E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
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 see how well the study regime suppresses the HIV-1 virus after 48 weeks of therapy. |
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E.2.2 | Secondary objectives of the trial |
-To see how well the study regime suppresses the HIV-1 virus at weeks 4, 8, 12 and 24 of therapy. -To investigate the different levels of darunavir, ritonavir and rilpivirine in the blood when given in combination -To explore the relationship between the different levels of study drugs in the blood and their effect on the body, based on how well they suppress the HIV-1 virus -To determine the effect of the combination of darunavir/ ritonavir/ rilpivirine on the heart (measured using an electrocardiogram or ECG) |
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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 |
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E.3 | Principal inclusion criteria |
- Patient has signed and dated informed consent document, confirming their knowledge of the pertinent aspects of the study and willingness to comply with all study requirements, prior to screening procedures. - Male or female aged 18 to 65 years. - HIV-1 infected with less than and including 14 days total exposure to antiretroviral therapy – prior antiretrovirals as post-exposure prophylaxis permissible if documented negative test at 3 months following exposure. If patient has previously taken up to and including 14 days antiretroviral therapy during HIV-1 infection, this must not be within 12 weeks of the screening visit and there must be an available genotypic resistance test after last intake which indicates full viral susceptibility to study medication. - CD4 count >50 cells/mm3 at screening. - HIV-1 RNA > 1000 copies/mL at screening. - Women of childbearing potential (WoCBP); negative urine β-hCG pregnancy test at screen and baseline visit. - WOCBP, male patients and their partners must use two forms of contraception, one of which is an effective barrier method, when participating in sexual activity which could result in conception throughout the study and for 28 days following the last dose of study medication. |
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E.4 | Principal exclusion criteria |
- Infected with HIV-2 - Any medical, psychiatric or substance misuse disorders felt by the investigator to impact on the subject’s ability to participate in the study, including a positive urine test for drugs of abuse (cannabinoids are not exclusionary). - Disallowed concomitant medication as per the summary of product characteristics for darunavir or rilpivirine - Any genotypic resistance mutations on screening or prior tests to darunavir (V11I, V32I, L33F, I47V, I50V, I54M, I54L, T74P, L76V, I84V and L89V) or rilpivirine (K101E, K101P, E138A, E138G, E138K, E138R, E138Q, V179L, Y181C, Y181I, Y181V, H221Y, F227C, M230I, and M230L). - Screening ALT or AST elevation greater than 5 times the upper limit of normal. - Any active opportunistic infection within 4 weeks prior to planned baseline visit. - Any active cardiovascular, pulmonary, hepatic, renal or metabolic disease, or therapy used to treat these diseases, which in the opinion of the investigator could affect the absorption, distribution, metabolism or efficacy of the study medication. - Any known or suspected allergic reaction to the investigational products or excipients (including E110 allergy with regard to darunavir tablets). - Hepatitis B or C co-infection (defined as positive hepatitis B surface antigen or positive hepatitis C antibody; patients with positive hepatitis C antibody with undetectable RNA will be eligible for inclusion). - Estimated GFR (MDRD method) less than 50 ml/min - Use of proton pump inhibitors, or H-2 antagonists more than once daily - Subject has one or more of the following risk factors for QTc prolongation: i. a confirmed prolongation of QT/QTc interval, e.g., repeated demonstration of QTcF (Fridericia correction) interval > 450 ms in the screening ECG. ii. pathological Q-waves (defined as Q-wave > 40 ms or depth > 0.4-0.5 mV). iii. evidence of ventricular pre-excitation. iv. electrocardiographic evidence of complete or incomplete left bundle branch block or complete or clinically significant incomplete right bundle branch block. v. evidence of second or third degree heart block. vi. intraventricular conduction delay with QRS duration > 120 ms. vii. bradycardia as defined by sinus rate < 50 bpm. viii. personal or family history of long QT syndrome. ix. personal history of cardiac disease (including congenital heart disease), symptomatic or asymptomatic arrhythmias, with the exception of sinus arrhythmia. x. syncopal episodes. xi. risk factors for Torsades de Pointes (e.g., heart failure, hypokalemia, hypomagnesemia). |
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E.5 End points |
E.5.1 | Primary end point(s) |
The proportion of patients with HIV-1 RNA less than or equal to 40 copies/mL at week 48 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
The proportion of enrolled patients with a reduction from baseline in HIV-1 RNA >1 log10 copies /mL at weeks 4, 8, 12 and proportion with HIV-1 RNA 400 copies/mL at week 24.
The PK parameters (Cmax, C24, AUC0-24, and t1/2) for darunavir, rilpivirine and ritonavir at steady-state on day 28
Correlation between parameters of PK drug exposure with rate of viral load decay after initiation of therapy.
To describe and quantify changes in QT interval on resting ECG from baseline to week 48
To relate any observed changes in QT interval on resting ECG to pharmacokinetic exposure or pharmacodynamic response (change in HIV- 1 RNA level) from baseline to week 48 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
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) | 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 | No |
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 | 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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
High viral load cohort and low viral load cohort |
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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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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 | 4 |
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 | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |