MONET: Treatment Simplification by Darunavir/Ritonavir 800/100 mg Once a Day Versus a Triple Combination Therapy With Darunavir/Ritonavir
Study Details
Study Description
Brief Summary
The purpose of the study is to compare the efficacy, safety and tolerability of darunavir/ritonavir 800/100 mg once a day (O.D.) as a monotherapy versus a triple combination therapy containing 2 nucleosides and darunavir/ritonavir in 250 HIV-1 infected patients who have been on Highly Active Antiretroviral Therapy (HAART) and have plasma viral load below 50 copies/ml for at least 24 weeks.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
This study is randomised (patients are assigned different treatments based on chance), controlled, open-label trial to compare the efficacy, safety and tolerability of darunavir/ritonavir (DRV/r) 800/100 mg once a day (O.D.) as a monotherapy versus a triple combination therapy containing 2 nucleosides and DRV/r in 250 HIV-1 infected patients. Patients will be considered eligible if they have not changed any antiretroviral drugs for at least 8 weeks prior to screening and have documented evidence of plasma viral load (or plasma HIV-1 RNA) < 50 copies/mL for at least 24 weeks prior to being screened. The trial will consist of a screening period up to 4 weeks, a 48-week treatment period, followed by a 4-week follow-up (FU) period. The primary objective is to demonstrate non-inferiority in efficacy of DRV/r versus the triple combination therapy containing DRV/r, with respect to confirmed virologic response, defined as plasma HIV-1 RNA < 50 copies/mL at 48 weeks.Patients will be assigned a study medication based on a 1:1 ratio to either switch to a triple combination therapy containing 2 nucleosides and DRV/r 800/100 mg O.D, or initiate monotherapy with DRV/r 800/100 mg O.D. Patients in the triple combination arm who are already on 2 nucleosides prior to randomisation may remain on these or switch them at baseline. Patients randomised to the monotherapy arm will discontinue Highly Active Antiretroviral Therapy (HAART) at baseline and commence DRV/r 800/100 mg O.D. A Data and Safety Monitoring Board (DSMB) has been commissioned for this study. The role of the DSMB is to review the progress of the trial and the accumulating data to detect evidence of early safety issues for the patients while the trial is ongoing. An interim analysis will be performed after 24 weeks of treatment. The results of the Week 24 analysis will be used to determine whether long-term follow-up to 72 and 96 weeks will be done. The protease inhibitor (PI) component of the regimen cannot be changed until the end of the treatment period and the nucleoside reverse transcriptase inhibitors (NRTIs) cannot be modified until the end of the treatment period with the following exception: single antiretroviral (ARV) substitutions will be allowed for tolerability/toxicity reasons, as long as this can be linked to an adverse event (AE) or an serious adverse event (SAE). After withdrawal of the patient from the trial, changes in the ARV regimen are allowed after the assessments of the withdrawal visit have been performed.
Temporary interruption of all ARVs will be allowed in the event of suspected toxicity, as long as the temporary interruption is associated with and can be linked to an AE or a SAE. For the control arm, the nucleoside analogues could be re-optimized at baseline or on study, and all approved ARVs allowed. However, PIs other than DRV/r are not allowed during the treatment period. Patients who cannot resume study medication will have to be withdrawn. A physical examination will be done at protocol-scheduled visits and vital signs will be monitored at each study visit. In addition, at each study visit, every patient will be asked about the occurrence of or change to AEs since they were last seen by the investigator. Laboratory samples for haematology and serum chemistry will be drawn and the results determined and transmitted to the investigator. Urinalysis will be performed. Pregnancy test will be done at each visit for female participants of child-bearing potential. The primary endpoint will be the proportion with virologic response, defined as a confirmed plasma HIV-1 RNA < 50 copies/mL at Week 48.The study hypothesis is that DRV/r monotherapy will be as effective as a triple combination regimen and will be well tolerated in this early pre-treated HIV-1 patients. Two 400mg tablets of darunavir once daily orally within 30 minutes after completion of a meal for 48 weeks.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: darunavir monotherapy darunavir (DRV, TMC114) 800 mg qd (2 x 400 mg tablet) monotherapy for 144 weeks |
Drug: darunavir (DRV, TMC114)
800 mg qd (2 x 400 mg tablet) monotherapy for 144 weeks
|
| Experimental: darunavir + 2 NRTI darunavir (DRV, TMC114) 800 mg qd (2 x 400 mg tablet) + 2 NRTI for 144 weeks |
Drug: darunavir (DRV, TMC114)
800 mg qd (2 x 400 mg tablet) + 2 NRTI for 144 weeks
|
Outcome Measures
Primary Outcome Measures
- Virological Response [Per Protocol (PP) - Time to Loss of Virologic Response (TLOVR), < 50 Copies/ml, Week 48] [Week 48]
Virological response is defined as the number of patients in the PP population with a plasma viral load < 50 HIV RNA copies/ml at Week 48. Treatment failure was defined as two consecutive HIV RNA levels ≥ 50 copies/mL, or discontinuation of randomised treatment (known as TLOVR). In addition, any switch in background nucleoside reverse transcriptase inhibitors (NRTIs) equaled failure* (referred to as a Switch Equals Failure analysis). *Discontinuations and rechallenge with NRTIs are taken into account until Week 48
