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 | 10020192 |
E.1.2 | Term | HIV-1 |
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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 the trial is to evaluate the antiviral activity as measured by the change in viral load from baseline in the 14 days following initiation of treatment with 4 different dose regimens of TMC310911 coadministered with ritonavir. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are: - To assess the viral characteristics during a 14-day treatment of 4 differentdose regimens of TMC310911 coadministered with 100 mg ritonavir - To assess the pharmacokinetics and pharmacokinetic/pharmacodynamic relationship of a 14-day treatment of 4 different dose regimens of TMC310911 coadministered with 100 mg ritonavir - To assess the safety and tolerability of a 14-day treatment of 4 different dose regimens of TMC310911 coadministered with 100 mg ritonavir |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subjects must meet all of the following inclusion criteria: 1. Male or female subjects, aged between 18 and 60 years, extremes included; 2. Documented HIV-1 infection for at least 6 months prior to the screening date; 3. Subject has not been treated with a therapeutic HIV vaccine within 1 year prior to enrolment and and has never been treated with an ARV drug indicated for the treatment of HIV-infection or ARVs for treatment of hepatitis B-infection with anti-HIV activity (e.g., adefovir, lamivudine, and emtricitabine); 4. Subject agrees not to start ART before the baseline visit; 5. ICF signed voluntarily before the first trial related activity; 6. Able to comply with the protocol requirements and having good accessible veins; 7. HIV-1 plasma viral load at screening visit of above 5,000 HIV-1 RNA copies/mL; 8. CD4+ cell count above 200 cells/mm3 at screening. |
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E.4 | Principal exclusion criteria |
Subjects must not have any of the following characteristics: 1. Any condition (including but not limited to alcohol and drug use), which, in the opinion of the investigator, could compromise the subject’s safety and adherence to the protocol; 2. HIV-2 infected patients and/or patients with any active or chronic hepato-renal disease; 3. Life expectancy of less than 6 months; 4. Subject has a documented acute (primary) HIV-1 infection; Note: Primary or acute HIV infection is the first phase of HIV disease, occurring in the weeks immediately following infection by HIV and lasting for approximately 3 to 6 months. A viral load test at this stage will usually show extremely high levels of HIV in the blood - often higher than at any other stage of HIV infection, and may therefore not be reliable when evaluating the need for initiating antiretroviral therapy. 5. Subject has pre-existing PI drug resistance, based upon the presence of one or more primary PI mutations in the screening sample, using the most recent list of the International AIDS Society (IAS-USA). 6. Subject has any currently active Acquired Immunodeficiency Syndrome (AIDS) defining illness (Category C conditions according to the Centers for Disease Control and Prevention [CDC] Classification System for HIV Infection 1993) with the following exceptions (to be discussed and agreed on with the sponsor prior to enrolment): - Stable, cutaneous Kaposi Sarcoma (i.e., no pulmonary or gastrointestinal involvement other than oral lesions) that is unlikely to require any form of systemic therapy during the trial period; - Wasting syndrome due to HIV infection if, in the investigator’s opinion, it is not actively progressive and its treatment does not require hospitalization or compromise the subject’s safety or compliance to adhere to the trial protocol procedures. If the subject is on maintenance therapy (which may include human Growth Hormone, appetite stimulants and anabolic steroids) for previously diagnosed wasting, he/she may be eligible for the trial only if such treatment is not included in the list of disallowed medications; Note: Primary or secondary prophylaxis for an AIDS defining illness is allowed in case the medication used is not part of the disallowed medication. 7. Any active clinically significant disease (e.g., pancreatitis, cardiac dysfunction), or findings during screening or medical history or physical examination that in the investigator’s opinion, would compromise the outcome of the trial; 8. Receipt of any investigational drug or vaccine within 90 days prior to the first trial drug administration; 9. Previously demonstrated clinically significant allergy or hypersensitivity; 10. Non-vasectomized heterosexually active males who have a female partner of childbearing potential without the use of effective birth control methods or not willing to continue practicing these birth control methods from screening onwards until 30 days after the end of the trial. 11. Women of child bearing potential; 12. Any confirmed grade 3 or 4 toxicity according to the Division of AIDS (DAIDS) grading scale at screening, except for: - Asymptomatic grade 3 pancreatic amylase elevation; - Asymptomatic grade 3 triglyceride/cholesterol/hyperglycemia; - Asymptomatic grade 4 triglyceride elevation. 13. Subject has any kind of clinically significant cardiac disease including: - Heart block, arrhythmias, congestive heart, and others; - A confirmed prolongation of QT/QTc interval, e.g., repeated demonstration of QTcF interval > 480 ms in the screening ECG (i.e., retesting to reassess eligibility will be allowed once using an unscheduled visit during the screening period); - Risk factors for Torsade de Pointes (e.g., heart failure, hypokalemia); - Intraventricular conduction delay with QRS duration > 120 ms; - Bradycardia as defined by sinus rate < 40 bpm; - Syncopal episodes. |
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E.5 End points |
E.5.1 | Primary end point(s) |
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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 | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | No |
E.8.5.1 | Number of sites anticipated in the EEA | 4 |
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 | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
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 | |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | |