E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
HIV-1 infected subjects who are virologically suppressed on a regimen of 2 NRTIs plus any 3rd agent, but experience safety and/or tolerability issues to this regimen. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 15.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10068341 |
E.1.2 | Term | HIV-1 infection |
E.1.2 | System Organ Class | 100000004862 |
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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 of this study is to estimate the proportion of subjects with HIV 1 RNA < 40 c/mL through 24 weeks, following a switch due to treatment related safety and/or tolerability issues, from a regimen consisting of 2 NRTI + any 3rd agent, to a regimen consisting of ATV/RTVHS 300/100mg QD + RAL 400 mg BID |
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E.2.2 | Secondary objectives of the trial |
Secondary Objectives:
To assess the proportion of subjects with HIV-1 RNA < 40 c/mL through Week 48.
To assess safety, as measured by the frequency of SAEs, the frequency of AEs leading to discontinuation, the frequency of AEs and the frequency of laboratory abnormalities through Weeks 24 and 48, and by changes from baseline in fasting lipids at Weeks 24 and 48.
To assess the incidence of resistance, and characterization of this resistance following a virological rebound (based on HIV-1 RNA 40 c/mL).
Exploratory Objectives
To assess time to treatment failure (based on HIV-1 RNA 40 c/mL) through Weeks 24 and 48
To assess changes from baseline in CD4 cell count at Weeks 24 and 48.
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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 |
Intensive PK assessment, included in protocol V2.0, 15-Feb-11
Trough PK assessment, included in protocol V2.0, 15-Feb-11
Exploratory Objectives:
To characterize the PK of ATV and RAL when given in the combination of ATV/RTVHS 300/100 mg QD + RAL 400 mg BID
To characterize the PK of ATV when given in the combination of ATV/RTVHS 300/100 mg QD + TDF/FTC 300/200 mg QD
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E.3 | Principal inclusion criteria |
1) Signed Written Informed Consent
a) Freely given informed consent must be obtained from subjects prior to clinical trial participation, including informed consent for any screening procedures conducted to establish subject eligibility for the trial.
b) A freely given PK sub-study consent form must be obtained from the subset of subjects participating in the intensive PK sub-study.
2) Target Population
a) Subjects who are on a treatment regimen consisting of 2 NRTI + any 3rd agent for at least 3 months immediately prior to screening.
b) Subjects who are virologically suppressed (HIV-1 RNA < 50 c/mL) for at least 3 months immediately prior to screening.
c) Subjects who are virologically suppressed (HIV-1 RNA < 40 c/mL, using the Abbott m2000rt® PCR assay) during screening period.
d) Subjects who are experiencing treatment related safety and/or tolerability issues to a regimen consisting of 2 NRTI + any 3rd agent.
e) Medically stable to participate in the study (as determined by subject’s physician following review of medical history, physical examination, and clinical laboratory evaluations)
3) Age and Reproductive Status
a) Men and women, 18 years of age or older (or minimum age as determined by local regulatory or as legal requirements dictate, whichever is higher).
b) Women of childbearing potential (WOCBP) and men must be using an acceptable method of contraception to avoid pregnancy throughout the study, and for up to 8 weeks after the last dose of investigational product, in such a manner that the risk of pregnancy is minimized. See Section 3.3.3 for the definition of WOCBP. Since acceptable and available methods of contraception vary among different countries, participating women may choose their preferred contraceptive method based on physician recommendations. Caution is warranted with co administration of oral contraceptives (ethinyl estradiol and norethindrone).
c) WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to the start of investigational product.
d) Women must not be breastfeeding
e) Sexually active fertile men must use effective birth control if their partners are WOCBP.
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E.4 | Principal exclusion criteria |
1) History of HAART treatment regimen switch due to virological failure
2) History of genotypic resistance to any component of the study regimen (ATV, RAL, TDF/FTC).
3) History of previous exposure to ATV (with or without RTV) or RAL prior to entering the study.
4) Subjects experiencing safety and/or tolerability issues to TDF/FTC or RTV.
5) Subjects who have switched any component of their HIV ARV medication in the last 3 months immediately prior to screening or during the screening period
6) Use of medications which are contra-indicated for concurrent use with the IMP
7) Use of proton pump inhibitors (PPI) and use of H2-antagonists.
8) History of or current cardiac disease, defined by presence of
a) arrhythmias (including torsades de pointes)
b) ischemic disease
c) conduction abnormality including:
i) left bundle branch block (LBB)
ii) left anterior fascicular block (LAFB)
iii) 2nd or 3rd. degree atrioventricular (AV) block
d) any cardiac abnormality deemed clinically significant by investigator.
9) The following ECG findings:
a) PR Interval > 260 msec (severe 1st. degree AV block)
b) QRS Interval > 120 msec
10) Subjects using the following:
a) class Ib antiarrhythmics: lidocaine
b) class Ic antiarrhythmics: flecainide and propafenone
c) calcium channel blocker: bepridil
11) Presence of a newly diagnosed HIV-related opportunistic infection or any medical condition requiring acute therapy at the time of screening.
12) Positive HBSAg test results. Patients who are currently receiving treatment for HCV or are planning to receive treatment for HCV in the next 6 months.
13) History or ongoing psychiatry disorder. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The proportion of subjects with HIV-1 RNA < 40 c/mL through Week 24. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Interim analysis when the first 45 subjects randomized are treated for 12 weeks.
Primary analysis after the last randomized subject is treated for 24 weeks. |
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E.5.2 | Secondary end point(s) |
1) The proportion of subjects with HIV-1 RNA < 40 c/mL through Week 48.
2) The frequency and severity of SAEs, of AEs leading to discontinuation and of all AEs through Weeks 24 and 48; the frequency of laboratory abnormalities through Weeks 24 and 48; percent change from baseline in fasting lipid parameters (total cholesterol, LDL cholesterol, HDL cholesterol, non-HDL cholesterol, and triglycerides) at Weeks 24 and 48.
3) Emergence of genotypic substitutions and phenotypic resistance among subjects with virologic rebound (HIV RNA 40 c/mL; for the criteria of resistance testing, see Section 5.4.2.2.).
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Interim analysis when the first 45 subjects randomized are treated for 12 weeks.
Primary analysis after the last randomized subject is treated for 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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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 | No |
E.8.2.3.1 | Comparator description |
Norvir, Isentress, Truvada |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 27 |
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 | No |
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 |
France |
Germany |
Italy |
Poland |
Spain |
United Kingdom |
United States |
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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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date of the last study-related visit of the last subject |
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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 | 10 |
E.8.9.1 | In the Member State concerned days | 30 |
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 | 10 |
E.8.9.2 | In all countries concerned by the trial days | 30 |