| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Treatment of HIV-1 infection |
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| MedDRA Classification |
| 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 |
| To select a GW873140 dose and dosage regimen for further evaluation based on comparison of the short-term antiviral activity, safety and tolerability of different oral doses of GW873140 in combination with LPV/r in HIV-1 infected therapy-naïve subjects. |
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| E.2.2 | Secondary objectives of the trial |
• To assess the HIV-1 RNA decay rate over the initial weeks of treatment.
•To assess the long-term safety and antiviral activity of GW873140 in combination with LPV/r in HIV-1 infected therapy-naïve subjects.
•To explore the longitudinal effects of a GW873140-containing or control regimen on plasma viral tropism.
•To assess the development of viral resistance to GW873140 and other on-study drugs.
•To describe the PK parameters of GW873140 in HIV-1 infected subjects receiving combination therapy.
•To explore exposure-response relationships (e.g. the relationship between PK parameters and HIV-1 RNA or occurrence of adverse events [AEs]) and to explore the effect of various demographic factors on PK parameters.
•To evaluate the safety and antiviral activity of different doses and dosing regimens of GW873140 plus LPV/r on selected virologic and immunologic markers of HIV infection relative to a standard of care regimen.
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| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
1.HIV-1 infected subjects aged 13 years or older (or ≥ 18 where required by local regulatory agencies). Females must fall into one of the following categories:
• Non-childbearing potential defined as women who are surgically sterile or post- menopausal, the latter indicated by history of no menses for a minimum of one year from the date of the screening visit.
•Childbearing potential: has a negative pregnancy test within 28 days prior to administration of investigational product
2.Screening plasma HIV-1 RNA ≥ 50,000 copies/mL.
3.CD4 cell count >100 cells/mm3 at screening visit.
4.R5-tropic or R5/X4-tropic virus based on viral tropism assessment at screening visit. Not more than 20 subjects harboring R5/X4-tropic virus will be randomized.
5. ART-naïve, defined as ≤ 2 weeks of treatment with either a PI or an NRTI/NtRTI, or ≤ 7 days of therapy with an NNRTI.
6. Ability to understand and comply with protocol requirements
7. Signed and dated written informed consent .
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| E.4 | Principal exclusion criteria |
1.Detection of plasma X4-tropic virus only at screening.
2.Subjects with active Class C AIDS-defining illness according to the 1993 Centers for Disease Control and Prevention (CDC) AIDS surveillance definition. Subjects with an historic or current CD4+ cell count nadir <200 cells/mm3 will not be excluded on that criterion. Subjects with a history of a CDC class C event will be permitted to enroll, providing they are not receiving any prohibited medications.
3.Any acute laboratory abnormality at screen
4.Significant blood loss (≥500mL) within 56 days prior to the screening visit. 5.Pregnant women or women who are breastfeeding.
6.Any clinically significant finding on screening or baseline ECG.
7.History of clinically relevant pancreatitis or hepatitis within the previous 6 months [asymptomatic individuals with chronic hepatitis C virus (HCV) or hepatitis B virus (HBV) infection will not be excluded.
8.Any condition which, in the opinion of the investigator, may interfere with the subject’s ability to comply with the dosing schedule and protocol evaluations
9.Any condition which, in the opinion of the investigator, might interfere with the absorption, distribution, metabolism or excretion of the drug.
10.History of a drug or other allergy which, in the opinion of the investigator, contraindicates the subject’s participation in the study or known hypersensitivity to any study medication or excipients.
11.Treatment with radiation therapy or cytotoxic chemotherapeutic agents within 30 days of investigational product administration or anticipated need for such treatment during the study.
12.Treatment with immunomodulating agents or any agent with known anti-HIV activity within 90 days of investigational product administration
13. Any immunization within 30 days prior to first dose of investigational product.
14. Previous participation in an experimental drug and/or vaccine trial(s) within 30 days or 5 half-lives, or twice the duration of the biological effect of any drug – whichever is longer, prior to the screening visit of the study.
15. Use of prescription or OTC medications that are on the prohibited medication list.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| • Proportion of subjects with plasma HIV-1 RNA <400 copies/mL remaining on randomized treatment regimen through Week 12. |
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| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | Information not present in EudraCT |
| E.6.2 | Prophylaxis | Information not present in EudraCT |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | No |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
| E.6.13 | Others | Information not present in EudraCT |
| 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 | No |
| 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 |
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| E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.5 | The trial involves multiple Member States | Yes |
| 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 | Information not present in EudraCT |
| 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 | 3 |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
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