Chronic Lymphocytic Leukemia
Conditions
Keywords
CLL, CAL-101, CAL 101, GS-1101, GS 1101, PI3K, Leukemia, GS-US-312-0116, idelalisib
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.
Interventions
DRUGIdelalisib
Idelalisib tablet(s) administered orally twice daily
Sponsors
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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). |
| 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). |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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) | — |
| 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. |
| 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. |
| Plasma Trough (Predose) and Peak (1.5 Hours Postdose) Concentrations of Idelalisib | Weeks 4, 12, and 24 | — |
| 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. |
| 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. |
| 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. |
Countries
France, Germany, Italy, United Kingdom, United States
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 details
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.
Participants by arm
| Arm | Count |
|---|---|
| IDL+R to IDL 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. | 110 |
| Placebo+R (PD) to IDL 150 mg 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. | 42 |
| Placebo+R to IDL 150 mg 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. | 44 |
| Total | 196 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Study GS-US-312-0116 | Adverse Event | 9 | 0 | 0 | 0 |
| Study GS-US-312-0116 | Other | 1 | 0 | 0 | 0 |
| Study GS-US-312-0116 | Physician Decision | 1 | 0 | 0 | 0 |
| Study GS-US-312-0116 | Study Terminated by Sponsor | 2 | 0 | 0 | 0 |
| Study GS-US-312-0116 | Withdrawal by Subject | 12 | 0 | 0 | 0 |
| Study GS-US-312-0117 | Adverse Event | 22 | 1 | 9 | 12 |
| Study GS-US-312-0117 | Other | 2 | 1 | 1 | 1 |
| Study GS-US-312-0117 | Physician Decision | 9 | 0 | 6 | 4 |
| Study GS-US-312-0117 | Study Terminated by Sponsor | 3 | 0 | 0 | 5 |
| Study GS-US-312-0117 | Withdrawal by Subject | 5 | 0 | 6 | 4 |
Baseline characteristics
| Characteristic | Total | IDL+R to IDL | Placebo+R (PD) to IDL 150 mg | Placebo+R to IDL 150 mg |
|---|---|---|---|---|
| 17p Deletion and/or TP53 Mutation Status Either | 81 Participants | 46 Participants | 21 Participants | 14 Participants |
| 17p Deletion and/or TP53 Mutation Status Neither | 115 Participants | 64 Participants | 21 Participants | 30 Participants |
| Age, Customized < 65 years | 44 Participants | 21 Participants | 13 Participants | 10 Participants |
| Age, Customized ≥ 65 years | 152 Participants | 89 Participants | 29 Participants | 34 Participants |
| Immunoglobulin heavy chain variable region (IgHV) Mutation Status Mutated | 32 Participants | 19 Participants | 6 Participants | 7 Participants |
| Immunoglobulin heavy chain variable region (IgHV) Mutation Status Unmutated | 164 Participants | 91 Participants | 36 Participants | 37 Participants |
| Karnofsky Performance Status (KPS) KPS = 100 | 27 Participants | 15 Participants | 4 Participants | 8 Participants |
| Karnofsky Performance Status (KPS) KPS = 40 | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Karnofsky Performance Status (KPS) KPS = 50 | 4 Participants | 3 Participants | 1 Participants | 0 Participants |
| Karnofsky Performance Status (KPS) KPS = 60 | 8 Participants | 6 Participants | 2 Participants | 0 Participants |
| Karnofsky Performance Status (KPS) KPS = 70 | 28 Participants | 20 Participants | 4 Participants | 4 Participants |
| Karnofsky Performance Status (KPS) KPS = 80 | 81 Participants | 42 Participants | 19 Participants | 20 Participants |
| Karnofsky Performance Status (KPS) KPS = 90 | 47 Participants | 23 Participants | 12 Participants | 12 Participants |
| Race/Ethnicity, Customized Ethnicity Hispanic or Latino | 5 Participants | 3 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Ethnicity Not Hispanic or Latino | 182 Participants | 101 Participants | 39 Participants | 42 Participants |
| Race/Ethnicity, Customized Ethnicity Not Permitted | 9 Participants | 6 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized Race American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Black or African American | 6 Participants | 3 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized Race Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Not Permitted | 9 Participants | 5 Participants | 3 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Other | 4 Participants | 2 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized Race White | 177 Participants | 100 Participants | 37 Participants | 40 Participants |
| Region of Enrollment France | 4 Participants | 3 Participants | 0 Participants | 1 Participants |
| Region of Enrollment Germany | 10 Participants | 7 Participants | 0 Participants | 3 Participants |
| Region of Enrollment Italy | 7 Participants | 2 Participants | 1 Participants | 4 Participants |
| Region of Enrollment United Kingdom | 27 Participants | 18 Participants | 3 Participants | 6 Participants |
