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

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ClinicalTrials.gov Identifier: NCT02275780
Recruitment Status : Active, not recruiting
First Posted : October 27, 2014
Results First Posted : October 23, 2018
Last Update Posted : October 23, 2018
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition HIV-1
Interventions Drug: Doravirine
Drug: Darunavir
Drug: Ritonavir
Drug: TRUVADA™ or EPZICOM™/KIVEXA™
Enrollment 769
Recruitment Details  
Pre-assignment Details A total of 1027 participants were screened and 769 were randomized. This report covers results for the 96-month Base Study. Results for the ongoing open-label study extensions will be reported when the extensions are completed.
Arm/Group Title Doravirine 100 mg Daurunavir 800 mg + Ritonavir 100 mg
Hide Arm/Group Description Double-blind Doravirine 100 mg administered orally (p.o.) once daily (q.d.) + investigator-selected TRUVADA™ or EPZICOM™/KIVEXA™ administered p.o., q.d. for 96 weeks in the Base Study. Eligible participants may continue in Study Extension 1 with open-label Doravirine 100 mg administered p.o., q.d. + investigator-selected TRUVADA™ or EPZICOM™/ KIVEXA™ administered p.o., q.d. for an additional 96 weeks. Eligible participants may continue to receive the same treatment regimen in Study Extension 2 until doravirine becomes locally available, or for an additional 96 weeks, whichever comes first. Double-blind Darunavir 800 mg and Ritonavir 100 mg administered p.o., q.d. + investigator-selected TRUVADA™ or EPZICOM™/ KIVEXA™ administered p.o., q.d. for 96 weeks. Eligible participants may continue in Study Extension 1 with open-label Doravirine 100 mg administered p.o., q.d. + investigator-selected TRUVADA™ or EPZICOM™/ KIVEXA™ administered p.o., q.d. for an additional 96 weeks. Eligible participants may continue to receive the same treatment regimen in Study Extension 2 until doravirine becomes locally available, or for an additional 96 weeks, whichever comes first.
Period Title: Base Study: 96 Weeks
Started 385 384
Treated 383 383
Completed 292 273
Not Completed 93 111
Reason Not Completed
Adverse Event             6             14
Death             3             1
Lack of Efficacy             21             32
Lost to Follow-up             28             24
Protocol Violation             1             6
Withdrawal by Subject             19             22
Noncompliance with drug             9             6
Physician Decision             2             4
Pregnancy             2             1
Randomized not treated             2             1
Period Title: Extension Study: up to 192 Weeks
Started 260 [1] 233 [1]
Completed 0 [2] 0 [2]
Not Completed 260 233
Reason Not Completed
Ongoing             260             233
[1]
The extension study is optional; not all eligible participants enrolled
[2]
The extension study is ongoing
Arm/Group Title Doravirine 100 mg Daurunavir 800 mg + Ritonavir 100 mg Total
Hide Arm/Group Description Double-blind Doravirine 100 mg administered orally (p.o.) once daily (q.d.) + investigator-selected TRUVADA™ or EPZICOM™/KIVEXA™ administered p.o., q.d. for 96 weeks in the Base Study. Double-blind Darunavir 800 mg and Ritonavir 100 mg administered p.o., q.d. + investigator-selected TRUVADA™ or EPZICOM™/ KIVEXA™ administered p.o., q.d. for 96 weeks in the Base Study. Total of all reporting groups
Overall Number of Baseline Participants 383 383 766
Hide Baseline Analysis Population Description
All participants who received at least 1 dose of study drug
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 383 participants 383 participants 766 participants
34.8  (10.5) 35.7  (10.7) 35.2  (10.6)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 383 participants 383 participants 766 participants
Female
64
  16.7%
57
  14.9%
121
  15.8%
Male
319
  83.3%
326
  85.1%
645
  84.2%
Mean Cluster of Differentiation 4 (CD4+) T-cell Count   [1] 
Mean (Standard Deviation)
Unit of measure:  Cells/mm^3
Number Analyzed 383 participants 383 participants 766 participants
432.6  (208.4) 411.9  (229.6) 422.2  (219.4)
[1]
Measure Description: CD4+ T-cell count was quantified by a central laboratory using a commercially available assay
Plasma HIV-1 RNA   [1] [2] 
Median (Full Range)
Unit of measure:  Copies/mL
Number Analyzed 383 participants 382 participants 765 participants
27073.0
(105 to 2776658)
27357.0
(235 to 3272236)
27073.0
(105 to 3272236)
[1]
Measure Description: Plasma HIV-1 RNA levels were quantified with the Abbott RealTime HIV-1 Assay
[2]
Measure Analysis Population Description: All participants who received at least 1 dose of study drug and had Baseline data available
1.Primary Outcome
Title Percentage of Participants Achieving Plasma HIV-1 RNA <50 Copies/mL at Week 48
Hide Description The percentage of participants in each arm achieving 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 and all missing data were considered treatment failures, regardless of the reason.