Secondary Outcome Measures
- Virological Response [Intent To Treat (ITT) - TLOVR, < 50 Copies/ml, Week 48] [Week 48]
Virological response is defined as the number of patients in the ITT population with a plasma viral load < 50 HIV RNA copies/ml at Week 48. Treatment failure was defined as two consecutive HIV RNA levels ≥ 50 copies/mL, or discontinuation of randomised treatment (known as TLOVR). In addition, any switch in background nucleoside reverse transcriptase inhibitors (NRTIs) equaled failure* (referred to as a Switch Equals Failure analysis). *Discontinuations and rechallenge with NRTIs are taken into account until start of Week 48 window
- Virological Response [Per Protocol (PP), TLOVR - Switch Equals Failure, < 50 Copies/ml, Week 144] [Week 144]
Virological response is defined as the number of patients in the PP population with a plasma viral load < 50 HIV RNA copies/ml at Week 144. Treatment failure was defined as two consecutive HIV RNA levels ≥ 50 copies/mL, or discontinuation of randomised treatment (known as TLOVR). In addition, any switch in background nucleoside reverse transcriptase inhibitors (NRTIs) equaled failure* (referred to as a Switch Equals Failure analysis). *Discontinuations and rechallenge with NRTIs are taken into account until Week 144
- Virological Response [Intent To Treat (ITT), TLOVR - All Switches Included, < 50 Copies/ml, Week 144] [Week 144]
Virological response is defined as the number of patients in the ITT population with a plasma viral load < 50 HIV RNA copies/ml at Week 144. Treatment failure was defined as two consecutive HIV RNA levels ≥ 50 copies/mL, or discontinuation of randomised treatment (known as TLOVR). All switches included means that all data even after any changes of treatment were kept. *Discontinuations and rechallenge with NRTIs are taken into account until start of Week 144 window.
- Virological Response [Per Protocol (PP), TLOVR - Switch Equals Failure, <200 Copies/ml, Week 144] [week 144]
Virological response is defined as the number of patients in the PP population with a plasma viral load < 200 HIV RNA copies/ml at Week 144. Treatment failure was defined as two consecutive HIV RNA levels ≥ 50 copies/mL, or discontinuation of randomised treatment (known as TLOVR). In addition, any switch in background nucleoside reverse transcriptase inhibitors (NRTIs) equaled failure* (referred to as a Switch Equals Failure analysis). *Discontinuations and rechallenge with NRTIs are taken into account until Week 144
- Mean Change From Baseline in CD4+ Cell Count [at week 4, 12, 24, 36, 48, 60, 72, 84, 96, 112, 128, 144]
The mean change in CD4+ cell count from baseline was calculated with a last observation carried forward method; i.e. the last observed value was carried forward, irrespective of the reason for discontinuation.
- Resistance Determinations [at each visit from baseline to week 144]
Number of patients with resistance mutations at any time point when a patient had a viral load > 50 copies/mL after randomization.
- Change From Baseline in Health-Related Quality of Life - FAHI Questionnaire Total Score [at baseline, week 48, 96 and 144]
The FAHI is a validated health-related quality of life questionnaire. The questionnaire consist of 44 items and includes 5 functional scales (physical, social, emotional, functional and global well-being and cognitive function). Each item is assessing the impact of HIV on a scale from 0 (not at all) to 5 (very much).
- Change From Baseline in Health-Related Quality of Life - FAHI Questionnaire Cognitive Function Subscale [at baseline, week 48, 96 and 144]
The FAHI cognitive function subscale. Each item is assessing the impact of HIV on cognitive function on a scale from 0 (not at all) to 5 (very much).
- Change From Baseline in Health-Related Quality of Life - FAHI Questionnaire Emotional Well-Being Subscale [at baseline, week 48, 96 and 144]
The FAHI emotional well-being subscale. Each item is assessing the impact of HIV on emotional well-being on a scale from 0 (not at all) to 5 (very much).
- Change From Baseline in Health-Related Quality of Life - FAHI Questionnaire Functional and Global Well-Being Subscale [at baseline, week 48, 96 and 144]
The FAHI functional and global well-being subscale. Each item is assessing the impact of HIV on functional and global well-being on a scale from 0 (not at all) to 5 (very much).
- Change From Baseline in Health-Related Quality of Life - FAHI Questionnaire Physical Well-Being Subscale [at baseline, week 48, 96 and 144]
The FAHI physical well-being subscale. Each item is assessing the impact of HIV on physical well-being on a scale from 0 (not at all) to 5 (very much).
- Change From Baseline in Health-Related Quality of Life - FAHI Questionnaire Social Well-Being Subscale [at baseline, week 48, 96 and 144]
The FAHI social well-being subscale. Each item is assessing the impact of HIV on physical well-being on a scale from 0 (not at all) to 5 (very much).
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Patients with documented HIV-1 infection
-
Patients currently receiving HAART for at least 24 weeks
-
Plasma viral load < 50 copies/mL for at least 24 weeks prior to screening (two results must be documented)
-
Patients taking the same antiretroviral combination for at least 8 weeks before screening
-
Patients and physician's preference to change the current HAART regimen for reasons of simplification and/or toxicity
-
CD4 > 100/mm3 at the start of HAART and > 200/mm3 at screening.
