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Extension Study of Idelalisib in Participants With Chronic Lymphocytic Leukemia (CLL) Who Participated in GS-US-312-0116 (NCT01539512)

Sponsor
Gilead Sciences (Industry)
Overall Status
Terminated
CT.gov ID
NCT01539291
Collaborator
(none)
161
Enrollment
45
Locations
2
Arms
68.8
Actual Duration (Months)
3.6
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary objective of this extension study (GS-US-312-0117) that is a companion study to Study GS-US-312-0116 (NCT01539512), is to evaluate the effect of idelalisib on the onset, magnitude, and duration of tumor control. Randomization was done in study GS-US-312-0116, and carried forward to study GS-US-312-117.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
161 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Phase 3, Double-Blind Extension Study Evaluating the Efficacy and Safety of Two Different Dose Levels of Single-Agent Idelalisib (GS-1101) for Previously Treated Chronic Lymphocytic Leukemia A Companion Trial to Study GS-US-312-0116: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of Idelalisib (GS-1101) in Combination With Rituximab for Previously Treated Chronic Lymphocytic Leukemia
Actual Study Start Date :
Oct 3, 2012
Actual Primary Completion Date :
May 21, 2018
Actual Study Completion Date :
Jun 29, 2018

Arms and Interventions

Arm Intervention/Treatment
Experimental: High-dose Idelalisib

Participants will receive idelalisib 300 mg twice daily (600 mg per day).

Drug: Idelalisib
Idelalisib tablet(s) administered orally twice daily
Other Names:
  • Zydelig®
  • GS-1101
  • CAL 101

    		•
    Experimental: Standard-dose Idelalisib

    Participants will receive idelalisib 150 mg twice daily (300 mg per day)

    Drug: Idelalisib
    Idelalisib tablet(s) administered orally twice daily
    Other Names:
  • Zydelig®
  • GS-1101
  • CAL 101

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Progression-Free Survival (PFS) [GS-US-312-0116 Baseline to end of study GS-US-312-0117 (maximum: up to 67.6 months)]

      PFS was defined as the interval from the start of study therapy to the earlier of the first documentation of definitive disease progression or death from any cause; definitive disease progression is chronic lymphocytic leukemia (CLL) progression based on standard criteria other than lymphocytosis alone. PFS was analyzed using Kaplan-Meier (KM) estimates.

    2. Safety: Percentage of Participants With Any Treatment-Emergent Adverse Events (TEAE), ≥ Grade 3 TEAE, Study Drug-Related TEAE, ≥ Grade 3 Study Drug-Related TEAE, Serious TEAE, Study Drug-Related Serious TEAE, and TEAE Leading to Study Drug Discontinuation [First IDL dose date in study GS-US-312-0116 or GS-US-312-0117 to last IDL dose date in study GS-US-312-0117 (maximum: 67.3 months) plus 4 weeks]

      The TEAEs were defined as events in a given study period that met one of the following criteria: Events with onset dates on or after the start of treatment and up to 30 days after the permanent discontinuation of the study treatment. The continuing adverse events (AEs) diagnosed prior to the start of treatment and worsened in severity grade, or non-serious AEs at baseline which became serious, or AEs resulting in treatment discontinuation after the start of treatment. The severity of AEs was graded by the investigator according to the common terminology criteria for adverse events (CTCAE), Version 4.03, whenever possible. The relationship of an AE to study drug (idelalisib) was assessed using clinical judgment by the investigator, describing the event as either unrelated or related. Events for which the investigator did not record relationship to study drug were considered related to study drug.

    Secondary Outcome Measures

    1. Overall Response Rate (ORR) [GS-US-312-0116 Baseline to end of study GS-US-312-0117 (maximum: up to 67.6 months)]

      ORR was defined as the percentage of participants who achieved a complete response (CR) or partial response (PR). The determination of CLL response and progression were based on standardized International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria, as specifically modified for this study to reflect current recommendations which considered the mechanism of action of idelalisib and similar drugs. CR and PR are defined in Protocol Amendment 9, Sections 7.5.1 and 7.5.2.

    2. Lymph Node Response Rate [GS-US-312-0116 Baseline to end of study GS-US-312-0117 (maximum: up to 67.6 months)]

      Lymph node response rate was defined as the percentage of participants who achieved a ≥ 50% decrease from baseline in the sum of the products of the greatest perpendicular diameters (SPD) of index lymph nodes.

    3. Complete Response (CR) Rate [GS-US-312-0116 Baseline to end of study GS-US-312-0117 (maximum: up to 67.6 months)]

      CR rate was defined as the percentage of participants who achieved a CR (full definition in Protocol Amendment 9, Section 7.5.1). The determination of CLL response and progression were based on standardized IWCLL criteria, as specifically modified for this study to reflect current recommendations which considered the mechanism of action of idelalisib and similar drugs.

    4. Time to Response (TTR) [GS-US-312-0116 Baseline to end of study GS-US-312-0117 (maximum: up to 67.6 months)]

      TTR was defined as the time interval from start of study therapy to the first documentation of CR or PR.

    5. Duration of Response (DOR) [From first documentation of CR or PR to end of study GS-US-312-0117 (maximum: up to 67.6 months)]

      DOR was defined as the time interval from the first documentation of CR or PR to the earlier of the first documentation of definitive disease progression or death from any cause. DOR was analyzed using KM estimates.

    6. Best Percent Change in Lymph Node Area [GS-US-312-0116 Baseline to end of study GS-US-312-0117 (maximum: up to 67.6 months)]

      The best percent change from baseline in lymph node area (SPD) was defined as the largest decrease in tumor size during the study. The baseline SPD was the last value prior to the baseline reference date. For the participants who only had increases in tumor size from baseline, the smallest increase was considered as the best change from baseline in SPD.

    7. Splenomegaly Response Rate [GS-US-312-0116 Baseline to end of study GS-US-312-0117 (maximum: up to 67.6 months)]

      Splenomegaly response rate was defined as the percentage of participants with baseline splenomegaly who achieved an on-study normalization or a 50% decrease (minimum 2 cm) from baseline in the enlargement of the splenic longest vertical dimension (LVD) (by imaging).

    8. Hepatomegaly Response Rate [GS-US-312-0116 Baseline to end of study GS-US-312-0117 (maximum: up to 67.6 months)]

      Hepatomegaly response rate was defined as the percentage of participants with baseline hepatomegaly who achieved an on-study normalization or a 50% decrease (minimum 2 cm) from baseline in the hepatic LVD (by imaging).

    9. Absolute Lymphocyte Count (ALC) Response Rate [GS-US-312-0116 Baseline to end of study GS-US-312-0117 (maximum: up to 67.6 months)]

      ALC response rate was defined as the percentage of participants with baseline lymphocytosis (ALC ≥ 4 x 10^9 cells/L) who achieved an on-study ALC < 4 x 10^9 cells/L or demonstrated a ≥ 50% decrease in ALC from baseline; ALC values within 4 weeks post-baseline were excluded from the ALC response rate evaluation.

    10. Platelet Response Rate [GS-US-312-0116 Baseline to end of study GS-US-312-0117 (maximum: up to 67.6 months)]

      Platelet response rate was defined as the percentage of participants with baseline thrombocytopenia (platelet count < 100 x 10^9/L) who achieved an on-study platelet count ≥ 100 x 10^9/L or demonstrated a ≥ 50% increase in platelet count from baseline; platelet values within 4 weeks post-baseline or after 8 days post transfusion were excluded from the platelet response rate evaluation.

    11. Hemoglobin Response Rate [GS-US-312-0116 Baseline to end of study GS-US-312-0117 (maximum: up to 67.6 months)]

      Hemoglobin response rate was defined as the percentage of participants with baseline anemia (hemoglobin < 110 g/L [11.0 g/dL]) who achieved an on-study hemoglobin ≥ 110 g/L (11.0 g/dL) or demonstrated a ≥ 50% increase in hemoglobin from baseline; hemoglobin values within 4 weeks post-baseline or after 4 weeks of receiving packed cell/whole blood transfusion or after 6 weeks of receiving exogenous growth factors (eg, darbepoetin alfa) were excluded from the hemoglobin response evaluation.

    12. Neutrophil Response Rate [GS-US-312-0116 Baseline to end of study GS-US-312-0117 (maximum: up to 67.6 months)]

      Neutrophil response rate was defined as the percentage of participants with baseline neutropenia (absolute neutrophil count [ANC] ≤ 1.5 x 10^9/L) who achieved an ANC > 1.5 x 10^9/L or demonstrated a ≥ 50% increase in ANC from baseline; ANC values within 4 weeks of post-baseline or after 2 weeks of receiving exogenous growth factors (eg, filgrastim, granulocyte-colony stimulating factor [G-CSF], lenograstim) or after 4 weeks of receiving Neulasta® were excluded from response evaluation.

    13. Overall Survival [GS-US-312-0116 Baseline to end of study GS-US-312-0117 (maximum: up to 67.6 months)]

      Overall survival was defined as the time interval from start of study therapy to death from any cause. Overall survival was analyzed using KM estimates. Data presented includes all available survival information from Study GS-US-312-0116 (including data in long-term follow-up) and Study GS-US-312-0117 (including any data in long-term follow-up) up to the database finalization dates. Data from surviving participants were censored at the last time that the participant was known to be alive on study or long-term follow-up. Data presented includes all participants who were randomized to Study GS-US-312-0116 regardless if they entered Study GS-US-312-0117 or not.

    14. Best Change From Baseline in Health-Related Quality of Life (HRQL) Domain and Symptom Scores Based on the Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu) Questionnaire [Study GS-US-312-0116 or GS-US-312-0117 Baseline up to Week 184]

      The FACT-Leu questionnaire included subscales for physical well-being (PWB, 7 items), social/family well-being (SWB, 7 items), emotional well-being (EWB, 6 items), functional well-being (FWB, 7 items), and additional concerns or Leukemia-Specific Subscale (LeuS, 17 items). The FACT-Leu scoring guide identified those negatively stated items that must have been reversed before being added to obtain subscale totals. Negatively stated items were reversed by subtracting the response from "4". After reversing proper items, all subscale items were summed to get total subscale scores with the range of 0-28, 0-28, 0-24, 0-28, 0-68 for PWB, SWB, EWB, FWB, and LeuS, respectively. FACT-Leu total score ranged from 0 to 176. Higher scores indicated a better quality of life. Best change from baseline was defined as the highest value of change from baseline among all postbaseline visits. For participants who did not enter Study GS-US-312-0117, baseline values were from Study GS-US-312-0116.

    15. Best Change From Baseline in Karnofsky Performance Status (KPS) [Study GS-US-312-0116 or GS-US-312-0117 Baseline up to Week 190]

      KPS is a tool used to measure the ability to perform ordinary tasks. The score ranges from 0 to 100, with a higher score indicating that the participant is better able to carry out daily activities. Best change from baseline was defined as the highest value of change from baseline among all postbaseline visits. For participants who did not enter Study GS-US-312-0117, baseline values were from Study GS-US-312-0116.

    16. Changes From Baseline in Phosphatidylinositol 3-kinase (PI3Kδ)/Akt/Mammalian Target of Rapamycin (mTOR) Pathway Activation as a Measure of PI3Kδ Pathway Activity [GS-US-312-0116 Baseline to end of study GS-US-312-0117 (maximum: up to 67.6 months)]

    17. Overall Change From Baseline in the Plasma Concentrations of Disease-Associated Chemokines and Cytokines [GS-US-312-0116 Baseline to end of study GS-US-312-0117 (maximum: up to 67.6 months)]

      The percent of average on-treatment biomarker concentration of baseline (%Baseline) was used to evaluate the overall pharmacodynamics change on the biomarkers with IDL treatment. The average on-treatment biomarker concentration is calculated using area under curve (AUC) following the trapezoidal rule. The biomarkers with median AUC value of 100 indicated no overall on-treatment biomarker changes compared to the baseline. The biomarkers with median AUC value greater than 100 or less than 100 indicated an increase or decrease, respectively, on-treatment biomarker changes from the baseline.

    18. Study Drug Compliance as Assessed by the Percentage of Participants Adhering to Treatment [First IDL dose date in study GS-US-312-0116 or GS-US-312-0117 to last IDL dose date in study GS-US-312-0117 (maximum: 67.3 months)]

      Adherence percentage was calculated as the sum of tablets dispensed - the sum of tablets returned divided by the sum of the overall dosing period (total daily tablets x dosing duration), taking into account investigator-prescribed interruptions.

    19. Plasma Trough (Predose) and Peak (1.5 Hours Postdose) Concentrations of Idelalisib [Weeks 4, 12, and 24]

    20. Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure [Study GS-US-312-0116 or GS-US-312-0117 Baseline; Weeks 24 and 48]

      Change in health status was defined as the change from baseline in overall health and single-item dimension scores as assessed using the EQ-5D utility measure. Percentage of participants with different level of problem were reported. Level 1: indicated no problem; Level 2: indicated some problems; and Level 3: indicated extreme problems. For participants who did not enter Study GS-US-312-0117, baseline values were from Study GS-US-312-0116.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Key Inclusion Criteria:

    • Individuals in the primary Phase 3 study (Study GS-US-312-0116) who are compliant

    • Tolerating primary study therapy

    Note: Other protocol defined Inclusion/Exclusion criteria may apply.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Clearview Cancer Institute Huntsville Alabama United States 35805
    2 Arizona Oncology Associates Tucson Arizona United States 85704
    3 University of California, San Diego - Moores Cancer Center La Jolla California United States 92093
    4 Ventura County Hematology Oncology Specialists Oxnard California United States 93030
    5 UCLA Santa Monica California United States 90404
    6 Stanford Cancer Center Stanford California United States 94305
    7 Rocky Mountain Blood and Marrow Transplant Program Denver Colorado United States 80218
    8 Rocky Mountain Cancer Center Denver Colorado United States 80218
    9 Georgetown University Medical Center Lombardi Cancer Center Washington District of Columbia United States 20007
    10 Collaborative Research Group Boynton Beach Florida United States 33435
    11 Florida Cancer Specialists Fort Myers Florida United States 33916
    12 Florida Cancer Specialists Saint Petersburg Florida United States 33705
    13 Northwestern University Chicago Illinois United States 60611
    14 Hackensack University Medical Center Hackensack New Jersey United States 07601
    15 Long Island Jewish Medical Center New Hyde Park New York United States 11042
    16 Weill Cornell Medical College New York New York United States 10021
    17 Columbia University Medical Center New York New York United States 10032
    18 Memorial Sloan Kettering Cancer Center New York New York United States 10065
    19 Willamette Valley Cancer Center Springfield Oregon United States 97477
    20 Northwest Cancer Specialists, PC Tualatin Oregon United States 97062
    21 Cancer Centers of the Carolinas Greenville South Carolina United States 29605
    22 Sarah Cannon Research Institute Nashville Tennessee United States 37203
    23 Texas Oncology, P.A. Fort Worth Texas United States 76104
    24 M.D. Anderson Cancer Center Houston Texas United States 77030
    25 Cancer Care Network of South Texas San Antonio Texas United States 78217
    26 Virginia Cancer Specialists, PC Fairfax Virginia United States 22031
    27 Oncology and Hematology Associates of Southwest Virginia, Inc. Roanoke Virginia United States 24014
    28 Seattle Cancer Care Alliance Seattle Washington United States 98109-1024
    29 Yakima Valley Memorial Hospital/North Star Lodge Yakima Washington United States 98902
    30 Medical College of Wisconsin Milwaukee Wisconsin United States 53226
    31 Centre Hospitalier Lyon Sud Pierre Benite France 69495
    32 Centre Henri Becquerel Rouen France 76038
    33 Hämatologische und Internistische Gemeinschaftspraxis Dres. Eckart / Häcker Erlangen Germany 91052
    34 Universitätsklinikum Köln Köln Germany 50937
    35 Ospedale San Raffaele S.r.l. Milano Italy 20132
    36 Azienda Ospedaliera Città della Salute e della Scienza di Torino Torino Italy 10126
    37 Royal Bournemouth Hospital Bournemouth United Kingdom BH7 7DW
    38 Addenbrooke's Hospital Cambridge United Kingdom CB2 0QQ
    39 Dorset County Hospital Dorchester United Kingdom DT1 2JY
    40 Northwick Park Hospital Harrow United Kingdom HA1 3UJ
    41 St James's University Hospital Leeds United Kingdom LS9 7TF
    42 Royal Liverpool University Hospital Liverpool United Kingdom L7 8XP
    43 Hammersmith Hospital London United Kingdom W12 0NN
    44 Princess Royal University Hospital Orpington United Kingdom BR6 8ND
    45 Southampton General Hospital Southampton United Kingdom SO16 6YD

    Sponsors and Collaborators

    • Gilead Sciences

    Investigators

    • Study Director: Gilead Study Director, Gilead Sciences

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Gilead Sciences
    ClinicalTrials.gov Identifier:
    NCT01539291
    Other Study ID Numbers:
    • GS-US-312-0117
    • 2011-006293-72
    First Posted:
    Feb 27, 2012
    Last Update Posted:
    Aug 20, 2019
    Last Verified:
    Aug 1, 2019
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Gilead Sciences
    CLL
    CAL-101
    CAL 101
    GS-1101
    GS 1101
    PI3K
    Leukemia
    GS-US-312-0116
    idelalisib
    Additional relevant MeSH terms:
    Leukemia
    Leukemia, Lymphoid
    Leukemia, Lymphocytic, Chronic, B-Cell
    Idelalisib

    Study Results

    Participant Flow

    Recruitment Details Participants were enrolled at study sites in the United States and Europe. The first participant was screened on 03 October 2012. The last study visit occurred on 29 June 2018.
    Pre-assignment Detail Participants must have been enrolled in Gilead-sponsored Study GS-US-312-0116 (NCT01539512) to be eligible to continued access to idelalisib (IDL) in this study.
    Arm/Group Title IDL+R to IDL 150 mg IDL+R (PD) to IDL 300 mg Placebo+R (PD) to IDL 150 mg Placebo+R to IDL 150 mg
    Arm/Group Description Participants received IDL 150 mg tablet twice daily plus rituximab (R) (8 infusions intravenously) in Study GS-US-312-0116 and may have entered Study GS-US-312-0117 to receive IDL 150 mg tablet twice daily. Participants received IDL 150 mg tablet twice daily plus rituximab (8 infusions intravenously) in Study GS-US-312-0116 and met the primary endpoint of progressive disease (PD) and entered Study GS-US-312-0117 to receive IDL 300 mg tablet twice daily. Due to the small number of participants in this group, data from this group were combined with the IDL+R to IDL 150 mg group for Baseline Characteristics and Outcome Measures sections. Participants received placebo tablet twice daily plus rituximab (8 infusions intravenously) in Study GS-US-312-0116 and met the primary endpoint of PD and entered Study GS-US-312-0117 to receive IDL 150 mg tablet twice daily. Participants received placebo tablet twice daily plus rituximab (8 infusions intravenously) in Study GS-US-312-0116 and entered Study GS-US-312-0117 to receive IDL 150 mg tablet twice daily.
    Period Title: Study GS-US-312-0116
    STARTED 106 4 42 44
    COMPLETED 81 4 42 44
    NOT COMPLETED 25 0 0 0
    Period Title: Study GS-US-312-0116
    STARTED 71 4 42 44
    COMPLETED 30 2 20 18
    NOT COMPLETED 41 2 22 26

    Baseline Characteristics

    Arm/Group Title IDL+R to IDL Placebo+R (PD) to IDL 150 mg Placebo+R to IDL 150 mg Total
    Arm/Group Description Participants received IDL 150 mg tablet twice daily plus rituximab (8 infusions intravenously) in Study GS-US-312-0116 and may have entered Study GS-US-312-0117 to receive IDL 150 mg or 300 mg tablet twice daily. Due to the small number of participants in the IDL+R (PD) to IDL 300 mg group, data from this group were combined with the IDL+R to IDL 150 mg group for Baseline Characteristics and Outcome Measures sections. Participants received placebo tablet twice daily plus rituximab (8 infusions intravenously) in Study GS-US-312-0116 and met the primary endpoint of PD and entered Study GS-US-312-0117 to receive IDL 150 mg tablet twice daily. Participants received placebo tablet twice daily plus rituximab (8 infusions intravenously) in Study GS-US-312-0116 and entered Study GS-US-312-0117 to receive IDL 150 mg tablet twice daily. Total of all reporting groups
    Overall Participants 110 42 44 196
    Age, Customized (Count of Participants)
    < 65 years
    21
    19.1%
    13
    31%
    10
    22.7%
    44
    22.4%
    ≥ 65 years
    89
    80.9%
    29
    69%
    34
    77.3%
    152
    77.6%
    Sex: Female, Male (Count of Participants)
    Female
    34
    30.9%
    11
    26.2%
    18
    40.9%
    63
    32.1%
    Male
    76
    69.1%
    31
    73.8%
    26
    59.1%
    133
    67.9%
    Race/Ethnicity, Customized (Count of Participants)
    Hispanic or Latino
    3
    2.7%
    1
    2.4%
    1
    2.3%
    5
    2.6%
    Not Hispanic or Latino
    101
    91.8%
    39
    92.9%
    42
    95.5%
    182
    92.9%
    Not Permitted
    6
    5.5%
    2
    4.8%
    1
    2.3%
    9
    4.6%
    Race/Ethnicity, Customized (Count of Participants)
    White
    100
    90.9%
    37
    88.1%
    40
    90.9%
    177
    90.3%
    Black or African American
    3
    2.7%
    0
    0%
    3
    6.8%
    6
    3.1%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Other
    2
    1.8%
    2
    4.8%
    0
    0%
    4
    2%
    Not Permitted
    5
    4.5%
    3
    7.1%
    1
    2.3%
    9
    4.6%
    Region of Enrollment (Count of Participants)
    United States
    80
    72.7%
    38
    90.5%
    30
    68.2%
    148
    75.5%
    United Kingdom
    18
    16.4%
    3
    7.1%
    6
    13.6%
    27
    13.8%
    Italy
    2
    1.8%
    1
    2.4%
    4
    9.1%
    7
    3.6%
    France
    3
    2.7%
    0
    0%
    1
    2.3%
    4
    2%
    Germany
    7
    6.4%
    0
    0%
    3
    6.8%
    10
    5.1%
    17p Deletion and/or TP53 Mutation Status (Count of Participants)
    Either
    46
    41.8%
    21
    50%
    14
    31.8%
    81
    41.3%
    Neither
    64
    58.2%
    21
    50%
    30
    68.2%
    115
    58.7%
    Immunoglobulin heavy chain variable region (IgHV) Mutation Status (Count of Participants)
    Mutated
    19
    17.3%
    6
    14.3%
    7
    15.9%
    32
    16.3%
    Unmutated
    91
    82.7%
    36
    85.7%
    37
    84.1%
    164
    83.7%
    Karnofsky Performance Status (KPS) (Count of Participants)
    KPS = 40
    1
    0.9%
    0
    0%
    0
    0%
    1
    0.5%
    KPS = 50
    3
    2.7%
    1
    2.4%
    0
    0%
    4
    2%
    KPS = 60
    6
    5.5%
    2
    4.8%
    0
    0%
    8
    4.1%
    KPS = 70
    20
    18.2%
    4
    9.5%
    4
    9.1%
    28
    14.3%
    KPS = 80
    42
    38.2%
    19
    45.2%
    20
    45.5%
    81
    41.3%
    KPS = 90
    23
    20.9%
    12
    28.6%
    12
    27.3%
    47
    24%
    KPS = 100
    15
    13.6%
    4
    9.5%
    8
    18.2%
    27
    13.8%

    Outcome Measures

    1. Primary Outcome
    Title Progression-Free Survival (PFS)
    Description PFS was defined as the interval from the start of study therapy to the earlier of the first documentation of definitive disease progression or death from any cause; definitive disease progression is chronic lymphocytic leukemia (CLL) progression based on standard criteria other than lymphocytosis alone. PFS was analyzed using Kaplan-Meier (KM) estimates.
    Time Frame GS-US-312-0116 Baseline to end of study GS-US-312-0117 (maximum: up to 67.6 months)

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set included participants in the Intent-to-Treat (ITT) Analysis Set (all participants randomized in Study GS-US-312-0116) who received ≥ 1 dose of IDL, with treatment assignments designated according to randomization in Study GS-US-312-0116.
    Arm/Group Title IDL+R to IDL Placebo+R (PD) to IDL 150 mg Placebo+R to IDL 150 mg
    Arm/Group Description Participants received IDL 150 mg tablet twice daily plus rituximab (8 infusions intravenously) in Study GS-US-312-0116 and may have entered Study GS-US-312-0117 to receive IDL 150 mg or 300 mg tablet twice daily. Due to the small number of participants in the IDL+R (PD) to IDL 300 mg group, data from this group were combined with the IDL+R to IDL 150 mg group for Baseline Characteristics and Outcome Measures sections. Participants received placebo tablet twice daily plus rituximab (8 infusions intravenously) in Study GS-US-312-0116 and met the primary endpoint of PD and entered Study GS-US-312-0117 to receive IDL 150 mg tablet twice daily. Participants received placebo tablet twice daily plus rituximab (8 infusions intravenously) in Study GS-US-312-0116 and entered Study GS-US-312-0117 to receive IDL 150 mg tablet twice daily.
    Measure Participants 110 42 44
    Median (95% Confidence Interval) [months]
    20.3
    6.9
    16.2
    2. Primary Outcome
    Title Safety: Percentage of Participants With Any Treatment-Emergent Adverse Events (TEAE), ≥ Grade 3 TEAE, Study Drug-Related TEAE, ≥ Grade 3 Study Drug-Related TEAE, Serious TEAE, Study Drug-Related Serious TEAE, and TEAE Leading to Study Drug Discontinuation
    Description The TEAEs were defined as events in a given study period that met one of the following criteria: Events with onset dates on or after the start of treatment and up to 30 days after the permanent discontinuation of the study treatment. The continuing adverse events (AEs) diagnosed prior to the start of treatment and worsened in severity grade, or non-serious AEs at baseline which became serious, or AEs resulting in treatment discontinuation after the start of treatment. The severity of AEs was graded by the investigator according to the common terminology criteria for adverse events (CTCAE), Version 4.03, whenever possible. The relationship of an AE to study drug (idelalisib) was assessed using clinical judgment by the investigator, describing the event as either unrelated or related. Events for which the investigator did not record relationship to study drug were considered related to study drug.
    Time Frame First IDL dose date in study GS-US-312-0116 or GS-US-312-0117 to last IDL dose date in study GS-US-312-0117 (maximum: 67.3 months) plus 4 weeks

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set were analyzed.
    Arm/Group Title IDL+R to IDL Placebo+R (PD) to IDL 150 mg Placebo+R to IDL 150 mg
    Arm/Group Description Participants received IDL 150 mg tablet twice daily plus rituximab (8 infusions intravenously) in Study GS-US-312-0116 and may have entered Study GS-US-312-0117 to receive IDL 150 mg or 300 mg tablet twice daily. Due to the small number of participants in the IDL+R (PD) to IDL 300 mg group, data from this group were combined with the IDL+R to IDL 150 mg group for Baseline Characteristics and Outcome Measures sections. Participants received placebo tablet twice daily plus rituximab (8 infusions intravenously) in Study GS-US-312-0116 and met the primary endpoint of PD and entered Study GS-US-312-0117 to receive IDL 150 mg tablet twice daily. Participants received placebo tablet twice daily plus rituximab (8 infusions intravenously) in Study GS-US-312-0116 and entered Study GS-US-312-0117 to receive IDL 150 mg tablet twice daily.
    Measure Participants 110 42 44
    Any TEAE
    98.2
    89.3%
    100.0
    238.1%
    97.7
    222%
    ≥ Grade 3 TEAE
    90.9
    82.6%
    88.1
    209.8%
    90.9
    206.6%
    Study Drug-Related TEAE
    68.2
    62%
    59.5
    141.7%
    72.7
    165.2%
    ≥ Grade 3 Study Drug-Related TEAE
    47.3
    43%
    45.2
    107.6%
    45.5
    103.4%
    Serious TEAE
    80.9
    73.5%
    81.0
    192.9%
    72.7
    165.2%
    Study Drug-Related Serious TEAE
    35.5
    32.3%
    26.2
    62.4%
    29.5
    67%
    TEAE Leading to Study Drug Discontinuation
    47.3
    43%
    64.3
    153.1%
    50.0
    113.6%
    3. Secondary Outcome
    Title Overall Response Rate (ORR)
    Description ORR was defined as the percentage of participants who achieved a complete response (CR) or partial response (PR). The determination of CLL response and progression were based on standardized International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria, as specifically modified for this study to reflect current recommendations which considered the mechanism of action of idelalisib and similar drugs. CR and PR are defined in Protocol Amendment 9, Sections 7.5.1 and 7.5.2.
    Time Frame GS-US-312-0116 Baseline to end of study GS-US-312-0117 (maximum: up to 67.6 months)

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set were analyzed.
    Arm/Group Title IDL+R to IDL Placebo+R (PD) to IDL 150 mg Placebo+R to IDL 150 mg
    Arm/Group Description Participants received IDL 150 mg tablet twice daily plus rituximab (8 infusions intravenously) in Study GS-US-312-0116 and may have entered Study GS-US-312-0117 to receive IDL 150 mg or 300 mg tablet twice daily. Due to the small number of participants in the IDL+R (PD) to IDL 300 mg group, data from this group were combined with the IDL+R to IDL 150 mg group for Baseline Characteristics and Outcome Measures sections. Participants received placebo tablet twice daily plus rituximab (8 infusions intravenously) in Study GS-US-312-0116 and met the primary endpoint of PD and entered Study GS-US-312-0117 to receive IDL 150 mg tablet twice daily. Participants received placebo tablet twice daily plus rituximab (8 infusions intravenously) in Study GS-US-312-0116 and entered Study GS-US-312-0117 to receive IDL 150 mg tablet twice daily.
    Measure Participants 110 42 44
    Number (95% Confidence Interval) [percentage of participants]
    85.5
    77.7%
    47.6
    113.3%
    68.2
    155%
    4. Secondary Outcome
    Title Lymph Node Response Rate
    Description Lymph node response rate was defined as the percentage of participants who achieved a ≥ 50% decrease from baseline in the sum of the products of the greatest perpendicular diameters (SPD) of index lymph nodes.
    Time Frame GS-US-312-0116 Baseline to end of study GS-US-312-0117 (maximum: up to 67.6 months)

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set with available data were analyzed.
    Arm/Group Title IDL+R to IDL Placebo+R (PD) to IDL 150 mg Placebo+R to IDL 150 mg
    Arm/Group Description Participants received IDL 150 mg tablet twice daily plus rituximab (8 infusions intravenously) in Study GS-US-312-0116 and may have entered Study GS-US-312-0117 to receive IDL 150 mg or 300 mg tablet twice daily. Due to the small number of participants in the IDL+R (PD) to IDL 300 mg group, data from this group were combined with the IDL+R to IDL 150 mg group for Baseline Characteristics and Outcome Measures sections. Participants received placebo tablet twice daily plus rituximab (8 infusions intravenously) in Study GS-US-312-0116 and met the primary endpoint of PD and entered Study GS-US-312-0117 to receive IDL 150 mg tablet twice daily. Participants received placebo tablet twice daily plus rituximab (8 infusions intravenously) in Study GS-US-312-0116 and entered Study GS-US-312-0117 to receive IDL 150 mg tablet twice daily.
    Measure Participants 106 36 43
    Number (95% Confidence Interval) [percentage of participants]
    97.2
    88.4%
    77.8
    185.2%
    83.7
    190.2%
    5. Secondary Outcome
    Title Complete Response (CR) Rate
    Description CR rate was defined as the percentage of participants who achieved a CR (full definition in Protocol Amendment 9, Section 7.5.1). The determination of CLL response and progression were based on standardized IWCLL criteria, as specifically modified for this study to reflect current recommendations which considered the mechanism of action of idelalisib and similar drugs.
    Time Frame GS-US-312-0116 Baseline to end of study GS-US-312-0117 (maximum: up to 67.6 months)

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set were analyzed.
    Arm/Group Title IDL+R to IDL Placebo+R (PD) to IDL 150 mg Placebo+R to IDL 150 mg
    Arm/Group Description Participants received IDL 150 mg tablet twice daily plus rituximab (8 infusions intravenously) in Study GS-US-312-0116 and may have entered Study GS-US-312-0117 to receive IDL 150 mg or 300 mg tablet twice daily. Due to the small number of participants in the IDL+R (PD) to IDL 300 mg group, data from this group were combined with the IDL+R to IDL 150 mg group for Baseline Characteristics and Outcome Measures sections. Participants received placebo tablet twice daily plus rituximab (8 infusions intravenously) in Study GS-US-312-0116 and met the primary endpoint of PD and entered Study GS-US-312-0117 to receive IDL 150 mg tablet twice daily. Participants received placebo tablet twice daily plus rituximab (8 infusions intravenously) in Study GS-US-312-0116 and entered Study GS-US-312-0117 to receive IDL 150 mg tablet twice daily.
    Measure Participants 110 42 44
    Number [percentage of participants]
    0.9
    0.8%
    0.0
    0%
    0.0
    0%
    6. Secondary Outcome
    Title Time to Response (TTR)
    Description TTR was defined as the time interval from start of study therapy to the first documentation of CR or PR.
    Time Frame GS-US-312-0116 Baseline to end of study GS-US-312-0117 (maximum: up to 67.6 months)

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set who achieved a CR or PR were analyzed.
    Arm/Group Title IDL+R to IDL Placebo+R (PD) to IDL 150 mg Placebo+R to IDL 150 mg
    Arm/Group Description Participants received IDL 150 mg tablet twice daily plus rituximab (8 infusions intravenously) in Study GS-US-312-0116 and may have entered Study GS-US-312-0117 to receive IDL 150 mg or 300 mg tablet twice daily. Due to the small number of participants in the IDL+R (PD) to IDL 300 mg group, data from this group were combined with the IDL+R to IDL 150 mg group for Baseline Characteristics and Outcome Measures sections. Participants received placebo tablet twice daily plus rituximab (8 infusions intravenously) in Study GS-US-312-0116 and met the primary endpoint of PD and entered Study GS-US-312-0117 to receive IDL 150 mg tablet twice daily. Participants received placebo tablet twice daily plus rituximab (8 infusions intravenously) in Study GS-US-312-0116 and entered Study GS-US-312-0117 to receive IDL 150 mg tablet twice daily.
    Measure Participants 94 20 30
    Median (Inter-Quartile Range) [months]
    2.1
    3.6
    2.8
    7. Secondary Outcome
    Title Duration of Response (DOR)
    Description DOR was defined as the time interval from the first documentation of CR or PR to the earlier of the first documentation of definitive disease progression or death from any cause. DOR was analyzed using KM estimates.
    Time Frame From first documentation of CR or PR to end of study GS-US-312-0117 (maximum: up to 67.6 months)

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set who achieved a CR or PR were analyzed.
    Arm/Group Title IDL+R to IDL Placebo+R (PD) to IDL 150 mg Placebo+R to IDL 150 mg
    Arm/Group Description Participants received IDL 150 mg tablet twice daily plus rituximab (8 infusions intravenously) in Study GS-US-312-0116 and may have entered Study GS-US-312-0117 to receive IDL 150 mg or 300 mg tablet twice daily. Due to the small number of participants in the IDL+R (PD) to IDL 300 mg group, data from this group were combined with the IDL+R to IDL 150 mg group for Baseline Characteristics and Outcome Measures sections. Participants received placebo tablet twice daily plus rituximab (8 infusions intravenously) in Study GS-US-312-0116 and met the primary endpoint of PD and entered Study GS-US-312-0117 to receive IDL 150 mg tablet twice daily. Participants received placebo tablet twice daily plus rituximab (8 infusions intravenously) in Study GS-US-312-0116 and entered Study GS-US-312-0117 to receive IDL 150 mg tablet twice daily.
    Measure Participants 94 20 30
    Median (95% Confidence Interval) [months]
    21.4
    11.0
    17.6
    8. Secondary Outcome
    Title Best Percent Change in Lymph Node Area
    Description The best percent change from baseline in lymph node area (SPD) was defined as the largest decrease in tumor size during the study. The baseline SPD was the last value prior to the baseline reference date. For the participants who only had increases in tumor size from baseline, the smallest increase was considered as the best change from baseline in SPD.
    Time Frame GS-US-312-0116 Baseline to end of study GS-US-312-0117 (maximum: up to 67.6 months)

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set with available data were analyzed.
    Arm/Group Title IDL+R to IDL Placebo+R (PD) to IDL 150 mg Placebo+R to IDL 150 mg
    Arm/Group Description Participants received IDL 150 mg tablet twice daily plus rituximab (8 infusions intravenously) in Study GS-US-312-0116 and may have entered Study GS-US-312-0117 to receive IDL 150 mg or 300 mg tablet twice daily. Due to the small number of participants in the IDL+R (PD) to IDL 300 mg group, data from this group were combined with the IDL+R to IDL 150 mg group for Baseline Characteristics and Outcome Measures sections. Participants received placebo tablet twice daily plus rituximab (8 infusions intravenously) in Study GS-US-312-0116 and met the primary endpoint of PD and entered Study GS-US-312-0117 to receive IDL 150 mg tablet twice daily. Participants received placebo tablet twice daily plus rituximab (8 infusions intravenously) in Study GS-US-312-0116 and entered Study GS-US-312-0117 to receive IDL 150 mg tablet twice daily.
    Measure Participants 106 36 43
    Median (Inter-Quartile Range) [percent change]
    -80.1
    -69.7
    -71.4
    9. Secondary Outcome
    Title Splenomegaly Response Rate
    Description Splenomegaly response rate was defined as the percentage of participants with baseline splenomegaly who achieved an on-study normalization or a 50% decrease (minimum 2 cm) from baseline in the enlargement of the splenic longest vertical dimension (LVD) (by imaging).
    Time Frame GS-US-312-0116 Baseline to end of study GS-US-312-0117 (maximum: up to 67.6 months)

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set who had splenomegaly at baseline and at least 1 evaluable postbaseline spleen measurement were analyzed.
    Arm/Group Title IDL+R to IDL Placebo+R (PD) to IDL 150 mg Placebo+R to IDL 150 mg
    Arm/Group Description Participants received IDL 150 mg tablet twice daily plus rituximab (8 infusions intravenously) in Study GS-US-312-0116 and may have entered Study GS-US-312-0117 to receive IDL 150 mg or 300 mg tablet twice daily. Due to the small number of participants in the IDL+R (PD) to IDL 300 mg group, data from this group were combined with the IDL+R to IDL 150 mg group for Baseline Characteristics and Outcome Measures sections. Participants received placebo tablet twice daily plus rituximab (8 infusions intravenously) in Study GS-US-312-0116 and met the primary endpoint of PD and entered Study GS-US-312-0117 to receive IDL 150 mg tablet twice daily. Participants received placebo tablet twice daily plus rituximab (8 infusions intravenously) in Study GS-US-312-0116 and entered Study GS-US-312-0117 to receive IDL 150 mg tablet twice daily.
    Measure Participants 76 23 24
    Number (95% Confidence Interval) [percentage of participants]
    80.3
    73%
    47.8
    113.8%
    66.7
    151.6%
    10. Secondary Outcome
    Title Hepatomegaly Response Rate
    Description Hepatomegaly response rate was defined as the percentage of participants with baseline hepatomegaly who achieved an on-study normalization or a 50% decrease (minimum 2 cm) from baseline in the hepatic LVD (by imaging).
    Time Frame GS-US-312-0116 Baseline to end of study GS-US-312-0117 (maximum: up to 67.6 months)

