Trial Outcomes & Findings for Study of Lopinavir/Ritonavir Tablets Comparing Once-Daily Versus Twice-Daily Administration When Coadministered With Nucleoside/Nucleotide Reverse Transcriptase Inhibitors in Antiretroviral-Experienced Human Immunodeficiency Virus Type 1 Infected Subjects (NCT NCT00358917)
NCT ID: NCT00358917
Last Updated: 2011-04-11
Results Overview
A participant was classified as a responder at the first of 2 consecutive human immunodeficiency virus type 1 (HIV-1) ribonucleic acid (RNA) levels \<50 copies/mL. The participant continued to be a responder until 2 consecutive values \>=50 copies/mL were reached, until the final value if that value was \>=50 copies/mL, or until discontinuation or death.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
599 participants
Primary outcome timeframe
Week 48 (End of Study)
Results posted on
2011-04-11
Participant Flow
Participant milestones
| Measure |
LPV/r 800/200 mg QD Tablet
lopinavir/ritonavir 800/200 milligram (mg) once daily (QD) tablet
|
LPV/r 400/100 mg BID Tablet
lopinavir/ritonavir 400/100 milligram (mg) twice daily (BID) tablet
|
|---|---|---|
|
Overall Study
STARTED
|
300
|
299
|
|
Overall Study
COMPLETED
|
234
|
230
|
|
Overall Study
NOT COMPLETED
|
66
|
69
|
Reasons for withdrawal
| Measure |
LPV/r 800/200 mg QD Tablet
lopinavir/ritonavir 800/200 milligram (mg) once daily (QD) tablet
|
LPV/r 400/100 mg BID Tablet
lopinavir/ritonavir 400/100 milligram (mg) twice daily (BID) tablet
|
|---|---|---|
|
Overall Study
Adverse Event
|
14
|
21
|
|
Overall Study
Withdrawal by Subject
|
5
|
7
|
|
Overall Study
Lost to Follow-up
|
20
|
17
|
|
Overall Study
Noncompliance
|
12
|
11
|
|
Overall Study
Death
|
2
|
3
|
|
Overall Study
Virologic failure
|
11
|
8
|
|
Overall Study
Unable to Continue Participation
|
2
|
2
|
Baseline Characteristics
Study of Lopinavir/Ritonavir Tablets Comparing Once-Daily Versus Twice-Daily Administration When Coadministered With Nucleoside/Nucleotide Reverse Transcriptase Inhibitors in Antiretroviral-Experienced Human Immunodeficiency Virus Type 1 Infected Subjects
Baseline characteristics by cohort
| Measure |
LPV/r 800/200 mg QD Tablet
n=300 Participants
lopinavir/ritonavir 800/200 mg once daily (QD) tablet
|
LPV/r 400/100 mg BID Tablet
n=299 Participants
lopinavir/ritonavir 400/100 mg twice daily (BID) tablet
|
Total
n=599 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
|
40.4 years
STANDARD_DEVIATION 9.22 • n=5 Participants
|
40.8 years
STANDARD_DEVIATION 8.63 • n=7 Participants
|
40.6 years
STANDARD_DEVIATION 8.92 • n=5 Participants
|
|
Sex: Female, Male
Female
|
103 Participants
n=5 Participants
|
103 Participants
n=7 Participants
|
206 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
197 Participants
n=5 Participants
|
196 Participants
n=7 Participants
|
393 Participants
n=5 Participants
|
|
Received Prior Nonnucleoside Reverse Transcriptase Inhibitor (NNRTI)
Received Prior NNRTI
|
264 participants
n=5 Participants
|
241 participants
n=7 Participants
|
505 participants
n=5 Participants
|
|
Received Prior Nonnucleoside Reverse Transcriptase Inhibitor (NNRTI)
Did Not Receive Prior NNRTI
|
36 participants
n=5 Participants
|
58 participants
n=7 Participants
|
94 participants
