FLAMINGO: Dolutegravir Compared to Darunavir/Ritonavir , Each in Combination With Dual Nucleoside Reverse Transcriptase Inhibitors (NRTIs) in ART-naive Subjects
Sponsor
ViiV Healthcare (Industry)
Overall Status
Completed
CT.gov ID
NCT01449929
Collaborator
GlaxoSmithKline (Industry)
488
66
2
61.9
7.4
0.1
Study Details
Study Description
Brief Summary
This study will be conducted in approximately 468 HIV-1 infected antiretroviral therapy (ART)-naïve subjects. Subjects will be randomized 1:1 to receive dolutegravir (DTG) 50 mg once daily (approximately 234 subjects) or darunavir/ritonavir (DRV/r) 800 mg/100 mg once daily (approximately 234 subjects), each in combination with fixed-dose dual nucleoside reverse transriptase inhibitor (NRTI) therapy (either abacavir/lamivudine (ABC/3TC) or tenofovir/emtricitabine (TDF/FTC). Subjects will be stratified by screening HIV-1 RNA and background NRTI selection. The primary analysis will take place after the last subject completes 48 weeks on therapy; an additional analysis will be conducted after the last subject completes Week 96 on study.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
ING114915 is a Phase IIIb randomized, open-label, active-controlled, multicentre, parallel group, fully-powered non-inferiority study. The study will be conducted in approximately 468 HIV-1 infected ART-naïve subjects. Subjects will be randomized 1:1 to receive DTG 50 mg once daily (approximately 234 subjects) or DRV/r 800 mg/100 mg once daily (approximately 234 subjects), each in combination with fixed-dose dual NRTI therapy (either ABC/3TC or TDF/FTC). The primary analysis will take place after the last subject completes 48 weeks on therapy; an additional analysis will be conducted after the last subject completes Week 96 on study.
Subjects who fulfil eligibility requirements will be randomized 1:1 to receive DTG 50 mg once daily or DRV/r 800 mg/100 mg once daily. In order to achieve balance across the two treatment groups of the study, randomization will be stratified by: screening plasma HIV-1 RNA >/ 100,000 copies/mL (c/mL) or > 100,000 c/mL and background dual NRTI (ABC/3TC or TDF/FTC) The DTG and DRV/r doses will be administered in an open-label fashion throughout the study.
Subjects randomized to receive DTG and who successfully complete 96 weeks of treatment will continue to have access to DTG until either it is locally approved and commercially available, the patient no longer derives clinical benefit, the patient meets a protocol-defined reason for discontinuation or until development of DTG is terminated. Subjects randomized to the DRV/r arm will receive DRV/r through their Week 96 visit, after which they will be discontinued from the study and will need to make alternative arrangements to access antiretroviral medication. All subjects will receive background dual-NRTI therapy through their Week 96 visit.
Study Design
Study Type:
Interventional
Actual Enrollment
:
488 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase IIIb, Randomized, Open-label Study of the Safety and Efficacy of GSK1349572 (Dolutegravir, DTG) 50 mg Once Daily Compared to Darunavir/Ritonavir (DRV/r) 800 mg/100 mg Once Daily Each Administered With Fixed-dose Dual Nucleoside Reverse Transcriptase Inhibitor Therapy Over 96 Weeks in HIV-1 Infected Antiretroviral naïve Adult Subjects
Actual Study Start Date
:
Oct 31, 2011
Actual Primary Completion Date
:
Apr 22, 2013
Actual Study Completion Date
:
Dec 26, 2016
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: dolutegravir 50mg once daily (OAD) in combination with either abacavir/lamivudine fixed dose combination tablet OAD or tenofovir disoproxil fumarate/emtricitabline fixed dose combination tablet OAD |
Drug: dolutegravir 50 mg OAD
1 x 50 mg tablet OAD
|
| Active Comparator: darunavir 800mg OAD in combination with ritonavir 100mg OAD in combination with either abacavir/lamivudine fixed dose combination tablet OAD or tenofovir disoproxil fumarate/emtricitabline fixed dose combination tablet OAD |
Drug: darunavir 800mg OAD
2 x 400mg tablets OAD
Drug: ritonavir 100mg OAD
1 x 100mg tablet OAD
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants With Plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) <50 Copies/Milliliter (c/mL) at Week 48 [Week 48]
Assessment was done using Missing, Switch or Discontinuation = Failure (MSDF), as codified by the Food and Drug Administration (FDA) "snapshot" algorithm.This algorithm treated all participants without HIV-1 RNA data at Week 48 as nonresponders, as well as participants who switched their concomitant ART prior to Week 48 as follows: background ART substitutions non-permitted per protocol (one background ART substitution was permitted for safety or tolerability); background ART substitutions permitted per protocol unless the decision to switch was documented as being before or at the first on-treatment visit where HIV-1 RNA was assessed. Otherwise, virologic success or failure was determined by the last available HIV-1 RNA assessment while the participant was on-treatment in the snapshot window (Week 48 +/- 6 weeks). Modified Intent-To-Treat Exposed (mITT-E) Population:all randomized participants who received at least one dose of investigational product
Secondary Outcome Measures
- Time to Virologic Suppression (<50 Copies/mL) Through Week 48 [From Baseline through Week 48]
The time to viral suppression (i.e. first viral load value <50 copies/mL) through Week 48 was derived and summarized using Kaplan-Meier plots. Participants who withdrew for any reason without having suppressed prior to the analysis were censored. Confidence intervals were estimated using the Brookmeyer-Crowley method.
- Percentage of Participants With Plasma HIV-1 RNA <400 c/mL at Week 48 [Week 48]
The percentage of participants with Plasma HIV-1 RNA <400 c/mL at Week 48 was assessed MSDF, as codified by the FDA "snapshot" algorithm. This algorithm treated all participants without HIV-1 RNA data at Week 48 as nonresponders, as well as participants who switched their concomitant ART prior to Week 48 as follows: background ART substitutions non-permitted per protocol (one background ART substitution was permitted for safety or tolerability); background ART substitutions permitted per protocol unless the decision to switch was documented as being before or at the first on-treatment visit where HIV-1 RNA was assessed. Otherwise, virologic success or failure was determined by the last available HIV-1 RNA assessment while the participant was on-treatment in the snapshot window (Week 48 +/- 6 weeks).
- Change From Baseline in Plasma HIV-1 RNA (log10 c/mL) at Weeks 4, 8, 12, 16, 24, 36 and 48 [Baseline, Weeks 4, 8, 12, 16, 24, 36 and 48]
Change from Baseline in plasma HIV-1 RNA (log10 c/mL) was assessed at Weeks 4, 8, 12, 16, 24, 36 and 48 . Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different visits, so the overall number of participants analyzed reflects everyone in the mITT-E Population.
- Change From Baseline in CD4+ and CD8+ Cell Counts [Baseline and Weeks 4, 8, 12, 16, 36 and 48 for CD4+ and Baseline and Weeks 4, 12, 24 and 48 for CD8+]
Change from Baseline in CD4+ cell counts was assessed at Weeks 4, 8, 12, 16, 36 and 48. Change from Baseline in CD8+ cell counts was assessed at Weeks 4, 12, 24 and 48. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different visits and parameters, so the overall number of participants analyzed reflects everyone in the mITT-E Population.
- Number of Participants With HIV-1 Associated Disease Progression With the Indicated Shift to CDC Class C, or New CDC Class C or Death at Week 48 [Week 48]
The number of participants with HIV-1 disease progression (AIDS or death) was assessed per the Centers for Disease Control and Prevention (CDC) 1993 revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. The CDC classifies HIV infection as Category A (participants with asymptomatic HIV infection, acute HIV infection with accompanying illness, or persistent generalized lymphadenopathy), Category B (participants with symptomatic non-AIDS condition, i.e., conditions that are attributed to HIV infection or are indicative of a defect in cell-mediated immunity; or conditions are considered by physicians to have a clinical course or to require management that is complicated by HIV infection), and Category C (includes AIDS indicator conditions as defined by diagnostic or presumptive measures).
- Change From Baseline in Fasting Low-density Lipoprotein (LDL) Cholesterol Through Week 48 [From Baseline through Week 48]
Fasting LDL cholesterol change from Baseline was analyzed. Values represented are for adjusted means. Estimates are calculated from a repeated measures model including the following covariates: treatment, visit, Baseline plasma HIV-1 RNA, background dual NRTI therapy, Baseline LDL cholesterol, treatment*visit interaction and Baseline LDL cholesterol*visit interaction. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Only those participants with data available at the specified time points were analyzed.
- Percentage of Participants With Grade 2 or Higher Abnormalities in Fasting LDL Cholesterol Through Week 48 [From Baseline through Week 48]
Hematology and clinical chemistry data were summarized according to the division of AIDS (DAIDS) table for grading the Severity of adverse events, version 1.0. Grade 1, Mild; Grade 2, Moderate; Grade 3 (G3), Severe; Grade 4 (G4), Life-threatening or disabling; Grade 5, Death. Data are presented for which an increase in fasting LDL cholesterol to Grade 2 or higher occurred. Only those participants with data available at the specified time points were analyzed.
- Number of Participants With the Indicated Grade 3 and Grade 4 Maximum Post-Baseline Chemistry and Hematology Laboratory Toxicities [From Baseline through Week 48]
Hematology and clinical chemistry data were summarized according to the division of AIDS (DAIDS) table for grading the Severity of adverse events, version 1.0. Grade 1, Mild; Grade 2, Moderate; Grade 3 (G3), Severe; Grade 4 (G4), Life-threatening or disabling; Grade 5, Death. Data are presented for only those parameters for which an increase to Grade 3 or Grade 4 occurred.
- Number of Participants (Par.) With Detectable Virus That Has Genotypic or Phenotypic Evidence of Treatment-emergent Resistance to DTG, DRV+RTV and Other On-study ART at Time of Protocol Defined Virology Failure (PDVF) [Baseline until PDVF up to Week 48]
An assessment was made of every change across all amino acids within the integrase (IN), reverse transcriptase (RT), and Protease (PRO) encoding region at Baseline and at time of suspected PDVF. PDVF is defined as the confirmed plasma HIV-1 RNA >200 c/mL >=Week 24. PDVF Genotypic Population included all participants in the mITT-E population with available on-treatment genotypic resistance data, at time of PDVF. Only those participants with data available at the specified time points were analyzed.
- Change From Baseline in Acquired Immune Deficiency Syndrome (AIDS) Clinical Trials Group (ACTG) Symptom Distress Module (SDM) Bother Score at Week 4, Week 24, and Week 48 [Baseline, Week 4, Week 24, and Week 48]
SDM is a 20-item self-reported measure that addresses the presence and perceived distress linked to symptoms commonly associated with HIV or its treatment. Each item is rated from 0 to 4 where 0 (complete absence of symptom) and 4 (very bothersome symptom). Overall score calculated as the sum of the scores for each of the 20 items of the questionnaire and ranged from 0 (best health) and 80 (worst health). Values represented are for adjusted mean. Estimates are calculated from an ANCOVA model adjusting for age, sex, race, baseline viral load, background dual NRTI therapy and baseline symptom bother score. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. A positive change from Baseline indicates a decline in a participant's quality of life over that period.
- Change From Baseline in European Quality of Life -5 Dimensions (EQ-5D) Utility Scores at Week 24 and Week 48 [Baseline, Week 24, and Week 48]
The EQ-5D is a 5-question quality of life instrument that provides a utility score and visual analogue scale score that describes the participants' health status. The primary reason for including the EQ-5D is to elicit utility values for potential cost-effectiveness analysis for submission to health technology assessment agencies. The EQ-5D total score ranges from 0 (worst health state) to 1 (perfect health state) and 1 reflects the best outcome. Values represented are for adjusted mean. Estimates are calculated from an ANCOVA model adjusting for age, sex, race, baseline viral load, background dual NRTI therapy and Baseline EQ-5D utility score. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
- Change From Baseline in EQ-5D Thermometer Scores at Week 24 and Week 48 [Baseline, Week 24, and Week 48]
The European Quality of Life -5 Dimensions (EQ-5D) is a 5-question quality of life instrument that provides a utility score and visual analogue scale score that describes the participants' health status. The primary reason for including the EQ-5D is to elicit utility values for potential cost-effectiveness analysis for submission to health technology assessment agencies. Thermometer score is based on a visual analogue scale (VAS) ranging from 100 (best imaginable health state) to 0 (worst imaginable health state).Values represented are for adjusted mean. Estimates are calculated from an ANCOVA model adjusting for age, sex, race, Baseline viral load, background dual NRTI therapy and Baseline EQ-5D thermometer score. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
- Human Immunodeficiency Virus Treatment Satisfaction Questionnaire (HIVTSQ) Total Score at Week 4, Week 24, and Week 48 [Week 4, Week 24, and Week 48]
Participant treatment satisfaction was measured using the self-reported scale (HIVTSQ), which consists of 10 items (1-satisfaction, 2-HIV control, 3-adverse effects, 4-level of demand, 5-convenience, 6-flexibility, 7-knowledge, 8-life habits, 9-recommendability, and 10-willingness to continue). Items are scored from 0 (very dissatisfied) to 6 (very satisfied), other than item 4, which has an inverted score from 6 (very demanding) to 0 (very undemanding). The treatment satisfaction score (range: 0-60) was the sum of the individual items. HIVTSQ mITT-E Population=Only participants from USA, France, Germany, Italy, Spain for whom valid translations were available from the mITT-E Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different visits, so the overall number of participants analyzed reflects everyone in the HIVTSQ mITT-E population.
