A Phase 2B Multicenter, Randomized, Comparative Trial Of UK-453,061 Versus Etravirine In Combination With Darunavir/Ritonavir And A Nucleos(t)Ide Reverse Transcriptase Inhibitor For The Treatment Of Antiretroviral Experienced HIV-1 Infected Subjects With Evidence Of NNRTI Resistant HIV-1
Sponsor
Pfizer (Industry)
Overall Status
Terminated
CT.gov ID
NCT00823979
Collaborator
(none)
105
63
3
42.8
1.7
0
Study Details
Study Description
Brief Summary
This is a 96 week study to determine if UK- 453,061 in combination with Darunavir /ritonavir and a Nucleos(t)ide Reverse Transcriptase inhibitor is as efficacious, safe and tolerable as etravirine in combination with Darunavir /ritonavir and a Nucleos(t)ide Reverse Transcriptase inhibitor in HIV-1 infected patients who have been previously treated with antiretroviral drugs and have NNRTI resistance mutations.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
The trial was terminated on 12 April, 2012 due to lack of efficacy at the Week 24 analysis. The decision to terminate the trial was not based on any safety concerns.
Study Design
Study Type:
Interventional
Actual Enrollment
:
105 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double
Primary Purpose:
Treatment
Official Title:
A Phase 2b Multicenter, Randomized, Comparative Trial Of Uk-453,061 Versus Etravirine In Combination With Darunavir/Ritonavir And A Nucleotide/Nucleoside Reverse Transcriptase Inhibitor For The Treatment Of Antiretroviral Experienced Hiv-1 Infected Subjects With Evidence Of Nnrti Resistant Hiv-1
Actual Study Start Date
:
Mar 25, 2009
Actual Primary Completion Date
:
Oct 18, 2012
Actual Study Completion Date
:
Oct 18, 2012
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: UK- 453,061 Dose One
|
Drug: UK-453,061 Dose 1
UK 453,061 750 mg QD + one optimized NRTI + darunavir/ritonavir.
|
| Experimental: UK- 453,061 Dose Two
|
Drug: UK-453,061 Dose 2
UK 453,061 1000 mg QD + one optimized NRTI + darunavir/ritonavir.
|
| Active Comparator: Comparator
|
Drug: Etravirine
Etravirine 200 mg BID + one optimized NRTI + darunavir/ritonavir.
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants With Human Immunodeficiency Virus Type 1 Ribonucleic Acid (HIV-1 RNA) Levels Less Than (<) 50 Copies/Milliliter (mL) at Week 24 [Week 24]
Plasma HIV-1 RNA level was determined by the Roche Amplicor HIV-1 Monitor standard assay (version 1.5).
Secondary Outcome Measures
- Percentage of Participants With HIV-1 RNA Levels <50 Copies/mL at Week 48 and 96 [Weeks 48, 96]
Plasma HIV-1 RNA level was determined by the Roche Amplicor HIV-1 Monitor standard assay (version 1.5).
- Percentage of Participants With HIV-1 RNA Levels <400 Copies/mL at Week 24, 48 and 96 [Week 24, 48, 96]
Plasma HIV-1 RNA level was determined by the Roche Amplicor HIV-1 Monitor standard assay (version 1.5).
- Change From Baseline in log10 Transformed HIV-1 RNA Levels at Week 24, 48 and 96 [Baseline, Week 24, 48, 96]
Plasma HIV-1 RNA level was determined by the Roche Amplicor HIV-1 Monitor standard assay (version 1.5). For the log10 scale, all the HIV-1 RNA levels were log10 transformed prior to the average calculations. Baseline value calculated as average of measurements collected prior to and including Day 1 pre-dose.
- Time-Averaged Difference (TAD) in log10 Transformed HIV-1 RNA Levels at Week 24, 48 and 96 [Week 24, 48, 96]
TAD was calculated as (area under the curve of HIV-1 RNA levels [log10 copies/mL] from baseline to the time point of interest divided by time period in weeks) minus baseline HIV-1 RNA level (log10 copies/mL). Baseline value calculated as average of measurements collected at prior to and including Day 1 pre-dose. Due to early termination of the study decision was made not to derive TAD results for Week 96.
- Percentage of Participants With Response as Determined by the Time to Loss of Virologic Response (TLOVR50) Algorithm at Week 24, 48 and 96 [Week 24, 48, 96]
TLOVR50 response (50 denotes lower limit of quantification [LLOQ] of assay=50 copies/mL): compliment to TLOVR50 failure. TLOVR50 failure based on observed HIV-1 RNA levels and failure events (death; permanent discontinuation of drug; lost to follow-up; new ARV drug; met treatment failure [TF] criteria). TF: an increase of at least (>=)3 times the baseline plasma HIV-1 RNA level at Week 2 or thereafter; failure to achieve HIV-1 RNA level <50 copies/mL at Week 24; starting at Week 2, an increase in HIV-1 RNA level to detectable levels (>50 copies/mL); HIV-1 RNA <1 log10 decrease from baseline at Week 4 or thereafter. TF were confirmed by second measurement >=14 days after first. Baseline value was calculated as the average of the measurements collected prior to and including Day 1 pre-dose.
- Change From Baseline in Cluster of Differentiation 4 (CD4+) Absolute Lymphocyte Counts at Week 24, 48 and 96 [Baseline, Week 24, 48, 96]
Blood samples for immunological status assessed by CD4+ lymphocyte count. Baseline value was calculated as the average of the measurements collected prior to and including Day 1 pre-dose.
- Change From Baseline in Cluster of Differentiation 4 (CD4+) Percentage Lymphocyte Counts at Week 24, 48, 96 [Baseline, Week 24, 48, 96]
Blood samples for immunological status assessed by CD4+ lymphocyte count. Baseline value was calculated as the average of the measurements collected prior to and including Day 1 pre-dose.
- Number of Participants With Non-nucleoside Reverse Transcriptase Inhibitors (NNRTI) Resistance-Associated Mutations (RAMs) and/or Phenotypic Susceptibility at Time of Treatment Failure Through Week 48 [Baseline through Week 48]
Genotypic and phenotypic resistance to NNRTIs based on International Acquired Immunodeficiency Syndrome (AIDS) Society, United States of America (IAS-USA) RAM guidelines were evaluated using Monogram Biosciences PhenoSenseGT Assay at Baseline. This was then repeated for all participants with HIV-1 viral load >500 copies/mL at treatment failure, up to Week 48.
- Number of Participants With Laboratory Test Abnormalities [Baseline up to Week 48 or early termination]
Laboratory analysis included blood chemistry, hematology and urinalysis.
- Population Pharmacokinetics (PK) of Lersivirine [Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48]
Data for this Outcome Measure are not reported here because the analysis population includes participants who were not enrolled in this study. ClinicalTrials.gov is designed for reporting results from only those participants who were enrolled in the study and described in the Participant Flow and Baseline Characteristics modules.
- Lersivirine Success Percentage With Reference to Median Minimum Observed Plasma Concentration (Cmin) [Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48]
Simple quartile exposure analysis of success rate (viral load <50 copies/mL) versus median Cmin assesses the exposure response relationship. Percentage of participants with HIV-1 RNA level <50 copies/mL at median Cmin quartile were planned to be reported.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 65 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Male or female at least 18 years of age available for a follow-up period of at least 96 weeks.
-
HIV 1 RNA viral load of greater then 500 copies/mL.
-
Negative urine pregnancy test.
Exclusion Criteria:
-
Suspected or documented active, untreated HIV-1 related opportunistic infection or other condition requiring acute therapy at the time of randomization.
-
Subjects with acute Hepatitis B and/or C within 30 days of randomization.