| Region of Enrollment United States | 148 Participants | 80 Participants | 38 Participants | 30 Participants |
| Sex: Female, Male Female | 63 Participants | 34 Participants | 11 Participants | 18 Participants |
| Sex: Female, Male Male | 133 Participants | 76 Participants | 31 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 37 / 71 | 3 / 4 | 25 / 42 | 16 / 44 |
| other Total, other adverse events | 70 / 71 | 4 / 4 | 41 / 42 | 43 / 44 |
| serious Total, serious adverse events | 54 / 71 | 2 / 4 | 34 / 42 | 32 / 44 |
Outcome results
Primary
Progression-Free Survival (PFS)
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)
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| IDL+R to IDL | Progression-Free Survival (PFS) | 20.3 months |
| Placebo+R (PD) to IDL 150 mg | Progression-Free Survival (PFS) | 6.9 months |
| Placebo+R to IDL 150 mg | Progression-Free Survival (PFS) | 16.2 months |
Primary
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
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
Population: Participants in the Full Analysis Set were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| IDL+R to IDL | 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 | ≥ Grade 3 TEAE | 90.9 percentage of participants |
| IDL+R to IDL | 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 | Serious TEAE | 80.9 percentage of participants |
| IDL+R to IDL | 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 | ≥ Grade 3 Study Drug-Related TEAE | 47.3 percentage of participants |
| IDL+R to IDL | 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 | Any TEAE | 98.2 percentage of participants |
| IDL+R to IDL | 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 | TEAE Leading to Study Drug Discontinuation | 47.3 percentage of participants |
| IDL+R to IDL | 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 | Study Drug-Related Serious TEAE | 35.5 percentage of participants |
| IDL+R to IDL | 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 | Study Drug-Related TEAE | 68.2 percentage of participants |
| Placebo+R (PD) to IDL 150 mg | 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 | ≥ Grade 3 Study Drug-Related TEAE | 45.2 percentage of participants |
| Placebo+R (PD) to IDL 150 mg | 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 | Any TEAE | 100.0 percentage of participants |
| Placebo+R (PD) to IDL 150 mg | 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 | ≥ Grade 3 TEAE | 88.1 percentage of participants |
| Placebo+R (PD) to IDL 150 mg | 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 | Study Drug-Related TEAE | 59.5 percentage of participants |
| Placebo+R (PD) to IDL 150 mg | 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 | Serious TEAE | 81.0 percentage of participants |
| Placebo+R (PD) to IDL 150 mg | 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 | Study Drug-Related Serious TEAE | 26.2 percentage of participants |
| Placebo+R (PD) to IDL 150 mg | 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 | TEAE Leading to Study Drug Discontinuation | 64.3 percentage of participants |
| Placebo+R to IDL 150 mg | 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 | Serious TEAE | 72.7 percentage of participants |
| Placebo+R to IDL 150 mg | 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 | ≥ Grade 3 TEAE | 90.9 percentage of participants |
| Placebo+R to IDL 150 mg | 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 | TEAE Leading to Study Drug Discontinuation | 50.0 percentage of participants |
| Placebo+R to IDL 150 mg | 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 | Study Drug-Related Serious TEAE | 29.5 percentage of participants |
| Placebo+R to IDL 150 mg | 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 | ≥ Grade 3 Study Drug-Related TEAE | 45.5 percentage of participants |
| Placebo+R to IDL 150 mg | 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 | Study Drug-Related TEAE | 72.7 percentage of participants |
| Placebo+R to IDL 150 mg | 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 | Any TEAE | 97.7 percentage of participants |
Secondary
Absolute Lymphocyte Count (ALC) Response Rate
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)
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| IDL+R to IDL | Absolute Lymphocyte Count (ALC) Response Rate | 94.3 percentage of participants |
| Placebo+R (PD) to IDL 150 mg | Absolute Lymphocyte Count (ALC) Response Rate | 66.7 percentage of participants |
| Placebo+R to IDL 150 mg | Absolute Lymphocyte Count (ALC) Response Rate | 64.7 percentage of participants |
Secondary
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
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
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| IDL+R to IDL | 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 | Total Score: Baseline | 128.4 units on a scale | Standard Deviation 22.72 |
| IDL+R to IDL | 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 | PWB: Baseline | 22.8 units on a scale | Standard Deviation 4.42 |
| IDL+R to IDL | 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 | SWB: Baseline | 22.5 units on a scale | Standard Deviation 5.53 |