- Human Immunodeficiency Virus Treatment Satisfaction Questionnaire (HIVTSQ) Lifestyle/Ease Sub Score at Week 4, Week 24, and Week 48 [Week 4, Week 24, and Week 48]
Participant treatment satisfaction was measured using the self-reported scale (HIVTSQ), which consists of 10 items (1-satisfaction, 2-HIV control, 3-adverse effects, 4-level of demand, 5-convenience, 6-flexibility, 7-knowledge, 8-life habits, 9-recommendability, and 10-willingness to continue). Items are scored from 0 (very dissatisfied) to 6 (very satisfied), other than item 4, which has an inverted score from 6 (very demanding) to 0 (very undemanding). The lifestyle/ease score is the sum of items 4, 5, 6, 7 and 8 (range: 0-30). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different visits, so the overall number of participants analyzed reflects everyone in the HIVTSQ mITT-E population.
- Human Immunodeficiency Virus Treatment Satisfaction Questionnaire (HIVTSQ) Convenience Score at Week 4, Week 24, and Week 48 [Week 4, Week 24, and Week 48]
Participant treatment satisfaction was measured using the self-reported scale (HIVTSQ), which consists of 10 items (1-satisfaction, 2-HIV control, 3-adverse effects, 4-level of demand, 5-convenience, 6-flexibility, 7-knowledge, 8-life habits, 9-recommendability, and 10-willingness to continue). Items are scored from 0 (very dissatisfied) to 6 (very satisfied), other than item 4, which has an inverted score from 6 (very demanding) to 0 (very undemanding). The convenience score is the score for item 5 (range: 0-6). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different visits, so the overall number of participants analyzed reflects everyone in the HIVTSQ mITT-E population.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
HIV-1 infected adults greater than or equal to 18 years of age. Females are eligible to enter and participate in the study if she is (1) non-childbearing potential, (2) child bearing potential with negative pregnancy test at screening and Day 1 and agrees to use protocol-specified methods of birth control while on study.
-
HIV-1 infection with a screening plasma HIV-1 RNA greater than or equal to 1000copies/mL
-
Antiretroviral-naïve (less than or equal to 10 days of prior therapy with any antiretroviral agent following a diagnosis of HIV-1 infection)
-
Signed and dated written informed consent is obtained from the subject or the subject's legal representative prior to screening
Exclusion Criteria:
-
Women who are pregnant or breastfeeding
-
Any evidence of an active Centers for Disease and Prevention Control (CDC) Category C disease [CDC, 1993], except cutaneous Kaposi's sarcoma not requiring systemic therapy
-
Subjects with moderate to severe hepatic impairment (Class B or C) as determined by Child-Pugh classification
-
Anticipated need for Hepatitis C virus (HCV) therapy during the study
-
History or presence of allergy or intolerance to the study drugs or their components or drugs of their class
-
History of malignancy within the past 5 years or ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous cell carcinoma; other localized malignancies require agreement between the investigator and the Study medical monitor for inclusion of the subject
-
Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening
-
Treatment with any of the following agents within 28 days of Screening: radiation therapy; cytotoxic chemotherapeutic agents; any immunomodulators
-
Treatment with any agent, except recognized ART as allowed above, with documented activity against HIV-1 in vitro within 28 days of first dose of investigational product
-
Exposure to an experimental drug or experimental vaccine within either 28 days, 5 half-lives of the test agent, or twice the duration of the biological effect of the test agent, whichever is longer, prior to the first dose of investigational product
-
Any evidence of primary viral resistance based on the presence of any major resistance-associated mutation [IAS-USA, 2010] in the Screening result or, if known, any historical resistance test result
-
Any verified Grade 4 laboratory abnormality. Any acute laboratory abnormality at Screening, which, in the opinion of the Investigator, would preclude the subject's participation in the study of an investigational compound is exclusionary
-
Alanine aminotransferase (ALT) greater than 5 times the upper limit of normal
-
ALT greater than 3 times the upper limit of normal and bilirubin greater than or equal to 1.5 times the upper limit of normal (with greater than 35% direct bilirubin)
-
Subject has creatinine clearance of less than 50 mL/min via Cockroft-Gault method
-
Recent history (less than or equal to 3 months) of any upper or lower gastrointestinal bleed, with the exception of anal or rectal bleeding
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | GSK Investigational Site | Birmingham | Alabama | United States | 35294 |
| 2 | GSK Investigational Site | Los Angeles | California | United States | 90027 |
| 3 | GSK Investigational Site | Los Angeles | California | United States | 90069 |
| 4 | GSK Investigational Site | Aurora | Colorado | United States | 80045 |
| 5 | GSK Investigational Site | Denver | Colorado | United States | 80209 |
| 6 | GSK Investigational Site | Norwalk | Connecticut | United States | 06851 |
| 7 | GSK Investigational Site | Washington | District of Columbia | United States | 20007 |
| 8 | GSK Investigational Site | Washington | District of Columbia | United States | 20009 |
| 9 | GSK Investigational Site | Washington | District of Columbia | United States | 20037 |
| 10 | GSK Investigational Site | Daytona Beach | Florida | United States | 32117 |
| 11 | GSK Investigational Site | Orlando | Florida | United States | 32803 |
| 12 | GSK Investigational Site | Tampa | Florida | United States | 33614 |
| 13 | GSK Investigational Site | Vero Beach | Florida | United States | 32690 |
| 14 | GSK Investigational Site | Augusta | Georgia | United States | 30912 |
| 15 | GSK Investigational Site | Decatur | Georgia | United States | 30033 |
| 16 | GSK Investigational Site | Macon | Georgia | United States | 31201 |
| 17 | GSK Investigational Site | Savannah | Georgia | United States | 31401 |
| 18 | GSK Investigational Site | Springfield | Massachusetts | United States | 01105 |
| 19 | GSK Investigational Site | Detroit | Michigan | United States | 48202 |
| 20 | GSK Investigational Site | Minneapolis | Minnesota | United States | 55415 |
| 21 | GSK Investigational Site | Kansas City | Missouri | United States | 64111 |
| 22 | GSK Investigational Site | Chapel Hill | North Carolina | United States | 27514 |
| 23 | GSK Investigational Site | Charlotte | North Carolina | United States | 28209 |
| 24 | GSK Investigational Site | Winston-Salem | North Carolina | United States | 27157-1042 |
| 25 | GSK Investigational Site | Cincinnati | Ohio | United States | 45267 |
| 26 | GSK Investigational Site | Portland | Oregon | United States | 97210 |
| 27 | GSK Investigational Site | Philadelphia | Pennsylvania | United States | 19104 |
| 28 | GSK Investigational Site | Providence | Rhode Island | United States | 02906 |
| 29 | GSK Investigational Site | Dallas | Texas | United States | 75204 |
| 30 | GSK Investigational Site | Dallas | Texas | United States | 75219 |
| 31 | GSK Investigational Site | Dallas | Texas | United States | 75246 |
| 32 | GSK Investigational Site | Longview | Texas | United States | 75605 |
| 33 | GSK Investigational Site | Seattle | Washington | United States | 98104 |
| 34 | GSK Investigational Site | Montpellier Cedex 5 | France | 34295 | |
| 35 | GSK Investigational Site | Nantes | France | 44093 | |
| 36 | GSK Investigational Site | Paris Cedex 10 | France | 75475 | |
| 37 | GSK Investigational Site | Paris Cedex 20 | France | 75970 | |
| 38 | GSK Investigational Site | Paris | France | 75018 | |
| 39 | GSK Investigational Site | Saint Denis Cedex 01 | France | 93205 | |
| 40 | GSK Investigational Site | Freiburg | Baden-Wuerttemberg | Germany | 79106 |
| 41 | GSK Investigational Site | Frankfurt | Hessen | Germany | 60590 |
| 42 | GSK Investigational Site | Hamburg | Germany | 20246 | |
| 43 | GSK Investigational Site | Modena | Emilia-Romagna | Italy | 41150 |
| 44 | GSK Investigational Site | Roma | Lazio | Italy | 00149 |
| 45 | GSK Investigational Site | Milano | Lombardia | Italy | 20127 |
| 46 | GSK Investigational Site | Milano | Lombardia | Italy | 20142 |
| 47 | GSK Investigational Site | Torino | Piemonte | Italy | 10149 |
| 48 | GSK Investigational Site | Ponce | Puerto Rico | 00717 | |
| 49 | GSK Investigational Site | San Juan | Puerto Rico | 00909 | |
| 50 | GSK Investigational Site | San Juan | Puerto Rico | ||
| 51 | GSK Investigational Site | Bucharest | Romania | 021105 | |
| 52 | GSK Investigational Site | Bucharest | Romania | 030303 | |
| 53 | GSK Investigational Site | Constanta | Romania | 900708 | |
| 54 | GSK Investigational Site | Krasnodar | Russian Federation | 350015 | |
| 55 | GSK Investigational Site | Moscow | Russian Federation | 105275 | |
| 56 | GSK Investigational Site | Saratov | Russian Federation | 410009 | |
| 57 | GSK Investigational Site | St. Petersburg | Russian Federation | 196645 | |
| 58 | GSK Investigational Site | Volgograd | Russian Federation | 400040 | |
| 59 | GSK Investigational Site | Badalona | Spain | 08916 | |
| 60 | GSK Investigational Site | Barcelona | Spain | 08036 | |
| 61 | GSK Investigational Site | Barcelona | Spain | 08907 | |
| 62 | GSK Investigational Site | Madrid | Spain | 28041 | |
| 63 | GSK Investigational Site | Sevilla | Spain | 41013 | |
| 64 | GSK Investigational Site | Bern | Switzerland | 3010 | |
| 65 | GSK Investigational Site | Lausanne | Switzerland | 1011 | |
| 66 | GSK Investigational Site | Zurich | Switzerland | CH-8091 |
Sponsors and Collaborators
- ViiV Healthcare
- GlaxoSmithKline
Investigators
- Study Director: GSK Clinical Trials, ViiV Healthcare
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
ViiV Healthcare
ClinicalTrials.gov Identifier:
NCT01449929
Other Study ID Numbers:
- 114915
First Posted:
Oct 10, 2011
Last Update Posted:
Jan 16, 2018
Last Verified:
Oct 1, 2017
Studies a U.S. FDA-regulated Drug Product:
Yes
Keywords provided by ViiV Healthcare
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | This was a 2 sequential treatment period study. In first period (Randomization phase) participants received either dolutegravir (DTG) 50 milligram (mg) or darunavir (DRV) 800 mg with ritonavir (RTV) 100 mg once daily (QD) for 96 weeks. DTG participants who completed 96 Weeks of DTG then continued to receive DTG 50 mg in Extension phase. |
|---|---|
| Pre-assignment Detail | A total of 595 participants were screened; 107 were screen failures; 488 were randomized; 485 received at least 1 dose of study medication and comprised the Intent-To-Treat exposed (ITT-E) population of which 1 participant was removed, creating the modified ITT-E population with 484 participants. 123 participants enrolled in Extension Phase. |
| Arm/Group Title | DTG 50 mg QD | DRV 800 mg + RTV 100 mg QD | Extension DTG 50 mg |
|---|---|---|---|
| Arm/Group Description | Participants received DTG 50 mg QD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks. Participants were then given the opportunity to receive DTG 50 mg QD during an Extension Phase of the study. | Participants received DRV 800 mg + RTV 100 mg QD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks. | DTG participants who successfully completed 96 Weeks of randomized phase continued to receive DTG 50 mg QD during Extension phase |
| Period Title: Randomization Phase 96 Week | |||
| STARTED | 242 | 242 | 0 |
| COMPLETED | 209 | 189 | 0 |
| NOT COMPLETED | 33 | 53 | 0 |
| Period Title: Randomization Phase 96 Week | |||
| STARTED | 0 | 0 | 123 |
| COMPLETED | 0 | 0 | 115 |
| NOT COMPLETED | 0 | 0 | 8 |
Baseline Characteristics
| Arm/Group Title | DTG 50 mg QD | DRV 800 mg + RTV 100 mg QD | Total |
|---|---|---|---|
| Arm/Group Description | Participants received DTG 50 mg QD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks. Participants were then given the opportunity to receive DTG 50 mg QD during an Extension Phase of the study. | Participants received DRV 800 mg + RTV 100 mg QD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks. | Total of all reporting groups |
| Overall Participants | 242 | 242 | 484 |
| Age (Years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [Years] |
35.7
(10.66)
|
36.2
(10.64)
|
35.9
(10.64)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
31
12.8%
|
41
16.9%
|
72
14.9%
|
| Male |
211
87.2%
|
201
83.1%
|
412
85.1%
|
| Race/Ethnicity, Customized (Number) [Number] | |||
| African American/African Heritage |
60
24.8%
|
53
21.9%
|
113
23.3%
|
| American Indian or Alaska Native |
3
1.2%
|
9
3.7%
|
12
2.5%
|
| Asian - Central/South Asian Heritage |
0
0%
|
1
0.4%
|
1
0.2%
|
| Asian - Japanese Heritage |
1
0.4%
|
0
0%
|
1
0.2%
|
| Asian - South East Asian Heritage |
1
0.4%
|
0
0%
|
1
0.2%
|
| Native Hawaiian or other Pacific Islander |
2
0.8%
|
0
0%
|
2
0.4%
|
| White - Arabic/North African Heritage |
4
1.7%
|
3
1.2%
|
7
1.4%
|
| White - White/Caucasian/European Heritage |
169
69.8%
|
173
71.5%
|
342
70.7%
|
| Mixed Race |
1
0.4%
|
3
1.2%
|
4
0.8%
|
| Missing |
1
0.4%
|
0
0%
|
1
0.2%
|
Outcome Measures
| Title | Percentage of Participants With Plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) <50 Copies/Milliliter (c/mL) at Week 48 |
