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Study of Lopinavir/Ritonavir Tablets Versus Soft Gel Capsules and Once Daily Versus Twice Daily Administration, When Coadministered With Nucleoside Reverse Transcriptase Inhibitors in Antiretroviral Naive Human Immunodeficiency Virus Type 1 Infected Subjects

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Abbott
ClinicalTrials.gov Identifier:
NCT00262522
First received: December 5, 2005
Last updated: February 3, 2012
Last verified: February 2012
Results First Received: July 9, 2009  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Human Immunodeficiency Virus Infections
Intervention: Drug: lopinavir/ritonavir (LPV/r) (tablet or capsule) with nucleoside reverse transcriptase inhibitors (NRTIs)

  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
Subjects were enrolled at 131 sites in 19 countries.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Of the 672 subjects randomized, 8 discontinued from the study prior to receiving study drug due to withdrawal of consent (3), acute illness (2), lost to follow-up (1), other (1), and required prohibited medication (1).

Reporting Groups
  Description
LPV/r 800/200 mg QD Tablet lopinavir/ritonavir 800/200 mg once daily (QD) tablet
LPV/r 800/200 mg QD SGC (Through Week 8) lopinavir/ritonavir 800/200 mg once daily (QD) soft gel capsule (SGC)
LPV/r 400/100 mg BID Tablet lopinavir/ritonavir 400/100 mg twice daily (BID) tablet
LPV/r 400/100 mg BID SGC (Through Week 8) lopinavir/ritonavir 400/100 mg twice daily (BID) soft gel capsule (SGC)

Participant Flow for 3 periods

Period 1:   Study Start Through 8 Weeks
    LPV/r 800/200 mg QD Tablet   LPV/r 800/200 mg QD SGC (Through Week 8)   LPV/r 400/100 mg BID Tablet   LPV/r 400/100 mg BID SGC (Through Week 8)
STARTED   167   166   166   165 
COMPLETED   163   161   155   160 
NOT COMPLETED   4   5   11   5 
Adverse Event                1                2                3                1 
Withdrawal by Subject                1                1                3                0 
Lost to Follow-up                1                2                3                2 
Noncompliance                0                0                2                2 
Death                1                0                0                0 

Period 2:   Study Start Through 48 Weeks
    LPV/r 800/200 mg QD Tablet   LPV/r 800/200 mg QD SGC (Through Week 8)   LPV/r 400/100 mg BID Tablet   LPV/r 400/100 mg BID SGC (Through Week 8)
STARTED   333 [1]   0 [2]   331 [1]   0 [3] 
COMPLETED   284   0   276   0 
NOT COMPLETED   49   0   55   0 
Adverse Event                16                0                10                0 
Withdrawal by Subject                10                0                11                0 
Lost to Follow-up                8                0                14                0 
Noncompliance                3                0                8                0 
Death                2                0                1                0 
Virologic failure                2                0                4                0 
Relocated, Needed to take twice daily                8                0                7                0 
[1] Number of subjects who started the study, not the number who completed the first 8 weeks.
[2] After Week 8, these subjects received the tablet formulation once daily through the end of study.
[3] After Week 8, these subjects received the tablet formulation twice daily through the end of study.

Period 3:   Study Start Through 96 Weeks
    LPV/r 800/200 mg QD Tablet   LPV/r 800/200 mg QD SGC (Through Week 8)   LPV/r 400/100 mg BID Tablet   LPV/r 400/100 mg BID SGC (Through Week 8)
STARTED   333 [1]   0 [2]   331 [1]   0 [3] 
COMPLETED   256   0   254   0 
NOT COMPLETED   77   0   77   0 
Adverse Event                20                0                16                0 
Withdrawal by Subject                15                0                13                0 
Lost to Follow-up                19                0                18                0 
Noncompliance                6                0                11                0 
Death                2                0                2                0 
Virologic failure                5                0                8                0 
Relocated, Needed to take twice daily                10                0                9                0 
[1] Number of subjects who started the study, not the number who completed the first 48 weeks.
[2] After Week 8, these subjects received the tablet formulation once daily through the end of study.
[3] After Week 8, these subjects received the tablet formulation twice daily through the end of study.



  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
LPV/r 800/200 mg QD Tablet lopinavir/ritonavir 800/200 mg once daily (QD) tablet
LPV/r 800/200 mg QD SGC (Through Week 8) lopinavir/ritonavir 800/200 mg once daily (QD) soft gel capsule (SGC)
LPV/r 400/100 mg BID Tablet lopinavir/ritonavir 400/100 mg twice daily (BID) tablet
LPV/r 400/100 mg BID SGC (Through Week 8) lopinavir/ritonavir 400/100 mg twice daily (BID) soft gel capsule (SGC)
Total Total of all reporting groups

Baseline Measures
   LPV/r 800/200 mg QD Tablet   LPV/r 800/200 mg QD SGC (Through Week 8)   LPV/r 400/100 mg BID Tablet   LPV/r 400/100 mg BID SGC (Through Week 8)   Total 
Overall Participants Analyzed 
[Units: Participants]
 167   166   166   165   664 
Age 
[Units: Years]
Mean (Standard Deviation)
 38.7  (9.80)   38.2  (9.63)   38.3  (9.69)   39.5  (10.31)   38.7  (9.85) 
Gender 
[Units: Participants]
         
Female   36   31   39   38   144 
Male   131   135   127   127   520 
CD4+ T Cell Count [1] 
[Units: Cells/mm3]
Mean (Standard Deviation)
 209.9  (125.10)   222.6  (127.37)   226.4  (136.64)   202.9  (139.57)   215.5  (132.34) 
[1] For once daily (QD) soft gel capsule (SGC), N=165.
Plasma HIV-1 RNA Level 
[Units: Log10 copies/mL]
Mean (Standard Deviation)
 4.92  (0.64)   4.94  (0.67)   5.04  (0.68)   5.06  (0.64)   4.99  (0.66) 


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Percentage of Subjects With Adverse Events of Diarrhea During the First 8 Weeks   [ Time Frame: Week 8 ]

2.  Primary:   Percentage of Subjects With Plasma Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) Levels < 50 Copies/mL at Week 48   [ Time Frame: Week 48 ]

3.  Secondary:   Percentage of Subjects With Plasma Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) Levels < 50 Copies/mL at Week 96   [ Time Frame: Week 96 (End of Study) ]

4.  Secondary:   Mean Change From Baseline to Week 96 in CD4+ T Cell Counts   [ Time Frame: Week 96 (End of Study) ]


  Serious Adverse Events
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Time Frame No text entered.
Additional Description No text entered.

Reporting Groups
  Description
LPV/r 800/200 mg QD Tablet lopinavir/ritonavir 800/200 mg once daily (QD) tablet
LPV/r 400/100 mg BID Tablet lopinavir/ritonavir 400/100 mg twice daily (BID) tablet

