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Trial record 37 of 243 for:    "Viral Infectious Disease" | "Lopinavir"

Safety and Efficacy of a Switch to MK-1439A in Human Immunodeficiency Virus (HIV-1)-Infected Participants Virologically Suppressed on an Anti-retroviral Regimen in Combination With Two Nucleoside Reverse Transcriptase Inhibitors (MK-1439A-024) (DRIVE-SHIFT)

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ClinicalTrials.gov Identifier: NCT02397096
Recruitment Status : Active, not recruiting
First Posted : March 24, 2015
Results First Posted : April 3, 2019
Last Update Posted : April 3, 2019
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition HIV-1 Infection
Interventions Drug: MK-1439A
Drug: Baseline regimen of ritonavir- or cobicistat-boosted protease inhibitor
Drug: Baseline regimen of cobicistat-boosted elvitegravir
Drug: Baseline regimen of a non-nucleoside reverse transcriptase inhibitor
Drug: Baseline regimen of two nucleoside reverse transcriptase inhibitors
Enrollment 673
Recruitment Details Out of 852 participants screened, 673 were randomized to study treatment, and 670 were treated. There were 122 global study sites utilized.
Pre-assignment Details This report covers results for the 48-week base study plus follow-up (up to 50 weeks). Results for the ongoing open-label study extensions will be reported when the extensions are completed.
Arm/Group Title Immediate Switch Group (ISG) Delayed Switch Group (DSG)
Hide Arm/Group Description Participants receiving continuous antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir or a non nucleoside reverse transcriptase inhibitor (NNRTI) (specifically, efavirenz, nevirapine, or rilpivirine) in combination with 2 (nuceloside/nucleotide reverse transcriptase inhibitors) NRTIs for >=6 months with undetectable HIV-1 RNA will switch on Day 1 to MK-1439A single tablet by mouth once daily for 48 weeks in the Base Study and, optionally, for up to an additional 4 years in the Study Extensions. Participants receiving continuous antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir or a NNRTI (specifically, efavirenz, nevirapine, or rilpivirine) in combination with 2 NRTIs for >=6 months with undetectable HIV-1 RNA will continue on this therapy until Week 24, at which time they will switch to MK-1439A single tablet by mouth once daily for 24 weeks in the Base Study and, optionally, for up to an additional 4 years in the Study Extensions.
Period Title: Day 1 to Week 24
Started 447 223
Completed 427 209
Not Completed 20 14
Reason Not Completed
Adverse Event             7             1
Death             1             0
Lack of Efficacy             0             1
Lost to Follow-up             3             4
Physician Decision             2             3
Protocol Violation             1             4
Withdrawal by Subject             6             1
Period Title: Week 24 to Week 48
Started 427 209
Completed 407 202
Not Completed 20 7
Reason Not Completed
Adverse Event             6             2
Lack of Efficacy             5             1
Non-Compliance With Study Drug             0             1
Physician Decision             2             1
Withdrawal by Subject             5             2
Lost to Follow-up             2             0
Period Title: Study Extensions
Started 399 [1] 202 [1]
Completed 0 [2] 0 [2]
Not Completed 399 202
Reason Not Completed
Ongoing             399             202
[1]
The extension study is optional; not all eligible participants enrolled.
[2]
The extension study is ongoing.
Arm/Group Title Immediate Switch Group (ISG) Delayed Switch Group (DSG) Total
Hide Arm/Group Description Participants receiving continuous antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir or a non nucleoside reverse transcriptase inhibitor (NNRTI) (specifically, efavirenz, nevirapine, or rilpivirine) in combination with 2 (nuceloside/nucleotide reverse transcriptase inhibitors) NRTIs for >=6 months with undetectable HIV-1 RNA will switch on Day 1 to MK-1439A single tablet by mouth once daily for 48 weeks in the Base Study and, optionally, for up to an additional 4 years in the Study Extensions. Participants receiving continuous antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir or a NNRTI (specifically, efavirenz, nevirapine, or rilpivirine) in combination with 2 NRTIs for >=6 months with undetectable HIV-1 RNA will continue on this therapy until Week 24, at which time they will switch to MK-1439A single tablet by mouth once daily for 24 weeks in the Base Study and, optionally, for up to an additional 4 years in the Study Extensions. Total of all reporting groups
Overall Number of Baseline Participants 447 223 670
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 447 participants 223 participants 670 participants
43.1  (10.1) 43.7  (10.6) 43.3  (10.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 447 participants 223 participants 670 participants
Female
75
  16.8%
29
  13.0%
104
  15.5%
Male
372
  83.2%
194
  87.0%
566
  84.5%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 447 participants 223 participants 670 participants
Hispanic or Latino
99
  22.1%
45
  20.2%
144
  21.5%
Not Hispanic or Latino
341
  76.3%
175
  78.5%
516
  77.0%
Unknown or Not Reported
7
   1.6%
3
   1.3%
10
   1.5%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 447 participants 223 participants 670 participants
American Indian or Alaska Native
5
   1.1%
2
   0.9%
7
   1.0%
Asian
17
   3.8%
8
   3.6%
25
   3.7%
Native Hawaiian or Other Pacific Islander
1
   0.2%
0
   0.0%
1
   0.1%
Black or African American
56
  12.5%
34
  15.2%
90
  13.4%
White
344
  77.0%
168
  75.3%
512
  76.4%
More than one race
24
   5.4%
11
   4.9%
35
   5.2%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title Percentage of Participants Maintaining Human Immunodeficiency Virus–1 Ribonucleic Acid (HIV-1 RNA) <50 Copies/mL
Hide Description The percentage of participants in each arm achieving HIV-1 RNA levels <50 copies/mL was determined. Plasma HIV-1 RNA levels were quantified with the Abbott RealTime HIV-1 Assay. Data were handled according to the US Food and Drug Administration (FDA) "snapshot" approach and all missing data were considered treatment failures, regardless of the reason.