-
Previous use of Darunavir or etravirine
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Jeffrey Goodman Special Care Clinic | Los Angeles | California | United States | 90028 |
| 2 | Office of Anthony Mills, MD, Inc. | Los Angeles | California | United States | 90069 |
| 3 | CARES | Sacramento | California | United States | 95814 |
| 4 | University of California Davis Medical Center | Sacramento | California | United States | 95817 |
| 5 | San Francisco Veterans Affairs Medical Center | San Francisco | California | United States | 94121 |
| 6 | The Kinder Medical Group | Miami | Florida | United States | 33133 |
| 7 | Care Resource | Miami | Florida | United States | 33137 |
| 8 | Orlando Immunology Center | Orlando | Florida | United States | 32803 |
| 9 | Infectious Diseases Associates of Northwest Florida, PA | Pensacola | Florida | United States | 32504 |
| 10 | Hillsborough County Health Department | Tampa | Florida | United States | 33602 |
| 11 | AIDS Research Consortium of Atlanta | Atlanta | Georgia | United States | 30308 |
| 12 | Ruth M. Rothstein CORE Center | Chicago | Illinois | United States | 60612 |
| 13 | Nassau University Medical Center | East Meadow | New York | United States | 11554 |
| 14 | Greiger Clinic | Mount Vernon | New York | United States | 10550 |
| 15 | Rosedale Infectious Diseases | Huntersville | North Carolina | United States | 28078 |
| 16 | University of Cincinnati Medical Center | Cincinnati | Ohio | United States | 45267-0405 |
| 17 | Saint Hope Foundation - Bellaire Clinic | Bellaire | Texas | United States | 77401 |
| 18 | Saint Hope Foundation - Conroe Clinic | Conroe | Texas | United States | 77301 |
| 19 | Nicholaos C. Bellos, MD, PA | Dallas | Texas | United States | 75204 |
| 20 | University of Texas Southwestern Medical Center at Dallas | Dallas | Texas | United States | 75235 |
| 21 | Saint Hope Foundation - Stafford Clinic | Stafford | Texas | United States | 77477 |
| 22 | Instituto A.Z. de Pesquisa e Ensino | Curitiba | PR | Brazil | 80240-280 |
| 23 | Hospital Geral de Nova Iguacu | Nova Iguacu | RJ | Brazil | 26030-381 |
| 24 | Hospital Nossa Senhora da Conceicao | PoA | RS | Brazil | 91350-200 |
| 25 | Instituto de Infectologia Campinas | Campinas | SP | Brazil | 13015-080 |
| 26 | Centro de Referencia e Treinamento DST/AIDS | Sao Paulo | SP | Brazil | 04121-000 |
| 27 | Hospital Heliopolis | Sao Paulo | SP | Brazil | 04231-030 |
| 28 | Klinikum der Universitaet zu Koeln, Klinik I fuer Innere Medizin | Koeln | Germany | 50937 | |
| 29 | Unita' Operativa Malattie Infettive | Bologna | Italy | 40138 | |
| 30 | U.O.S. Immunologia Clinica | Roma | Italy | 00184 | |
| 31 | Hospital Raja Perempuan Zainab II | Kota Bharu | Kelantan | Malaysia | 15586 |
| 32 | University Malaya Medical Centre | Kuala Lumpur | Malaysia | 59100 | |
| 33 | Oddzial do Leczenia HIV | Szczecin | Poland | 71-455 | |
| 34 | SPZOZ Wojewodzki Szpital Zakazny | Warszawa | Poland | 01-201 | |
| 35 | Hospitais da Universidade de Coimbra | Coimbra | Portugal | 3000-075 | |
| 36 | Centro Hospitalar de Lisboa - Zona Central - Hospital Santo António Capuchos | Lisboa | Portugal | 1169-050 | |
| 37 | Centro Hospitalar de Lisboa Ocidental, EPE. | Lisboa | Portugal | 1349-019 | |
| 38 | Hospital São João | Porto | Portugal | 4200-319 | |
| 39 | Hospital de Joaquim Urbano | Porto | Portugal | 4369-004 | |
| 40 | Innovative Care PSC | Bayamon | Puerto Rico | 00959 | |
| 41 | Ararat Research Center | Ponce | Puerto Rico | 00717-1563 | |
| 42 | University of Puerto Rico - Medical Sciences Campus - Puerto Rico Medical Center | Rio Piedras | Puerto Rico | 00935 | |
| 43 | HOPE Clinical Research | San Juan | Puerto Rico | 00909 | |
| 44 | UPR-CTU Pharmacy | San Juan | Puerto Rico | 00935 | |
| 45 | Soweto Clinical Trials Centre | Johannesburg | Gauteng | South Africa | 1818 |
| 46 | University of Witwatersrand | Johannesburg | Gauteng | South Africa | 2193 |
| 47 | Chris Hani Baragwanath Hospital | Soweto | Johannesburg | South Africa | 2013 |
| 48 | Dr. J Fourie Medical Centre | Dundee | Kwazulu-natal | South Africa | 3000 |
| 49 | 203 Maxwell Centre | Durban | Kwazulu-natal | South Africa | 4001 |
| 50 | Willowmead Medical Center | Cape Town | Western CAPE | South Africa | 7780 |
| 51 | Desmond Tutu HIV Foundation | Cape Town | Western CAPE | South Africa | 7925 |
| 52 | Hospital Universitari Germans Trias I Pujol | Badalona | Barcelona | Spain | 08916 |
| 53 | Hospital Universitario La Paz | Madrid | Spain | 28046 | |
| 54 | Department of Infectious Disease, E-Da Hospital | Kaohsiung County | Taiwan | 82445 | |
| 55 | Veterans General Hospital - Taipei | Taipei | Taiwan | ||
| 56 | Vinnitsa Regional center for AIDS Prevention and Control | Berezyna | Vinnitsa District, Vinnitsa Region | Ukraine | 23222 |
| 57 | Donetsk Regional Center of AIDSs prophylaxis and control | Donetsk | Ukraine | 83045 | |
| 58 | Lugansk Regional Center of AIDS prophylaxis and control | Lugansk | Ukraine | 91045 | |
| 59 | Brighton and Sussex University Hospitals NHS Trust | Brighton | EAST Sussex | United Kingdom | BN2 1ES |
| 60 | North Manchester General Hospital | Crumpsall | Greater Manchester | United Kingdom | M8 5RB |
| 61 | Royal Infirmary GUM Clinic | Edinburgh | United Kingdom | EH3 9HA | |
| 62 | Western General Hospital | Edinburgh | United Kingdom | EH4 2XU | |
| 63 | Royal Free Hospital | London | United Kingdom | NW3 2QG |
Sponsors and Collaborators
- Pfizer
Investigators
- Study Director: Pfizer CT.gov Call Center, Pfizer
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT00823979
Other Study ID Numbers:
- A5271022
- 2007-004392-19
First Posted:
Jan 16, 2009
Last Update Posted:
Dec 4, 2018
Last Verified:
Nov 1, 2018
Keywords provided by Pfizer
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Lersivirine 750 mg | Lersivirine 1000 mg | Etravirine 200 mg |
|---|---|---|---|
| Arm/Group Description | Lersivirine (UK-453,061) 250 milligram (mg) 3 tablets equivalent to lersivirine 750 mg and 1 placebo tablet matched to lersivirine 250 mg tablet, orally once daily up to 96 weeks in combination with 1 optimized nucleoside reverse transcriptase inhibitors (NRTI) as per individual prescribing information, darunavir 600 mg tablet orally twice daily and ritonavir 100 mg tablet or capsule orally twice daily. | Lersivirine (UK-453,061) 250 mg 4 tablets equivalent to lersivirine 1000 mg, orally once daily up to 96 weeks in combination with 1 optimized NRTI as per individual prescribing information, darunavir 600 mg tablet orally twice daily and ritonavir 100 mg tablet or capsule orally twice daily. | Etravirine 100 mg 2 tablets equivalent to etravirine 200 mg, orally twice daily up to 96 weeks in combination with 1 optimized NRTI as per individual prescribing information, darunavir 600 mg tablet orally twice daily and ritonavir 100 mg tablet or capsule orally twice daily. |
