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Attachment Inhibitor Comparison in Heavily Treatment Experienced Patients

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ClinicalTrials.gov Identifier: NCT02362503
Recruitment Status : Active, not recruiting
First Posted : February 13, 2015
Results First Posted : September 18, 2018
Last Update Posted : October 15, 2018
Sponsor:
Information provided by (Responsible Party):
ViiV Healthcare

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition HIV Infections
Interventions Drug: BMS-663068
Other: Placebo
Enrollment 371
Recruitment Details This was a 2 cohort Phase 3 study conducted in heavily treatment experienced (HTE) participants infected with multi-drug resistant human immunodeficiency virus (HIV)-1. Based on the number of fully active and available antiretroviral drug classes at Screening, participants were assigned to either Randomized Cohort or Non-randomized Cohort.
Pre-assignment Details A total of 731 participants were screened, of which 371 were included in either Randomized Cohort (fostemsavir or placebo) or Non-randomized Cohort (fostemsavir) and received at least one dose of study treatment. The study was conducted in 24 countries. The results presented are based on the Week 48 Interim Analysis.
Arm/Group Title Randomized Cohort-Placebo Randomized Cohort-fostemsavir 600 mg BID Non-randomized Cohort-fostemsavir 600 mg BID
Hide Arm/Group Description HTE HIV-1 infected participants with <=2 classes of antiretrovirals remaining with at least 1 but no more than 2 remaining fully active antiretrovirals that can be effectively combined to form a viable new regimen were included in the Randomized Cohort. Participants received placebo twice daily (BID) along with their currently failing antiretroviral regimen for 8 days during the randomized, double-blind period. During the open-label period, all participants received fostemsavir 600 mg BID with an optimized background therapy (OBT). HTE HIV-1 infected participants with <=2 classes of antiretrovirals remaining with at least 1 but no more than 2 remaining fully active antiretrovirals that can be effectively combined to form a viable new regimen were included in the Randomized Cohort. Participants received fostemsavir 600 milligram (mg) BID along with currently failing antiretroviral regimen for 8 days during the randomized, double-blind period. During the open-label period, all participants continued to receive fostemsavir 600 mg BID with an OBT. HTE HIV-1 infected participants with no remaining classes of fully active antiretroviral that could be combined in a new drug regimen were included in the Non-randomized Cohort. Participants received fostemsavir 600 mg BID in combination with OBT.
Period Title: Double-blind Period-Up to 8 Days
Started 69 203 0
Completed 68 198 0
Not Completed 1 5 0
Reason Not Completed
Adverse Event             0             2             0
Death             1             1             0
Lost to Follow-up             0             1             0
No longer meets study criteria             0             1             0
Period Title: Open Label Period-Up to Atleast 96 Weeks
Started 68 198 [1] 99
Completed 0 0 0
Not Completed 68 198 99
Reason Not Completed
Lack of Efficacy             3             9             6
Adverse Event             3             4             5
Death             1             5             12
Withdrawal by Subject             0             5             1
Lost to Follow-up             3             3             1
Non-compliance with study drug             3             8             5
Pregnancy             0             1             0
No longer meets study criteria             0             2             2
Progression of disease             0             1             0
Ongoing at the time of analysis             55             160             67
[1]
Subject withdrawn due to progression of disease died during study due to squamous cell carcinoma.
Arm/Group Title Randomized Cohort-Placebo Randomized Cohort-fostemsavir 600 mg BID Non-randomized Cohort-fostemsavir 600 mg BID Total
Hide Arm/Group Description HTE HIV-1 infected participants with <=2 classes of antiretrovirals remaining with at least 1 but no more than 2 remaining fully active antiretrovirals that can be effectively combined to form a viable new regimen were included in the Randomized Cohort. Participants received placebo twice daily (BID) along with their currently failing antiretroviral regimen for 8 days during the randomized, double-blind period. During the open-label period, all participants received fostemsavir 600 mg BID with an optimized background therapy (OBT). HTE HIV-1 infected participants with <=2 classes of antiretrovirals remaining with at least 1 but no more than 2 remaining fully active antiretrovirals that can be effectively combined to form a viable new regimen were included in the Randomized Cohort. Participants received fostemsavir 600 milligram (mg) BID along with currently failing antiretroviral regimen for 8 days during the randomized, double-blind period. During the open-label period, all participants continued to receive fostemsavir 600 mg BID with an OBT. HTE HIV-1 infected participants with no remaining classes of fully active antiretroviral that could be combined in a new drug regimen were included in the Non-randomized Cohort. Participants received fostemsavir 600 mg BID in combination with OBT. Total of all reporting groups
Overall Number of Baseline Participants 69 203 99 371
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 69 participants 203 participants 99 participants 371 participants
43.0  (11.02) 45.2  (12.72) 48.1  (11.53) 45.6  (12.20)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 69 participants 203 participants 99 participants 371 participants
Female
12
  17.4%
60
  29.6%
10
  10.1%
82
  22.1%
Male
57
  82.6%
143
  70.4%
89
  89.9%
289
  77.9%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Race customized Number Analyzed 69 participants 203 participants 99 participants 371 participants
African American/African Heritage
18
  26.1%
42
  20.7%
23
  23.2%
83
  22.4%
American Indian or Alaska Native
1
   1.4%
6
   3.0%
1
   1.0%
8
   2.2%
Asian
0
   0.0%
2
   1.0%
0
   0.0%
2
   0.5%
Native Hawaiian or other Pacific islander
0
   0.0%
1
   0.5%
0
   0.0%
1
   0.3%
White
47
  68.1%
137
  67.5%
73
  73.7%
257
  69.3%
Mixed
1
   1.4%
6
   3.0%
1
   1.0%
8
   2.2%
Hispanic
1
   1.4%
2
   1.0%
1
   1.0%
4
   1.1%
Mestizo
1
   1.4%
2
   1.0%
0
   0.0%
3
   0.8%
North African
0
   0.0%
1
   0.5%
0
   0.0%
1
   0.3%
Mulatto
0
   0.0%
1
   0.5%
0
   0.0%
1
   0.3%
Brown
0
   0.0%
2
   1.0%
0
   0.0%
2
   0.5%
White and African descent
0
   0.0%
1
   0.5%
0
   0.0%
1
   0.3%
1.Primary Outcome
Title Mean Change in Logarithm to the Base 10 (log10) HIV-1 Ribonucleic Acid (RNA) From Day 1 at Day 8-Randomized Cohort
Hide Description Plasma samples were collected for analysis of HIV-1 RNA. Mean change in log10 HIV-1 RNA from Day 1 was estimated using analysis of covariance (ANCOVA) with log10 HIV-1 RNA change from Day 1 at Day 8 as dependent variable, treatment (fostemsavir or placebo) as an independent variable, and Day 1 log10 HIV-1 RNA as a continuous covariate. Change from Day 1 was calculated as value at Day 8 minus value at Day 1. The analysis was performed on Intent-to-Treat Exposed (ITT-E) Population which comprised of all randomized participants who received at least one dose of study treatment. Missing HIV-1 RNA values at Day 8 were imputed using (a) Day 1 Observation Carried Forward (D1OCF) for participants without a value during blinded treatment (i.e, imputing a zero change from Day 1) or (b) Last Observation Carried Forward (LOCF) for participants with an early value during blinded treatment before the Day 8 analysis visit window.
Time Frame Day 1 and Day 8
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT-E Population. Participants with missing Day 1 HIV-1 RNA values were not analyzed.
Arm/Group Title Randomized Cohort-Placebo Randomized Cohort-fostemsavir 600 mg BID
Hide Arm/Group Description:
HTE HIV-1 infected participants with <=2 classes of antiretrovirals remaining with at least 1 but no more than 2 remaining fully active antiretrovirals that can be effectively combined to form a viable new regimen were included in the Randomized Cohort. Participants received placebo twice daily (BID) along with their currently failing antiretroviral regimen for 8 days during the randomized, double-blind period. During the open-label period, all participants received fostemsavir 600 mg BID with an optimized background therapy (OBT).