Time Frame Immediate Switch to MK-1439A arm: Week 48; Delayed Switch to MK-1439A arm: Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study drug.
Arm/Group Title Immediate Switch Group (ISG) Delayed Switch Group (DSG)
Hide Arm/Group Description:
Participants receiving continuous antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir or a non nucleoside reverse transcriptase inhibitor (NNRTI) (specifically, efavirenz, nevirapine, or rilpivirine) in combination with 2 (nuceloside/nucleotide reverse transcriptase inhibitors) NRTIs for >=6 months with undetectable HIV-1 RNA will switch on Day 1 to MK-1439A single tablet by mouth once daily for 48 weeks in the Base Study and, optionally, for up to an additional 4 years in the Study Extensions.
Participants receiving continuous antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir or a NNRTI (specifically, efavirenz, nevirapine, or rilpivirine) in combination with 2 NRTIs for >=6 months with undetectable HIV-1 RNA will continue on this therapy until Week 24, at which time they will switch to MK-1439A single tablet by mouth once daily for 24 weeks in the Base Study and, optionally, for up to an additional 4 years in the Study Extensions.
Overall Number of Participants Analyzed 447 223
Measure Type: Number
Unit of Measure: Percentage of Participants
90.8 94.6
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Immediate Switch Group (ISG), Delayed Switch Group (DSG)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate (DOR/3TC/TDF) once daily (QD) ISG is concluded to be non-inferior to baseline regimen DSG if the lower bound of the 95% CI for the difference in percent response is above -8 percentage points.
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -3.784
Confidence Interval (2-Sided) 95%
-7.877 to 0.310
Estimation Comments Stratum-adjusted Mantel-Haenszel method with the difference weighted by the harmonic mean of sample size per arm for each stratum.
Other Statistical Analysis Superiority of an immediate switch to DOR/3TC/TDF over continuation of the baseline regimen was defined by a lower bound of the two-sided 95% CI for the difference in response rates being greater than zero (contingent upon satisfying the multiplicity criteria).
2.Secondary Outcome
Title Mean Change From Baseline in Fasting Low-density Lipoprotein Cholesterol (LDL-C)
Hide Description To evaluate the effect on fasting LDL-C of an immediate switch to DOR/3TC/TDF on Study Day 1 compared with continuation of a ritonavir-boosted, PI-based regimen, as measured by mean change from baseline in each treatment group. The Last Observation Carry Forward (LOCF) approach was applied to missing data and data collected after a participant initiated lipid-modifying therapy.
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants in the ritonavir-boosted PI-based regimen who received at least 1 dose of study drug and had a measurement at baseline and had at least one post baseline time point assessed.
Arm/Group Title Immediate Switch (Ritonavir--boosted, PI-based) Group (ISG) Delayed Switch (Ritonavir-boosted, PI-based) Group (DSG)
Hide Arm/Group Description:
Participants receiving continuous antiretroviral therapy with a ritonavir-boosted, PI-based regimen for >=6 months with undetectable HIV-1 RNA will switch on Day 1 to MK-1439A single tablet by mouth once daily for 48 weeks in the Base Study and, optionally, for up to an additional 4 years in the Study Extensions.
Participants receiving continuous antiretroviral therapy with a ritonavir-boosted, PI-based regimen for >=6 months with undetectable HIV-1 RNA will continue on this therapy until Week 24, at which time they will switch to MK-1439A single tablet by mouth once daily for 24 weeks in the Base Study and, optionally, for up to an additional 4 years in the Study Extensions.
Overall Number of Participants Analyzed 256 125
Mean (Standard Deviation)
Unit of Measure: mg/dL
Baseline 108.82  (34.21) 109.00  (33.58)
Change from Baseline -16.54  (23.10) -1.94  (25.74)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Immediate Switch (Ritonavir--boosted, PI-based) Group (ISG), Delayed Switch (Ritonavir-boosted, PI-based) Group (DSG)
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -14.65
Confidence Interval (2-Sided) 95%
-18.92 to -10.38
Estimation Comments 95% CIs and 2-sided p-values were calculated from an ANCOVA model with terms for baseline lipid level, use of lipid-lowering therapy at Study Day 1 and treatment.