Exclusion Criteria:
-
No history of virological failure defined as two consecutive plasma HIV-1 RNA > 500 copies/mL while on previous or current antiretroviral therapy
-
No history of any primary PI mutations as defined by the IAS-USA guidelines 2006
-
No patients co-infected with hepatitis B
-
No pregnant or breastfeeding women
-
No active clinically significant disease or life threatening disease or findings during screening of medical history or physical examination that, in the investigator's opinion, would compromise the patient's safety or outcome of the study.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Wien | Austria | |||
| 2 | Antwerpen | Belgium | |||
| 3 | Bruxelles | Belgium | |||
| 4 | Aarhus | Denmark | |||
| 5 | Copenhagen | Denmark | |||
| 6 | Hvidovre | Denmark | |||
| 7 | Odense | Denmark | |||
| 8 | Berlin | Germany | |||
| 9 | Frankfurt | Germany | |||
| 10 | Hamburg | Germany | |||
| 11 | Hannover | Germany | |||
| 12 | Kÿln N/A | Germany | |||
| 13 | Budapest | Hungary | |||
| 14 | Jerusalem | Israel | |||
| 15 | Tel Aviv | Israel | |||
| 16 | Tel Hashomer | Israel | |||
| 17 | Lisbon | Portugal | |||
| 18 | Porto | Portugal | |||
| 19 | Moscow | Russian Federation | |||
| 20 | Saint-Petersburg | Russian Federation | |||
| 21 | Barcelona N/A | Spain | |||
| 22 | Barcelona | Spain | |||
| 23 | Donostia Guipuzcoa | Spain | |||
| 24 | Granada | Spain | |||
| 25 | Madrid | Spain | |||
| 26 | Valladolid N/A | Spain | |||
| 27 | St Gallen | Switzerland | |||
| 28 | London | United Kingdom |
Sponsors and Collaborators
- Janssen-Cilag International NV
Investigators
- Study Director: Janssen-Cilag International NV Clinical Trial, Janssen-Cilag International NV
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CR013159
- TMC114HIV3006
- 2006-006437-40
Study Results
Participant Flow
| Recruitment Details | xxxxx |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | DRV/r+2NRTIs | DRV/r |
|---|---|---|
| Arm/Group Description | 800 mg qd (2 x 400 mg tablet) + 2 NRTI for 144 weeks | 800 mg qd (2 x 400 mg tablet) monotherapy for 144 weeks |
| Period Title: Overall Study | ||
| STARTED | 129 | 127 |
| COMPLETED | 109 | 103 |
| NOT COMPLETED | 20 | 24 |
Baseline Characteristics
| Arm/Group Title | DRV/r+2NRTIs | DRV/r | Total |
|---|---|---|---|
| Arm/Group Description | 800 mg qd (2 x 400 mg tablet) + 2 NRTI for 144 weeks | 800 mg qd (2 x 400 mg tablet) monotherapy for 144 weeks | Total of all reporting groups |
| Overall Participants | 129 | 127 | 256 |
| Age (Count of Participants) | |||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
128
99.2%
|
125
98.4%
|
253
98.8%
|
| >=65 years |
1
0.8%
|
2
1.6%
|
3
1.2%
|
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
44.1
(9.74)
|
43.4
(9.14)
|
43.7
(9.43)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
22
17.1%
|
28
22%
|
50
19.5%
|
| Male |
107
82.9%
|
99
78%
|
206
80.5%
|
| Region of Enrollment (participants) [Number] | |||
| AUSTRIA |
9
7%
|
7
5.5%
|
16
6.3%
|
| BELGIUM |
12
9.3%
|
12
9.4%
|
24
9.4%
|
| DENMARK |
14
10.9%
|
14
11%
|
28
10.9%
|
| GERMANY |
14
10.9%
|
14
11%
|
28
10.9%
|
| HUNGARY |
6
4.7%
|
5
3.9%
|
11
4.3%
|
| ISRAEL |
1
0.8%
|
7
5.5%
|
8
3.1%
|
| ITALY |
11
8.5%
|
5
3.9%
|
16
6.3%
|
| POLAND |
9
7%
|
20
15.7%
|
29
11.3%
|
| PORTUGAL |
7
5.4%
|
7
5.5%
|
14
5.5%
|
| RUSSIAN FEDERATION |
9
7%
|
2
1.6%
|
11
4.3%
|
| SPAIN |
24
18.6%
|
24
18.9%
|
48
18.8%
|
| SWITZERLAND |
1
0.8%
|
1
0.8%
|
2
0.8%
|
| UNITED KINGDOM |
12
9.3%
|
9
7.1%
|
21
8.2%
|
| plasma viral load (participants) [Number] | |||
| < 50 |
125
96.9%
|
118
92.9%
|
243
94.9%
|
| 50-400 |
4
3.1%
|
7
5.5%
|
11
4.3%
|
| 400-1000 |
0
0%
|
0
0%
|
0
0%
|
| > 1000 |
0
0%
|
2
1.6%
|
2
0.8%
|
| CD4+ cell count (absolute count) (cells/µl) [Median (Full Range) ] | |||
| Median (Full Range) [cells/µl] |
579.0
|
571.0
|
573.5
|
Outcome Measures
| Title | Virological Response [Per Protocol (PP) - Time to Loss of Virologic Response (TLOVR), < 50 Copies/ml, Week 48] |
|---|---|
| Description | Virological response is defined as the number of patients in the PP population with a plasma viral load < 50 HIV RNA copies/ml at Week 48. Treatment failure was defined as two consecutive HIV RNA levels ≥ 50 copies/mL, or discontinuation of randomised treatment (known as TLOVR). In addition, any switch in background nucleoside reverse transcriptase inhibitors (NRTIs) equaled failure* (referred to as a Switch Equals Failure analysis). *Discontinuations and rechallenge with NRTIs are taken into account until Week 48 |