|---|---|
| Description | Assessment was done using Missing, Switch or Discontinuation = Failure (MSDF), as codified by the Food and Drug Administration (FDA) "snapshot" algorithm.This algorithm treated all participants without HIV-1 RNA data at Week 48 as nonresponders, as well as participants who switched their concomitant ART prior to Week 48 as follows: background ART substitutions non-permitted per protocol (one background ART substitution was permitted for safety or tolerability); background ART substitutions permitted per protocol unless the decision to switch was documented as being before or at the first on-treatment visit where HIV-1 RNA was assessed. Otherwise, virologic success or failure was determined by the last available HIV-1 RNA assessment while the participant was on-treatment in the snapshot window (Week 48 +/- 6 weeks). Modified Intent-To-Treat Exposed (mITT-E) Population:all randomized participants who received at least one dose of investigational product |
| Time Frame | Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| mITT-E Population |
| Arm/Group Title | DTG 50 mg QD | DRV 800 mg + RTV 100 mg QD |
|---|---|---|
| Arm/Group Description | Participants received DTG 50 mg QD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks. Participants were then given the opportunity to receive DTG 50 mg QD during an Extension Phase of the study. | Participants received DRV 800 mg + RTV 100 mg QD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks. |
| Measure Participants | 242 | 242 |
| Number [Percentage of participants] |
90
37.2%
|
83
34.3%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | DTG 50 mg QD, DRV 800 mg + RTV 100 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | Non-inferiority of DTG 50 mg and DRV+RTV at Week 48 can be concluded if the lower bound of a two-sided 95% confidence interval (CI) for the difference in percentages (DTG - DRV+RTV) is greater than -12%. If non-inferiority is established, superiority can be tested at the nominal 5% level based on a pre-specified testing procedure. | |
| Statistical Test of Hypothesis | p-Value | 0.025 |
| Comments | P-value is for test of superiority. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified analysis | |
| Method of Estimation | Estimation Parameter | Difference in percentage |
| Estimated Value | 7.1 | |
| Confidence Interval |
(2-Sided) 95% 0.9 to 13.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Analysis was adjusted for the Baseline (BL) stratification factors: Baseline plasma HIV-1 RNA (<=100,000 c/mL vs >100,000 c/mL) and Baseline background dual NRTI therapy (ABC/3TC vs TDF/FTC). | |
| Title | Time to Virologic Suppression (<50 Copies/mL) Through Week 48 |
|---|---|
| Description | The time to viral suppression (i.e. first viral load value <50 copies/mL) through Week 48 was derived and summarized using Kaplan-Meier plots. Participants who withdrew for any reason without having suppressed prior to the analysis were censored. Confidence intervals were estimated using the Brookmeyer-Crowley method. |
| Time Frame | From Baseline through Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| mITT-E Population |
| Arm/Group Title | DTG 50 mg QD | DRV 800 mg + RTV 100 mg QD |
|---|---|---|
| Arm/Group Description | Participants received DTG 50 mg QD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks. Participants were then given the opportunity to receive DTG 50 mg QD during an Extension Phase of the study. | Participants received DRV 800 mg + RTV 100 mg QD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks. |
| Measure Participants | 242 | 242 |
| Median (95% Confidence Interval) [Days] |
28.0
|
85.0
|
| Title | Percentage of Participants With Plasma HIV-1 RNA <400 c/mL at Week 48 |
|---|---|
| Description | The percentage of participants with Plasma HIV-1 RNA <400 c/mL at Week 48 was assessed MSDF, as codified by the FDA "snapshot" algorithm. This algorithm treated all participants without HIV-1 RNA data at Week 48 as nonresponders, as well as participants who switched their concomitant ART prior to Week 48 as follows: background ART substitutions non-permitted per protocol (one background ART substitution was permitted for safety or tolerability); background ART substitutions permitted per protocol unless the decision to switch was documented as being before or at the first on-treatment visit where HIV-1 RNA was assessed. Otherwise, virologic success or failure was determined by the last available HIV-1 RNA assessment while the participant was on-treatment in the snapshot window (Week 48 +/- 6 weeks). |
| Time Frame | Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| mITT-E Population |
| Arm/Group Title | DTG 50 mg QD | DRV 800 mg + RTV 100 mg QD |
|---|---|---|
| Arm/Group Description | Participants received DTG 50 mg QD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks. Participants were then given the opportunity to receive DTG 50 mg QD during an Extension Phase of the study. | Participants received DRV 800 mg + RTV 100 mg QD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks. |
| Measure Participants | 242 | 242 |
| Number [Percentage of participants] |
92
38%
|
87
36%
|
| Title | Change From Baseline in Plasma HIV-1 RNA (log10 c/mL) at Weeks 4, 8, 12, 16, 24, 36 and 48 |
|---|---|
| Description | Change from Baseline in plasma HIV-1 RNA (log10 c/mL) was assessed at Weeks 4, 8, 12, 16, 24, 36 and 48 . Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different visits, so the overall number of participants analyzed reflects everyone in the mITT-E Population. |
| Time Frame | Baseline, Weeks 4, 8, 12, 16, 24, 36 and 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| mITT-E Population. |
| Arm/Group Title | DTG 50 mg OD | DRV 800 mg + RTV 100 mg OD |
|---|---|---|
| Arm/Group Description | Participants received DTG 50 mg OD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks. Participants were then given the opportunity to receive DTG 50 mg OD during an Extension Phase of the study. | Participants received DRV 800 mg + RTV 100 mg OD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks. |
| Measure Participants | 242 | 242 |
| Week 4, n=238, 235 |
-2.80
(0.625)
|
-2.01
(0.454)
|
| Week 8, n=237, 236 |
-2.86
(0.649)
|
-2.40
(0.524)
|
| Week 12, n=234, 227 |
-2.88
(0.653)
|
-2.61
(0.537)
|
| Week 16, n=229, 228 |
-2.86
(0.691)
|
-2.71
(0.618)
|
| Week 24, n=234, 227 |
-2.86
(0.765)
|
-2.83
(0.663)
|
| Week 36, n=232, 218 |
-2.87
(0.715)
|
-2.85
(0.683)
|
| Week 48, n=227, 212 |
-2.89
(0.739)
|
-2.86
(0.663)
|
| Title | Change From Baseline in CD4+ and CD8+ Cell Counts |
|---|---|
| Description | Change from Baseline in CD4+ cell counts was assessed at Weeks 4, 8, 12, 16, 36 and 48. Change from Baseline in CD8+ cell counts was assessed at Weeks 4, 12, 24 and 48. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different visits and parameters, so the overall number of participants analyzed reflects everyone in the mITT-E Population. |
| Time Frame | Baseline and Weeks 4, 8, 12, 16, 36 and 48 for CD4+ and Baseline and Weeks 4, 12, 24 and 48 for CD8+ |
Outcome Measure Data
| Analysis Population Description |
|---|
| mITT-E Population. |
| Arm/Group Title | DTG 50 mg QD | DRV 800 mg + RTV 100 mg QD |
|---|---|---|
| Arm/Group Description | Participants received DTG 50 mg QD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks. Participants were then given the opportunity to receive DTG 50 mg QD during an Extension Phase of the study. | Participants received DRV 800 mg + RTV 100 mg QD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks. |
| Measure Participants | 242 | 242 |
| CD4+ cell count, Week 4, n=237, 236 |
80.1
(101.36)
|
75.6
(124.36)
|
| CD4+ cell count, Week 8, n=236, 236 |
126.9
(124.13)
|
118.8
(142.54)
|
| CD4+ cell count, Week 12, n=234, 228 |
135.2
(120.03)
|
131.8
(143.88)
|
| CD4+ cell count, Week 16, n=227, 227 |
156.8
(146.60)
|
146.1
(166.08)
|
| CD4+ cell count, Week 24, n=233, 227 |
165.1
(145.85)
|
164.3
(180.00)
|
| CD4+ cell count, Week 36, n=232, 218 |
206.1
(159.06)
|
186.5
(183.61)
|
| CD4+ cell count, Week 48, n=227, 212 |
243.8
(180.68)
|
215.4
(177.26)
|
| CD8+ cell count, Week 4, n=235, 235 |
-47.4
(276.01)
|
-3.7
(375.94)
|
| CD8+ cell count, Week 12, n=231, 227 |
-42.0
(343.81)
|
-68.9
(373.38)
|
| CD8+ cell count, Week 24, n=231, 224 |
-108.0
(350.03)
|
-132.9
(389.70)
|
| CD8+ cell count, Week 48, n=224, 210 |
-109.5
(360.94)
|
-162.1
(421.07)
|
| Title | Number of Participants With HIV-1 Associated Disease Progression With the Indicated Shift to CDC Class C, or New CDC Class C or Death at Week 48 |
|---|---|
| Description | The number of participants with HIV-1 disease progression (AIDS or death) was assessed per the Centers for Disease Control and Prevention (CDC) 1993 revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. The CDC classifies HIV infection as Category A (participants with asymptomatic HIV infection, acute HIV infection with accompanying illness, or persistent generalized lymphadenopathy), Category B (participants with symptomatic non-AIDS condition, i.e., conditions that are attributed to HIV infection or are indicative of a defect in cell-mediated immunity; or conditions are considered by physicians to have a clinical course or to require management that is complicated by HIV infection), and Category C (includes AIDS indicator conditions as defined by diagnostic or presumptive measures). |
| Time Frame | Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| mITT-E Population |
| Arm/Group Title | DTG 50 mg QD | DRV 800 mg + RTV 100 mg QD |
|---|---|---|
| Arm/Group Description | Participants received DTG 50 mg QD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks. Participants were then given the opportunity to receive DTG 50 mg QD during an Extension Phase of the study. | Participants received DRV 800 mg + RTV 100 mg QD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks. |
| Measure Participants | 242 | 242 |
| Number [Participants] |
0
0%
|
0
0%
|
| Title | Change From Baseline in Fasting Low-density Lipoprotein (LDL) Cholesterol Through Week 48 |
|---|---|
| Description | Fasting LDL cholesterol change from Baseline was analyzed. Values represented are for adjusted means. Estimates are calculated from a repeated measures model including the following covariates: treatment, visit, Baseline plasma HIV-1 RNA, background dual NRTI therapy, Baseline LDL cholesterol, treatment*visit interaction and Baseline LDL cholesterol*visit interaction. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Only those participants with data available at the specified time points were analyzed. |
| Time Frame | From Baseline through Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| mSafety Population. |
| Arm/Group Title | DTG 50 mg QD | DRV 800 mg + RTV 100 mg QD |
|---|---|---|
| Arm/Group Description | Participants received DTG 50 mg QD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks. Participants were then given the opportunity to receive DTG 50 mg QD during an Extension Phase of the study. | Participants received DRV 800 mg + RTV 100 mg QD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks. |
| Measure Participants | 182 | 178 |
| Mean (Standard Error) [Millimoles per liter (mmol/L)] |
0.07
(0.041)
|
0.37
(0.041)
|
| Title | Percentage of Participants With Grade 2 or Higher Abnormalities in Fasting LDL Cholesterol Through Week 48 |
|---|---|
| Description | Hematology and clinical chemistry data were summarized according to the division of AIDS (DAIDS) table for grading the Severity of adverse events, version 1.0. Grade 1, Mild; Grade 2, Moderate; Grade 3 (G3), Severe; Grade 4 (G4), Life-threatening or disabling; Grade 5, Death. Data are presented for which an increase in fasting LDL cholesterol to Grade 2 or higher occurred. Only those participants with data available at the specified time points were analyzed. |
| Time Frame | From Baseline through Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| mSafety Population. |
| Arm/Group Title | DTG 50 mg QD | DRV 800 mg + RTV 100 mg QD |
|---|---|---|
| Arm/Group Description | Participants received DTG 50 mg QD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks. Participants were then given the opportunity to receive DTG 50 mg QD during an Extension Phase of the study. | Participants received DRV 800 mg + RTV 100 mg QD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks. |
| Measure Participants | 242 | 242 |
| Number [Percentage of Participants] |
2
0.8%
|
7
2.9%
|
| Title | Number of Participants With the Indicated Grade 3 and Grade 4 Maximum Post-Baseline Chemistry and Hematology Laboratory Toxicities |
|---|---|
| Description | Hematology and clinical chemistry data were summarized according to the division of AIDS (DAIDS) table for grading the Severity of adverse events, version 1.0. Grade 1, Mild; Grade 2, Moderate; Grade 3 (G3), Severe; Grade 4 (G4), Life-threatening or disabling; Grade 5, Death. Data are presented for only those parameters for which an increase to Grade 3 or Grade 4 occurred. |
| Time Frame | From Baseline through Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| mSafety Population |
| Arm/Group Title | DTG 50 mg QD | DRV 800 mg + RTV 100 mg QD |
|---|---|---|
