at risk     2/357 (0.56%)     0/362 (0.00%)  
Alcohol abuse † 1    
# participants affected / at risk     1/357 (0.28%)     0/362 (0.00%)  
Anxiety † 1    
# participants affected / at risk     0/357 (0.00%)     1/362 (0.28%)  
Depression suicidal † 1    
# participants affected / at risk     0/357 (0.00%)     1/362 (0.28%)  
Substance abuse † 1    
# participants affected / at risk     0/357 (0.00%)     1/362 (0.28%)  
Renal and urinary disorders      
Renal failure acute † 1    
# participants affected / at risk     2/357 (0.56%)     1/362 (0.28%)  
Nephrolithiasis † 1    
# participants affected / at risk     1/357 (0.28%)     0/362 (0.00%)  
Reproductive system and breast disorders      
Cervical dysplasia † 1    
# participants affected / at risk     0/357 (0.00%)     1/362 (0.28%)  
Uterine haemorrhage † 1    
# participants affected / at risk     0/357 (0.00%)     1/362 (0.28%)  
Respiratory, thoracic and mediastinal disorders      
Alveolar proteinosis † 1    
# participants affected / at risk     0/357 (0.00%)     1/362 (0.28%)  
Dyspnoea † 1    
# participants affected / at risk     0/357 (0.00%)     1/362 (0.28%)  
Epistaxis † 1    
# participants affected / at risk     0/357 (0.00%)     1/362 (0.28%)  
Respiratory distress † 1    
# participants affected / at risk     1/357 (0.28%)     0/362 (0.00%)  
Sinus disorder † 1    
# participants affected / at risk     0/357 (0.00%)     1/362 (0.28%)  
Skin and subcutaneous tissue disorders      
Rash pruritic † 1    
# participants affected / at risk     0/357 (0.00%)     1/362 (0.28%)  
Vascular disorders      
Aortic arteriosclerosis † 1    
# participants affected / at risk     0/357 (0.00%)     1/362 (0.28%)  
Arteriosclerosis † 1    
# participants affected / at risk     0/357 (0.00%)     1/362 (0.28%)  
Hypertension † 1    
# participants affected / at risk     0/357 (0.00%)     1/362 (0.28%)  
Malignant hypertension † 1    
# participants affected / at risk     0/357 (0.00%)     1/362 (0.28%)  
Peripheral arterial † 1    
# participants affected / at risk     0/357 (0.00%)     1/362 (0.28%)  
Occlusive disease † 1    
# participants affected / at risk     0/357 (0.00%)     1/362 (0.28%)  
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA




  Other Adverse Events


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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.  


Results Point of Contact:  
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
phone: 866-435-7343


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Publications automatically indexed to this study:

Responsible Party: ViiV Healthcare
ClinicalTrials.gov Identifier: NCT01231516     History of Changes
Other Study ID Numbers: 111762
Study First Received: October 21, 2010
Results First Received: August 15, 2013
Last Updated: March 20, 2014
Health Authority: Spain: Agencia Española del Medicamento y Productos Sanitarios
Argentina: Ministry of Health - A.N.M.A.T
Italy: Comitato Etico Fondazione Centro San Raffaele del Monte Tabor - Via Olgettina, 60 - 20132 Milano
Brazil: National Health Surveillance Agency
Chile:Ministerio de Salud de Chile
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Belgium: Federal Agency for Medicines and Health Products, FAMHP
United States: Food and Drug Administration
Taiwan: Department of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Hungary: Országos Gyógyszerészeti Intézet
South Africa: Medicines Control Council
Romania: National Medicines Agency
Russia: Roszdrav Nadzor
France: Agence Française de Sécurité Sanitaire des Produits de Santé
Canada: Health Canada
Mexico: COFEPRIS
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Australia: Therapeutic Goods Administration
Greece: National Drug Organisation