Time Frame Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study drug
Arm/Group Title Doravirine 100 mg Daurunavir 800 mg + Ritonavir 100 mg
Hide Arm/Group Description:
Double-blind Doravirine 100 mg administered orally (p.o.) once daily (q.d.) + investigator-selected TRUVADA™ or EPZICOM™/KIVEXA™ administered p.o., q.d. for 96 weeks in the Base Study.
Double-blind Darunavir 800 mg and Ritonavir 100 mg administered p.o., q.d. + investigator-selected TRUVADA™ or EPZICOM™/ KIVEXA™ administered p.o., q.d. for 96 weeks in the Base Study.
Overall Number of Participants Analyzed 383 383
Measure Type: Number
Unit of Measure: Percentage of participants
83.8 79.9
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Doravirine 100 mg, Daurunavir 800 mg + Ritonavir 100 mg
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Doravirine is concluded to be non-inferior to darunavir + ritonavir if the lower bound of the 95% CI for the difference in percent response is above -10 percentage points.
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value 3.913
Confidence Interval (2-Sided) 95%
-1.590 to 9.415
Estimation Comments Stratum-adjusted Mantel-Haenszel method with the difference weighted by the harmonic mean of sample size per arm for each stratum.
2.Secondary Outcome
Title Percentage of Participants Achieving Plasma HIV-1 RNA <50 Copies/mL at Week 96
Hide Description The percentage of participants in each arm achieving HIV-1 RNA levels <50 copies/mL at Week 96 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 96
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study drug and had data for the outcome measure. Participants with missing HIV-1 RNA due to an Abbott RealTime manufacturing agent recall were excluded from the analysis.
Arm/Group Title Doravirine 100 mg Daurunavir 800 mg + Ritonavir 100 mg
Hide Arm/Group Description:
Double-blind Doravirine 100 mg administered orally (p.o.) once daily (q.d.) + investigator-selected TRUVADA™ or EPZICOM™/KIVEXA™ administered p.o., q.d. for 96 weeks in the Base Study.
Double-blind Darunavir 800 mg and Ritonavir 100 mg administered p.o., q.d. + investigator-selected TRUVADA™ or EPZICOM™/ KIVEXA™ administered p.o., q.d. for 96 weeks in the Base Study.
Overall Number of Participants Analyzed 379 376
Measure Type: Number
Unit of Measure: Percentage of participants
73.1 66.0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Doravirine 100 mg, Daurunavir 800 mg + Ritonavir 100 mg
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Doravirine is concluded to be non-inferior to darunavir + ritonavir if the lower bound of the 95% CI for the difference in percent response is above -10 percentage points.
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value 7.082
Confidence Interval (2-Sided) 95%
0.508 to 13.656
Estimation Comments Stratum-adjusted Mantel-Haenszel method with the difference weighted by the harmonic mean of sample size per arm for each stratum.
3.Secondary Outcome
Title Change From Baseline in Mean CD4+ T-cell Count at Week 48
Hide Description CD4+ T-cell counts were quantified by a central laboratory using a commercially available assay.
Time Frame Baseline and Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study drug and had data for the outcome measure. Baseline values were carried forward for participants who discontinued therapy due to lack of efficacy.
Arm/Group Title Doravirine 100 mg Daurunavir 800 mg + Ritonavir 100 mg
Hide Arm/Group Description:
Double-blind Doravirine 100 mg administered orally (p.o.) once daily (q.d.) + investigator-selected TRUVADA™ or EPZICOM™/KIVEXA™ administered p.o., q.d. for 96 weeks in the Base Study.
Double-blind Darunavir 800 mg and Ritonavir 100 mg administered p.o., q.d. + investigator-selected TRUVADA™ or EPZICOM™/ KIVEXA™ administered p.o., q.d. for 96 weeks in the Base Study.