| Time Frame | Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PP population: all randomised patients who took study drug, and who did not deviate from the protocol.This excludes 10 patients with major protocol deviations. |
| Arm/Group Title | DRV/r+2NRTIs | DRV/r |
|---|---|---|
| Arm/Group Description | 800 mg qd (2 x 400 mg tablet) + 2 NRTI for 144 weeks | 800 mg qd (2 x 400 mg tablet) monotherapy for 144 weeks |
| Measure Participants | 123 | 123 |
| Number [participants] |
108
83.7%
|
106
83.5%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | DRV/r+2NRTIs, DRV/r |
|---|---|---|
| Comments | Assuming a virologic response rate of 90% at 48 weeks for both treatment arms, 111 patients were required per treatment arm to establish non-inferiority of DRV/r versus triple regimen with a maximum allowable difference of 12%, with a one-sided significance level of p=0.025 and 80% power. To account for a maximum of 10% major protocol violations that would be excluded from the on-protocol analysis, 125 patients were recruited in each treatment arm, so 250 patients in total. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | The primary comparison was performed at Week 48. If at Week 48, the lower limit of the 95% two-sided confidence interval of the difference between DRV/r and DRV/r+2NRTIs exceeds -12%, non-inferiority of the DRV/r 800/100 once a day (O.D) monotherapy versus the DRV/r 800/100 mg O.D. plus two NRTIs triple combination therapy was concluded. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in proportion of response |
| Estimated Value | -1.6 | |
| Confidence Interval |
(2-Sided) 95% -10.1 to 6.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference in proportion of response DRV/r minus DRV/r+2NRTIs. | |
| Title | Virological Response [Intent To Treat (ITT) - TLOVR, < 50 Copies/ml, Week 48] |
|---|---|
| Description | Virological response is defined as the number of patients in the ITT population with a plasma viral load < 50 HIV RNA copies/ml at Week 48. Treatment failure was defined as two consecutive HIV RNA levels ≥ 50 copies/mL, or discontinuation of randomised treatment (known as TLOVR). In addition, any switch in background nucleoside reverse transcriptase inhibitors (NRTIs) equaled failure* (referred to as a Switch Equals Failure analysis). *Discontinuations and rechallenge with NRTIs are taken into account until start of Week 48 window |
| Time Frame | Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population: all randomised patients who took study drug, regardless of their compliance with the protocol. |
| Arm/Group Title | DRV/r+2NRTIs | DRV/r |
|---|---|---|
| Arm/Group Description | 800 mg qd (2 x 400 mg tablet) + 2 NRTI for 144 weeks | 800 mg qd (2 x 400 mg tablet) monotherapy for 144 weeks |
| Measure Participants | 129 | 127 |
| Number [participants] |
110
85.3%
|
107
84.3%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | DRV/r+2NRTIs, DRV/r |
|---|---|---|
| Comments | Assuming a virologic response rate of 90% at 48 weeks for both treatment arms, 111 patients were required per treatment arm to establish non-inferiority of DRV/r versus triple regimen with a maximum allowable difference of 12%, with a one-sided significance level of p=0.025 and 80% power. To account for a maximum of 10% major protocol violations that would be excluded from the on-protocol analysis, 125 patients were recruited in each treatment are, so 250 patients in total. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | If at Week 48, the lower limit of the 95% two-sided confidence interval of the difference between DRV/r and DRV/r+2NRTIs exceeds -12%, non-inferiority of the DRV/r 800/100 once a day (O.D) monotherapy versus the DRV/r 800/100 mg O.D. plus two NRTIs triple combination therapy was concluded. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in proportion of response |
| Estimated Value | -1.0 | |
| Confidence Interval |
(2-Sided) 95% -9.9 to 7.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference in proportion of response DRV/r minus DRV/r+2NRTIs. | |
| Title | Virological Response [Per Protocol (PP), TLOVR - Switch Equals Failure, < 50 Copies/ml, Week 144] |
|---|---|