| Arm/Group Description | Participants received DTG 50 mg QD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks. Participants were then given the opportunity to receive DTG 50 mg QD during an Extension Phase of the study. | Participants received DRV 800 mg + RTV 100 mg QD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks. |
| Measure Participants | 242 | 242 |
| Alanine Amino Transferase, G3 |
2
0.8%
|
1
0.4%
|
| Alanine Amino Transferase, G4 |
1
0.4%
|
3
1.2%
|
| Aspartate Amino Transferase, G3 |
6
2.5%
|
3
1.2%
|
| Aspartate Amino Transferase, G4 |
2
0.8%
|
0
0%
|
| Cholesterol, G3 |
0
0%
|
3
1.2%
|
| Creatine Kinase, G3 |
8
3.3%
|
5
2.1%
|
| Creatine Kinase, G4 |
8
3.3%
|
4
1.7%
|
| Hyperglycaemia, G3 |
1
0.4%
|
2
0.8%
|
| Hypoglycaemia, G3 |
0
0%
|
1
0.4%
|
| LDL Cholesterol, G3 |
2
0.8%
|
6
2.5%
|
| Lipase, G3 |
5
2.1%
|
5
2.1%
|
| Lipase, G4 |
2
0.8%
|
0
0%
|
| Phosphorus, inorganic, G3 |
7
2.9%
|
7
2.9%
|
| Total Bilirubin, G3 |
1
0.4%
|
0
0%
|
| Triglycerides, G3 |
1
0.4%
|
2
0.8%
|
| Triglycerides, G4 |
0
0%
|
1
0.4%
|
| Hemoglobin, G3 |
1
0.4%
|
0
0%
|
| Hemoglobin, G4 |
1
0.4%
|
0
0%
|
| Platelet count, G4 |
0
0%
|
1
0.4%
|
| Total Neutrophils, G3 |
5
2.1%
|
0
0%
|
| Total Neutrophils, G4 |
3
1.2%
|
1
0.4%
|
| Title | Number of Participants (Par.) With Detectable Virus That Has Genotypic or Phenotypic Evidence of Treatment-emergent Resistance to DTG, DRV+RTV and Other On-study ART at Time of Protocol Defined Virology Failure (PDVF) |
|---|---|
| Description | An assessment was made of every change across all amino acids within the integrase (IN), reverse transcriptase (RT), and Protease (PRO) encoding region at Baseline and at time of suspected PDVF. PDVF is defined as the confirmed plasma HIV-1 RNA >200 c/mL >=Week 24. PDVF Genotypic Population included all participants in the mITT-E population with available on-treatment genotypic resistance data, at time of PDVF. Only those participants with data available at the specified time points were analyzed. |
| Time Frame | Baseline until PDVF up to Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PDVF Genotypic Population |
| Arm/Group Title | DTG 50 mg OD | DRV 800 mg + RTV 100 mg OD |
|---|---|---|
| Arm/Group Description | Participants received DTG 50 mg OD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks. Participants were then given the opportunity to receive DTG 50 mg OD during an Extension Phase of the study. | Participants received DRV 800 mg + RTV 100 mg OD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks. |
| Measure Participants | 2 | 2 |
| Number [Participants] |
0
0%
|
0
0%
|
| Title | Change From Baseline in Acquired Immune Deficiency Syndrome (AIDS) Clinical Trials Group (ACTG) Symptom Distress Module (SDM) Bother Score at Week 4, Week 24, and Week 48 |
|---|---|
| Description | SDM is a 20-item self-reported measure that addresses the presence and perceived distress linked to symptoms commonly associated with HIV or its treatment. Each item is rated from 0 to 4 where 0 (complete absence of symptom) and 4 (very bothersome symptom). Overall score calculated as the sum of the scores for each of the 20 items of the questionnaire and ranged from 0 (best health) and 80 (worst health). Values represented are for adjusted mean. Estimates are calculated from an ANCOVA model adjusting for age, sex, race, baseline viral load, background dual NRTI therapy and baseline symptom bother score. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. A positive change from Baseline indicates a decline in a participant's quality of life over that period. |
| Time Frame | Baseline, Week 4, Week 24, and Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| mITT-E Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different visits, so the overall number of participants analyzed reflects everyone in the mITT-E Population. |
| Arm/Group Title | DTG 50 mg QD | DRV 800 mg + RTV 100 mg QD |
|---|---|---|
| Arm/Group Description | Participants received DTG 50 mg QD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks. Participants were then given the opportunity to receive DTG 50 mg QD during an Extension Phase of the study. | Participants received DRV 800 mg + RTV 100 mg OD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks. |
| Measure Participants | 242 | 242 |
| Week 4, n=218, 210 |
-3.20
(0.56)
|
-2.19
(0.56)
|
| Week 24, n=222, 214 |
-2.71
(0.64)
|
-1.65
(0.65)
|
| Week 48, n= 222, 215 |
-2.46
(0.68)
|
-0.77
(0.69)
|
| Title | Change From Baseline in European Quality of Life -5 Dimensions (EQ-5D) Utility Scores at Week 24 and Week 48 |
|---|---|
| Description | The EQ-5D is a 5-question quality of life instrument that provides a utility score and visual analogue scale score that describes the participants' health status. The primary reason for including the EQ-5D is to elicit utility values for potential cost-effectiveness analysis for submission to health technology assessment agencies. The EQ-5D total score ranges from 0 (worst health state) to 1 (perfect health state) and 1 reflects the best outcome. Values represented are for adjusted mean. Estimates are calculated from an ANCOVA model adjusting for age, sex, race, baseline viral load, background dual NRTI therapy and Baseline EQ-5D utility score. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). |
| Time Frame | Baseline, Week 24, and Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| mITT-E Population. |
| Arm/Group Title | DTG 50 mg QD | DRV 800 mg + RTV 100 mg QD |
|---|---|---|
| Arm/Group Description | Participants received DTG 50 mg QD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks. Participants were then given the opportunity to receive DTG 50 mg QD during an Extension Phase of the study. | Participants received DRV 800 mg + RTV 100 mg QD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks. |
| Measure Participants | 242 | 242 |
| Week 24, n=217, 213 |
0.00
(0.012)
|
0.02
(0.012)
|
| Week 48, n=224, 217 |
0.01
(0.012)
|
0.01
(0.012)
|
| Title | Change From Baseline in EQ-5D Thermometer Scores at Week 24 and Week 48 |
|---|---|
| Description | The European Quality of Life -5 Dimensions (EQ-5D) is a 5-question quality of life instrument that provides a utility score and visual analogue scale score that describes the participants' health status. The primary reason for including the EQ-5D is to elicit utility values for potential cost-effectiveness analysis for submission to health technology assessment agencies. Thermometer score is based on a visual analogue scale (VAS) ranging from 100 (best imaginable health state) to 0 (worst imaginable health state).Values represented are for adjusted mean. Estimates are calculated from an ANCOVA model adjusting for age, sex, race, Baseline viral load, background dual NRTI therapy and Baseline EQ-5D thermometer score. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). |
| Time Frame | Baseline, Week 24, and Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| mITT-E Population. |
| Arm/Group Title | DTG 50 mg QD | DRV 800 mg + RTV 100 mg QD |
|---|---|---|
| Arm/Group Description | Participants received DTG 50 mg QD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks. Participants were then given the opportunity to receive DTG 50 mg QD during an Extension Phase of the study. | Participants received DRV 800 mg + RTV 100 mg QD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks. |
| Measure Participants | 242 | 242 |
| Week 24, n=221, 216 |
4.95
(0.885)
|
5.96
(0.895)
|
| Week 48, n=224, 220 |
5.78
(0.762)
|
6.95
(0.769)
|
| Title | Human Immunodeficiency Virus Treatment Satisfaction Questionnaire (HIVTSQ) Total Score at Week 4, Week 24, and Week 48 |
|---|---|
| Description | Participant treatment satisfaction was measured using the self-reported scale (HIVTSQ), which consists of 10 items (1-satisfaction, 2-HIV control, 3-adverse effects, 4-level of demand, 5-convenience, 6-flexibility, 7-knowledge, 8-life habits, 9-recommendability, and 10-willingness to continue). Items are scored from 0 (very dissatisfied) to 6 (very satisfied), other than item 4, which has an inverted score from 6 (very demanding) to 0 (very undemanding). The treatment satisfaction score (range: 0-60) was the sum of the individual items. HIVTSQ mITT-E Population=Only participants from USA, France, Germany, Italy, Spain for whom valid translations were available from the mITT-E Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different visits, so the overall number of participants analyzed reflects everyone in the HIVTSQ mITT-E population. |
| Time Frame | Week 4, Week 24, and Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| HIVTSQ mITT-E Population. |
| Arm/Group Title | DTG 50 mg QD | DRV 800 mg + RTV 100 mg QD |
|---|---|---|
| Arm/Group Description | Participants received DTG 50 mg QD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks. Participants were then given the opportunity to receive DTG 50 mg QD during an Extension Phase of the study. | Participants received DRV 800 mg + RTV 100 mg QD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks. |
| Measure Participants | 214 | 206 |
| Week 4, n=206, 192 |
54.1
(6.43)
|
52.4
(7.94)
|
| Week 24, n= 211, 200 |
56.1
(5.16)
|
54.3
(6.94)
|
| Week 48, n=212, 201 |
56.1
(4.60)
|
54.5
(6.78)
|
| Title | Human Immunodeficiency Virus Treatment Satisfaction Questionnaire (HIVTSQ) Lifestyle/Ease Sub Score at Week 4, Week 24, and Week 48 |
|---|---|
| Description | Participant treatment satisfaction was measured using the self-reported scale (HIVTSQ), which consists of 10 items (1-satisfaction, 2-HIV control, 3-adverse effects, 4-level of demand, 5-convenience, 6-flexibility, 7-knowledge, 8-life habits, 9-recommendability, and 10-willingness to continue). Items are scored from 0 (very dissatisfied) to 6 (very satisfied), other than item 4, which has an inverted score from 6 (very demanding) to 0 (very undemanding). The lifestyle/ease score is the sum of items 4, 5, 6, 7 and 8 (range: 0-30). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different visits, so the overall number of participants analyzed reflects everyone in the HIVTSQ mITT-E population. |
| Time Frame | Week 4, Week 24, and Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| HIVTSQ mITT-E Population. |
| Arm/Group Title | DTG 50 mg QD | DRV 800 mg + RTV 100 mg QD |
|---|---|---|
| Arm/Group Description | Participants received DTG 50 mg QD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks. Participants were then given the opportunity to receive DTG 50 mg QD during an Extension Phase of the study. | Participants received DRV 800 mg + RTV 100 mg QD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks. |
| Measure Participants | 214 | 206 |
| Week 4, n=202, 190 |
26.7
(3.61)
|
25.8
(4.48)
|
| Week 24, n=210, 199 |
27.5
(3.16)
|
26.6
(4.11)
|
| Week 48, n=211, 201 |
27.6
(3.00)
|
26.6
(4.11)
|
| Title | Human Immunodeficiency Virus Treatment Satisfaction Questionnaire (HIVTSQ) Convenience Score at Week 4, Week 24, and Week 48 |
|---|---|
| Description | Participant treatment satisfaction was measured using the self-reported scale (HIVTSQ), which consists of 10 items (1-satisfaction, 2-HIV control, 3-adverse effects, 4-level of demand, 5-convenience, 6-flexibility, 7-knowledge, 8-life habits, 9-recommendability, and 10-willingness to continue). Items are scored from 0 (very dissatisfied) to 6 (very satisfied), other than item 4, which has an inverted score from 6 (very demanding) to 0 (very undemanding). The convenience score is the score for item 5 (range: 0-6). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different visits, so the overall number of participants analyzed reflects everyone in the HIVTSQ mITT-E population. |
| Time Frame | Week 4, Week 24, and Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| HIVTSQ mITT-E Population. |
| Arm/Group Title | DTG 50 mg QD | DRV 800 mg + RTV 100 mg QD |
|---|---|---|
| Arm/Group Description | Participants received DTG 50 mg QD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks. Participants were then given the opportunity to receive DTG 50 mg QD during an Extension Phase of the study. | Participants received DRV 800 mg + RTV 100 mg QD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks. |
| Measure Participants | 214 | 206 |
| Week 4, n=204, 190 |
5.6
(0.71)
|
5.2
(1.11)
|
| Week 24, n=211, 200, |
5.6
(0.64)
|
5.4
(1.01)
|
| Week 48, n=212, 201 |
5.7
(0.62)
|
5.4
(1.02)
|
Adverse Events
| Time Frame | Serious adverse events (SAEs) and non-serious adverse events (AEs) are presented from the available safety data from the start of the study medication up to end of study. | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | SAEs and non-serious AEs were reported for members of the Modified Safety Population, comprised of all participants who received at least one dose of investigational product excluding one participant at one site, which was closed due to GCP non-compliance issues in another ViiV Healthcare sponsored trial. | |||||
| Arm/Group Title | DTG 50mg QD | DRV 800 mg + RTV 100 mg QD | Extension DTG 50 mg | |||
| Arm/Group Description | Participants received DTG 50 mg QD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks. Participants were then given the opportunity to receive DTG 50 mg QD during an Extension Phase of the study. | Participants received DRV 800 mg + RTV 100 mg QD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks. | DTG participants who successfully completed 96 Weeks of randomized phase continued to receive DTG 50 mg QD during Extension phase | |||
All Cause Mortality |
||||||
| DTG 50mg QD | DRV 800 mg + RTV 100 mg QD | Extension DTG 50 mg | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/242 (0.4%) | 0/242 (0%) | 0/123 (0%) | |||
Serious Adverse Events |
||||||
| DTG 50mg QD | DRV 800 mg + RTV 100 mg QD | Extension DTG 50 mg | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 36/242 (14.9%) | 21/242 (8.7%) | 4/123 (3.3%) | |||
| Blood and lymphatic system disorders | ||||||
| Methaemoglobinaemia | 0/242 (0%) | 0 | 0/242 (0%) | 0 | 1/123 (0.8%) | 1 |
| Cardiac disorders | ||||||
| Cardiomyopathy alcoholic | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Congestive cardiomyopathy | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Coronary artery disease | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Myocardial infarction | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Myocarditis | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Gastrointestinal disorders | ||||||
| Abdominal adhesions | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Anal fistula | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Constipation | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Diarrhoea haemorrhagic | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Haematemesis | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Haemorrhoids | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Odynophagia | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Pancreatitis acute | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Small intestinal obstruction | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Hepatobiliary disorders | ||||||
| Cholelithiasis | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Immune system disorders | ||||||
| Allergy to arthropod sting | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Drug hypersensitivity | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Infections and infestations | ||||||
| Acute hepatitis C | 1/242 (0.4%) | 1 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Acute sinusitis | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Appendicitis | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Bronchitis | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Gastroenteritis | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Herpes zoster disseminated | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Herpes zoster infection neurological | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Neurosyphilis | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Perineal abscess | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Pneumonia | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Pneumonia bacterial | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Proctitis infectious | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Pulmonary tuberculosis | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Pyelonephritis | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Sepsis | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Staphylococcal infection | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Subcutaneous abscess | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Tonsillitis | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Urinary tract infection | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||
| Accidental overdose | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Back injury | 0/242 (0%) | 0 | 0/242 (0%) | 0 | 1/123 (0.8%) | 1 |
| Postoperative ileus | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Stab wound | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Tendon rupture | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Tibia fracture | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Toxicity to various agents | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||
| Arthralgia | 1/242 (0.4%) | 1 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Intervertebral disc protrusion | 0/242 (0%) | 0 | 0/242 (0%) | 0 | 1/123 (0.8%) | 1 |
| Myofascial pain syndrome | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Polyarthritis | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Hodgkin's disease | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Nervous system disorders | ||||||
| Cerebrovascular accident | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Epilepsy | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Generalised tonic-clonic seizure | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Lacunar stroke | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Syncope | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Pregnancy, puerperium and perinatal conditions | ||||||
| Abortion spontaneous | 1/242 (0.4%) | 1 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Complication of pregnancy | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Psychiatric disorders | ||||||
| Suicide attempt | 3/242 (1.2%) | 3 | 0/242 (0%) | 0 | 1/123 (0.8%) | 1 |
| Depression | 1/242 (0.4%) | 1 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Completed suicide | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Drug use disorder | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Renal and urinary disorders | ||||||
| Acute kidney injury | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Calculus urinary | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| Asthma | 2/242 (0.8%) | 3 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Chronic obstructive pulmonary disease | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||
| DTG 50mg QD | DRV 800 mg + RTV 100 mg QD | Extension DTG 50 mg | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 221/242 (91.3%) | 214/242 (88.4%) | 52/123 (42.3%) | |||
| Blood and lymphatic system disorders | ||||||
| Lymphadenopathy | 7/242 (2.9%) | 7 | 6/242 (2.5%) | 6 | 0/123 (0%) | 0 |
| Neutropenia | 3/242 (1.2%) | 3 | 3/242 (1.2%) | 3 | 0/123 (0%) | 0 |
| Anaemia | 3/242 (1.2%) | 3 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Eosinophilia | 2/242 (0.8%) | 2 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Haemorrhagic anaemia | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Leukocytosis | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Leukopenia | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Cardiac disorders | ||||||
| Palpitations | 4/242 (1.7%) | 4 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Extrasystoles | 2/242 (0.8%) | 2 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Tachycardia | 1/242 (0.4%) | 1 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Arrhythmia | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Atrioventricular block second degree | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Bradycardia | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Bundle branch block left | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Cardiac failure | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Cardiac failure congestive | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Myocardial infarction | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Pericarditis | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Ventricular hypertrophy | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Congenital, familial and genetic disorders | ||||||
| Bicuspid aortic valve | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Type V hyperlipidaemia | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Ear and labyrinth disorders | ||||||
| Ear congestion | 2/242 (0.8%) | 3 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Tinnitus | 1/242 (0.4%) | 3 | 1/242 (0.4%) | 1 | 1/123 (0.8%) | 1 |
| Vertigo | 0/242 (0%) | 0 | 3/242 (1.2%) | 4 | 0/123 (0%) | 0 |
| Deafness | 1/242 (0.4%) | 1 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Cerumen impaction | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Ear canal erythema | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Tympanic membrane perforation | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Endocrine disorders | ||||||
| Hypogonadism | 2/242 (0.8%) | 2 | 2/242 (0.8%) | 2 | 0/123 (0%) | 0 |
| Eye disorders | ||||||
| Vision blurred | 2/242 (0.8%) | 2 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Chalazion | 1/242 (0.4%) | 1 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Vitreous floaters | 1/242 (0.4%) | 1 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Cataract | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Keratitis | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Scleral discolouration | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Xerophthalmia | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Gastrointestinal disorders | ||||||
| Diarrhoea | 43/242 (17.8%) | 46 | 74/242 (30.6%) | 98 | 2/123 (1.6%) | 2 |
| Nausea | 40/242 (16.5%) | 45 | 48/242 (19.8%) | 56 | 2/123 (1.6%) | 2 |
| Vomiting | 15/242 (6.2%) | 16 | 17/242 (7%) | 22 | 0/123 (0%) | 0 |
| Abdominal pain | 13/242 (5.4%) | 14 | 12/242 (5%) | 12 | 0/123 (0%) | 0 |
| Constipation | 13/242 (5.4%) | 13 | 5/242 (2.1%) | 5 | 0/123 (0%) | 0 |
| Abdominal distension | 8/242 (3.3%) | 10 | 9/242 (3.7%) | 9 | 0/123 (0%) | 0 |
| Flatulence | 5/242 (2.1%) | 6 | 11/242 (4.5%) | 11 | 0/123 (0%) | 0 |
| Haemorrhoids | 8/242 (3.3%) | 8 | 6/242 (2.5%) | 6 | 1/123 (0.8%) | 1 |
| Abdominal pain upper | 10/242 (4.1%) | 10 | 4/242 (1.7%) | 4 | 0/123 (0%) | 0 |
| Dyspepsia | 5/242 (2.1%) | 6 | 7/242 (2.9%) | 9 | 0/123 (0%) | 0 |
| Gastrooesophageal reflux disease | 6/242 (2.5%) | 8 | 4/242 (1.7%) | 4 | 0/123 (0%) | 0 |
| Abdominal discomfort | 3/242 (1.2%) | 3 | 6/242 (2.5%) | 7 | 0/123 (0%) | 0 |
| Rectal haemorrhage | 4/242 (1.7%) | 4 | 3/242 (1.2%) | 3 | 1/123 (0.8%) | 1 |
| Faeces soft | 3/242 (1.2%) | 3 | 3/242 (1.2%) | 3 | 0/123 (0%) | 0 |
| Anal fissure | 2/242 (0.8%) | 2 | 3/242 (1.2%) | 3 | 0/123 (0%) | 0 |
| Dry mouth | 3/242 (1.2%) | 4 | 2/242 (0.8%) | 2 | 0/123 (0%) | 0 |
| Toothache | 2/242 (0.8%) | 2 | 3/242 (1.2%) | 3 | 0/123 (0%) | 0 |
| Dental caries | 2/242 (0.8%) | 2 | 2/242 (0.8%) | 2 | 0/123 (0%) | 0 |
| Gastritis | 1/242 (0.4%) | 1 | 3/242 (1.2%) | 3 | 0/123 (0%) | 0 |
| Proctalgia | 4/242 (1.7%) | 4 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Aphthous ulcer | 3/242 (1.2%) | 3 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Colitis | 2/242 (0.8%) | 2 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Haematochezia | 2/242 (0.8%) | 2 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Proctitis | 2/242 (0.8%) | 2 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Anal ulcer | 2/242 (0.8%) | 2 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Anogenital dysplasia | 0/242 (0%) | 0 | 2/242 (0.8%) | 2 | 0/123 (0%) | 0 |
| Anorectal disorder | 2/242 (0.8%) | 2 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Diarrhoea haemorrhagic | 1/242 (0.4%) | 1 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Enterocolitis | 1/242 (0.4%) | 1 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Food poisoning | 0/242 (0%) | 0 | 2/242 (0.8%) | 2 | 0/123 (0%) | 0 |
| Frequent bowel movements | 1/242 (0.4%) | 1 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Haemorrhoidal haemorrhage | 1/242 (0.4%) | 1 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Oral pain | 0/242 (0%) | 0 | 2/242 (0.8%) | 2 | 0/123 (0%) | 0 |
| Tongue coated | 0/242 (0%) | 0 | 2/242 (0.8%) | 2 | 0/123 (0%) | 0 |
| Abdominal hernia | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Abdominal pain lower | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Abdominal tenderness | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Anal haemorrhage | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Anal pruritus | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Anorectal discomfort | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Colitis microscopic | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Crohn's disease | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Dysphagia | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Epigastric discomfort | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Gastrointestinal disorder | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Gastrointestinal erosion | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Gastrointestinal inflammation | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Gingival disorder | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Gingival recession | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Glossodynia | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Haemorrhoids thrombosed | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Hyperchlorhydria | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Inguinal hernia | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Intestinal polyp | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Leukoplakia oral | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Mouth ulceration | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Mucous stools | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Noninfective gingivitis | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Odynophagia | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Oedema mouth | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Oesophagitis | 0/242 (0%) | 0 | 0/242 (0%) | 0 | 1/123 (0.8%) | 1 |