Overall Number of Participants Analyzed 363 353
Mean (95% Confidence Interval)
Unit of Measure: Cells/mm^3
192.7
(171.5 to 213.9)
185.6
(167.5 to 203.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Doravirine 100 mg, Daurunavir 800 mg + Ritonavir 100 mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean treatment difference
Estimated Value 7.1
Confidence Interval (2-Sided) 95%
-20.8 to 35.0
Estimation Comments Stratum-adjusted Mantel-Haenszel method with the difference weighted by the harmonic mean of sample size per arm for each stratum.
4.Secondary Outcome
Title Change From Baseline in Mean CD4+ T-cell Count at Week 96
Hide Description CD4+ T-cell counts were quantified by a central laboratory using a commercially available assay.
Time Frame Baseline and Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study drug and had data for the outcome measure. Baseline values were carried forward for participants who discontinued therapy due to lack of efficacy.
Arm/Group Title Doravirine 100 mg Daurunavir 800 mg + Ritonavir 100 mg
Hide Arm/Group Description:
Double-blind Doravirine 100 mg administered orally (p.o.) once daily (q.d.) + investigator-selected TRUVADA™ or EPZICOM™/KIVEXA™ administered p.o., q.d. for 96 weeks in the Base Study.
Double-blind Darunavir 800 mg and Ritonavir 100 mg administered p.o., q.d. + investigator-selected TRUVADA™ or EPZICOM™/ KIVEXA™ administered p.o., q.d. for 96 weeks in the Base Study.
Overall Number of Participants Analyzed 342 327
Mean (95% Confidence Interval)
Unit of Measure: Cells/mm^3
224.1
(200.8 to 247.4)
206.7
(184.9 to 228.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Doravirine 100 mg, Daurunavir 800 mg + Ritonavir 100 mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean treatment difference
Estimated Value 17.4
Confidence Interval (2-Sided) 95%
-14.5 to 49.3
Estimation Comments Stratum-adjusted Mantel-Haenszel method with the difference weighted by the harmonic mean of sample size per arm for each stratum.
5.Secondary Outcome
Title Mean Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 48
Hide Description Serum LDL-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 48
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 at the time point assessed.
Arm/Group Title Doravirine 100 mg Daurunavir 800 mg + Ritonavir 100 mg
Hide Arm/Group Description:
Double-blind Doravirine 100 mg administered orally (p.o.) once daily (q.d.) + investigator-selected TRUVADA™ or EPZICOM™/KIVEXA™ administered p.o., q.d. for 96 weeks in the Base Study.
Double-blind Darunavir 800 mg and Ritonavir 100 mg administered p.o., q.d. + investigator-selected TRUVADA™ or EPZICOM™/ KIVEXA™ administered p.o., q.d. for 96 weeks in the Base Study.
Overall Number of Participants Analyzed 326 318
Mean (Standard Deviation)
Unit of Measure: mg/dL
Baseline 91.10  (28.61) 91.76  (30.36)
Change from Baseline -4.51  (20.64) 9.92  (27.31)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Doravirine 100 mg, Daurunavir 800 mg + Ritonavir 100 mg
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 Terms for Baseline lipid level and treatment group
Method of Estimation Estimation Parameter Treatment Difference (mg/dL)
Estimated Value -14.61
Confidence Interval (2-Sided) 95%
-18.15 to -11.06
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Mean Change From Baseline in Fasting Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 48
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 LOCF approach was applied for missing data or data collected after modifying lipid-lowering therapy.
Time Frame Baseline and Week 48
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 at the time point assessed.
Arm/Group Title Doravirine 100 mg Daurunavir 800 mg + Ritonavir 100 mg
Hide Arm/Group Description:
Double-blind Doravirine 100 mg administered orally (p.o.) once daily (q.d.) + investigator-selected TRUVADA™ or EPZICOM™/KIVEXA™ administered p.o., q.d. for 96 weeks in the Base Study.
Double-blind Darunavir 800 mg and Ritonavir 100 mg administered p.o., q.d. + investigator-selected TRUVADA™ or EPZICOM™/ KIVEXA™ administered p.o., q.d. for 96 weeks in the Base Study.
Overall Number of Participants Analyzed 329 325
Mean (Standard Deviation)
Unit of Measure: mg/dL
Baseline 113.34  (34.25) 114.44  (35.01)
Change from Baseline -5.30  (23.28) 13.75  (31.08)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Doravirine 100 mg, Daurunavir 800 mg + Ritonavir 100 mg
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 Terms for Baseline lipid level and treatment group
Method of Estimation Estimation Parameter Treatment Difference (mg/dL)
Estimated Value -19.34
Confidence Interval (2-Sided) 95%
-23.33 to -15.35
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Mean Change From Baseline in Fasting High Density Lipoprotein Cholesterol (HDL-C) at Week 48
Hide Description Serum 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 LOCF approach was applied for missing data or data collected after modifying lipid-lowering therapy.