| IDL+R to IDL | 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 | EWB: Baseline | 19.1 units on a scale | Standard Deviation 3.44 |
| IDL+R to IDL | 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 | FWB: Baseline | 18.0 units on a scale | Standard Deviation 6.57 |
| IDL+R to IDL | 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 | LeuS: Baseline | 46.0 units on a scale | Standard Deviation 10.64 |
| IDL+R to IDL | 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 | Total Score: Best Change from Baseline | 21.8 units on a scale | Standard Deviation 19.64 |
| IDL+R to IDL | 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 | PWB: Best Change from Baseline | 3.1 units on a scale | Standard Deviation 4.65 |
| IDL+R to IDL | 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 | SWB: Best Change from Baseline | 2.9 units on a scale | Standard Deviation 5.21 |
| IDL+R to IDL | 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 | EWB: Best Change from Baseline | 3.1 units on a scale | Standard Deviation 2.75 |
| IDL+R to IDL | 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 | FWB: Best Change from Baseline | 5.1 units on a scale | Standard Deviation 5.8 |
| IDL+R to IDL | 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 | LeuS: Best Change from Baseline | 11.3 units on a scale | Standard Deviation 9.13 |
| Placebo+R (PD) to IDL 150 mg | 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 | LeuS: Best Change from Baseline | 10.1 units on a scale | Standard Deviation 8.78 |
| Placebo+R (PD) to IDL 150 mg | 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 | Total Score: Baseline | 116.7 units on a scale | Standard Deviation 29.56 |
| Placebo+R (PD) to IDL 150 mg | 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 | Total Score: Best Change from Baseline | 20.2 units on a scale | Standard Deviation 19.91 |
| Placebo+R (PD) to IDL 150 mg | 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 | SWB: Best Change from Baseline | 2.0 units on a scale | Standard Deviation 2.88 |
| Placebo+R (PD) to IDL 150 mg | 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 | PWB: Baseline | 20.2 units on a scale | Standard Deviation 5.93 |
| Placebo+R (PD) to IDL 150 mg | 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 | LeuS: Baseline | 41.7 units on a scale | Standard Deviation 12.74 |
| Placebo+R (PD) to IDL 150 mg | 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 | FWB: Best Change from Baseline | 4.1 units on a scale | Standard Deviation 5.01 |
| Placebo+R (PD) to IDL 150 mg | 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 | SWB: Baseline | 22.5 units on a scale | Standard Deviation 5.06 |
| Placebo+R (PD) to IDL 150 mg | 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 | PWB: Best Change from Baseline | 3.6 units on a scale | Standard Deviation 4.26 |
| Placebo+R (PD) to IDL 150 mg | 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 | FWB: Baseline | 15.0 units on a scale | Standard Deviation 7.17 |
| Placebo+R (PD) to IDL 150 mg | 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 | EWB: Baseline | 17.3 units on a scale | Standard Deviation 4.97 |
| Placebo+R (PD) to IDL 150 mg | 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 | EWB: Best Change from Baseline | 3.1 units on a scale | Standard Deviation 3.68 |
| Placebo+R to IDL 150 mg | 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 | EWB: Baseline | 17.6 units on a scale | Standard Deviation 4.48 |
| Placebo+R to IDL 150 mg | 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 | FWB: Baseline | 18.0 units on a scale | Standard Deviation 6.88 |
| Placebo+R to IDL 150 mg | 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 | EWB: Best Change from Baseline | 2.8 units on a scale | Standard Deviation 3.14 |
| Placebo+R to IDL 150 mg | 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 | LeuS: Baseline | 47.0 units on a scale | Standard Deviation 12.01 |
| Placebo+R to IDL 150 mg | 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 | Total Score: Best Change from Baseline | 14.9 units on a scale | Standard Deviation 12.04 |
| Placebo+R to IDL 150 mg | 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 | PWB: Best Change from Baseline | 3.4 units on a scale | Standard Deviation 3.81 |
| Placebo+R to IDL 150 mg | 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 | FWB: Best Change from Baseline | 3.1 units on a scale | Standard Deviation 2.94 |
| Placebo+R to IDL 150 mg | 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 | Total Score: Baseline | 128.1 units on a scale | Standard Deviation 29.16 |
| Placebo+R to IDL 150 mg | 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 | PWB: Baseline | 21.9 units on a scale | Standard Deviation 5.41 |
| Placebo+R to IDL 150 mg | 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 | SWB: Best Change from Baseline | 2.1 units on a scale | Standard Deviation 2.39 |
| Placebo+R to IDL 150 mg | 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 | SWB: Baseline | 23.5 units on a scale | Standard Deviation 5.04 |