Serious Adverse Events
    LPV/r 800/200 mg QD Tablet   LPV/r 400/100 mg BID Tablet
Total, serious adverse events     
# participants affected / at risk   37/333 (11.11%)   50/331 (15.11%) 
Blood and lymphatic system disorders     
Anemia † 1     
# participants affected / at risk   1/333 (0.30%)   0/331 (0.00%) 
Febrile neutropenia † 1     
# participants affected / at risk   0/333 (0.00%)   1/331 (0.30%) 
Lymphadenopathy † 1     
# participants affected / at risk   0/333 (0.00%)   1/331 (0.30%) 
Lymphatic disorder † 1     
# participants affected / at risk   1/333 (0.30%)   0/331 (0.00%) 
Neutropenia † 1     
# participants affected / at risk   0/333 (0.00%)   2/331 (0.60%) 
Cardiac disorders     
Atrioventricular block † 1     
# participants affected / at risk   0/333 (0.00%)   1/331 (0.30%) 
Cardiac failure † 1     
# participants affected / at risk   0/333 (0.00%)   1/331 (0.30%) 
Palpitations † 1     
# participants affected / at risk   1/333 (0.30%)   0/331 (0.00%) 
Endocrine disorders     
Cushing's syndrome † 1     
# participants affected / at risk   1/333 (0.30%)   0/331 (0.00%) 
Hypothyroidism † 1     
# participants affected / at risk   1/333 (0.30%)   0/331 (0.00%) 
Gastrointestinal disorders     
Abdominal discomfort † 1     
# participants affected / at risk   0/333 (0.00%)   1/331 (0.30%) 
Abdominal pain † 1     
# participants affected / at risk   0/333 (0.00%)   2/331 (0.60%) 
Appendicitis perforated † 1     
# participants affected / at risk   1/333 (0.30%)   0/331 (0.00%) 
Diarrhea † 1     
# participants affected / at risk   0/333 (0.00%)   1/331 (0.30%) 
Enterocolitis † 1     
# participants affected / at risk   1/333 (0.30%)   1/331 (0.30%) 
Food poisoning † 1     
# participants affected / at risk   0/333 (0.00%)   1/331 (0.30%) 
Gastrointestinal obstruction † 1     
# participants affected / at risk   0/333 (0.00%)   1/331 (0.30%) 
Inguinal hernia † 1     
# participants affected / at risk   1/333 (0.30%)   0/331 (0.00%) 
Intestinal obstruction † 1     
# participants affected / at risk   0/333 (0.00%)   1/331 (0.30%) 
Nausea † 1     
# participants affected / at risk   0/333 (0.00%)   2/331 (0.60%) 
Esophagitis † 1     
# participants affected / at risk   1/333 (0.30%)   0/331 (0.00%) 
Peritonitis † 1     
# participants affected / at risk   1/333 (0.30%)   0/331 (0.00%) 
Small intestinal obstruction † 1     
# participants affected / at risk   1/333 (0.30%)   0/331 (0.00%) 
Umbilical hernia † 1     
# participants affected / at risk   0/333 (0.00%)   1/331 (0.30%) 
General disorders     
Chills † 1     
# participants affected / at risk   0/333 (0.00%)   1/331 (0.30%) 
Death † 1     
# participants affected / at risk   0/333 (0.00%)   2/331 (0.60%) 
Malaise † 1     
# participants affected / at risk   0/333 (0.00%)   1/331 (0.30%) 
Pyrexia † 1     
# participants affected / at risk   2/333 (0.60%)   6/331 (1.81%) 
Hepatobiliary disorders     
Cholangitis † 1     
# participants affected / at risk   0/333 (0.00%)   1/331 (0.30%) 
Cholelithiasis † 1     
# participants affected / at risk   0/333 (0.00%)   1/331 (0.30%) 
Cytolytic hepatitis † 1     
# participants affected / at risk   1/333 (0.30%)   0/331 (0.00%) 
Immune system disorders     
Hypersensitivity † 1     
# participants affected / at risk   1/333 (0.30%)   0/331 (0.00%) 
Immune reconstitution syndrome † 1     
# participants affected / at risk   0/333 (0.00%)   1/331 (0.30%) 
Infections and infestations     
Abdominal infection † 1     
# participants affected / at risk   1/333 (0.30%)   0/331 (0.00%) 
Anogenital warts † 1     
# participants affected / at risk   0/333 (0.00%)   1/331 (0.30%) 
Appendicitis † 1     
# participants affected / at risk   1/333 (0.30%)   1/331 (0.30%) 
Bronchopneumonia † 1     
# participants affected / at risk   0/333 (0.00%)   1/331 (0.30%) 
Cellulitis † 1     