n=5 Participants
|
|
Received Prior Nucleoside/nucleotide Reverse Transcriptase Inhibitor (NRTI)
Received Prior NRTI
|
299 participants
n=5 Participants
|
297 participants
n=7 Participants
|
596 participants
n=5 Participants
|
|
Received Prior Nucleoside/nucleotide Reverse Transcriptase Inhibitor (NRTI)
Did Not Receive Prior NRTI
|
1 participants
n=5 Participants
|
2 participants
n=7 Participants
|
3 participants
n=5 Participants
|
|
Received Prior Protease Inhibitor (PI)
Received Prior PI
|
140 participants
n=5 Participants
|
136 participants
n=7 Participants
|
276 participants
n=5 Participants
|
|
Received Prior Protease Inhibitor (PI)
Did Not Receive Prior PI
|
160 participants
n=5 Participants
|
163 participants
n=7 Participants
|
323 participants
n=5 Participants
|
|
Cluster of Differentiation 4 Single-Positive Thymocyte (CD4+ T) Cell Count
|
239.3 cells/microliter
STANDARD_DEVIATION 158.39 • n=5 Participants
|
268.3 cells/microliter
STANDARD_DEVIATION 183.55 • n=7 Participants
|
253.9 cells/microliter
STANDARD_DEVIATION 171.98 • n=5 Participants
|
|
Plasma Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) Level
|
4.26 log10 copies/milliliter (mL)
STANDARD_DEVIATION 0.826 • n=5 Participants
|
4.26 log10 copies/milliliter (mL)
STANDARD_DEVIATION 0.809 • n=7 Participants
|
4.26 log10 copies/milliliter (mL)
STANDARD_DEVIATION 0.817 • n=5 Participants
|
PRIMARY outcome
Timeframe: Week 48 (End of Study)Population: Intention to treat analysis of all randomized participants who received at least 1 dose of study drug.
A participant was classified as a responder at the first of 2 consecutive human immunodeficiency virus type 1 (HIV-1) ribonucleic acid (RNA) levels \<50 copies/mL. The participant continued to be a responder until 2 consecutive values \>=50 copies/mL were reached, until the final value if that value was \>=50 copies/mL, or until discontinuation or death.
Outcome measures
| Measure |
LPV/r 800/200 mg QD Tablet
n=300 Participants
lopinavir/ritonavir 800/200 mg once daily (QD) tablet
|
LPV/r 400/100 mg BID Tablet
n=299 Participants
lopinavir/ritonavir 400/100 mg twice daily (BID) tablet
|
|---|---|---|
|
Percentage of Participants Responding at Week 48 Based on the Food and Drug Administration (FDA) Time to Loss of Virologic Response (TLOVR) Algorithm
|
55.3 Percentage of Participants
|
51.8 Percentage of Participants
|
SECONDARY outcome
Timeframe: Week 48 (End of Study)Population: Observed data analysis using all available Week 48 data from all randomized participants who received at least 1 dose of study drug.
Outcome measures
| Measure |
LPV/r 800/200 mg QD Tablet
n=225 Participants
lopinavir/ritonavir 800/200 mg once daily (QD) tablet
|
LPV/r 400/100 mg BID Tablet
n=223 Participants
lopinavir/ritonavir 400/100 mg twice daily (BID) tablet
|
|---|---|---|
|
Percentage of Participants With Plasma Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) Levels < 50 Copies/Milliliter (mL) at Week 48
|
76.0 Percentage of Participants
|
72.2 Percentage of Participants
|
SECONDARY outcome
Timeframe: Week 48 (End of Study)Population: All randomized participants who received at least 1 dose of study drug and who had CD4+ T cell counts at both the Baseline Visit and Week 48.