| Period Title: Overall Study | |||
| STARTED | 35 | 35 | 35 |
| Treated | 31 | 32 | 34 |
| COMPLETED | 6 | 3 | 11 |
| NOT COMPLETED | 29 | 32 | 24 |
Baseline Characteristics
| Arm/Group Title | Lersivirine 750 mg | Lersivirine 1000 mg | Etravirine 200 mg | Total |
|---|---|---|---|---|
| Arm/Group Description | Lersivirine (UK-453,061) 250 milligram (mg) 3 tablets equivalent to lersivirine 750 mg and 1 placebo tablet matched to lersivirine 250 mg tablet, orally once daily up to 96 weeks in combination with 1 optimized nucleoside reverse transcriptase inhibitors (NRTI) as per individual prescribing information, darunavir 600 mg tablet orally twice daily and ritonavir 100 mg tablet or capsule orally twice daily. | Lersivirine (UK-453,061) 250 mg 4 tablets equivalent to lersivirine 1000 mg, orally once daily up to 96 weeks in combination with 1 optimized NRTI as per individual prescribing information, darunavir 600 mg tablet orally twice daily and ritonavir 100 mg tablet or capsule orally twice daily. | Etravirine 100 mg 2 tablets equivalent to etravirine 200 mg, orally twice daily up to 96 weeks in combination with 1 optimized NRTI as per individual prescribing information, darunavir 600 mg tablet orally twice daily and ritonavir 100 mg tablet or capsule orally twice daily. | Total of all reporting groups |
| Overall Participants | 31 | 32 | 34 | 97 |
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
41.1
(8.9)
|
40.0
(8.7)
|
41.9
(9.1)
|
41.0
(8.9)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
15
48.4%
|
18
56.3%
|
18
52.9%
|
51
52.6%
|
| Male |
16
51.6%
|
14
43.8%
|
16
47.1%
|
46
47.4%
|
Outcome Measures
| Title | Percentage of Participants With Human Immunodeficiency Virus Type 1 Ribonucleic Acid (HIV-1 RNA) Levels Less Than (<) 50 Copies/Milliliter (mL) at Week 24 |
|---|---|
| Description | Plasma HIV-1 RNA level was determined by the Roche Amplicor HIV-1 Monitor standard assay (version 1.5). |
| Time Frame | Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population. Participants who died, discontinued, lost to follow-up, switched/changed dose of anti-retro viral (ARV) drug not allowed by protocol, had missing plasma HIV-1 RNA data at 24 weeks were considered to have plasma HIV-1 RNA >=50 copies/mL and were referred to as failure. |
| Arm/Group Title | Lersivirine 750 mg | Lersivirine 1000 mg | Etravirine 200 mg |
|---|---|---|---|
| Arm/Group Description | Lersivirine (UK-453,061) 250 milligram (mg) 3 tablets equivalent to lersivirine 750 mg and 1 placebo tablet matched to lersivirine 250 mg tablet, orally once daily up to 96 weeks in combination with 1 optimized nucleoside reverse transcriptase inhibitors (NRTI) as per individual prescribing information, darunavir 600 mg tablet orally twice daily and ritonavir 100 mg tablet or capsule orally twice daily. | Lersivirine (UK-453,061) 250 mg 4 tablets equivalent to lersivirine 1000 mg, orally once daily up to 96 weeks in combination with 1 optimized NRTI as per individual prescribing information, darunavir 600 mg tablet orally twice daily and ritonavir 100 mg tablet or capsule orally twice daily. | Etravirine 100 mg 2 tablets equivalent to etravirine 200 mg, orally twice daily up to 96 weeks in combination with 1 optimized NRTI as per individual prescribing information, darunavir 600 mg tablet orally twice daily and ritonavir 100 mg tablet or capsule orally twice daily. |
| Measure Participants | 31 | 32 | 34 |
| Number [percentage of participants] |
48.4
156.1%
|
43.8
136.9%
|
67.6
198.8%
|
| Title | Percentage of Participants With HIV-1 RNA Levels <50 Copies/mL at Week 48 and 96 |
|---|---|
| Description | Plasma HIV-1 RNA level was determined by the Roche Amplicor HIV-1 Monitor standard assay (version 1.5). |
| Time Frame | Weeks 48, 96 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population. Participants who died, discontinued,lost to follow-up,switched/changed dose of ARV drug not allowed by protocol,had missing plasma HIV-1 RNA data at 48, 96 weeks were considered to have plasma HIV-1 RNA >=50 copies/mL and were referred to as failure. n=participants evaluable at specified time point for each arm group, respectively. |
| Arm/Group Title | Lersivirine 750 mg | Lersivirine 1000 mg | Etravirine 200 mg |
|---|---|---|---|
| Arm/Group Description | Lersivirine (UK-453,061) 250 milligram (mg) 3 tablets equivalent to lersivirine 750 mg and 1 placebo tablet matched to lersivirine 250 mg tablet, orally once daily up to 96 weeks in combination with 1 optimized nucleoside reverse transcriptase inhibitors (NRTI) as per individual prescribing information, darunavir 600 mg tablet orally twice daily and ritonavir 100 mg tablet or capsule orally twice daily. | Lersivirine (UK-453,061) 250 mg 4 tablets equivalent to lersivirine 1000 mg, orally once daily up to 96 weeks in combination with 1 optimized NRTI as per individual prescribing information, darunavir 600 mg tablet orally twice daily and ritonavir 100 mg tablet or capsule orally twice daily. | Etravirine 100 mg 2 tablets equivalent to etravirine 200 mg, orally twice daily up to 96 weeks in combination with 1 optimized NRTI as per individual prescribing information, darunavir 600 mg tablet orally twice daily and ritonavir 100 mg tablet or capsule orally twice daily. |
| Measure Participants | 31 | 32 | 34 |
| Week 48 (n=31, 32, 34) |
41.9
135.2%
|
31.3
97.8%
|
61.8
181.8%
|
| Week 96 (n=28, 28, 27) |
25.0
80.6%
|
14.3
44.7%
|
37.0
108.8%
|
| Title | Percentage of Participants With HIV-1 RNA Levels <400 Copies/mL at Week 24, 48 and 96 |
|---|---|
| Description | Plasma HIV-1 RNA level was determined by the Roche Amplicor HIV-1 Monitor standard assay (version 1.5). |
| Time Frame | Week 24, 48, 96 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population. Participants who died,discontinued,lost to follow-up,switched/changed dose of ARV drug not allowed by protocol,had missing plasma HIV-1 RNA data at 24, 48, 96 weeks were considered to have plasma HIV-1 RNA >=400 copies/mL and referred to as failure. n=participants evaluable at specified time point for each arm group, respectively. |
| Arm/Group Title | Lersivirine 750 mg | Lersivirine 1000 mg | Etravirine 200 mg |
|---|---|---|---|