3.Secondary Outcome
Title Mean Change From Baseline in Fasting Non-high-density Lipoprotein Cholesterol (Non-HDL-C)
Hide Description Serum non-HDL-C was determined after an overnight fast. Change from Baseline was analyzed using ANCOVA models with terms for Baseline lipid level and treatment group. The Last Observation Carry Forward (LOCF) approach was applied for missing data or data collected after modifying lipid lowering therapy.
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received the ritonavir-boosted PI-based regimen at least 1 dose of study drug and had a measurement at baseline and had at least one post baseline time point assessed.
Arm/Group Title Immediate Switch (Ritonavir--boosted, PI-based) Group (ISG) Delayed Switch (Ritonavir-boosted, PI-based) Group (DSG)
Hide Arm/Group Description:
Participants receiving continuous antiretroviral therapy with a ritonavir-boosted, PI-based regimen for >=6 months with undetectable HIV-1 RNA will switch on Day 1 to MK-1439A single tablet by mouth once daily for 48 weeks in the Base Study and, optionally, for up to an additional 4 years in the Study Extensions.
Participants receiving continuous antiretroviral therapy with a ritonavir-boosted, PI-based regimen for >=6 months with undetectable HIV-1 RNA will continue on this therapy until Week 24, at which time they will switch to MK-1439A single tablet by mouth once daily for 24 weeks in the Base Study and, optionally, for up to an additional 4 years in the Study Extensions.
Overall Number of Participants Analyzed 266 133
Mean (Standard Deviation)
Unit of Measure: mg/dL
Baseline 139.14  (42.12) 137.99  (38.46)
Change from Baseline -24.74  (29.26) -1.31  (28.45)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Immediate Switch (Ritonavir--boosted, PI-based) Group (ISG), Delayed Switch (Ritonavir-boosted, PI-based) Group (DSG)
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -23.03
Confidence Interval (2-Sided) 95%
-28.00 to -18.05
Estimation Comments 95% CIs and 2-sided p-values were calculated from an ANCOVA model with terms for baseline lipid level, use of lipid-lowering therapy at Study Day 1 and treatment.
4.Secondary Outcome
Title Percentage of Participants Maintaining HIV-1 RNA <50 Copies/mL
Hide Description The percentage of participants in each arm achieving HIV-1 RNA levels <50 copies/mL was determined. Plasma HIV-1 RNA levels were quantified with the Abbott RealTime HIV-1 Assay. Data were handled according to the US Food and Drug Administration (FDA) "snapshot" approach and all missing data were considered treatment failures, regardless of the reason.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study drug.
Arm/Group Title Immediate Switch Group (ISG) Delayed Switch Group (DSG)
Hide Arm/Group Description:
Participants receiving continuous antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir or a non nucleoside reverse transcriptase inhibitor (NNRTI) (specifically, efavirenz, nevirapine, or rilpivirine) in combination with 2 (nuceloside/nucleotide reverse transcriptase inhibitors) NRTIs for >=6 months with undetectable HIV-1 RNA will switch on Day 1 to MK-1439A single tablet by mouth once daily for 48 weeks in the Base Study and, optionally, for up to an additional 4 years in the Study Extensions.
Participants receiving continuous antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir or a NNRTI (specifically, efavirenz, nevirapine, or rilpivirine) in combination with 2 NRTIs for >=6 months with undetectable HIV-1 RNA will continue on this therapy until Week 24, at which time they will switch to MK-1439A single tablet by mouth once daily for 24 weeks in the Base Study and, optionally, for up to an additional 4 years in the Study Extensions.
Overall Number of Participants Analyzed 447 223
Measure Type: Number
Unit of Measure: Percentage of Participants
93.7 94.6
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Immediate Switch Group (ISG), Delayed Switch Group (DSG)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments DOR/3TC/TDF QD ISG is concluded to be non-inferior to baseline regimen DSG if the lower bound of the 95% CI for the difference in percent response is above -8 percentage points.
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -0.877
Confidence Interval (2-Sided) 95%
-4.706 to 2.952
Estimation Comments Stratum-adjusted Mantel-Haenszel method with the difference weighted by the harmonic mean of sample size per arm for each stratum.
Other Statistical Analysis Superiority of an immediate switch to DOR/3TC/TDF over continuation of the baseline regimen was defined by a lower bound of the two-sided 95% CI for the difference in response rates being greater than zero (contingent upon satisfying the multiplicity criteria).
5.Secondary Outcome
Title Mean Change From Baseline in Cluster of Differentiation (CD4) Cell Counts
Hide Description The mean change from baseline in CD4 cell counts was assessed using the Observed Failure (OF) approach. With the OF approach, baseline values were carried forward for participants who discontinued due to lack of efficacy. Cell counts were measured and expressed as cells/mm^3, and percent change was then calculated. CD4 cell counts were quantified by a central laboratory using a commercially available assay.
Time Frame Immediate Switch to MK-1439A arm: Baseline and Week 48; Delayed Switch to MK-1439A arm: Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study drug and had a measurement at baseline and had at least one post baseline time point assessed.
Arm/Group Title Immediate Switch Group (ISG) Delayed Switch Group (DSG)
Hide Arm/Group Description:
Participants receiving continuous antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir or a non nucleoside reverse transcriptase inhibitor (NNRTI) (specifically, efavirenz, nevirapine, or rilpivirine) in combination with 2 (nuceloside/nucleotide reverse transcriptase inhibitors) NRTIs for >=6 months with undetectable HIV-1 RNA will switch on Day 1 to MK-1439A single tablet by mouth once daily for 48 weeks in the Base Study and, optionally, for up to an additional 4 years in the Study Extensions.
Participants receiving continuous antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir or a NNRTI (specifically, efavirenz, nevirapine, or rilpivirine) in combination with 2 NRTIs for >=6 months with undetectable HIV-1 RNA will continue on this therapy until Week 24, at which time they will switch to MK-1439A single tablet by mouth once daily for 24 weeks in the Base Study and, optionally, for up to an additional 4 years in the Study Extensions.
Overall Number of Participants Analyzed 402 209
Mean (Standard Deviation)
Unit of Measure: cells/mm^3
Baseline 660.5  (293.4) 655.6  (279.3)
Change from Baseline 13.9  (168.1) 18.0  (157.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Immediate Switch Group (ISG), Delayed Switch Group (DSG)
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -4.0
Confidence Interval (2-Sided) 95%
-31.6 to 23.5
Estimation Comments 95% CIs were calculated based on t-distribution.
6.Secondary Outcome
Title Mean Change From Baseline in Cluster of Differentiation (CD4) Cell Counts
Hide Description The mean change from baseline in CD4 cell counts at Week 48 was assessed using the Observed Failure (OF) approach. With the OF approach, baseline values were carried forward for participants who discontinued due to lack of efficacy. Cell counts were measured and expressed as cells/mm^3, and percent change was then calculated. CD4 cell counts were quantified by a central laboratory using a commercially available assay.
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study drug and had a measurement at baseline and had at least one post baseline time point assessed.
Arm/Group Title Immediate Switch Group (ISG) Delayed Switch Group (DSG)
Hide Arm/Group Description:
Participants receiving continuous antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir or a non nucleoside reverse transcriptase inhibitor (NNRTI) (specifically, efavirenz, nevirapine, or rilpivirine) in combination with 2 (nuceloside/nucleotide reverse transcriptase inhibitors) NRTIs for >=6 months with undetectable HIV-1 RNA will switch on Day 1 to MK-1439A single tablet by mouth once daily for 48 weeks in the Base Study and, optionally, for up to an additional 4 years in the Study Extensions.
Participants receiving continuous antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir or a NNRTI (specifically, efavirenz, nevirapine, or rilpivirine) in combination with 2 NRTIs for >=6 months with undetectable HIV-1 RNA will continue on this therapy until Week 24, at which time they will switch to MK-1439A single tablet by mouth once daily for 24 weeks in the Base Study and, optionally, for up to an additional 4 years in the Study Extensions.
Overall Number of Participants Analyzed 412 209
Geometric Mean (Standard Deviation)
Unit of Measure: cells/mm^3
Baseline 664.5  (300.7) 655.6  (279.3)
Change from Baseline 5.1  (174.9) 18.0  (157.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Immediate Switch Group (ISG), Delayed Switch Group (DSG)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -12.8
Confidence Interval (2-Sided) 95%
-41.1 to 15.4
Estimation Comments 95% Confidence Intervals were based on t-distribution.
7.Secondary Outcome
Title Percentage of Participants Maintaining HIV-1 RNA <40 Copies/mL
Hide Description The percentage of participants in each arm achieving HIV-1 RNA levels <40 copies/mL was determined. Plasma HIV-1 RNA levels were quantified with the Abbott RealTime HIV-1 Assay. Data were handled according to the US Food and Drug Administration (FDA) "snapshot" approach and all missing data were considered treatment failures, regardless of the reason.
Time Frame Immediate Switch to MK-1439A arm: Week 48; Delayed Switch to MK-1439A arm: Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study drug.
Arm/Group Title Immediate Switch Group (ISG) Delayed Switch Group (DSG)
Hide Arm/Group Description:
Participants receiving continuous antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir or a non nucleoside reverse transcriptase inhibitor (NNRTI) (specifically, efavirenz, nevirapine, or rilpivirine) in combination with 2 (nuceloside/nucleotide reverse transcriptase inhibitors) NRTIs for >=6 months with undetectable HIV-1 RNA will switch on Day 1 to MK-1439A single tablet by mouth once daily for 48 weeks in the Base Study and, optionally, for up to an additional 4 years in the Study Extensions.
Participants receiving continuous antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir or a NNRTI (specifically, efavirenz, nevirapine, or rilpivirine) in combination with 2 NRTIs for >=6 months with undetectable HIV-1 RNA will continue on this therapy until Week 24, at which time they will switch to MK-1439A single tablet by mouth once daily for 24 weeks in the Base Study and, optionally, for up to an additional 4 years in the Study Extensions.
Overall Number of Participants Analyzed 447 223
Measure Type: Number
Unit of Measure: Percentage of Participants
89.7 93.3
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Immediate Switch Group (ISG), Delayed Switch Group (DSG)
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -3.556
Confidence Interval (2-Sided) 95%
-7.977 to 0.864
Estimation Comments Stratum-adjusted Mantel-Haenszel method with the difference weighted by the harmonic mean of sample size per arm for each stratum.
8.Secondary Outcome
Title Percentage of Participants Maintaining HIV-1 RNA <40 Copies/mL
Hide Description To evaluate the immunological effect of an immediate switch to MK -1439A on Study Day 1 compared with continuation of a ritonavir boosted, PI-based regimen, as measured by the proportion of subjects maintaining HIV-1 RNA below the limit of quantification (BLoQ) by the Abbott RealTime HIV-1 Assay (<40 copies/mL) in both treatment groups.
Time Frame Immediate Switch to MK-1439A arm: Week 24; Delayed Switch to MK-1439A arm: Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study drug.
Arm/Group Title Immediate Switch Group (ISG) Delayed Switch Group (DSG)
Hide Arm/Group Description:
Participants receiving continuous antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir or a non nucleoside reverse transcriptase inhibitor (NNRTI) (specifically, efavirenz, nevirapine, or rilpivirine) in combination with 2 (nuceloside/nucleotide reverse transcriptase inhibitors) NRTIs for >=6 months with undetectable HIV-1 RNA will switch on Day 1 to MK-1439A single tablet by mouth once daily for 48 weeks in the Base Study and, optionally, for up to an additional 4 years in the Study Extensions.
Participants receiving continuous antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir or a NNRTI (specifically, efavirenz, nevirapine, or rilpivirine) in combination with 2 NRTIs for >=6 months with undetectable HIV-1 RNA will continue on this therapy until Week 24, at which time they will switch to MK-1439A single tablet by mouth once daily for 24 weeks in the Base Study and, optionally, for up to an additional 4 years in the Study Extensions.
Overall Number of Participants Analyzed 447 223
Measure Type: Number
Unit of Measure: Percentage of Participants
92.8 93.3
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Immediate Switch Group (ISG), Delayed Switch Group (DSG)
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -0.427
Confidence Interval (2-Sided) 95%
-4.591 to 3.738
Estimation Comments Stratum-adjusted Mantel-Haenszel method with the difference weighted by the harmonic mean of sample size per arm for each stratum.
9.Secondary Outcome
Title Percentage of Participants With HIV-1 RNA >=50 Copies/mL
Hide Description The percentage of participants in each arm achieving HIV-1 RNA levels >=50 copies/mL was determined. Plasma HIV-1 RNA levels were quantified with the Abbott RealTime HIV-1 Assay. Data were handled according to the US Food and Drug Administration (FDA) "snapshot" approach.
Time Frame Immediate Switch to MK-1439A arm: Week 48; Delayed Switch to MK-1439A arm: Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study drug.
Arm/Group Title Immediate Switch Group (ISG) Delayed Switch Group (DSG)
Hide Arm/Group Description:
Participants receiving continuous antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir or a non nucleoside reverse transcriptase inhibitor (NNRTI) (specifically, efavirenz, nevirapine, or rilpivirine) in combination with 2 (nuceloside/nucleotide reverse transcriptase inhibitors) NRTIs for >=6 months with undetectable HIV-1 RNA will switch on Day 1 to MK-1439A single tablet by mouth once daily for 48 weeks in the Base Study and, optionally, for up to an additional 4 years in the Study Extensions.
Participants receiving continuous antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir or a NNRTI (specifically, efavirenz, nevirapine, or rilpivirine) in combination with 2 NRTIs for >=6 months with undetectable HIV-1 RNA will continue on this therapy until Week 24, at which time they will switch to MK-1439A single tablet by mouth once daily for 24 weeks in the Base Study and, optionally, for up to an additional 4 years in the Study Extensions.
Overall Number of Participants Analyzed 447 223
Measure Type: Number
Unit of Measure: Percentage of Participants
1.6 1.8
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Immediate Switch Group (ISG), Delayed Switch Group (DSG)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments DOR/3TC/TDF QD ISG is concluded to be non-inferior to baseline regimen DSG if the lower bound of the 95% CI for the difference in percent response is above -4 percentage points.
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -0.232
Confidence Interval (2-Sided) 95%
-2.529 to 2.064
Estimation Comments Stratum-adjusted Mantel-Haenszel method with the difference weighted by the harmonic mean of sample size per arm for each stratum.
10.Secondary Outcome
Title Percentage of Participants Experiencing ≥1 Adverse Event (AE)
Hide Description An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Time Frame Up to week 24
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study drug.
Arm/Group Title Immediate Switch Group (ISG) Delayed Switch Group (DSG)
Hide Arm/Group Description:
Participants receiving continuous antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir or a non nucleoside reverse transcriptase inhibitor (NNRTI) (specifically, efavirenz, nevirapine, or rilpivirine) in combination with 2 (nuceloside/nucleotide reverse transcriptase inhibitors) NRTIs for >=6 months with undetectable HIV-1 RNA will switch on Day 1 to MK-1439A single tablet by mouth once daily for 48 weeks in the Base Study and, optionally, for up to an additional 4 years in the Study Extensions.
Participants receiving continuous antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir or a NNRTI (specifically, efavirenz, nevirapine, or rilpivirine) in combination with 2 NRTIs for >=6 months with undetectable HIV-1 RNA will continue on this therapy until Week 24, at which time they will switch to MK-1439A single tablet by mouth once daily for 24 weeks in the Base Study and, optionally, for up to an additional 4 years in the Study Extensions.
Overall Number of Participants Analyzed 447 223
Measure Type: Number
Unit of Measure: Percentage of Participants
68.9 52.5
11.Secondary Outcome
Title Percentage of Participants Experiencing ≥1 Serious Adverse Event (SAE)
Hide Description A serious adverse event is an AE that results in death, is life threatening, results in persistent or significant disability or incapacity, results in or prolongs a hospitalization, is a congenital anomaly or birth defect, is a cancer, is associated with an overdose, or is another important medical event. The percentage of participants with any SAE was assessed.
Time Frame Up to 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study drug.
Arm/Group Title Immediate Switch Group (ISG) Delayed Switch Group (DSG)
Hide Arm/Group Description:
Participants receiving continuous antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir or a non nucleoside reverse transcriptase inhibitor (NNRTI) (specifically, efavirenz, nevirapine, or rilpivirine) in combination with 2 (nuceloside/nucleotide reverse transcriptase inhibitors) NRTIs for >=6 months with undetectable HIV-1 RNA will switch on Day 1 to MK-1439A single tablet by mouth once daily for 48 weeks in the Base Study and, optionally, for up to an additional 4 years in the Study Extensions.
Participants receiving continuous antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir or a NNRTI (specifically, efavirenz, nevirapine, or rilpivirine) in combination with 2 NRTIs for >=6 months with undetectable HIV-1 RNA will continue on this therapy until Week 24, at which time they will switch to MK-1439A single tablet by mouth once daily for 24 weeks in the Base Study and, optionally, for up to an additional 4 years in the Study Extensions.
Overall Number of Participants Analyzed 447 223
Measure Type: Number
Unit of Measure: Percentage of Participants
2.9 3.6
12.Secondary Outcome
Title Percentage of Participants Discontinuing From Study Medication Due to an AE(s)
Hide Description An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Time Frame Up to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study drug.
Arm/Group Title Immediate Switch Group (ISG) Delayed Switch Group (DSG)
Hide Arm/Group Description:
Participants receiving continuous antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir or a non nucleoside reverse transcriptase inhibitor (NNRTI) (specifically, efavirenz, nevirapine, or rilpivirine) in combination with 2 (nuceloside/nucleotide reverse transcriptase inhibitors) NRTIs for >=6 months with undetectable HIV-1 RNA will switch on Day 1 to MK-1439A single tablet by mouth once daily for 48 weeks in the Base Study and, optionally, for up to an additional 4 years in the Study Extensions.
Participants receiving continuous antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir or a NNRTI (specifically, efavirenz, nevirapine, or rilpivirine) in combination with 2 NRTIs for >=6 months with undetectable HIV-1 RNA will continue on this therapy until Week 24, at which time they will switch to MK-1439A single tablet by mouth once daily for 24 weeks in the Base Study and, optionally, for up to an additional 4 years in the Study Extensions.
Overall Number of Participants Analyzed 447 223
Measure Type: Number
Unit of Measure: Percentage of Participants
2.5 0.4
Time Frame 48 week base study plus follow-up (Up to 50 weeks)
Adverse Event Reporting Description The at-risk population is all participants who received at least 1 dose of study drug during the base study.