| Placebo+R to IDL 150 mg | 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 | LeuS: Best Change from Baseline | 7.8 units on a scale | Standard Deviation 5.59 |
Secondary
Best Change From Baseline in Karnofsky Performance Status (KPS)
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
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| IDL+R to IDL | Best Change From Baseline in Karnofsky Performance Status (KPS) | Baseline | 80.7 units on a scale | Standard Deviation 12.47 |
| IDL+R to IDL | Best Change From Baseline in Karnofsky Performance Status (KPS) | Best Change From Baseline | 11.1 units on a scale | Standard Deviation 10.31 |
| Placebo+R (PD) to IDL 150 mg | Best Change From Baseline in Karnofsky Performance Status (KPS) | Baseline | 78.1 units on a scale | Standard Deviation 14.18 |
| Placebo+R (PD) to IDL 150 mg | Best Change From Baseline in Karnofsky Performance Status (KPS) | Best Change From Baseline | 7.1 units on a scale | Standard Deviation 8.67 |
| Placebo+R to IDL 150 mg | Best Change From Baseline in Karnofsky Performance Status (KPS) | Baseline | 86.8 units on a scale | Standard Deviation 8.83 |
| Placebo+R to IDL 150 mg | Best Change From Baseline in Karnofsky Performance Status (KPS) | Best Change From Baseline | 4.3 units on a scale | Standard Deviation 6.98 |
Secondary
Best Percent Change in Lymph Node Area
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)
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| IDL+R to IDL | Best Percent Change in Lymph Node Area | -80.1 percent change |
| Placebo+R (PD) to IDL 150 mg | Best Percent Change in Lymph Node Area | -69.7 percent change |
| Placebo+R to IDL 150 mg | Best Percent Change in Lymph Node Area | -71.4 percent change |
Secondary
Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure
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
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| IDL+R to IDL | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 24: Anxiety/Depression, Level 1 | 83.1 percentage of participants |
| IDL+R to IDL | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Baseline: Anxiety/Depression, Level 3 | 0.9 percentage of participants |
| IDL+R to IDL | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 48: Anxiety/Depression, Level 1 | 84.1 percentage of participants |
| IDL+R to IDL | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 24: Anxiety/Depression, Level 2 | 15.6 percentage of participants |
| IDL+R to IDL | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Baseline: Anxiety/Depression, Level 1 | 70.4 percentage of participants |
| IDL+R to IDL | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 24: Usual Activities, Level 3 | 2.6 percentage of participants |
| IDL+R to IDL | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 24: Anxiety/Depression, Level 3 | 1.3 percentage of participants |
| IDL+R to IDL | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Baseline: Pain/Discomfort, Level 1 | 53.3 percentage of participants |
| IDL+R to IDL | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 24: Usual Activities, Level 2 | 28.9 percentage of participants |
| IDL+R to IDL | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 24: Mobility, Level 1 | 70.1 percentage of participants |
| IDL+R to IDL | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Baseline: Anxiety/Depression, Level 2 | 28.7 percentage of participants |
| IDL+R to IDL | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 24: Usual Activities, Level 1 | 68.4 percentage of participants |
| IDL+R to IDL | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 24: Mobility, Level 2 | 29.9 percentage of participants |
| IDL+R to IDL | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 48: Self-Care, Level 1 | 95.5 percentage of participants |
| IDL+R to IDL | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 24: Self-Care, Level 3 | 1.3 percentage of participants |
| IDL+R to IDL | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 24: Mobility, Level 3 | 0.0 percentage of participants |
| IDL+R to IDL | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Baseline: Pain/Discomfort, Level 2 | 39.3 percentage of participants |
| IDL+R to IDL | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 24: Self-Care, Level 2 | 6.5 percentage of participants |
| IDL+R to IDL | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 24: Pain/Discomfort, Level 1 | 62.3 percentage of participants |
| IDL+R to IDL | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 48: Usual Activities, Level 1 | 72.7 percentage of participants |
| IDL+R to IDL | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 24: Self-Care, Level 1 | 92.2 percentage of participants |
| IDL+R to IDL | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 24: Pain/Discomfort, Level 2 | 35.1 percentage of participants |
| IDL+R to IDL | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 48: Pain/Discomfort, Level 3 | 0.0 percentage of participants |
| IDL+R to IDL | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 24: Pain/Discomfort, Level 3 | 2.6 percentage of participants |