| Arm/Group Description | Lersivirine (UK-453,061) 250 milligram (mg) 3 tablets equivalent to lersivirine 750 mg and 1 placebo tablet matched to lersivirine 250 mg tablet, orally once daily up to 96 weeks in combination with 1 optimized nucleoside reverse transcriptase inhibitors (NRTI) as per individual prescribing information, darunavir 600 mg tablet orally twice daily and ritonavir 100 mg tablet or capsule orally twice daily. | Lersivirine (UK-453,061) 250 mg 4 tablets equivalent to lersivirine 1000 mg, orally once daily up to 96 weeks in combination with 1 optimized NRTI as per individual prescribing information, darunavir 600 mg tablet orally twice daily and ritonavir 100 mg tablet or capsule orally twice daily. | Etravirine 100 mg 2 tablets equivalent to etravirine 200 mg, orally twice daily up to 96 weeks in combination with 1 optimized NRTI as per individual prescribing information, darunavir 600 mg tablet orally twice daily and ritonavir 100 mg tablet or capsule orally twice daily. |
| Measure Participants | 31 | 32 | 34 |
| Week 24 (n=31, 32, 34) |
54.8
176.8%
|
50.0
156.3%
|
79.4
233.5%
|
| Week 48 (n=31, 32, 34) |
41.9
135.2%
|
34.4
107.5%
|
70.6
207.6%
|
| Week 96 (n=28, 28, 27) |
25.0
80.6%
|
14.3
44.7%
|
37.0
108.8%
|
| Title | Change From Baseline in log10 Transformed HIV-1 RNA Levels at Week 24, 48 and 96 |
|---|---|
| Description | Plasma HIV-1 RNA level was determined by the Roche Amplicor HIV-1 Monitor standard assay (version 1.5). For the log10 scale, all the HIV-1 RNA levels were log10 transformed prior to the average calculations. Baseline value calculated as average of measurements collected prior to and including Day 1 pre-dose. |
| Time Frame | Baseline, Week 24, 48, 96 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population. Participant discontinued before a visit of interest: value imputed as zero; not discontinued but observation is missing: last observation carried forward (LOCF) imputation used; missing baseline or no HIV-1 RNA level assessment: value imputed as zero. |
| Arm/Group Title | Lersivirine 750 mg | Lersivirine 1000 mg | Etravirine 200 mg |
|---|---|---|---|
| Arm/Group Description | Lersivirine (UK-453,061) 250 milligram (mg) 3 tablets equivalent to lersivirine 750 mg and 1 placebo tablet matched to lersivirine 250 mg tablet, orally once daily up to 96 weeks in combination with 1 optimized nucleoside reverse transcriptase inhibitors (NRTI) as per individual prescribing information, darunavir 600 mg tablet orally twice daily and ritonavir 100 mg tablet or capsule orally twice daily. | Lersivirine (UK-453,061) 250 mg 4 tablets equivalent to lersivirine 1000 mg, orally once daily up to 96 weeks in combination with 1 optimized NRTI as per individual prescribing information, darunavir 600 mg tablet orally twice daily and ritonavir 100 mg tablet or capsule orally twice daily. | Etravirine 100 mg 2 tablets equivalent to etravirine 200 mg, orally twice daily up to 96 weeks in combination with 1 optimized NRTI as per individual prescribing information, darunavir 600 mg tablet orally twice daily and ritonavir 100 mg tablet or capsule orally twice daily. |
| Measure Participants | 31 | 32 | 34 |
| Baseline |
4.28
(0.99)
|
4.76
(0.82)
|
4.59
(0.79)
|
| Change at Week 24 |
-1.53
(1.58)
|
-1.89
(1.46)
|
-2.32
(1.21)
|
| Change at Week 48 |
-1.30
(1.64)
|
-1.08
(1.48)
|
-2.06
(1.42)
|
| Change at Week 96 |
-0.69
(1.39)
|
-0.36
(1.00)
|
-0.96
(1.49)
|
| Title | Time-Averaged Difference (TAD) in log10 Transformed HIV-1 RNA Levels at Week 24, 48 and 96 |
|---|---|
| Description | TAD was calculated as (area under the curve of HIV-1 RNA levels [log10 copies/mL] from baseline to the time point of interest divided by time period in weeks) minus baseline HIV-1 RNA level (log10 copies/mL). Baseline value calculated as average of measurements collected at prior to and including Day 1 pre-dose. Due to early termination of the study decision was made not to derive TAD results for Week 96. |
| Time Frame | Week 24, 48, 96 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population. Participant discontinued before a visit of interest: TAD imputed as zero; not discontinued but observation was missing at visit: TAD to the last non-missing timepoint; not discontinued and missing values between baseline and visit: ignore missing values; missing baseline or no HIV-1 RNA level assessment: TAD imputed as zero. |
| Arm/Group Title | Lersivirine 750 mg | Lersivirine 1000 mg | Etravirine 200 mg |
|---|---|---|---|
| Arm/Group Description | Lersivirine (UK-453,061) 250 milligram (mg) 3 tablets equivalent to lersivirine 750 mg and 1 placebo tablet matched to lersivirine 250 mg tablet, orally once daily up to 96 weeks in combination with 1 optimized nucleoside reverse transcriptase inhibitors (NRTI) as per individual prescribing information, darunavir 600 mg tablet orally twice daily and ritonavir 100 mg tablet or capsule orally twice daily. | Lersivirine (UK-453,061) 250 mg 4 tablets equivalent to lersivirine 1000 mg, orally once daily up to 96 weeks in combination with 1 optimized NRTI as per individual prescribing information, darunavir 600 mg tablet orally twice daily and ritonavir 100 mg tablet or capsule orally twice daily. | Etravirine 100 mg 2 tablets equivalent to etravirine 200 mg, orally twice daily up to 96 weeks in combination with 1 optimized NRTI as per individual prescribing information, darunavir 600 mg tablet orally twice daily and ritonavir 100 mg tablet or capsule orally twice daily. |
| Measure Participants | 31 | 32 | 34 |
| Week 24 |
-1.46
(1.12)
|
-1.72
(1.11)
|
-2.10
(0.92)
|
| Week 48 |
-1.28
(1.39)
|
-1.19
(1.35)
|
-1.89
(1.27)
|
| Title | Percentage of Participants With Response as Determined by the Time to Loss of Virologic Response (TLOVR50) Algorithm at Week 24, 48 and 96 |
|---|---|
| Description | TLOVR50 response (50 denotes lower limit of quantification [LLOQ] of assay=50 copies/mL): compliment to TLOVR50 failure. TLOVR50 failure based on observed HIV-1 RNA levels and failure events (death; permanent discontinuation of drug; lost to follow-up; new ARV drug; met treatment failure [TF] criteria). TF: an increase of at least (>=)3 times the baseline plasma HIV-1 RNA level at Week 2 or thereafter; failure to achieve HIV-1 RNA level <50 copies/mL at Week 24; starting at Week 2, an increase in HIV-1 RNA level to detectable levels (>50 copies/mL); HIV-1 RNA <1 log10 decrease from baseline at Week 4 or thereafter. TF were confirmed by second measurement >=14 days after first. Baseline value was calculated as the average of the measurements collected prior to and including Day 1 pre-dose. |
| Time Frame | Week 24, 48, 96 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT.Participants who died,discontinued,lost to follow-up,switched/changed dose of ARV drug not allowed by protocol,had missing plasma HIV-1 RNA data at 24,48 weeks were considered to have plasma HIV-1 RNA>=50 copies/mL;were referred as failure. Due to early termination of study,decision was made not to derive TLOVR50 responder analysis for Week 96. |
| Arm/Group Title | Lersivirine 750 mg | Lersivirine 1000 mg | Etravirine 200 mg |