 
Arm/Group Title Baseline Regimen DSG (Study Weeks 0-24) DOR/3TC/TDF QD DSG (Study Weeks 24-48) DOR/3TC/TDF QD ISG (Study Weeks 0-48) ALL DOR: DOR/3TC/TDF ISG (Weeks 0-48)+DSG (Weeks 24-48)
Hide Arm/Group Description Participants in the delayed switch group (DSG) that received the baseline regimen of continuous antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir (EVG) or a NNRTI (specifically, efavirenz, nevirapine, or rilpivirine) in combination with 2 NRTIs for 24 weeks. Participants in the delayed switch group (DSG) that received continuous antiretroviral therapy with an oral tablet of doravirine (DOR)/lamivudine (3TC) /tenofovir disoproxil fumarate (TDF) once daily from study week 24 to week 48. Participants in the immediate switch group (ISG) that received continuous antiretroviral therapy with an oral tablet of doravirine (DOR)/lamivudine (3TC) /tenofovir disoproxil fumarate (TDF) once daily for 48 weeks.

Participants in the immediate switch group (ISG) that received continuous antiretroviral therapy with an oral tablet of doravirine (DOR)/lamivudine (3TC) /tenofovir disoproxil fumarate (TDF) once daily for 48 weeks.

AND Participants in the delayed switch group (DSG) that received continuous antiretroviral therapy with an oral tablet of doravirine (DOR)/lamivudine (3TC) /tenofovir disoproxil fumarate (TDF) once daily from study week 24 to week 48.

All-Cause Mortality
Baseline Regimen DSG (Study Weeks 0-24) DOR/3TC/TDF QD DSG (Study Weeks 24-48) DOR/3TC/TDF QD ISG (Study Weeks 0-48) ALL DOR: DOR/3TC/TDF ISG (Weeks 0-48)+DSG (Weeks 24-48)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/223 (0.00%)      0/209 (0.00%)      1/447 (0.22%)      1/656 (0.15%)    
Show Serious Adverse Events Hide Serious Adverse Events
Baseline Regimen DSG (Study Weeks 0-24) DOR/3TC/TDF QD DSG (Study Weeks 24-48) DOR/3TC/TDF QD ISG (Study Weeks 0-48) ALL DOR: DOR/3TC/TDF ISG (Weeks 0-48)+DSG (Weeks 24-48)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   8/223 (3.59%)      4/209 (1.91%)      23/447 (5.15%)      27/656 (4.12%)    
Cardiac disorders         
Angina pectoris  1  0/223 (0.00%)  0 0/209 (0.00%)  0 1/447 (0.22%)  1 1/656 (0.15%)  1
Atrial fibrillation  1  0/223 (0.00%)  0 0/209 (0.00%)  0 1/447 (0.22%)  1 1/656 (0.15%)  1
Gastrointestinal disorders         
Gastrooesophageal reflux disease  1  0/223 (0.00%)  0 0/209 (0.00%)  0 1/447 (0.22%)  1 1/656 (0.15%)  1
General disorders         
Death  1  0/223 (0.00%)  0 0/209 (0.00%)  0 1/447 (0.22%)  1 1/656 (0.15%)  1
Infections and infestations         
Appendicitis  1  0/223 (0.00%)  0 1/209 (0.48%)  1 1/447 (0.22%)  1 2/656 (0.30%)  2
Endocarditis  1  0/223 (0.00%)  0 0/209 (0.00%)  0 1/447 (0.22%)  1 1/656 (0.15%)  1
Pneumonia  1  3/223 (1.35%)  3 0/209 (0.00%)  0 1/447 (0.22%)  1 1/656 (0.15%)  1
Respiratory syncytial virus infection  1  0/223 (0.00%)  0 0/209 (0.00%)  0 1/447 (0.22%)  1 1/656 (0.15%)  1
Shigella infection  1  0/223 (0.00%)  0 0/209 (0.00%)  0 1/447 (0.22%)  1 1/656 (0.15%)  1
Tuberculous pleurisy  1  1/223 (0.45%)  1 0/209 (0.00%)  0 0/447 (0.00%)  0 0/656 (0.00%)  0
Injury, poisoning and procedural complications         
Foot fracture  1  0/223 (0.00%)  0 0/209 (0.00%)  0 1/447 (0.22%)  1 1/656 (0.15%)  1
Hand fracture  1  0/223 (0.00%)  0 1/209 (0.48%)  1 0/447 (0.00%)  0 1/656 (0.15%)  1
Hip fracture  1  0/223 (0.00%)  0 0/209 (0.00%)  0 1/447 (0.22%)  1 1/656 (0.15%)  1
Investigations         
Alanine aminotransferase increased  1  0/223 (0.00%)  0 0/209 (0.00%)  0 2/447 (0.45%)  2 2/656 (0.30%)  2
Amylase increased  1  0/223 (0.00%)  0 0/209 (0.00%)  0 1/447 (0.22%)  1 1/656 (0.15%)  1
Aspartate aminotransferase increased  1  0/223 (0.00%)  0 0/209 (0.00%)  0 2/447 (0.45%)  2 2/656 (0.30%)  2
Blood creatine phosphokinase increased  1  0/223 (0.00%)  0 0/209 (0.00%)  0 2/447 (0.45%)  2 2/656 (0.30%)  2