Time Frame Baseline and Week 48
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 at the time point assessed.
Arm/Group Title Doravirine 100 mg Daurunavir 800 mg + Ritonavir 100 mg
Hide Arm/Group Description:
Double-blind Doravirine 100 mg administered orally (p.o.) once daily (q.d.) + investigator-selected TRUVADA™ or EPZICOM™/KIVEXA™ administered p.o., q.d. for 96 weeks in the Base Study.
Double-blind Darunavir 800 mg and Ritonavir 100 mg administered p.o., q.d. + investigator-selected TRUVADA™ or EPZICOM™/ KIVEXA™ administered p.o., q.d. for 96 weeks in the Base Study.
Overall Number of Participants Analyzed 329 325
Mean (Standard Deviation)
Unit of Measure: mg/dL
Baseline 43.58  (12.99) 43.27  (13.96)
Change from Baseline 3.94  (10.66) 4.15  (11.01)
8.Secondary Outcome
Title Mean Change From Baseline in Fasting Total Cholesterol at Week 48
Hide Description Serum total cholesterol was determined after an overnight fast. Change from Baseline was analyzed using ANCOVA models with terms for Baseline lipid level and treatment group. The LOCF approach was applied for missing data or data collected after modifying lipid-lowering therapy.
Time Frame Baseline and Week 48
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 at the time point assessed.
Arm/Group Title Doravirine 100 mg Daurunavir 800 mg + Ritonavir 100 mg
Hide Arm/Group Description:
Double-blind Doravirine 100 mg administered orally (p.o.) once daily (q.d.) + investigator-selected TRUVADA™ or EPZICOM™/KIVEXA™ administered p.o., q.d. for 96 weeks in the Base Study.
Double-blind Darunavir 800 mg and Ritonavir 100 mg administered p.o., q.d. + investigator-selected TRUVADA™ or EPZICOM™/ KIVEXA™ administered p.o., q.d. for 96 weeks in the Base Study.
Overall Number of Participants Analyzed 329 325
Mean (Standard Deviation)
Unit of Measure: mg/dL
Baseline 156.92  (35.82) 157.71  (37.34)
Change from Baseline -1.37  (25.47) 17.90  (33.95)
9.Secondary Outcome
Title Mean Change From Baseline in Fasting Triglyceride at Week 48
Hide Description Serum triglyceride was determined after an overnight fast. Change from Baseline was analyzed using ANCOVA models with terms for Baseline lipid level and treatment group. The LOCF approach was applied for missing data or data collected after modifying lipid-lowering therapy.
Time Frame Baseline and Week 48
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 at the time point assessed.
Arm/Group Title Doravirine 100 mg Daurunavir 800 mg + Ritonavir 100 mg
Hide Arm/Group Description:
Double-blind Doravirine 100 mg administered orally (p.o.) once daily (q.d.) + investigator-selected TRUVADA™ or EPZICOM™/KIVEXA™ administered p.o., q.d. for 96 weeks in the Base Study.
Double-blind Darunavir 800 mg and Ritonavir 100 mg administered p.o., q.d. + investigator-selected TRUVADA™ or EPZICOM™/ KIVEXA™ administered p.o., q.d. for 96 weeks in the Base Study.
Overall Number of Participants Analyzed 329 325
Mean (Standard Deviation)
Unit of Measure: mg/dL
Baseline 111.16  (75.31) 117.02  (97.30)
Change from Baseline -3.14  (68.81) 21.97  (92.59)
10.Secondary Outcome
Title Percentage of Participants With Any Adverse Event
Hide Description An adverse event (AE) is defined as any untoward medical occurrence in a study participant and which does not necessarily have to have a causal relationship to treatment. An adverse event can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the study treatment or protocol-specified procedure, whether or not considered related to study treatment or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the study treatment is also an AE. The percentage of participants with any AE was assessed.
Time Frame Up to 98 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study drug
Arm/Group Title Doravirine 100 mg Daurunavir 800 mg + Ritonavir 100 mg
Hide Arm/Group Description:
Double-blind Doravirine 100 mg administered orally (p.o.) once daily (q.d.) + investigator-selected TRUVADA™ or EPZICOM™/KIVEXA™ administered p.o., q.d. for 96 weeks in the Base Study.
