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

• Sponsor: Merck Sharp & Dohme LLC (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT02275780
• Collaborator: (none)
• Enrollment: 769
• Arms: 2
• Anticipated Duration (Months): 99.4

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
HIV-1	Drug: Doravirine; Drug: Darunavir; Drug: Ritonavir; Drug: TRUVADA™ or EPZICOM™/KIVEXA™	Phase 3

Detailed Description

Participants in Australia, Russia, and South Africa who are deriving benefit from MK-1439A are also eligible to continue receiving study drug during Study Extension 3, which will last for 2 years or until drug is available locally, whichever comes first.

Study Design

• Study Type: Interventional
• Actual Enrollment: 769 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 3 Multicenter, Double-Blind, Randomized, Active Comparator-Controlled Clinical Trial to Evaluate the Safety and Efficacy of Doravirine (MK-1439) 100 mg Once Daily Versus Darunavir 800 mg Once Daily Plus Ritonavir 100 mg Once Daily, Each in Combination With TRUVADA™ or EPZICOM™/KIVEXA™, in Treatment-Naïve HIV-1 Infected Subjects
• Actual Study Start Date: Dec 1, 2014
• Actual Primary Completion Date: Sep 29, 2016
• Anticipated Study Completion Date: Mar 16, 2023

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Achieving Plasma HIV-1 RNA <50 Copies/mL at Week 48 [Week 48]

   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.

Secondary Outcome Measures

1. Percentage of Participants Achieving Plasma HIV-1 RNA <50 Copies/mL at Week 96 [Week 96]

   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.

2. Change From Baseline in Mean CD4+ T-cell Count at Week 48 [Baseline and Week 48]

   CD4+ T-cell counts were quantified by a central laboratory using a commercially available assay.

3. Change From Baseline in Mean CD4+ T-cell Count at Week 96 [Baseline and Week 96]

   CD4+ T-cell counts were quantified by a central laboratory using a commercially available assay.

4. Mean Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 48 [Baseline and Week 48]

   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.

5. Mean Change From Baseline in Fasting Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 48 [Baseline and Week 48]

   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.

6. Mean Change From Baseline in Fasting High Density Lipoprotein Cholesterol (HDL-C) at Week 48 [Baseline and Week 48]

   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.

7. Mean Change From Baseline in Fasting Total Cholesterol at Week 48 [Baseline and Week 48]

   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.

8. Mean Change From Baseline in Fasting Triglyceride at Week 48 [Baseline and Week 48]

   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.

9. Percentage of Participants With Any Adverse Event [Up to 98 weeks]

   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.

10. Percentage of Participants With Any Serious Adverse Event [Up to 98 weeks]

    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.

11. Percentage of Participants With Any Drug-related Adverse Event [Up to 98 weeks]

    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.

12. Percentage of Participants With Any Drug-related Serious Adverse Event [Up to 98 weeks]

    The percentage of participants with any drug-related SAE was assessed.

13. Percentage of Participants Who Discontinued Study Treatment Due to an Adverse Event [Up to 96 weeks]

    The percentage of participants who discontinued study treatment due to an AE was assessed.

14. Percentage of Participants Achieving Plasma HIV-1 RNA <40 Copies/mL at Week 48 [Week 48]

    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.

15. Percentage of Participants Achieving Plasma HIV-1 RNA <40 Copies/mL at Week 96 [Week 96]

    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.

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 and has HIV treatment indicated based on physician assessment.

• Has received no (0 days of) antiretroviral therapy (ART), including investigational antiretroviral agents.

• Is considered clinically stable with no signs or symptoms of active infection for at least 2 weeks prior to the start of treatment.

• Female is highly unlikely to become pregnant, or male is highly unlikely to impregnate a partner because they are not of reproductive potential, or agree to practice abstinence or use acceptable contraception for up to 14 days after the last dose of study drug.

• Eligibility for the Study Extension 1 at the Week 96 visit: 1) completed the Week 96 visit, 2) derived benefit from participation through Week 96 in the opinion of the investigator, 3) is a clinically-appropriate candidate for an additional 96 weeks of treatment with the Study Extension regimen.

