DRIVE-AHEAD: Comparison of Doravirine, Tenofovir, Lamivudine (MK-1439A) and ATRIPLA™ in Treatment-Naive Human Immunodeficiency Virus Type 1 (HIV-1)-Infected Participants (MK-1439A-021)
Sponsor
Merck Sharp & Dohme LLC (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT02403674
Collaborator
(none)
734
2
101.4
Study Details
Study Description
Brief Summary
The purpose of this study is to compare the antiretroviral activity of doravirine, tenofovir, lamivudine (MK-1439A), a single-tablet, once-daily (q.d.) fixed-dose combination (FDC) containing doravirine (MK-1439) 100 mg + lamivudine 300 mg + tenofovir disoproxil fumarate 300 mg, with ATRIPLA™, a single-tablet FDC containing efavirenz 600 mg + emtricitabine 200 mg
- tenofovir disoproxil fumarate 300 mg, in treatment-naive participants infected with human immunodeficiency virus (HIV). The primary hypothesis is that doravirine, tenofovir, lamivudine q.d. is non-inferior to ATRIPLA™ q.d. as assessed by the proportion of participants with HIV-1 ribonucleic acid (RNA) <50 copies/mL (by the Abbott RealTime HIV-1 Assay) at Week 48. This study has a total duration of 192 weeks, including a 96-week double-blind period and a 96-week open-label period. The present results are based on the first 48 weeks of this ongoing study.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
Participants in Australia, Colombia, Guatemala, Honduras, Israel, New Zealand, Peru, Russia, South Africa, and Thailand who are deriving benefit from doravirine, tenofovir, lamivudine are also eligible to continue receiving study drug during additional open-label extensions which will last for 2 years or until drug is available locally, whichever comes first.
Study Design
Study Type:
Interventional
Actual Enrollment
:
734 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Phase III Multicenter, Double-Blind, Randomized, Active Comparator-Controlled Clinical Trial to Evaluate the Safety and Efficacy of MK-1439A Once-Daily Versus ATRIPLA™ Once-Daily in Treatment-Naïve HIV-1 Infected Subjects
Actual Study Start Date
:
Jun 5, 2015
Actual Primary Completion Date
:
Mar 20, 2017
Anticipated Study Completion Date
:
Nov 15, 2023
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Doravirine, Tenofovir, Lamivudine Treatment-naive HIV-infected participants will receive doravirine, tenofovir, lamivudine, a single-tablet FDC containing doravirine 100 mg + lamivudine 300 mg + tenofovir disoproxil fumarate 300 mg, q.d. by mouth for 96 weeks. Participants will also take 1 placebo tablet matched to ATRIPLA™ q.d. by mouth for 96 weeks in order to maintain blinding. |
Drug: Doravirine, Tenofovir, Lamivudine
One doravirine, tenofovir, lamivudine tablet taken q.d. by mouth.
Other Names:
Drug: Placebo
Placebo tablets matched to ATRIPLA® or Doravirine, Tenofovir, Lamivudine.
|
| Active Comparator: ATRIPLA™ Treatment-naive HIV-infected participants will receive ATRIPLA™, a single-tablet FDC containing efavirenz 600 mg + emtricitabine 200 mg + tenofovir disoproxil fumarate 300 mg (equivalent to 245 mg tenofovir disoproxil), q.d. by mouth for 96 weeks. Participants will also take 1 placebo tablet matched to doravirine, tenofovir, lamivudine q.d. by mouth for 96 weeks in order to maintain blinding. |
Drug: ATRIPLA™
One ATRIPLA™ tablet taken q.d. by mouth
Drug: Placebo
Placebo tablets matched to ATRIPLA® or Doravirine, Tenofovir, Lamivudine.
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants With HIV-1 Ribonucleic Acid (RNA) <50 Copies/mL at Week 48 [Week 48]
The percentage of participants in each arm with HIV-1 RNA levels <50 copies/mL at Week 48 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 in which all missing data are considered treatment failures, regardless of the reason.
- Percentage of Participants With Tier-1 Neuropsychiatric Adverse Events (AEs) [Up to Week 48]
The percentage of participants in each arm experiencing ≥1 pre-specified Tier-1 neuropsychiatric AEs was determined. The list of Tier-1 neuropsychiatric AE categories included "dizziness", "sleep disorders and disturbances", and "altered sensorium" (including disturbance in attention).
Secondary Outcome Measures
- Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 96 [Week 96]
The percentage of participants in each arm with HIV-1 RNA levels <50 copies/mL at Week 96 will be determined. Plasma HIV-1 RNA levels will be quantified with the Abbott RealTime HIV-1 Assay. The US Food and Drug Administration (FDA) "snapshot" approach (i.e., all missing data handled as treatment failures, regardless of the reason) will be used for efficacy analyses.
- Percentage of Participants With HIV-1 RNA <40 Copies/mL at Week 48 [Week 48]
The percentage of participants in each arm with HIV-1 RNA levels <40 copies/mL (including target detected and target not detected) at Week 48 was determined. Plasma HIV 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 in which all missing data are considered treatment failures, regardless of the reason.
- Percentage of Participants With HIV-1 RNA <40 Copies/mL at Week 96 [Week 96]
The percentage of participants in each arm with HIV-1 RNA levels <40 copies/mL (including target detected and target not detected) at Week 96 will be determined. Plasma HIV-1 RNA levels will be quantified with the Abbott RealTime HIV-1 Assay. The US Food and Drug Administration (FDA) "snapshot" approach (i.e., all missing data handled as treatment failures, regardless of the reason) will be used for efficacy analyses.
- Change From Baseline in CD4 Cell Counts at Week 48 [Baseline (Day 1) and Week 48]
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 prior to Week 48 due to lack of efficacy. Cell counts at Baseline and Week 48 were measured and expressed as cells/mm^3, and percent change was then calculated as [(Baseline counts - Week 48 counts)*100]. CD4 cell counts were quantified by a central laboratory using a commercially available assay.
- Change From Baseline in CD4 Cell Counts at Week 96 [Baseline (Day 1) and Week 96]
The mean change from baseline in CD4 cell counts at Week 96 will be assessed using the Observed Failure (OF) approach. With the OF approach, baseline values will be carried forward for participants who discontinued prior to Week 96 due to lack of efficacy. Cell counts at Baseline and Week 96 will be measured and expressed as cells/mm^3, and percent change will then be calculated as [(Baseline counts - Week 96 counts)*100]. CD4 cell counts will be quantified by a central laboratory using a commercially available assay.
- Percentage of Participants Experiencing ≥1 AE [Up to Week 48]
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.
- Percentage of Participants Discontinuing From Study Medication Due to an AE(s) [Up to Week 48]
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.
- Percentage of Participants With Tier-2 Neuropsychiatric AEs [Up to Week 48]
The percentage of participants in each arm experiencing ≥1 pre-specified Tier-2 neuropsychiatric AEs was determined. The list of Tier-2 neuropsychiatric AE categories included "depression and suicide/self-injury" and "psychosis and psychotic disorders".
- Change From Baseline in Fasting LDL-C at Week 48 [Baseline (Day 1) and Week 48]
The mean percent change from baseline in fasting (fast duration of ≥8 hours) LDL-C levels at Week 48 was determined for each arm. The Last Observation Carry Forward (LOCF) approach was applied to missing data and data collected after a participant initiated lipid-modifying therapy.
- Change From Baseline in Fasting Non-HDL-C at Week 48 [Baseline (Day 1) and Week 48]
The mean percent change from baseline in fasting (fast duration of ≥8 hours) non-HDL-C levels at Week 48 was determined for each arm. The LOCF approach was applied to missing data and data collected after a participant initiated lipid-modifying therapy.
- Change From Baseline in Fasting Cholesterol at Week 48 [Baseline (Day 1) and Week 48]
The mean percent change from baseline in fasting (fast duration of ≥8 hours) cholesterol levels at Week 48 was determined for each arm. The LOCF approach was applied to missing data and data collected after a participant initiated lipid-modifying therapy.
