Switch to MK-1439A (once a day) from a Ritonavir-boosted Protease Inhibitor regimen in HIV-1 infected subjects
- Conditions
- Human Immunodeficiency Virus-1 infectionTherapeutic area: Diseases [C] - Virus Diseases [C02]MedDRA version: 18.0Level: LLTClassification code 10068341Term: HIV-1 infectionSystem Organ Class: 100000004862
- Registration Number
- EUCTR2014-005550-18-ES
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 660
1. be at least 18 years of age on the day of signing the informed consent.
2. understand the study procedures and voluntarily agree to participate by giving written informed consent (or have a legal representative provide written informed consent) for the trial. The subject or his/her legal representative may also provide consent for Future Biomedical Research. However, the subject may participate in the main trial without participating in Future Biomedical Research.
3. have plasma HIV-1 RNA levels BLoQ (<40 copies/mL by the Abbott RealTime HIV-1 Assay as determined by the central laboratory) at the screening visit.
4. have been receiving antiretroviral therapy with atazanavir/ritonavir, darunavir/ritonavir or lopinavir/ritonavir in combination with 2 NRTIs (and no other ART) continuously with HIV-1 RNA at undetectable levels for ? 6 months prior to the screening visit (as measured at ? 2 time points) and have no history of prior virologic failure.
5. be receiving his/her first or second PI-based antiretroviral regimen
6. have no history of using any approved or experimental NNRTI for any length of time.
7. have had a genotype prior to starting his/her initial antiretroviral regimen and have no known resistance to any of the study agents (MK-1439, TDF, or lamivudine).
8. be on either no lipid lowering therapy or on a stable dose of lipid lowering therapy at the time of enrollment
9. have the following laboratory values at screening within 30 days prior to the
treatment phase of this study:
a) Alkaline phosphatase ? 3.0 x upper limit of normal (ULN)
b) AST (SGOT) and ALT (SGPT) ? 5.0 x ULN
c) Hemoglobin ?9.0 g/dL (if female) or ?10.0 g/dL (if male).
10. have a calculated creatinine clearance at the time of screening ? 50 mL/min, based on the Cockcroft-Gault equation which is as follows:
For Men:
Clcr (mL/min) = (140-age) x weight (in kg)
72 x serum creatinine (mg/dL)
For Women:
Clcr (mL/min) = (140-age) x weight (in kg)
72 x serum creatinine (mg/dL)
X 0.85
11. in the opinion of the investigator, 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).
12. be highly unlikely to become pregnant or to impregnate a partner since the subject falls into at least one of the following categories:
a. The subject is a male who is not of reproductive potential, defined as a male who has azoospermia (whether due to having had a vasectomy or due to an underlying medical condition).
b. The subject is a female who is not of reproductive potential, defined as a female who either: (1) is postmenopausal (defined as at least 12 months with no menses in women ? 45 years of age); (2) has had a hysterectomy and/or bilateral oophorectomy, bilateral salpingectomy, or bilateral tubal ligation/occlusion at least 6 weeks prior to screening; OR (3) has a congenital or acquired condition that prevents childbearing.
c. The subject is a female or a male who is of reproductive potential and agrees to avoid becoming pregnant or impregnating a partner while receiving study drug and for 14 days after the last dose of study drug by complying with one of the following: (1) practice abstinence* from heterosexual activity OR (2) use (or have their partner use) acceptable contraception during heterosexual activity.
Acceptable methods of contraception are:
Single method (one o
1. 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 subject´s participation for the full duration of the study, such that it is not in the best interest of the subject to participate.
2. is, at the time of signing informed consent, a user of recreational or illicit drugs or has had a recent history of drug or alcohol abuse or dependence. The nature and potential clinical context of the subject's illicit drug use, in relation to their exclusion from this trial, will be at the discretion of the Investigator.
3. has been treated for a viral infection other than HIV-1, such as hepatitis B, with an agent that is active against HIV-1 including, but not limited to, adefovir, emtricitabine, entecavir, lamivudine or tenofovir.
Note: Subjects may be enrolled if treatment occurred prior to the diagnosis of HIV or in the context of a complete regimen for HIV
4. has documented or known resistance to study drugs including MK-1439, lamivudine, and/or tenofovir, as defined below:
a. Resistance to MK-1439 for the purpose of this study is considered to include the following NNRTI mutations (as single mutations or components of double or triple mutations): L100I, K101E, K101P, K103S, V106A, V106I, V106M, V108I, E138A, E138G, E138K, E138Q, E138R, V179L, Y181I, Y181V, Y188C, Y188H, Y188L, G190S, H221Y, L234I, P225H, F227C, F227L, F227V, M230L, M230I.
b. Resistance to lamivudine and tenofovir includes the following mutations: K65R, M41L, T69S (insertion complex), Q151M, M184I, M184V, L210W, T215F, T215Y, K219E, K219Q, D67N, K70R and K70E.
5. has participated in a study with an investigational compound/device within 30 days prior to signing informed consent or anticipates participating in such a study involving an investigational compound/device during the course of this study.
6. has used systemic immunosuppressive therapy or immune modulators within 30 days prior to treatment in this study or is anticipated to need them during the course of the study.
7. requires or is anticipated to require any of the prohibited medications noted in the protocol
8. has significant hypersensitivity or other contraindication to any of the components of the study drugs as determined by the investigator.
9. has a current (active) diagnosis of acute hepatitis due to any cause.
10. has evidence of decompensated liver disease manifested by the presence of or a history of ascites, esophageal or gastric variceal bleeding, hepatic encephalopathy or other signs or symptoms of advanced liver diseases
or
has liver cirrhosis and a Child-Pugh Class C score or Pugh-Turcotte (CPT) score > 9
11. is pregnant, breastfeeding, or expecting to conceive.
12. is female and is expecting to donate eggs (at any time during the study) or is male and is expecting to donate sperm (at any time during the study).
13. is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling or child) who is investigational site or sponsor staff directly involved with this trial.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method