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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00824421




Registration number
NCT00824421
Ethics application status
Date submitted
15/01/2009
Date registered
15/01/2009
Date last updated
9/12/2013

Titles & IDs
Public title
A Study Of Different Doses Of UK-453, 061 Plus Truvada Compared To Efavirenz Plus Truvada In Patients Who Have Not Been Previously Treated For HIV-1
Scientific title
A Phase 2B Multicenter, Randomized, Double-Blind, Comparative Trial Of UK-453,061, In Combination With Tenofovir Df And Emtricitabine Versus Efavirenz In Combination With Tenofovir DF And Emtricitabine For The Treatment Of Antiretroviral-Naive HIV-1 Infected Subjects
Secondary ID [1] 0 0
A5271015
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
HIV-1 0 0
HIV-1 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - UK-453, 061
Treatment: Drugs - UK-453, 061
Treatment: Drugs - EFV +TVA
Treatment: Drugs - UK-453, 061
Treatment: Drugs - UK-453, 061
Treatment: Drugs - EFV +TVA

Experimental: UK- 453,061 Dose One - UK 453,061 Dose One plus Truvada

Experimental: UK-453,061 Dose Two - UK 453,061 Dose Two plus Truvada

Active Comparator: Efavirenz + Truvada - Efavirenz + Truvada

Experimental: UK- 453,061 Dose One - UK 453,061 Dose One plus Truvada

Experimental: UK-453,061 Dose Two - UK 453,061 Dose Two plus Truvada

Active Comparator: Efavirenz + Truvada - Efavirenz + Truvada


Treatment: Drugs: UK-453, 061
UK-453,061 500 mg tablets PO QD + Tenofovir DF 300 mg/Emtricitabine 200 mg tablets PO QD.

Treatment: Drugs: UK-453, 061
UK-453,061 750 mg tablets PO QD + Tenofovir DF 300 mg/Emtricitabine 200 mg tablets PO QD.

Treatment: Drugs: EFV +TVA
Efavirenz 600 mg tablets PO QD + Tenofovir DF 300 mg/Emtricitabine 200 tablets mg PO QD.

Treatment: Drugs: UK-453, 061
UK-453,061 500 mg tablets PO QD + Tenofovir DF 300 mg/Emtricitabine 200 mg tablets PO QD.

Treatment: Drugs: UK-453, 061
UK-453,061 750 mg tablets PO QD + Tenofovir DF 300 mg/Emtricitabine 200 mg tablets PO QD.

