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

History of Changes

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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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
Number of Participants [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
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

[1]	For once daily (QD) soft gel capsule (SGC), N=165.

Outcome Measures

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1. Primary:

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

Show Outcome Measure 1

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 ]

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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) ]

Show Outcome Measure 3

4. Secondary:

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

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Serious Adverse Events

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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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More Information

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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:

	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.
	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.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: Provide ABBOTT at least thirty (30) days prior to submission for review, ABBOTT shall return comments within thirty (30) days of receipt of draft. Proposed draft shall be delayed an additional sixty (60) days in addition to the Review Period

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
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Results Point of Contact:

Name/Title: Global Medical Services
Organization: Abbott
phone: 800-633-9110

No publications provided

Responsible Party:	Abbott
ClinicalTrials.gov Identifier:	NCT00262522 History of Changes
Other Study ID Numbers:	M05-730, 2005-001430-32
Study First Received:	December 5, 2005
Results First Received:	July 9, 2009
Last Updated:	February 3, 2012
Health Authority:	Australia: Department of Health and Ageing Therapeutic Goods Administration Belgium: Ministry of Social Affairs, Public Health and the Environment Canada: Health Canada Czech Republic: State Institute for Drug Control France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis) Germany: Federal Institute for Drugs and Medical Devices Greece: National Organization of Medicines Ireland: Irish Medicines Board Italy: The Italian Medicines Agency Netherlands: Medicines Evaluation Board (MEB) Poland: Ministry of Health Russia: Ministry of Health of the Russian Federation Singapore: Health Sciences Authority Spain: Spanish Agency of Medicines Switzerland: Swissmedic Taiwan : Food and Drug Administration United Kingdom: Medicines and Healthcare Products Regulatory Agency United States: Food and Drug Administration

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