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Safety and Efficacy of Doravirine (MK-1439) in Participants With Human Immunodeficiency Virus 1 (HIV-1) (MK-1439-018)

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ClinicalTrials.gov Identifier: NCT02275780
Recruitment Status : Active, not recruiting
First Posted : October 27, 2014
Last Update Posted : May 14, 2018
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Study Description
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Brief Summary:
To establish a new treatment option for treatment-naïve participants with HIV-1, the efficacy and safety of doravirine will be determined relative to a protease inhibitor (PI). Participants will receive double-blind treatment during the 96-week Base Study. Eligible participants in either of the Base Study groups will continue to receive the doravirine-containing regimen open label for an additional 96 weeks in the Study Extension 1. Eligible participants who are deriving benefit will continue in Study Extension 2 to receive the doravirine-containing regimen open label until doravirine becomes locally available or for an additional 96 weeks, whichever comes first. The primary hypothesis is that doravirine 100 mg once a day (q.d.) is non-inferior to darunavir/ritonavir (800 mg/100 mg) q.d., each in combination with TRUVADA™ or EPZICOM™/KIVEXA™, as assessed by the proportion of participants with HIV-1 ribonucleic acid (RNA) <50 copies/mL at Week 48. If non-inferiority is established, then the superiority of doravirine 100 mg q.d. compared to darunavir/ ritonavir (800 mg/100 mg) q.d. will be assessed.

Condition or disease Intervention/treatment Phase
HIV-1 Drug: Doravirine Drug: Darunavir Drug: Ritonavir Drug: TRUVADA™ or EPZICOM™/KIVEXA™ Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 769 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 3 Multicenter, Double-Blind, Randomized, Active Comparator-Controlled Clinical Trial to Evaluate the Safety and Efficacy of Doravirine (MK-1439) 100 mg Once Daily Versus Darunavir 800 mg Once Daily Plus Ritonavir 100 mg Once Daily, Each in Combination With TRUVADA™ or EPZICOM™/KIVEXA™, in Treatment-Naïve HIV-1 Infected Subjects
Actual Study Start Date : December 1, 2014
Actual Primary Completion Date : September 29, 2016
Estimated Study Completion Date : June 23, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arms and Interventions
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Arm Intervention/treatment
Experimental: Doravirine 100 mg
Double-blind Doravirine 100 mg administered orally (p.o.) once daily (q.d.) + investigator selected TRUVADA™ or EPZICOM™/KIVEXA™ administered p.o., q.d. for 96 weeks in the Base Study. Eligible participants may continue in Study Extension 1 with open-label Doravirine 100 mg administered p.o., q.d. + investigator selected TRUVADA™ or EPZICOM™/KIVEXA™ administered p.o., q.d. for an additional 96 weeks. Eligible participants may continue to receive the same treatment regimen in Study Extension 2 until doravirine becomes locally available, or for an additional 96 weeks, whichever comes first.
 Drug: Doravirine
Doravirine 100 mg tablet administered p.o., q.d.

Drug: TRUVADA™ or EPZICOM™/KIVEXA™
The investigator selects either TRUVADA™, a tablet containing 200 mg emtricitabine and 300 mg tenofovir disoproxil fumarate, p.o., q.d., or EPZICOM™/KIVEXA™, a tablet containing 600 mg abacavir sulfate and 300 mg lamivudine, p.o., q.d.
Active Comparator: Darunavir 800 mg and Ritonavir 100 mg
Double-blind Darunavir 800 mg and Ritonavir 100 mg administered p.o., q.d. + investigator selected TRUVADA™ or EPZICOM™/KIVEXA™ administered p.o., q.d. for 96 weeks. Eligible participants may continue in Study Extension 1 with open-label Doravirine 100 mg administered p.o., q.d. + investigator selected TRUVADA™ or EPZICOM™/KIVEXA™ administered p.o., q.d. for an additional 96 weeks. Eligible participants may continue to receive the same treatment regimen in Study Extension 2 until doravirine becomes locally available, or for an additional 96 weeks, whichever comes first.
 Drug: Doravirine
Doravirine 100 mg tablet administered p.o., q.d.

Drug: Darunavir
Darunavir 800 mg tablet administered p.o., q.d.

Drug: Ritonavir
Ritonavir 100 mg tablet administered p.o., q.d.

Drug: TRUVADA™ or EPZICOM™/KIVEXA™
The investigator selects either TRUVADA™, a tablet containing 200 mg emtricitabine and 300 mg tenofovir disoproxil fumarate, p.o., q.d., or EPZICOM™/KIVEXA™, a tablet containing 600 mg abacavir sulfate and 300 mg lamivudine, p.o., q.d.