• Eligibility for the Study Extension 2 at the Week 192 visit: 1) completed the Week 192 visit, 2) derived benefit from participation through Week 192 in the opinion of the investigator, 3) is a clinically-appropriate candidate for 96 weeks of treatment with the Study Extension regimen.

Exclusion Criteria:

• Uses or has had a recent history of using recreational or illicit drugs.

• Has been treated for a viral infection other than HIV-1, such as hepatitis B, with an agent that is active against HIV-1.

• Has documented or known resistance to study drugs including doravirine, darunavir, ritonavir, emtricitabine, tenofovir, abacavir and/or lamivudine.

• Has participated in a study with an investigational compound/device within the prior month, or anticipates doing so during this study.

• Has used systemic immunosuppressive therapy or immune modulators within the prior 30 days, or anticipates doing so during this study.

• Has significant hypersensitivity or other contraindication to any of the components of the study drugs.

• Has a current (active) diagnosis of acute hepatitis due to any cause.

• Is pregnant, breastfeeding or expecting to conceive at any time during the study.

• Female who expects to donate eggs, or male who expects to donate sperm at any time during the study.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Merck Sharp & Dohme LLC

Investigators

• Study Director: Medical Director, Merck Sharp & Dohme LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT02275780
• Other Study ID Numbers: 1439-018; MK-1439-018; 2014-001127-69
• First Posted: Oct 27, 2014
• 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: Ritonavir; Darunavir; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination

Study Results

Participant Flow

Pre-assignment Detail	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
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
Period Title: Base Study: 96 Weeks
STARTED	260	233
COMPLETED	0	0
NOT COMPLETED	260	233

Baseline Characteristics

Arm/Group Title	Doravirine 100 mg	Daurunavir 800 mg + Ritonavir 100 mg	Total
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 Participants	383	383	766
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	34.8 (10.5)	35.7 (10.7)	35.2 (10.6)
Sex: Female, Male (Count of 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 (Cells/mm^3) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Cells/mm^3]	432.6 (208.4)	411.9 (229.6)	422.2 (219.4)
Plasma HIV-1 RNA (Copies/mL) [Median (Full Range) ]
Median (Full Range) [Copies/mL]	27073.0	27357.0	27073.0

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Achieving Plasma HIV-1 RNA <50 Copies/mL at Week 48
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

Outcome Measure Data

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
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.
Measure Participants	383	383
Number [Percentage of participants]	83.8 21.9%	79.9 20.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Doravirine 100 mg, Daurunavir 800 mg + Ritonavir 100 mg
	Comments
	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.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment Difference
	Estimated Value	3.913
	Confidence Interval	(2-Sided) 95%; -1.590 to 9.415
	Parameter Dispersion	Type: Value:
	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
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

Outcome Measure Data

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
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.
Measure Participants	379	376
Number [Percentage of participants]	73.1 19.1%	66.0 17.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Doravirine 100 mg, Daurunavir 800 mg + Ritonavir 100 mg
	Comments
	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.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment Difference
	Estimated Value	7.082
	Confidence Interval	(2-Sided) 95%; 0.508 to 13.656
	Parameter Dispersion	Type: Value:
	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
Description	CD4+ T-cell counts were quantified by a central laboratory using a commercially available assay.
Time Frame	Baseline and Week 48

Outcome Measure Data

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
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.
Measure Participants	363	353
Mean (95% Confidence Interval) [Cells/mm^3]	192.7	185.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Doravirine 100 mg, Daurunavir 800 mg + Ritonavir 100 mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean treatment difference
	Estimated Value	7.1
	Confidence Interval	(2-Sided) 95%; -20.8 to 35.0
	Parameter Dispersion	Type: Value:
	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
Description	CD4+ T-cell counts were quantified by a central laboratory using a commercially available assay.
Time Frame	Baseline and Week 96

