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Effects of Switching From ATRIPLA^TM (Efavirenz, Tenofovir, Emtricitabine) to MK-1439A (Doravirine, Tenofovir, Lamivudine) in Virologically-Suppressed Participants (MK-1439A-028)

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ClinicalTrials.gov Identifier: NCT02652260
Recruitment Status : Active, not recruiting
First Posted : January 11, 2016
Last Update Posted : December 21, 2017
Sponsor:
Information provided by (Responsible Party):

Study Description
Brief Summary:
This study aims to evaluate a switch from fixed dose combination (FDC) treatment with ATRIPLA^TM for 12 weeks prior to screening to FDC treatment with MK-1439A in virologically-suppressed, human immunodeficiency virus type 1 (HIV-1)-infected participants. The primary hypothesis is that switching from ATRIPLA^TM to MK-1439A results in a lower proportion of participants with at least one CNS toxicity of at least Grade 2 intensity at Week 12 than continuation of ATRIPLA^TM treatment.

Condition or disease Intervention/treatment Phase
HIV-1 Infection CNS Toxicity Drug: MK-1439A - Blinded Drug: MK-1439A - Open-Label Drug: ATRIPLA^TM Drug: Placebo to ATRIPLA^TM Drug: Placebo to MK-1439A Phase 2

Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 84 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Phase IIb, Double-Blinded, Multicenter, Randomized Study to Assess the Effect on Central Nervous System (CNS) Toxicity of Switching From ATRIPLA™ (Efavirenz, Tenofovir, Emtricitabine) to MK-1439A (Doravirine, Tenofovir, Lamivudine) in Virologically-Suppressed Subjects.
Actual Study Start Date : March 4, 2016
Estimated Primary Completion Date : February 26, 2018
Estimated Study Completion Date : September 24, 2018

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: Immediate Switch to MK-1439A
Participants on a baseline regimen of ATRIPLA^TM for at least 12 weeks prior to screening will be switched to blinded MK-1439A orally, once daily for 12 weeks, followed by open-label MK-1439A orally, once daily for an additional 12 weeks. Participants who meet eligibility criteria can enter the study extension to receive open-label MK-1439A for an additional 96 weeks.
Drug: MK-1439A - Blinded
A single tablet FDC containing doravirine 100 mg, lamivudine (3TC) 300 mg and tenofovir disoproxil fumarate (TDF) 300 mg administered orally, once daily for 12 weeks during the Blinded Period
Drug: MK-1439A - Open-Label
A single-tablet FDC containing doravirine 100 mg, 3TC 300 mg and TDF 300 mg administered orally, once daily for either 12 or 24 weeks during the Open-Label Period; and also an additional 96 weeks during the Open-Label Extension period.
Drug: Placebo to ATRIPLA^TM
A single placebo to ATRIPLA^TM tablet administered orally, once daily for 12 weeks during the Blinded Period
Experimental: Deferred Switch to MK-1439A
Participants will continue on their ongoing ATRIPLA^TM regimen orally, once daily for 12 weeks, followed by open-label MK-1439A orally, once daily for 24 weeks. Participants who meet eligibility criteria can enter the study extension to receive open-label MK-1439A for an additional 96 weeks.
Drug: MK-1439A - Open-Label
A single-tablet FDC containing doravirine 100 mg, 3TC 300 mg and TDF 300 mg administered orally, once daily for either 12 or 24 weeks during the Open-Label Period; and also an additional 96 weeks during the Open-Label Extension period.
Drug: ATRIPLA^TM
A single tablet FDC containing efavirenz (EFV) 600 mg, emtricitabine (FTC) 200 mg, and TDF 300 mg administered orally, once daily for 12 weeks during the Blinded Period
Drug: Placebo to MK-1439A
A single placebo to MK-1439A tablet administered orally, once daily for 12 weeks during the Blinded Period


Outcome Measures

Primary Outcome Measures :
  1. Percentage of participants with at least one CNS toxicity of at least Grade 2 intensity at Week 12 [ Time Frame: Week 12 ]

Secondary Outcome Measures :
  1. Percentage of participants with at least one CNS toxicity of at least Grade 2 intensity at Week 4 [ Time Frame: Week 4 ]
  2. Change from baseline in CNS toxicity score at Week 4 [ Time Frame: Baseline and Week 4 ]
  3. Change from baseline in CNS toxicity score at Week 12 [ Time Frame: Baseline and Week 12 ]
  4. Number of participants with one or more Adverse Events (AEs) [ Time Frame: Up to Week 38 ]
  5. Number of participants who discontinued treatment due to an AE [ Time Frame: Up to Week 36 ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • is taking ATRIPLA^TM, generic versions of ATRIPLA^TM, or the components of ATRIPLATM (EFV,TDF plus emtricitabine),
  • has documentation of HIV-1 ribonucleic acid (RNA) < 50 copies/mL during the 12 weeks prior to screening while on ATRIPLA^TM.
  • has plasma HIV-1 RNA levels below the limits of quantification (BLoQ) at the screening visit.
  • if genotyped prior to starting initial antiretroviral regimen, must have no known resistance to any of the study agents
  • has at least one EFV-associated CNS toxicities of Grade 2 or worse intensity both at the time of screening and at Study Day 1
  • is highly unlikely to become pregnant or to impregnate a partner

Exclusion Criteria:

  • is a user of recreational or illicit drugs or has had a recent history of drug or alcohol abuse or dependence.
  • has ongoing Grade 4 CNS toxicity during screening period that requires a prompt change in ART
  • 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.
  • has documented or known resistance to study drugs including MK-1439, lamivudine, and/or tenofovir
  • has participated in, or anticipates participating in a study with an investigational compound/device within 30 days prior to signing informed consent
  • has used systemic immunosuppressive therapy or immune modulators or anticipates using them within 30 days prior to this study
  • requires or anticipates requiring any of the prohibited medications
  • has significant hypersensitivity or other contraindication to any of the components of the study drugs
  • has a current (active) diagnosis of acute hepatitis due to any cause.
  • 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.
  • is pregnant, breastfeeding, or expecting to conceive.
  • female is expecting to donate eggs (at any time during the study) or male is expecting to donate sperm (at any time during the study).
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02652260


Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.
More Information

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT02652260     History of Changes
Other Study ID Numbers: 1439A-028
2015-003617-18 ( EudraCT Number )
First Posted: January 11, 2016    Key Record Dates
Last Update Posted: December 21, 2017
Last Verified: December 2017

Additional relevant MeSH terms:
Tenofovir
Lamivudine
Emtricitabine
Efavirenz
Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Anti-HIV Agents
Cytochrome P-450 CYP2C9 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Cytochrome P-450 CYP2C19 Inhibitors
Cytochrome P-450 CYP2B6 Inducers
Cytochrome P-450 Enzyme Inducers
Cytochrome P-450 CYP3A Inducers