HTE HIV-1 infected participants with <=2 classes of antiretrovirals remaining with at least 1 but no more than 2 remaining fully active antiretrovirals that can be effectively combined to form a viable new regimen were included in the Randomized Cohort. Participants received fostemsavir 600 milligram (mg) BID along with currently failing antiretroviral regimen for 8 days during the randomized, double-blind period. During the open-label period, all participants continued to receive fostemsavir 600 mg BID with an OBT.
Overall Number of Participants Analyzed 69 201
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Log10 copies per milliliter (c/mL)
-0.166
(-0.326 to -0.007)
-0.791
(-0.885 to -0.698)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Randomized Cohort-Placebo, Randomized Cohort-fostemsavir 600 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Hypothesis test:µfostemsavir=µPlacebo where µ is a common intercept.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.625
Confidence Interval (2-Sided) 95%
-0.810 to -0.441
Estimation Comments Difference in covariate-adjusted least squares means between treatment groups (Fostemsavir 600 mg BID-Placebo) is presented.
2.Secondary Outcome
Title Percentage of Participants With HIV-1 RNA Decreases From Day 1 That Exceed 0.5 log10 c/mL and 1.0 log10 c/mL at Day 8-Randomized Cohort
Hide Description The percentage of participants in the Randomized Cohort with HIV-1 RNA decreases from Day 1 that exceed 0.5 log10 c/mL and 1.0 log10 c/mL at Day 8 was determined by comparing HIV-1 RNA Day 1 measurement of each participant to their Day 8 measurement. This was an ITT analysis that classified participants without HIV-1 RNA at Day 1 or Day 8 as failures. The percentage of responders along with 95% confidence interval based on Wilson score is presented.
Time Frame Day 1 and Day 8
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT-E Population
Arm/Group Title Randomized Cohort-Placebo Randomized Cohort-fostemsavir 600 mg BID
Hide Arm/Group Description:
HTE HIV-1 infected participants with <=2 classes of antiretrovirals remaining with at least 1 but no more than 2 remaining fully active antiretrovirals that can be effectively combined to form a viable new regimen were included in the Randomized Cohort. Participants received placebo twice daily (BID) along with their currently failing antiretroviral regimen for 8 days during the randomized, double-blind period. During the open-label period, all participants received fostemsavir 600 mg BID with an optimized background therapy (OBT).
HTE HIV-1 infected participants with <=2 classes of antiretrovirals remaining with at least 1 but no more than 2 remaining fully active antiretrovirals that can be effectively combined to form a viable new regimen were included in the Randomized Cohort. Participants received fostemsavir 600 milligram (mg) BID along with currently failing antiretroviral regimen for 8 days during the randomized, double-blind period. During the open-label period, all participants continued to receive fostemsavir 600 mg BID with an OBT.
Overall Number of Participants Analyzed 69 203
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
>0.5 log10 c/mL
18.84
(11.35 to 29.61)
64.53
(57.74 to 70.79)
>1.0 log10 c/mL
10.14
(5.00 to 19.49)
45.81
(39.10 to 52.68)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Randomized Cohort-Placebo, Randomized Cohort-fostemsavir 600 mg BID
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 45.69
Confidence Interval (2-Sided) 95%
32.95 to 55.45
Estimation Comments Difference between treatment groups (fostemsavir 600 mg BID-Placebo) and 95% confidence interval using Newcombe method is presented for >0.5 log10 c/mL.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Randomized Cohort-Placebo, Randomized Cohort-fostemsavir 600 mg BID
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 35.67
Confidence Interval (2-Sided) 95%
24.16 to 44.25
Estimation Comments Difference between treatment groups (fostemsavir 600 mg BID-Placebo) and 95% confidence interval using Newcombe method is presented for >1.0 log10 c/mL.
3.Secondary Outcome
Title Percentage of Participants With HIV-1 RNA <40 c/mL at Weeks 24 and 48-Randomized Cohort
Hide Description The durability of response (that is, the number of participants achieving HIV-1 RNA <40 c/mL) at Weeks 24 and 48 of open-label fostemsavir plus OBT in the Randomized Cohort was assessed using the Food and Drug Administration (FDA) snapshot algorithm in which participants without HIV-1 RNA at Weeks 24 and 48 or those who changed OBT due to lack of efficacy through Weeks 24 and 48 were counted as failures. The percentage of participants in the Randomized Cohort who achieved virologic success (HIV-1 RNA <40 c/mL) at Weeks 24 and 48 is presented along with 95% Wilson confidence interval. All the participants received fostemsavir during the open-label period irrespective of the original arms to which they were randomized; hence, the combined totals for Randomized Cohort is presented as pre-specified in protocol and reporting and analysis plan.
Time Frame Weeks 24 and 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT-E Population
Arm/Group Title Randomized Cohort
Hide Arm/Group Description:
HTE HIV-1 infected participants with <=2 classes of antiretrovirals remaining with at least 1 but no more than 2 remaining fully active antiretrovirals that can be effectively combined to form a viable new regimen were included in the Randomized Cohort. Participants were randomized to receive fostemsavir 600 mg BID or placebo along with their current failing antiretroviral regimen during the double-blind period for 8 days. During the open-label period, all participants received open-label fostemsavir 600 mg BID in combination with OBT for at least 96 weeks.
Overall Number of Participants Analyzed 272
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
Week 24
53
(47.0 to 58.8)
Week 48
54
(47.7 to 59.5)
4.Secondary Outcome
Title Number of Participants With On-treatment Serious Adverse Events (SAEs) and Adverse Events (AEs) Leading to Discontinuation (AELD)-Randomized Cohort
Hide Description An SAE is any untoward medical occurrence that at any dose: results in death; is life-threatening; requires inpatient hospitalization or causes prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; an important medical event that may jeopardize the participant or require intervention. Number of participants with on-treatment SAEs and AEs leading to withdrawal of study treatment is presented. SAEs and AELDs were collected in Safety Population which comprised of all participants who received at least one dose of study treatment. All the participants received fostemsavir during the open-label period irrespective of the original arms to which they were randomized; hence, the combined totals for Randomized Cohort is presented as pre-specified in protocol and reporting and analysis plan.
Time Frame Up to Week 48 analysis cut-off date
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population.
Arm/Group Title Randomized Cohort
Hide Arm/Group Description:
HTE HIV-1 infected participants with <=2 classes of antiretrovirals remaining with at least 1 but no more than 2 remaining fully active antiretrovirals that can be effectively combined to form a viable new regimen were included in the Randomized Cohort. Participants were randomized to receive fostemsavir 600 mg BID or placebo along with their current failing antiretroviral regimen during the double-blind period for 8 days. During the open-label period, all participants received open-label fostemsavir 600 mg BID in combination with OBT for at least 96 weeks.
Overall Number of Participants Analyzed 272
Measure Type: Count of Participants
Unit of Measure: Participants
SAE
85
  31.3%
AELD
14
   5.1%
5.Secondary Outcome
Title Number of Participants With Toxicity Grade Increase in Clinical Chemistry Results to Grade 3-4 Relative to Baseline-Randomized Cohort
Hide Description Laboratory toxicities were graded for severity according to the Division of Acquired Immunodeficiency Syndrome (DAIDS) grading system: Grade 1 (mild); Grade 2 (moderate); Grade 3 (severe); Grade 4 (potentially life-threatening). Baseline is defined as the latest pre-dose assessment. The number of participants with clinical chemistry toxicity grade increase to Grade 3-4 at anytime post-Baseline relative to Baseline is presented. Only participants with data available at the specified time points were analyzed (represented by n=X in category titles). All the participants received fostemsavir during the open-label period irrespective of the original arms to which they were randomized; hence, the combined totals for Randomized Cohort is presented as pre-specified in protocol and reporting and analysis plan.
Time Frame Baseline and up to Week 48 analysis cut-off date
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Randomized Cohort
Hide Arm/Group Description:
HTE HIV-1 infected participants with <=2 classes of antiretrovirals remaining with at least 1 but no more than 2 remaining fully active antiretrovirals that can be effectively combined to form a viable new regimen were included in the Randomized Cohort. Participants were randomized to receive fostemsavir 600 mg BID or placebo along with their current failing antiretroviral regimen during the double-blind period for 8 days. During the open-label period, all participants received open-label fostemsavir 600 mg BID in combination with OBT for at least 96 weeks.
