E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020178 |
E.1.2 | Term | HIV infection with specific secondary infections |
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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 the efficacy of UK-453,061 when used in combination with darunavir/ritonavir and an optimized NRTI for the treatment of subjects with prior NNRTI use and documented evidence of NNRTI resistance associated mutations. Efficacy will be measured by the percentage of subjects with HIV-1 RNA <48 copies/mL at 24 weeks. |
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E.2.2 | Secondary objectives of the trial |
To assess efficacy as measured by percentage of subjects with HIV-1 RNA <48 copies/mL at 48 and 96 weeks. To assess efficacy as measured by percentage of subjects with HIV-1 RNA <400 copies/mL. To assess efficacy as measured by change from baseline in log10 transformed HIV-1 RNA levels. To assess the pharmacokinetics (PK) and pharmacokinetic/pharmacodynamic (PK/PD)-relationship of UK-453,061. To assess pharmacokinetic parameters of UK-453,061 AUC24, Cmax and C24h (PK sub-study). To assess safety and tolerability of UK-453,061. |
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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 |
FARMACOGENETICA: Versione: Data:2008/09/12 Titolo:MOLECULAR PROFILING SUPPLEMENT SAMPLES FOR PFIZERS EXPLORATORY RESEARCH BIOBANK Obiettivi:
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E.3 | Principal inclusion criteria |
1. Evidence of a 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 &#8805;1,000 copies/mL measured by the Roche COBAS AmpliPrep/COBAS TaqMan HIV-1 test at the screening visit.4. Virologically failed a single NNRTI-based regimen with documented evidence of NNRTI resistance mutations at screening or on historical genotype. Subjects may have PI experience/resistance. 5. 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. 6. 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. 7. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures. |
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E.4 | Principal exclusion criteria |
1. Suspected or documented active, untreated HIV-1 related opportunistic infection (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 on therapy >60 days. 2. On therapy for Hepatitis B. 3. Acute Hepatitis B and/or C within 30 days of randomization. 4. 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. Lack of prior use of a NNRTI, even if the current or historical HIV-1 genotype exhibits resistance to NNRTIs. 8. Active alcohol or substance abuse sufficient, in the investigators judgment, to prevent adherence to study medication and/or follow-up. 9. Previous use of darunavir or etravirine. 10. Inability to use an active NRTI based on resistance testing and treatment history. 11. Previous use of CCR5 antagonists, fusion inhibitors or integrase inhibitors for greater than 14 days cumulatively. 12. Lactating (if female), or planned pregnancy during the trial period. 13. Suspected acute HIV-1 infection. 14. Initiation of therapy with a potentially myelosuppressive, neurotoxic, hepatotoxic and/or cytotoxic agent within 60 days prior to randomization or the expected need for such therapy during the study period. 15. Malignancy requiring parenteral therapy that must be continued during the trial. 16. Documented or suspected pancreatitis within 30 days prior to randomization. 17. Renal insufficiency defined as a serum creatinine greater than 3 times the upper limit of normal. 18. Total bilirubin &#8805;1.5 times the upper limit of normal. 19. AST and/or ALT >3 times the upper limit of normal. 20. Male with a baseline QT of >450 msec or female with a baseline QT of >470 msec. 21. 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. 22. Cardiac events (MI, bypass surgery, angioplasty) within 6 months of randomization. 23. Cirrhosis of the liver. 24. Absolute neutrophil count &#8804;750 cells/mm3. 25. Platelet count &#8804;50,000 cells/mm3. 26. Hemoglobin &#8804;7 g/dL. 27. Presence of gross hematuria or grade 4 proteinuria at the time of screening.28. Clinically significant malabsorption syndrome (eg, &#8805;6 loose stools per day for at least 7 consecutive days) within 30 days prior to randomization. 29. Inability to tolerate oral medication. 30. Concomitant therapy with other investigational agents within 30 days prior to enrollment into the study. 31. Participation in other investigational studies within 30 days prior to study start and/or during study participation. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The percentage of subjects with HIV-1 RNA <48 copies/mL at 24 weeks |
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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 | Yes |
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
placebo per coprire la dose UK-453061. NRTI, darunavir / ritonavir, e etravirine saranno open-label |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
- same IMP used at different dosage |
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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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 24 |
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 |
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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
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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 | 7 |
E.8.9.1 | In the Member State concerned days | |
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 | 7 |