CD4 lymphocytes decreased  1  0/223 (0.00%)  0 0/209 (0.00%)  0 1/447 (0.22%)  1 1/656 (0.15%)  1
Lipase increased  1  0/223 (0.00%)  0 0/209 (0.00%)  0 2/447 (0.45%)  2 2/656 (0.30%)  2
Musculoskeletal and connective tissue disorders         
Intervertebral disc protrusion  1  0/223 (0.00%)  0 0/209 (0.00%)  0 1/447 (0.22%)  1 1/656 (0.15%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Squamous cell carcinoma  1  1/223 (0.45%)  1 0/209 (0.00%)  0 0/447 (0.00%)  0 0/656 (0.00%)  0
Nervous system disorders         
Amyotrophic lateral sclerosis  1  0/223 (0.00%)  0 0/209 (0.00%)  0 1/447 (0.22%)  1 1/656 (0.15%)  1
Headache  1  0/223 (0.00%)  0 0/209 (0.00%)  0 1/447 (0.22%)  1 1/656 (0.15%)  1
Lacunar infarction  1  0/223 (0.00%)  0 0/209 (0.00%)  0 1/447 (0.22%)  1 1/656 (0.15%)  1
Psychiatric disorders         
Depression  1  1/223 (0.45%)  1 0/209 (0.00%)  0 1/447 (0.22%)  1 1/656 (0.15%)  1
Suicidal ideation  1  1/223 (0.45%)  1 0/209 (0.00%)  0 0/447 (0.00%)  0 0/656 (0.00%)  0
Suicide attempt  1  0/223 (0.00%)  0 0/209 (0.00%)  0 1/447 (0.22%)  1 1/656 (0.15%)  1
Renal and urinary disorders         
Nephrolithiasis  1  1/223 (0.45%)  1 0/209 (0.00%)  0 0/447 (0.00%)  0 0/656 (0.00%)  0
Renal cyst  1  1/223 (0.45%)  1 0/209 (0.00%)  0 0/447 (0.00%)  0 0/656 (0.00%)  0
Renal failure  1  0/223 (0.00%)  0 1/209 (0.48%)  1 1/447 (0.22%)  1 2/656 (0.30%)  2
Respiratory, thoracic and mediastinal disorders         
Asthma  1  0/223 (0.00%)  0 0/209 (0.00%)  0 1/447 (0.22%)  1 1/656 (0.15%)  1
Chronic obstructive pulmonary disease  1  1/223 (0.45%)  1 0/209 (0.00%)  0 0/447 (0.00%)  0 0/656 (0.00%)  0
Cough  1  1/223 (0.45%)  1 0/209 (0.00%)  0 0/447 (0.00%)  0 0/656 (0.00%)  0
Sleep apnoea syndrome  1  0/223 (0.00%)  0 1/209 (0.48%)  1 0/447 (0.00%)  0 1/656 (0.15%)  1
Skin and subcutaneous tissue disorders         
Rash maculo-papular  1  0/223 (0.00%)  0 0/209 (0.00%)  0 1/447 (0.22%)  1 1/656 (0.15%)  1
1
Term from vocabulary, MedDRA 20.1
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Baseline Regimen DSG (Study Weeks 0-24) DOR/3TC/TDF QD DSG (Study Weeks 24-48) DOR/3TC/TDF QD ISG (Study Weeks 0-48) ALL DOR: DOR/3TC/TDF ISG (Weeks 0-48)+DSG (Weeks 24-48)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   25/223 (11.21%)      30/209 (14.35%)      126/447 (28.19%)      156/656 (23.78%)    
Gastrointestinal disorders         
Diarrhoea  1  5/223 (2.24%)  5 9/209 (4.31%)  10 31/447 (6.94%)  33 40/656 (6.10%)  43
Infections and infestations         
Nasopharyngitis  1  12/223 (5.38%)  14 9/209 (4.31%)  10 45/447 (10.07%)  55 54/656 (8.23%)  65
Musculoskeletal and connective tissue disorders         
Back pain  1  4/223 (1.79%)  4 1/209 (0.48%)  1 23/447 (5.15%)  24 24/656 (3.66%)  25
Nervous system disorders         
Headache  1  5/223 (2.24%)  5 14/209 (6.70%)  14 38/447 (8.50%)  43 52/656 (7.93%)  57
1
Term from vocabulary, MedDRA 20.1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The SPONSOR must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the SPONSOR as confidential must be deleted prior to submission. SPONSOR review can be expedited to meet publication timelines.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Senior Vice President, Global Clinical Development
Organization: Merck Sharp & Dohme Corp.
Phone: 1-800-672-6372
EMail: ClinicalTrialsDisclosure@merck.com
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Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT02397096     History of Changes
Other Study ID Numbers: 1439A-024
2014-005550-18 ( EudraCT Number )
MK-1439A-024 ( Other Identifier: Merck )
First Submitted: March 18, 2015
First Posted: March 24, 2015
Results First Submitted: February 4, 2019
Results First Posted: April 3, 2019
Last Update Posted: April 3, 2019