Double-blind Darunavir 800 mg and Ritonavir 100 mg administered p.o., q.d. + investigator-selected TRUVADA™ or EPZICOM™/ KIVEXA™ administered p.o., q.d. for 96 weeks in the Base Study.
Overall Number of Participants Analyzed 383 383
Measure Type: Number
Unit of Measure: Percentage of Participants
84.6 82.8
11.Secondary Outcome
Title Percentage of Participants With Any Serious Adverse Event
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 98 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study drug
Arm/Group Title Doravirine 100 mg Daurunavir 800 mg + Ritonavir 100 mg
Hide Arm/Group Description:
Double-blind Doravirine 100 mg administered orally (p.o.) once daily (q.d.) + investigator-selected TRUVADA™ or EPZICOM™/KIVEXA™ administered p.o., q.d. for 96 weeks in the Base Study.
Double-blind Darunavir 800 mg and Ritonavir 100 mg administered p.o., q.d. + investigator-selected TRUVADA™ or EPZICOM™/ KIVEXA™ administered p.o., q.d. for 96 weeks in the Base Study.
Overall Number of Participants Analyzed 383 383
Measure Type: Number
Unit of Measure: Percentage of Participants
7.0 8.6
12.Secondary Outcome
Title Percentage of Participants With Any Drug-related Adverse Event
Hide Description The investigator was to determine if an AE had a reasonable possibility of a relationship to the study drug. The percentage of participants with any drug-related AE was assessed.
Time Frame Up to 98 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study drug
Arm/Group Title Doravirine 100 mg Daurunavir 800 mg + Ritonavir 100 mg
Hide Arm/Group Description:
Double-blind Doravirine 100 mg administered orally (p.o.) once daily (q.d.) + investigator-selected TRUVADA™ or EPZICOM™/KIVEXA™ administered p.o., q.d. for 96 weeks in the Base Study.
Double-blind Darunavir 800 mg and Ritonavir 100 mg administered p.o., q.d. + investigator-selected TRUVADA™ or EPZICOM™/ KIVEXA™ administered p.o., q.d. for 96 weeks in the Base Study.
Overall Number of Participants Analyzed 383 383
Measure Type: Number
Unit of Measure: Percentage of Participants
32.1 32.1
13.Secondary Outcome
Title Percentage of Participants With Any Drug-related Serious Adverse Event
Hide Description The percentage of participants with any drug-related SAE was assessed.
Time Frame Up to 98 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study drug
Arm/Group Title Doravirine 100 mg Daurunavir 800 mg + Ritonavir 100 mg
Hide Arm/Group Description:
Double-blind Doravirine 100 mg administered orally (p.o.) once daily (q.d.) + investigator-selected TRUVADA™ or EPZICOM™/KIVEXA™ administered p.o., q.d. for 96 weeks in the Base Study.
Double-blind Darunavir 800 mg and Ritonavir 100 mg administered p.o., q.d. + investigator-selected TRUVADA™ or EPZICOM™/ KIVEXA™ administered p.o., q.d. for 96 weeks in the Base Study.
Overall Number of Participants Analyzed 383 383
Measure Type: Number
Unit of Measure: Percentage of Participants
0.3 0.3
14.Secondary Outcome
Title Percentage of Participants Who Discontinued Study Treatment Due to an Adverse Event
Hide Description The percentage of participants who discontinued study treatment due to an AE was assessed.
Time Frame Up to 96 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study drug
Arm/Group Title Doravirine 100 mg Daurunavir 800 mg + Ritonavir 100 mg
Hide Arm/Group Description:
Double-blind Doravirine 100 mg administered orally (p.o.) once daily (q.d.) + investigator-selected TRUVADA™ or EPZICOM™/KIVEXA™ administered p.o., q.d. for 96 weeks in the Base Study.
Double-blind Darunavir 800 mg and Ritonavir 100 mg administered p.o., q.d. + investigator-selected TRUVADA™ or EPZICOM™/ KIVEXA™ administered p.o., q.d. for 96 weeks in the Base Study.
Overall Number of Participants Analyzed 383 383
Measure Type: Number
Unit of Measure: Percentage of Participants
1.6 3.4
15.Secondary Outcome
Title Percentage of Participants Achieving Plasma HIV-1 RNA <40 Copies/mL at Week 48
Hide Description The percentage of participants in each arm achieving HIV-1 RNA levels <40 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 and all missing data were considered treatment failures, regardless of the reason.