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set who had hepatomegaly at baseline and at least 1 evaluable postbaseline liver measurement were analyzed.
    Arm/Group Title IDL+R to IDL Placebo+R (PD) to IDL 150 mg Placebo+R to IDL 150 mg
    Arm/Group Description Participants received IDL 150 mg tablet twice daily plus rituximab (8 infusions intravenously) in Study GS-US-312-0116 and may have entered Study GS-US-312-0117 to receive IDL 150 mg or 300 mg tablet twice daily. Due to the small number of participants in the IDL+R (PD) to IDL 300 mg group, data from this group were combined with the IDL+R to IDL 150 mg group for Baseline Characteristics and Outcome Measures sections. Participants received placebo tablet twice daily plus rituximab (8 infusions intravenously) in Study GS-US-312-0116 and met the primary endpoint of PD and entered Study GS-US-312-0117 to receive IDL 150 mg tablet twice daily. Participants received placebo tablet twice daily plus rituximab (8 infusions intravenously) in Study GS-US-312-0116 and entered Study GS-US-312-0117 to receive IDL 150 mg tablet twice daily.
    Measure Participants 54 22 20
    Number (95% Confidence Interval) [percentage of participants]
    63.0
    57.3%
    36.4
    86.7%
    30.0
    68.2%
    11. Secondary Outcome
    Title Absolute Lymphocyte Count (ALC) Response Rate
    Description ALC response rate was defined as the percentage of participants with baseline lymphocytosis (ALC ≥ 4 x 10^9 cells/L) who achieved an on-study ALC < 4 x 10^9 cells/L or demonstrated a ≥ 50% decrease in ALC from baseline; ALC values within 4 weeks post-baseline were excluded from the ALC response rate evaluation.
    Time Frame GS-US-312-0116 Baseline to end of study GS-US-312-0117 (maximum: up to 67.6 months)

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set who had lymphocytosis (ALC ≥ 4 × 10^9/L) at baseline and at least 1 evaluable postbaseline value were analyzed.
    Arm/Group Title IDL+R to IDL Placebo+R (PD) to IDL 150 mg Placebo+R to IDL 150 mg
    Arm/Group Description Participants received IDL 150 mg tablet twice daily plus rituximab (8 infusions intravenously) in Study GS-US-312-0116 and may have entered Study GS-US-312-0117 to receive IDL 150 mg or 300 mg tablet twice daily. Due to the small number of participants in the IDL+R (PD) to IDL 300 mg group, data from this group were combined with the IDL+R to IDL 150 mg group for Baseline Characteristics and Outcome Measures sections. Participants received placebo tablet twice daily plus rituximab (8 infusions intravenously) in Study GS-US-312-0116 and met the primary endpoint of PD and entered Study GS-US-312-0117 to receive IDL 150 mg tablet twice daily. Participants received placebo tablet twice daily plus rituximab (8 infusions intravenously) in Study GS-US-312-0116 and entered Study GS-US-312-0117 to receive IDL 150 mg tablet twice daily.
    Measure Participants 88 27 34
    Number (95% Confidence Interval) [percentage of participants]
    94.3
    85.7%
    66.7
    158.8%
    64.7
    147%
    12. Secondary Outcome
    Title Platelet Response Rate
    Description Platelet response rate was defined as the percentage of participants with baseline thrombocytopenia (platelet count < 100 x 10^9/L) who achieved an on-study platelet count ≥ 100 x 10^9/L or demonstrated a ≥ 50% increase in platelet count from baseline; platelet values within 4 weeks post-baseline or after 8 days post transfusion were excluded from the platelet response rate evaluation.
    Time Frame GS-US-312-0116 Baseline to end of study GS-US-312-0117 (maximum: up to 67.6 months)

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set who had thrombocytopenia (platelet count < 100 × 10^9/L) at baseline and at least 1 evaluable postbaseline value were analyzed.
    Arm/Group Title IDL+R to IDL Placebo+R (PD) to IDL 150 mg Placebo+R to IDL 150 mg
    Arm/Group Description Participants received IDL 150 mg tablet twice daily plus rituximab (8 infusions intravenously) in Study GS-US-312-0116 and may have entered Study GS-US-312-0117 to receive IDL 150 mg or 300 mg tablet twice daily. Due to the small number of participants in the IDL+R (PD) to IDL 300 mg group, data from this group were combined with the IDL+R to IDL 150 mg group for Baseline Characteristics and Outcome Measures sections. Participants received placebo tablet twice daily plus rituximab (8 infusions intravenously) in Study GS-US-312-0116 and met the primary endpoint of PD and entered Study GS-US-312-0117 to receive IDL 150 mg tablet twice daily. Participants received placebo tablet twice daily plus rituximab (8 infusions intravenously) in Study GS-US-312-0116 and entered Study GS-US-312-0117 to receive IDL 150 mg tablet twice daily.
    Measure Participants 50 23 10
    Number (95% Confidence Interval) [percentage of participants]
    98.0
    89.1%
    73.9
    176%
    100.0
    227.3%
    13. Secondary Outcome
    Title Hemoglobin Response Rate
    Description Hemoglobin response rate was defined as the percentage of participants with baseline anemia (hemoglobin < 110 g/L [11.0 g/dL]) who achieved an on-study hemoglobin ≥ 110 g/L (11.0 g/dL) or demonstrated a ≥ 50% increase in hemoglobin from baseline; hemoglobin values within 4 weeks post-baseline or after 4 weeks of receiving packed cell/whole blood transfusion or after 6 weeks of receiving exogenous growth factors (eg, darbepoetin alfa) were excluded from the hemoglobin response evaluation.
    Time Frame GS-US-312-0116 Baseline to end of study GS-US-312-0117 (maximum: up to 67.6 months)

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set who had anemia (hemoglobin < 110 g/L [11 g/dL]) at baseline and at least 1 evaluable postbaseline value were analyzed.
    Arm/Group Title IDL+R to IDL Placebo+R (PD) to IDL 150 mg Placebo+R to IDL 150 mg
    Arm/Group Description Participants received IDL 150 mg tablet twice daily plus rituximab (8 infusions intravenously) in Study GS-US-312-0116 and may have entered Study GS-US-312-0117 to receive IDL 150 mg or 300 mg tablet twice daily. Due to the small number of participants in the IDL+R (PD) to IDL 300 mg group, data from this group were combined with the IDL+R to IDL 150 mg group for Baseline Characteristics and Outcome Measures sections. Participants received placebo tablet twice daily plus rituximab (8 infusions intravenously) in Study GS-US-312-0116 and met the primary endpoint of PD and entered Study GS-US-312-0117 to receive IDL 150 mg tablet twice daily. Participants received placebo tablet twice daily plus rituximab (8 infusions intravenously) in Study GS-US-312-0116 and entered Study GS-US-312-0117 to receive IDL 150 mg tablet twice daily.
    Measure Participants 59 24 11
    Number (95% Confidence Interval) [percentage of participants]
    83.1
    75.5%
    45.8
    109%
    81.8
    185.9%
    14. Secondary Outcome
    Title Neutrophil Response Rate
    Description Neutrophil response rate was defined as the percentage of participants with baseline neutropenia (absolute neutrophil count [ANC] ≤ 1.5 x 10^9/L) who achieved an ANC > 1.5 x 10^9/L or demonstrated a ≥ 50% increase in ANC from baseline; ANC values within 4 weeks of post-baseline or after 2 weeks of receiving exogenous growth factors (eg, filgrastim, granulocyte-colony stimulating factor [G-CSF], lenograstim) or after 4 weeks of receiving Neulasta® were excluded from response evaluation.
    Time Frame GS-US-312-0116 Baseline to end of study GS-US-312-0117 (maximum: up to 67.6 months)

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set who had neutropenia (ANC ≤ 1.5 × 10^9/L) at baseline and at least 1 evaluable postbaseline value were analyzed.
    Arm/Group Title IDL+R to IDL Placebo+R (PD) to IDL 150 mg Placebo+R to IDL 150 mg
    Arm/Group Description Participants received IDL 150 mg tablet twice daily plus rituximab (8 infusions intravenously) in Study GS-US-312-0116 and may have entered Study GS-US-312-0117 to receive IDL 150 mg or 300 mg tablet twice daily. Due to the small number of participants in the IDL+R (PD) to IDL 300 mg group, data from this group were combined with the IDL+R to IDL 150 mg group for Baseline Characteristics and Outcome Measures sections. Participants received placebo tablet twice daily plus rituximab (8 infusions intravenously) in Study GS-US-312-0116 and met the primary endpoint of PD and entered Study GS-US-312-0117 to receive IDL 150 mg tablet twice daily. Participants received placebo tablet twice daily plus rituximab (8 infusions intravenously) in Study GS-US-312-0116 and entered Study GS-US-312-0117 to receive IDL 150 mg tablet twice daily.
    Measure Participants 27 11 6
    Number (95% Confidence Interval) [percentage of participants]
    96.3
    87.5%
    90.9
    216.4%
    100.0
    227.3%
    15. Secondary Outcome
    Title Overall Survival
    Description Overall survival was defined as the time interval from start of study therapy to death from any cause. Overall survival was analyzed using KM estimates. Data presented includes all available survival information from Study GS-US-312-0116 (including data in long-term follow-up) and Study GS-US-312-0117 (including any data in long-term follow-up) up to the database finalization dates. Data from surviving participants were censored at the last time that the participant was known to be alive on study or long-term follow-up. Data presented includes all participants who were randomized to Study GS-US-312-0116 regardless if they entered Study GS-US-312-0117 or not.
    Time Frame GS-US-312-0116 Baseline to end of study GS-US-312-0117 (maximum: up to 67.6 months)

    Outcome Measure Data

    Analysis Population Description
    Per the analysis plan, overall survival data was analyzed in the ITT Analysis Set (participants who were randomized in the study) by treatment group according to the original randomization in Study GS-US-312-0116, regardless of whether participants received any study drug, or received a different regimen from the regimen they were randomized to.
    Arm/Group Title IDL+R Placebo+R
    Arm/Group Description Participants were randomized to receive IDL 150 mg tablet twice daily plus rituximab (8 infusions intravenously) in Study GS-US-312-0116. Participants were randomized to receive placebo tablet twice daily plus rituximab (8 infusions intravenously) in Study GS-US-312-0116.
    Measure Participants 110 110
    Median (95% Confidence Interval) [months]
    40.6
    34.6
    16. Secondary Outcome
    Title Best Change From Baseline in Health-Related Quality of Life (HRQL) Domain and Symptom Scores Based on the Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu) Questionnaire
    Description The FACT-Leu questionnaire included subscales for physical well-being (PWB, 7 items), social/family well-being (SWB, 7 items), emotional well-being (EWB, 6 items), functional well-being (FWB, 7 items), and additional concerns or Leukemia-Specific Subscale (LeuS, 17 items). The FACT-Leu scoring guide identified those negatively stated items that must have been reversed before being added to obtain subscale totals. Negatively stated items were reversed by subtracting the response from "4". After reversing proper items, all subscale items were summed to get total subscale scores with the range of 0-28, 0-28, 0-24, 0-28, 0-68 for PWB, SWB, EWB, FWB, and LeuS, respectively. FACT-Leu total score ranged from 0 to 176. Higher scores indicated a better quality of life. Best change from baseline was defined as the highest value of change from baseline among all postbaseline visits. For participants who did not enter Study GS-US-312-0117, baseline values were from Study GS-US-312-0116.
    Time Frame Study GS-US-312-0116 or GS-US-312-0117 Baseline up to Week 184