Overall Number of Participants Analyzed 272
Measure Type: Count of Participants
Unit of Measure: Participants
Albumin; n=268 Number Analyzed 268 participants
1
   0.4%
Alkaline phosphatase; n=268 Number Analyzed 268 participants
3
   1.1%
Alanine aminotransferase; n=268 Number Analyzed 268 participants
13
   4.9%
Amylase; n=268 Number Analyzed 268 participants
2
   0.7%
Aspartate aminotransferase; n=268 Number Analyzed 268 participants
9
   3.4%
Bicarbonate; n=268 Number Analyzed 268 participants
1
   0.4%
Direct bilirubin; n=268 Number Analyzed 268 participants
19
   7.1%
Bilirubin; n=268 Number Analyzed 268 participants
6
   2.2%
Calcium; n=268 Number Analyzed 268 participants
9
   3.4%
Cholesterol; n=221 Number Analyzed 221 participants
10
   4.5%
Creatine kinase; n=268 Number Analyzed 268 participants
6
   2.2%
Creatinine; n=268 Number Analyzed 268 participants
43
  16.0%
Estimated creatinine clearance; n=268 Number Analyzed 268 participants
69
  25.7%
Glucose/hyperglycemia; n=267 Number Analyzed 267 participants
6
   2.2%
Glucose/hypoglycemia; n=267 Number Analyzed 267 participants
1
   0.4%
Potassium/hyperkalemia; n=268 Number Analyzed 268 participants
3
   1.1%
Potassium/hypokalemia; n=268 Number Analyzed 268 participants
0
   0.0%
Low density lipoprotein (LDL) cholesterol; n=216 Number Analyzed 216 participants
7
   3.2%
Lipase; n=268 Number Analyzed 268 participants
12
   4.5%
Sodium/hypernatremia; n=268 Number Analyzed 268 participants
0
   0.0%
Sodium/hyponatremia; n=268 Number Analyzed 268 participants
0
   0.0%
Triglycerides; n=221 Number Analyzed 221 participants
10
   4.5%
Urate; n=268 Number Analyzed 268 participants
7
   2.6%
6.Secondary Outcome
Title Number of Participants With Toxicity Grade Increase in Hematology Results to Grade 3-4 Relative to Baseline-Randomized Cohort
Hide Description Laboratory toxicities were graded for severity according to the DAIDS grading system: Grade 1 (mild); Grade 2 (moderate); Grade 3 (severe); Grade 4 (potentially life-threatening). Baseline is defined as the latest pre-dose assessment. The number of participants with hematology toxicity grade increase to Grade 3-4 at anytime post-Baseline relative to Baseline is presented. Only participants with data available at the specified time points were analyzed (represented by n=X in category titles). All the participants received fostemsavir during the open-label period irrespective of the original arms to which they were randomized; hence, the combined totals for Randomized Cohort is presented as pre-specified in protocol and reporting and analysis plan.
Time Frame Baseline and up to Week 48 analysis cut-off date
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Randomized Cohort
Hide Arm/Group Description:
HTE HIV-1 infected participants with <=2 classes of antiretrovirals remaining with at least 1 but no more than 2 remaining fully active antiretrovirals that can be effectively combined to form a viable new regimen were included in the Randomized Cohort. Participants were randomized to receive fostemsavir 600 mg BID or placebo along with their current failing antiretroviral regimen during the double-blind period for 8 days. During the open-label period, all participants received open-label fostemsavir 600 mg BID in combination with OBT for at least 96 weeks.
Overall Number of Participants Analyzed 272
Measure Type: Count of Participants
Unit of Measure: Participants
Hemoglobin; n=268 Number Analyzed 268 participants
14
   5.2%
Neutrophils; n=268 Number Analyzed 268 participants
8
   3.0%
Platelets; n=267 Number Analyzed 267 participants
2
   0.7%
Leukocytes; n=268 Number Analyzed 268 participants
4
   1.5%
7.Secondary Outcome
Title Number of Participants With Centers for Disease Control (CDC) Class C Events-Randomized Cohort
Hide Description Disease progression during open label fostemsavir plus OBT was assessed based on the occurrence of new AIDS defining events (CDC Class C events) or death. The number of participants with on-treatment CDC Class C AIDS events is presented. All the participants received fostemsavir during the open-label period irrespective of the original arms to which they were randomized; hence, the combined totals for Randomized Cohort is presented as pre-specified in protocol and reporting and analysis plan.
Time Frame Up to Week 48 analysis cut-off date
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Randomized Cohort
Hide Arm/Group Description:
HTE HIV-1 infected participants with <=2 classes of antiretrovirals remaining with at least 1 but no more than 2 remaining fully active antiretrovirals that can be effectively combined to form a viable new regimen were included in the Randomized Cohort. Participants were randomized to receive fostemsavir 600 mg BID or placebo along with their current failing antiretroviral regimen during the double-blind period for 8 days. During the open-label period, all participants received open-label fostemsavir 600 mg BID in combination with OBT for at least 96 weeks.
Overall Number of Participants Analyzed 272
Measure Type: Count of Participants
Unit of Measure: Participants
24
   8.8%
8.Secondary Outcome
Title Change From Day 1 in Cluster of Differentiation (CD) 4+ T-cell Count at Day 8-Randomized Cohort
Hide Description CD4+ T- cell counts were assessed by flow cytometry. Mean change in CD4+ T- cell count from Day 1 at Day 8 was analyzed using one-way ANCOVA with change of CD4+ cell counts from Day 1 at Day 8 as the dependent variable, treatment (fostemsavir or placebo) as an in-dependent variable, and Day 1 CD4+ cell count as a continuous covariate. Change from Day 1 was calculated as value at Day 8 minus value at Day 1. Missing CD4+ cell count values at Day 8 were imputed using (a) D1OCF for participants without a value during blinded treatment (i.e., imputing a zero change from Day 1), or (b) LOCF for participants with an early value during blinded treatment before the Day 8 analysis visit window.
Time Frame Day 1 and Day 8
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT-E Population. Only those participants with data available at the specified time points were analyzed.
Arm/Group Title Randomized Cohort-Placebo Randomized Cohort-fostemsavir 600 mg BID
Hide Arm/Group Description:
HTE HIV-1 infected participants with <=2 classes of antiretrovirals remaining with at least 1 but no more than 2 remaining fully active antiretrovirals that can be effectively combined to form a viable new regimen were included in the Randomized Cohort. Participants received placebo twice daily (BID) along with their currently failing antiretroviral regimen for 8 days during the randomized, double-blind period. During the open-label period, all participants received fostemsavir 600 mg BID with an optimized background therapy (OBT).
HTE HIV-1 infected participants with <=2 classes of antiretrovirals remaining with at least 1 but no more than 2 remaining fully active antiretrovirals that can be effectively combined to form a viable new regimen were included in the Randomized Cohort. Participants received fostemsavir 600 milligram (mg) BID along with currently failing antiretroviral regimen for 8 days during the randomized, double-blind period. During the open-label period, all participants continued to receive fostemsavir 600 mg BID with an OBT.
Overall Number of Participants Analyzed 69 196
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Cells per cubic millimeter
18.9
(4.7 to 33.0)
18.5
(10.1 to 26.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Randomized Cohort-Placebo, Randomized Cohort-fostemsavir 600 mg BID
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.4
Confidence Interval (2-Sided) 95%
-16.8 to 16.0
Estimation Comments Difference in covariate-adjusted least squares means between treatment groups (Fostemsavir 600 mg BID-Placebo) is presented.