Time Frame Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study drug
Arm/Group Title Doravirine 100 mg Daurunavir 800 mg + Ritonavir 100 mg
Hide Arm/Group Description:
Double-blind Doravirine 100 mg administered orally (p.o.) once daily (q.d.) + investigator-selected TRUVADA™ or EPZICOM™/KIVEXA™ administered p.o., q.d. for 96 weeks in the Base Study.
Double-blind Darunavir 800 mg and Ritonavir 100 mg administered p.o., q.d. + investigator-selected TRUVADA™ or EPZICOM™/ KIVEXA™ administered p.o., q.d. for 96 weeks in the Base Study.
Overall Number of Participants Analyzed 383 383
Measure Type: Number
Unit of Measure: Percentage of participants
83.3 79.1
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Doravirine 100 mg, Daurunavir 800 mg + Ritonavir 100 mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value 4.169
Confidence Interval (2-Sided) 95%
-1.404 to 9.743
Estimation Comments Stratum-adjusted Mantel-Haenszel method with the difference weighted by the harmonic mean of sample size per arm for each stratum.
16.Secondary Outcome
Title Percentage of Participants Achieving Plasma HIV-1 RNA <40 Copies/mL at Week 96
Hide Description The percentage of participants in each arm achieving HIV-1 RNA levels <40 copies/mL at Week 96 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 96
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study drug and had data for the outcome measure. Participants with missing HIV-1 RNA due to an Abbott RealTime manufacturing agent recall were excluded from the analysis.
Arm/Group Title Doravirine 100 mg Daurunavir 800 mg + Ritonavir 100 mg
Hide Arm/Group Description:
Double-blind Doravirine 100 mg administered orally (p.o.) once daily (q.d.) + investigator-selected TRUVADA™ or EPZICOM™/KIVEXA™ administered p.o., q.d. for 96 weeks in the Base Study.
Double-blind Darunavir 800 mg and Ritonavir 100 mg administered p.o., q.d. + investigator-selected TRUVADA™ or EPZICOM™/ KIVEXA™ administered p.o., q.d. for 96 weeks in the Base Study.
Overall Number of Participants Analyzed 379 376
Measure Type: Number
Unit of Measure: Percentage of participants
72.0 64.4
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Doravirine 100 mg, Daurunavir 800 mg + Ritonavir 100 mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value 7.606
Confidence Interval (2-Sided) 95%
0.980 to 14.232
Estimation Comments Stratum-adjusted Mantel-Haenszel method with the difference weighted by the harmonic mean of sample size per arm for each stratum.
Time Frame Up to Week 98
Adverse Event Reporting Description The at-risk population is all participants who received at least 1 dose of study drug
 
Arm/Group Title Doravirine 100 mg Daurunavir 800 mg + Ritonavir 100 mg
Hide Arm/Group Description Double-blind Doravirine 100 mg administered orally (p.o.) once daily (q.d.) + investigator-selected TRUVADA™ or EPZICOM™/KIVEXA™ administered p.o., q.d. for 96 weeks in the Base Study. Double-blind Darunavir 800 mg and Ritonavir 100 mg administered p.o., q.d. + investigator-selected TRUVADA™ or EPZICOM™/ KIVEXA™ administered p.o., q.d. for 96 weeks in the Base Study.