| Description | Virological response is defined as the number of patients in the PP population with a plasma viral load < 50 HIV RNA copies/ml at Week 144. Treatment failure was defined as two consecutive HIV RNA levels ≥ 50 copies/mL, or discontinuation of randomised treatment (known as TLOVR). In addition, any switch in background nucleoside reverse transcriptase inhibitors (NRTIs) equaled failure* (referred to as a Switch Equals Failure analysis). *Discontinuations and rechallenge with NRTIs are taken into account until Week 144 |
| Time Frame | Week 144 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PP population: all randomised subjects who took study drug, and who did not deviate from the protocol.This excludes 13 subjects with major protocol deviations. |
| Arm/Group Title | DRV/r+2NRTIs | DRV/r |
|---|---|---|
| Arm/Group Description | 800 mg qd (2 x 400 mg tablet) + 2 NRTI for 144 weeks | 800 mg qd (2 x 400 mg tablet) monotherapy for 144 weeks |
| Measure Participants | 121 | 122 |
| Number [participants] |
94
72.9%
|
88
69.3%
|
| Title | Virological Response [Intent To Treat (ITT), TLOVR - All Switches Included, < 50 Copies/ml, Week 144] |
|---|---|
| Description | Virological response is defined as the number of patients in the ITT population with a plasma viral load < 50 HIV RNA copies/ml at Week 144. Treatment failure was defined as two consecutive HIV RNA levels ≥ 50 copies/mL, or discontinuation of randomised treatment (known as TLOVR). All switches included means that all data even after any changes of treatment were kept. *Discontinuations and rechallenge with NRTIs are taken into account until start of Week 144 window. |
| Time Frame | Week 144 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population: all randomised patients who took study drug, regardless of their compliance with the protocol. |
| Arm/Group Title | DRV/r+2NRTIs | DRV/r |
|---|---|---|
| Arm/Group Description | 800 mg qd (2 x 400 mg tablet) + 2 NRTI for 144 weeks | 800 mg qd (2 x 400 mg tablet) monotherapy for 144 weeks |
| Measure Participants | 129 | 127 |
| Number [participants] |
106
82.2%
|
106
83.5%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | DRV/r+2NRTIs, DRV/r |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in proportion of response |
| Estimated Value | 1.29 | |
| Confidence Interval |
(2-Sided) 95% -7.99 to 10.58 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference in proportion of response DRV/r minus DRV/r+2NRTIs. | |
| Title | Virological Response [Per Protocol (PP), TLOVR - Switch Equals Failure, <200 Copies/ml, Week 144] |
|---|---|
| Description | Virological response is defined as the number of patients in the PP population with a plasma viral load < 200 HIV RNA copies/ml at Week 144. Treatment failure was defined as two consecutive HIV RNA levels ≥ 50 copies/mL, or discontinuation of randomised treatment (known as TLOVR). In addition, any switch in background nucleoside reverse transcriptase inhibitors (NRTIs) equaled failure* (referred to as a Switch Equals Failure analysis). *Discontinuations and rechallenge with NRTIs are taken into account until Week 144 |
| Time Frame | week 144 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PP population: all randomised patients who took study drug, and who did not deviate from the protocol. This excludes 13 patients with major protocol deviations. |
| Arm/Group Title | DRV/r+2NRTIs | DRV/r |
|---|---|---|
| Arm/Group Description | 800 mg qd (2 x 400 mg tablet) + 2 NRTI for 144 weeks | 800 mg qd (2 x 400 mg tablet) monotherapy for 144 weeks |
| Measure Participants | 121 | 122 |
| Number [Participants] |
102
79.1%
|
95
74.8%
|
| Title | Mean Change From Baseline in CD4+ Cell Count |
|---|---|
| Description | The mean change in CD4+ cell count from baseline was calculated with a last observation carried forward method; i.e. the last observed value was carried forward, irrespective of the reason for discontinuation. |
| Time Frame | at week 4, 12, 24, 36, 48, 60, 72, 84, 96, 112, 128, 144 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT: all randomized patients who had at least 1 dose of study medication, regardless of their adherence to the protocol |
| Arm/Group Title | DRV/r+2NRTIs | DRV/r |
|---|---|---|
| Arm/Group Description | 800 mg qd (2 x 400 mg tablet) + 2 NRTI for 144 weeks | 800 mg qd (2 x 400 mg tablet) monotherapy for 144 weeks |
| Measure Participants | 129 | 127 |
| week 4 |
-16.9
(15.7)
|
-32.9
(14.6)
|
| week 12 |
-23.6
(14.7)
|
-20.7
(15.2)
|
| week 24 |
-5.4
(14.6)
|
-35.8
(14.2)
|
| week 36 |
-1.2
(15.8)
|
-21.1
(14.3)
|
| week 48 |
-19.0
(14.7)
|
-15.1
(16.0)
|
| week 60 |
-4.0
(14.9)
|
-2.3
(14.4)
|
| week 72 |
24.1
(16.1)