9.Secondary Outcome
Title Change in CD4+ T- Cell Count Percentage From Day 1 at Day 8-Randomized Cohort
Hide Description CD4+ T- cell counts were assessed by flow cytometry. Mean change in CD4+ T- cell count percentage from Day 1 at Day 8 was analyzed using one-way ANCOVA with change of CD4+ cell count percentage from Day 1 at Day 8 as the dependent variable, treatment (fostemsavir or placebo) as an independent variable, and Day 1 CD4+ cell count percentage as a continuous covariate. Change from Day 1 was calculated as value at Day 8 minus value at Day 1. Missing CD4+ cell count values at Day 8 were imputed using (a) D1OCF for participants without a value during blinded treatment (ie, imputing a zero change from Day 1), or (b) LOCF for participants with an early value during blinded treatment before the Day 8 analysis visit window.
Time Frame Day 1 and Day 8
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ITT-E Population. Only those participants with data available at the specified time points were analyzed.
Arm/Group Title Randomized Cohort-Placebo Randomized Cohort-fostemsavir 600 mg BID
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HTE HIV-1 infected participants with <=2 classes of antiretrovirals remaining with at least 1 but no more than 2 remaining fully active antiretrovirals that can be effectively combined to form a viable new regimen were included in the Randomized Cohort. Participants received placebo twice daily (BID) along with their currently failing antiretroviral regimen for 8 days during the randomized, double-blind period. During the open-label period, all participants received fostemsavir 600 mg BID with an optimized background therapy (OBT).
HTE HIV-1 infected participants with <=2 classes of antiretrovirals remaining with at least 1 but no more than 2 remaining fully active antiretrovirals that can be effectively combined to form a viable new regimen were included in the Randomized Cohort. Participants received fostemsavir 600 milligram (mg) BID along with currently failing antiretroviral regimen for 8 days during the randomized, double-blind period. During the open-label period, all participants continued to receive fostemsavir 600 mg BID with an OBT.
Overall Number of Participants Analyzed 69 196
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Percentage of CD4+T- cells
0.243
(-0.216 to 0.703)
0.860
(0.588 to 1.133)
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Statistical Analysis Overview Comparison Group Selection Randomized Cohort-Placebo, Randomized Cohort-fostemsavir 600 mg BID
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.617
Confidence Interval (2-Sided) 95%
0.082 to 1.151
Estimation Comments Difference in covariate-adjusted least squares means between treatment groups (Fostemsavir 600 mg BID-Placebo) is presented.
10.Secondary Outcome
Title Change From Baseline in log10 HIV-1 RNA for Fostemsavir When Given With OBT Through Week 48-Randomized Cohort
Hide Description Blood samples were collected for the analysis of HIV-1 RNA. Baseline is defined as the last non-missing value on or before the date of first dose of study treatment. Change from Baseline was calculated as the value at post-dose visit minus the value at Baseline. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles). All the participants received fostemsavir during the open-label period irrespective of the original arms to which they were randomized; hence, the combined totals for Randomized Cohort is presented as pre-specified in protocol and reporting and analysis plan.
Time Frame Baseline and up to Week 48
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ITT-E Population
Arm/Group Title Randomized Cohort
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HTE HIV-1 infected participants with <=2 classes of antiretrovirals remaining with at least 1 but no more than 2 remaining fully active antiretrovirals that can be effectively combined to form a viable new regimen were included in the Randomized Cohort. Participants were randomized to receive fostemsavir 600 mg BID or placebo along with their current failing antiretroviral regimen during the double-blind period for 8 days. During the open-label period, all participants received open-label fostemsavir 600 mg BID in combination with OBT for at least 96 weeks.
Overall Number of Participants Analyzed 272
Mean (Standard Deviation)
Unit of Measure: Log10 c/mL
Day 8; n=262 Number Analyzed 262 participants
-0.656  (0.7536)
Week 4; n=262 Number Analyzed 262 participants
-2.051  (1.0717)
Week 8; n=256 Number Analyzed 256 participants
-2.207  (1.1416)
Week 12; n=248 Number Analyzed 248 participants
-2.237  (1.2105)
Week 16; n=249 Number Analyzed 249 participants
-2.277  (1.2834)
Week 24; n=246 Number Analyzed 246 participants
-2.297  (1.2788)
Week 36; n=238 Number Analyzed 238 participants
-2.332  (1.2265)
Week 48; n=233 Number Analyzed 233 participants
-2.324  (1.2876)
11.Secondary Outcome
Title Change From Baseline in CD4+ T- Cell Count Through Week 48-Randomized Cohort
Hide Description CD4+ T- cell counts were assessed by flow cytometry. Baseline is defined as the last non-missing value on or before the date of first dose of study treatment. Change from Baseline was calculated as the value at post-dose visit minus the value at Baseline. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles). All the participants received fostemsavir during the open-label period irrespective of the original arms to which they were randomized; hence, the combined totals for Randomized Cohort is presented as pre-specified in protocol and reporting and analysis plan.
Time Frame Baseline and up to Week 48
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ITT-E Population
Arm/Group Title Randomized Cohort
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HTE HIV-1 infected participants with <=2 classes of antiretrovirals remaining with at least 1 but no more than 2 remaining fully active antiretrovirals that can be effectively combined to form a viable new regimen were included in the Randomized Cohort. Participants were randomized to receive fostemsavir 600 mg BID or placebo along with their current failing antiretroviral regimen during the double-blind period for 8 days. During the open-label period, all participants received open-label fostemsavir 600 mg BID in combination with OBT for at least 96 weeks.
Overall Number of Participants Analyzed 272
Mean (Standard Deviation)
Unit of Measure: Cells per cubic millimeter
Day 8; n=255 Number Analyzed 255 participants
19.8  (60.98)
Week 4; n=259 Number Analyzed 259 participants
48.9  (131.75)
Week 8; n=254 Number Analyzed 254 participants
61.5  (113.47)
Week 12; n=249 Number Analyzed 249 participants
79.0  (123.31)
Week 16; n=245 Number Analyzed 245 participants
84.1  (107.26)
Week 24; n=247 Number Analyzed 247 participants
90.4  (112.10)
Week 36; n=234 Number Analyzed 234 participants
109.7  (119.50)
Week 48; n=228 Number Analyzed 228 participants
138.9  (135.06)
12.Secondary Outcome
Title Change From Baseline in CD4+ T- Cell Count Percentage Through Week 48
Hide Description CD4+ T- cell counts were assessed by flow cytometry. Baseline is defined as the last non-missing value on or before the date of first dose of study treatment. Change from Baseline was calculated as the value at post-dose visit minus the value at Baseline. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles). All the participants received fostemsavir during the open-label period irrespective of the original arms to which they were randomized; hence, the combined totals for Randomized Cohort is presented as pre-specified in protocol and reporting and analysis plan.
Time Frame Baseline and up to Week 48
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ITT-E Population
Arm/Group Title Randomized Cohort
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HTE HIV-1 infected participants with <=2 classes of antiretrovirals remaining with at least 1 but no more than 2 remaining fully active antiretrovirals that can be effectively combined to form a viable new regimen were included in the Randomized Cohort. Participants were randomized to receive fostemsavir 600 mg or placebo along with their current failing antiretroviral regimen during the double-blind period for 8 days. During the open-label period, all participants received open-label fostemsavir 600 mg BID in combination with OBT for at least 96 weeks
Overall Number of Participants Analyzed 272
Mean (Standard Deviation)
Unit of Measure: Percentage of CD4+ T- cells
Day 8; n=255 Number Analyzed 255 participants
0.75  (1.970)
Week 4; n=259 Number Analyzed 259 participants
2.30  (4.643)
Week 8; n=254 Number Analyzed 254 participants
2.36  (4.392)
Week 12; n=249 Number Analyzed 249 participants
3.00  (4.945)
Week 16; n=245 Number Analyzed 245 participants
3.51  (4.979)
Week 24; n=247 Number Analyzed 247 participants
4.26  (4.828)
Week 36; n=234 Number Analyzed 234 participants
5.06  (5.256)
Week 48; n=228 Number Analyzed 228 participants
6.51  (5.531)
13.Secondary Outcome
Title Number of Participants With Treatment-emergent Viral Genotypic Substitution of Interest in the GP160 Domain as a Measure of Genotypic Resistance-Randomized Cohort
Hide Description Plasma samples were collected for drug resistance testing. Participants with emergent viral genotypic substitutions of interest in GP160 domain was identified by next-generation sequencing (NGS) assay. Virologic failure (VF) Population comprised of all participants with available phenotypic and genotypic resistance data meeting at the time protocol defined virologic failure (PDVF) was met. Criteria for PDVF was a) Confirmed, or last available prior to discontinuation, HIV-1 RNA >=400 c/mL at any time after prior confirmed suppression to <400 c/mL prior to Week 24 or Confirmed, or last available prior to discontinuation, >1 log10 c/mL increase in HIV-1 RNA at any time above nadir level where nadir is >=40 c/mL prior to Week 24. b) Confirmed, or last available prior to discontinuation, HIV-1 RNA >=400 c/mL at or after Week 24. All participants received fostemsavir during open-label period irrespective of original randomization; hence, combined totals for Randomized Cohort is presented.