- Change From Baseline in Fasting Triglycerides at Week 48 [Baseline (Day 1) and Week 48]
The mean percent change from baseline in fasting (fast duration of ≥8 hours) triglycerides levels at Week 48 was determined for each arm. The LOCF approach was applied to missing data and data collected after a participant initiated lipid-modifying therapy.
- Change From Baseline in Fasting HDL-C at Week 48 [Baseline (Day 1) and Week 48]
The mean percent change from baseline in fasting (fast duration of ≥8 hours) HDL-C levels at Week 48 was determined for each arm. The LOCF approach was applied to missing data and data collected after a participant initiated lipid-modifying therapy.
- Percentage of Participants With HIV-1 RNA Below the Limit of Quantification (BLoQ) at Week 48 [Week 48]
The percentage of participants in each arm with HIV-1 RNA levels BLoQ of 40 copies/mL and target not detected at Week 48 was determined. Plasma HIV RNA levels were quantified with the Abbott RealTime HIV-1 Assay. Data were handled as observed.
- Percentage of Participants With HIV-1 RNA BLoQ at Week 96 [Week 48]
The percentage of participants in each arm with HIV-1 RNA levels BLoQ of 40 copies/mL and target not detected at Week 96 will be determined. Plasma HIV RNA levels will be quantified with the Abbott RealTime HIV-1 Assay. Data will be handled as observed.
- Plasma Concentration of Doravirine at Week 48 [0 hours post-dose and 2 hours post-dose on Week 48]
Plasma samples were collected for analysis of doravirine concentration at Week 48. A total of 2 samples were collected: 1 prior to dosing and 1 collected between 0.5 and 2 hours post-dose.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Is HIV-1 positive as determined by a positive result on an enzyme-immunoassay, has screening plasma HIV-1 RNA (determined by the central laboratory) ≥1000 copies/mL within 45 days prior to the treatment phase of this study, and has HIV treatment indicated based on physician assessment
-
Has never received antiretroviral therapy (ART)
-
Is highly unlikely to either become pregnant or impregnate a partner
Exclusion Criteria:
-
Has a history or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that might confound results of the study
-
Is a user of recreational or illicit drugs or has a recent history of alcohol/drug abuse
-
Has been treated for a viral infection other than HIV-1 (e.g., hepatitis B) with an agent that is active against HIV-1
-
Has participated in a study with an investigational drug/device within 30 days prior to Screening
-
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
-
Has a current (active) diagnosis of acute hepatitis due to any cause (note: participants with chronic hepatitis B and C may enter the study as long as they fulfill all entry criteria, have stable liver function tests, and have no significant impairment of hepatic synthetic function)
-
Is a female who is pregnant, breastfeeding, or expecting to conceive
-
Is a female and is expecting to donate eggs or is male and is expecting to donate sperm (investigators will provide appropriate guidance regarding egg and/or sperm donation after completion of the study treatment regimen)
-
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
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Merck Sharp & Dohme LLC
Investigators
- Study Director: Medical Director, Merck Sharp & Dohme LLC
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Merck Sharp & Dohme LLC
ClinicalTrials.gov Identifier:
NCT02403674
Other Study ID Numbers:
- 1439A-021
- MK-1439A-021
- 2014-003382-17
First Posted:
Mar 31, 2015
Last Update Posted:
Aug 22, 2022
Last Verified:
Aug 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Treatment-naïve participants with human immunodeficiency virus type 1 (HIV-1) infection have been recruited at 126 study sites worldwide. The present results are based on the first 48 weeks of this ongoing 96-week study. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | MK-1439A | ATRIPLA™ |
|---|---|---|
| Arm/Group Description | Treatment-naive participants with HIV-1 infection took MK-1439A, a single-tablet fixed dose combination (FDC) containing doravirine 100 mg + lamivudine 300 mg + tenofovir disoproxil fumarate 300 mg, once daily (q.d.) by mouth for 48 weeks (and will take MK-1439A for an additional 48 weeks for a total of 96 weeks). Participants also took 1 placebo tablet matched to ATRIPLA™ q.d. by mouth for 48 weeks (and will take placebo for an additional 48 weeks for a total of 96 weeks) in order to maintain blinding. | Treatment-naive participants with HIV-1 infection took ATRIPLA™, a single-tablet FDC containing efavirenz 600 mg + emtricitabine 200 mg + tenofovir disoproxil fumarate 300 mg (equivalent to 245 mg tenofovir disoproxil), q.d. by mouth for 48 weeks (and will take ATRIPLA for an additional 48 weeks for a total of 96 weeks). Participants also took 1 placebo tablet matched to MK-1439A q.d. by mouth for 48 weeks (and will take placebo for an additional 48 weeks for a total of 96 weeks) in order to maintain blinding. |
| Period Title: Overall Study | ||
| STARTED | 368 | 366 |
| Treated | 364 | 364 |
| COMPLETED | 313 | 303 |
| NOT COMPLETED | 55 | 63 |
Baseline Characteristics
| Arm/Group Title | MK-1439A | ATRIPLA™ | Total |
|---|---|---|---|
| Arm/Group Description | Treatment-naive participants with HIV-1 infection took MK-1439A, a single-tablet FDC containing doravirine 100 mg + lamivudine 300 mg + tenofovir disoproxil fumarate 300 mg, q.d. by mouth for 48 weeks (and will take MK-1439A for an additional 48 weeks for a total of 96 weeks). Participants also took 1 placebo tablet matched to ATRIPLA™ q.d. by mouth for 48 weeks (and will take placebo for an additional 48 weeks for a total of 96 weeks) in order to maintain blinding. | Treatment-naive participants with HIV-1 infection took ATRIPLA™, a single-tablet FDC containing efavirenz 600 mg + emtricitabine 200 mg + tenofovir disoproxil fumarate 300 mg (equivalent to 245 mg tenofovir disoproxil), q.d. by mouth for 48 weeks (and will take ATRIPLA for an additional 48 weeks for a total of 96 weeks). Participants also took 1 placebo tablet matched to MK-1439A q.d. by mouth for 48 weeks (and will take placebo for an additional 48 weeks for a total of 96 weeks) in order to maintain blinding. | Total of all reporting groups |
| Overall Participants | 364 | 364 | 728 |
| Age (Years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [Years] |
33.6
(10.5)
|
32.7
(9.9)
|
33.1
(10.2)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
59
16.2%
|
53
14.6%
|
112
15.4%
|
| Male |
305
83.8%
|
311
85.4%
|
616
84.6%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
10
2.7%
|
6
1.6%
|
16
2.2%
|
| Asian |
59
16.2%
|
65
17.9%
|
124
17%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
67
18.4%
|
68
18.7%
|
135
18.5%
|
| White |
177
48.6%
|
170
46.7%
|
347
47.7%
|
| More than one race |
51
14%
|
55
15.1%
|
106
14.6%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Baseline cluster of differentiation 4 (CD4) cell counts (cells/mm^3) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [cells/mm^3] |
434.9
(217.9)
|
415.5
(210.6)
|
425.2
(214.3)
|
| Baseline fasting low-density lipoprotein cholesterol (LDL-C) (mg/dL) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [mg/dL] |
92.08
(32.32)
|
90.47
(30.64)
|
91.27
(31.48)
|
| Baseline fasting non-high-density lipoprotein cholesterol (non-HDL-C) (mg/dL) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [mg/dL] |
115.39
(34.67)
|
114.63
(33.55)
|
115.01
(34.09)
|
| Baseline fasting cholesterol (mg/dL) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [mg/dL] |
157.29
(36.43)
|
156.07
(36.51)
|
156.68
(36.45)
|