Outcome Measures
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Primary Outcome Measures :
  1. Percentage of participants achieving HIV-1 RNA <50 copies/mL at Week 48 [ Time Frame: Week 48 ]

Secondary Outcome Measures :
  1. Percentage of participants achieving HIV-1 RNA <50 copies/mL at Week 96 [ Time Frame: Week 96 ]
  2. Change from baseline in cluster of differentiation 4 (CD4) cell counts at Week 48 [ Time Frame: Baseline and Week 48 ]
  3. Change from baseline in CD4 cell counts at Week 96 [ Time Frame: Baseline and Week 96 ]
  4. Change from baseline in fasting low density lipoprotein cholesterol (LDL-C) at Week 48 [ Time Frame: Baseline and Week 48 ]
  5. Change from baseline in fasting non-high density lipoprotein cholesterol (non-HDL-C) at Week 48 [ Time Frame: Baseline and Week 48 ]
  6. Change from baseline in fasting high density lipoprotein cholesterol (HDL-C) at Week 48 [ Time Frame: Baseline and Week 48 ]
  7. Change from baseline in fasting total cholesterol at Week 48 [ Time Frame: Baseline and Week 48 ]
  8. Change from baseline in fasting triglycerides at Week 48 [ Time Frame: Baseline and Week 48 ]
  9. Percentage of participants with any adverse event (AE) [ Time Frame: Up to 14 day post study (up to 98 weeks) ]
  10. Percentage of participants with any serious adverse event (SAE) [ Time Frame: Up to 14 day post study (up to 98 weeks) ]
  11. Percentage of participants with any drug-related AE [ Time Frame: Up to 14 day post study (up to 98 weeks) ]
  12. Percentage of participants with any SAE and drug-related AE [ Time Frame: Up to 14 day post study (up to 98 weeks) ]
  13. Percentage of participants who discontinued treatment due to an AE [ Time Frame: Up to 96 weeks ]
  14. Percentage of Participants Achieving HIV-1 RNA <40 copies/mL at Week 48 [ Time Frame: Week 48 ]
  15. Percentage of Participants Achieving HIV-1 RNA <40 copies/mL at Week 96 [ Time Frame: Week 96 ]

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

Inclusion Criteria:

  • Is HIV-1 positive and has HIV treatment indicated based on physician assessment.
  • Has received no (0 days of) antiretroviral therapy (ART), including investigational antiretroviral agents.
  • Is considered clinically stable with no signs or symptoms of active infection for at least 2 weeks prior to the start of treatment.
  • Female is highly unlikely to become pregnant, or male is highly unlikely to impregnate a partner because they are not of reproductive potential, or agree to practice abstinence or use acceptable contraception for up to 14 days after the last dose of study drug.
  • Eligibility for the Study Extension 1 at the Week 96 visit: 1) completed the Week 96 visit, 2) derived benefit from participation through Week 96 in the opinion of the investigator, 3) is a clinically-appropriate candidate for an additional 96 weeks of treatment with the Study Extension regimen.
  • Eligibility for the Study Extension 2 at the Week 192 visit: 1) completed the Week 192 visit, 2) derived benefit from participation through Week 192 in the opinion of the investigator, 3) is a clinically-appropriate candidate for 96 weeks of treatment with the Study Extension regimen.

Exclusion Criteria:

  • Uses or has had a recent history of using recreational or illicit drugs.
  • Has been treated for a viral infection other than HIV-1, such as hepatitis B, with an agent that is active against HIV-1.
  • Has documented or known resistance to study drugs including doravirine, darunavir, ritonavir, emtricitabine, tenofovir, abacavir and/or lamivudine.
  • Has participated in a study with an investigational compound/device within the prior month, or anticipates doing so during this study.
  • Has used systemic immunosuppressive therapy or immune modulators within the prior 30 days, or anticipates doing so during this study.
  • 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.
  • Is pregnant, breastfeeding or expecting to conceive at any time during the study.
  • Female who expects to donate eggs, or male who expects to donate sperm at any time during the study.
Contacts and Locations
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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): NCT02275780


Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT02275780     History of Changes
Other Study ID Numbers: 1439-018
2014-001127-69 ( EudraCT Number )
DRIVE-FORWARD ( Other Identifier: Merck Sharp & Dohme Corp. )
First Posted: October 27, 2014    Key Record Dates
Last Update Posted: May 14, 2018
Last Verified: May 2018

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