Time Frame Week 48
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VF Population
Arm/Group Title Randomized Cohort
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HTE HIV-1 infected participants with <=2 classes of antiretrovirals remaining with at least 1 but no more than 2 remaining fully active antiretrovirals that can be effectively combined to form a viable new regimen were included in the Randomized Cohort. Participants were randomized to receive fostemsavir 600 mg BID or placebo along with their current failing antiretroviral regimen during the double-blind period for 8 days. During the open-label period, all participants received open-label fostemsavir 600 mg BID in combination with OBT for at least 96 weeks.
Overall Number of Participants Analyzed 47
Measure Type: Count of Participants
Unit of Measure: Participants
20
  42.6%
14.Secondary Outcome
Title Number of Participants With Indicated Fold Change Ratio (FCR) Using the Monogram PhenoSense Entry Assay-Randomized Cohort
Hide Description The phenotypic resistance to a drug is defined in terms of a fold change (FC) in IC50s, ie, the ratio of the 50% inhibitory concentration (IC50) of the clinical isolate to the IC50 of a reference strain (wild type control). FCR was calculated as FC at PDVF divided by Baseline FC. The number of participants with the indicated change (ratio) in the two values at the time of PDVF is presented. FCR<1 indicates that FC is smaller on-treatment than at Baseline. FCR >3 indicates that on-treatment FC is 3 times greater than it was at Baseline. All the participants received fostemsavir during open-label period irrespective of the original arms to which they were randomized; hence, combined totals for Randomized Cohort is presented as pre-specified in protocol and reporting and analysis plan.
Time Frame Week 48
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VF Population. Only participants available at the specified time point were analyzed.
Arm/Group Title Randomized Cohort
Hide Arm/Group Description:
HTE HIV-1 infected participants with <=2 classes of antiretrovirals remaining with at least 1 but no more than 2 remaining fully active antiretrovirals that can be effectively combined to form a viable new regimen were included in the Randomized Cohort. Participants were randomized to receive fostemsavir 600 mg BID or placebo along with their current failing antiretroviral regimen during the double-blind period for 8 days. During the open-label period, all participants received open-label fostemsavir 600 mg BID in combination with OBT for at least 96 weeks.
Overall Number of Participants Analyzed 44
Measure Type: Count of Participants
Unit of Measure: Participants
<=1
15
  34.1%
>1 to 3
8
  18.2%
>3 to 10
4
   9.1%
>10 to 100
1
   2.3%
>100 to 3000
9
  20.5%
>3000
7
  15.9%
Time Frame On-treatment non-SAEs and SAEs were collected from the start of study treatment until the Week 48 data cut-off date. The data presented for Randomized Cohort-Placebo and Randomized Cohort-fostemsavir 600 mg BID represent safety events during the double-blind period (Up to Day 8). The safety data presented in the Randomized Cohort-Total, Non-Randomized Cohort-fostemsavir 600 mg BID and Fostemsavir Total columns represent safety events during fostemsavir dosing until the Week 48 data cut-off date.
Adverse Event Reporting Description Non-SAEs and SAEs were collected in the Safety Population which comprised of all participants who received at least one dose of study treatment. One participant was excluded from the Total fostemsavir population as the participant took only placebo and had discontinued during the double-blind period.
 
Arm/Group Title Randomized Cohort-Placebo Randomized Cohort-fostemsavir 600 mg BID Randomized Cohort-Total Non-randomized Cohort-fostemsavir 600 mg BID Total Fostemsavir
Hide Arm/Group Description This reporting group includes HTE HIV-1 infected participants who were assigned to the Randomized Cohort and randomized to placebo twice daily (BID) along with their currently failing antiretroviral regimen for the double-blind period. During the open-label period, all participants received fostemsavir 600 mg BID and an optimized background therapy (OBT). Randomized Cohort participants are assigned based on their screening status of having <=2 classes of antiretrovirals remaining with at least 1 but no more than 2 remaining fully active antiretrovirals that can be effectively combined to form a viable new regimen. The data reported are safety events during the 8-day double-blind period. This reporting group includes HTE HIV-1 infected participants who were assigned to the Randomized Cohort and randomized to fostemsavir 600 mg BID along with their currently failing antiretroviral regimen for the double-blind period. During the open-label period, all participants received fostemsavir 600 mg BID and OBT. Randomized Cohort participants are assigned based on their screening status of having <=2 classes of antiretrovirals remaining with at least 1 but no more than 2 remaining fully active antiretrovirals that can be effectively combined to form a viable new regimen. The data reported are safety events during the 8-day double-blind period. This reporting group includes all participants in the Randomized Cohort. The data reported are safety events during fostemsavir dosing until the Week 48 data cut-off date. This reporting group includes HTE HIV-1 infected participants who were assigned to the Non-randomized Cohort and received fostemsavir 600 mg BID and OBT. Non-randomized Cohort participants are assigned based on their screening status of having no remaining classes of fully active antiretroviral that can combined in a new drug regimen. The data reported are safety events during fostemsavir dosing until the Week 48 data cut-off date. This reporting group included all enrolled participants (Randomized Cohort and Non-randomized Cohort) and who received fostemsavir 600 mg during the open-label period. The data reported are safety events during fostemsavir dosing until the Week 48 data cut-off date.