| Baseline fasting triglycerides (mg/dL) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [mg/dL] |
120.85
(83.06)
|
123.23
(82.73)
|
122.04
(82.84)
|
| Baseline fasting high-density lipoprotein cholesterol (HDL-C) (mg/dL) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [mg/dL] |
41.90
(11.67)
|
41.44
(13.08)
|
41.67
(12.38)
|
Outcome Measures
| Title | Percentage of Participants With HIV-1 Ribonucleic Acid (RNA) <50 Copies/mL at Week 48 |
|---|---|
| Description | The percentage of participants in each arm with HIV-1 RNA levels <50 copies/mL at Week 48 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 in which all missing data are considered treatment failures, regardless of the reason. |
| Time Frame | Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population consists of all randomized participants who received ≥1 dose of study medication and had baseline HIV-1 RNA data available. |
| Arm/Group Title | MK-1439A | ATRIPLA™ |
|---|---|---|
| Arm/Group Description | Treatment-naive participants with HIV-1 infection took MK-1439A, a single-tablet FDC containing doravirine 100 mg + lamivudine 300 mg + tenofovir disoproxil fumarate 300 mg, q.d. by mouth for 48 weeks (and will take MK-1439A for an additional 48 weeks for a total of 96 weeks). Participants also took 1 placebo tablet matched to ATRIPLA™ q.d. by mouth for 48 weeks (and will take placebo for an additional 48 weeks for a total of 96 weeks) in order to maintain blinding. | Treatment-naive participants with HIV-1 infection took ATRIPLA™, a single-tablet FDC containing efavirenz 600 mg + emtricitabine 200 mg + tenofovir disoproxil fumarate 300 mg (equivalent to 245 mg tenofovir disoproxil), q.d. by mouth for 48 weeks (and will take ATRIPLA for an additional 48 weeks for a total of 96 weeks). Participants also took 1 placebo tablet matched to MK-1439A q.d. by mouth for 48 weeks (and will take placebo for an additional 48 weeks for a total of 96 weeks) in order to maintain blinding. |
| Measure Participants | 364 | 364 |
| Number [Percentage of Participants] |
84.3
23.2%
|
80.8
22.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | MK-1439A, ATRIPLA™ |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Non-Inferiority | |
| Comments | Non-inferiority was declared if the lower bound of the 95% CI of the mean treatment difference was greater than -10. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in percentages |
| Estimated Value | 3.537 | |
| Confidence Interval |
(2-Sided) 95% -1.951 to 9.026 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The 95% CIs for difference in percentages were calculated using stratum-adjusted Mantel-Haenszel method for each stratum (HIV-1 RNA ≤100,000 or >100,000 copies/mL). | |
| Title | Percentage of Participants With Tier-1 Neuropsychiatric Adverse Events (AEs) |
|---|---|
| Description | The percentage of participants in each arm experiencing ≥1 pre-specified Tier-1 neuropsychiatric AEs was determined. The list of Tier-1 neuropsychiatric AE categories included "dizziness", "sleep disorders and disturbances", and "altered sensorium" (including disturbance in attention). |
| Time Frame | Up to Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population consists of all randomized participants who received ≥1 dose of study medication. |
| Arm/Group Title | MK-1439A | ATRIPLA™ |
|---|---|---|
| Arm/Group Description | Treatment-naive participants with HIV-1 infection took MK-1439A, a single-tablet FDC containing doravirine 100 mg + lamivudine 300 mg + tenofovir disoproxil fumarate 300 mg, q.d. by mouth for 48 weeks (and will take MK-1439A for an additional 48 weeks for a total of 96 weeks). Participants also took 1 placebo tablet matched to ATRIPLA™ q.d. by mouth for 48 weeks (and will take placebo for an additional 48 weeks for a total of 96 weeks) in order to maintain blinding. | Treatment-naive participants with HIV-1 infection took ATRIPLA™, a single-tablet FDC containing efavirenz 600 mg + emtricitabine 200 mg + tenofovir disoproxil fumarate 300 mg (equivalent to 245 mg tenofovir disoproxil), q.d. by mouth for 48 weeks (and will take ATRIPLA for an additional 48 weeks for a total of 96 weeks). Participants also took 1 placebo tablet matched to MK-1439A q.d. by mouth for 48 weeks (and will take placebo for an additional 48 weeks for a total of 96 weeks) in order to maintain blinding. |
| Measure Participants | 364 | 364 |
| Dizziness |
8.8
2.4%
|
37.1
10.2%
|
| Sleep disorders and disturbances |
12.1
3.3%
|
25.5
7%
|
| Altered sensorium |
4.4
1.2%
|
8.2
2.3%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | MK-1439A, ATRIPLA™ |
|---|---|---|
| Comments | Dizziness difference | |
| Type of Statistical Test | Superiority | |
| Comments | Superiority was declared when the 1-sided p-value comparing treatment difference was <0.02497. | |
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | 2-sided P-value | |
| Method | t-test, 2 sided | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in percentages |
| Estimated Value | -28.3 | |
| Confidence Interval |
(2-Sided) 95% -34.0 to -22.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | 95% CIs were calculated using the Miettinen and Nurminen method. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | MK-1439A, ATRIPLA™ |
|---|---|---|
| Comments | Sleep disorders and disturbances difference | |
| Type of Statistical Test | Superiority | |
| Comments | Superiority was declared when the 1-sided p-value comparing treatment difference was <0.02497. | |
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | 2-sided P-value | |
| Method | t-test, 2 sided | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in percentages |
| Estimated Value | -13.5 | |
| Confidence Interval |
(2-Sided) 95% -19.1 to -7.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | 95% CIs were calculated using the Miettinen and Nurminen method. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | MK-1439A, ATRIPLA™ |
|---|---|---|
| Comments | Altered sensorium difference | |
| Type of Statistical Test | Superiority | |
| Comments | Superiority was declared when the 1-sided p-value comparing treatment difference was <0.02497. | |
| Statistical Test of Hypothesis | p-Value | 0.033 |
| Comments | 2-sided P-value | |
| Method | t-test, 2 sided | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in percentages |
| Estimated Value | -3.8 | |
| Confidence Interval |
(2-Sided) 95% -7.6 to -0.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | 95% CIs were calculated using the Miettinen and Nurminen method. | |
| Title | Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 96 |
|---|---|
| Description | The percentage of participants in each arm with HIV-1 RNA levels <50 copies/mL at Week 96 will be determined. Plasma HIV-1 RNA levels will be quantified with the Abbott RealTime HIV-1 Assay. The US Food and Drug Administration (FDA) "snapshot" approach (i.e., all missing data handled as treatment failures, regardless of the reason) will be used for efficacy analyses. |
| Time Frame | Week 96 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population will consist of all randomized participants who received ≥1 dose of study medication and had baseline HIV-1 RNA data available. The current results are based on the first 48 weeks of the study; Week 96 results will be provided in a future report. |
| Arm/Group Title | MK-1439A | ATRIPLA™ |
|---|---|---|
