E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Adult, HIV-1 infected, tenofovir DF- and emtricitabine-naive subjects on a stable HAART regimen of Kivexa (abacavir/lamivudine) and efavirenz, with raised total fasting cholesterol |
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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 |
To determine if switching from a stable HAART regimen of Kivexa + EFV to once daily Atripla leads to a reduction in total fasting cholesterol at 12 weeks. |
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E.2.2 | Secondary objectives of the trial |
•Evaluation of fasting metabolic parameters (e.g., LDL, HDL, triglycerides, non-HDL cholesterol 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. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• ≥ 18 years old • Plasma HIV RNA < 50 copies/mL ≥ 12 weeks prior to Screening • Stable HAART regimen of Kivexa + EFV for ≥ 24 weeks prior to Screening • Documented confirmed raised total cholesterol ≥ 5.2 mmol/L for last two consecutive tests (at least 4 weeks apart) with the last result ≤ 4 weeks prior to 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 • 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) • Hepatic Total Bilirubin ≤ 22 umol/L • Adequate haematologic function of absolute neutrophil count ≥ 1000/mm3, platelets ≥ 25,000/mm3, Haemoglobin ≥ 8.0g/dL • Women of childbearing potential (WOCBP) must be using two methods of contraception to avoid pregnancy throughout the study and for up to 12 weeks after the last dose of study drugs in such a manner that the risk of pregnancy is minimized. • Female subjects who are postmenopausal for less than 2 years are required to have 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 • 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 12 weeks 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 |
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E.4 | Principal exclusion criteria |
• Pregnant or lactating subjects • Previous treatment with emtricitabine (FTC), tenofovir DF (TDF) or adefovir dipivoxil (ADV) • Known hypersensitivity to emtricitabine (FTC), tenofovir DF (TDF), efavirenz (EFV) or Truvada • Documented resistance to any of the study drugs (either genotypic or phenotypic) • Severe hepatic impairment Hepatic transaminases (AST and 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. • 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. Asymptomatic grade 4 abnormalities will be permitted at the discretion of the Investigator if deemed clinically appropriate (excluding AEs and laboratory parameters mentioned elsewhere in the inclusion/exclusion criteria). Abnormalities deemed insignificant by the Investigator must be discussed with the Sponsor 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 • 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 |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in total fasting cholesterol at 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 | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Information not present in EudraCT |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
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) | Information not present in EudraCT |
E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
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 | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 17 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 18 |
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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Last Patient Last Visit is defined as the last protocol required follow-up visit completed by a subject enrolled in this study (30 day follow-up assessment). |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 11 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 11 |