|
-12.3
(14.3)
|
| week 84 |
34.6
(17.2)
|
-3.7
(15.0)
|
| week 96 |
49.1
(15.9)
|
54.8
(16.2)
|
| week 112 |
106.0
(16.7)
|
87.5
(16.2)
|
| week 128 |
117.3
(18.3)
|
90.4
(14.9)
|
| week 144 |
99.3
(15.7)
|
94.9
(15.0)
|
| Title | Resistance Determinations |
|---|---|
| Description | Number of patients with resistance mutations at any time point when a patient had a viral load > 50 copies/mL after randomization. |
| Time Frame | at each visit from baseline to week 144 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT: all randomised patients who had at least 1 dose of study medication, regardless of their adherence to the protocol. |
| Arm/Group Title | DRV/r+2NRTIs | DRV/r |
|---|---|---|
| Arm/Group Description | 800 mg qd (2 x 400 mg tablet) + 2 NRTI for 144 weeks | 800 mg qd (2 x 400 mg tablet) monotherapy for 144 weeks |
| Measure Participants | 129 | 127 |
| >= 1 HIV-1 RNA > 50 copies/mL |
42
32.6%
|
48
37.8%
|
| >= 1 successful genotype after baseline |
23
17.8%
|
31
24.4%
|
| >= 1 IAS-USA primary PI mutations |
1
0.8%
|
1
0.8%
|
| >= 1 DRV RAMs |
0
0%
|
1
0.8%
|
| NRTI RAMs |
1
0.8%
|
0
0%
|
| M184V mutation |
1
0.8%
|
0
0%
|
| no primary PI, DRV, NRTI or M184 V mutations |
22
17.1%
|
30
23.6%
|
| Title | Change From Baseline in Health-Related Quality of Life - FAHI Questionnaire Total Score |
|---|---|
| Description | The FAHI is a validated health-related quality of life questionnaire. The questionnaire consist of 44 items and includes 5 functional scales (physical, social, emotional, functional and global well-being and cognitive function). Each item is assessing the impact of HIV on a scale from 0 (not at all) to 5 (very much). |
| Time Frame | at baseline, week 48, 96 and 144 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT: all randomised patients who had at least 1 dose of study medication, regardless of protocol adherence. A LOCF method was used for calculation. |
| Arm/Group Title | DRV/r+2NRTIs | DRV/r |
|---|---|---|
| Arm/Group Description | 800 mg qd (2 x 400 mg tablet) + 2 NRTI for 144 weeks | 800 mg qd (2 x 400 mg tablet) monotherapy for 144 weeks |
| Measure Participants | 126 | 112 |
| week 48 |
1.7
(1.7)
|
1.7
(2.0)
|
| week 96 |
0.4
(1.6)
|
3.5
(2.4)
|
| week 144 |
0.7
(1.7)
|
3.1
(2.4)
|
| Title | Change From Baseline in Health-Related Quality of Life - FAHI Questionnaire Cognitive Function Subscale |
|---|---|
| Description | The FAHI cognitive function subscale. Each item is assessing the impact of HIV on cognitive function on a scale from 0 (not at all) to 5 (very much). |
| Time Frame | at baseline, week 48, 96 and 144 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT: all randomised patients who had at least 1 dose of study medication, regardless of protocol adherence. A LOCF method was used for calculation. |
| Arm/Group Title | DRV/r+2NRTIs | DRV/r |
|---|---|---|
| Arm/Group Description | 800 mg qd (2 x 400 mg tablet) + 2 NRTI for 144 weeks | 800 mg qd (2 x 400 mg tablet) monotherapy for 144 weeks |
| Measure Participants | 127 | 115 |
| week 48 |
0.1
(0.2)
|
-0.1
(0.2)
|
| week 96 |
-0.1
(0.2)
|
-0.1
(0.2)
|
| week 144 |
0.1
(0.2)
|
-0.1
(0.2)
|
| Title | Change From Baseline in Health-Related Quality of Life - FAHI Questionnaire Emotional Well-Being Subscale |
|---|---|
| Description | The FAHI emotional well-being subscale. Each item is assessing the impact of HIV on emotional well-being on a scale from 0 (not at all) to 5 (very much). |
| Time Frame | at baseline, week 48, 96 and 144 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT: all randomised patients who had at least 1 dose of study medication, regardless of protocol adherence. A LOCF method was used for calculation. |
| Arm/Group Title | DRV/r+2NRTIs | DRV/r |
|---|---|---|
| Arm/Group Description | 800 mg qd (2 x 400 mg tablet) + 2 NRTI for 144 weeks | 800 mg qd (2 x 400 mg tablet) monotherapy for 144 weeks |
| Measure Participants | 128 | 118 |
| week 48 |
0.1
(0.6)
|
1.8
(0.7)
|
| week 96 |
1.0
(0.5)
|
1.3
(0.7)
|
| week 144 |
1.4
(0.5)
|
1.7
(0.7)
|
| Title | Change From Baseline in Health-Related Quality of Life - FAHI Questionnaire Functional and Global Well-Being Subscale |
|---|---|
| Description | The FAHI functional and global well-being subscale. Each item is assessing the impact of HIV on functional and global well-being on a scale from 0 (not at all) to 5 (very much). |
