| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Adult HIV-1 infected subjects on a stable HAART regimen of Kivexa + Kaletra, with raised cholesterol |
|
| 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 |
|
| 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 determine if switching the NRTI backbone from a Kivexa to Truvada leads to a reduction in fasting total cholesterol at 12 weeks. |
|
| E.2.2 | Secondary objectives of the trial |
• Evaluation of fasting metabolic parameters (e.g., LDL, HDL, non-HDL cholesterol, triglycerides, and cholesterol ratios).
• Evaluation of efficacy and safety by assessing adverse events, clinical laboratory tests, physical examinations and vital signs at every visit.
• Evaluation of changes in the 10-year risk factor for coronary heart disease outcomes as measured by total cholesterol, HDL, blood pressure, smoking status, treatment for hypertension, sex and age. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Subjects must meet all of the following inclusion criteria to be eligible for participation in this study:
• ≥ 18 years old
• Plasma HIV 1 RNA < 50 copies/mL at Screening and ≥ 12 weeks prior to Screening
• Stable HAART regimen of Kivexa + Kaletra for ≥ 24 weeks prior to Screening
• Documented confirmed raised total cholesterol ≥ 5.2 mmol/L (≥ 200 mg/dL) for the last two consecutive tests (at least 4 weeks apart)
• Documented confirmed total cholesterol ≥ 5.2 mmol/L (≥ 200 mg/dL) for last two consecutive testings (at least 4 weeks apart) prior to Screening and fasting total cholesterol ≥ 5.2 mmol/L at Screening
• Subject willing to continue current unmodified HAART for 12 weeks if randomized to Group 2
• Subjects requiring concomitant lipid regulating therapy must be established on a stable dose/frequency ≥ 12 weeks prior to Screening and be expected to remain stable in dose and frequency throughout the treatment phase of the study. Simvastatin and lovastatin are not allowed (see 4.3. Exclusion Criteria and Appendix 5 in the protocol)
• Adequate renal function by calculated creatinine clearance ≥ 60 mL/min according to the Cockcroft–Gault formula
• Negative serum pregnancy test (females of childbearing potential only i.e., not surgically sterile or at least 2 years post-menopausal)
• Serum Total Bilirubin ≤ 1.5 mg/dL
Note: In cases of clinically insignificant, asymptomatic elevated Serum Total Bilirubin (e.g. due to Gilbert Syndrome) the subject may be enrolled in the study with Serum Total Bilirubin > 1.5 mg/dL with the agreement of the Medical Monitor
• Women of childbearing potential (WOCBP) must be using a highly effective method of contraception to avoid pregnancy throughout the study and for up to 30 days after the last dose of study drugs in such a manner that the risk of pregnancy is minimized – refer to Section 7.8 for the definition of highly effective method of birth control.
• Female subjects who are postmenopausal for less than 2 years are required to have follicle stimulating hormone (FSH) ≥ 40 mIU/mL. If the FSH is < 40 mIU/mL, the subject must agree to use highly effective method of birth control to participate in the study– refer to Section 7.8 for the definition of highly effective method of birth control.
• Male subjects who are sexually active must be willing to use effective barrier contraception (e.g. condom with spermicide) during heterosexual intercourse from screening through completion of the study and continuing for up to 30 days after the last dose of study drugs
• Life expectancy ≥ 1 year
• The ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures. |
|
| E.4 | Principal exclusion criteria |
Subjects who meet any of the following exclusion criteria are not to be enrolled in this study:
• Pregnant or lactating subjects
• Previous treatment with emtricitabine (FTC), tenofovir DF (TDF) or adefovir dipivoxil (ADV)
• Known hypersensitivity to emtricitabine (FTC), tenofovir DF (TDF), Truvada or any of the excipients (e.g., lactose monohydrate, see 5.2.1)
• Documented resistance to any of the study drugs (either genotypic or phenotypic)
• Severe hepatic impairment
• Hepatitis B infection with viral load > 1.000 copies/ml at Screening or Hepatitis C infection requiring therapy.
• Treatment with any interferon or pegylated interferon within 18 months prior to Screening.
• Hepatic transaminases (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) ≥ 5 × upper limit of normal (ULN)
• Subjects receiving ongoing therapy with any of the medications that are contraindicated with any of the study drugs. Administration of any of these medications must be discontinued at least 28 days prior to the Baseline visit and for the duration of the study period. The full list of disallowed medications can be found in Appendix 5 of the protocol.
• Active, serious infections (other than HIV infection) requiring parenteral antibiotic therapy within 15 days prior to screening
• Prior history of significant renal or bone disease
• Any current known clinical or symptomatic laboratory parameter of GSI Grade 4 (see Appendix 4). Asymptomatic Grade 4 abnormalities will be permitted at the discretion of the investigator if deemed clinically appropriate (excluding adverse events and laboratory parameters mentioned elsewhere in the inclusion/exclusion criteria). Abnormalities deemed insignificant by the investigator must be discussed with the Medical Monitor prior to enrollment.
• Malignancy other than cutaneous Kaposi sarcoma (KS) or basal cell carcinoma. Subjects with biopsy-confirmed cutaneous KS are eligible, but must not have received any systemic therapy for KS within 30 days of baseline and are not anticipated to require systemic therapy during the study
• Current alcohol or substance use judged by the investigator to potentially interfere with subject study compliance
• Subjects currently taking part in any other clinical trial using an investigational product, with the exception of studies where the treatment studied has been stopped for more than 1 month prior to baseline
• Any other clinical condition or prior therapy that, in the opinion of the investigator, would make the subject unsuitable for the study or unable to comply with the dosing requirements. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary efficacy endpoint is change from baseline in total cholesterol at Week 12. |
|
| 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 | No |
| 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 | 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) | Yes |
| 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 | 9 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 30 |
| 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
|
| Last Patient Last Visit (LPLV) is defined as the last protocol required follow-up visit completed by a subject enrolled in this study. |
|
| 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 | 6 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
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