Outcome measures
| Measure |
LPV/r 800/200 mg QD Tablet
n=195 Participants
lopinavir/ritonavir 800/200 mg once daily (QD) tablet
|
LPV/r 400/100 mg BID Tablet
n=193 Participants
lopinavir/ritonavir 400/100 mg twice daily (BID) tablet
|
|---|---|---|
|
Mean Change From Baseline to Week 48 in Cluster of Differentiation 4 Single-Positive Thymocyte (CD4+ T) Cell Counts
|
135.3 cells/microliter
Standard Error 9.03
|
121.5 cells/microliter
Standard Error 9.08
|
SECONDARY outcome
Timeframe: Week 48 (End of Study)Population: Dropouts-as-censored: participants were responders if they had HIV-1 RNA \<50 copies/mL at Week 48. Participants who discontinued (d/c'd) while suppressed or w/o post baseline (BL) levels were excluded. Those d/c'd \<Day 85 were excluded unless they had \>=1 post BL level \& didn't achieve a decrease \>=1.0 log10 copies/mL, then they were nonresponders.
Substitutions considered in the analysis were L10F/I/R/V, K20M/N/R, L24I, L33F, M36I, I47V, G48V, I54L/T/V, V82A/C/F/S/T, and I84V as defined in the proposed United States Package Insert.
Outcome measures
| Measure |
LPV/r 800/200 mg QD Tablet
n=255 Participants
lopinavir/ritonavir 800/200 mg once daily (QD) tablet
|
LPV/r 400/100 mg BID Tablet
n=250 Participants
lopinavir/ritonavir 400/100 mg twice daily (BID) tablet
|
|---|---|---|
|
Virologic Response (HIV-1 RNA <50 Copies/mL) at Week 48 for Participants With 0-2 Protease Inhibitor Substitutions at Baseline Associated With Reduced Response to Lopinavir/Ritonavir
|
65.5 Percentage of Participants
|
61.6 Percentage of Participants
|
SECONDARY outcome
Timeframe: Week 48 (End of Study)Population: All randomized participants who received at least 1 dose of study drug and had post baseline genotypic resistance assay results.
Emergence of new primary protease inhibitor mutations (i.e., mutations at codons 30, 32, 48, 50, 82, 84, and 90 that were not present at baseline).
Outcome measures
| Measure |
LPV/r 800/200 mg QD Tablet
n=75 Participants
lopinavir/ritonavir 800/200 mg once daily (QD) tablet
|
LPV/r 400/100 mg BID Tablet
n=77 Participants
lopinavir/ritonavir 400/100 mg twice daily (BID) tablet
|
|---|---|---|
|
Percentage of Participants With New Primary Protease Mutations at Week 48
|
8.0 Percentage of Participants
|
15.6 Percentage of Participants
|
Adverse Events
LPV/r 800/200 mg QD Tablet
Serious events: 27 serious events
Other events: 201 other events
Deaths: 0 deaths
LPV/r 400/100 mg BID Tablet
Serious events: 37 serious events
Other events: 180 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
LPV/r 800/200 mg QD Tablet
n=300 participants at risk
lopinavir/ritonavir 800/200 mg once daily (QD) tablet
|
LPV/r 400/100 mg BID Tablet
n=299 participants at risk
lopinavir/ritonavir 400/100 mg twice daily (BID) tablet
|
|---|---|---|
|
Hepatobiliary disorders
Jaundice
|
0.33%
1/300
|
0.00%
0/299
|
|
Immune system disorders
Drug hypersensitivity
|
0.00%
0/300
|
0.33%
1/299
|
|
Blood and lymphatic system disorders
Anaemia
|
0.67%
2/300
|
0.00%
0/299
|
|
Blood and lymphatic system disorders
Leukocytosis
|
0.33%
1/300
|
0.00%
0/299
|
|
Blood and lymphatic system disorders
Lymphadenopathy
|
0.00%
0/300
|
0.33%
1/299
|
|
Cardiac disorders
Angina pectoris
|
0.33%
1/300
|
0.00%
0/299
|
|
Cardiac disorders
Cardiac failure congestive
|
0.00%
0/300
|
0.33%
1/299
|
|
Cardiac disorders
Cardiogenic shock
|
0.33%
1/300
|
0.00%
0/299
|
|
Cardiac disorders
Tricuspid valve incompetence
|
0.33%
1/300
|
0.00%
0/299
|
|
Gastrointestinal disorders
Abdominal distension
|
0.00%
0/300
|
0.33%
1/299
|
|
Gastrointestinal disorders
Abdominal pain
|
0.33%
1/300
|
0.00%
0/299
|
|
Gastrointestinal disorders
Diarrhoea
|
0.33%
1/300
|
0.33%
1/299
|
|
Gastrointestinal disorders
Gastritis
|
0.33%
1/300
|
0.00%
0/299
|
|
Gastrointestinal disorders
Inguinal hernia
|
0.00%
0/300
|
0.33%
1/299
|
|
Gastrointestinal disorders
Nausea
|
0.67%
2/300
|
0.33%
1/299
|
|
Gastrointestinal disorders
Vomiting
|
0.33%
1/300
|
0.33%
1/299
|
|
General disorders
Asthenia
|
0.00%
0/300
|
0.33%
1/299
|
|
General disorders
Chest pain
|
0.33%
1/300
|
0.33%
1/299
|
|
General disorders
Chills
|
0.33%
1/300
|
0.00%
0/299
|
|
General disorders
Death
|
0.00%
0/300
|
0.67%
2/299
|
|
General disorders
Oedema peripheral
|
0.00%
0/300
|
0.33%
1/299
|
|
General disorders
Pyrexia
|
0.67%
2/300
|
0.33%
1/299
|
|
General disorders
Unevaluable event
|
0.00%
0/300
|
0.33%
1/299
|
|
Hepatobiliary disorders
Cholecystitis
|
0.33%
1/300
|
0.00%
0/299
|
|
Hepatobiliary disorders
Cholecystitis chronic
|
0.00%
0/300
|
0.33%
1/299
|
|
Infections and infestations
Abscess limb
|
0.33%
1/300
|
0.00%
0/299
|
|
Infections and infestations
Appendicitis
|
0.00%
0/300
|
0.33%
1/299
|
|
Infections and infestations
Bacterial disease carrier
|
0.33%
1/300
|
0.00%
0/299
|
|
Infections and infestations
Bronchitis
|
0.00%
0/300
|
0.33%
1/299
|
|
Infections and infestations
Cellulitis
|
0.00%
0/300
|
0.33%
1/299
|
|
Infections and infestations
Cerebral toxoplasmosis
|
0.33%
1/300
|
0.00%
0/299
|
|
Infections and infestations
Cryptococcosis
|
0.33%
1/300
|
0.00%
0/299
|
|
Infections and infestations
Dengue fever
|
0.33%
1/300
|
0.00%
0/299
|
|
Infections and infestations
Disseminated tuberculosis
|
0.00%
0/300
|
0.33%
1/299
|
|
Infections and infestations
Gastroenteritis
|
0.33%
1/300
|
0.00%
0/299
|
|
Infections and infestations
Helicobacter infection
|
0.00%
0/300
|
0.33%
1/299
|
|
Infections and infestations
Herpes zoster
|
0.00%
0/300
|
0.33%
1/299
|
|
Infections and infestations
Meningitis
|
0.00%
0/300
|
0.33%
1/299
|
|
Infections and infestations
Meningitis tuberculous
|
0.33%
1/300
|
0.00%
0/299
|
|
Infections and infestations
Oral candidiasis
|
0.00%
0/300
|
0.33%
1/299
|
|
Infections and infestations
Pneumonia
|
1.0%
3/300
|
1.7%
5/299
|
|
Infections and infestations
Sepsis
|
0.33%
1/300
|
0.00%
0/299
|
|
Infections and infestations
Staphylococcal bacteraemia
|
0.00%
0/300
|
0.33%
1/299
|
|
Infections and infestations
Staphylococcal infection
|
0.33%
1/300
|
0.33%
1/299
|
|
Infections and infestations
Staphylococcal skin infection
|
0.00%
0/300
|
0.33%
1/299
|
|
Infections and infestations
Syphilis
|
0.33%
1/300
|
0.00%
0/299
|
|