All-Cause Mortality
Randomized Cohort-Placebo Randomized Cohort-fostemsavir 600 mg BID Randomized Cohort-Total Non-randomized Cohort-fostemsavir 600 mg BID Total Fostemsavir
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/69 (1.45%)      1/203 (0.49%)      10/271 (3.69%)      14/99 (14.14%)      24/370 (6.49%)    
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Randomized Cohort-Placebo Randomized Cohort-fostemsavir 600 mg BID Randomized Cohort-Total Non-randomized Cohort-fostemsavir 600 mg BID Total Fostemsavir
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/69 (2.90%)      5/203 (2.46%)      85/271 (31.37%)      44/99 (44.44%)      129/370 (34.86%)    
Blood and lymphatic system disorders           
Iron deficiency anaemia  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 1/99 (1.01%)  1 2/370 (0.54%)  2
Anaemia  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 1/99 (1.01%)  1 1/370 (0.27%)  1
Febrile neutropenia  1  0/69 (0.00%)  0 0/203 (0.00%)  0 0/271 (0.00%)  0 1/99 (1.01%)  1 1/370 (0.27%)  1
Cardiac disorders           
Acute myocardial infarction  1  0/69 (0.00%)  0 0/203 (0.00%)  0 3/271 (1.11%)  3 0/99 (0.00%)  0 3/370 (0.81%)  3
Coronary artery disease  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 1/99 (1.01%)  1 2/370 (0.54%)  2
Angina pectoris  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Angina unstable  1  0/69 (0.00%)  0 0/203 (0.00%)  0 0/271 (0.00%)  0 1/99 (1.01%)  1 1/370 (0.27%)  1
Atrial fibrillation  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Mitral valve incompetence  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Myocarditis  1  0/69 (0.00%)  0 0/203 (0.00%)  0 0/271 (0.00%)  0 1/99 (1.01%)  1 1/370 (0.27%)  1
Pulseless electrical activity  1  0/69 (0.00%)  0 0/203 (0.00%)  0 0/271 (0.00%)  0 1/99 (1.01%)  1 1/370 (0.27%)  1
Ear and labyrinth disorders           
Vertigo  1  0/69 (0.00%)  0 0/203 (0.00%)  0 0/271 (0.00%)  0 1/99 (1.01%)  1 1/370 (0.27%)  1
Endocrine disorders           
Hyperthyroidism  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Gastrointestinal disorders           
Diarrhoea  1  0/69 (0.00%)  0 0/203 (0.00%)  0 4/271 (1.48%)  5 0/99 (0.00%)  0 4/370 (1.08%)  5
Small intestinal obstruction  1  0/69 (0.00%)  0 0/203 (0.00%)  0 2/271 (0.74%)  2 0/99 (0.00%)  0 2/370 (0.54%)  2
Abdominal pain  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Anal ulcer  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Anogenital dysplasia  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Duodenal ulcer  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Enteritis  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Incarcerated umbilical hernia  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Inflammatory bowel disease  1  0/69 (0.00%)  0 0/203 (0.00%)  0 0/271 (0.00%)  0 1/99 (1.01%)  1 1/370 (0.27%)  1
Inguinal hernia  1  0/69 (0.00%)  0 0/203 (0.00%)  0 0/271 (0.00%)  0 1/99 (1.01%)  1 1/370 (0.27%)  1
Malabsorption  1  0/69 (0.00%)  0 0/203 (0.00%)  0 0/271 (0.00%)  0 1/99 (1.01%)  1 1/370 (0.27%)  1
Oesophagitis  1  1/69 (1.45%)  1 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Reactive gastropathy  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Vomiting  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
General disorders           
Asthenia  1  0/69 (0.00%)  0 0/203 (0.00%)  0 0/271 (0.00%)  0 2/99 (2.02%)  2 2/370 (0.54%)  2
Mucosal inflammation  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 1/99 (1.01%)  1 2/370 (0.54%)  2
Pyrexia  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 1/99 (1.01%)  2 2/370 (0.54%)  3
Adverse event  1  0/69 (0.00%)  0 0/203 (0.00%)  0 0/271 (0.00%)  0 1/99 (1.01%)  1 1/370 (0.27%)  1
Chest pain  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Facial pain  1  0/69 (0.00%)  0 0/203 (0.00%)  0 0/271 (0.00%)  0 1/99 (1.01%)  1 1/370 (0.27%)  1
General physical health deterioration  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Generalised oedema  1  0/69 (0.00%)  0 0/203 (0.00%)  0 0/271 (0.00%)  0 1/99 (1.01%)  1 1/370 (0.27%)  1
Systemic inflammatory response syndrome  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Hepatobiliary disorders           
Cholelithiasis  1  0/69 (0.00%)  0 0/203 (0.00%)  0 2/271 (0.74%)  2 0/99 (0.00%)  0 2/370 (0.54%)  2
Hepatic failure  1  0/69 (0.00%)  0 0/203 (0.00%)  0 0/271 (0.00%)  0 2/99 (2.02%)  2 2/370 (0.54%)  2
Cholecystitis  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Cholecystitis acute  1  0/69 (0.00%)  0 0/203 (0.00%)  0 0/271 (0.00%)  0 1/99 (1.01%)  1 1/370 (0.27%)  1
Hepatocellular injury  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Immune system disorders           
Immune reconstitution inflammatory syndrome  1  0/69 (0.00%)  0 1/203 (0.49%)  1 2/271 (0.74%)  2 1/99 (1.01%)  1 3/370 (0.81%)  3
Hypersensitivity  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Infections and infestations           
Pneumonia  1  0/69 (0.00%)  0 2/203 (0.99%)  2 12/271 (4.43%)  14 3/99 (3.03%)  4 15/370 (4.05%)  18
Cellulitis  1  0/69 (0.00%)  0 0/203 (0.00%)  0 5/271 (1.85%)  5 3/99 (3.03%)  4 8/370 (2.16%)  9
Oesophageal candidiasis  1  0/69 (0.00%)  0 0/203 (0.00%)  0 3/271 (1.11%)  5 1/99 (1.01%)  2 4/370 (1.08%)  7
Pneumocystis jirovecii pneumonia  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 3/99 (3.03%)  3 4/370 (1.08%)  4
Sepsis  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 3/99 (3.03%)  3 4/370 (1.08%)  4
Chronic sinusitis  1  0/69 (0.00%)  0 0/203 (0.00%)  0 2/271 (0.74%)  2 1/99 (1.01%)  1 3/370 (0.81%)  3
Cytomegalovirus colitis  1  0/69 (0.00%)  0 0/203 (0.00%)  0 0/271 (0.00%)  0 2/99 (2.02%)  2 2/370 (0.54%)  2
Escherichia bacteraemia  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 1/99 (1.01%)  1 2/370 (0.54%)  2
Gastroenteritis  1  0/69 (0.00%)  0 1/203 (0.49%)  1 2/271 (0.74%)  2 0/99 (0.00%)  0 2/370 (0.54%)  2
HIV-associated neurocognitive disorder  1  0/69 (0.00%)  0 0/203 (0.00%)  0 2/271 (0.74%)  2 0/99 (0.00%)  0 2/370 (0.54%)  2
Oral candidiasis  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 1/99 (1.01%)  3 2/370 (0.54%)  4
Pneumonia pneumococcal  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 1/99 (1.01%)  1 2/370 (0.54%)  2
Progressive multifocal leukoencephalopathy  1  0/69 (0.00%)  0 0/203 (0.00%)  0 2/271 (0.74%)  2 0/99 (0.00%)  0 2/370 (0.54%)  2
Pseudomonal sepsis  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 1/99 (1.01%)  1 2/370 (0.54%)  2
Abdominal wall abscess  1  0/69 (0.00%)  0 0/203 (0.00%)  0 0/271 (0.00%)  0 1/99 (1.01%)  1 1/370 (0.27%)  1
Anorectal cellulitis  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Appendicitis  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Bacteraemia  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Bacterial sepsis  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Bronchitis  1  0/69 (0.00%)  0 0/203 (0.00%)  0 0/271 (0.00%)  0 1/99 (1.01%)  1 1/370 (0.27%)  1
Bronchitis bacterial  1  0/69 (0.00%)  0 0/203 (0.00%)  0 0/271 (0.00%)  0 1/99 (1.01%)  1 1/370 (0.27%)  1
Bronchopulmonary aspergillosis  1  0/69 (0.00%)  0 0/203 (0.00%)  0 0/271 (0.00%)  0 1/99 (1.01%)  1 1/370 (0.27%)  1
Clostridium difficile colitis  1  0/69 (0.00%)  0 0/203 (0.00%)  0 0/271 (0.00%)  0 1/99 (1.01%)  1 1/370 (0.27%)  1
Clostridium difficile infection  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  2 0/99 (0.00%)  0 1/370 (0.27%)  2
Cytomegalovirus chorioretinitis  1  0/69 (0.00%)  0 0/203 (0.00%)  0 0/271 (0.00%)  0 1/99 (1.01%)  2 1/370 (0.27%)  2
