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

HIV-1 Clinical Trial

Official 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00824421
• Other study ID #: A5271015
• Status: Completed
• Phase: Phase 2
• First received: January 15, 2009
• Last updated: December 9, 2013
• Start date: February 2009
• Est. completion date: October 2011

Study information

• Verified date: November 2011
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Research Ethics Committee
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 195
• Est. completion date: October 2011
• Est. primary completion date: October 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV-1

Intervention

Drug:
• UK-453, 061
UK-453,061 500 mg tablets PO QD + Tenofovir DF 300 mg/Emtricitabine 200 mg tablets PO QD.
• UK-453, 061
UK-453,061 750 mg tablets PO QD + Tenofovir DF 300 mg/Emtricitabine 200 mg tablets PO QD.
• EFV +TVA
Efavirenz 600 mg tablets PO QD + Tenofovir DF 300 mg/Emtricitabine 200 tablets mg PO QD.

Locations

Country	Name	City	State
Argentina	Pfizer Investigational Site	Buenos Aires
Australia	Pfizer Investigational Site	Darlinghurst	New South Wales
Australia	Pfizer Investigational Site	Melbourne	Victoria
Canada	Pfizer Investigational Site	Montreal	Quebec
Canada	Pfizer Investigational Site	Montreal	Quebec
Canada	Pfizer Investigational Site	Toronto	Ontario
Italy	Pfizer Investigational Site	Milano
Italy	Pfizer Investigational Site	Milano
Italy	Pfizer Investigational Site	Torino
Mexico	Pfizer Investigational Site	Mexico	Distrito Federal
Poland	Pfizer Investigational Site	Bydgoszcz
Poland	Pfizer Investigational Site	Gdansk
Poland	Pfizer Investigational Site	Lodz
Poland	Pfizer Investigational Site	Warszawa
South Africa	Pfizer Investigational Site	Cape Town	Western Cape
South Africa	Pfizer Investigational Site	Durban	Kwa Zulu Natal
South Africa	Pfizer Investigational Site	Johannesburg	Gauteng
South Africa	Pfizer Investigational Site	Namakgale	Limpopo
South Africa	Pfizer Investigational Site	Pretoria	Gauteng
South Africa	Pfizer Investigational Site	Pretoria
South Africa	Pfizer Investigational Site	Soweto	Gauteng
Switzerland	Pfizer Investigational Site	CH-8091 Zurich
Switzerland	Pfizer Investigational Site	Lugano
Switzerland	Pfizer Investigational Site	St. Gallen
United Kingdom	Pfizer Investigational Site	Brighton
United Kingdom	Pfizer Investigational Site	Crumpsall	Greater Manchester
United Kingdom	Pfizer Investigational Site	Edinburgh
United Kingdom	Pfizer Investigational Site	Edinburgh
United Kingdom	Pfizer Investigational Site	London
United Kingdom	Pfizer Investigational Site	London
United Kingdom	Pfizer Investigational Site	London

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

Argentina,  Australia,  Canada,  Italy,  Mexico,  Poland,  South Africa,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Week 48	No
Secondary	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.	Week 24, 96	No
Secondary	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.	Week 24, 48, 96	No
Secondary	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.	Baseline, Week 24, 48, 96	No
Secondary	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.	Baseline up to Week 24, 48, 96	No
Secondary	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.	Week 24, 48, 96	No
Secondary	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.	Baseline, Week 24, 48, 96	No
Secondary	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.	Baseline, Week 24, 48, 96	No
Secondary	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.	Day 1 (pre-dose) through Week 24, 48, 96	No
Secondary	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.	Baseline up to Week 96 or early termination	Yes
Secondary	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.	Week 2, 4, 8, 12, 16, 24, 32, 40, 48	No
Secondary	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.	Week 2, 4, 8, 12, 16, 24, 32, 40, 48	No
Secondary	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.	0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 24 hours (hrs) post-dose on Week 4	No
Secondary	Maximum Observed Plasma Concentration (Cmax) of Lersivirine		0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 24 hrs post-dose on Week 4	No
Secondary	Time to Reach Maximum Observed Plasma Concentration (Tmax) of Lersivirine		0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 24 hrs post-dose on Week 4	No
Secondary	Plasma Concentration of Lersivirine at 24 Hour	The observed plasma concentration at 24 hours post-dose (C 24h).	24 hrs post-dose on Week 4	No

External Links

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