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set with available data were analyzed.
    Arm/Group Title IDL+R to IDL Placebo+R (PD) to IDL 150 mg Placebo+R to IDL 150 mg
    Arm/Group Description Participants received IDL 150 mg tablet twice daily plus rituximab (8 infusions intravenously) in Study GS-US-312-0116 and may have entered Study GS-US-312-0117 to receive IDL 150 mg or 300 mg tablet twice daily. Due to the small number of participants in the IDL+R (PD) to IDL 300 mg group, data from this group were combined with the IDL+R to IDL 150 mg group for Baseline Characteristics and Outcome Measures sections. Participants received placebo tablet twice daily plus rituximab (8 infusions intravenously) in Study GS-US-312-0116 and met the primary endpoint of PD and entered Study GS-US-312-0117 to receive IDL 150 mg tablet twice daily. Participants received placebo tablet twice daily plus rituximab (8 infusions intravenously) in Study GS-US-312-0116 and entered Study GS-US-312-0117 to receive IDL 150 mg tablet twice daily.
    Measure Participants 107 42 44
    Total Score: Baseline
    128.4
    (22.72)
    116.7
    (29.56)
    128.1
    (29.16)
    PWB: Baseline
    22.8
    (4.42)
    20.2
    (5.93)
    21.9
    (5.41)
    SWB: Baseline
    22.5
    (5.53)
    22.5
    (5.06)
    23.5
    (5.04)
    EWB: Baseline
    19.1
    (3.44)
    17.3
    (4.97)
    17.6
    (4.48)
    FWB: Baseline
    18.0
    (6.57)
    15.0
    (7.17)
    18.0
    (6.88)
    LeuS: Baseline
    46.0
    (10.64)
    41.7
    (12.74)
    47.0
    (12.01)
    Total Score: Best Change from Baseline
    21.8
    (19.64)
    20.2
    (19.91)
    14.9
    (12.04)
    PWB: Best Change from Baseline
    3.1
    (4.65)
    3.6
    (4.26)
    3.4
    (3.81)
    SWB: Best Change from Baseline
    2.9
    (5.21)
    2.0
    (2.88)
    2.1
    (2.39)
    EWB: Best Change from Baseline
    3.1
    (2.75)
    3.1
    (3.68)
    2.8
    (3.14)
    FWB: Best Change from Baseline
    5.1
    (5.80)
    4.1
    (5.01)
    3.1
    (2.94)
    LeuS: Best Change from Baseline
    11.3
    (9.13)
    10.1
    (8.78)
    7.8
    (5.59)
    17. Secondary Outcome
    Title Best Change From Baseline in Karnofsky Performance Status (KPS)
    Description KPS is a tool used to measure the ability to perform ordinary tasks. The score ranges from 0 to 100, with a higher score indicating that the participant is better able to carry out daily activities. Best change from baseline was defined as the highest value of change from baseline among all postbaseline visits. For participants who did not enter Study GS-US-312-0117, baseline values were from Study GS-US-312-0116.
    Time Frame Study GS-US-312-0116 or GS-US-312-0117 Baseline up to Week 190

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set with available data were analyzed.
    Arm/Group Title IDL+R to IDL Placebo+R (PD) to IDL 150 mg Placebo+R to IDL 150 mg
    Arm/Group Description Participants received IDL 150 mg tablet twice daily plus rituximab (8 infusions intravenously) in Study GS-US-312-0116 and may have entered Study GS-US-312-0117 to receive IDL 150 mg or 300 mg tablet twice daily. Due to the small number of participants in the IDL+R (PD) to IDL 300 mg group, data from this group were combined with the IDL+R to IDL 150 mg group for Baseline Characteristics and Outcome Measures sections. Participants received placebo tablet twice daily plus rituximab (8 infusions intravenously) in Study GS-US-312-0116 and met the primary endpoint of PD and entered Study GS-US-312-0117 to receive IDL 150 mg tablet twice daily. Participants received placebo tablet twice daily plus rituximab (8 infusions intravenously) in Study GS-US-312-0116 and entered Study GS-US-312-0117 to receive IDL 150 mg tablet twice daily.
    Measure Participants 110 42 44
    Baseline
    80.7
    (12.47)
    78.1
    (14.18)
    86.8
    (8.83)
    Best Change From Baseline
    11.1
    (10.31)
    7.1
    (8.67)
    4.3
    (6.98)
    18. Secondary Outcome
    Title Changes From Baseline in Phosphatidylinositol 3-kinase (PI3Kδ)/Akt/Mammalian Target of Rapamycin (mTOR) Pathway Activation as a Measure of PI3Kδ Pathway Activity
    Description
    Time Frame GS-US-312-0116 Baseline to end of study GS-US-312-0117 (maximum: up to 67.6 months)

    Outcome Measure Data

    Analysis Population Description
    Data were not collected because there was insufficient volume of sample (not enough material) to perform the analysis for any participant.
    Arm/Group Title IDL+R to IDL Placebo+R (PD) to IDL 150 mg Placebo+R to IDL 150 mg
    Arm/Group Description Participants received IDL 150 mg tablet twice daily plus rituximab (8 infusions intravenously) in Study GS-US-312-0116 and may have entered Study GS-US-312-0117 to receive IDL 150 mg or 300 mg tablet twice daily. Participants received placebo tablet twice daily plus rituximab (8 infusions intravenously) in Study GS-US-312-0116 and met the primary endpoint of PD and entered Study GS-US-312-0117 to receive IDL 150 mg tablet twice daily. Participants received placebo tablet twice daily plus rituximab (8 infusions intravenously) in Study GS-US-312-0116 and entered Study GS-US-312-0117 to receive IDL 150 mg tablet twice daily.
    Measure Participants 0 0 0
    19. Secondary Outcome
    Title Overall Change From Baseline in the Plasma Concentrations of Disease-Associated Chemokines and Cytokines
    Description The percent of average on-treatment biomarker concentration of baseline (%Baseline) was used to evaluate the overall pharmacodynamics change on the biomarkers with IDL treatment. The average on-treatment biomarker concentration is calculated using area under curve (AUC) following the trapezoidal rule. The biomarkers with median AUC value of 100 indicated no overall on-treatment biomarker changes compared to the baseline. The biomarkers with median AUC value greater than 100 or less than 100 indicated an increase or decrease, respectively, on-treatment biomarker changes from the baseline.
    Time Frame GS-US-312-0116 Baseline to end of study GS-US-312-0117 (maximum: up to 67.6 months)

    Outcome Measure Data

    Analysis Population Description
    The cytokine and T-cell subsets biomarker analysis set included all participants who received at least one dose of study drug, consented for optional future study, and had at least one evaluable measurement for any biomarker at any visit on IDL treatment. Available samples were batched for analysis as prespecified.
    Arm/Group Title IDL/Placebo+R to IDL
    Arm/Group Description Participants received IDL 150 mg tablet or placebo tablet twice daily plus rituximab (8 infusions intravenously) in Study GS-US-312-0116 (either met or not met the primary endpoint of PD) and may have entered Study GS-US-312-0117 to receive IDL 150 mg or 300 mg tablet twice daily.
    Measure Participants 174
    Tumor Necrosis Factor (TNF)-alpha
    36.73
    Macrophage Inflammatory Protein (MIP)1-alpha
    26.55
    Interleukin (IL)-10
    58.65
    IL-15
    111.18
    IL-12p40
    64.89
    RANTES (CCL5)
    131.94
    IL-1ra
    114.22
    Interferon (IFN)-gamma
    127.72
    C-Reactive Protein (CRP)
    132.38
    IFN-gamma-induced protein (IP)-10 (CXCL10)
    88.5
    IL-7
    91.82
    Granulocyte-colony stimulating factor (G-CSF)
    96.59
    IL-17A
    100
    IL-6
    100
    IL-8
    102.59
    20. Secondary Outcome
    Title Study Drug Compliance as Assessed by the Percentage of Participants Adhering to Treatment
    Description Adherence percentage was calculated as the sum of tablets dispensed - the sum of tablets returned divided by the sum of the overall dosing period (total daily tablets x dosing duration), taking into account investigator-prescribed interruptions.
    Time Frame First IDL dose date in study GS-US-312-0116 or GS-US-312-0117 to last IDL dose date in study GS-US-312-0117 (maximum: 67.3 months)

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set were analyzed.
    Arm/Group Title IDL+R to IDL Placebo+R (PD) to IDL 150 mg Placebo+R to IDL 150 mg
    Arm/Group Description Participants received IDL 150 mg tablet twice daily plus rituximab (8 infusions intravenously) in Study GS-US-312-0116 and may have entered Study GS-US-312-0117 to receive IDL 150 mg or 300 mg tablet twice daily. Due to the small number of participants in the IDL+R (PD) to IDL 300 mg group, data from this group were combined with the IDL+R to IDL 150 mg group for Baseline Characteristics and Outcome Measures sections. Participants received placebo tablet twice daily plus rituximab (8 infusions intravenously) in Study GS-US-312-0116 and met the primary endpoint of PD and entered Study GS-US-312-0117 to receive IDL 150 mg tablet twice daily. Participants received placebo tablet twice daily plus rituximab (8 infusions intravenously) in Study GS-US-312-0116 and entered Study GS-US-312-0117 to receive IDL 150 mg tablet twice daily.
    Measure Participants 110 42 44
    Adherence ≥ 75%
    100.0
    90.9%
    97.6
    232.4%
    100.0
    227.3%
    Adherence < 75%
    0.0
    0%
    2.4
    5.7%
    0.0
    0%
    21. Secondary Outcome
    Title Plasma Trough (Predose) and Peak (1.5 Hours Postdose) Concentrations of Idelalisib
    Description
    Time Frame Weeks 4, 12, and 24

    Outcome Measure Data

    Analysis Population Description
    Participants in the pharmacokinetic (PK) Analysis Set (participants in the Full Analysis Set who had the necessary baseline and on-study measurements to provide interpretable results for the specific parameters of interest) with available data were analyzed.
    Arm/Group Title IDL+R to IDL 150 mg IDL+R (PD) to IDL 300 mg Placebo+R (PD) to IDL 150 mg Placebo+R to IDL 150 mg
    Arm/Group Description Participants who received IDL 150 mg tablet twice daily plus rituximab (8 infusions intravenously) in Study GS-US-312-0116 and entered Study GS-US-312-0117 to receive IDL 150 mg tablet twice daily. Participants received IDL 150 mg tablet twice daily plus rituximab (8 infusions intravenously) in Study GS-US-312-0116 and met the primary endpoint of PD and entered Study GS-US-312-0117 to receive IDL 300 mg tablet twice daily. Participants received placebo tablet twice daily plus rituximab (8 infusions intravenously) in Study GS-US-312-0116 and met the primary endpoint of PD and entered Study GS-US-312-0117 to receive IDL 150 mg tablet twice daily. Participants received placebo tablet twice daily plus rituximab (8 infusions intravenously) in Study GS-US-312-0116 and entered Study GS-US-312-0117 to receive IDL 150 mg tablet twice daily.
    Measure Participants 40 3 30 29
    Week 4: Predose
    384.0
    470.0
    301.5
    412.0
    Week 4: 1.5 Hours Postdose
    2115.0
    3940.0
    2580.0
    1720.0
    Week 12: Predose
    370.0
    570.0
    335.0
    298.0
    Week 12: 1.5 Hours Postdose
    2110.0
    3800.0
    2245.0
    1940.0
    Week 24: Predose
    307.0
    637.0
    362.0
    350.5
    Week 24: 1.5 Hours Postdose
    2270.0
    5630.0
    2180.0
    2010.0
    22. Secondary Outcome
    Title Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure
    Description Change in health status was defined as the change from baseline in overall health and single-item dimension scores as assessed using the EQ-5D utility measure. Percentage of participants with different level of problem were reported. Level 1: indicated no problem; Level 2: indicated some problems; and Level 3: indicated extreme problems. For participants who did not enter Study GS-US-312-0117, baseline values were from Study GS-US-312-0116.
    Time Frame Study GS-US-312-0116 or GS-US-312-0117 Baseline; Weeks 24 and 48