Infections and infestations
Tuberculosis
|
0.33%
1/300
|
0.00%
0/299
|
|
Infections and infestations
Urinary tract infection
|
0.33%
1/300
|
0.00%
0/299
|
|
Injury, poisoning and procedural complications
Clavicle fracture
|
0.33%
1/300
|
0.00%
0/299
|
|
Injury, poisoning and procedural complications
Head injury
|
0.00%
0/300
|
0.33%
1/299
|
|
Injury, poisoning and procedural complications
Hip fracture
|
0.00%
0/300
|
0.33%
1/299
|
|
Injury, poisoning and procedural complications
Injury
|
0.33%
1/300
|
0.00%
0/299
|
|
Injury, poisoning and procedural complications
Lung injury
|
0.33%
1/300
|
0.00%
0/299
|
|
Injury, poisoning and procedural complications
Rib fracture
|
0.33%
1/300
|
0.00%
0/299
|
|
Injury, poisoning and procedural complications
Road traffic accident
|
0.33%
1/300
|
0.00%
0/299
|
|
Injury, poisoning and procedural complications
Scapula fracture
|
0.33%
1/300
|
0.00%
0/299
|
|
Injury, poisoning and procedural complications
Skin laceration
|
0.00%
0/300
|
0.33%
1/299
|
|
Injury, poisoning and procedural complications
Upper limb fracture
|
0.00%
0/300
|
0.33%
1/299
|
|
Investigations
Haemoglobin decreased
|
0.00%
0/300
|
0.33%
1/299
|
|
Metabolism and nutrition disorders
Dehydration
|
0.33%
1/300
|
0.33%
1/299
|
|
Metabolism and nutrition disorders
Gout
|
0.33%
1/300
|
0.00%
0/299
|
|
Metabolism and nutrition disorders
Hyperlactacidaemia
|
0.00%
0/300
|
0.33%
1/299
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
0.33%
1/300
|
0.00%
0/299
|
|
Musculoskeletal and connective tissue disorders
Foot deformity
|
0.33%
1/300
|
0.00%
0/299
|
|
Musculoskeletal and connective tissue disorders
Lumbar spinal stenosis
|
0.00%
0/300
|
0.33%
1/299
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/300
|
0.33%
1/299
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Ocular neoplasm
|
0.00%
0/300
|
0.33%
1/299
|
|
Nervous system disorders
Cerebral haemorrhage
|
0.00%
0/300
|
0.33%
1/299
|
|
Nervous system disorders
Cerebral infarction
|
0.33%
1/300
|
0.00%
0/299
|
|
Nervous system disorders
Cerebrovascular accident
|
0.00%
0/300
|
0.33%
1/299
|
|
Nervous system disorders
Dizziness
|
0.00%
0/300
|
0.33%
1/299
|
|
Nervous system disorders
Encephalitis
|
0.00%
0/300
|
0.33%
1/299
|
|
Nervous system disorders
Mononeuritis
|
0.00%
0/300
|
0.33%
1/299
|
|
Nervous system disorders
Paraesthesia
|
0.00%
0/300
|
0.33%
1/299
|
|
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous
|
0.33%
1/300
|
0.00%
0/299
|
|
Pregnancy, puerperium and perinatal conditions
Ectopic pregnancy
|
0.00%
0/300
|
0.33%
1/299
|
|
Psychiatric disorders
Anxiety
|
0.33%
1/300
|
0.33%
1/299
|
|
Psychiatric disorders
Major depression
|
0.33%
1/300
|
0.00%
0/299
|
|
Psychiatric disorders
Personality disorder
|
0.00%
0/300
|
0.33%
1/299
|
|
Renal and urinary disorders
Acute prerenal failure
|
0.33%
1/300
|
0.00%
0/299
|
|
Renal and urinary disorders
Choluria
|
0.33%
1/300
|
0.00%
0/299
|
|
Renal and urinary disorders
Renal failure
|
0.33%
1/300
|
0.00%
0/299
|
|
Renal and urinary disorders
Renal failure acute
|
0.00%
0/300
|
0.33%
1/299
|
|
Reproductive system and breast disorders