| Arm/Group Description | Treatment-naive participants with HIV-1 infection took MK-1439A, a single-tablet FDC containing doravirine 100 mg + lamivudine 300 mg + tenofovir disoproxil fumarate 300 mg, q.d. by mouth for 48 weeks (and will take MK-1439A for an additional 48 weeks for a total of 96 weeks). Participants also took 1 placebo tablet matched to ATRIPLA™ q.d. by mouth for 48 weeks (and will take placebo for an additional 48 weeks for a total of 96 weeks) in order to maintain blinding. | Treatment-naive participants with HIV-1 infection took ATRIPLA™, a single-tablet FDC containing efavirenz 600 mg + emtricitabine 200 mg + tenofovir disoproxil fumarate 300 mg (equivalent to 245 mg tenofovir disoproxil), q.d. by mouth for 48 weeks (and will take ATRIPLA for an additional 48 weeks for a total of 96 weeks). Participants also took 1 placebo tablet matched to MK-1439A q.d. by mouth for 48 weeks (and will take placebo for an additional 48 weeks for a total of 96 weeks) in order to maintain blinding. |
| Measure Participants | 0 | 0 |
| Title | Percentage of Participants With HIV-1 RNA <40 Copies/mL at Week 48 |
|---|---|
| Description | The percentage of participants in each arm with HIV-1 RNA levels <40 copies/mL (including target detected and target not detected) at Week 48 was determined. Plasma HIV 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 in which all missing data are considered treatment failures, regardless of the reason. |
| Time Frame | Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population consists of all randomized participants who received ≥1 dose of study medication and had baseline HIV-1 RNA data available. |
| Arm/Group Title | MK-1439A | ATRIPLA™ |
|---|---|---|
| Arm/Group Description | Treatment-naive participants with HIV-1 infection took MK-1439A, a single-tablet FDC containing doravirine 100 mg + lamivudine 300 mg + tenofovir disoproxil fumarate 300 mg, q.d. by mouth for 48 weeks (and will take MK-1439A for an additional 48 weeks for a total of 96 weeks). Participants also took 1 placebo tablet matched to ATRIPLA™ q.d. by mouth for 48 weeks (and will take placebo for an additional 48 weeks for a total of 96 weeks) in order to maintain blinding. | Treatment-naive participants with HIV-1 infection took ATRIPLA™, a single-tablet FDC containing efavirenz 600 mg + emtricitabine 200 mg + tenofovir disoproxil fumarate 300 mg (equivalent to 245 mg tenofovir disoproxil), q.d. by mouth for 48 weeks (and will take ATRIPLA for an additional 48 weeks for a total of 96 weeks). Participants also took 1 placebo tablet matched to MK-1439A q.d. by mouth for 48 weeks (and will take placebo for an additional 48 weeks for a total of 96 weeks) in order to maintain blinding. |
| Measure Participants | 364 | 364 |
| Number (95% Confidence Interval) [Percentage of Participants] |
83.8
23%
|
79.7
21.9%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | MK-1439A, ATRIPLA™ |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Non-Inferiority | |
| Comments | Non-inferiority was declared if the lower bound of the 95% CI of the mean treatment difference was greater than -10. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in percentages |
| Estimated Value | 4.1 | |
| Confidence Interval |
(2-Sided) 95% -1.5 to 9.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The 95% CIs for difference in percentages were calculated using stratum-adjusted Mantel-Haenszel method for each stratum (HIV-1 RNA ≤100,000 or >100,000 copies/mL). | |
| Title | Percentage of Participants With HIV-1 RNA <40 Copies/mL at Week 96 |
|---|---|
| Description | The percentage of participants in each arm with HIV-1 RNA levels <40 copies/mL (including target detected and target not detected) at Week 96 will be determined. Plasma HIV-1 RNA levels will be quantified with the Abbott RealTime HIV-1 Assay. The US Food and Drug Administration (FDA) "snapshot" approach (i.e., all missing data handled as treatment failures, regardless of the reason) will be used for efficacy analyses. |
| Time Frame | Week 96 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population will consist of all randomized participants who received ≥1 dose of study medication and had baseline HIV-1 RNA data available. The current results are based on the first 48 weeks of the study; Week 96 results will be provided in a future report. |
| Arm/Group Title | MK-1439A | ATRIPLA™ |
|---|---|---|
| Arm/Group Description | Treatment-naive participants with HIV-1 infection took MK-1439A, a single-tablet FDC containing doravirine 100 mg + lamivudine 300 mg + tenofovir disoproxil fumarate 300 mg, q.d. by mouth for 48 weeks (and will take MK-1439A for an additional 48 weeks for a total of 96 weeks). Participants also took 1 placebo tablet matched to ATRIPLA™ q.d. by mouth for 48 weeks (and will take placebo for an additional 48 weeks for a total of 96 weeks) in order to maintain blinding. | Treatment-naive participants with HIV-1 infection took ATRIPLA™, a single-tablet FDC containing efavirenz 600 mg + emtricitabine 200 mg + tenofovir disoproxil fumarate 300 mg (equivalent to 245 mg tenofovir disoproxil), q.d. by mouth for 48 weeks (and will take ATRIPLA for an additional 48 weeks for a total of 96 weeks). Participants also took 1 placebo tablet matched to MK-1439A q.d. by mouth for 48 weeks (and will take placebo for an additional 48 weeks for a total of 96 weeks) in order to maintain blinding. |
| Measure Participants | 0 | 0 |
| Title | Change From Baseline in CD4 Cell Counts at Week 48 |
|---|---|
| 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 prior to Week 48 due to lack of efficacy. Cell counts at Baseline and Week 48 were measured and expressed as cells/mm^3, and percent change was then calculated as [(Baseline counts - Week 48 counts)*100]. CD4 cell counts were quantified by a central laboratory using a commercially available assay. |
| Time Frame | Baseline (Day 1) and Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population consisted of all randomized participants who received ≥1 dose of study medication and had baseline and Week 48 CD4 data available. |
| Arm/Group Title | MK-1439A | ATRIPLA™ |
|---|---|---|
| Arm/Group Description | Treatment-naive participants with HIV-1 infection took MK-1439A, a single-tablet FDC containing doravirine 100 mg + lamivudine 300 mg + tenofovir disoproxil fumarate 300 mg, q.d. by mouth for 48 weeks (and will take MK-1439A for an additional 48 weeks for a total of 96 weeks). Participants also took 1 placebo tablet matched to ATRIPLA™ q.d. by mouth for 48 weeks (and will take placebo for an additional 48 weeks for a total of 96 weeks) in order to maintain blinding. | Treatment-naive participants with HIV-1 infection took ATRIPLA™, a single-tablet FDC containing efavirenz 600 mg + emtricitabine 200 mg + tenofovir disoproxil fumarate 300 mg (equivalent to 245 mg tenofovir disoproxil), q.d. by mouth for 48 weeks (and will take ATRIPLA for an additional 48 weeks for a total of 96 weeks). Participants also took 1 placebo tablet matched to MK-1439A q.d. by mouth for 48 weeks (and will take placebo for an additional 48 weeks for a total of 96 weeks) in order to maintain blinding. |
| Measure Participants | 344 | 329 |
| Mean (95% Confidence Interval) [Percent Change from Baseline] |
198.4
|
188.4
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | MK-1439A, ATRIPLA™ |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | Superiority was declared when group difference (MK-1439A-ATRIPLA®) was a positive value. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in mean %change from baseline |
| Estimated Value | 10.1 | |
| Confidence Interval |
(2-Sided) 95% -16.1 to 36.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | 95% CIs were calculated based on t-distribution. | |
| Title | Change From Baseline in CD4 Cell Counts at Week 96 |
|---|---|