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set with available data were analyzed.
    Arm/Group Title IDL+R to IDL Placebo+R (PD) to IDL 150 mg Placebo+R to IDL 150 mg
    Arm/Group Description Participants received IDL 150 mg tablet twice daily plus rituximab (8 infusions intravenously) in Study GS-US-312-0116 and may have entered Study GS-US-312-0117 to receive IDL 150 mg or 300 mg tablet twice daily. Due to the small number of participants in the IDL+R (PD) to IDL 300 mg group, data from this group were combined with the IDL+R to IDL 150 mg group for Baseline Characteristics and Outcome Measures sections. Participants received placebo tablet twice daily plus rituximab (8 infusions intravenously) in Study GS-US-312-0116 and met the primary endpoint of PD and entered Study GS-US-312-0117 to receive IDL 150 mg tablet twice daily. Participants received placebo tablet twice daily plus rituximab (8 infusions intravenously) in Study GS-US-312-0116 and entered Study GS-US-312-0117 to receive IDL 150 mg tablet twice daily.
    Measure Participants 108 42 44
    Baseline: Anxiety/Depression, Level 1
    70.4
    64%
    50.0
    119%
    56.8
    129.1%
    Baseline: Anxiety/Depression, Level 2
    28.7
    26.1%
    42.9
    102.1%
    43.2
    98.2%
    Baseline: Anxiety/Depression, Level 3
    0.9
    0.8%
    7.1
    16.9%
    0.0
    0%
    Baseline: Mobility, Level 1
    60.2
    54.7%
    38.1
    90.7%
    61.4
    139.5%
    Baseline: Mobility, Level 2
    39.8
    36.2%
    59.5
    141.7%
    38.6
    87.7%
    Baseline: Mobility, Level 3
    0.0
    0%
    2.4
    5.7%
    0.0
    0%
    Baseline: Pain/Discomfort, Level 1
    53.3
    48.5%
    50.0
    119%
    45.5
    103.4%
    Baseline: Pain/Discomfort, Level 2
    39.3
    35.7%
    45.2
    107.6%
    50.0
    113.6%
    Baseline: Pain/Discomfort, Level 3
    7.5
    6.8%
    4.8
    11.4%
    4.5
    10.2%
    Baseline: Self-Care, Level 1
    90.7
    82.5%
    76.2
    181.4%
    84.1
    191.1%
    Baseline: Self-Care, Level 2
    9.3
    8.5%
    19.0
    45.2%
    15.9
    36.1%
    Baseline: Self-Care, Level 3
    0.0
    0%
    4.8
    11.4%
    0.0
    0%
    Baseline: Usual Activities, Level 1
    56.5
    51.4%
    28.6
    68.1%
    52.3
    118.9%
    Baseline: Usual Activities, Level 2
    36.1
    32.8%
    52.4
    124.8%
    45.5
    103.4%
    Baseline: Usual Activities, Level 3
    7.4
    6.7%
    19.0
    45.2%
    2.3
    5.2%
    Week 24: Anxiety/Depression, Level 1
    83.1
    75.5%
    65.0
    154.8%
    69.6
    158.2%
    Week 24: Anxiety/Depression, Level 2
    15.6
    14.2%
    35.0
    83.3%
    30.4
    69.1%
    Week 24: Anxiety/Depression, Level 3
    1.3
    1.2%
    0.0
    0%
    0.0
    0%
    Week 24: Mobility, Level 1
    70.1
    63.7%
    65.0
    154.8%
    69.6
    158.2%
    Week 24: Mobility, Level 2
    29.9
    27.2%
    35.0
    83.3%
    30.4
    69.1%
    Week 24: Mobility, Level 3
    0.0
    0%
    0.0
    0%
    0.0
    0%
    Week 24: Pain/Discomfort, Level 1
    62.3
    56.6%
    65.0
    154.8%
    43.5
    98.9%
    Week 24: Pain/Discomfort, Level 2
    35.1
    31.9%
    30.0
    71.4%
    47.8
    108.6%
    Week 24: Pain/Discomfort, Level 3
    2.6
    2.4%
    5.0
    11.9%
    8.7
    19.8%
    Week 24: Self-Care, Level 1
    92.2
    83.8%
    85.0
    202.4%
    91.3
    207.5%
    Week 24: Self-Care, Level 2
    6.5
    5.9%
    15.0
    35.7%
    8.7
    19.8%
    Week 24: Self-Care, Level 3
    1.3
    1.2%
    0.0
    0%
    0.0
    0%
    Week 24: Usual Activities, Level 1
    68.4
    62.2%
    75.0
    178.6%
    60.9
    138.4%
    Week 24: Usual Activities, Level 2
    28.9
    26.3%
    25.0
    59.5%
    34.8
    79.1%
    Week 24: Usual Activities, Level 3
    2.6
    2.4%
    0.0
    0%
    4.3
    9.8%
    Week 48: Anxiety/Depression, Level 1
    84.1
    76.5%
    90.0
    214.3%
    50.0
    113.6%
    Week 48: Anxiety/Depression, Level 2
    15.9
    14.5%
    10.0
    23.8%
    50.0
    113.6%
    Week 48: Anxiety/Depression, Level 3
    0.0
    0%
    0.0
    0%
    0.0
    0%
    Week 48: Mobility, Level 1
    72.7
    66.1%
    60.0
    142.9%
    66.7
    151.6%
    Week 48: Mobility, Level 2
    27.3
    24.8%
    40.0
    95.2%
    33.3
    75.7%
    Week 48: Mobility, Level 3
    0.0
    0%
    0.0
    0%
    0.0
    0%
    Week 48: Pain/Discomfort, Level 1
    56.8
    51.6%
    60.0
    142.9%
    50.0
    113.6%
    Week 48: Pain/Discomfort, Level 2
    43.2
    39.3%
    30.0
    71.4%
    50.0
    113.6%
    Week 48: Pain/Discomfort, Level 3
    0.0
    0%
    10.0
    23.8%
    0.0
    0%
    Week 48: Self-Care, Level 1
    95.5
    86.8%
    90.0
    214.3%
    83.3
    189.3%
    Week 48: Self-Care, Level 2
    4.5
    4.1%
    0.0
    0%
    16.7
    38%
    Week 48: Self-Care, Level 3
    0.0
    0%
    10.0
    23.8%
    0.0
    0%
    Week 48: Usual Activities, Level 1
    72.7
    66.1%
    70.0
    166.7%
    50.0
    113.6%
    Week 48: Usual Activities, Level 2
    25.0
    22.7%
    20.0
    47.6%
    33.3
    75.7%
    Week 48: Usual Activities, Level 3
    2.3
    2.1%
    10.0
    23.8%
    16.7
    38%

    Adverse Events

    Time Frame Adverse Events: First IDL dose date in study GS-US-312-0116 or GS-US-312-0117 to last IDL dose date in study GS-US-312-0117 (maximum: 67.3 months) plus 30 days; All-Cause Mortality: First IDL dose date up to 67.6 months
    Adverse Event Reporting Description Only adverse events occurring in participants who enrolled into the extension Study GS-US-312-0117 were included. Adverse events occurring in the parent study, GS-US-312-0116, are reported in ClinicalTrials.gov record NCT01539512.
    Arm/Group Title IDL+R to IDL 150 mg IDL+R (PD) to IDL 300 mg Placebo+R (PD) to IDL 150 mg Placebo+R to IDL 150 mg
    Arm/Group Description Adverse events reported in this group occurred during the extension Study GS-US-312-0117 in participants who received IDL 150 mg tablet twice daily plus rituximab (8 infusions intravenously) in Study GS-US-312-0116 and entered Study GS-US-312-0117 to receive IDL 150 mg tablet twice daily. Adverse events reported in this group occurred during the extension Study GS-US-312-0117 in participants who received IDL 150 mg tablet twice daily plus rituximab (8 infusions intravenously) in Study GS-US-312-0116 and entered Study GS-US-312-0117 to receive IDL 300 mg tablet twice daily. Adverse events reported in this group occurred during the extension Study GS-US-312-0117 in participants who received placebo tablet twice daily plus rituximab (8 infusions intravenously) in Study GS-US-312-0116 and met the primary endpoint of PD and entered Study GS-US-312-0117 to receive IDL 150 mg tablet twice daily. Adverse events reported in this group occurred during the extension Study GS-US-312-0117 in participants who received placebo tablet twice daily plus rituximab (8 infusions intravenously) in Study GS-US-312-0116 and entered Study GS-US-312-0117 to receive IDL 150 mg tablet twice daily.
    All Cause Mortality
    IDL+R to IDL 150 mg IDL+R (PD) to IDL 300 mg Placebo+R (PD) to IDL 150 mg Placebo+R to IDL 150 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 37/71 (52.1%) 3/4 (75%) 25/42 (59.5%) 16/44 (36.4%)
    Serious Adverse Events
    IDL+R to IDL 150 mg IDL+R (PD) to IDL 300 mg Placebo+R (PD) to IDL 150 mg Placebo+R to IDL 150 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 54/71 (76.1%) 2/4 (50%) 34/42 (81%) 32/44 (72.7%)
    Blood and lymphatic system disorders
    Anaemia 1/71 (1.4%) 0/4 (0%) 1/42 (2.4%) 0/44 (0%)
    Autoimmune haemolytic anaemia 0/71 (0%) 0/4 (0%) 1/42 (2.4%) 0/44 (0%)
    Febrile neutropenia 4/71 (5.6%) 0/4 (0%) 5/42 (11.9%) 1/44 (2.3%)
    Neutropenia 2/71 (2.8%) 0/4 (0%) 0/42 (0%) 0/44 (0%)
    Pancytopenia 0/71 (0%) 0/4 (0%) 0/42 (0%) 1/44 (2.3%)
    Thrombocytopenia 1/71 (1.4%) 0/4 (0%) 1/42 (2.4%) 0/44 (0%)
    Cardiac disorders
    Acute myocardial infarction 0/71 (0%) 0/4 (0%) 1/42 (2.4%) 0/44 (0%)
    Angina unstable 0/71 (0%) 0/4 (0%) 1/42 (2.4%) 0/44 (0%)
    Atrial fibrillation 1/71 (1.4%) 0/4 (0%) 0/42 (0%) 2/44 (4.5%)
    Atrioventricular block complete 0/71 (0%) 0/4 (0%) 0/42 (0%) 1/44 (2.3%)
    Cardiac arrest 1/71 (1.4%) 0/4 (0%) 1/42 (2.4%) 0/44 (0%)
    Cardiac failure congestive 0/71 (0%) 0/4 (0%) 1/42 (2.4%) 0/44 (0%)
    Cardio-respiratory arrest 0/71 (0%) 0/4 (0%) 2/42 (4.8%) 0/44 (0%)
    Eye disorders
    Vitreous haemorrhage 1/71 (1.4%) 0/4 (0%) 0/42 (0%) 0/44 (0%)
    Gastrointestinal disorders
    Abdominal pain 2/71 (2.8%) 0/4 (0%) 0/42 (0%) 2/44 (4.5%)
    Abdominal pain upper 1/71 (1.4%) 0/4 (0%) 0/42 (0%) 0/44 (0%)
    Colitis 5/71 (7%) 0/4 (0%) 1/42 (2.4%) 3/44 (6.8%)
    Diarrhoea 7/71 (9.9%) 0/4 (0%) 4/42 (9.5%) 8/44 (18.2%)
    Enterocolitis haemorrhagic 0/71 (0%) 0/4 (0%) 1/42 (2.4%) 0/44 (0%)
    Gastritis 0/71 (0%) 0/4 (0%) 0/42 (0%) 2/44 (4.5%)
    Haematochezia 0/71 (0%) 0/4 (0%) 1/42 (2.4%) 0/44 (0%)
    Nausea 2/71 (2.8%) 0/4 (0%) 0/42 (0%) 0/44 (0%)
    Oesophagitis 0/71 (0%) 0/4 (0%) 0/42 (0%) 1/44 (2.3%)
    Rectal haemorrhage 1/71 (1.4%) 0/4 (0%) 0/42 (0%) 0/44 (0%)
    Small intestinal obstruction 1/71 (1.4%) 0/4 (0%) 0/42 (0%) 0/44 (0%)
    Stomatitis 0/71 (0%) 0/4 (0%) 0/42 (0%) 1/44 (2.3%)
    Umbilical hernia 1/71 (1.4%) 0/4 (0%) 0/42 (0%) 0/44 (0%)
    Vomiting 2/71 (2.8%) 0/4 (0%) 0/42 (0%) 0/44 (0%)
    General disorders
    Asthenia 0/71 (0%) 0/4 (0%) 2/42 (4.8%) 1/44 (2.3%)
    Drug withdrawal syndrome 1/71 (1.4%) 0/4 (0%) 0/42 (0%) 0/44 (0%)
    Fatigue 0/71 (0%) 0/4 (0%) 0/42 (0%) 2/44 (4.5%)
    General physical health deterioration 0/71 (0%) 0/4 (0%) 0/42 (0%) 1/44 (2.3%)
    Mucosal inflammation 0/71 (0%) 0/4 (0%) 0/42 (0%) 1/44 (2.3%)
    Non-cardiac chest pain 1/71 (1.4%) 0/4 (0%) 0/42 (0%) 0/44 (0%)
    Pain 0/71 (0%) 0/4 (0%) 0/42 (0%) 1/44 (2.3%)
    Pyrexia 4/71 (5.6%) 0/4 (0%) 1/42 (2.4%) 4/44 (9.1%)
    Systemic inflammatory response syndrome 1/71 (1.4%) 0/4 (0%) 0/42 (0%) 0/44 (0%)
    Infections and infestations
    Abscess limb 0/71 (0%) 0/4 (0%) 0/42 (0%) 1/44 (2.3%)
    Acute sinusitis 1/71 (1.4%) 0/4 (0%) 0/42 (0%) 0/44 (0%)
    Appendicitis 0/71 (0%) 0/4 (0%) 1/42 (2.4%) 0/44 (0%)
    Atypical pneumonia 1/71 (1.4%) 0/4 (0%) 0/42 (0%) 0/44 (0%)
    Bacteraemia 1/71 (1.4%) 0/4 (0%) 0/42 (0%) 1/44 (2.3%)
    Candida infection 0/71 (0%) 0/4 (0%) 1/42 (2.4%) 0/44 (0%)
    Cellulitis 4/71 (5.6%) 0/4 (0%) 0/42 (0%) 4/44 (9.1%)
    Cerebral fungal infection 0/71 (0%) 0/4 (0%) 1/42 (2.4%) 0/44 (0%)
    Clostridium difficile colitis 0/71 (0%) 0/4 (0%) 1/42 (2.4%) 0/44 (0%)
    Diverticulitis 1/71 (1.4%) 0/4 (0%) 0/42 (0%) 0/44 (0%)
    Ear infection 0/71 (0%) 0/4 (0%) 1/42 (2.4%) 0/44 (0%)
    Encephalitis 0/71 (0%) 0/4 (0%) 1/42 (2.4%) 0/44 (0%)
    Erysipelas 1/71 (1.4%) 0/4 (0%) 0/42 (0%) 0/44 (0%)
    Furuncle 0/71 (0%) 0/4 (0%) 1/42 (2.4%) 0/44 (0%)
    Herpes zoster 0/71 (0%) 0/4 (0%) 1/42 (2.4%) 0/44 (0%)
    Infective exacerbation of bronchiectasis 0/71 (0%) 0/4 (0%) 0/42 (0%) 1/44 (2.3%)
    Lower respiratory tract infection 5/71 (7%) 0/4 (0%) 0/42 (0%) 3/44 (6.8%)
    Lung infection 1/71 (1.4%) 0/4 (0%) 0/42 (0%) 0/44 (0%)
    Mastoiditis 0/71 (0%) 0/4 (0%) 1/42 (2.4%) 0/44 (0%)
    Neutropenic sepsis 2/71 (2.8%) 0/4 (0%) 1/42 (2.4%) 0/44 (0%)
    Oesophageal infection 0/71 (0%) 0/4 (0%) 1/42 (2.4%) 0/44 (0%)
    Pneumocystis jirovecii pneumonia 1/71 (1.4%) 0/4 (0%) 0/42 (0%) 0/44 (0%)
    Pneumonia 6/71 (8.5%) 2/4 (50%) 10/42 (23.8%) 3/44 (6.8%)
    Pneumonia escherichia 0/71 (0%) 0/4 (0%) 0/42 (0%) 1/44 (2.3%)
    Pneumonia haemophilus 0/71 (0%) 0/4 (0%) 1/42 (2.4%) 0/44 (0%)
    Pneumonia influenzal 0/71 (0%) 0/4 (0%) 1/42 (2.4%) 0/44 (0%)
    Pneumonia pneumococcal 0/71 (0%) 0/4 (0%) 0/42 (0%) 1/44 (2.3%)
    Pneumonia pseudomonal 0/71 (0%) 0/4 (0%) 1/42 (2.4%) 0/44 (0%)
    Pneumonia respiratory syncytial viral 1/71 (1.4%) 0/4 (0%) 0/42 (0%) 0/44 (0%)
    Pneumonia viral 1/71 (1.4%) 0/4 (0%) 0/42 (0%) 0/44 (0%)
    Progressive multifocal leukoencephalopathy 1/71 (1.4%) 0/4 (0%) 0/42 (0%) 0/44 (0%)
    Pseudomonal bacteraemia 0/71 (0%) 0/4 (0%) 1/42 (2.4%) 1/44 (2.3%)
    Pseudomonal sepsis 0/71 (0%) 0/4 (0%) 1/42 (2.4%) 0/44 (0%)
    Pseudomonas infection 0/71 (0%) 0/4 (0%) 1/42 (2.4%) 0/44 (0%)
    Pyelonephritis 0/71 (0%) 0/4 (0%) 1/42 (2.4%) 0/44 (0%)
    Respiratory tract infection 0/71 (0%) 0/4 (0%) 1/42 (2.4%) 0/44 (0%)
    Sepsis 5/71 (7%) 0/4 (0%) 1/42 (2.4%) 0/44 (0%)
    Sepsis pasteurella 0/71 (0%) 1/4 (25%) 0/42 (0%) 0/44 (0%)
    Septic shock 2/71 (2.8%) 0/4 (0%) 1/42 (2.4%) 2/44 (4.5%)
    Sinusitis 1/71 (1.4%) 0/4 (0%) 0/42 (0%) 0/44 (0%)
    Sinusitis fungal 0/71 (0%) 0/4 (0%) 0/42 (0%) 1/44 (2.3%)
    Stenotrophomonas infection 0/71 (0%) 0/4 (0%) 1/42 (2.4%) 0/44 (0%)
    Streptococcal sepsis 0/71 (0%) 0/4 (0%) 0/42 (0%) 1/44 (2.3%)
    Subcutaneous abscess 0/71 (0%) 0/4 (0%) 0/42 (0%) 1/44 (2.3%)
    Tuberculosis 0/71 (0%) 0/4 (0%) 1/42 (2.4%) 0/44 (0%)
    Upper respiratory tract infection 1/71 (1.4%) 0/4 (0%) 0/42 (0%) 0/44 (0%)
    Urinary tract infection 2/71 (2.8%) 0/4 (0%) 0/42 (0%) 1/44 (2.3%)
    Injury, poisoning and procedural complications
    Contusion 0/71 (0%) 0/4 (0%) 1/42 (2.4%) 0/44 (0%)
    Fall 1/71 (1.4%) 0/4 (0%) 0/42 (0%) 0/44 (0%)
    Femur fracture 0/71 (0%) 0/4 (0%) 0/42 (0%) 1/44 (2.3%)
    Hip fracture 1/71 (1.4%) 0/4 (0%) 0/42 (0%) 1/44 (2.3%)
    Ligament rupture 1/71 (1.4%) 0/4 (0%) 0/42 (0%) 0/44 (0%)
    Limb injury 1/71 (1.4%) 0/4 (0%) 0/42 (0%) 0/44 (0%)
    Spinal compression fracture 0/71 (0%) 0/4 (0%) 1/42 (2.4%) 0/44 (0%)
    Splenic rupture 0/71 (0%) 0/4 (0%) 1/42 (2.4%) 0/44 (0%)
    Tendon rupture 1/71 (1.4%) 0/4 (0%) 0/42 (0%) 0/44 (0%)
    Tibia fracture 1/71 (1.4%) 0/4 (0%) 0/42 (0%) 0/44 (0%)
    Investigations
    Blood creatinine increased 1/71 (1.4%) 0/4 (0%) 0/42 (0%) 0/44 (0%)
    C-reactive protein increased 1/71 (1.4%) 0/4 (0%) 0/42 (0%) 0/44 (0%)
    Weight decreased 1/71 (1.4%) 0/4 (0%) 0/42 (0%) 0/44 (0%)
    Metabolism and nutrition disorders
    Decreased appetite 0/71 (0%) 0/4 (0%) 0/42 (0%) 1/44 (2.3%)
    Dehydration 1/71 (1.4%) 0/4 (0%) 0/42 (0%) 0/44 (0%)
    Failure to thrive 1/71 (1.4%) 0/4 (0%) 0/42 (0%) 0/44 (0%)
    Feeding intolerance 1/71 (1.4%) 0/4 (0%) 0/42 (0%) 0/44 (0%)
    Hypercalcaemia 2/71 (2.8%) 0/4 (0%) 0/42 (0%) 0/44 (0%)
    Hyperkalaemia 0/71 (0%) 0/4 (0%) 2/42 (4.8%) 0/44 (0%)
    Hypokalaemia 1/71 (1.4%) 0/4 (0%) 0/42 (0%) 1/44 (2.3%)
    Hyponatraemia 1/71 (1.4%) 0/4 (0%) 0/42 (0%) 0/44 (0%)
    Hypophosphataemia 0/71 (0%) 0/4 (0%) 1/42 (2.4%) 0/44 (0%)
    Tumour lysis syndrome 0/71 (0%) 0/4 (0%) 1/42 (2.4%) 0/44 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 0/71 (0%) 0/4 (0%) 0/42 (0%) 1/44 (2.3%)
    Back pain 0/71 (0%) 0/4 (0%) 2/42 (4.8%) 0/44 (0%)
    Polymyalgia rheumatica 1/71 (1.4%) 0/4 (0%) 0/42 (0%) 0/44 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Anal squamous cell carcinoma 1/71 (1.4%) 0/4 (0%) 0/42 (0%) 0/44 (0%)
    Bladder papilloma 1/71 (1.4%) 0/4 (0%) 0/42 (0%) 0/44 (0%)
    Bladder transitional cell carcinoma 1/71 (1.4%) 0/4 (0%) 0/42 (0%) 0/44 (0%)
    Intraductal proliferative breast lesion 0/71 (0%) 0/4 (0%) 0/42 (0%) 1/44 (2.3%)
    Kaposi's sarcoma 0/71 (0%) 0/4 (0%) 0/42 (0%) 1/44 (2.3%)
    Lung neoplasm malignant 0/71 (0%) 0/4 (0%) 1/42 (2.4%) 1/44 (2.3%)
    Lung squamous cell carcinoma metastatic 1/71 (1.4%) 0/4 (0%) 0/42 (0%) 0/44 (0%)
    Melanoma recurrent 0/71 (0%) 0/4 (0%) 0/42 (0%) 1/44 (2.3%)
    Meningioma 1/71 (1.4%) 0/4 (0%) 0/42 (0%) 0/44 (0%)