Disseminated cytomegaloviral infection  1  0/69 (0.00%)  0 0/203 (0.00%)  0 0/271 (0.00%)  0 1/99 (1.01%)  1 1/370 (0.27%)  1
Disseminated tuberculosis  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Hepatitis A  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Hepatitis B reactivation  1  0/69 (0.00%)  0 0/203 (0.00%)  0 0/271 (0.00%)  0 1/99 (1.01%)  1 1/370 (0.27%)  1
Histoplasmosis disseminated  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Influenza  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Liver abscess  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Meningitis coccidioides  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  2 0/99 (0.00%)  0 1/370 (0.27%)  2
Meningoencephalitis viral  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Orchitis  1  0/69 (0.00%)  0 0/203 (0.00%)  0 0/271 (0.00%)  0 1/99 (1.01%)  1 1/370 (0.27%)  1
Osteomyelitis  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Osteomyelitis acute  1  0/69 (0.00%)  0 0/203 (0.00%)  0 0/271 (0.00%)  0 1/99 (1.01%)  1 1/370 (0.27%)  1
Parainfluenzae virus infection  1  0/69 (0.00%)  0 0/203 (0.00%)  0 0/271 (0.00%)  0 1/99 (1.01%)  1 1/370 (0.27%)  1
Peritonsillar abscess  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Pharyngitis  1  0/69 (0.00%)  0 0/203 (0.00%)  0 0/271 (0.00%)  0 1/99 (1.01%)  1 1/370 (0.27%)  1
Pneumonia cytomegaloviral  1  0/69 (0.00%)  0 0/203 (0.00%)  0 0/271 (0.00%)  0 1/99 (1.01%)  1 1/370 (0.27%)  1
Postoperative wound infection  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Rectal abscess  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Respiratory tract infection  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Salmonella bacteraemia  1  0/69 (0.00%)  0 1/203 (0.49%)  1 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Septic rash  1  0/69 (0.00%)  0 0/203 (0.00%)  0 0/271 (0.00%)  0 1/99 (1.01%)  1 1/370 (0.27%)  1
Septic shock  1  0/69 (0.00%)  0 0/203 (0.00%)  0 0/271 (0.00%)  0 1/99 (1.01%)  1 1/370 (0.27%)  1
Staphylococcal bacteraemia  1  0/69 (0.00%)  0 0/203 (0.00%)  0 0/271 (0.00%)  0 1/99 (1.01%)  1 1/370 (0.27%)  1
Tooth abscess  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Tuberculosis liver  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Urinary tract infection  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Urosepsis  1  0/69 (0.00%)  0 0/203 (0.00%)  0 0/271 (0.00%)  0 1/99 (1.01%)  1 1/370 (0.27%)  1
Injury, poisoning and procedural complications           
Ankle fracture  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Arterial bypass thrombosis  1  0/69 (0.00%)  0 0/203 (0.00%)  0 0/271 (0.00%)  0 1/99 (1.01%)  1 1/370 (0.27%)  1
Burns third degree  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Kidney rupture  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Open fracture  1  0/69 (0.00%)  0 0/203 (0.00%)  0 0/271 (0.00%)  0 1/99 (1.01%)  1 1/370 (0.27%)  1
Overdose  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Shunt thrombosis  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Investigations           
Blood HIV RNA increased  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Blood creatine phosphokinase increased  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Blood creatinine increased  1  0/69 (0.00%)  0 0/203 (0.00%)  0 0/271 (0.00%)  0 1/99 (1.01%)  1 1/370 (0.27%)  1
Blood triglycerides increased  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Transaminases increased  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Metabolism and nutrition disorders           
Dehydration  1  0/69 (0.00%)  0 0/203 (0.00%)  0 0/271 (0.00%)  0 1/99 (1.01%)  1 1/370 (0.27%)  1
Electrolyte imbalance  1  0/69 (0.00%)  0 0/203 (0.00%)  0 0/271 (0.00%)  0 1/99 (1.01%)  1 1/370 (0.27%)  1
Hyperkalaemia  1  0/69 (0.00%)  0 0/203 (0.00%)  0 0/271 (0.00%)  0 1/99 (1.01%)  1 1/370 (0.27%)  1
Cachexia  1  1/69 (1.45%)  1 0/203 (0.00%)  0 0/271 (0.00%)  0 0/99 (0.00%)  0 0/370 (0.00%)  0
Musculoskeletal and connective tissue disorders           
Arthralgia  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Arthritis  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Back pain  1  0/69 (0.00%)  0 0/203 (0.00%)  0 0/271 (0.00%)  0 1/99 (1.01%)  1 1/370 (0.27%)  1
Lumbar spinal stenosis  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Rhabdomyolysis  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
Squamous cell carcinoma  1  0/69 (0.00%)  0 0/203 (0.00%)  0 3/271 (1.11%)  4 1/99 (1.01%)  1 4/370 (1.08%)  5
Anal squamous cell carcinoma  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 1/99 (1.01%)  1 2/370 (0.54%)  2
Hodgkin's disease  1  0/69 (0.00%)  0 0/203 (0.00%)  0 0/271 (0.00%)  0 2/99 (2.02%)  2 2/370 (0.54%)  2
Squamous cell carcinoma of skin  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 1/99 (1.01%)  1 2/370 (0.54%)  2
Anal cancer metastatic  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Anogenital warts  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
B-cell lymphoma  1  0/69 (0.00%)  0 0/203 (0.00%)  0 0/271 (0.00%)  0 1/99 (1.01%)  1 1/370 (0.27%)  1
Basal cell carcinoma  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Cholangiocarcinoma  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Colon cancer  1  0/69 (0.00%)  0 0/203 (0.00%)  0 0/271 (0.00%)  0 1/99 (1.01%)  1 1/370 (0.27%)  1
Diffuse large B-cell lymphoma  1  0/69 (0.00%)  0 0/203 (0.00%)  0 0/271 (0.00%)  0 1/99 (1.01%)  1 1/370 (0.27%)  1
Diffuse large B-cell lymphoma recurrent  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Kaposi's sarcoma  1  0/69 (0.00%)  0 0/203 (0.00%)  0 0/271 (0.00%)  0 1/99 (1.01%)  1 1/370 (0.27%)  1
Keratoacanthoma  1  0/69 (0.00%)  0 0/203 (0.00%)  0 0/271 (0.00%)  0 1/99 (1.01%)  1 1/370 (0.27%)  1
Lung adenocarcinoma  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Lung squamous cell carcinoma stage IV  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Lymphoma  1  0/69 (0.00%)  0 0/203 (0.00%)  0 0/271 (0.00%)  0 1/99 (1.01%)  1 1/370 (0.27%)  1
Malignant melanoma  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Oropharyngeal squamous cell carcinoma  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Ovarian cancer metastatic  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Penile squamous cell carcinoma  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Tonsil cancer  1  0/69 (0.00%)  0 0/203 (0.00%)  0 0/271 (0.00%)  0 1/99 (1.01%)  1 1/370 (0.27%)  1
Uterine leiomyoma  1  0/69 (0.00%)  0 0/203 (0.00%)  0 0/271 (0.00%)  0 1/99 (1.01%)  1 1/370 (0.27%)  1
Nervous system disorders           
Seizure  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 2/99 (2.02%)  3 3/370 (0.81%)  4
Cerebral infarction  1  0/69 (0.00%)  0 0/203 (0.00%)  0 0/271 (0.00%)  0 1/99 (1.01%)  1 1/370 (0.27%)  1
Dizziness  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Dysarthria  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Haemorrhagic stroke  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Headache  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Hemiparesis  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Lacunar infarction  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Loss of consciousness  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Mononeuropathy  1  0/69 (0.00%)  0 0/203 (0.00%)  0 0/271 (0.00%)  0 1/99 (1.01%)  1 1/370 (0.27%)  1
