E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment of HIV-1 infections |
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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 for further evaluation based on comparison of the short-term antiviral activity, safety and tolerability of different oral doses of GW873140 in combination with COM(ZDV/3TC) in HIV-1 infected therapy-naive subjects. |
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E.2.2 | Secondary objectives of the trial |
• Long-term safety and antiviral activity of GW873140 in combination with COMBIVIR in HIV-1 infected therapy-naïve subjects. •Longitudinal effects of a GW873140-containing or control regimen on plasma viral tropism. • Development of viral resistance to GW873140 and other on-study drugs. • PK parameters of GW873140 in HIV-1 infected subjects receiving combination therapy. •Potential for PK interaction between GW873140 and ZDV or 3TC. •Exposure-response relationships and to explore the effect of various demographic factors on PK parameters. • Effect of different doses of GW873140 plus COMBIVIR on selected virological and immunological markers of HIV infection relative to a standard of care regimen. •Explore how bothersome certain symptoms are for subjects taking COMBIVIR + GW873140 or efavirenz, and how symptoms impact on health related quality of life.
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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. •Childbearing potential: has a negative pregnancy test within 28 days prior to administration of investigational products and agrees to use a proven double barrier method of contraception. 2.Screening plasma HIV-1 RNA ≥ 10,000 copies/mL. 3.CD4 cell count > 100 cells/mm3 at screening. 4.R5-tropic virus at screening. 5.No drug resistance mutations in HIV-1 RT based on pol genotype determined at screening.
6.ART-naïve, defined as ≤ 2 weeks of treatment with either a PI or an NRTI/NtRTI, or < 7 days of therapy with an NNRTI. Prior treatment with any entry inhibitor, attachment inhibitor, or fusion inhibitor (experimental or approved) will not be permitted. 7.Ability to understand and comply with protocol requirements
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E.4 | Principal exclusion criteria |
1.Detection of any X4-tropic virus, at screening. 2.Detection of any resistance-conferring mutation in HIV-1 RT based on genotypic testing at screening. 3Subject 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 4.Any acute laboratory abnormality at screen 5.Significant blood loss within 56 days prior to screening. 6.Pregnant or lacatating women 7.Any clinically significant finding on screening or baseline ECG. 8.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 9.Any condition may interfere with subject’s ability to comply with the dosing schedule and protocol evaluations or compromise safety of subject. 10.Any condition which might interfere with ADME of drug 11.History of a drug or other allergy or known hypersensitivity to any study medication or excipients. 12.Treatment with radiation therapy or cytotoxic chemotherapeutic agents within 30 days of administration. 13.Treatment with immunomodulating agents or any agent with known anti-HIV activity within 90 days of administration. 14.Any immunisation within 30 days prior to first dose. 15.Prior investigational drug and/or vaccine trial(s) within 30 days or 5 half-lives, or twice the duration of the biological effect(whichever is longer), prior screening.
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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 the randomised 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 | No |
E.6.2 | Prophylaxis | No |
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 | No |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Antiviral effect of GW873140 in combination with COMBIVIR |
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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 | Information not present in EudraCT |
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 |
Subjects on GW873140 will be blinded until 48 weeks and then will be open label for a further 48 wee |
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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 | Yes |
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 |