# participants affected / at risk   1/333 (0.30%)   1/331 (0.30%) 
Clostridium difficile colitis † 1     
# participants affected / at risk   0/333 (0.00%)   1/331 (0.30%) 
Gangrene † 1     
# participants affected / at risk   0/333 (0.00%)   1/331 (0.30%) 
Gastroenteritis † 1     
# participants affected / at risk   1/333 (0.30%)   1/331 (0.30%) 
Infected skin ulcer † 1     
# participants affected / at risk   0/333 (0.00%)   1/331 (0.30%) 
Influenza † 1     
# participants affected / at risk   1/333 (0.30%)   0/331 (0.00%) 
Lower respiratory tract infection † 1     
# participants affected / at risk   1/333 (0.30%)   0/331 (0.00%) 
Malaria † 1     
# participants affected / at risk   0/333 (0.00%)   1/331 (0.30%) 
Meningitis † 1     
# participants affected / at risk   1/333 (0.30%)   0/331 (0.00%) 
Meningitis tuberculous † 1     
# participants affected / at risk   1/333 (0.30%)   0/331 (0.00%) 
Perichondritis † 1     
# participants affected / at risk   1/333 (0.30%)   0/331 (0.00%) 
Pneumonia † 1     
# participants affected / at risk   2/333 (0.60%)   1/331 (0.30%) 
Pneumonia bacterial † 1     
# participants affected / at risk   0/333 (0.00%)   1/331 (0.30%) 
Pyelonephritis † 1     
# participants affected / at risk   0/333 (0.00%)   2/331 (0.60%) 
Rectal abscess † 1     
# participants affected / at risk   1/333 (0.30%)   0/331 (0.00%) 
Respiratory tract infection † 1     
# participants affected / at risk   2/333 (0.60%)   1/331 (0.30%) 
Sepsis † 1     
# participants affected / at risk   0/333 (0.00%)   1/331 (0.30%) 
Sinusitis † 1     
# participants affected / at risk   1/333 (0.30%)   0/331 (0.00%) 
Syphilis † 1     
# participants affected / at risk   1/333 (0.30%)   2/331 (0.60%) 
Typhoid fever † 1     
# participants affected / at risk   0/333 (0.00%)   1/331 (0.30%) 
Viral infection † 1     
# participants affected / at risk   0/333 (0.00%)   1/331 (0.30%) 
Injury, poisoning and procedural complications     
Anastomotic ulcer † 1     
# participants affected / at risk   0/333 (0.00%)   1/331 (0.30%) 
Back injury † 1     
# participants affected / at risk   0/333 (0.00%)   1/331 (0.30%) 
Facial bones fracture † 1     
# participants affected / at risk   1/333 (0.30%)   0/331 (0.00%) 
Meniscus lesion † 1     
# participants affected / at risk   0/333 (0.00%)   1/331 (0.30%) 
Traumatic fracture † 1     
# participants affected / at risk   1/333 (0.30%)   0/331 (0.00%) 
Investigations     
Blood urine present † 1     
# participants affected / at risk   0/333 (0.00%)   1/331 (0.30%) 
Creatinine renal clearance decreased † 1     
# participants affected / at risk   1/333 (0.30%)   0/331 (0.00%) 
Neutrophil count decreased † 1     
# participants affected / at risk   1/333 (0.30%)   0/331 (0.00%) 
Metabolism and nutrition disorders     
Anorexia † 1     
# participants affected / at risk   1/333 (0.30%)   0/331 (0.00%) 
Dehydration † 1     
# participants affected / at risk   1/333 (0.30%)   2/331 (0.60%) 
Hypokalemia † 1     
# participants affected / at risk   0/333 (0.00%)   1/331 (0.30%) 
Musculoskeletal and connective tissue disorders     
Intervertebral disc degeneration † 1     
# participants affected / at risk   1/333 (0.30%)   0/331 (0.00%) 
Myalgia † 1     
# participants affected / at risk   0/333 (0.00%)   1/331 (0.30%) 
Rhabdomyolysis † 1     
# participants affected / at risk   0/333 (0.00%)   2/331 (0.60%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Hepatic adenoma † 1     
# participants affected / at risk   0/333 (0.00%)   1/331 (0.30%) 
Non-Hodgkin's lymphoma † 1     
# participants affected / at risk   1/333 (0.30%)   0/331 (0.00%) 
Non-Hodgkin's lymphoma recurrent † 1     
# participants affected / at risk   1/333 (0.30%)   0/331 (0.00%) 
Squamous cell carcinoma † 1     