| Palatal disorder | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Pancreatitis chronic | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Rectal lesion | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Stomatitis | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Tongue disorder | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Tongue dry | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Tongue ulceration | 0/242 (0%) | 0 | 0/242 (0%) | 0 | 1/123 (0.8%) | 1 |
| Tooth impacted | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| General disorders | ||||||
| Pyrexia | 16/242 (6.6%) | 17 | 16/242 (6.6%) | 17 | 0/123 (0%) | 0 |
| Fatigue | 15/242 (6.2%) | 17 | 14/242 (5.8%) | 15 | 0/123 (0%) | 0 |
| Asthenia | 5/242 (2.1%) | 7 | 11/242 (4.5%) | 11 | 2/123 (1.6%) | 2 |
| Influenza like illness | 9/242 (3.7%) | 11 | 6/242 (2.5%) | 7 | 0/123 (0%) | 0 |
| Chest pain | 3/242 (1.2%) | 3 | 7/242 (2.9%) | 8 | 0/123 (0%) | 0 |
| Pain | 3/242 (1.2%) | 3 | 5/242 (2.1%) | 6 | 0/123 (0%) | 0 |
| Chills | 2/242 (0.8%) | 2 | 4/242 (1.7%) | 4 | 0/123 (0%) | 0 |
| Feeling hot | 2/242 (0.8%) | 2 | 4/242 (1.7%) | 5 | 0/123 (0%) | 0 |
| Malaise | 3/242 (1.2%) | 3 | 2/242 (0.8%) | 2 | 0/123 (0%) | 0 |
| Peripheral swelling | 3/242 (1.2%) | 3 | 2/242 (0.8%) | 2 | 0/123 (0%) | 0 |
| Local swelling | 1/242 (0.4%) | 1 | 2/242 (0.8%) | 2 | 0/123 (0%) | 0 |
| Chest discomfort | 1/242 (0.4%) | 1 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Discomfort | 0/242 (0%) | 0 | 2/242 (0.8%) | 2 | 0/123 (0%) | 0 |
| Thirst | 1/242 (0.4%) | 1 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Abscess sterile | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Axillary pain | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Cyst | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Dysplasia | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Feeling abnormal | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Hunger | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Nodule | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Oedema peripheral | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Submandibular mass | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Systemic inflammatory response syndrome | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Thirst decreased | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Vaccination site erythema | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Hepatobiliary disorders | ||||||
| Cholelithiasis | 1/242 (0.4%) | 1 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Hepatic steatosis | 2/242 (0.8%) | 2 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Gallbladder cholesterolosis | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Hepatitis alcoholic | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Hepatosplenomegaly | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Immune system disorders | ||||||
| Seasonal allergy | 3/242 (1.2%) | 3 | 3/242 (1.2%) | 3 | 1/123 (0.8%) | 1 |
| Hypersensitivity | 4/242 (1.7%) | 5 | 1/242 (0.4%) | 1 | 1/123 (0.8%) | 1 |
| Multiple allergies | 1/242 (0.4%) | 1 | 3/242 (1.2%) | 3 | 0/123 (0%) | 0 |
| Drug hypersensitivity | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Food allergy | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Jarisch-Herxheimer reaction | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Infections and infestations | ||||||
| Viral upper respiratory tract infection | 26/242 (10.7%) | 33 | 24/242 (9.9%) | 26 | 5/123 (4.1%) | 5 |
| Upper respiratory tract infection | 16/242 (6.6%) | 22 | 27/242 (11.2%) | 30 | 1/123 (0.8%) | 1 |
| Bronchitis | 12/242 (5%) | 12 | 17/242 (7%) | 20 | 0/123 (0%) | 0 |
| Gastroenteritis | 12/242 (5%) | 13 | 14/242 (5.8%) | 16 | 3/123 (2.4%) | 3 |
| Pharyngitis | 11/242 (4.5%) | 11 | 14/242 (5.8%) | 15 | 1/123 (0.8%) | 1 |
| Syphilis | 11/242 (4.5%) | 12 | 12/242 (5%) | 12 | 2/123 (1.6%) | 2 |
| Sinusitis | 9/242 (3.7%) | 10 | 13/242 (5.4%) | 14 | 0/123 (0%) | 0 |
| Influenza | 4/242 (1.7%) | 4 | 11/242 (4.5%) | 11 | 2/123 (1.6%) | 2 |
| Folliculitis | 7/242 (2.9%) | 7 | 6/242 (2.5%) | 6 | 0/123 (0%) | 0 |
| Urethritis | 8/242 (3.3%) | 8 | 4/242 (1.7%) | 4 | 1/123 (0.8%) | 1 |
| Conjunctivitis | 4/242 (1.7%) | 4 | 7/242 (2.9%) | 7 | 1/123 (0.8%) | 1 |
| Gonorrhoea | 8/242 (3.3%) | 9 | 4/242 (1.7%) | 4 | 0/123 (0%) | 0 |
| Rhinitis | 4/242 (1.7%) | 4 | 6/242 (2.5%) | 8 | 1/123 (0.8%) | 1 |
| Urinary tract infection | 7/242 (2.9%) | 7 | 4/242 (1.7%) | 5 | 0/123 (0%) | 0 |
| Tonsillitis | 5/242 (2.1%) | 5 | 3/242 (1.2%) | 4 | 1/123 (0.8%) | 1 |
| Oral herpes | 6/242 (2.5%) | 6 | 2/242 (0.8%) | 2 | 0/123 (0%) | 0 |
| Respiratory tract infection | 2/242 (0.8%) | 3 | 5/242 (2.1%) | 5 | 1/123 (0.8%) | 1 |
| Furuncle | 3/242 (1.2%) | 3 | 4/242 (1.7%) | 5 | 0/123 (0%) | 0 |
| Herpes zoster | 2/242 (0.8%) | 2 | 5/242 (2.1%) | 5 | 0/123 (0%) | 0 |
| Nasopharyngitis | 3/242 (1.2%) | 3 | 2/242 (0.8%) | 2 | 2/123 (1.6%) | 2 |
| Tooth abscess | 1/242 (0.4%) | 1 | 5/242 (2.1%) | 7 | 1/123 (0.8%) | 1 |
| Viral infection | 6/242 (2.5%) | 6 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Acarodermatitis | 5/242 (2.1%) | 5 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Chlamydial infection | 2/242 (0.8%) | 2 | 3/242 (1.2%) | 3 | 1/123 (0.8%) | 1 |
| Fungal skin infection | 2/242 (0.8%) | 2 | 4/242 (1.7%) | 5 | 0/123 (0%) | 0 |
| Tooth infection | 1/242 (0.4%) | 1 | 5/242 (2.1%) | 5 | 0/123 (0%) | 0 |
| Gastroenteritis viral | 3/242 (1.2%) | 3 | 1/242 (0.4%) | 1 | 1/123 (0.8%) | 1 |
| Cellulitis | 4/242 (1.7%) | 4 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Fungal infection | 2/242 (0.8%) | 2 | 2/242 (0.8%) | 2 | 0/123 (0%) | 0 |
| Genital herpes | 3/242 (1.2%) | 4 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Gingivitis | 2/242 (0.8%) | 2 | 2/242 (0.8%) | 2 | 0/123 (0%) | 0 |
| Herpes simplex | 4/242 (1.7%) | 4 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Hordeolum | 1/242 (0.4%) | 1 | 3/242 (1.2%) | 4 | 0/123 (0%) | 0 |
| Tinea pedis | 1/242 (0.4%) | 1 | 3/242 (1.2%) | 3 | 0/123 (0%) | 0 |
| Abscess | 2/242 (0.8%) | 2 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Abscess limb | 2/242 (0.8%) | 2 | 1/242 (0.4%) | 2 | 0/123 (0%) | 0 |
| Body tinea | 3/242 (1.2%) | 3 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Dermatophytosis | 2/242 (0.8%) | 2 | 1/242 (0.4%) | 2 | 0/123 (0%) | 0 |
| Ear infection | 1/242 (0.4%) | 1 | 2/242 (0.8%) | 2 | 0/123 (0%) | 0 |
| Herpes virus infection | 2/242 (0.8%) | 2 | 1/242 (0.4%) | 2 | 0/123 (0%) | 0 |
| Lower respiratory tract infection | 2/242 (0.8%) | 2 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Onychomycosis | 2/242 (0.8%) | 2 | 0/242 (0%) | 0 | 1/123 (0.8%) | 1 |
| Oral fungal infection | 0/242 (0%) | 0 | 3/242 (1.2%) | 3 | 0/123 (0%) | 0 |
| Pharyngitis streptococcal | 1/242 (0.4%) | 1 | 2/242 (0.8%) | 2 | 0/123 (0%) | 0 |
| Pneumonia | 2/242 (0.8%) | 2 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Staphylococcal infection | 1/242 (0.4%) | 1 | 2/242 (0.8%) | 2 | 0/123 (0%) | 0 |
| Abdominal abscess | 1/242 (0.4%) | 1 | 1/242 (0.4%) | 2 | 0/123 (0%) | 0 |
| Acute sinusitis | 1/242 (0.4%) | 1 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Anal abscess | 1/242 (0.4%) | 1 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Anal chlamydia infection | 0/242 (0%) | 0 | 2/242 (0.8%) | 2 | 0/123 (0%) | 0 |
| Cystitis | 1/242 (0.4%) | 1 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Ear infection fungal | 2/242 (0.8%) | 2 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Hepatitis C | 0/242 (0%) | 0 | 2/242 (0.8%) | 2 | 0/123 (0%) | 0 |
| Infected bite | 2/242 (0.8%) | 2 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Latent tuberculosis | 2/242 (0.8%) | 2 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Molluscum contagiosum | 0/242 (0%) | 0 | 2/242 (0.8%) | 2 | 0/123 (0%) | 0 |
| Oral candidiasis | 2/242 (0.8%) | 2 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Papilloma viral infection | 2/242 (0.8%) | 2 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Parainfluenzae virus infection | 2/242 (0.8%) | 2 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Paronychia | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 1/123 (0.8%) | 1 |
| Periodontitis | 2/242 (0.8%) | 3 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Proctitis gonococcal | 2/242 (0.8%) | 2 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Rash pustular | 1/242 (0.4%) | 1 | 1/242 (0.4%) | 2 | 0/123 (0%) | 0 |
| Respiratory tract infection viral | 0/242 (0%) | 0 | 1/242 (0.4%) | 2 | 1/123 (0.8%) | 1 |
| Secondary syphilis | 1/242 (0.4%) | 1 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Subcutaneous abscess | 1/242 (0.4%) | 1 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Tinea cruris | 0/242 (0%) | 0 | 2/242 (0.8%) | 2 | 0/123 (0%) | 0 |
| Tinea versicolour | 1/242 (0.4%) | 1 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Trichomoniasis | 2/242 (0.8%) | 2 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Urethritis chlamydial | 1/242 (0.4%) | 1 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Urethritis gonococcal | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 1/123 (0.8%) | 1 |
| Viral rash | 2/242 (0.8%) | 2 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Viral rhinitis | 2/242 (0.8%) | 2 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Vulvovaginal candidiasis | 0/242 (0%) | 0 | 2/242 (0.8%) | 2 | 0/123 (0%) | 0 |
| Vulvovaginal mycotic infection | 0/242 (0%) | 0 | 2/242 (0.8%) | 3 | 0/123 (0%) | 0 |
| Anal infection | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Bacterial vaginosis | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Borrelia infection | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Bronchitis viral | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Candida infection | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Carbuncle | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Chronic sinusitis | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Chronic tonsillitis | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Clostridium difficile colitis | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Condyloma latum | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Diarrhoea infectious | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Empyema | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Enterobiasis | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Escherichia urinary tract infection | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Eye infection syphilitic | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Genital candidiasis | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Genitourinary chlamydia infection | 0/242 (0%) | 0 | 0/242 (0%) | 0 | 1/123 (0.8%) | 1 |
| Groin abscess | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Helicobacter gastritis | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Infected fistula | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Infection | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Labyrinthitis | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Laryngitis | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Latent syphilis | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Localised infection | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Orchitis | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Oropharyngeal candidiasis | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Oropharyngitis fungal | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Osteomyelitis | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Otitis externa | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Otitis media | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Parotitis | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Peritonsillar abscess | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Pertussis | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Primary syphilis | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Proctitis chlamydial | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Pulmonary tuberculosis | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Pyelonephritis acute | 1/242 (0.4%) | 2 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Rotavirus infection | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Salmonellosis | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Shigella infection | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Sialoadenitis | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Skin candida | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Strongyloidiasis | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Superinfection bacterial | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Tinea capitis | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Tongue fungal infection | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Tonsillitis bacterial | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Tracheitis | 0/242 (0%) | 0 | 0/242 (0%) | 0 | 1/123 (0.8%) | 1 |
| Ureaplasma infection | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Vaginal infection | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Viral pharyngitis | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Wound infection staphylococcal | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||
| Arthropod bite | 4/242 (1.7%) | 4 | 2/242 (0.8%) | 2 | 0/123 (0%) | 0 |