| Description | The mean change from baseline in CD4 cell counts at Week 96 will be assessed using the Observed Failure (OF) approach. With the OF approach, baseline values will be carried forward for participants who discontinued prior to Week 96 due to lack of efficacy. Cell counts at Baseline and Week 96 will be measured and expressed as cells/mm^3, and percent change will then be calculated as [(Baseline counts - Week 96 counts)*100]. CD4 cell counts will be quantified by a central laboratory using a commercially available assay. |
| Time Frame | Baseline (Day 1) and Week 96 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population will consist of all randomized participants who received ≥1 dose of study medication and had baseline CD4 data available. The current results are based on the first 48 weeks of the study; Week 96 results will be provided in a future report. |
| Arm/Group Title | MK-1439A | ATRIPLA™ |
|---|---|---|
| Arm/Group Description | Treatment-naive participants with HIV-1 infection took MK-1439A, a single-tablet FDC containing doravirine 100 mg + lamivudine 300 mg + tenofovir disoproxil fumarate 300 mg, q.d. by mouth for 48 weeks (and will take MK-1439A for an additional 48 weeks for a total of 96 weeks). Participants also took 1 placebo tablet matched to ATRIPLA™ q.d. by mouth for 48 weeks (and will take placebo for an additional 48 weeks for a total of 96 weeks) in order to maintain blinding. | Treatment-naive participants with HIV-1 infection took ATRIPLA™, a single-tablet FDC containing efavirenz 600 mg + emtricitabine 200 mg + tenofovir disoproxil fumarate 300 mg (equivalent to 245 mg tenofovir disoproxil), q.d. by mouth for 48 weeks (and will take ATRIPLA for an additional 48 weeks for a total of 96 weeks). Participants also took 1 placebo tablet matched to MK-1439A q.d. by mouth for 48 weeks (and will take placebo for an additional 48 weeks for a total of 96 weeks) in order to maintain blinding. |
| Measure Participants | 0 | 0 |
| Title | Percentage of Participants Experiencing ≥1 AE |
|---|---|
| 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 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population consisted of all randomized participants who received ≥1 dose of study medication. |
| Arm/Group Title | MK-1439A | ATRIPLA™ |
|---|---|---|
| Arm/Group Description | Treatment-naive participants with HIV-1 infection took MK-1439A, a single-tablet FDC containing doravirine 100 mg + lamivudine 300 mg + tenofovir disoproxil fumarate 300 mg, q.d. by mouth for 48 weeks (and will take MK-1439A for an additional 48 weeks for a total of 96 weeks). Participants also took 1 placebo tablet matched to ATRIPLA™ q.d. by mouth for 48 weeks (and will take placebo for an additional 48 weeks for a total of 96 weeks) in order to maintain blinding. | Treatment-naive participants with HIV-1 infection took ATRIPLA™, a single-tablet FDC containing efavirenz 600 mg + emtricitabine 200 mg + tenofovir disoproxil fumarate 300 mg (equivalent to 245 mg tenofovir disoproxil), q.d. by mouth for 48 weeks (and will take ATRIPLA for an additional 48 weeks for a total of 96 weeks). Participants also took 1 placebo tablet matched to MK-1439A q.d. by mouth for 48 weeks (and will take placebo for an additional 48 weeks for a total of 96 weeks) in order to maintain blinding. |
| Measure Participants | 364 | 364 |
| Number [Percentage of participants] |
82.7
22.7%
|
90.7
24.9%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | MK-1439A, ATRIPLA™ |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | Difference in percentage of participants with ≥1 AE(s) | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in percentages |
| Estimated Value | -8.0 | |
| Confidence Interval |
(2-Sided) 95% -13.0 to -3.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | 95% CIs were calculated with the Miettinen & Nurminen method. | |
| Title | Percentage of Participants Discontinuing From Study Medication Due to an AE(s) |
|---|---|
| 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 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population consisted of all randomized participants who received ≥1 dose of study medication. |
| Arm/Group Title | MK-1439A | ATRIPLA™ |
|---|---|---|
| Arm/Group Description | Treatment-naive participants with HIV-1 infection took MK-1439A, a single-tablet FDC containing doravirine 100 mg + lamivudine 300 mg + tenofovir disoproxil fumarate 300 mg, q.d. by mouth for 48 weeks (and will take MK-1439A for an additional 48 weeks for a total of 96 weeks). Participants also took 1 placebo tablet matched to ATRIPLA™ q.d. by mouth for 48 weeks (and will take placebo for an additional 48 weeks for a total of 96 weeks) in order to maintain blinding. | Treatment-naive participants with HIV-1 infection took ATRIPLA™, a single-tablet FDC containing efavirenz 600 mg + emtricitabine 200 mg + tenofovir disoproxil fumarate 300 mg (equivalent to 245 mg tenofovir disoproxil), q.d. by mouth for 48 weeks (and will take ATRIPLA for an additional 48 weeks for a total of 96 weeks). Participants also took 1 placebo tablet matched to MK-1439A q.d. by mouth for 48 weeks (and will take placebo for an additional 48 weeks for a total of 96 weeks) in order to maintain blinding. |
| Measure Participants | 364 | 364 |
| Number [Percentage of participants] |
3.0
0.8%
|
6.6
1.8%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | MK-1439A, ATRIPLA™ |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | Difference in percentage of participants with ≥1 AE(s) | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in percentages |
| Estimated Value | -3.6 | |
| Confidence Interval |
(2-Sided) 95% -6.9 to -0.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | 95% CIs were calculated with the Miettinen & Nurminen method. | |
| Title | Percentage of Participants With Tier-2 Neuropsychiatric AEs |
|---|---|
| Description | The percentage of participants in each arm experiencing ≥1 pre-specified Tier-2 neuropsychiatric AEs was determined. The list of Tier-2 neuropsychiatric AE categories included "depression and suicide/self-injury" and "psychosis and psychotic disorders". |
| Time Frame | Up to Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population consists of all randomized participants who received ≥1 dose of study medication. |
| Arm/Group Title | MK-1439A | ATRIPLA™ |
|---|---|---|
| Arm/Group Description | Treatment-naive participants with HIV-1 infection took MK-1439A, a single-tablet FDC containing doravirine 100 mg + lamivudine 300 mg + tenofovir disoproxil fumarate 300 mg, q.d. by mouth for 48 weeks (and will take MK-1439A for an additional 48 weeks for a total of 96 weeks). Participants also took 1 placebo tablet matched to ATRIPLA™ q.d. by mouth for 48 weeks (and will take placebo for an additional 48 weeks for a total of 96 weeks) in order to maintain blinding. | Treatment-naive participants with HIV-1 infection took ATRIPLA™, a single-tablet FDC containing efavirenz 600 mg + emtricitabine 200 mg + tenofovir disoproxil fumarate 300 mg (equivalent to 245 mg tenofovir disoproxil), q.d. by mouth for 48 weeks (and will take ATRIPLA for an additional 48 weeks for a total of 96 weeks). Participants also took 1 placebo tablet matched to MK-1439A q.d. by mouth for 48 weeks (and will take placebo for an additional 48 weeks for a total of 96 weeks) in order to maintain blinding. |
| Measure Participants | 364 | 364 |
| Depression and suicide/self-injury |
4.1
1.1%
|
6.6
1.8%
|
| Psychosis and psychotic disorders |
0.3
0.1%
|
1.1
0.3%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | MK-1439A, ATRIPLA™ |
|---|---|---|
| Comments | Depression and suicide/self-injury difference | |
| Type of Statistical Test | Superiority | |
| Comments | Superiority was declared when the 1-sided p-value comparing treatment difference was <0.02497. | |