Cervical dysplasia
|
0.00%
0/300
|
0.33%
1/299
|
|
Reproductive system and breast disorders
Epididymitis
|
0.33%
1/300
|
0.00%
0/299
|
|
Reproductive system and breast disorders
Metrorrhagia
|
0.00%
0/300
|
0.33%
1/299
|
|
Reproductive system and breast disorders
Vaginal dysplasia
|
0.00%
0/300
|
0.33%
1/299
|
|
Reproductive system and breast disorders
Vaginal haemorrhage
|
0.33%
1/300
|
0.00%
0/299
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
0.00%
0/300
|
0.33%
1/299
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.00%
0/300
|
0.67%
2/299
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.33%
1/300
|
0.00%
0/299
|
|
Respiratory, thoracic and mediastinal disorders
Haemothorax
|
0.33%
1/300
|
0.00%
0/299
|
|
Respiratory, thoracic and mediastinal disorders
Lung disorder
|
0.00%
0/300
|
0.33%
1/299
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
0.33%
1/300
|
0.00%
0/299
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.00%
0/300
|
0.33%
1/299
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema
|
0.00%
0/300
|
0.33%
1/299
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.33%
1/300
|
0.00%
0/299
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
0.33%
1/300
|
0.00%
0/299
|
|
Skin and subcutaneous tissue disorders
Stevens-Johnson syndrome
|
0.00%
0/300
|
0.33%
1/299
|
|
Vascular disorders
Arteriosclerosis
|
0.00%
0/300
|
0.33%
1/299
|
|
Vascular disorders
Deep vein thrombosis
|
0.00%
0/300
|
0.33%
1/299
|
Other adverse events
| Measure |
LPV/r 800/200 mg QD Tablet
n=300 participants at risk
lopinavir/ritonavir 800/200 mg once daily (QD) tablet
|
LPV/r 400/100 mg BID Tablet
n=299 participants at risk
lopinavir/ritonavir 400/100 mg twice daily (BID) tablet
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
5.7%
17/300
|
2.7%
8/299
|
|
Gastrointestinal disorders
Diarrhoea
|
49.7%
149/300
|
38.5%
115/299
|
|
Gastrointestinal disorders
Nausea
|
15.7%
47/300
|
22.1%
66/299
|
|
Gastrointestinal disorders
Vomiting
|
12.0%
36/300
|
12.4%
37/299
|
|
Infections and infestations
Influenza
|
7.0%
21/300
|
6.4%
19/299
|
|
Infections and infestations
Nasopharyngitis
|
4.3%
13/300
|
5.4%
16/299
|
|
Infections and infestations
Upper respiratory tract infection
|
9.7%
29/300
|
8.7%
26/299
|
|
Nervous system disorders
Headache
|
6.7%
20/300
|
7.0%
21/299
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
5.0%
15/300
|
5.0%
15/299
|
Additional Information
Medical Information Specialist
Abbott
Phone: 800-633-9110
Results disclosure agreements
- Principal investigator is a sponsor employee This study has varying agreements that have been negotiated individually; however, it appears that the most restrictive of the agreements states that following the first publication/presentation of the study by Abbott (or twelve \[12\] months after the completion of the study at all sites, whichever occurs first), the Principal Investigator (PI) shall, during a period of twelve (12) months, have the right to publish/present the results of the site.
- Publication restrictions are in place
Restriction type: OTHER