Outcome Measure Data

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
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.
Measure Participants	342	327
Mean (95% Confidence Interval) [Cells/mm^3]	224.1	206.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Doravirine 100 mg, Daurunavir 800 mg + Ritonavir 100 mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean treatment difference
	Estimated Value	17.4
	Confidence Interval	(2-Sided) 95%; -14.5 to 49.3
	Parameter Dispersion	Type: Value:
	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
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

Outcome Measure Data

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
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.
Measure Participants	326	318
Baseline	91.10 (28.61)	91.76 (30.36)
Change from Baseline	-4.51 (20.64)	9.92 (27.31)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Doravirine 100 mg, Daurunavir 800 mg + Ritonavir 100 mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	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
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Mean Change From Baseline in Fasting Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 48
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

Outcome Measure Data

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
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.
Measure Participants	329	325
Baseline	113.34 (34.25)	114.44 (35.01)
Change from Baseline	-5.30 (23.28)	13.75 (31.08)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Doravirine 100 mg, Daurunavir 800 mg + Ritonavir 100 mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	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
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Mean Change From Baseline in Fasting High Density Lipoprotein Cholesterol (HDL-C) at Week 48
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

Outcome Measure Data

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
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.
Measure Participants	329	325
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
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

Outcome Measure Data

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
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.
Measure Participants	329	325
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
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

Outcome Measure Data

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
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.
Measure Participants	329	325
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
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

Outcome Measure Data

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
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.
Measure Participants	383	383
Number [Percentage of Participants]	84.6 22.1%	82.8 21.6%

11. Secondary Outcome

Title	Percentage of Participants With Any Serious Adverse Event
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

Outcome Measure Data

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
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.
Measure Participants	383	383
Number [Percentage of Participants]	7.0 1.8%	8.6 2.2%

12. Secondary Outcome

Title	Percentage of Participants With Any Drug-related Adverse Event
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

Outcome Measure Data

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
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.
Measure Participants	383	383
Number [Percentage of Participants]	32.1 8.4%	32.1 8.4%

13. Secondary Outcome

Title	Percentage of Participants With Any Drug-related Serious Adverse Event
Description	The percentage of participants with any drug-related SAE was assessed.
Time Frame	Up to 98 weeks

Outcome Measure Data

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
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.
Measure Participants	383	383
Number [Percentage of Participants]	0.3 0.1%	0.3 0.1%

14. Secondary Outcome

Title	Percentage of Participants Who Discontinued Study Treatment Due to an Adverse Event
Description	The percentage of participants who discontinued study treatment due to an AE was assessed.
Time Frame	Up to 96 weeks

Outcome Measure Data

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
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.
Measure Participants	383	383
Number [Percentage of Participants]	1.6 0.4%	3.4 0.9%

15. Secondary Outcome

Title	Percentage of Participants Achieving Plasma HIV-1 RNA <40 Copies/mL at Week 48
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

Outcome Measure Data

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
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.
Measure Participants	383	383
Number [Percentage of participants]	83.3 21.7%	79.1 20.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Doravirine 100 mg, Daurunavir 800 mg + Ritonavir 100 mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment Difference
	Estimated Value	4.169
	Confidence Interval	(2-Sided) 95%; -1.404 to 9.743
	Parameter Dispersion	Type: Value:
	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
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

Outcome Measure Data

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
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.
Measure Participants	379	376
Number [Percentage of participants]	72.0 18.8%	64.4 16.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Doravirine 100 mg, Daurunavir 800 mg + Ritonavir 100 mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment Difference
	Estimated Value	7.606
	Confidence Interval	(2-Sided) 95%; 0.980 to 14.232
	Parameter Dispersion	Type: Value:
	Estimation Comments	Stratum-adjusted Mantel-Haenszel method with the difference weighted by the harmonic mean of sample size per arm for each stratum.

Adverse Events

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
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 (%)	# Events	Affected / at Risk (%)	# Events
Total	3/383 (0.8%)		1/383 (0.3%)
Serious Adverse Events
	Doravirine 100 mg		Daurunavir 800 mg + Ritonavir 100 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	27/383 (7%)		33/383 (8.6%)
Ear and labyrinth disorders
Vertigo	0/383 (0%)	0	1/383 (0.3%)	1
Gastrointestinal disorders
Abdominal distension	0/383 (0%)	0	1/383 (0.3%)	1
Abdominal pain	0/383 (0%)	0	1/383 (0.3%)	1
Anal fistula	1/383 (0.3%)	1	1/383 (0.3%)	1
Anal skin tags	1/383 (0.3%)	1	0/383 (0%)	0
Colitis	1/383 (0.3%)	1	0/383 (0%)	0
Inguinal hernia	0/383 (0%)	0	1/383 (0.3%)	1
Nausea	1/383 (0.3%)	1	0/383 (0%)	0
Vomiting	1/383 (0.3%)	1	0/383 (0%)	0
General disorders
Death	1/383 (0.3%)	1	0/383 (0%)	0
Non-cardiac chest pain	0/383 (0%)	0	1/383 (0.3%)	5
Oedema peripheral	0/383 (0%)	0	1/383 (0.3%)	1
Hepatobiliary disorders
Cholecystitis acute	1/383 (0.3%)	1	0/383 (0%)	0
Infections and infestations
Abdominal abscess	1/383 (0.3%)	1	0/383 (0%)	0
Acute hepatitis C	1/383 (0.3%)	1	0/383 (0%)	0
Acute sinusitis	0/383 (0%)	0	1/383 (0.3%)	1
Appendicitis	1/383 (0.3%)	1	0/383 (0%)	0
Atypical pneumonia	0/383 (0%)	0	1/383 (0.3%)	1
Bronchitis	0/383 (0%)	0	1/383 (0.3%)	1
Cellulitis	0/383 (0%)	0	1/383 (0.3%)	1
Cellulitis staphylococcal	1/383 (0.3%)	1	0/383 (0%)	0
Gastroenteritis	1/383 (0.3%)	1	0/383 (0%)	0
Influenza	0/383 (0%)	0	1/383 (0.3%)	1
Meningitis tuberculous	0/383 (0%)	0	1/383 (0.3%)	1
Necrotising fasciitis	1/383 (0.3%)	1	0/383 (0%)	0
Neurosyphilis	1/383 (0.3%)	1	0/383 (0%)	0
Orchitis	0/383 (0%)	0	1/383 (0.3%)	1
Parotitis	1/383 (0.3%)	1	0/383 (0%)	0
Perirectal abscess	1/383 (0.3%)	1	0/383 (0%)	0
Pharyngitis	0/383 (0%)	0	1/383 (0.3%)	1
Pneumonia	1/383 (0.3%)	1	1/383 (0.3%)	1
Post procedural infection	0/383 (0%)	0	2/383 (0.5%)	2
Scrotal abscess	0/383 (0%)	0	1/383 (0.3%)	1
Tuberculosis	0/383 (0%)	0	2/383 (0.5%)	2
Tuberculosis of central nervous system	0/383 (0%)	0	1/383 (0.3%)	1
Injury, poisoning and procedural complications
Accidental overdose	0/383 (0%)	0	1/383 (0.3%)	1
Carbon monoxide poisoning	1/383 (0.3%)	1	0/383 (0%)	0
Femur fracture	1/383 (0.3%)	1	0/383 (0%)	0
Post procedural haemorrhage	0/383 (0%)	0	2/383 (0.5%)	2
Rectal injury	0/383 (0%)	0	1/383 (0.3%)	1
Subdural haematoma	0/383 (0%)	0	1/383 (0.3%)	1
Traumatic intracranial haemorrhage	0/383 (0%)	0	1/383 (0.3%)	1
Wrist fracture	1/383 (0.3%)	1	0/383 (0%)	0
Metabolism and nutrition disorders
Hyponatraemia	0/383 (0%)	0	1/383 (0.3%)	1
Hypovolaemia	1/383 (0.3%)	1	0/383 (0%)	0
Musculoskeletal and connective tissue disorders
Back pain	0/383 (0%)	0	2/383 (0.5%)	2
Intervertebral disc protrusion	1/383 (0.3%)	1	0/383 (0%)	0