All-Cause Mortality
Doravirine 100 mg Daurunavir 800 mg + Ritonavir 100 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   3/383 (0.78%)      1/383 (0.26%)    
Show Serious Adverse Events Hide Serious Adverse Events
Doravirine 100 mg Daurunavir 800 mg + Ritonavir 100 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   27/383 (7.05%)      33/383 (8.62%)    
Ear and labyrinth disorders     
Vertigo  1  0/383 (0.00%)  0 1/383 (0.26%)  1
Gastrointestinal disorders     
Abdominal distension  1  0/383 (0.00%)  0 1/383 (0.26%)  1
Abdominal pain  1  0/383 (0.00%)  0 1/383 (0.26%)  1
Anal fistula  1  1/383 (0.26%)  1 1/383 (0.26%)  1
Anal skin tags  1  1/383 (0.26%)  1 0/383 (0.00%)  0
Colitis  1  1/383 (0.26%)  1 0/383 (0.00%)  0
Inguinal hernia  1  0/383 (0.00%)  0 1/383 (0.26%)  1
Nausea  1  1/383 (0.26%)  1 0/383 (0.00%)  0
Vomiting  1  1/383 (0.26%)  1 0/383 (0.00%)  0
General disorders     
Death  1  1/383 (0.26%)  1 0/383 (0.00%)  0
Non-cardiac chest pain  1  0/383 (0.00%)  0 1/383 (0.26%)  5
Oedema peripheral  1  0/383 (0.00%)  0 1/383 (0.26%)  1
Hepatobiliary disorders     
Cholecystitis acute  1  1/383 (0.26%)  1 0/383 (0.00%)  0
Infections and infestations     
Abdominal abscess  1  1/383 (0.26%)  1 0/383 (0.00%)  0
Acute hepatitis C  1  1/383 (0.26%)  1 0/383 (0.00%)  0
Acute sinusitis  1  0/383 (0.00%)  0 1/383 (0.26%)  1
Appendicitis  1  1/383 (0.26%)  1 0/383 (0.00%)  0
Atypical pneumonia  1  0/383 (0.00%)  0 1/383 (0.26%)  1
Bronchitis  1  0/383 (0.00%)  0 1/383 (0.26%)  1
Cellulitis  1  0/383 (0.00%)  0 1/383 (0.26%)  1
Cellulitis staphylococcal  1  1/383 (0.26%)  1 0/383 (0.00%)  0
Gastroenteritis  1  1/383 (0.26%)  1 0/383 (0.00%)  0
Influenza  1  0/383 (0.00%)  0 1/383 (0.26%)  1
Meningitis tuberculous  1  0/383 (0.00%)  0 1/383 (0.26%)  1
Necrotising fasciitis  1  1/383 (0.26%)  1 0/383 (0.00%)  0
Neurosyphilis  1  1/383 (0.26%)  1 0/383 (0.00%)  0
Orchitis  1  0/383 (0.00%)  0 1/383 (0.26%)  1
Parotitis  1  1/383 (0.26%)  1 0/383 (0.00%)  0
Perirectal abscess  1  1/383 (0.26%)  1 0/383 (0.00%)  0
Pharyngitis  1  0/383 (0.00%)  0 1/383 (0.26%)  1
Pneumonia  1  1/383 (0.26%)  1 1/383 (0.26%)  1
Post procedural infection  1  0/383 (0.00%)  0 2/383 (0.52%)  2
Scrotal abscess  1  0/383 (0.00%)  0 1/383 (0.26%)  1
Tuberculosis  1  0/383 (0.00%)  0 2/383 (0.52%)  2
Tuberculosis of central nervous system  1  0/383 (0.00%)  0 1/383 (0.26%)  1
Injury, poisoning and procedural complications     
Accidental overdose  1  0/383 (0.00%)  0 1/383 (0.26%)  1
Carbon monoxide poisoning  1  1/383 (0.26%)  1 0/383 (0.00%)  0
Femur fracture  1  1/383 (0.26%)  1 0/383 (0.00%)  0
Post procedural haemorrhage  1  0/383 (0.00%)  0 2/383 (0.52%)  2
Rectal injury  1  0/383 (0.00%)  0 1/383 (0.26%)  1
Subdural haematoma  1  0/383 (0.00%)  0 1/383 (0.26%)  1
Traumatic intracranial haemorrhage  1  0/383 (0.00%)  0 1/383 (0.26%)  1
Wrist fracture  1  1/383 (0.26%)  1 0/383 (0.00%)  0
Metabolism and nutrition disorders     
Hyponatraemia  1  0/383 (0.00%)  0 1/383 (0.26%)  1
Hypovolaemia  1  1/383 (0.26%)  1 0/383 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Back pain  1  0/383 (0.00%)  0 2/383 (0.52%)  2
Intervertebral disc protrusion  1  1/383 (0.26%)  1 0/383 (0.00%)  0
Muscular weakness  1  1/383 (0.26%)  1 0/383 (0.00%)  0
Rhabdomyolysis  1  0/383 (0.00%)  0 1/383 (0.26%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Anal squamous cell carcinoma  1  0/383 (0.00%)  0 1/383 (0.26%)  1
Pancreatic carcinoma  1  0/383 (0.00%)  0 1/383 (0.26%)  1