Treatment: Drugs: EFV +TVA
Efavirenz 600 mg tablets PO QD + Tenofovir DF 300 mg/Emtricitabine 200 tablets mg PO QD.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With Less Than 50 Copies Per Milliliter (Copies/mL) of Human Immunodeficiency Virus Type 1 Ribonucleic Acid (HIV-1 RNA) at Week 48 - Plasma HIV-1 RNA level was determined by validated Roche Amplicor HIV-1 Monitor standard assay.
Timepoint [1] 0 0
Week 48
Primary outcome [2] 0 0
Percentage of Participants With Less Than 50 Copies Per Milliliter (Copies/mL) of Human Immunodeficiency Virus Type 1 Ribonucleic Acid (HIV-1 RNA) at Week 48 - Plasma HIV-1 RNA level was determined by validated Roche Amplicor HIV-1 Monitor standard assay.
Timepoint [2] 0 0
Week 48
Secondary outcome [1] 0 0
Percentage of Participants With Less Than 50 Copies/mL of HIV-1 RNA at Week 24 and 96 - Plasma HIV-1 RNA level was determined by validated Roche Amplicor HIV-1 Monitor standard assay.
Timepoint [1] 0 0
Week 24, 96
Secondary outcome [2] 0 0
Percentage of Participants With Less Than 400 Copies/mL of HIV-1 RNA at Week 24, 48 and 96 - Plasma HIV-1 RNA level was determined by validated Roche Amplicor HIV-1 Monitor standard assay.
Timepoint [2] 0 0
Week 24, 48, 96
Secondary outcome [3] 0 0
Change From Baseline in Log 10 Transformed HIV-1 RNA Levels at Week 24, 48 and 96 - For the log 10 scale, all the HIV-1 RNA levels were log 10 transformed prior to the average calculations. Baseline value was calculated as the average of all the measurements collected prior to and including Day 1 pre-dose.
Timepoint [3] 0 0
Baseline, Week 24, 48, 96
Secondary outcome [4] 0 0
Time-Averaged Difference (TAD) in Log 10 Transformed HIV-1 RNA Levels at Week 24, 48 and 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 was calculated as the average of all the measurements collected prior to and including Day 1 pre-dose.
Timepoint [4] 0 0
Baseline up to Week 24, 48, 96
Secondary outcome [5] 0 0
Percentage of Participants With Response as Determined Using the Time-to Loss of Virologic Response (TLOVR50) Algorithm at Week 24, 48 and 96 - TLOVR50 response is 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; met treatment failure [TF] criteria). TF: an increase to at least 3 times 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). TF criteria's defined above were confirmed by second measurement at least 14 days after first. In 'TLOVR50', '50' denotes the lower limit of quantification (LLOQ) of assay (which is 50 copies/mL). Baseline value was calculated as the average of all the measurements collected prior to and including Day 1 pre-dose.
Timepoint [5] 0 0
Week 24, 48, 96
Secondary outcome [6] 0 0
Change From Baseline in Cluster of Differentiation (CD4+) Absolute Cell Count at Week 24, 48 and 96 - Baseline value was calculated as the average of all the measurements collected prior to and including Day 1 pre-dose.
Timepoint [6] 0 0
Baseline, Week 24, 48, 96
Secondary outcome [7] 0 0
Change From Baseline in Cluster of Differentiation (CD4+) Percentage Cell Count at Week 24, 48 and 96 - Baseline value was calculated as the average of all the measurements collected prior to and including Day 1 pre-dose.
Timepoint [7] 0 0
Baseline, Week 24, 48, 96
Secondary outcome [8] 0 0
Number of Participants With NRTI and NNRTI Resistance-Associated Mutations (RAMs) at Time of Treatment Failure Through Week 24, 48 and 96 - Phenotypic resistance and genotypic resistance was assessed for all participants at Day 1 predose, and was evaluated for nucleotide reverse transcriptase inhibitors (NRTIs), and non-NRTIs (NNRTIs) resistance-associated mutations at time of treatment failure using Monogram GenoSeq and/or PhenoSenseGT assays. This was then repeated for all participants with HIV-1 viral load more than 500 copies/mL at treatment failure, up to Week 96.
Timepoint [8] 0 0
Day 1 (pre-dose) through Week 24, 48, 96
Secondary outcome [9] 0 0
Number of Participants With Laboratory Test Abnormalities - Laboratory analysis included hematology, blood chemistry, serum and urine pregnancy test, hepatitis testing and urinalysis. Laboratory values that met the criteria of the Division of Acquired Immuno Deficiency Syndrome (DAIDS) grade 1 (mild, symptoms causing no or minimal interference with usual social and functional activities) or greater were considered as abnormal.
Timepoint [9] 0 0
Baseline up to Week 96 or early termination
Secondary outcome [10] 0 0
Population Pharmacokinetic (PK) of Lersivirine - 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.
Timepoint [10] 0 0
Week 2, 4, 8, 12, 16, 24, 32, 40, 48
Secondary outcome [11] 0 0
Lersivirine Success Percentage With Reference to Median Minimum Observed Plasma Concentration (Cmin) - 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.
Timepoint [11] 0 0
Week 2, 4, 8, 12, 16, 24, 32, 40, 48
Secondary outcome [12] 0 0
Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC[0-24]) of Lersivirine - AUC (0-24)= Area under the plasma concentration versus time curve from time zero (pre-dose) to 24 hours post-dose (0-24). Only participants from Lersivirine treatment arms were planned to be analyzed for Pharmacokinetic (PK) sub-study.
Timepoint [12] 0 0
0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 24 hours (hrs) post-dose on Week 4
Secondary outcome [13] 0 0
Maximum Observed Plasma Concentration (Cmax) of Lersivirine
Timepoint [13] 0 0
0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 24 hrs post-dose on Week 4
Secondary outcome [14] 0 0