Muscular weakness	1/383 (0.3%)	1	0/383 (0%)	0
Rhabdomyolysis	0/383 (0%)	0	1/383 (0.3%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Anal squamous cell carcinoma	0/383 (0%)	0	1/383 (0.3%)	1
Pancreatic carcinoma	0/383 (0%)	0	1/383 (0.3%)	1
Prostate cancer	1/383 (0.3%)	1	0/383 (0%)	0
Squamous cell carcinoma	1/383 (0.3%)	1	0/383 (0%)	0
Squamous cell carcinoma of skin	0/383 (0%)	0	1/383 (0.3%)	1
Nervous system disorders
Aphasia	0/383 (0%)	0	1/383 (0.3%)	1
Cerebrovascular accident	1/383 (0.3%)	1	0/383 (0%)	0
Facial paralysis	0/383 (0%)	0	1/383 (0.3%)	1
Hemiparesis	1/383 (0.3%)	1	0/383 (0%)	0
Hypoaesthesia	1/383 (0.3%)	1	0/383 (0%)	0
Osmotic demyelination syndrome	0/383 (0%)	0	1/383 (0.3%)	1
Syncope	0/383 (0%)	0	1/383 (0.3%)	1
Pregnancy, puerperium and perinatal conditions
Post abortion haemorrhage	1/383 (0.3%)	1	0/383 (0%)	0
Psychiatric disorders
Depression	0/383 (0%)	0	1/383 (0.3%)	1
Psychotic disorder	1/383 (0.3%)	1	0/383 (0%)	0
Schizoaffective disorder depressive type	0/383 (0%)	0	1/383 (0.3%)	1
Substance-induced mood disorder	1/383 (0.3%)	1	0/383 (0%)	0
Renal and urinary disorders
Acute kidney injury	1/383 (0.3%)	1	0/383 (0%)	0
Nephrolithiasis	0/383 (0%)	0	1/383 (0.3%)	1
Respiratory, thoracic and mediastinal disorders
Asthma	1/383 (0.3%)	1	0/383 (0%)	0
Bronchospasm	0/383 (0%)	0	1/383 (0.3%)	1
Chronic obstructive pulmonary disease	0/383 (0%)	0	1/383 (0.3%)	2
Pulmonary embolism	0/383 (0%)	0	1/383 (0.3%)	1
Stridor	0/383 (0%)	0	1/383 (0.3%)	1
Social circumstances
Drug abuser	1/383 (0.3%)	1	0/383 (0%)	0
Vascular disorders
Deep vein thrombosis	1/383 (0.3%)	1	0/383 (0%)	0
Other (Not Including Serious) Adverse Events
	Doravirine 100 mg		Daurunavir 800 mg + Ritonavir 100 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	228/383 (59.5%)		216/383 (56.4%)
Gastrointestinal disorders
Abdominal pain upper	20/383 (5.2%)	23	13/383 (3.4%)	13
Diarrhoea	65/383 (17%)	74	91/383 (23.8%)	120
Nausea	44/383 (11.5%)	53	52/383 (13.6%)	59
General disorders
Fatigue	34/383 (8.9%)	36	23/383 (6%)	25
Infections and infestations
Bronchitis	23/383 (6%)	27	28/383 (7.3%)	30
Syphilis	22/383 (5.7%)	27	23/383 (6%)	26
Upper respiratory tract infection	51/383 (13.3%)	74	30/383 (7.8%)	43
Viral upper respiratory tract infection	44/383 (11.5%)	61	50/383 (13.1%)	70
Musculoskeletal and connective tissue disorders
Back pain	28/383 (7.3%)	29	10/383 (2.6%)	11
Nervous system disorders
Dizziness	20/383 (5.2%)	23	19/383 (5%)	20
Headache	57/383 (14.9%)	86	46/383 (12%)	68
Psychiatric disorders
Insomnia	18/383 (4.7%)	18	20/383 (5.2%)	22
Respiratory, thoracic and mediastinal disorders
Cough	23/383 (6%)	28	10/383 (2.6%)	10

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. 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.