| Procedural pain | 5/242 (2.1%) | 5 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Contusion | 1/242 (0.4%) | 1 | 4/242 (1.7%) | 4 | 0/123 (0%) | 0 |
| Ligament sprain | 4/242 (1.7%) | 4 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Hand fracture | 2/242 (0.8%) | 2 | 2/242 (0.8%) | 3 | 0/123 (0%) | 0 |
| Animal bite | 1/242 (0.4%) | 1 | 2/242 (0.8%) | 3 | 0/123 (0%) | 0 |
| Fall | 1/242 (0.4%) | 1 | 2/242 (0.8%) | 2 | 0/123 (0%) | 0 |
| Laceration | 3/242 (1.2%) | 3 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Muscle strain | 2/242 (0.8%) | 2 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Thermal burn | 1/242 (0.4%) | 1 | 2/242 (0.8%) | 2 | 0/123 (0%) | 0 |
| Burn oral cavity | 1/242 (0.4%) | 1 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Foot fracture | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 1/123 (0.8%) | 1 |
| Joint injury | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 1/123 (0.8%) | 1 |
| Ligament rupture | 1/242 (0.4%) | 1 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Meniscus injury | 1/242 (0.4%) | 1 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Rib fracture | 2/242 (0.8%) | 2 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Road traffic accident | 0/242 (0%) | 0 | 2/242 (0.8%) | 2 | 0/123 (0%) | 0 |
| Skin abrasion | 0/242 (0%) | 0 | 2/242 (0.8%) | 2 | 0/123 (0%) | 0 |
| Tooth fracture | 1/242 (0.4%) | 1 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Arthropod sting | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Axillary nerve injury | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Back injury | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Burns first degree | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Burns second degree | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Burns third degree | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Concussion | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Corneal abrasion | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Epicondylitis | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Eye injury | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Head injury | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Incision site haemorrhage | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Incision site pain | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Limb injury | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Patella fracture | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Penis injury | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Post procedural swelling | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Post-traumatic pain | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Product use complaint | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Scrotal haematoma | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Skin injury | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Sports injury | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Sunburn | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Tendon rupture | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Investigations | ||||||
| Blood creatine phosphokinase increased | 9/242 (3.7%) | 9 | 2/242 (0.8%) | 2 | 0/123 (0%) | 0 |
| Aspartate aminotransferase increased | 2/242 (0.8%) | 2 | 4/242 (1.7%) | 4 | 0/123 (0%) | 0 |
| Blood triglycerides increased | 1/242 (0.4%) | 1 | 3/242 (1.2%) | 3 | 1/123 (0.8%) | 1 |
| Weight increased | 3/242 (1.2%) | 3 | 2/242 (0.8%) | 2 | 0/123 (0%) | 0 |
| Blood cholesterol increased | 1/242 (0.4%) | 3 | 3/242 (1.2%) | 3 | 0/123 (0%) | 0 |
| Blood creatinine increased | 4/242 (1.7%) | 4 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Transaminases increased | 2/242 (0.8%) | 2 | 2/242 (0.8%) | 2 | 0/123 (0%) | 0 |
| Weight decreased | 1/242 (0.4%) | 1 | 3/242 (1.2%) | 3 | 0/123 (0%) | 0 |
| Alanine aminotransferase increased | 0/242 (0%) | 0 | 3/242 (1.2%) | 3 | 0/123 (0%) | 0 |
| Lipase increased | 0/242 (0%) | 0 | 3/242 (1.2%) | 4 | 0/123 (0%) | 0 |
| Blood phosphorus decreased | 0/242 (0%) | 0 | 2/242 (0.8%) | 3 | 0/123 (0%) | 0 |
| Blood testosterone decreased | 0/242 (0%) | 0 | 2/242 (0.8%) | 2 | 0/123 (0%) | 0 |
| High density lipoprotein decreased | 1/242 (0.4%) | 1 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Blood alkaline phosphatase increased | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Blood creatine phosphokinase abnormal | 0/242 (0%) | 0 | 1/242 (0.4%) | 2 | 0/123 (0%) | 0 |
| Blood creatinine abnormal | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Blood glucose increased | 0/242 (0%) | 0 | 1/242 (0.4%) | 3 | 0/123 (0%) | 0 |
| Blood pressure increased | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Blood urine present | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Campylobacter test positive | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Creatinine renal clearance decreased | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Electrocardiogram abnormal | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Electrocardiogram repolarisation abnormality | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Glomerular filtration rate decreased | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Lipids increased | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Liver function test increased | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Low density lipoprotein increased | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Lymph node palpable | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Neutrophil count decreased | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Neutrophil count increased | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Parasite stool test positive | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Protein urine present | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| White blood cells urine positive | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||
| Decreased appetite | 4/242 (1.7%) | 4 | 8/242 (3.3%) | 8 | 0/123 (0%) | 0 |
| Vitamin D deficiency | 5/242 (2.1%) | 5 | 5/242 (2.1%) | 5 | 0/123 (0%) | 0 |
| Dyslipidaemia | 3/242 (1.2%) | 4 | 4/242 (1.7%) | 4 | 0/123 (0%) | 0 |
| Hyperlipidaemia | 1/242 (0.4%) | 1 | 5/242 (2.1%) | 5 | 0/123 (0%) | 0 |
| Hypercholesterolaemia | 0/242 (0%) | 0 | 5/242 (2.1%) | 5 | 0/123 (0%) | 0 |
| Hypertriglyceridaemia | 0/242 (0%) | 0 | 3/242 (1.2%) | 3 | 1/123 (0.8%) | 1 |
| Hyponatraemia | 2/242 (0.8%) | 2 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Hypophosphataemia | 1/242 (0.4%) | 1 | 2/242 (0.8%) | 2 | 0/123 (0%) | 0 |
| Abnormal loss of weight | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Abnormal weight gain | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Dehydration | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Diabetes mellitus | 0/242 (0%) | 0 | 0/242 (0%) | 0 | 1/123 (0.8%) | 1 |
| Diabetes mellitus inadequate control | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Gout | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Hyperglycaemia | 0/242 (0%) | 0 | 0/242 (0%) | 0 | 1/123 (0.8%) | 1 |
| Hyperlipasaemia | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Hypoglycaemia | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Hypokalaemia | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Hypovolaemia | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Iron deficiency | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Lipid metabolism disorder | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Metabolic acidosis | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Obesity | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Type 1 diabetes mellitus | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Type 2 diabetes mellitus | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||
| Back pain | 14/242 (5.8%) | 14 | 17/242 (7%) | 17 | 0/123 (0%) | 0 |
| Arthralgia | 9/242 (3.7%) | 10 | 15/242 (6.2%) | 19 | 0/123 (0%) | 0 |
| Myalgia | 7/242 (2.9%) | 7 | 12/242 (5%) | 13 | 1/123 (0.8%) | 1 |
| Pain in extremity | 9/242 (3.7%) | 9 | 9/242 (3.7%) | 12 | 0/123 (0%) | 0 |
| Muscle spasms | 3/242 (1.2%) | 3 | 3/242 (1.2%) | 3 | 0/123 (0%) | 0 |
| Neck pain | 2/242 (0.8%) | 2 | 4/242 (1.7%) | 4 | 0/123 (0%) | 0 |
| Muscle contracture | 3/242 (1.2%) | 3 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Osteopenia | 3/242 (1.2%) | 3 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Tendonitis | 3/242 (1.2%) | 3 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Flank pain | 2/242 (0.8%) | 2 | 1/242 (0.4%) | 2 | 0/123 (0%) | 0 |
| Joint swelling | 0/242 (0%) | 0 | 3/242 (1.2%) | 3 | 0/123 (0%) | 0 |
| Osteoporosis | 1/242 (0.4%) | 1 | 2/242 (0.8%) | 2 | 0/123 (0%) | 0 |
| Pain in jaw | 2/242 (0.8%) | 2 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Arthritis | 2/242 (0.8%) | 2 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Bursitis | 0/242 (0%) | 0 | 2/242 (0.8%) | 2 | 0/123 (0%) | 0 |
| Groin pain | 1/242 (0.4%) | 1 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Intervertebral disc protrusion | 1/242 (0.4%) | 1 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Musculoskeletal chest pain | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 1/123 (0.8%) | 1 |
| Musculoskeletal pain | 0/242 (0%) | 0 | 2/242 (0.8%) | 2 | 0/123 (0%) | 0 |
| Osteoarthritis | 1/242 (0.4%) | 1 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Spinal disorder | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 1/123 (0.8%) | 1 |
| Axillary mass | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Costochondritis | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Fibromyalgia | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Foot deformity | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Intervertebral disc disorder | 0/242 (0%) | 0 | 0/242 (0%) | 0 | 1/123 (0.8%) | 1 |
| Joint range of motion decreased | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Joint stiffness | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Metatarsalgia | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Muscular weakness | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Musculoskeletal stiffness | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Rhabdomyolysis | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Rotator cuff syndrome | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Temporomandibular joint syndrome | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Tendon disorder | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Torticollis | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Anogenital warts | 8/242 (3.3%) | 10 | 13/242 (5.4%) | 17 | 1/123 (0.8%) | 1 |
| Lipoma | 2/242 (0.8%) | 2 | 2/242 (0.8%) | 2 | 0/123 (0%) | 0 |
| Melanocytic naevus | 1/242 (0.4%) | 1 | 3/242 (1.2%) | 3 | 0/123 (0%) | 0 |
| Basal cell carcinoma | 0/242 (0%) | 0 | 2/242 (0.8%) | 2 | 0/123 (0%) | 0 |
| Seborrhoeic keratosis | 0/242 (0%) | 0 | 2/242 (0.8%) | 3 | 0/123 (0%) | 0 |
| Skin papilloma | 0/242 (0%) | 0 | 2/242 (0.8%) | 2 | 0/123 (0%) | 0 |
| Acrochordon | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Fibroma | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Oral neoplasm | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Papilloma | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Squamous cell carcinoma of skin | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Nervous system disorders | ||||||
| Headache | 40/242 (16.5%) | 45 | 26/242 (10.7%) | 29 | 2/123 (1.6%) | 2 |
| Dizziness | 14/242 (5.8%) | 15 | 13/242 (5.4%) | 14 | 0/123 (0%) | 0 |
| Hypoaesthesia | 4/242 (1.7%) | 4 | 2/242 (0.8%) | 2 | 0/123 (0%) | 0 |
| Paraesthesia | 1/242 (0.4%) | 1 | 4/242 (1.7%) | 5 | 0/123 (0%) | 0 |
| Sciatica | 4/242 (1.7%) | 4 | 0/242 (0%) | 0 | 1/123 (0.8%) | 1 |
| Somnolence | 2/242 (0.8%) | 2 | 3/242 (1.2%) | 3 | 0/123 (0%) | 0 |
| Migraine | 0/242 (0%) | 0 | 4/242 (1.7%) | 4 | 0/123 (0%) | 0 |
| Balance disorder | 0/242 (0%) | 0 | 3/242 (1.2%) | 3 | 0/123 (0%) | 0 |
| Memory impairment | 1/242 (0.4%) | 1 | 2/242 (0.8%) | 2 | 0/123 (0%) | 0 |
| Syncope | 2/242 (0.8%) | 2 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Carpal tunnel syndrome | 2/242 (0.8%) | 2 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Dysgeusia | 0/242 (0%) | 0 | 2/242 (0.8%) | 2 | 0/123 (0%) | 0 |
| Burning sensation | 1/242 (0.4%) | 2 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Cervicobrachial syndrome | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Disturbance in attention | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Dysarthria | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Facial paralysis | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Lethargy | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Lumbar radiculopathy | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Mental impairment | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Nerve compression | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Neuropathy peripheral | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Post herpetic neuralgia | 0/242 (0%) | 0 | 1/242 (0.4%) | 2 | 0/123 (0%) | 0 |
| Sinus headache | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Pregnancy, puerperium and perinatal conditions | ||||||
| Vomiting in pregnancy | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Psychiatric disorders | ||||||