    Myelodysplastic syndrome 0/71 (0%) 0/4 (0%) 0/42 (0%) 1/44 (2.3%)
    Neuroendocrine carcinoma of the skin 0/71 (0%) 0/4 (0%) 0/42 (0%) 1/44 (2.3%)
    Oesophageal carcinoma 1/71 (1.4%) 0/4 (0%) 0/42 (0%) 0/44 (0%)
    Prostate cancer 1/71 (1.4%) 0/4 (0%) 0/42 (0%) 0/44 (0%)
    Squamous cell carcinoma 2/71 (2.8%) 0/4 (0%) 0/42 (0%) 1/44 (2.3%)
    Squamous cell carcinoma of lung 1/71 (1.4%) 0/4 (0%) 0/42 (0%) 0/44 (0%)
    Squamous cell carcinoma of skin 1/71 (1.4%) 0/4 (0%) 1/42 (2.4%) 1/44 (2.3%)
    Nervous system disorders
    Central nervous system haemorrhage 0/71 (0%) 0/4 (0%) 1/42 (2.4%) 0/44 (0%)
    Dizziness 1/71 (1.4%) 0/4 (0%) 0/42 (0%) 0/44 (0%)
    Haemorrhage intracranial 1/71 (1.4%) 0/4 (0%) 1/42 (2.4%) 0/44 (0%)
    Psychiatric disorders
    Confusional state 0/71 (0%) 0/4 (0%) 1/42 (2.4%) 0/44 (0%)
    Renal and urinary disorders
    Renal failure 0/71 (0%) 0/4 (0%) 1/42 (2.4%) 0/44 (0%)
    Urinary retention 0/71 (0%) 0/4 (0%) 0/42 (0%) 1/44 (2.3%)
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory distress syndrome 1/71 (1.4%) 0/4 (0%) 0/42 (0%) 0/44 (0%)
    Acute respiratory failure 1/71 (1.4%) 0/4 (0%) 2/42 (4.8%) 0/44 (0%)
    Bronchiectasis 0/71 (0%) 0/4 (0%) 0/42 (0%) 1/44 (2.3%)
    Chronic obstructive pulmonary disease 0/71 (0%) 0/4 (0%) 0/42 (0%) 1/44 (2.3%)
    Dyspnoea 0/71 (0%) 0/4 (0%) 2/42 (4.8%) 3/44 (6.8%)
    Hypoxia 1/71 (1.4%) 1/4 (25%) 0/42 (0%) 0/44 (0%)
    Pleural effusion 1/71 (1.4%) 0/4 (0%) 2/42 (4.8%) 0/44 (0%)
    Pneumonitis 2/71 (2.8%) 0/4 (0%) 1/42 (2.4%) 1/44 (2.3%)
    Pulmonary congestion 0/71 (0%) 0/4 (0%) 1/42 (2.4%) 0/44 (0%)
    Pulmonary embolism 1/71 (1.4%) 0/4 (0%) 0/42 (0%) 1/44 (2.3%)
    Respiratory failure 2/71 (2.8%) 0/4 (0%) 2/42 (4.8%) 1/44 (2.3%)
    Skin and subcutaneous tissue disorders
    Erythema multiforme 0/71 (0%) 0/4 (0%) 0/42 (0%) 1/44 (2.3%)
    Rash 2/71 (2.8%) 0/4 (0%) 0/42 (0%) 1/44 (2.3%)
    Rash maculo-papular 1/71 (1.4%) 0/4 (0%) 0/42 (0%) 0/44 (0%)
    Rash pruritic 1/71 (1.4%) 0/4 (0%) 0/42 (0%) 0/44 (0%)
    Vascular disorders
    Aortic aneurysm 0/71 (0%) 1/4 (25%) 0/42 (0%) 0/44 (0%)
    Aortic dissection 1/71 (1.4%) 0/4 (0%) 0/42 (0%) 0/44 (0%)
    Aortic stenosis 0/71 (0%) 0/4 (0%) 1/42 (2.4%) 0/44 (0%)
    Arteriosclerosis 0/71 (0%) 0/4 (0%) 1/42 (2.4%) 0/44 (0%)
    Deep vein thrombosis 3/71 (4.2%) 0/4 (0%) 0/42 (0%) 1/44 (2.3%)
    Haematoma 1/71 (1.4%) 0/4 (0%) 0/42 (0%) 0/44 (0%)
    Hypotension 0/71 (0%) 1/4 (25%) 0/42 (0%) 1/44 (2.3%)
    Jugular vein thrombosis 0/71 (0%) 0/4 (0%) 0/42 (0%) 1/44 (2.3%)
    Shock haemorrhagic 1/71 (1.4%) 0/4 (0%) 0/42 (0%) 0/44 (0%)
    Other (Not Including Serious) Adverse Events
    IDL+R to IDL 150 mg IDL+R (PD) to IDL 300 mg Placebo+R (PD) to IDL 150 mg Placebo+R to IDL 150 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 70/71 (98.6%) 4/4 (100%) 41/42 (97.6%) 43/44 (97.7%)
    Blood and lymphatic system disorders
    Anaemia 8/71 (11.3%) 2/4 (50%) 5/42 (11.9%) 4/44 (9.1%)
    Neutropenia 14/71 (19.7%) 1/4 (25%) 9/42 (21.4%) 6/44 (13.6%)
    Thrombocytopenia 5/71 (7%) 2/4 (50%) 3/42 (7.1%) 4/44 (9.1%)
    Gastrointestinal disorders
    Abdominal distension 3/71 (4.2%) 1/4 (25%) 0/42 (0%) 1/44 (2.3%)
    Abdominal pain 8/71 (11.3%) 1/4 (25%) 5/42 (11.9%) 5/44 (11.4%)
    Colitis 1/71 (1.4%) 0/4 (0%) 4/42 (9.5%) 6/44 (13.6%)
    Constipation 11/71 (15.5%) 1/4 (25%) 7/42 (16.7%) 4/44 (9.1%)
    Diarrhoea 30/71 (42.3%) 2/4 (50%) 17/42 (40.5%) 26/44 (59.1%)
    Dry mouth 0/71 (0%) 0/4 (0%) 0/42 (0%) 3/44 (6.8%)
    Dyspepsia 4/71 (5.6%) 0/4 (0%) 2/42 (4.8%) 2/44 (4.5%)
    Dysphagia 0/71 (0%) 1/4 (25%) 1/42 (2.4%) 1/44 (2.3%)
    Flatulence 2/71 (2.8%) 0/4 (0%) 0/42 (0%) 4/44 (9.1%)
    Gastrooesophageal reflux disease 2/71 (2.8%) 1/4 (25%) 5/42 (11.9%) 2/44 (4.5%)
    Haemorrhoids 2/71 (2.8%) 0/4 (0%) 4/42 (9.5%) 6/44 (13.6%)
    Mouth ulceration 0/71 (0%) 1/4 (25%) 2/42 (4.8%) 0/44 (0%)
    Nausea 11/71 (15.5%) 0/4 (0%) 12/42 (28.6%) 12/44 (27.3%)
    Oesophageal ulcer 0/71 (0%) 1/4 (25%) 0/42 (0%) 0/44 (0%)
    Stomatitis 1/71 (1.4%) 0/4 (0%) 0/42 (0%) 3/44 (6.8%)
    Vomiting 7/71 (9.9%) 0/4 (0%) 7/42 (16.7%) 9/44 (20.5%)
    General disorders
    Asthenia 5/71 (7%) 0/4 (0%) 7/42 (16.7%) 2/44 (4.5%)
    Chills 7/71 (9.9%) 0/4 (0%) 6/42 (14.3%) 4/44 (9.1%)
    Fatigue 15/71 (21.1%) 2/4 (50%) 13/42 (31%) 9/44 (20.5%)
    Malaise 2/71 (2.8%) 0/4 (0%) 2/42 (4.8%) 3/44 (6.8%)
    Mucosal inflammation 1/71 (1.4%) 0/4 (0%) 1/42 (2.4%) 3/44 (6.8%)
    Oedema 0/71 (0%) 0/4 (0%) 0/42 (0%) 3/44 (6.8%)
    Oedema peripheral 12/71 (16.9%) 0/4 (0%) 7/42 (16.7%) 8/44 (18.2%)
    Pain 3/71 (4.2%) 0/4 (0%) 3/42 (7.1%) 5/44 (11.4%)
    Peripheral swelling 1/71 (1.4%) 0/4 (0%) 1/42 (2.4%) 3/44 (6.8%)
    Pyrexia 17/71 (23.9%) 0/4 (0%) 12/42 (28.6%) 16/44 (36.4%)
    Immune system disorders
    Hypogammaglobulinaemia 3/71 (4.2%) 0/4 (0%) 2/42 (4.8%) 4/44 (9.1%)
    Infections and infestations
    Bronchitis 4/71 (5.6%) 1/4 (25%) 2/42 (4.8%) 6/44 (13.6%)
    Cellulitis 4/71 (5.6%) 0/4 (0%) 0/42 (0%) 2/44 (4.5%)
    Ear infection 4/71 (5.6%) 0/4 (0%) 1/42 (2.4%) 0/44 (0%)
    Herpes zoster 2/71 (2.8%) 0/4 (0%) 2/42 (4.8%) 3/44 (6.8%)
    Lower respiratory tract infection 3/71 (4.2%) 0/4 (0%) 1/42 (2.4%) 4/44 (9.1%)
    Nasopharyngitis 1/71 (1.4%) 0/4 (0%) 1/42 (2.4%) 5/44 (11.4%)
    Oral candidiasis 2/71 (2.8%) 0/4 (0%) 0/42 (0%) 3/44 (6.8%)
    Pharyngitis 1/71 (1.4%) 0/4 (0%) 1/42 (2.4%) 4/44 (9.1%)
    Pneumonia 4/71 (5.6%) 0/4 (0%) 9/42 (21.4%) 6/44 (13.6%)
    Sinusitis 14/71 (19.7%) 1/4 (25%) 1/42 (2.4%) 4/44 (9.1%)
    Upper respiratory tract infection 10/71 (14.1%) 0/4 (0%) 8/42 (19%) 11/44 (25%)
    Urinary tract infection 7/71 (9.9%) 0/4 (0%) 3/42 (7.1%) 1/44 (2.3%)
    Injury, poisoning and procedural complications
    Contusion 1/71 (1.4%) 0/4 (0%) 3/42 (7.1%) 1/44 (2.3%)
    Fall 3/71 (4.2%) 0/4 (0%) 0/42 (0%) 3/44 (6.8%)
    Humerus fracture 1/71 (1.4%) 1/4 (25%) 0/42 (0%) 0/44 (0%)
    Joint injury 1/71 (1.4%) 1/4 (25%) 0/42 (0%) 0/44 (0%)
    Laceration 3/71 (4.2%) 1/4 (25%) 0/42 (0%) 1/44 (2.3%)
    Post procedural haemorrhage 0/71 (0%) 1/4 (25%) 0/42 (0%) 0/44 (0%)
    Investigations
    Alanine aminotransferase increased 1/71 (1.4%) 0/4 (0%) 1/42 (2.4%) 3/44 (6.8%)
    Aspartate aminotransferase increased 1/71 (1.4%) 0/4 (0%) 1/42 (2.4%) 3/44 (6.8%)
    Computerised tomogram thorax abnormal 1/71 (1.4%) 1/4 (25%) 0/42 (0%) 1/44 (2.3%)
    Weight decreased 5/71 (7%) 1/4 (25%) 4/42 (9.5%) 5/44 (11.4%)
    Metabolism and nutrition disorders
    Decreased appetite 9/71 (12.7%) 1/4 (25%) 1/42 (2.4%) 6/44 (13.6%)
    Dehydration 6/71 (8.5%) 0/4 (0%) 1/42 (2.4%) 0/44 (0%)
    Gout 0/71 (0%) 0/4 (0%) 4/42 (9.5%) 0/44 (0%)
    Hypokalaemia 8/71 (11.3%) 0/4 (0%) 3/42 (7.1%) 7/44 (15.9%)
    Hypomagnesaemia 4/71 (5.6%) 0/4 (0%) 3/42 (7.1%) 2/44 (4.5%)
    Hyponatraemia 0/71 (0%) 0/4 (0%) 3/42 (7.1%) 3/44 (6.8%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 6/71 (8.5%) 0/4 (0%) 0/42 (0%) 3/44 (6.8%)
    Back pain 6/71 (8.5%) 1/4 (25%) 5/42 (11.9%) 7/44 (15.9%)
    Myalgia 2/71 (2.8%) 0/4 (0%) 2/42 (4.8%) 3/44 (6.8%)
    Pain in extremity 8/71 (11.3%) 0/4 (0%) 2/42 (4.8%) 3/44 (6.8%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Squamous cell carcinoma 5/71 (7%) 0/4 (0%) 0/42 (0%) 1/44 (2.3%)
    Nervous system disorders
    Dizziness 2/71 (2.8%) 0/4 (0%) 5/42 (11.9%) 5/44 (11.4%)
    Headache 6/71 (8.5%) 0/4 (0%) 3/42 (7.1%) 6/44 (13.6%)
    Lethargy 6/71 (8.5%) 0/4 (0%) 3/42 (7.1%) 1/44 (2.3%)
    Product Issues
    Device occlusion 0/71 (0%) 1/4 (25%) 0/42 (0%) 0/44 (0%)
    Psychiatric disorders
    Anxiety 2/71 (2.8%) 0/4 (0%) 3/42 (7.1%) 2/44 (4.5%)
    Depression 3/71 (4.2%) 0/4 (0%) 0/42 (0%) 3/44 (6.8%)
    Insomnia 6/71 (8.5%) 0/4 (0%) 3/42 (7.1%) 2/44 (4.5%)
    Renal and urinary disorders
    Acute kidney injury 6/71 (8.5%) 0/4 (0%) 1/42 (2.4%) 1/44 (2.3%)
    Dysuria 0/71 (0%) 0/4 (0%) 0/42 (0%) 3/44 (6.8%)
    Haematuria 5/71 (7%) 1/4 (25%) 1/42 (2.4%) 0/44 (0%)
    Reproductive system and breast disorders
    Benign prostatic hyperplasia 4/71 (5.6%) 0/4 (0%) 0/42 (0%) 0/44 (0%)
    Vaginal haemorrhage 0/71 (0%) 1/4 (25%) 0/42 (0%) 1/44 (2.3%)
    Respiratory, thoracic and mediastinal disorders
    Cough 21/71 (29.6%) 0/4 (0%) 12/42 (28.6%) 16/44 (36.4%)
    Dyspnoea 7/71 (9.9%) 0/4 (0%) 4/42 (9.5%) 10/44 (22.7%)
    Dyspnoea exertional 5/71 (7%) 0/4 (0%) 1/42 (2.4%) 1/44 (2.3%)
    Epistaxis 2/71 (2.8%) 1/4 (25%) 3/42 (7.1%) 4/44 (9.1%)
    Hypoxia 1/71 (1.4%) 1/4 (25%) 0/42 (0%) 1/44 (2.3%)
    Lung infiltration 5/71 (7%) 0/4 (0%) 3/42 (7.1%) 0/44 (0%)
    Nasal congestion 5/71 (7%) 0/4 (0%) 1/42 (2.4%) 0/44 (0%)
    Nasal ulcer 0/71 (0%) 1/4 (25%) 0/42 (0%) 0/44 (0%)
    Oropharyngeal pain 4/71 (5.6%) 0/4 (0%) 1/42 (2.4%) 2/44 (4.5%)
    Pleural effusion 2/71 (2.8%) 0/4 (0%) 4/42 (9.5%) 2/44 (4.5%)
    Pneumonitis 3/71 (4.2%) 0/4 (0%) 1/42 (2.4%) 3/44 (6.8%)
    Productive cough 7/71 (9.9%) 0/4 (0%) 0/42 (0%) 7/44 (15.9%)
    Pulmonary congestion 0/71 (0%) 0/4 (0%) 3/42 (7.1%) 0/44 (0%)
    Sinus congestion 2/71 (2.8%) 0/4 (0%) 4/42 (9.5%) 0/44 (0%)
    Skin and subcutaneous tissue disorders
    Dermatitis acneiform 0/71 (0%) 1/4 (25%) 0/42 (0%) 0/44 (0%)
    Dry skin 2/71 (2.8%) 0/4 (0%) 0/42 (0%) 3/44 (6.8%)
    Erythema 2/71 (2.8%) 0/4 (0%) 0/42 (0%) 3/44 (6.8%)
    Night sweats 6/71 (8.5%) 1/4 (25%) 10/42 (23.8%) 2/44 (4.5%)
    Pruritus 0/71 (0%) 0/4 (0%) 3/42 (7.1%) 3/44 (6.8%)
    Rash 5/71 (7%) 0/4 (0%) 4/42 (9.5%) 7/44 (15.9%)
    Rash macular 0/71 (0%) 0/4 (0%) 0/42 (0%) 3/44 (6.8%)
    Rash maculo-papular 5/71 (7%) 0/4 (0%) 2/42 (4.8%) 2/44 (4.5%)
    Skin lesion 3/71 (4.2%) 0/4 (0%) 2/42 (4.8%) 3/44 (6.8%)
    Vascular disorders
    Hypertension 4/71 (5.6%) 0/4 (0%) 0/42 (0%) 2/44 (4.5%)
    Hypotension 4/71 (5.6%) 0/4 (0%) 2/42 (4.8%) 4/44 (9.1%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or The study has been completed at all study sites for at least 2 years

    Results Point of Contact

    Name/Title Gilead Clinical Study Information Center
    Organization Gilead Sciences
    Phone 1-833-445-3230 (GILEAD-0)
    Email GileadClinicalTrials@gilead.com
    Responsible Party:
    Gilead Sciences
    ClinicalTrials.gov Identifier:
    NCT01539291
    Other Study ID Numbers:
    • GS-US-312-0117
    • 2011-006293-72
    First Posted:
    Feb 27, 2012
    Last Update Posted:
    Aug 20, 2019
    Last Verified:
    Aug 1, 2019