| Time Frame | at baseline, week 48, 96 and 144 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT: all randomised patients who had at least 1 dose of study medication, regardless of protocol adherence. A LOCF method was used for calculation. |
| Arm/Group Title | DRV/r+2NRTIs | DRV/r |
|---|---|---|
| Arm/Group Description | 800 mg qd (2 x 400 mg tablet) + 2 NRTI for 144 weeks | 800 mg qd (2 x 400 mg tablet) monotherapy for 144 weeks |
| Measure Participants | 127 | 116 |
| week 48 |
0.3
(0.8)
|
-0.8
(0.7)
|
| week 96 |
-0.1
(0.7)
|
0.4
(0.9)
|
| week 144 |
-0.6
(0.8)
|
0.0
(1.0)
|
| Title | Change From Baseline in Health-Related Quality of Life - FAHI Questionnaire Physical Well-Being Subscale |
|---|---|
| Description | The FAHI physical well-being subscale. Each item is assessing the impact of HIV on physical well-being on a scale from 0 (not at all) to 5 (very much). |
| Time Frame | at baseline, week 48, 96 and 144 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT: all randomised patients who had at least 1 dose of study medication, regardless of protocol adherence. A LOCF method was used for calculation. |
| Arm/Group Title | DRV/r+2NRTIs | DRV/r |
|---|---|---|
| Arm/Group Description | 800 mg qd (2 x 400 mg tablet) + 2 NRTI for 144 weeks | 800 mg qd (2 x 400 mg tablet) monotherapy for 144 weeks |
| Measure Participants | 128 | 118 |
| week 48 |
0.6
(0.5)
|
1.0
(0.8)
|
| week 96 |
0.4
(0.5)
|
1.4
(0.9)
|
| week 144 |
0.0
(0.5)
|
1.0
(0.8)
|
| Title | Change From Baseline in Health-Related Quality of Life - FAHI Questionnaire Social Well-Being Subscale |
|---|---|
| Description | The FAHI social well-being subscale. Each item is assessing the impact of HIV on physical well-being on a scale from 0 (not at all) to 5 (very much). |
| Time Frame | at baseline, week 48, 96 and 144 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT: all randomised patients who had at least 1 dose of study medication, regardless of protocol adherence. A LOCF method was used for calculation. |
| Arm/Group Title | DRV/r+2NRTIs | DRV/r |
|---|---|---|
| Arm/Group Description | 800 mg qd (2 x 400 mg tablet) + 2 NRTI for 144 weeks | 800 mg qd (2 x 400 mg tablet) monotherapy for 144 weeks |
| Measure Participants | 126 | 115 |
| week 48 |
0.4
(0.5)
|
-0.2
(0.5)
|
| week 96 |
-0.6
(0.5)
|
0.8
(0.6)
|
| week 144 |
-0.3
(0.5)
|
0.6
(0.6)
|
Adverse Events
| Time Frame | Adverse events were collected for the duration of the study. Mean exposure at the time of primary analysis (Week 48) was 457.3 days for the overall study population (462.3 days for the DRV/r+2NRTIs group and 452.2 days for the DRV/r group). | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Adverse events were either reported by the subjects voluntarily or were obtained by means of interviewing subjects in a non-directed manner at study visits. | |||||
| Arm/Group Title | DRV/r+2NRTIs | DRV/r | Total | |||
| Arm/Group Description | 800 mg qd (2 x 400 mg tablet) + 2 NRTI for 144 weeks | 800 mg qd (2 x 400 mg tablet) monotherapy for 144 weeks | ||||
All Cause Mortality |
||||||
| DRV/r+2NRTIs | DRV/r | Total | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| DRV/r+2NRTIs | DRV/r | Total | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 14/129 (10.9%) | 14/127 (11%) | 28/256 (10.9%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 1/129 (0.8%) | 0/127 (0%) | 1/256 (0.4%) | |||
| Thrombocytopenia | 1/129 (0.8%) | 0/127 (0%) | 1/256 (0.4%) | |||
| Cardiac disorders | ||||||
| Acute Myocardial Infarction | 1/129 (0.8%) | 0/127 (0%) | 1/256 (0.4%) | |||
| Eye disorders | ||||||
| Uveitis | 0/129 (0%) | 1/127 (0.8%) | 1/256 (0.4%) | |||
| Gastrointestinal disorders | ||||||
| Duodenal Ulcer | 1/129 (0.8%) | 0/127 (0%) | 1/256 (0.4%) | |||
| Dysphagia | 0/129 (0%) | 1/127 (0.8%) | 1/256 (0.4%) | |||
| Vomiting | 0/129 (0%) | 1/127 (0.8%) | 1/256 (0.4%) | |||
| General disorders | ||||||
| Pyrexia | 1/129 (0.8%) | 1/127 (0.8%) | 2/256 (0.8%) | |||
| Hepatobiliary disorders | ||||||
| Jaundice | 0/129 (0%) | 1/127 (0.8%) | 1/256 (0.4%) | |||
| Infections and infestations | ||||||
| Gastroenteritis | 1/129 (0.8%) | 0/127 (0%) | 1/256 (0.4%) | |||
| Hepatitis A | 1/129 (0.8%) | 0/127 (0%) | 1/256 (0.4%) | |||
| Pneumonia | 1/129 (0.8%) | 0/127 (0%) | 1/256 (0.4%) | |||
| Respiratory Tract Infection | 1/129 (0.8%) | 0/127 (0%) | 1/256 (0.4%) | |||
| Subcutaneous Abscess | 1/129 (0.8%) | 0/127 (0%) | 1/256 (0.4%) | |||
| Bronchitis | 0/129 (0%) | 1/127 (0.8%) | 1/256 (0.4%) | |||
| Hepatitis C | 0/129 (0%) | 1/127 (0.8%) | 1/256 (0.4%) | |||