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | 2-sided P-value | |
| Method | t-test, 2 sided | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in percentages |
| Estimated Value | -2.5 | |
| Confidence Interval |
(2-Sided) 95% -5.9 to 0.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | 95% CIs were calculated using the Miettinen and Nurminen method. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | MK-1439A, ATRIPLA™ |
|---|---|---|
| Comments | Psychosis and psychotic disorders difference | |
| Type of Statistical Test | Superiority | |
| Comments | Superiority was declared when the 1-sided p-value comparing treatment difference was <0.02497. | |
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | 2-sided P-value | |
| Method | t-test, 2 sided | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in percentages |
| Estimated Value | -0.8 | |
| Confidence Interval |
(2-Sided) 95% -2.5 to 0.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | 95% CIs were calculated using the Miettinen and Nurminen method. | |
| Title | Change From Baseline in Fasting LDL-C at Week 48 |
|---|---|
| Description | The mean percent change from baseline in fasting (fast duration of ≥8 hours) LDL-C levels at Week 48 was determined for each arm. 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 (Day 1) and Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population consists of all randomized participants who had baseline LDL-C data available as well as ≥1 LDL-C measurement after initiating study treatment. |
| Arm/Group Title | MK-1439A | ATRIPLA™ |
|---|---|---|
| Arm/Group Description | Treatment-naive participants with HIV-1 infection took MK-1439A, a single-tablet FDC containing doravirine 100 mg + lamivudine 300 mg + tenofovir disoproxil fumarate 300 mg, q.d. by mouth for 48 weeks (and will take MK-1439A for an additional 48 weeks for a total of 96 weeks). Participants also took 1 placebo tablet matched to ATRIPLA™ q.d. by mouth for 48 weeks (and will take placebo for an additional 48 weeks for a total of 96 weeks) in order to maintain blinding. | Treatment-naive participants with HIV-1 infection took ATRIPLA™, a single-tablet FDC containing efavirenz 600 mg + emtricitabine 200 mg + tenofovir disoproxil fumarate 300 mg (equivalent to 245 mg tenofovir disoproxil), q.d. by mouth for 48 weeks (and will take ATRIPLA for an additional 48 weeks for a total of 96 weeks). Participants also took 1 placebo tablet matched to MK-1439A q.d. by mouth for 48 weeks (and will take placebo for an additional 48 weeks for a total of 96 weeks) in order to maintain blinding. |
| Measure Participants | 330 | 305 |
| Mean (95% Confidence Interval) [Percent Change from Baseline] |
-1.58
|
8.74
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | MK-1439A, ATRIPLA™ |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in mean %change from baseline |
| Estimated Value | -10.01 | |
| Confidence Interval |
(2-Sided) 95% -13.53 to -6.49 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | 95% CIs and 2-sided p-values for treatment difference were calculated from an ANCOVA model with terms for baseline lipid level and treatment. | |
| Title | Change From Baseline in Fasting Non-HDL-C at Week 48 |
|---|---|
| Description | The mean percent change from baseline in fasting (fast duration of ≥8 hours) non-HDL-C levels at Week 48 was determined for each arm. The LOCF approach was applied to missing data and data collected after a participant initiated lipid-modifying therapy. |
| Time Frame | Baseline (Day 1) and Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population consists of all randomized participants who had baseline non-HDL-C data available as well as ≥1 non-HDL-C measurement after initiating study treatment. |
| Arm/Group Title | MK-1439A | ATRIPLA™ |
|---|---|---|
| Arm/Group Description | Treatment-naive participants with HIV-1 infection took MK-1439A, a single-tablet FDC containing doravirine 100 mg + lamivudine 300 mg + tenofovir disoproxil fumarate 300 mg, q.d. by mouth for 48 weeks (and will take MK-1439A for an additional 48 weeks for a total of 96 weeks). Participants also took 1 placebo tablet matched to ATRIPLA™ q.d. by mouth for 48 weeks (and will take placebo for an additional 48 weeks for a total of 96 weeks) in order to maintain blinding. | Treatment-naive participants with HIV-1 infection took ATRIPLA™, a single-tablet FDC containing efavirenz 600 mg + emtricitabine 200 mg + tenofovir disoproxil fumarate 300 mg (equivalent to 245 mg tenofovir disoproxil), q.d. by mouth for 48 weeks (and will take ATRIPLA for an additional 48 weeks for a total of 96 weeks). Participants also took 1 placebo tablet matched to MK-1439A q.d. by mouth for 48 weeks (and will take placebo for an additional 48 weeks for a total of 96 weeks) in order to maintain blinding. |
| Measure Participants | 333 | 314 |
| Mean (95% Confidence Interval) [Percent Change from Baseline] |
-3.83
|
13.26
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | MK-1439A, ATRIPLA™ |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in mean %change from baseline |
| Estimated Value | -17.02 | |
| Confidence Interval |
(2-Sided) 95% -20.89 to -13.16 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | 95% CIs and 2-sided p-values for treatment difference were calculated from an ANCOVA model with terms for baseline lipid level and treatment. | |
| Title | Change From Baseline in Fasting Cholesterol at Week 48 |
|---|---|
| Description | The mean percent change from baseline in fasting (fast duration of ≥8 hours) cholesterol levels at Week 48 was determined for each arm. The LOCF approach was applied to missing data and data collected after a participant initiated lipid-modifying therapy. |
| Time Frame | Baseline (Day 1) and Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population consists of all randomized participants who had baseline cholesterol data available as well as ≥1 cholesterol measurement after initiating study treatment. |
| Arm/Group Title | MK-1439A | ATRIPLA™ |
|---|---|---|
| Arm/Group Description | Treatment-naive participants with HIV-1 infection took MK-1439A, a single-tablet FDC containing doravirine 100 mg + lamivudine 300 mg + tenofovir disoproxil fumarate 300 mg, q.d. by mouth for 48 weeks (and will take MK-1439A for an additional 48 weeks for a total of 96 weeks). Participants also took 1 placebo tablet matched to ATRIPLA™ q.d. by mouth for 48 weeks (and will take placebo for an additional 48 weeks for a total of 96 weeks) in order to maintain blinding. | Treatment-naive participants with HIV-1 infection took ATRIPLA™, a single-tablet FDC containing efavirenz 600 mg + emtricitabine 200 mg + tenofovir disoproxil fumarate 300 mg (equivalent to 245 mg tenofovir disoproxil), q.d. by mouth for 48 weeks (and will take ATRIPLA for an additional 48 weeks for a total of 96 weeks). Participants also took 1 placebo tablet matched to MK-1439A q.d. by mouth for 48 weeks (and will take placebo for an additional 48 weeks for a total of 96 weeks) in order to maintain blinding. |
| Measure Participants | 333 | 314 |
| Mean (95% Confidence Interval) [Percent Change from Baseline] |
-1.97
|
21.77
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | MK-1439A, ATRIPLA™ |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in mean %change from baseline |
| Estimated Value | -23.44 | |
| Confidence Interval |
(2-Sided) 95% -27.57 to -19.32 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | 95% CIs for treatment difference were calculated from an ANCOVA model with terms for baseline lipid level and treatment. | |
| Title | Change From Baseline in Fasting Triglycerides at Week 48 |