# participants affected / at risk   0/333 (0.00%)   1/331 (0.30%) 
Uterine leiomyoma † 1     
# participants affected / at risk   0/333 (0.00%)   1/331 (0.30%) 
Nervous system disorders     
Convulsion † 1     
# participants affected / at risk   1/333 (0.30%)   0/331 (0.00%) 
Dizziness † 1     
# participants affected / at risk   1/333 (0.30%)   1/331 (0.30%) 
Grand mal convulsion † 1     
# participants affected / at risk   0/333 (0.00%)   1/331 (0.30%) 
Loss of consciousness † 1     
# participants affected / at risk   0/333 (0.00%)   1/331 (0.30%) 
Reversible ischemic neurological deficit † 1     
# participants affected / at risk   0/333 (0.00%)   1/331 (0.30%) 
Subarachnoid hemorrhage † 1     
# participants affected / at risk   0/333 (0.00%)   1/331 (0.30%) 
Panic attack † 1     
# participants affected / at risk   0/333 (0.00%)   1/331 (0.30%) 
Psychotic disorder † 1     
# participants affected / at risk   0/333 (0.00%)   1/331 (0.30%) 
Pregnancy, puerperium and perinatal conditions     
Abortion spontaneous † 1     
# participants affected / at risk   0/333 (0.00%)   2/331 (0.60%) 
Blighted ovum † 1     
# participants affected / at risk   1/333 (0.30%)   0/331 (0.00%) 
Premature separation of placenta † 1     
# participants affected / at risk   0/333 (0.00%)   1/331 (0.30%) 
Depression † 1     
# participants affected / at risk   1/333 (0.30%)   1/331 (0.30%) 
Psychiatric disorders     
Drug dependence † 1     
# participants affected / at risk   1/333 (0.30%)   0/331 (0.00%) 
Suicide attempt † 1     
# participants affected / at risk   0/333 (0.00%)   1/331 (0.30%) 
Renal and urinary disorders     
Calculus ureteric † 1     
# participants affected / at risk   1/333 (0.30%)   0/331 (0.00%) 
Hydronephrosis † 1     
# participants affected / at risk   1/333 (0.30%)   0/331 (0.00%) 
Renal failure † 1     
# participants affected / at risk   0/333 (0.00%)   1/331 (0.30%) 
Renal failure acute † 1     
# participants affected / at risk   1/333 (0.30%)   0/331 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Asthma † 1     
# participants affected / at risk   1/333 (0.30%)   0/331 (0.00%) 
Dyspnea † 1     
# participants affected / at risk   1/333 (0.30%)   0/331 (0.00%) 
Pleuritic pain † 1     
# participants affected / at risk   1/333 (0.30%)   0/331 (0.00%) 
Pulmonary embolism † 1     
# participants affected / at risk   1/333 (0.30%)   1/331 (0.30%) 
Sinus congestion † 1     
# participants affected / at risk   1/333 (0.30%)   0/331 (0.00%) 
Skin and subcutaneous tissue disorders     
Dermatitis allergic † 1     
# participants affected / at risk   0/333 (0.00%)   1/331 (0.30%) 
Erythema multiform † 1     
# participants affected / at risk   1/333 (0.30%)   0/331 (0.00%) 
Granuloma skin † 1     
# participants affected / at risk   1/333 (0.30%)   0/331 (0.00%) 
Hyperhidrosis † 1     
# participants affected / at risk   0/333 (0.00%)   1/331 (0.30%) 
Idiopathic capillaritis † 1     
# participants affected / at risk   0/333 (0.00%)   1/331 (0.30%) 
Surgical and medical procedures     
Abortion induced † 1     
# participants affected / at risk   2/333 (0.60%)   4/331 (1.21%) 
Vascular disorders     
Deep vein thrombosis † 1     
# participants affected / at risk   0/333 (0.00%)   1/331 (0.30%) 
Hypotension † 1     
# participants affected / at risk   0/333 (0.00%)   1/331 (0.30%) 
Jugular vein thrombosis † 1     
# participants affected / at risk   0/333 (0.00%)   1/331 (0.30%) 
Subclavian vein thrombosis † 1     
# participants affected / at risk   0/333 (0.00%)   1/331 (0.30%) 
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA 11.0




  Other Adverse Events


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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
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