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Lersivirine
Timepoint [14] 0 0
0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 24 hrs post-dose on Week 4
Secondary outcome [15] 0 0
Plasma Concentration of Lersivirine at 24 Hour - The observed plasma concentration at 24 hours post-dose (C 24h).
Timepoint [15] 0 0
24 hrs post-dose on Week 4
Secondary outcome [16] 0 0
Percentage of Participants With Less Than 50 Copies/mL of HIV-1 RNA at Week 24 and 96 - Plasma HIV-1 RNA level was determined by validated Roche Amplicor HIV-1 Monitor standard assay.
Timepoint [16] 0 0
Week 24, 96
Secondary outcome [17] 0 0
Percentage of Participants With Less Than 400 Copies/mL of HIV-1 RNA at Week 24, 48 and 96 - Plasma HIV-1 RNA level was determined by validated Roche Amplicor HIV-1 Monitor standard assay.
Timepoint [17] 0 0
Week 24, 48, 96
Secondary outcome [18] 0 0
Change From Baseline in Log 10 Transformed HIV-1 RNA Levels at Week 24, 48 and 96 - For the log 10 scale, all the HIV-1 RNA levels were log 10 transformed prior to the average calculations. Baseline value was calculated as the average of all the measurements collected prior to and including Day 1 pre-dose.
Timepoint [18] 0 0
Baseline, Week 24, 48, 96
Secondary outcome [19] 0 0
Time-Averaged Difference (TAD) in Log 10 Transformed HIV-1 RNA Levels at Week 24, 48 and 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 was calculated as the average of all the measurements collected prior to and including Day 1 pre-dose.
Timepoint [19] 0 0
Baseline up to Week 24, 48, 96
Secondary outcome [20] 0 0
Percentage of Participants With Response as Determined Using the Time-to Loss of Virologic Response (TLOVR50) Algorithm at Week 24, 48 and 96 - TLOVR50 response is 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; met treatment failure [TF] criteria). TF: an increase to at least 3 times 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). TF criteria's defined above were confirmed by second measurement at least 14 days after first. In 'TLOVR50', '50' denotes the lower limit of quantification (LLOQ) of assay (which is 50 copies/mL). Baseline value was calculated as the average of all the measurements collected prior to and including Day 1 pre-dose.
Timepoint [20] 0 0
Week 24, 48, 96
Secondary outcome [21] 0 0
Change From Baseline in Cluster of Differentiation (CD4+) Absolute Cell Count at Week 24, 48 and 96 - Baseline value was calculated as the average of all the measurements collected prior to and including Day 1 pre-dose.
Timepoint [21] 0 0
Baseline, Week 24, 48, 96
Secondary outcome [22] 0 0
Change From Baseline in Cluster of Differentiation (CD4+) Percentage Cell Count at Week 24, 48 and 96 - Baseline value was calculated as the average of all the measurements collected prior to and including Day 1 pre-dose.
Timepoint [22] 0 0
Baseline, Week 24, 48, 96
Secondary outcome [23] 0 0
Number of Participants With NRTI and NNRTI Resistance-Associated Mutations (RAMs) at Time of Treatment Failure Through Week 24, 48 and 96 - Phenotypic resistance and genotypic resistance was assessed for all participants at Day 1 predose, and was evaluated for nucleotide reverse transcriptase inhibitors (NRTIs), and non-NRTIs (NNRTIs) resistance-associated mutations at time of treatment failure using Monogram GenoSeq and/or PhenoSenseGT assays. This was then repeated for all participants with HIV-1 viral load more than 500 copies/mL at treatment failure, up to Week 96.
Timepoint [23] 0 0
Day 1 (pre-dose) through Week 24, 48, 96
Secondary outcome [24] 0 0
Number of Participants With Laboratory Test Abnormalities - Laboratory analysis included hematology, blood chemistry, serum and urine pregnancy test, hepatitis testing and urinalysis. Laboratory values that met the criteria of the Division of Acquired Immuno Deficiency Syndrome (DAIDS) grade 1 (mild, symptoms causing no or minimal interference with usual social and functional activities) or greater were considered as abnormal.
Timepoint [24] 0 0
Baseline up to Week 96 or early termination
Secondary outcome [25] 0 0
Population Pharmacokinetic (PK) of Lersivirine - 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.
Timepoint [25] 0 0
Week 2, 4, 8, 12, 16, 24, 32, 40, 48
Secondary outcome [26] 0 0
Lersivirine Success Percentage With Reference to Median Minimum Observed Plasma Concentration (Cmin) - 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.
Timepoint [26] 0 0
Week 2, 4, 8, 12, 16, 24, 32, 40, 48
Secondary outcome [27] 0 0
Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC[0-24]) of Lersivirine - AUC (0-24)= Area under the plasma concentration versus time curve from time zero (pre-dose) to 24 hours post-dose (0-24). Only participants from Lersivirine treatment arms were planned to be analyzed for Pharmacokinetic (PK) sub-study.
Timepoint [27] 0 0
0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 24 hours (hrs) post-dose on Week 4
Secondary outcome [28] 0 0
Maximum Observed Plasma Concentration (Cmax) of Lersivirine
Timepoint [28] 0 0
0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 24 hrs post-dose on Week 4
Secondary outcome [29] 0 0
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Lersivirine
Timepoint [29] 0 0
0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 24 hrs post-dose on Week 4
Secondary outcome [30] 0 0
Plasma Concentration of Lersivirine at 24 Hour - The observed plasma concentration at 24 hours post-dose (C 24h).
Timepoint [30] 0 0
24 hrs post-dose on Week 4