Prostate cancer  1  1/383 (0.26%)  1 0/383 (0.00%)  0
Squamous cell carcinoma  1  1/383 (0.26%)  1 0/383 (0.00%)  0
Squamous cell carcinoma of skin  1  0/383 (0.00%)  0 1/383 (0.26%)  1
Nervous system disorders     
Aphasia  1  0/383 (0.00%)  0 1/383 (0.26%)  1
Cerebrovascular accident  1  1/383 (0.26%)  1 0/383 (0.00%)  0
Facial paralysis  1  0/383 (0.00%)  0 1/383 (0.26%)  1
Hemiparesis  1  1/383 (0.26%)  1 0/383 (0.00%)  0
Hypoaesthesia  1  1/383 (0.26%)  1 0/383 (0.00%)  0
Osmotic demyelination syndrome  1  0/383 (0.00%)  0 1/383 (0.26%)  1
Syncope  1  0/383 (0.00%)  0 1/383 (0.26%)  1
Pregnancy, puerperium and perinatal conditions     
Post abortion haemorrhage  1  1/383 (0.26%)  1 0/383 (0.00%)  0
Psychiatric disorders     
Depression  1  0/383 (0.00%)  0 1/383 (0.26%)  1
Psychotic disorder  1  1/383 (0.26%)  1 0/383 (0.00%)  0
Schizoaffective disorder depressive type  1  0/383 (0.00%)  0 1/383 (0.26%)  1
Substance-induced mood disorder  1  1/383 (0.26%)  1 0/383 (0.00%)  0
Renal and urinary disorders     
Acute kidney injury  1  1/383 (0.26%)  1 0/383 (0.00%)  0
Nephrolithiasis  1  0/383 (0.00%)  0 1/383 (0.26%)  1
Respiratory, thoracic and mediastinal disorders     
Asthma  1  1/383 (0.26%)  1 0/383 (0.00%)  0
Bronchospasm  1  0/383 (0.00%)  0 1/383 (0.26%)  1
Chronic obstructive pulmonary disease  1  0/383 (0.00%)  0 1/383 (0.26%)  2
Pulmonary embolism  1  0/383 (0.00%)  0 1/383 (0.26%)  1
Stridor  1  0/383 (0.00%)  0 1/383 (0.26%)  1
Social circumstances     
Drug abuser  1  1/383 (0.26%)  1 0/383 (0.00%)  0
Vascular disorders     
Deep vein thrombosis  1  1/383 (0.26%)  1 0/383 (0.00%)  0
1
Term from vocabulary, MedDRA 20.0
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%
Doravirine 100 mg Daurunavir 800 mg + Ritonavir 100 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   228/383 (59.53%)      216/383 (56.40%)    
Gastrointestinal disorders     
Abdominal pain upper  1  20/383 (5.22%)  23 13/383 (3.39%)  13
Diarrhoea  1  65/383 (16.97%)  74 91/383 (23.76%)  120
Nausea  1  44/383 (11.49%)  53 52/383 (13.58%)  59
General disorders     
Fatigue  1  34/383 (8.88%)  36 23/383 (6.01%)  25
Infections and infestations     
Bronchitis  1  23/383 (6.01%)  27 28/383 (7.31%)  30
Syphilis  1  22/383 (5.74%)  27 23/383 (6.01%)  26
Upper respiratory tract infection  1  51/383 (13.32%)  74 30/383 (7.83%)  43
Viral upper respiratory tract infection  1  44/383 (11.49%)  61 50/383 (13.05%)  70
Musculoskeletal and connective tissue disorders     
Back pain  1  28/383 (7.31%)  29 10/383 (2.61%)  11
Nervous system disorders     
Dizziness  1  20/383 (5.22%)  23 19/383 (4.96%)  20
Headache  1  57/383 (14.88%)  86 46/383 (12.01%)  68
Psychiatric disorders     
Insomnia  1  18/383 (4.70%)  18 20/383 (5.22%)  22
Respiratory, thoracic and mediastinal disorders     
Cough  1  23/383 (6.01%)  28 10/383 (2.61%)  10
1
Term from vocabulary, MedDRA 20.0
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 trial 45 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results. 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: NCT02275780     History of Changes
Other Study ID Numbers: 1439-018
2014-001127-69 ( EudraCT Number )
DRIVE-FORWARD ( Other Identifier: Merck Sharp & Dohme Corp. )
MK-1439-018 ( Other Identifier: Merck Protocol Number )
First Submitted: October 23, 2014
First Posted: October 27, 2014
Results First Submitted: September 28, 2018
Results First Posted: October 23, 2018
Last Update Posted: October 23, 2018