|---|---|
| Description | The mean percent change from baseline in fasting (fast duration of ≥8 hours) triglycerides levels at Week 48 was determined for each arm. The LOCF approach was applied to missing data and data collected after a participant initiated lipid-modifying therapy. |
| Time Frame | Baseline (Day 1) and Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population consists of all randomized participants who had baseline triglyceride data available as well as ≥1 triglyceride measurement after initiating study treatment. |
| Arm/Group Title | MK-1439A | ATRIPLA™ |
|---|---|---|
| Arm/Group Description | Treatment-naive participants with HIV-1 infection took MK-1439A, a single-tablet FDC containing doravirine 100 mg + lamivudine 300 mg + tenofovir disoproxil fumarate 300 mg, q.d. by mouth for 48 weeks (and will take MK-1439A for an additional 48 weeks for a total of 96 weeks). Participants also took 1 placebo tablet matched to ATRIPLA™ q.d. by mouth for 48 weeks (and will take placebo for an additional 48 weeks for a total of 96 weeks) in order to maintain blinding. | Treatment-naive participants with HIV-1 infection took ATRIPLA™, a single-tablet FDC containing efavirenz 600 mg + emtricitabine 200 mg + tenofovir disoproxil fumarate 300 mg (equivalent to 245 mg tenofovir disoproxil), q.d. by mouth for 48 weeks (and will take ATRIPLA for an additional 48 weeks for a total of 96 weeks). Participants also took 1 placebo tablet matched to MK-1439A q.d. by mouth for 48 weeks (and will take placebo for an additional 48 weeks for a total of 96 weeks) in order to maintain blinding. |
| Measure Participants | 333 | 314 |
| Mean (95% Confidence Interval) [Percent Change from Baseline] |
-12.40
|
22.01
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | MK-1439A, ATRIPLA™ |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in mean %change from baseline |
| Estimated Value | -35.96 | |
| Confidence Interval |
(2-Sided) 95% -47.10 to -24.82 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | 95% CIs for treatment difference were calculated from an ANCOVA model with terms for baseline lipid level and treatment. | |
| Title | Change From Baseline in Fasting HDL-C at Week 48 |
|---|---|
| Description | The mean percent change from baseline in fasting (fast duration of ≥8 hours) HDL-C levels at Week 48 was determined for each arm. The LOCF approach was applied to missing data and data collected after a participant initiated lipid-modifying therapy. |
| Time Frame | Baseline (Day 1) and Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population consists of all randomized participants who had baseline HDL-C data available as well as ≥1 HDL-C measurement after initiating study treatment. |
| Arm/Group Title | MK-1439A | ATRIPLA™ |
|---|---|---|
| Arm/Group Description | Treatment-naive participants with HIV-1 infection took MK-1439A, a single-tablet FDC containing doravirine 100 mg + lamivudine 300 mg + tenofovir disoproxil fumarate 300 mg, q.d. by mouth for 48 weeks (and will take MK-1439A for an additional 48 weeks for a total of 96 weeks). Participants also took 1 placebo tablet matched to ATRIPLA™ q.d. by mouth for 48 weeks (and will take placebo for an additional 48 weeks for a total of 96 weeks) in order to maintain blinding. | Treatment-naive participants with HIV-1 infection took ATRIPLA™, a single-tablet FDC containing efavirenz 600 mg + emtricitabine 200 mg + tenofovir disoproxil fumarate 300 mg (equivalent to 245 mg tenofovir disoproxil), q.d. by mouth for 48 weeks (and will take ATRIPLA for an additional 48 weeks for a total of 96 weeks). Participants also took 1 placebo tablet matched to MK-1439A q.d. by mouth for 48 weeks (and will take placebo for an additional 48 weeks for a total of 96 weeks) in order to maintain blinding. |
| Measure Participants | 333 | 314 |
| Mean (95% Confidence Interval) [Percent Change from Baseline] |
1.86
|
8.51
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | MK-1439A, ATRIPLA™ |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in mean %change from baseline |
| Estimated Value | -6.47 | |
| Confidence Interval |
(2-Sided) 95% -7.97 to -4.96 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | 95% CIs for treatment difference were calculated from an ANCOVA model with terms for baseline lipid level and treatment. | |
| Title | Percentage of Participants With HIV-1 RNA Below the Limit of Quantification (BLoQ) at Week 48 |
|---|---|
| Description | The percentage of participants in each arm with HIV-1 RNA levels BLoQ of 40 copies/mL and target not detected at Week 48 was determined. Plasma HIV RNA levels were quantified with the Abbott RealTime HIV-1 Assay. Data were handled as observed. |
| Time Frame | Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population consists of all randomized participants who received ≥1 dose of study medication and had baseline HIV-1 RNA data available. |
| Arm/Group Title | MK-1439A | ATRIPLA™ |
|---|---|---|
| Arm/Group Description | Treatment-naive participants with HIV-1 infection took MK-1439A, a single-tablet FDC containing doravirine 100 mg + lamivudine 300 mg + tenofovir disoproxil fumarate 300 mg, q.d. by mouth for 48 weeks (and will take MK-1439A for an additional 48 weeks for a total of 96 weeks). Participants also took 1 placebo tablet matched to ATRIPLA™ q.d. by mouth for 48 weeks (and will take placebo for an additional 48 weeks for a total of 96 weeks) in order to maintain blinding. | Treatment-naive participants with HIV-1 infection took ATRIPLA™, a single-tablet FDC containing efavirenz 600 mg + emtricitabine 200 mg + tenofovir disoproxil fumarate 300 mg (equivalent to 245 mg tenofovir disoproxil), q.d. by mouth for 48 weeks (and will take ATRIPLA for an additional 48 weeks for a total of 96 weeks). Participants also took 1 placebo tablet matched to MK-1439A q.d. by mouth for 48 weeks (and will take placebo for an additional 48 weeks for a total of 96 weeks) in order to maintain blinding. |
| Measure Participants | 364 | 364 |
| Number [Percentage of Participants] |
59.6
16.4%
|
55.5
15.2%
|
| Title | Percentage of Participants With HIV-1 RNA BLoQ at Week 96 |
|---|---|
| Description | The percentage of participants in each arm with HIV-1 RNA levels BLoQ of 40 copies/mL and target not detected at Week 96 will be determined. Plasma HIV RNA levels will be quantified with the Abbott RealTime HIV-1 Assay. Data will be handled as observed. |
| Time Frame | Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population will consist of all randomized participants who receive ≥1 dose of study medication and have baseline HIV-1 RNA data available. The current results are based on the first 48 weeks of the study; Week 96 results will be provided in a future report. |
| Arm/Group Title | MK-1439A | ATRIPLA™ |
|---|---|---|
| Arm/Group Description | Treatment-naive participants with HIV-1 infection took MK-1439A, a single-tablet FDC containing doravirine 100 mg + lamivudine 300 mg + tenofovir disoproxil fumarate 300 mg, q.d. by mouth for 48 weeks (and will take MK-1439A for an additional 48 weeks for a total of 96 weeks). Participants also took 1 placebo tablet matched to ATRIPLA™ q.d. by mouth for 48 weeks (and will take placebo for an additional 48 weeks for a total of 96 weeks) in order to maintain blinding. | Treatment-naive participants with HIV-1 infection took ATRIPLA™, a single-tablet FDC containing efavirenz 600 mg + emtricitabine 200 mg + tenofovir disoproxil fumarate 300 mg (equivalent to 245 mg tenofovir disoproxil), q.d. by mouth for 48 weeks (and will take ATRIPLA for an additional 48 weeks for a total of 96 weeks). Participants also took 1 placebo tablet matched to MK-1439A q.d. by mouth for 48 weeks (and will take placebo for an additional 48 weeks for a total of 96 weeks) in order to maintain blinding. |