|---|---|---|---|
| Arm/Group Description | Lersivirine (UK-453,061) 250 milligram (mg) 3 tablets equivalent to lersivirine 750 mg and 1 placebo tablet matched to lersivirine 250 mg tablet, orally once daily up to 96 weeks in combination with 1 optimized nucleoside reverse transcriptase inhibitors (NRTI) as per individual prescribing information, darunavir 600 mg tablet orally twice daily and ritonavir 100 mg tablet or capsule orally twice daily. | Lersivirine (UK-453,061) 250 mg 4 tablets equivalent to lersivirine 1000 mg, orally once daily up to 96 weeks in combination with 1 optimized NRTI as per individual prescribing information, darunavir 600 mg tablet orally twice daily and ritonavir 100 mg tablet or capsule orally twice daily. | Etravirine 100 mg 2 tablets equivalent to etravirine 200 mg, orally twice daily up to 96 weeks in combination with 1 optimized NRTI as per individual prescribing information, darunavir 600 mg tablet orally twice daily and ritonavir 100 mg tablet or capsule orally twice daily. |
| Measure Participants | 31 | 32 | 34 |
| Week 24 |
48.4
156.1%
|
43.8
136.9%
|
67.6
198.8%
|
| Week 48 |
41.9
135.2%
|
28.1
87.8%
|
55.9
164.4%
|
| Title | Change From Baseline in Cluster of Differentiation 4 (CD4+) Absolute Lymphocyte Counts at Week 24, 48 and 96 |
|---|---|
| Description | Blood samples for immunological status assessed by CD4+ lymphocyte count. Baseline value was calculated as the average of the measurements collected prior to and including Day 1 pre-dose. |
| Time Frame | Baseline, Week 24, 48, 96 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population included all randomized participants who received at least 1 dose of study drug. Missing values were imputed using LOCF. Participants with missing baseline or no CD4+ count available on treatment imputed as no or zero change from baseline. |
| Arm/Group Title | Lersivirine 750 mg | Lersivirine 1000 mg | Etravirine 200 mg |
|---|---|---|---|
| Arm/Group Description | Lersivirine (UK-453,061) 250 milligram (mg) 3 tablets equivalent to lersivirine 750 mg and 1 placebo tablet matched to lersivirine 250 mg tablet, orally once daily up to 96 weeks in combination with 1 optimized nucleoside reverse transcriptase inhibitors (NRTI) as per individual prescribing information, darunavir 600 mg tablet orally twice daily and ritonavir 100 mg tablet or capsule orally twice daily. | Lersivirine (UK-453,061) 250 mg 4 tablets equivalent to lersivirine 1000 mg, orally once daily up to 96 weeks in combination with 1 optimized NRTI as per individual prescribing information, darunavir 600 mg tablet orally twice daily and ritonavir 100 mg tablet or capsule orally twice daily. | Etravirine 100 mg 2 tablets equivalent to etravirine 200 mg, orally twice daily up to 96 weeks in combination with 1 optimized NRTI as per individual prescribing information, darunavir 600 mg tablet orally twice daily and ritonavir 100 mg tablet or capsule orally twice daily. |
| Measure Participants | 31 | 32 | 34 |
| Baseline |
247
(143)
|
259
(187)
|
227
(146)
|
| Change at Week 24 |
98
(140)
|
66
(111)
|
110
(108)
|
| Change at Week 48 |
122
(148)
|
74
(128)
|
128
(127)
|
| Change at Week 96 |
148
(177)
|
89
(152)
|
184
(197)
|
| Title | Change From Baseline in Cluster of Differentiation 4 (CD4+) Percentage Lymphocyte Counts at Week 24, 48, 96 |
|---|---|
| Description | Blood samples for immunological status assessed by CD4+ lymphocyte count. Baseline value was calculated as the average of the measurements collected prior to and including Day 1 pre-dose. |
| Time Frame | Baseline, Week 24, 48, 96 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population included all randomized participants who received at least 1 dose of study drug. Missing values were imputed using LOCF. Participants with missing baseline or no CD4+ count available on treatment imputed as no or zero change from baseline. |
| Arm/Group Title | Lersivirine 750 mg | Lersivirine 1000 mg | Etravirine 200 mg |
|---|---|---|---|
| Arm/Group Description | Lersivirine (UK-453,061) 250 milligram (mg) 3 tablets equivalent to lersivirine 750 mg and 1 placebo tablet matched to lersivirine 250 mg tablet, orally once daily up to 96 weeks in combination with 1 optimized nucleoside reverse transcriptase inhibitors (NRTI) as per individual prescribing information, darunavir 600 mg tablet orally twice daily and ritonavir 100 mg tablet or capsule orally twice daily. | Lersivirine (UK-453,061) 250 mg 4 tablets equivalent to lersivirine 1000 mg, orally once daily up to 96 weeks in combination with 1 optimized NRTI as per individual prescribing information, darunavir 600 mg tablet orally twice daily and ritonavir 100 mg tablet or capsule orally twice daily. | Etravirine 100 mg 2 tablets equivalent to etravirine 200 mg, orally twice daily up to 96 weeks in combination with 1 optimized NRTI as per individual prescribing information, darunavir 600 mg tablet orally twice daily and ritonavir 100 mg tablet or capsule orally twice daily. |
| Measure Participants | 31 | 32 | 34 |
| Baseline |
16.1
(8.7)
|
15.0
(8.8)
|
14.6
(8.3)
|
| Change at Week 24 |
3.0
(4.0)
|
3.7
(3.6)
|
3.7
(3.2)
|
| Change at Week 48 |
4.6
(5.3)
|
4.0
(4.1)
|
4.4
(3.8)
|
| Change at Week 96 |
5.4
(6.1)
|
4.2
(4.9)
|
6.2
(6.2)
|
| Title | Number of Participants With Non-nucleoside Reverse Transcriptase Inhibitors (NNRTI) Resistance-Associated Mutations (RAMs) and/or Phenotypic Susceptibility at Time of Treatment Failure Through Week 48 |
|---|---|
| Description | Genotypic and phenotypic resistance to NNRTIs based on International Acquired Immunodeficiency Syndrome (AIDS) Society, United States of America (IAS-USA) RAM guidelines were evaluated using Monogram Biosciences PhenoSenseGT Assay at Baseline. This was then repeated for all participants with HIV-1 viral load >500 copies/mL at treatment failure, up to Week 48. |
| Time Frame | Baseline through Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Virology analysis set included a subset of participants from TLOVR50 failures who had valid genotypic or phenotypic susceptibility testing result and with plasma HIV-1 RNA >500 copies/mL at baseline and treatment failure. |
| Arm/Group Title | Lersivirine 750 mg | Lersivirine 1000 mg | Etravirine 200 mg |
|---|---|---|---|