Eligibility
Key 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 1,000 copies/mL

- Negative urine pregnancy test.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Suspected or documented active, untreated HIV-1 related opportunist 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.

- Absolute CD4 count <200 cells/mm3.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Pfizer Investigational Site - Darlinghurst
Recruitment hospital [2] 0 0
Pfizer Investigational Site - Melbourne
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
Argentina
State/province [1] 0 0
Buenos Aires
Country [2] 0 0
Canada
State/province [2] 0 0
Ontario
Country [3] 0 0
Canada
State/province [3] 0 0
Quebec
Country [4] 0 0
Italy
State/province [4] 0 0
Milano
Country [5] 0 0
Italy
State/province [5] 0 0
Torino
Country [6] 0 0
Mexico
State/province [6] 0 0
Distrito Federal
Country [7] 0 0
Poland
State/province [7] 0 0
Bydgoszcz
Country [8] 0 0
Poland
State/province [8] 0 0
Gdansk
Country [9] 0 0
Poland
State/province [9] 0 0
Lodz
Country [10] 0 0
Poland
State/province [10] 0 0
Warszawa
Country [11] 0 0
South Africa
State/province [11] 0 0
Gauteng
Country [12] 0 0
South Africa
State/province [12] 0 0
Kwa Zulu Natal
Country [13] 0 0
South Africa
State/province [13] 0 0
Limpopo
Country [14] 0 0
South Africa
State/province [14] 0 0
Western Cape
Country [15] 0 0
South Africa
State/province [15] 0 0
Pretoria
Country [16] 0 0
Switzerland
State/province [16] 0 0
CH-8091 Zurich
Country [17] 0 0
Switzerland
State/province [17] 0 0
Lugano
Country [18] 0 0
Switzerland
State/province [18] 0 0
St. Gallen
Country [19] 0 0
United Kingdom
State/province [19] 0 0
Greater Manchester
Country [20] 0 0
United Kingdom
State/province [20] 0 0
Brighton
Country [21] 0 0
United Kingdom
State/province [21] 0 0
Edinburgh
Country [22] 0 0
United Kingdom
State/province [22] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Pfizer
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a 96 week study to determine if UK- 453,061 in combination with Truvada is as
efficacious, safe and tolerable as efavirenz in combination with Truvada in HIV-1 infected
patients who have not been previously treated with antiretroviral drugs.
Trial website
https://clinicaltrials.gov/show/NCT00824421
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Pfizer CT.gov Call Center
Address 0 0
Pfizer
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications