| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Naive HIV-Infected Patients, |
|
| 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 | 10000807 |
| E.1.2 | Term | Acute HIV infection |
|
| 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 |
Objective: Evaluate the antiretroviral activity of once daily raltegravir, 800 mg q.d.,
compared to efavirenz 600 mg q.d., each in combination therapy with TRUVADA ,
as measured by proportion of patients achieving HIV RNA <50 copies/mL at Week
48.
Hypothesis: The proportion of patients achieving HIV RNA <50 copies/mL at Week
48 in the once daily raltegravir treatment group is non-inferior to that in the efavirenz
group, each in combination therapy with TRUVADA . Once daily raltegravir is
concluded non-inferior to efavirenz if the lower bound of the two-sided 95% CI for
the difference in response rate (raltegravir – efavirenz) remains above -10 percentage
points. Raltegravir superiority to efavirenz will be assessed if non-inferiority is
established.
2) Objective: Evaluate the tolerability of once daily raltegravir, 800 mg q.d., compared
to efavirenz 600 mg q.d., each in combination therapy with TRUVADA , as
assessed by review of the accumulated safety data. |
|
| E.2.2 | Secondary objectives of the trial |
Objective: Evaluate the antiretroviral activity of once daily raltegravir, 800 mg q.d.,
compared to efavirenz 600 mg q.d., each in combination therapy with TRUVADA ,
as measured by the following parameters at Week 48:
Proportion of patients achieving HIV RNA <400 copies/mL.
Change from baseline in CD4 cell counts
2) Objective: Evaluate the antiretroviral activity of once daily raltegravir, 800 mg q.d.,
compared to efavirenz 600 mg q.d., each in combination therapy with TRUVADA ,
as measured by the following parameters at Week 96:
Proportion of patients achieving HIV RNA <50 copies/mL.
Proportion of patients achieving HIV RNA <400 copies/mL.
Change from baseline in CD4 cell counts.
3) Objective: To evaluate the nervous system symptoms associated with the use of raltegravir |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Patient is a male or female at least 18 years of age on the day of signing the informed
consent.
2. Patient is HIV positive as determined by a positive result by enzyme-linked
immunosorbent assay (ELISA) and has screening plasma HIV RNA (determined by
the central laboratory) >5000 copies/mL within 45 days prior to the treatment phase
of this study, and is indicated for treatment based on physician assessment. Local
treatment guidelines should be considered in the decision to initiate therapy.
3. Patient is naive to antiretroviral therapy (ART) or defined as having received <7 days
total of any ART.
Patient has the following laboratory values within 45 days prior to the treatment
phase of this study:
4.1 Serum creatinine &#8804;2.0 x upper limit of normal
4.2 Alkaline phosphatase &#8804;5.0 x upper limit of normal
4.3 AST (SGOT) and ALT (SGPT) &#8804;5.0 x upper limit of normal
Note: A single repeat of a laboratory screening test will be allowed for test results that
are unexpected based on documented prior laboratory results.
5. Patient has a calculated creatinine clearance at time of screening >30 mL/min, based
on the Cockcroft-Gault equation which is as follows (and 0.85X this value for
females):
Clcr (mL/min) = (140-age) x weight (in kg)
72 x serum creatinine (mg/dL)
6. In the opinion of the investigator, the patient should be considered clinically stable
with no signs or symptoms of active infection, at the time of entry into the study; i.e.,
clinical status and all chronic medications should be unchanged for at least 2 weeks
prior to the start of treatment in this study.
7. Patient who is of reproductive potential agrees remain abstinent or use (or have their
partner use) 2 acceptable methods of birth control throughout the study. Acceptable
methods of birth control are: oral contraceptives, intrauterine device (IUD),diaphragm with spermicide, contraceptive sponge, condom, vasectomy. |
|
| E.4 | Principal exclusion criteria |
Patient has a history or current evidence of any condition, therapy, laboratory
abnormality or other circumstance that might confound the results of the study, or
interfere with the patient’s participation for the full duration of the study, such that it
is not in the best interest of the patient to participate.
2. Patient is, at the time of signing informed consent, a user of recreational or illicit
drugs or has had a recent history (within the last year) of drug or alcohol abuse or
dependence.
3. Patient has been treated for a viral infection other than HIV, such as hepatitis B, with
an agent that is active against HIV including but not limited to adefovir, tenofovir,
emtricitabine or lamivudine.
Note: Patients may be enrolled if treatment occurred prior to the diagnosis of HIV.
4. Patient has documented resistance to tenofovir, emtricitabine, and/or efavirenz.
5. Patient is currently participating or has participated in a study with an investigational
compound or device within 45 days of signing informed consent.
6. Patient has used another experimental HIV-integrase inhibitor.
7. Patient has used systemic immunosuppressive therapy within one month prior to
treatment in this study. Short courses of corticosteroids (e.g., as for asthma
exacerbation) will be allowed.
8. Patient requires hemodialysis. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary
endpoints are the proportion of patients achieving HIV RNA <50 copies/mL at Week 48
and the safety and tolerability of once daily raltegravir compared with efavirenz when
each is given in combination with TRUVADA for up to 48 weeks. |
|
| 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 | No |
| 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) | Yes |
| 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 | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| 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 | Yes |
| 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 | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 45 |
| 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 | Information not present in EudraCT |
| 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 |
|
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 2 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 2 |
Print