| Arm/Group Description | Lersivirine (UK-453,061) 250 milligram (mg) 3 tablets equivalent to lersivirine 750 mg and 1 placebo tablet matched to lersivirine 250 mg tablet, orally once daily up to 96 weeks in combination with 1 optimized nucleoside reverse transcriptase inhibitors (NRTI) as per individual prescribing information, darunavir 600 mg tablet orally twice daily and ritonavir 100 mg tablet or capsule orally twice daily. | Lersivirine (UK-453,061) 250 mg 4 tablets equivalent to lersivirine 1000 mg, orally once daily up to 96 weeks in combination with 1 optimized NRTI as per individual prescribing information, darunavir 600 mg tablet orally twice daily and ritonavir 100 mg tablet or capsule orally twice daily. | Etravirine 100 mg 2 tablets equivalent to etravirine 200 mg, orally twice daily up to 96 weeks in combination with 1 optimized NRTI as per individual prescribing information, darunavir 600 mg tablet orally twice daily and ritonavir 100 mg tablet or capsule orally twice daily. |
| Measure Participants | 12 | 16 | 4 |
| Number [participants] |
5
16.1%
|
3
9.4%
|
1
2.9%
|
| Title | Number of Participants With Laboratory Test Abnormalities |
|---|---|
| Description | Laboratory analysis included blood chemistry, hematology and urinalysis. |
| Time Frame | Baseline up to Week 48 or early termination |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety analysis set included all randomized participants who received at least 1 dose of study medication. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure. |
| Arm/Group Title | Lersivirine 750 mg | Lersivirine 1000 mg | Etravirine 200 mg |
|---|---|---|---|
| Arm/Group Description | Lersivirine (UK-453,061) 250 milligram (mg) 3 tablets equivalent to lersivirine 750 mg and 1 placebo tablet matched to lersivirine 250 mg tablet, orally once daily up to 96 weeks in combination with 1 optimized nucleoside reverse transcriptase inhibitors (NRTI) as per individual prescribing information, darunavir 600 mg tablet orally twice daily and ritonavir 100 mg tablet or capsule orally twice daily. | Lersivirine (UK-453,061) 250 mg 4 tablets equivalent to lersivirine 1000 mg, orally once daily up to 96 weeks in combination with 1 optimized NRTI as per individual prescribing information, darunavir 600 mg tablet orally twice daily and ritonavir 100 mg tablet or capsule orally twice daily. | Etravirine 100 mg 2 tablets equivalent to etravirine 200 mg, orally twice daily up to 96 weeks in combination with 1 optimized NRTI as per individual prescribing information, darunavir 600 mg tablet orally twice daily and ritonavir 100 mg tablet or capsule orally twice daily. |
| Measure Participants | 29 | 31 | 34 |
| Number [participants] |
27
87.1%
|
30
93.8%
|
33
97.1%
|
| Title | Population Pharmacokinetics (PK) of Lersivirine |
|---|---|
| Description | Data for this Outcome Measure are not reported here because the analysis population includes participants who were not enrolled in this study. ClinicalTrials.gov is designed for reporting results from only those participants who were enrolled in the study and described in the Participant Flow and Baseline Characteristics modules. |
| Time Frame | Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Lersivirine Success Percentage With Reference to Median Minimum Observed Plasma Concentration (Cmin) |
|---|---|
| Description | Simple quartile exposure analysis of success rate (viral load <50 copies/mL) versus median Cmin assesses the exposure response relationship. Percentage of participants with HIV-1 RNA level <50 copies/mL at median Cmin quartile were planned to be reported. |
| Time Frame | Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Due to the sparsity of the data, the ability to interpret the pharmacokinetic/pharmacodynamic (PK/PD) results was limited, thus the data was not reported. |
| Arm/Group Title | Lersivirine 750 mg | Lersivirine 1000 mg | Etravirine 200 mg |
|---|---|---|---|
| Arm/Group Description | Lersivirine (UK-453,061) 250 milligram (mg) 3 tablets equivalent to lersivirine 750 mg and 1 placebo tablet matched to lersivirine 250 mg tablet, orally once daily up to 96 weeks in combination with 1 optimized nucleoside reverse transcriptase inhibitors (NRTI) as per individual prescribing information, darunavir 600 mg tablet orally twice daily and ritonavir 100 mg tablet or capsule orally twice daily. | Lersivirine (UK-453,061) 250 mg 4 tablets equivalent to lersivirine 1000 mg, orally once daily up to 96 weeks in combination with 1 optimized NRTI as per individual prescribing information, darunavir 600 mg tablet orally twice daily and ritonavir 100 mg tablet or capsule orally twice daily. | Etravirine 100 mg 2 tablets equivalent to etravirine 200 mg, orally twice daily up to 96 weeks in combination with 1 optimized NRTI as per individual prescribing information, darunavir 600 mg tablet orally twice daily and ritonavir 100 mg tablet or capsule orally twice daily. |
| Measure Participants | 0 | 0 | 0 |
Adverse Events
| Time Frame | ||||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. | |||||
| Arm/Group Title | Lersivirine 750 mg | Lersivirine 1000 mg | Etravirine 200 mg | |||
| Arm/Group Description | Lersivirine (UK-453,061) 250 milligram (mg) 3 tablets equivalent to lersivirine 750 mg and 1 placebo tablet matched to lersivirine 250 mg tablet, orally once daily up to 96 weeks in combination with 1 optimized nucleoside reverse transcriptase inhibitors (NRTI) as per individual prescribing information, darunavir 600 mg tablet orally twice daily and ritonavir 100 mg tablet or capsule orally twice daily. | Lersivirine (UK-453,061) 250 mg 4 tablets equivalent to lersivirine 1000 mg, orally once daily up to 96 weeks in combination with 1 optimized NRTI as per individual prescribing information, darunavir 600 mg tablet orally twice daily and ritonavir 100 mg tablet or capsule orally twice daily. | Etravirine 100 mg 2 tablets equivalent to etravirine 200 mg, orally twice daily up to 96 weeks in combination with 1 optimized NRTI as per individual prescribing information, darunavir 600 mg tablet orally twice daily and ritonavir 100 mg tablet or capsule orally twice daily. | |||
All Cause Mortality |
||||||
| Lersivirine 750 mg | Lersivirine 1000 mg | Etravirine 200 mg | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| Lersivirine 750 mg | Lersivirine 1000 mg | Etravirine 200 mg | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/31 (3.2%) | 4/32 (12.5%) | 1/34 (2.9%) | |||
| Cardiac disorders | ||||||
| Coronary artery disease | 0/31 (0%) | 1/32 (3.1%) | 0/34 (0%) | |||
| Infections and infestations | ||||||
| Pneumocystis jiroveci pneumonia | 0/31 (0%) | 0/32 (0%) | 1/34 (2.9%) | |||
| Pneumonia | 0/31 (0%) | 0/32 (0%) | 1/34 (2.9%) | |||
| Pulmonary tuberculosis | 0/31 (0%) | 2/32 (6.3%) | 0/34 (0%) | |||
| Injury, poisoning and procedural complications | ||||||
| Head injury | 0/31 (0%) | 1/32 (3.1%) | 0/34 (0%) | |||
| Vascular disorders | ||||||
| Hypertension | 1/31 (3.2%) | 0/32 (0%) | 0/34 (0%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| Lersivirine 750 mg | Lersivirine 1000 mg | Etravirine 200 mg | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 27/31 (87.1%) | 25/32 (78.1%) | 32/34 (94.1%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 1/31 (3.2%) | 1/32 (3.1%) | 0/34 (0%) | |||
| Lymphadenopathy | 0/31 (0%) | 0/32 (0%) | 2/34 (5.9%) | |||
| Polycythaemia | 1/31 (3.2%) | 0/32 (0%) | 0/34 (0%) | |||
| Thrombocytopenia | 0/31 (0%) | 0/32 (0%) | 1/34 (2.9%) | |||
| Cardiac disorders | ||||||
| Coronary artery disease | 0/31 (0%) | 1/32 (3.1%) | 0/34 (0%) | |||
| Palpitations | 0/31 (0%) | 1/32 (3.1%) | 0/34 (0%) | |||
| Sinus bradycardia | 1/31 (3.2%) | 0/32 (0%) | 0/34 (0%) | |||
| Ear and labyrinth disorders | ||||||
| Ear pain | 0/31 (0%) | 2/32 (6.3%) | 0/34 (0%) | |||
| Hearing impaired | 1/31 (3.2%) | 0/32 (0%) | 0/34 (0%) | |||
| Endocrine disorders | ||||||
| Hypothyroidism | 0/31 (0%) | 1/32 (3.1%) | 0/34 (0%) | |||
| Eye disorders | ||||||
| Conjunctival haemorrhage | 0/31 (0%) | 1/32 (3.1%) | 0/34 (0%) | |||
| Conjunctivitis | 1/31 (3.2%) | 0/32 (0%) | 1/34 (2.9%) | |||
| Conjunctivitis allergic | 1/31 (3.2%) | 0/32 (0%) | 1/34 (2.9%) | |||
| Uveitis | 0/31 (0%) | 0/32 (0%) | 1/34 (2.9%) | |||
| Visual acuity reduced | 0/31 (0%) | 0/32 (0%) | 1/34 (2.9%) | |||
| Gastrointestinal disorders | ||||||
| Abdominal discomfort | 0/31 (0%) | 0/32 (0%) | 1/34 (2.9%) | |||
| Abdominal distension | 0/31 (0%) | 1/32 (3.1%) | 0/34 (0%) | |||
| Abdominal pain | 1/31 (3.2%) | 0/32 (0%) | 1/34 (2.9%) | |||
| Abdominal pain upper | 1/31 (3.2%) | 3/32 (9.4%) | 3/34 (8.8%) | |||
| Cheilitis | 1/31 (3.2%) | 0/32 (0%) | 1/34 (2.9%) | |||
| Constipation | 1/31 (3.2%) | 0/32 (0%) | 1/34 (2.9%) | |||
| Dental caries | 0/31 (0%) | 1/32 (3.1%) | 1/34 (2.9%) | |||
| Diarrhoea | 8/31 (25.8%) | 7/32 (21.9%) | 6/34 (17.6%) | |||
| Dry mouth | 1/31 (3.2%) | 0/32 (0%) | 0/34 (0%) | |||
| Dyspepsia | 1/31 (3.2%) | 2/32 (6.3%) | 1/34 (2.9%) | |||
| Faeces hard | 1/31 (3.2%) | 0/32 (0%) | 0/34 (0%) | |||
| Flatulence | 0/31 (0%) | 1/32 (3.1%) | 0/34 (0%) | |||
| Gastritis | 1/31 (3.2%) | 1/32 (3.1%) | 0/34 (0%) | |||
| Gastrooesophageal reflux disease | 1/31 (3.2%) | 1/32 (3.1%) | 1/34 (2.9%) | |||
| Glossodynia | 0/31 (0%) | 0/32 (0%) | 1/34 (2.9%) | |||
| Haematemesis | 0/31 (0%) | 1/32 (3.1%) | 0/34 (0%) | |||
| Haemorrhoids | 1/31 (3.2%) | 0/32 (0%) | 1/34 (2.9%) | |||
| Mouth ulceration | 0/31 (0%) | 0/32 (0%) | 1/34 (2.9%) | |||
| Nausea | 8/31 (25.8%) | 14/32 (43.8%) | 4/34 (11.8%) | |||
| Oesophagitis | 0/31 (0%) | 1/32 (3.1%) | 0/34 (0%) | |||
| Oral disorder | 1/31 (3.2%) | 1/32 (3.1%) | 0/34 (0%) | |||
| Rectal haemorrhage | 1/31 (3.2%) | 0/32 (0%) | 1/34 (2.9%) | |||
| Salivary hypersecretion | 0/31 (0%) | 1/32 (3.1%) | 0/34 (0%) | |||
| Vomiting | 6/31 (19.4%) | 3/32 (9.4%) | 3/34 (8.8%) | |||
| General disorders | ||||||
| Asthenia | 0/31 (0%) | 1/32 (3.1%) | 0/34 (0%) | |||
| Fat tissue increased | 0/31 (0%) | 0/32 (0%) | 1/34 (2.9%) | |||
| Fatigue | 0/31 (0%) | 2/32 (6.3%) | 0/34 (0%) | |||
| Gait disturbance | 1/31 (3.2%) | 0/32 (0%) | 0/34 (0%) | |||
| Pain | 0/31 (0%) | 1/32 (3.1%) | 0/34 (0%) | |||
| Hepatobiliary disorders | ||||||
| Hepatitis toxic | 0/31 (0%) | 0/32 (0%) | 1/34 (2.9%) | |||
| Immune system disorders | ||||||
| Hypersensitivity | 0/31 (0%) | 0/32 (0%) | 1/34 (2.9%) | |||
| Infections and infestations | ||||||
| Abscess neck | 1/31 (3.2%) | 0/32 (0%) | 0/34 (0%) | |||
| Acarodermatitis | 1/31 (3.2%) | 1/32 (3.1%) | 0/34 (0%) | |||
| Acute sinusitis | 0/31 (0%) | 1/32 (3.1%) | 0/34 (0%) | |||
| Asymptomatic bacteriuria | 0/31 (0%) | 1/32 (3.1%) | 0/34 (0%) | |||
| Body tinea | 2/31 (6.5%) | 1/32 (3.1%) | 0/34 (0%) | |||
| Bronchitis | 2/31 (6.5%) | 1/32 (3.1%) | 1/34 (2.9%) | |||
| Carbuncle | 0/31 (0%) | 0/32 (0%) | 1/34 (2.9%) | |||
| Cellulitis | 1/31 (3.2%) | 0/32 (0%) | 0/34 (0%) | |||
| Cystitis | 0/31 (0%) | 0/32 (0%) | 2/34 (5.9%) | |||
| Dermatophytosis | 1/31 (3.2%) | 0/32 (0%) | 0/34 (0%) | |||
| Folliculitis | 0/31 (0%) | 1/32 (3.1%) | 0/34 (0%) | |||
| Furuncle | 1/31 (3.2%) | 0/32 (0%) | 0/34 (0%) | |||
| Gastroenteritis | 0/31 (0%) | 1/32 (3.1%) | 2/34 (5.9%) | |||
| Gastroenteritis viral | 0/31 (0%) | 1/32 (3.1%) | 0/34 (0%) | |||
| Gingivitis | 0/31 (0%) | 0/32 (0%) | 1/34 (2.9%) | |||
| Hepatitis B | 0/31 (0%) | 0/32 (0%) | 1/34 (2.9%) | |||
| Herpes simplex | 0/31 (0%) | 1/32 (3.1%) | 0/34 (0%) | |||
| Herpes zoster | 0/31 (0%) | 0/32 (0%) | 5/34 (14.7%) | |||
| Hordeolum | 0/31 (0%) | 1/32 (3.1%) | 0/34 (0%) | |||
| Influenza | 4/31 (12.9%) | 0/32 (0%) | 4/34 (11.8%) | |||
| Labyrinthitis | 0/31 (0%) | 0/32 (0%) | 1/34 (2.9%) | |||
| Lower respiratory tract infection | 0/31 (0%) | 0/32 (0%) | 2/34 (5.9%) | |||
| Myringitis | 0/31 (0%) | 1/32 (3.1%) | 0/34 (0%) | |||
| Nasopharyngitis | 2/31 (6.5%) | 2/32 (6.3%) | 0/34 (0%) | |||
| Onychomycosis | 1/31 (3.2%) | 0/32 (0%) | 0/34 (0%) | |||
| Oral hairy leukoplakia | 0/31 (0%) | 1/32 (3.1%) | 1/34 (2.9%) | |||
| Otitis media | 0/31 (0%) | 1/32 (3.1%) | 0/34 (0%) | |||
| Papilloma viral infection | 0/31 (0%) | 1/32 (3.1%) | 0/34 (0%) | |||
| Paronychia | 1/31 (3.2%) | 0/32 (0%) | 0/34 (0%) | |||
| Pharyngitis | 0/31 (0%) | 1/32 (3.1%) | 0/34 (0%) | |||
| Respiratory tract infection | 1/31 (3.2%) | 0/32 (0%) | 1/34 (2.9%) | |||
| Respiratory tract infection viral | 0/31 (0%) | 1/32 (3.1%) | 0/34 (0%) | |||
| Rhinitis | 0/31 (0%) | 0/32 (0%) | 2/34 (5.9%) | |||
| Sinusitis | 2/31 (6.5%) | 2/32 (6.3%) | 0/34 (0%) | |||
| Tinea cruris | 1/31 (3.2%) | 0/32 (0%) | 0/34 (0%) | |||
| Tinea pedis | 1/31 (3.2%) | 1/32 (3.1%) | 1/34 (2.9%) | |||
| Tonsillitis | 0/31 (0%) | 1/32 (3.1%) | 0/34 (0%) | |||
| Tooth abscess | 0/31 (0%) | 0/32 (0%) | 2/34 (5.9%) | |||
| Trichomoniasis | 1/31 (3.2%) | 1/32 (3.1%) | 0/34 (0%) | |||
| Upper respiratory tract infection | 3/31 (9.7%) | 3/32 (9.4%) | 5/34 (14.7%) | |||
| Urinary tract infection | 0/31 (0%) | 3/32 (9.4%) | 3/34 (8.8%) | |||
| Vaginal infection | 0/31 (0%) | 1/32 (3.1%) | 0/34 (0%) | |||
| Viral upper respiratory tract infection | 0/31 (0%) | 0/32 (0%) | 1/34 (2.9%) | |||
| Vulvovaginal candidiasis | 2/31 (6.5%) | 0/32 (0%) | 0/34 (0%) | |||
| Injury, poisoning and procedural complications | ||||||
| Excoriation | 0/31 (0%) | 1/32 (3.1%) | 0/34 (0%) | |||
| Muscle strain | 0/31 (0%) | 1/32 (3.1%) | 1/34 (2.9%) | |||
| Radiation associated pain | 1/31 (3.2%) | 0/32 (0%) | 0/34 (0%) | |||
| Soft tissue injury | 0/31 (0%) | 1/32 (3.1%) | 0/34 (0%) | |||
| Wrist fracture | 1/31 (3.2%) | 0/32 (0%) | 0/34 (0%) | |||
| Investigations | ||||||
| Blood cholesterol increased | 0/31 (0%) | 1/32 (3.1%) | 1/34 (2.9%) | |||
| Blood creatine phosphokinase increased | 1/31 (3.2%) | 0/32 (0%) | 1/34 (2.9%) | |||
| Blood glucose increased | 1/31 (3.2%) | 1/32 (3.1%) | 2/34 (5.9%) | |||
| Blood thyroid stimulating hormone increased | 1/31 (3.2%) | 0/32 (0%) | 0/34 (0%) | |||