| Insomnia | 19/242 (7.9%) | 21 | 16/242 (6.6%) | 17 | 1/123 (0.8%) | 1 |
| Anxiety | 13/242 (5.4%) | 13 | 9/242 (3.7%) | 9 | 1/123 (0.8%) | 1 |
| Depression | 12/242 (5%) | 14 | 8/242 (3.3%) | 9 | 0/123 (0%) | 0 |
| Abnormal dreams | 3/242 (1.2%) | 3 | 3/242 (1.2%) | 3 | 0/123 (0%) | 0 |
| Drug use disorder | 4/242 (1.7%) | 4 | 2/242 (0.8%) | 2 | 0/123 (0%) | 0 |
| Sleep disorder | 3/242 (1.2%) | 3 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Depressed mood | 0/242 (0%) | 0 | 3/242 (1.2%) | 3 | 0/123 (0%) | 0 |
| Libido decreased | 1/242 (0.4%) | 1 | 2/242 (0.8%) | 2 | 0/123 (0%) | 0 |
| Nightmare | 3/242 (1.2%) | 3 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Panic attack | 2/242 (0.8%) | 2 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Adjustment disorder with depressed mood | 2/242 (0.8%) | 2 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Alcohol abuse | 1/242 (0.4%) | 1 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Bipolar disorder | 2/242 (0.8%) | 2 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Irritability | 1/242 (0.4%) | 1 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Libido disorder | 0/242 (0%) | 0 | 2/242 (0.8%) | 2 | 0/123 (0%) | 0 |
| Tobacco abuse | 1/242 (0.4%) | 1 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Adjustment disorder | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Aggression | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Alcohol withdrawal syndrome | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Anorexia nervosa | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Burnout syndrome | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Dissociation | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Eating disorder | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Flat affect | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Initial insomnia | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Intentional self-injury | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Loss of libido | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Middle insomnia | 0/242 (0%) | 0 | 0/242 (0%) | 0 | 1/123 (0.8%) | 1 |
| Mood swings | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Nervousness | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Persistent depressive disorder | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Psychomotor retardation | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Stress | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Substance use disorder | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Suicide attempt | 0/242 (0%) | 0 | 0/242 (0%) | 0 | 1/123 (0.8%) | 1 |
| Tic | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Renal and urinary disorders | ||||||
| Dysuria | 3/242 (1.2%) | 3 | 3/242 (1.2%) | 3 | 0/123 (0%) | 0 |
| Nephrolithiasis | 2/242 (0.8%) | 2 | 2/242 (0.8%) | 3 | 1/123 (0.8%) | 1 |
| Chromaturia | 2/242 (0.8%) | 2 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Haematuria | 1/242 (0.4%) | 1 | 2/242 (0.8%) | 2 | 0/123 (0%) | 0 |
| Pollakiuria | 2/242 (0.8%) | 2 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Renal colic | 0/242 (0%) | 0 | 1/242 (0.4%) | 2 | 2/123 (1.6%) | 2 |
| Acute kidney injury | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 1/123 (0.8%) | 1 |
| Renal tubular dysfunction | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 1/123 (0.8%) | 1 |
| Urine flow decreased | 2/242 (0.8%) | 2 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Bladder disorder | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Micturition disorder | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Micturition urgency | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Renal failure | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Urethral discharge | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Urinary hesitation | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Urinary incontinence | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Urinary retention | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Reproductive system and breast disorders | ||||||
| Erectile dysfunction | 4/242 (1.7%) | 5 | 4/242 (1.7%) | 4 | 0/123 (0%) | 0 |
| Prostatitis | 2/242 (0.8%) | 2 | 1/242 (0.4%) | 4 | 0/123 (0%) | 0 |
| Balanoposthitis | 1/242 (0.4%) | 1 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Breast cyst | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 1/123 (0.8%) | 1 |
| Genital lesion | 1/242 (0.4%) | 1 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Penile discharge | 2/242 (0.8%) | 2 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Varicocele | 1/242 (0.4%) | 1 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Asthenospermia | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Benign prostatic hyperplasia | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Breast discharge | 0/242 (0%) | 0 | 0/242 (0%) | 0 | 1/123 (0.8%) | 1 |
| Breast mass | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Cervical dysplasia | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Ejaculation failure | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Genital discomfort | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Genital rash | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Gynaecomastia | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Haematospermia | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Menorrhagia | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Ovarian cyst | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Testicular pain | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Vaginal haemorrhage | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Vulvovaginal pruritus | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| Cough | 18/242 (7.4%) | 20 | 19/242 (7.9%) | 21 | 1/123 (0.8%) | 1 |
| Oropharyngeal pain | 10/242 (4.1%) | 10 | 10/242 (4.1%) | 10 | 0/123 (0%) | 0 |
| Sinus congestion | 6/242 (2.5%) | 8 | 8/242 (3.3%) | 9 | 0/123 (0%) | 0 |
| Nasal congestion | 4/242 (1.7%) | 7 | 6/242 (2.5%) | 6 | 1/123 (0.8%) | 1 |
| Rhinitis allergic | 3/242 (1.2%) | 3 | 3/242 (1.2%) | 3 | 0/123 (0%) | 0 |
| Asthma | 1/242 (0.4%) | 3 | 4/242 (1.7%) | 4 | 0/123 (0%) | 0 |
| Chronic obstructive pulmonary disease | 4/242 (1.7%) | 4 | 0/242 (0%) | 0 | 1/123 (0.8%) | 1 |
| Productive cough | 2/242 (0.8%) | 3 | 3/242 (1.2%) | 3 | 0/123 (0%) | 0 |
| Rhinorrhoea | 3/242 (1.2%) | 3 | 2/242 (0.8%) | 3 | 0/123 (0%) | 0 |
| Dyspnoea | 2/242 (0.8%) | 2 | 2/242 (0.8%) | 2 | 0/123 (0%) | 0 |
| Epistaxis | 3/242 (1.2%) | 5 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Pharyngeal erythema | 1/242 (0.4%) | 2 | 2/242 (0.8%) | 2 | 0/123 (0%) | 0 |
| Pulmonary congestion | 3/242 (1.2%) | 4 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Tonsillar hypertrophy | 2/242 (0.8%) | 2 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Upper-airway cough syndrome | 2/242 (0.8%) | 3 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Allergic sinusitis | 0/242 (0%) | 0 | 2/242 (0.8%) | 2 | 0/123 (0%) | 0 |
| Dysphonia | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 1/123 (0.8%) | 1 |
| Dyspnoea exertional | 1/242 (0.4%) | 1 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Paranasal sinus hypersecretion | 2/242 (0.8%) | 3 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Respiratory tract congestion | 1/242 (0.4%) | 1 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Adenoidal hypertrophy | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Asthmatic crisis | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Emphysema | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Hypoventilation | 1/242 (0.4%) | 2 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Laryngeal oedema | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Lower respiratory tract congestion | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Nasal discharge discolouration | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Nasal oedema | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Pharyngeal disorder | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Pharyngeal ulceration | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Rales | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Sinus pain | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Sneezing | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Throat irritation | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Tonsillar exudate | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Vocal cord polyp | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Vocal cord thickening | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Wheezing | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||
| Rash | 13/242 (5.4%) | 13 | 17/242 (7%) | 19 | 0/123 (0%) | 0 |
| Pruritus | 5/242 (2.1%) | 6 | 7/242 (2.9%) | 9 | 0/123 (0%) | 0 |
| Night sweats | 2/242 (0.8%) | 2 | 6/242 (2.5%) | 6 | 1/123 (0.8%) | 1 |
| Alopecia | 5/242 (2.1%) | 5 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Dry skin | 3/242 (1.2%) | 3 | 3/242 (1.2%) | 3 | 0/123 (0%) | 0 |
| Acne | 4/242 (1.7%) | 4 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Eczema | 3/242 (1.2%) | 3 | 2/242 (0.8%) | 2 | 0/123 (0%) | 0 |
| Dermatitis | 1/242 (0.4%) | 1 | 3/242 (1.2%) | 3 | 0/123 (0%) | 0 |
| Erythema | 3/242 (1.2%) | 3 | 0/242 (0%) | 0 | 1/123 (0.8%) | 1 |
| Psoriasis | 0/242 (0%) | 0 | 4/242 (1.7%) | 4 | 0/123 (0%) | 0 |
| Rash macular | 2/242 (0.8%) | 2 | 2/242 (0.8%) | 2 | 0/123 (0%) | 0 |
| Seborrhoeic dermatitis | 0/242 (0%) | 0 | 4/242 (1.7%) | 4 | 0/123 (0%) | 0 |
| Urticaria | 1/242 (0.4%) | 1 | 3/242 (1.2%) | 4 | 0/123 (0%) | 0 |
| Dermal cyst | 3/242 (1.2%) | 3 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Dermatitis allergic | 1/242 (0.4%) | 1 | 2/242 (0.8%) | 2 | 0/123 (0%) | 0 |
| Dermatitis contact | 2/242 (0.8%) | 2 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Dyshidrotic eczema | 2/242 (0.8%) | 2 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Skin lesion | 3/242 (1.2%) | 3 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Drug eruption | 0/242 (0%) | 0 | 2/242 (0.8%) | 2 | 0/123 (0%) | 0 |
| Hyperhidrosis | 2/242 (0.8%) | 2 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Pruritus generalised | 1/242 (0.4%) | 1 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Seborrhoea | 1/242 (0.4%) | 1 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Alopecia areata | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Blister | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Cold sweat | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Dermatosis | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Guttate psoriasis | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Hair colour changes | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Hand dermatitis | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Hyperkeratosis | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Intertrigo | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Lipodystrophy acquired | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Miliaria | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Mucocutaneous ulceration | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Penile ulceration | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Pityriasis | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Prurigo | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Rash erythematous | 0/242 (0%) | 0 | 1/242 (0.4%) | 2 | 0/123 (0%) | 0 |
| Rash generalised | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Rash morbilliform | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Rash pruritic | 1/242 (0.4%) | 2 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Rosacea | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Skin disorder | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Skin erosion | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Skin exfoliation | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Skin fissures | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Skin hyperpigmentation | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Swelling face | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Social circumstances | ||||||
| Bereavement | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Family stress | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Substance use | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Treatment noncompliance | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Vascular disorders | ||||||
| Hypertension | 7/242 (2.9%) | 7 | 10/242 (4.1%) | 10 | 0/123 (0%) | 0 |
| Hot flush | 2/242 (0.8%) | 2 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Varicose vein | 1/242 (0.4%) | 1 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
| Deep vein thrombosis | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Haematoma | 1/242 (0.4%) | 1 | 0/242 (0%) | 0 | 0/123 (0%) | 0 |
| Hypertensive crisis | 0/242 (0%) | 0 | 1/242 (0.4%) | 1 | 0/123 (0%) | 0 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Results Point of Contact
| Name/Title | GSK Response Center |
|---|---|
| Organization | GlaxoSmithKline |
| Phone | 866-435-7343 |
Responsible Party:
ViiV Healthcare
ClinicalTrials.gov Identifier:
NCT01449929
Other Study ID Numbers:
- 114915
First Posted:
Oct 10, 2011
Last Update Posted:
Jan 16, 2018
Last Verified:
Oct 1, 2017