Multicenter, Double-Blind, Randomized, 2-Part, Dose Ranging Study to Compare the Safety, and Antiretroviral Activity of MK-1439 Plus TRUVADA® Versus Efavirenz Plus TRUVADA® in Antiretroviral Treatment-Naïve, HIV-1 Infected Patients

Phase 2

Completed

Conditions: HIV
Infection with the Human Immunodeficiency Virus
10021460
10047438

Registration Number: NL-OMON41652

Lead Sponsor: Merck Sharp & Dohme (MSD)

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 15

Inclusion Criteria

a. Patient is a male or female of at least 18 years of age on the day of signing the informed consent. Patient provides written informed consent for the trial. The patient will also provide consent for Future Biomedical Research; however, the patient may participate in the main trial without participating in Future Biomedical Research.;b. Patient is HIV positive as determined by a positive ELISA and has screening plasma HIV RNA (completed by the central laboratory) * 1,000 copies/mL within 45 days prior to the treatment phase of this study.;c. Patient has a screening CD4 cell count *100 cells/mm3(completed by the central laboratory) within 45 days prior to the treatment phase of this study.;d. Patient is naïve to antiretroviral therapy (ART).;e. Patient has had the following laboratory values within 45 days prior to the treatment phase of this study:;1) Serum creatinine within normal limits.;2) INR *1.2;3) Urinalysis within normal limits.;Note: Clinically insignificant abnormalities on urinalysis may be permitted after retest, provided these are documented as clinically insignificant per investigator.;4) Hemoglobin *9.0 g/dL (if female) or *10.0 g/dL (if male).;5) Absolute neutrophil count *1000/mm3.;6) Platelet count *100,000/ mm3.;7) Total serum bilirubin less than or equal to the upper limit of normal.;8) Alkaline phosphatase <1.5 x upper limit of normal.;9) AST (SGOT) and ALT (SGPT) <1.5 x upper limit of normal.;f. In the opinion of the investigator, the patient should be considered clinically stable with no signs or symptoms of acute 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.;g. Patient who is of reproductive potential agrees to remain abstinent or use (or have their partner use) 2 acceptable methods of birth control throughout the study and for 12 weeks post study. Acceptable methods of birth control are: oral contraceptives, intrauterine device (IUD), diaphragm with spermicide, contraceptive sponge, condom, and vasectomy.;OR;Patient who is not of reproductive potential1, is not sexually active, whose current partner(s) is not of reproductive potential, or whose sexual activity is exclusively homosexual is eligible without requiring the use of contraception.

Exclusion Criteria

a. Male patient is planning to impregnate or provide sperm donation for the duration of the study plus an additional 12 weeks. Female patient is pregnant or breast-feeding, or expecting to conceive or donate eggs for the duration of the study plus an additional 12 weeks.;b. Patient has received any approved or experimental antiretroviral agents or is anticipated to receive such medications (beyond those outlined as study medication in this protocol) during the course of the study.;c. Patient has used any immunomodulators or immunosuppressive therapy within one month prior to treatment in this study. Short courses of corticosteroids (e.g., as for asthma exacerbation) are allowed.;d. Patient requires or is anticipated to require any of the prohibited medications noted in Section 3.2.1.;e. 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 disoproxil fumarate, lamivudine, emtricitabine, or entecavir.;Note: Patients may be enrolled if treatment occurred prior to the diagnosis of HIV.;f. Patient has significant hypersensitivity or other contraindication to any of the components of the study drugs (emtricitabine, tenofovir disoproxil fumarate, and/or efavirenz).;g. Patient has documented or known HIV resistance to emtricitabine, tenofovir disoproxil fumarate, and/or efavirenz, based on genotypic resistance analysis.;h. Patient has a history of renal or urinary obstructive disease, requires dialysis (hemodialysis, continuous ambulatory peritoneal dialysis [CAPD], or other forms of dialysis), or has a calculated creatinine clearance at time of screening of *80 mL/min, based on the Cockcroft-Gault equation which is as follows (and 0.85 times this value for females):;Clcr (mL/min) = (140*age) x weight (in kg)____;72 x serum creatinine (mg/dL);i. Patient with active Hepatitis C virus (HCV) co-infection (defined as detectable HCV RNA) or Hepatitis B virus (HBV) co-infection (defined as HBsAg positive). Patients with prior/inactive HCV infection (defined as undetectable HCV RNA) or past HBV infection (defined as HBsAg negative and HBsAb positive) may be enrolled.;j. Patient has a history of alcohol or other substance abuse which in the opinion of the investigator would interfere with patient compliance or safety.;k. Patient has any condition or prestudy laboratory abnormality, or history of any illness, which, in the opinion of the investigator, might confound the results of the study or pose additional risk in administering the study drugs to the patient.;l. Patient has participated in a study with an investigational compound/device within one month of signing informed consent or is anticipating to participate in such a study involving an investigational compound/device during the course of this study.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary endpoints are the proportion of patients achieving HIV RNA <40<br /><br>copies/mL at Week 24, and the safety and tolerability of MK-1439 compared with<br /><br>efavirenz when each is given in combination with TRUVADA® through Week 24. A<br /><br>single dose will be selected for further study after all patients complete the<br /><br>Week 24 visit in Part I. Each site will receive an administrative letter<br /><br>communicating the selected dose, then patients on other doses of MK-1439 will<br /><br>be switched to the selected dose at the next planned study visit while<br /><br>maintaining the study blind. Secondarily, longer-term safety and efficacy data<br /><br>will be evaluated at Week 48 and Week 96.</p><br>

Secondary Outcome Measures