| Neurosyphilis | 0/129 (0%) | 2/127 (1.6%) | 2/256 (0.8%) | |||
| Secondary Syphilis | 0/129 (0%) | 1/127 (0.8%) | 1/256 (0.4%) | |||
| Injury, poisoning and procedural complications | ||||||
| Femoral Neck Fracture | 0/129 (0%) | 1/127 (0.8%) | 1/256 (0.4%) | |||
| Incisional Hernia | 0/129 (0%) | 1/127 (0.8%) | 1/256 (0.4%) | |||
| Procedural Pain | 0/129 (0%) | 1/127 (0.8%) | 1/256 (0.4%) | |||
| Investigations | ||||||
| Aspartate Aminotransferase Increased | 1/129 (0.8%) | 0/127 (0%) | 1/256 (0.4%) | |||
| Csf Pressure Decreased | 0/129 (0%) | 1/127 (0.8%) | 1/256 (0.4%) | |||
| Lipase Increased | 0/129 (0%) | 1/127 (0.8%) | 1/256 (0.4%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Intervertebral Disc Protrusion | 0/129 (0%) | 1/127 (0.8%) | 1/256 (0.4%) | |||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Hodgkin's Disease | 1/129 (0.8%) | 0/127 (0%) | 1/256 (0.4%) | |||
| Tongue Neoplasm Malignant Stage Unspecified | 1/129 (0.8%) | 0/127 (0%) | 1/256 (0.4%) | |||
| Nervous system disorders | ||||||
| Convulsion | 1/129 (0.8%) | 0/127 (0%) | 1/256 (0.4%) | |||
| Nervous System Disorder | 1/129 (0.8%) | 0/127 (0%) | 1/256 (0.4%) | |||
| Psychiatric disorders | ||||||
| Somatoform Disorder | 1/129 (0.8%) | 0/127 (0%) | 1/256 (0.4%) | |||
| Psychotic Disorder | 0/129 (0%) | 2/127 (1.6%) | 2/256 (0.8%) | |||
| Renal and urinary disorders | ||||||
| Nephrolithiasis | 1/129 (0.8%) | 0/127 (0%) | 1/256 (0.4%) | |||
| Reproductive system and breast disorders | ||||||
| Benign Prostatic Hyperplasia | 0/129 (0%) | 1/127 (0.8%) | 1/256 (0.4%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Asthma | 0/129 (0%) | 1/127 (0.8%) | 1/256 (0.4%) | |||
| Surgical and medical procedures | ||||||
| Cataract Operation | 1/129 (0.8%) | 0/127 (0%) | 1/256 (0.4%) | |||
| Varicose Vein Operation | 0/129 (0%) | 1/127 (0.8%) | 1/256 (0.4%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| DRV/r+2NRTIs | DRV/r | Total | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 98/129 (76%) | 103/127 (81.1%) | 201/256 (78.5%) | |||
| Gastrointestinal disorders | ||||||
| Diarrhoea | 26/129 (20.2%) | 26/127 (20.5%) | 52/256 (20.3%) | |||
| Vomiting | 9/129 (7%) | 1/127 (0.8%) | 10/256 (3.9%) | |||
| Nausea | 7/129 (5.4%) | 5/127 (3.9%) | 12/256 (4.7%) | |||
| General disorders | ||||||
| Fatigue | 6/129 (4.7%) | 7/127 (5.5%) | 13/256 (5.1%) | |||
| Infections and infestations | ||||||
| Bronchitis | 12/129 (9.3%) | 10/127 (7.9%) | 22/256 (8.6%) | |||
| Nasopharyngitis | 10/129 (7.8%) | 15/127 (11.8%) | 25/256 (9.8%) | |||
| Respiratory Tract Infection | 9/129 (7%) | 1/127 (0.8%) | 10/256 (3.9%) | |||
| Upper Respiratory Tract Infection | 7/129 (5.4%) | 12/127 (9.4%) | 19/256 (7.4%) | |||
| Investigations | ||||||
| Blood Cholesterol Increased | 2/129 (1.6%) | 7/127 (5.5%) | 9/256 (3.5%) | |||
| Metabolism and nutrition disorders | ||||||
| Hypercholesterolaemia | 6/129 (4.7%) | 19/127 (15%) | 25/256 (9.8%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Back Pain | 4/129 (3.1%) | 8/127 (6.3%) | 12/256 (4.7%) | |||
| Nervous system disorders | ||||||
| Headache | 10/129 (7.8%) | 12/127 (9.4%) | 22/256 (8.6%) | |||
| Psychiatric disorders | ||||||
| Depression | 7/129 (5.4%) | 12/127 (9.4%) | 19/256 (7.4%) | |||
| Renal and urinary disorders | ||||||
| Haematuria | 12/129 (9.3%) | 7/127 (5.5%) | 19/256 (7.4%) | |||
| Leukocyturia | 7/129 (5.4%) | 6/127 (4.7%) | 13/256 (5.1%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Cough | 8/129 (6.2%) | 7/127 (5.5%) | 15/256 (5.9%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| Rash | 4/129 (3.1%) | 8/127 (6.3%) | 12/256 (4.7%) | |||
| Vascular disorders | ||||||
| Hypertension | 9/129 (7%) | 6/127 (4.7%) | 15/256 (5.9%) | |||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Sponsor (SP) shall have the 1st right to present the Data without approval from the Principal Investigator (PI). If no publication is submitted by SP within 12 months after closure, or after SP confirms there will be no publication, the PI shall have the right to publish. Prior to submission, the PI will provide the SP with at least 45 days for review of a manuscript. If requested, the PI will withhold such publication for up to an additional 60 days to allow for filing of a patent application
Results Point of Contact
| Name/Title | EMEA Medical Affairs Director Virology |
|---|---|
| Organization | Jan-Cilag Germany |
| Phone | +49 7624 907580 |
- CR013159
- TMC114HIV3006
- 2006-006437-40