Muscle spasticity  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Transient ischaemic attack  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Tremor  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Pregnancy, puerperium and perinatal conditions           
Foetal growth restriction  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Psychiatric disorders           
Suicidal ideation  1  0/69 (0.00%)  0 0/203 (0.00%)  0 2/271 (0.74%)  2 0/99 (0.00%)  0 2/370 (0.54%)  2
Alcohol withdrawal syndrome  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Depression  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Disorientation  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Mental status changes  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Paranoia  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Psychotic disorder  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Schizophrenia  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Suicide attempt  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Renal and urinary disorders           
Acute kidney injury  1  0/69 (0.00%)  0 0/203 (0.00%)  0 2/271 (0.74%)  2 3/99 (3.03%)  3 5/370 (1.35%)  5
Nephrolithiasis  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 1/99 (1.01%)  1 2/370 (0.54%)  2
Renal failure  1  0/69 (0.00%)  0 0/203 (0.00%)  0 0/271 (0.00%)  0 2/99 (2.02%)  2 2/370 (0.54%)  2
Glomerulonephritis  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Renal impairment  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Ureterolithiasis  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Reproductive system and breast disorders           
Prostatitis  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 1/99 (1.01%)  1 2/370 (0.54%)  2
Cervical dysplasia  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Respiratory, thoracic and mediastinal disorders           
Cough  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Interstitial lung disease  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Nasal polyps  1  0/69 (0.00%)  0 0/203 (0.00%)  0 0/271 (0.00%)  0 1/99 (1.01%)  1 1/370 (0.27%)  1
Pharyngeal oedema  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Pulmonary embolism  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
Acute respiratory failure  1  1/69 (1.45%)  1 0/203 (0.00%)  0 0/271 (0.00%)  0 0/99 (0.00%)  0 0/370 (0.00%)  0
Vascular disorders           
Deep vein thrombosis  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 2/99 (2.02%)  2 3/370 (0.81%)  3
Thrombosis  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 0/99 (0.00%)  0 1/370 (0.27%)  1
1
Term from vocabulary, MedDRA 20.1
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Randomized Cohort-Placebo Randomized Cohort-fostemsavir 600 mg BID Randomized Cohort-Total Non-randomized Cohort-fostemsavir 600 mg BID Total Fostemsavir
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   16/69 (23.19%)      48/203 (23.65%)      207/271 (76.38%)      89/99 (89.90%)      296/370 (80.00%)    
Blood and lymphatic system disorders           
Neutropenia  1  0/69 (0.00%)  0 0/203 (0.00%)  0 1/271 (0.37%)  1 5/99 (5.05%)  5 6/370 (1.62%)  6
Gastrointestinal disorders           
Diarrhoea  1  3/69 (4.35%)  3 11/203 (5.42%)  11 58/271 (21.40%)  79 24/99 (24.24%)  43 82/370 (22.16%)  122
Nausea  1  4/69 (5.80%)  4 15/203 (7.39%)  15 40/271 (14.76%)  60 20/99 (20.20%)  28 60/370 (16.22%)  88
Vomiting  1  0/69 (0.00%)  0 2/203 (0.99%)  2 28/271 (10.33%)  44 9/99 (9.09%)  12 37/370 (10.00%)  56
Abdominal pain  1  0/69 (0.00%)  0 3/203 (1.48%)  3 22/271 (8.12%)  30 4/99 (4.04%)  4 26/370 (7.03%)  34
Constipation  1  0/69 (0.00%)  0 3/203 (1.48%)  3 20/271 (7.38%)  20 6/99 (6.06%)  7 26/370 (7.03%)  27
General disorders           
Pyrexia  1  1/69 (1.45%)  1 1/203 (0.49%)  1 24/271 (8.86%)  36 16/99 (16.16%)  23 40/370 (10.81%)  59
Fatigue  1  3/69 (4.35%)  3 3/203 (1.48%)  3 17/271 (6.27%)  18 16/99 (16.16%)  16 33/370 (8.92%)  34
Asthenia  1  2/69 (2.90%)  2 2/203 (0.99%)  2 11/271 (4.06%)  12 12/99 (12.12%)  12 23/370 (6.22%)  24
Infections and infestations           
Upper respiratory tract infection  1  0/69 (0.00%)  0 1/203 (0.49%)  1 37/271 (13.65%)  52 13/99 (13.13%)  17 50/370 (13.51%)  69
Nasopharyngitis  1  0/69 (0.00%)  0 2/203 (0.99%)  2 27/271 (9.96%)  39 16/99 (16.16%)  22 43/370 (11.62%)  61
Influenza  1  0/69 (0.00%)  0 1/203 (0.49%)  1 25/271 (9.23%)  29 13/99 (13.13%)  15 38/370 (10.27%)  44
Bronchitis  1  0/69 (0.00%)  0 0/203 (0.00%)  0 28/271 (10.33%)  35 5/99 (5.05%)  6 33/370 (8.92%)  41
Sinusitis  1  0/69 (0.00%)  0 0/203 (0.00%)  0 19/271 (7.01%)  24 9/99 (9.09%)  9 28/370 (7.57%)  33
Urinary tract infection  1  0/69 (0.00%)  0 0/203 (0.00%)  0 13/271 (4.80%)  15 10/99 (10.10%)  12 23/370 (6.22%)  27
Oral candidiasis  1  0/69 (0.00%)  0 1/203 (0.49%)  1 15/271 (5.54%)  18 7/99 (7.07%)  8 22/370 (5.95%)  26
Gastroenteritis  1  0/69 (0.00%)  0 1/203 (0.49%)  1 9/271 (3.32%)  9 6/99 (6.06%)  6 15/370 (4.05%)  15
Oral herpes  1  0/69 (0.00%)  0 0/203 (0.00%)  0 5/271 (1.85%)  5 5/99 (5.05%)  5 10/370 (2.70%)  10
Metabolism and nutrition disorders           
Decreased appetite  1  0/69 (0.00%)  0 0/203 (0.00%)  0 5/271 (1.85%)  5 8/99 (8.08%)  9 13/370 (3.51%)  14
Musculoskeletal and connective tissue disorders           
Arthralgia  1  0/69 (0.00%)  0 0/203 (0.00%)  0 20/271 (7.38%)  22 8/99 (8.08%)  9 28/370 (7.57%)  31
Back pain  1  1/69 (1.45%)  1 0/203 (0.00%)  0 15/271 (5.54%)  17 13/99 (13.13%)  16 28/370 (7.57%)  33
Pain in extremity  1  0/69 (0.00%)  0 0/203 (0.00%)  0 13/271 (4.80%)  15 6/99 (6.06%)  6 19/370 (5.14%)  21
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
Anogenital warts  1  0/69 (0.00%)  0 0/203 (0.00%)  0 10/271 (3.69%)  12 7/99 (7.07%)  8 17/370 (4.59%)  20
Skin papilloma  1  0/69 (0.00%)  0 0/203 (0.00%)  0 6/271 (2.21%)  6 5/99 (5.05%)  6 11/370 (2.97%)  12
Nervous system disorders           
Headache  1  5/69 (7.25%)  5 8/203 (3.94%)  8 34/271 (12.55%)  50 11/99 (11.11%)  12 45/370 (12.16%)  62
Dizziness  1  1/69 (1.45%)  1 2/203 (0.99%)  2 15/271 (5.54%)  15 5/99 (5.05%)  5 20/370 (5.41%)  20
Neuropathy peripheral  1  0/69 (0.00%)  0 1/203 (0.49%)  1 6/271 (2.21%)  7 5/99 (5.05%)  5 11/370 (2.97%)  12
Psychiatric disorders           
Depression  1  0/69 (0.00%)  0 0/203 (0.00%)  0 16/271 (5.90%)  17 3/99 (3.03%)  3 19/370 (5.14%)  20
Insomnia  1  1/69 (1.45%)  1 2/203 (0.99%)  2 16/271 (5.90%)  17 3/99 (3.03%)  3 19/370 (5.14%)  20
Respiratory, thoracic and mediastinal disorders           
Cough  1  1/69 (1.45%)  1 0/203 (0.00%)  0 32/271 (11.81%)  41 10/99 (10.10%)  11 42/370 (11.35%)  52
Skin and subcutaneous tissue disorders           
Rash  1  0/69 (0.00%)  0 0/203 (0.00%)  0 8/271 (2.95%)  15 5/99 (5.05%)  6 13/370 (3.51%)  21
Pruritus  1  0/69 (0.00%)  0 1/203 (0.49%)  1 6/271 (2.21%)  6 5/99 (5.05%)  8 11/370 (2.97%)  14
Eczema  1  0/69 (0.00%)  0 0/203 (0.00%)  0 5/271 (1.85%)  5 5/99 (5.05%)  5 10/370 (2.70%)  10
Night sweats  1  0/69 (0.00%)  0 0/203 (0.00%)  0 2/271 (0.74%)  15 5/99 (5.05%)  5 7/370 (1.89%)  20
1
Term from vocabulary, MedDRA 20.1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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: NCT02362503     History of Changes
Other Study ID Numbers: 205888
AI438-047 ( Other Identifier: Bristol-Myers Squibb )
First Submitted: February 9, 2015
First Posted: February 13, 2015
Results First Submitted: August 2, 2018
Results First Posted: September 18, 2018
Last Update Posted: October 15, 2018