| Blood triglycerides increased | 0/31 (0%) | 0/32 (0%) | 1/34 (2.9%) | |||
| Gamma-glutamyltransferase increased | 0/31 (0%) | 0/32 (0%) | 1/34 (2.9%) | |||
| Hepatic enzyme abnormal | 1/31 (3.2%) | 0/32 (0%) | 0/34 (0%) | |||
| Hepatic enzyme increased | 1/31 (3.2%) | 0/32 (0%) | 1/34 (2.9%) | |||
| Low density lipoprotein increased | 0/31 (0%) | 0/32 (0%) | 1/34 (2.9%) | |||
| Tetrahydrocortisol urine increased | 0/31 (0%) | 1/32 (3.1%) | 0/34 (0%) | |||
| Urine leukocyte esterase positive | 0/31 (0%) | 1/32 (3.1%) | 0/34 (0%) | |||
| Metabolism and nutrition disorders | ||||||
| Dehydration | 0/31 (0%) | 0/32 (0%) | 1/34 (2.9%) | |||
| Diabetes mellitus | 0/31 (0%) | 0/32 (0%) | 1/34 (2.9%) | |||
| Dyslipidaemia | 1/31 (3.2%) | 0/32 (0%) | 2/34 (5.9%) | |||
| Glucose tolerance impaired | 0/31 (0%) | 0/32 (0%) | 1/34 (2.9%) | |||
| Hypertriglyceridaemia | 0/31 (0%) | 0/32 (0%) | 1/34 (2.9%) | |||
| Hyperuricaemia | 0/31 (0%) | 0/32 (0%) | 1/34 (2.9%) | |||
| Impaired fasting glucose | 0/31 (0%) | 0/32 (0%) | 1/34 (2.9%) | |||
| Type 2 diabetes mellitus | 0/31 (0%) | 1/32 (3.1%) | 1/34 (2.9%) | |||
| Vitamin D deficiency | 0/31 (0%) | 1/32 (3.1%) | 1/34 (2.9%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Arthralgia | 2/31 (6.5%) | 1/32 (3.1%) | 1/34 (2.9%) | |||
| Back pain | 2/31 (6.5%) | 0/32 (0%) | 5/34 (14.7%) | |||
| Intervertebral disc degeneration | 1/31 (3.2%) | 0/32 (0%) | 0/34 (0%) | |||
| Joint range of motion decreased | 0/31 (0%) | 1/32 (3.1%) | 0/34 (0%) | |||
| Joint swelling | 1/31 (3.2%) | 1/32 (3.1%) | 0/34 (0%) | |||
| Monarthritis | 0/31 (0%) | 0/32 (0%) | 1/34 (2.9%) | |||
| Muscle spasms | 0/31 (0%) | 2/32 (6.3%) | 0/34 (0%) | |||
| Musculoskeletal pain | 1/31 (3.2%) | 1/32 (3.1%) | 1/34 (2.9%) | |||
| Myalgia | 0/31 (0%) | 0/32 (0%) | 2/34 (5.9%) | |||
| Neck pain | 1/31 (3.2%) | 0/32 (0%) | 0/34 (0%) | |||
| Pain in extremity | 0/31 (0%) | 0/32 (0%) | 3/34 (8.8%) | |||
| Pain in jaw | 0/31 (0%) | 0/32 (0%) | 1/34 (2.9%) | |||
| Tendonitis | 1/31 (3.2%) | 0/32 (0%) | 0/34 (0%) | |||
| Nervous system disorders | ||||||
| Aphasia | 0/31 (0%) | 0/32 (0%) | 1/34 (2.9%) | |||
| Burning sensation | 0/31 (0%) | 0/32 (0%) | 1/34 (2.9%) | |||
| Convulsion | 0/31 (0%) | 0/32 (0%) | 1/34 (2.9%) | |||
| Disturbance in attention | 0/31 (0%) | 1/32 (3.1%) | 0/34 (0%) | |||
| Dizziness | 2/31 (6.5%) | 2/32 (6.3%) | 1/34 (2.9%) | |||
| Headache | 2/31 (6.5%) | 2/32 (6.3%) | 4/34 (11.8%) | |||
| Hemiparesis | 1/31 (3.2%) | 0/32 (0%) | 0/34 (0%) | |||
| Hemiplegia | 0/31 (0%) | 0/32 (0%) | 1/34 (2.9%) | |||
| Hypersomnia | 1/31 (3.2%) | 0/32 (0%) | 0/34 (0%) | |||
| Hypoaesthesia | 0/31 (0%) | 0/32 (0%) | 1/34 (2.9%) | |||
| Hypogeusia | 0/31 (0%) | 1/32 (3.1%) | 0/34 (0%) | |||
| Memory impairment | 1/31 (3.2%) | 0/32 (0%) | 0/34 (0%) | |||
| Muscle spasticity | 0/31 (0%) | 0/32 (0%) | 1/34 (2.9%) | |||
| Neuropathy peripheral | 0/31 (0%) | 1/32 (3.1%) | 1/34 (2.9%) | |||
| Paraesthesia | 0/31 (0%) | 0/32 (0%) | 1/34 (2.9%) | |||
| Somnolence | 0/31 (0%) | 0/32 (0%) | 1/34 (2.9%) | |||
| VIIth nerve paralysis | 0/31 (0%) | 0/32 (0%) | 1/34 (2.9%) | |||
| Vasogenic cerebral oedema | 1/31 (3.2%) | 0/32 (0%) | 0/34 (0%) | |||
| Psychiatric disorders | ||||||
| Anxiety | 0/31 (0%) | 0/32 (0%) | 1/34 (2.9%) | |||
| Depressed mood | 1/31 (3.2%) | 0/32 (0%) | 0/34 (0%) | |||
| Depression | 0/31 (0%) | 0/32 (0%) | 3/34 (8.8%) | |||
| Insomnia | 2/31 (6.5%) | 0/32 (0%) | 1/34 (2.9%) | |||
| Nightmare | 0/31 (0%) | 1/32 (3.1%) | 0/34 (0%) | |||
| Renal and urinary disorders | ||||||
| Proteinuria | 1/31 (3.2%) | 0/32 (0%) | 0/34 (0%) | |||
| Renal failure acute | 0/31 (0%) | 0/32 (0%) | 1/34 (2.9%) | |||
| Reproductive system and breast disorders | ||||||
| Cervical dysplasia | 0/31 (0%) | 1/32 (3.1%) | 0/34 (0%) | |||
| Menorrhagia | 1/31 (3.2%) | 0/32 (0%) | 0/34 (0%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Asthma | 0/31 (0%) | 0/32 (0%) | 1/34 (2.9%) | |||
| Bronchospasm | 0/31 (0%) | 0/32 (0%) | 1/34 (2.9%) | |||
| Cough | 2/31 (6.5%) | 0/32 (0%) | 0/34 (0%) | |||
| Epistaxis | 1/31 (3.2%) | 0/32 (0%) | 0/34 (0%) | |||
| Lung cyst | 0/31 (0%) | 0/32 (0%) | 1/34 (2.9%) | |||
| Nasal congestion | 0/31 (0%) | 1/32 (3.1%) | 0/34 (0%) | |||
| Oropharyngeal pain | 0/31 (0%) | 0/32 (0%) | 1/34 (2.9%) | |||
| Pleural effusion | 0/31 (0%) | 1/32 (3.1%) | 0/34 (0%) | |||
| Productive cough | 0/31 (0%) | 0/32 (0%) | 1/34 (2.9%) | |||
| Rhinitis allergic | 0/31 (0%) | 1/32 (3.1%) | 0/34 (0%) | |||
| Rhinorrhoea | 0/31 (0%) | 0/32 (0%) | 1/34 (2.9%) | |||
| Sinus congestion | 0/31 (0%) | 1/32 (3.1%) | 0/34 (0%) | |||
| Upper-airway cough syndrome | 0/31 (0%) | 1/32 (3.1%) | 0/34 (0%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| Dermatitis | 1/31 (3.2%) | 0/32 (0%) | 1/34 (2.9%) | |||
| Dermatitis allergic | 1/31 (3.2%) | 1/32 (3.1%) | 0/34 (0%) | |||
| Dry skin | 1/31 (3.2%) | 1/32 (3.1%) | 0/34 (0%) | |||
| Dyshidrosis | 0/31 (0%) | 0/32 (0%) | 1/34 (2.9%) | |||
| Eczema | 0/31 (0%) | 2/32 (6.3%) | 0/34 (0%) | |||
| Ingrowing nail | 1/31 (3.2%) | 0/32 (0%) | 0/34 (0%) | |||
| Intertrigo | 1/31 (3.2%) | 0/32 (0%) | 0/34 (0%) | |||
| Lipodystrophy acquired | 1/31 (3.2%) | 0/32 (0%) | 0/34 (0%) | |||
| Prurigo | 1/31 (3.2%) | 0/32 (0%) | 0/34 (0%) | |||
| Pruritus | 2/31 (6.5%) | 2/32 (6.3%) | 1/34 (2.9%) | |||
| Psoriasis | 0/31 (0%) | 0/32 (0%) | 1/34 (2.9%) | |||
| Rash | 0/31 (0%) | 0/32 (0%) | 5/34 (14.7%) | |||
| Rash erythematous | 0/31 (0%) | 1/32 (3.1%) | 0/34 (0%) | |||
| Rash maculo-papular | 0/31 (0%) | 1/32 (3.1%) | 0/34 (0%) | |||
| Rash papular | 0/31 (0%) | 1/32 (3.1%) | 0/34 (0%) | |||
| Scar | 0/31 (0%) | 0/32 (0%) | 1/34 (2.9%) | |||
| Seborrhoeic dermatitis | 2/31 (6.5%) | 1/32 (3.1%) | 0/34 (0%) | |||
| Skin hypopigmentation | 0/31 (0%) | 0/32 (0%) | 1/34 (2.9%) | |||
| Skin lesion | 0/31 (0%) | 2/32 (6.3%) | 1/34 (2.9%) | |||
| Vascular disorders | ||||||
| Arterial spasm | 0/31 (0%) | 1/32 (3.1%) | 0/34 (0%) | |||
| Hypertension | 0/31 (0%) | 1/32 (3.1%) | 0/34 (0%) | |||
| Hypertensive crisis | 0/31 (0%) | 1/32 (3.1%) | 0/34 (0%) | |||
| Hypotension | 1/31 (3.2%) | 0/32 (0%) | 1/34 (2.9%) | |||
Limitations/Caveats
The trial was terminated on 12 April, 2012 due to lack of efficacy at the Week 24 analysis. The decision to terminate the trial was not based on any safety concerns.
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Results Point of Contact
| Name/Title | Pfizer ClinicalTrials.gov Call Center |
|---|---|
| Organization | Pfizer, Inc. |
| Phone | 1-800-718-1021 |
| ClinicalTrials.gov_Inquiries@pfizer.com |
Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT00823979
Other Study ID Numbers:
- A5271022
- 2007-004392-19
First Posted:
Jan 16, 2009
Last Update Posted:
Dec 4, 2018
Last Verified:
Nov 1, 2018