| Measure Participants | 0 | 0 |
| Title | Plasma Concentration of Doravirine at Week 48 |
|---|---|
| Description | Plasma samples were collected for analysis of doravirine concentration at Week 48. A total of 2 samples were collected: 1 prior to dosing and 1 collected between 0.5 and 2 hours post-dose. |
| Time Frame | 0 hours post-dose and 2 hours post-dose on Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population consists of all randomized participants in the MK-1439A arm who received ≥1 dose of study drug and had doravirine concentration data available. |
| Arm/Group Title | MK-1439A |
|---|---|
| Arm/Group Description | Treatment-naive participants with HIV-1 infection took MK-1439A, a single-tablet FDC containing doravirine 100 mg + lamivudine 300 mg + tenofovir disoproxil fumarate 300 mg, q.d. by mouth for 48 weeks (and will take MK-1439A for an additional 48 weeks for a total of 96 weeks). Participants also took 1 placebo tablet matched to ATRIPLA™ q.d. by mouth for 48 weeks (and will take placebo for an additional 48 weeks for a total of 96 weeks) in order to maintain blinding. |
| Measure Participants | 312 |
| Pre-dose |
1290
(799)
|
| 0.5 to 2 hours post-dose |
2330
(1230)
|
Adverse Events
| Time Frame | Up to 48 weeks | |||
|---|---|---|---|---|
| Adverse Event Reporting 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. All participants who received ≥1 dose of study drug are included. | |||
| Arm/Group Title | MK-1439A (DOR+LAM+TEN) | ATRIPLA (EFA+EMT+TEN) | ||
| Arm/Group Description | Treatment-naive participants with HIV-1 infection took MK-1439A, a single-tablet FDC containing doravirine 100 mg + lamivudine 300 mg + tenofovir disoproxil fumarate 300 mg, q.d. by mouth for 48 weeks (and will take MK-1439A for an additional 48 weeks for a total of 96 weeks). Participants also took 1 placebo tablet matched to ATRIPLA™ q.d. by mouth for 48 weeks (and will take placebo for an additional 48 weeks for a total of 96 weeks) in order to maintain blinding. | Treatment-naive participants with HIV-1 infection took ATRIPLA™, a single-tablet FDC containing efavirenz 600 mg + emtricitabine 200 mg + tenofovir disoproxil fumarate 300 mg (equivalent to 245 mg tenofovir disoproxil), q.d. by mouth for 48 weeks (and will take ATRIPLA for an additional 48 weeks for a total of 96 weeks). Participants also took 1 placebo tablet matched to MK-1439A q.d. by mouth for 48 weeks (and will take placebo for an additional 48 weeks for a total of 96 weeks) in order to maintain blinding. | ||
All Cause Mortality |
||||
| MK-1439A (DOR+LAM+TEN) | ATRIPLA (EFA+EMT+TEN) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/364 (0%) | 2/364 (0.5%) | ||
Serious Adverse Events |
||||
| MK-1439A (DOR+LAM+TEN) | ATRIPLA (EFA+EMT+TEN) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 13/364 (3.6%) | 21/364 (5.8%) | ||
| Blood and lymphatic system disorders | ||||
| Normochromic normocytic anaemia | 1/364 (0.3%) | 1 | 0/364 (0%) | 0 |
| Cardiac disorders | ||||
| Supraventricular tachycardia | 1/364 (0.3%) | 1 | 0/364 (0%) | 0 |
| Gastrointestinal disorders | ||||
| Colitis | 0/364 (0%) | 0 | 1/364 (0.3%) | 1 |
| Oesophageal obstruction | 1/364 (0.3%) | 1 | 0/364 (0%) | 0 |
| General disorders | ||||
| Asthenia | 1/364 (0.3%) | 1 | 0/364 (0%) | 0 |
| Death | 0/364 (0%) | 0 | 1/364 (0.3%) | 1 |
| Hepatobiliary disorders | ||||
| Bile duct stone | 1/364 (0.3%) | 1 | 0/364 (0%) | 0 |
| Infections and infestations | ||||
| Appendicitis | 1/364 (0.3%) | 1 | 1/364 (0.3%) | 1 |
| Clostridium difficile infection | 0/364 (0%) | 0 | 1/364 (0.3%) | 1 |
| Endometritis | 1/364 (0.3%) | 1 | 1/364 (0.3%) | 1 |
| Gastrointestinal viral infection | 0/364 (0%) | 0 | 1/364 (0.3%) | 1 |
| Nasopharyngitis | 1/364 (0.3%) | 1 | 0/364 (0%) | 0 |
| Oophoritis | 0/364 (0%) | 0 | 1/364 (0.3%) | 1 |
| Oral bacterial infection | 0/364 (0%) | 0 | 1/364 (0.3%) | 1 |
| Pilonidal cyst | 0/364 (0%) | 0 | 1/364 (0.3%) | 1 |
| Pneumonia | 1/364 (0.3%) | 1 | 1/364 (0.3%) | 1 |
| Pneumonia bacterial | 0/364 (0%) | 0 | 1/364 (0.3%) | 1 |
| Sepsis | 0/364 (0%) | 0 | 1/364 (0.3%) | 1 |
| Subcutaneous abscess | 1/364 (0.3%) | 1 | 0/364 (0%) | 0 |
| Viral infection | 1/364 (0.3%) | 1 | 0/364 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||
| Alcohol poisoning | 0/364 (0%) | 0 | 1/364 (0.3%) | 1 |
| Post procedural haemorrhage | 1/364 (0.3%) | 2 | 0/364 (0%) | 0 |
| Subdural haematoma | 0/364 (0%) | 0 | 1/364 (0.3%) | 1 |
| Traumatic haemothorax | 1/364 (0.3%) | 1 | 0/364 (0%) | 0 |
| Metabolism and nutrition disorders | ||||
| Hypertriglyceridaemia | 0/364 (0%) | 0 | 1/364 (0.3%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Anal squamous cell carcinoma | 1/364 (0.3%) | 1 | 0/364 (0%) | 0 |
| Anogenital warts | 2/364 (0.5%) | 4 | 0/364 (0%) | 0 |
| Basal cell carcinoma | 0/364 (0%) | 0 | 1/364 (0.3%) | 1 |
| Squamous cell carcinoma of the tongue | 1/364 (0.3%) | 1 | 0/364 (0%) | 0 |
| Nervous system disorders | ||||
| Syncope | 0/364 (0%) | 0 | 1/364 (0.3%) | 1 |
| Pregnancy, puerperium and perinatal conditions | ||||
| Abortion spontaneous | 0/364 (0%) | 0 | 1/364 (0.3%) | 1 |
| Psychiatric disorders | ||||
| Completed suicide | 0/364 (0%) | 0 | 1/364 (0.3%) | 1 |
| Insomnia | 1/364 (0.3%) | 1 | 0/364 (0%) | 0 |
| Nightmare | 1/364 (0.3%) | 1 | 0/364 (0%) | 0 |
| Suicide attempt | 0/364 (0%) | 0 | 1/364 (0.3%) | 1 |
| Renal and urinary disorders | ||||
| Acute kidney injury | 0/364 (0%) | 0 | 1/364 (0.3%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Asthma | 0/364 (0%) | 0 | 1/364 (0.3%) | 1 |
| Skin and subcutaneous tissue disorders | ||||
| Rash generalised | 0/364 (0%) | 0 | 1/364 (0.3%) | 1 |
| Rash macular | 0/364 (0%) | 0 | 1/364 (0.3%) | 1 |
| Rash maculo-papular | 0/364 (0%) | 0 | 1/364 (0.3%) | 1 |
| Vascular disorders | ||||
| Malignant hypertension | 0/364 (0%) | 0 | 1/364 (0.3%) | 1 |
Other (Not Including Serious) Adverse Events |
||||
| MK-1439A (DOR+LAM+TEN) | ATRIPLA (EFA+EMT+TEN) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 184/364 (50.5%) | 263/364 (72.3%) | ||
| Gastrointestinal disorders | ||||
| Diarrhoea | 39/364 (10.7%) | 59 | 49/364 (13.5%) | 55 |
| Nausea | 28/364 (7.7%) | 31 | 39/364 (10.7%) | 46 |
| Vomiting | 15/364 (4.1%) | 18 | 27/364 (7.4%) | 33 |
| General disorders | ||||
| Fatigue | 21/364 (5.8%) | 23 | 22/364 (6%) | 24 |
| Infections and infestations | ||||
| Nasopharyngitis | 39/364 (10.7%) | 54 | 31/364 (8.5%) | 38 |
| Pharyngitis | 20/364 (5.5%) | 25 | 15/364 (4.1%) | 17 |
| Upper respiratory tract infection | 33/364 (9.1%) | 37 | 23/364 (6.3%) | 28 |
| Nervous system disorders | ||||
| Dizziness | 32/364 (8.8%) | 42 | 135/364 (37.1%) | 146 |
| Headache | 47/364 (12.9%) | 64 | 45/364 (12.4%) | 59 |
| Somnolence | 12/364 (3.3%) | 12 | 27/364 (7.4%) | 27 |
| Psychiatric disorders | ||||
| Abnormal dreams | 17/364 (4.7%) | 18 | 42/364 (11.5%) | 44 |
| Insomnia | 18/364 (4.9%) | 22 | 32/364 (8.8%) | 34 |
| Skin and subcutaneous tissue disorders | ||||
| Rash | 17/364 (4.7%) | 19 | 44/364 (12.1%) | 47 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation.
Results Point of Contact
| Name/Title | Senior Vice President, Global Clinical Development |
|---|---|
| Organization | Merck Sharp & Dohme Corp. |
| Phone | 1-800-672-6372 |
| ClinicalTrialsDisclosure@merck.com |
Responsible Party:
Merck Sharp & Dohme LLC
ClinicalTrials.gov Identifier:
NCT02403674
Other Study ID Numbers:
- 1439A-021
- MK-1439A-021
- 2014-003382-17
First Posted:
Mar 31, 2015
Last Update Posted:
Aug 22, 2022
Last Verified:
Aug 1, 2022