E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
HIV in particular against drug-resistant virus, especially the clinically significant mutants (K103N, Y181C, and L100I) |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10020161 |
E.1.2 | Term | HIV infection |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective is to assess efficacy of UK-453,061 when used in combination with tenofovir DF/emtricitabine, as measured by the percentage of subjects with HIV-1 RNA <50 copies/mL at 48 weeks. |
|
E.2.2 | Secondary objectives of the trial |
• To assess efficacy as measured by percentage of subjects with HIV-1 RNA <50 and <400 copies/mL. •To assess Change from baseline in log10 transformed HIV-1 RNA levels. •To assess safety and tolerability of UK-453,061. • 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).
|
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
There is a PK sub-study written within the same protocol (A5271015). |
|
E.3 | Principal 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 Roche Amplicor® HIV-1 Monitor 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 12 weeks 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. |
|
E.4 | Principal exclusion criteria |
Key Exclusion Criteria have been selected (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 with the following exceptions: •Subjects on a stable (>30 days) secondary OI prophylaxis regimen or chronic treatment. •Subjects on a primary OI prophylaxis regimen of any duration. However, subjects being treated with trimethoprim-sulfamethoxazole must be on stable therapy (>60 days) to be eligible. 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. However, subjects diagnosed with Hepatitis C may be treated for Hepatitis C during the study if deemed appropriate by the subject’s physician. 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. 12. Malignancy requiring systemic therapy that must be continued during the trial. 14. Renal insufficiency defined as a serum creatinine greater than 3 times the upper limit of normal or creatinine clearance of less than 50mL/min. Creatinine clearance will be calculated by the Investigator using the Cockcroft and Gault equation 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. 18. Presence of risk factors for prolongation of QT interval including heart failure, chronic hypokalemia, family history of long QT syndrome, concomitant use of medications that are known to prolong QT interval. 24. Presence of gross hematuria or grade 4 proteinuria at the time of screening. 30. Contraindicated medications being taken by the subject at the time of randomization that must be continued during the study period, including immunomodulators for the treatment of HIV-1 infection. Interferon for the ongoing treatment of hepatitis C infection is permitted. Note: It is incumbent upon the investigator to be thoroughly familiar with the prescribing information for the study drugs.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Percentage of subjects with HIV-1 RNA <50 copies/mL at 48 weeks. |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 18 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |