A PHASE 2B MULTICENTER, RANDOMIZED, DOUBLE-BLIND, COMPARATIVE TRIAL OF UK-453,061, IN COMBINATION WITH TENOFOVIR AND EMTRICITABINE VERSUS EFAVIRENZ IN COMBINATION WITH TENOFOVIR DF AND EMTRICITABINE FOR THE TREATMENT OF ANTIRETROVIRAL-NAIVE HIV-1 INFECTED SUBJECTS

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2007-004379-20-PL
• Date of registration: 12/12/2008
• Prospective Registration: No
• Primary sponsor: Pfizer Inc., 235 East 42nd Street, New York, NY 10017
• Public title: A PHASE 2B MULTICENTER, RANDOMIZED, DOUBLE-BLIND, COMPARATIVE TRIAL OF UK-453,061, IN COMBINATION WITH TENOFOVIR AND EMTRICITABINE VERSUS EFAVIRENZ IN COMBINATION WITH TENOFOVIR DF AND EMTRICITABINE FOR THE TREATMENT OF ANTIRETROVIRAL-NAIVE HIV-1 INFECTED SUBJECTS
• Scientific title: A PHASE 2B MULTICENTER, RANDOMIZED, DOUBLE-BLIND, COMPARATIVE TRIAL OF UK-453,061, IN COMBINATION WITH TENOFOVIR AND EMTRICITABINE VERSUS EFAVIRENZ IN COMBINATION WITH TENOFOVIR DF AND EMTRICITABINE FOR THE TREATMENT OF ANTIRETROVIRAL-NAIVE HIV-1 INFECTED SUBJECTS
• Date of first enrolment: 26/11/2008
• Target sample size: 189
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-004379-20
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: no

Countries of recruitment

Italy, Poland, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the trial:
1. Evidence of a personally signed and dated informed consent document indicating that the subject (or a legally acceptable representative) has been informed of all pertinent aspects of the study.
2. Male or female at least 18 years of age available for a follow-up period of at least
96 weeks.
3. HIV-1 RNA viral load of =1,000 copies/mL measured by the Roche COBAS®
AmpliPrep/COBAS® TaqMan® HIV-1 test at the screening visit.
4. Negative urine pregnancy test at the Day 1 visit, prior to receiving the first dose of study medication, for Women of Child Bearing Potential (WOCBP).
• NOTE: WOCBP includes any female who has experienced menarche and who has not undergone successful surgical sterilization or is not post-menopausal (ie, no menstrual periods for at least 2 years). Even women who are using oral, implanted or injectable contraceptive hormones or mechanical products (intrauterine devices; barrier methods: eg,condom or diaphragm with spermicide) to prevent pregnancy, who are practicing abstinence, or who have a partner that is sterile (eg, vasectomy), should be considered to be of child bearing potential.
5. Effective barrier contraception for WOCBP and males. In addition, WOCBP must use another acceptable method of contraception for the duration of the study and for 28 days after leaving the study. Acceptable contraception includes, but is not limited to, oral, implanted or injectable hormone therapy and intrauterine devices.
6. Subjects who are willing and able to comply with scheduled visits, treatment plan,
laboratory tests, and other study procedures.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Key Exclusion Criteria have been selected due to limitations on space in the Annex 1 (please refer to Protocol for the completed list):

Subjects presenting with any of the following will not be included in the trial:
1. Suspected or documented active, untreated HIV-1 related OI or other condition requiring acute therapy at the time of randomization. Subjects on a stable (>30 days) secondary OI prophylaxis regimen or chronic treatment are eligible for the study, as are subjects on a primary OI prophylaxis regimen of any duration, except Trimethoprim-sulfamethoxazole.Subjects on primary, secondary prophylaxis and therapy with Trimethoprim-sulfamethoxazole must be in therapy >60 days.
2. Subjects on therapy for Hepatitis B.
3. Subjects with acute Hepatitis B and/or C within 30 days of randomization.
4. Subjects with Hepatitis C on therapy with interferon and/or ribavirin for <60 days.
5. Absolute CD4+ cell count <200 cells/mm3.
6. Treatment for an active OI, or unexplained temperature >38.5 °C, for 7 consecutive days within 30 days prior to randomization.
7. Prior treatment with efavirenz, emtricitabine, or tenofovir DF, or with any other antiretroviral therapy for more than 14 cumulative days at any time.
14. Renal insufficiency defined as a serum creatinine greater than 3 times the upper limit of normal or a creatinine clearance of less than 50 mL/min.
15. Total bilirubin greater than =1.5 times the upper limit of normal.
16. AST and/or ALT greater than 3 times the upper limit of normal.
17. Male subjects with a baseline QT of >450 msec and female subjects with a baseline QT of >470 msec.
24. Presence of gross hematuria or grade 4 proteinuria at the time of screening.
30. One or more resistance mutations associated with efavirenz, tenofovir, emtricitabine or UK- 453,061 as listed below:
• Efavirenz-associated mutations: A98G, L100I, K101E/P, K103N/S/T, V106M/A,
V108I E138K, V179D/E/F, Y181C/I/V, Y188L/H/C, G190A/S/E/Q, P225H, F227C;
M230L, K238T/N;
• Tenofovir-associated mutations: K65R/N, K70E, L74V, Y115F, M184V, 2 or more
Type 1 TAMs, T215 revertants:T215C/D/E/S/I/V, T69 insertion mutations,
Q151complex +/- V75I, F77L and F116Y, E44D +/- V118I;
• Emtricitabine-associated mutations: K65R/N, K70E, M184V/I, Q151complex +/-
V75I, F77L and F116Y, 2 or more Type 1 TAMs or 3 or more Type 2 TAMs, T69
insertion mutations, E44D+/-V118I;
• Potential UK-453,061 associated mutations: F227L, L234I.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

HIV in particular against drug-resistant virus, especially the clinicallysignificant mutants (K103N, Y181C, and L100I)
MedDRA version: 9.1 Level: PT Classification code 10020161 Term: HIV infection

Intervention(s)

Product Code: UK-453,061
Pharmaceutical Form: Tablet
CAS Number: 473921-12-9
Other descriptive name: 5-[[3,5-diethyl-1-(2-hydroxyethyl)- 1H-pyrazol-4-yl]oxy]-1,3-benzene- dicarbonitrile
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 250-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Trade Name: Sustiva
Pharmaceutical Form: Tablet
INN or Proposed INN: Efavirenz
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 600-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): Percentage of subjects with HIV-1 RNA <48 copies/mL at 48 weeks.

Main Objective: The primary objective is to assess efficacy of UK-453,061 when used in combination with tenofovir DF/emtricitabine, as measured by percentage of subjects with HIV-1 RNA <48 copies/mL at 48 weeks.

Secondary Objective: • To assess efficacy as measured by percentage of subjects with HIV-1 RNA <48 and <400 copies/mL.
• Change from baseline in log10 transformed HIV-1 RNA levels.
• To assess the pharmacokinetic (PK) and pharmacokinetic/pharmacodynamic (PK/PD)
relationship of UK-453,061.
• To assess pharmacokinetic parameters of UK-453,061 AUC24, Cmax and C24h (PK substudy).

Secondary ID(s)

2007-004379-20-GB

A5271015