| IDL+R to IDL | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Baseline: Pain/Discomfort, Level 3 | 7.5 percentage of participants |
| IDL+R to IDL | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Baseline: Mobility, Level 1 | 60.2 percentage of participants |
| IDL+R to IDL | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 48: Pain/Discomfort, Level 2 | 43.2 percentage of participants |
| IDL+R to IDL | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Baseline: Self-Care, Level 1 | 90.7 percentage of participants |
| IDL+R to IDL | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 48: Usual Activities, Level 3 | 2.3 percentage of participants |
| IDL+R to IDL | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 48: Pain/Discomfort, Level 1 | 56.8 percentage of participants |
| IDL+R to IDL | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Baseline: Self-Care, Level 2 | 9.3 percentage of participants |
| IDL+R to IDL | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 48: Self-Care, Level 3 | 0.0 percentage of participants |
| IDL+R to IDL | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 48: Mobility, Level 3 | 0.0 percentage of participants |
| IDL+R to IDL | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Baseline: Self-Care, Level 3 | 0.0 percentage of participants |
| IDL+R to IDL | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Baseline: Mobility, Level 2 | 39.8 percentage of participants |
| IDL+R to IDL | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 48: Mobility, Level 2 | 27.3 percentage of participants |
| IDL+R to IDL | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Baseline: Usual Activities, Level 1 | 56.5 percentage of participants |
| IDL+R to IDL | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 48: Usual Activities, Level 2 | 25.0 percentage of participants |
| IDL+R to IDL | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 48: Mobility, Level 1 | 72.7 percentage of participants |
| IDL+R to IDL | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Baseline: Usual Activities, Level 2 | 36.1 percentage of participants |
| IDL+R to IDL | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 48: Self-Care, Level 2 | 4.5 percentage of participants |
| IDL+R to IDL | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 48: Anxiety/Depression, Level 3 | 0.0 percentage of participants |
| IDL+R to IDL | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Baseline: Usual Activities, Level 3 | 7.4 percentage of participants |
| IDL+R to IDL | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Baseline: Mobility, Level 3 | 0.0 percentage of participants |
| IDL+R to IDL | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 48: Anxiety/Depression, Level 2 | 15.9 percentage of participants |
| Placebo+R (PD) to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 48: Self-Care, Level 1 | 90.0 percentage of participants |
| Placebo+R (PD) to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Baseline: Anxiety/Depression, Level 1 | 50.0 percentage of participants |
| Placebo+R (PD) to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Baseline: Anxiety/Depression, Level 2 | 42.9 percentage of participants |
| Placebo+R (PD) to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Baseline: Anxiety/Depression, Level 3 | 7.1 percentage of participants |
| Placebo+R (PD) to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Baseline: Mobility, Level 1 | 38.1 percentage of participants |
| Placebo+R (PD) to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Baseline: Mobility, Level 2 | 59.5 percentage of participants |
| Placebo+R (PD) to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Baseline: Mobility, Level 3 | 2.4 percentage of participants |
| Placebo+R (PD) to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Baseline: Pain/Discomfort, Level 1 | 50.0 percentage of participants |
| Placebo+R (PD) to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Baseline: Pain/Discomfort, Level 2 | 45.2 percentage of participants |
| Placebo+R (PD) to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Baseline: Pain/Discomfort, Level 3 | 4.8 percentage of participants |
| Placebo+R (PD) to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Baseline: Self-Care, Level 1 | 76.2 percentage of participants |
| Placebo+R (PD) to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Baseline: Self-Care, Level 2 | 19.0 percentage of participants |
| Placebo+R (PD) to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Baseline: Self-Care, Level 3 | 4.8 percentage of participants |
| Placebo+R (PD) to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Baseline: Usual Activities, Level 1 | 28.6 percentage of participants |
| Placebo+R (PD) to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Baseline: Usual Activities, Level 2 | 52.4 percentage of participants |
| Placebo+R (PD) to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Baseline: Usual Activities, Level 3 | 19.0 percentage of participants |
| Placebo+R (PD) to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 24: Anxiety/Depression, Level 1 | 65.0 percentage of participants |
| Placebo+R (PD) to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 24: Anxiety/Depression, Level 2 | 35.0 percentage of participants |
| Placebo+R (PD) to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 24: Anxiety/Depression, Level 3 | 0.0 percentage of participants |
| Placebo+R (PD) to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 24: Mobility, Level 1 | 65.0 percentage of participants |
| Placebo+R (PD) to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 24: Mobility, Level 2 | 35.0 percentage of participants |
| Placebo+R (PD) to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 24: Mobility, Level 3 | 0.0 percentage of participants |
| Placebo+R (PD) to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 24: Pain/Discomfort, Level 1 | 65.0 percentage of participants |
| Placebo+R (PD) to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 24: Pain/Discomfort, Level 2 | 30.0 percentage of participants |
| Placebo+R (PD) to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 24: Pain/Discomfort, Level 3 | 5.0 percentage of participants |
| Placebo+R (PD) to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 24: Self-Care, Level 1 | 85.0 percentage of participants |
| Placebo+R (PD) to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 24: Self-Care, Level 2 | 15.0 percentage of participants |
| Placebo+R (PD) to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 24: Self-Care, Level 3 | 0.0 percentage of participants |
| Placebo+R (PD) to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 24: Usual Activities, Level 1 | 75.0 percentage of participants |
| Placebo+R (PD) to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 24: Usual Activities, Level 2 | 25.0 percentage of participants |
| Placebo+R (PD) to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 24: Usual Activities, Level 3 | 0.0 percentage of participants |
| Placebo+R (PD) to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 48: Anxiety/Depression, Level 1 | 90.0 percentage of participants |
| Placebo+R (PD) to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 48: Anxiety/Depression, Level 2 | 10.0 percentage of participants |
| Placebo+R (PD) to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 48: Anxiety/Depression, Level 3 | 0.0 percentage of participants |
| Placebo+R (PD) to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 48: Mobility, Level 1 | 60.0 percentage of participants |
| Placebo+R (PD) to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 48: Mobility, Level 2 | 40.0 percentage of participants |
| Placebo+R (PD) to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 48: Mobility, Level 3 | 0.0 percentage of participants |
| Placebo+R (PD) to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 48: Pain/Discomfort, Level 1 | 60.0 percentage of participants |
| Placebo+R (PD) to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 48: Pain/Discomfort, Level 2 | 30.0 percentage of participants |
| Placebo+R (PD) to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 48: Pain/Discomfort, Level 3 | 10.0 percentage of participants |
| Placebo+R (PD) to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 48: Self-Care, Level 2 | 0.0 percentage of participants |
| Placebo+R (PD) to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 48: Self-Care, Level 3 | 10.0 percentage of participants |
| Placebo+R (PD) to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 48: Usual Activities, Level 1 | 70.0 percentage of participants |
| Placebo+R (PD) to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 48: Usual Activities, Level 2 | 20.0 percentage of participants |
| Placebo+R (PD) to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 48: Usual Activities, Level 3 | 10.0 percentage of participants |
| Placebo+R to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 24: Anxiety/Depression, Level 1 | 69.6 percentage of participants |
| Placebo+R to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 48: Usual Activities, Level 3 | 16.7 percentage of participants |
| Placebo+R to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 48: Anxiety/Depression, Level 1 | 50.0 percentage of participants |
| Placebo+R to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Baseline: Usual Activities, Level 3 | 2.3 percentage of participants |
| Placebo+R to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 48: Self-Care, Level 2 | 16.7 percentage of participants |
| Placebo+R to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 48: Anxiety/Depression, Level 2 | 50.0 percentage of participants |
| Placebo+R to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Baseline: Usual Activities, Level 2 | 45.5 percentage of participants |
| Placebo+R to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Baseline: Mobility, Level 1 | 61.4 percentage of participants |
| Placebo+R to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 48: Anxiety/Depression, Level 3 | 0.0 percentage of participants |
| Placebo+R to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Baseline: Usual Activities, Level 1 | 52.3 percentage of participants |
| Placebo+R to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 48: Usual Activities, Level 2 | 33.3 percentage of participants |
| Placebo+R to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 48: Mobility, Level 1 | 66.7 percentage of participants |
| Placebo+R to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Baseline: Self-Care, Level 3 | 0.0 percentage of participants |
| Placebo+R to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 48: Self-Care, Level 3 | 0.0 percentage of participants |
| Placebo+R to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 48: Mobility, Level 2 | 33.3 percentage of participants |
| Placebo+R to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Baseline: Self-Care, Level 2 | 15.9 percentage of participants |
| Placebo+R to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Baseline: Anxiety/Depression, Level 3 | 0.0 percentage of participants |
| Placebo+R to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 48: Mobility, Level 3 | 0.0 percentage of participants |
| Placebo+R to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Baseline: Self-Care, Level 1 | 84.1 percentage of participants |
| Placebo+R to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Baseline: Anxiety/Depression, Level 1 | 56.8 percentage of participants |
| Placebo+R to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 48: Pain/Discomfort, Level 1 | 50.0 percentage of participants |
| Placebo+R to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Baseline: Pain/Discomfort, Level 3 | 4.5 percentage of participants |
| Placebo+R to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 48: Usual Activities, Level 1 | 50.0 percentage of participants |
| Placebo+R to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 48: Pain/Discomfort, Level 2 | 50.0 percentage of participants |
| Placebo+R to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 24: Pain/Discomfort, Level 2 | 47.8 percentage of participants |
| Placebo+R to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Baseline: Pain/Discomfort, Level 2 | 50.0 percentage of participants |
| Placebo+R to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 24: Pain/Discomfort, Level 3 | 8.7 percentage of participants |
| Placebo+R to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 24: Pain/Discomfort, Level 1 | 43.5 percentage of participants |
| Placebo+R to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Baseline: Anxiety/Depression, Level 2 | 43.2 percentage of participants |
| Placebo+R to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 24: Self-Care, Level 1 | 91.3 percentage of participants |
| Placebo+R to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 24: Mobility, Level 3 | 0.0 percentage of participants |
| Placebo+R to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 48: Pain/Discomfort, Level 3 | 0.0 percentage of participants |
| Placebo+R to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 24: Self-Care, Level 2 | 8.7 percentage of participants |
| Placebo+R to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 24: Mobility, Level 2 | 30.4 percentage of participants |
| Placebo+R to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Baseline: Pain/Discomfort, Level 1 | 45.5 percentage of participants |
| Placebo+R to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 24: Self-Care, Level 3 | 0.0 percentage of participants |
| Placebo+R to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 24: Mobility, Level 1 | 69.6 percentage of participants |
| Placebo+R to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Baseline: Mobility, Level 3 | 0.0 percentage of participants |
| Placebo+R to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 24: Usual Activities, Level 1 | 60.9 percentage of participants |
| Placebo+R to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 24: Anxiety/Depression, Level 3 | 0.0 percentage of participants |
| Placebo+R to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 48: Self-Care, Level 1 | 83.3 percentage of participants |
| Placebo+R to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 24: Usual Activities, Level 2 | 34.8 percentage of participants |
| Placebo+R to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 24: Anxiety/Depression, Level 2 | 30.4 percentage of participants |
| Placebo+R to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Baseline: Mobility, Level 2 | 38.6 percentage of participants |
| Placebo+R to IDL 150 mg | Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure | Week 24: Usual Activities, Level 3 | 4.3 percentage of participants |
Secondary
Changes From Baseline in Phosphatidylinositol 3-kinase (PI3Kδ)/Akt/Mammalian Target of Rapamycin (mTOR) Pathway Activation as a Measure of PI3Kδ Pathway Activity
Time frame: GS-US-312-0116 Baseline to end of study GS-US-312-0117 (maximum: up to 67.6 months)
Population: Data were not collected because there was insufficient volume of sample (not enough material) to perform the analysis for any participant.
Secondary
Complete Response (CR) Rate
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)
Population: Participants in the Full Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IDL+R to IDL | Complete Response (CR) Rate | 0.9 percentage of participants |
| Placebo+R (PD) to IDL 150 mg | Complete Response (CR) Rate | 0.0 percentage of participants |
| Placebo+R to IDL 150 mg | Complete Response (CR) Rate | 0.0 percentage of participants |
Secondary
Duration of Response (DOR)
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)
Population: Participants in the Full Analysis Set who achieved a CR or PR were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| IDL+R to IDL | Duration of Response (DOR) | 21.4 months |
| Placebo+R (PD) to IDL 150 mg | Duration of Response (DOR) | 11.0 months |
| Placebo+R to IDL 150 mg | Duration of Response (DOR) | 17.6 months |
Secondary
Hemoglobin Response Rate
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)
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| IDL+R to IDL | Hemoglobin Response Rate | 83.1 percentage of participants |
| Placebo+R (PD) to IDL 150 mg | Hemoglobin Response Rate | 45.8 percentage of participants |
| Placebo+R to IDL 150 mg | Hemoglobin Response Rate | 81.8 percentage of participants |
Secondary
Hepatomegaly Response Rate
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)
Population: Participants in the Full Analysis Set who had hepatomegaly at baseline and at least 1 evaluable postbaseline liver measurement were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IDL+R to IDL | Hepatomegaly Response Rate | 63.0 percentage of participants |
| Placebo+R (PD) to IDL 150 mg | Hepatomegaly Response Rate | 36.4 percentage of participants |
| Placebo+R to IDL 150 mg | Hepatomegaly Response Rate | 30.0 percentage of participants |
Secondary
Lymph Node Response Rate
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)
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IDL+R to IDL | Lymph Node Response Rate | 97.2 percentage of participants |
| Placebo+R (PD) to IDL 150 mg | Lymph Node Response Rate | 77.8 percentage of participants |
| Placebo+R to IDL 150 mg | Lymph Node Response Rate | 83.7 percentage of participants |
Secondary
Neutrophil Response Rate
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)
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| IDL+R to IDL | Neutrophil Response Rate | 96.3 percentage of participants |
| Placebo+R (PD) to IDL 150 mg | Neutrophil Response Rate | 90.9 percentage of participants |
| Placebo+R to IDL 150 mg | Neutrophil Response Rate | 100.0 percentage of participants |
Secondary
Overall Change From Baseline in the Plasma Concentrations of Disease-Associated Chemokines and Cytokines
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)
Population: 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 | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| IDL+R to IDL | Overall Change From Baseline in the Plasma Concentrations of Disease-Associated Chemokines and Cytokines | Tumor Necrosis Factor (TNF)-alpha | 36.73 percentage of baseline |
| IDL+R to IDL | Overall Change From Baseline in the Plasma Concentrations of Disease-Associated Chemokines and Cytokines | Macrophage Inflammatory Protein (MIP)1-alpha | 26.55 percentage of baseline |
| IDL+R to IDL | Overall Change From Baseline in the Plasma Concentrations of Disease-Associated Chemokines and Cytokines | Interleukin (IL)-10 | 58.65 percentage of baseline |
| IDL+R to IDL | Overall Change From Baseline in the Plasma Concentrations of Disease-Associated Chemokines and Cytokines | IL-15 | 111.18 percentage of baseline |
| IDL+R to IDL | Overall Change From Baseline in the Plasma Concentrations of Disease-Associated Chemokines and Cytokines | IL-12p40 | 64.89 percentage of baseline |
| IDL+R to IDL | Overall Change From Baseline in the Plasma Concentrations of Disease-Associated Chemokines and Cytokines | RANTES (CCL5) | 131.94 percentage of baseline |
| IDL+R to IDL | Overall Change From Baseline in the Plasma Concentrations of Disease-Associated Chemokines and Cytokines | IL-1ra | 114.22 percentage of baseline |
| IDL+R to IDL | Overall Change From Baseline in the Plasma Concentrations of Disease-Associated Chemokines and Cytokines | Interferon (IFN)-gamma | 127.72 percentage of baseline |
| IDL+R to IDL | Overall Change From Baseline in the Plasma Concentrations of Disease-Associated Chemokines and Cytokines | C-Reactive Protein (CRP) | 132.38 percentage of baseline |
| IDL+R to IDL | Overall Change From Baseline in the Plasma Concentrations of Disease-Associated Chemokines and Cytokines | IFN-gamma-induced protein (IP)-10 (CXCL10) | 88.5 percentage of baseline |
| IDL+R to IDL | Overall Change From Baseline in the Plasma Concentrations of Disease-Associated Chemokines and Cytokines | IL-7 | 91.82 percentage of baseline |
| IDL+R to IDL | Overall Change From Baseline in the Plasma Concentrations of Disease-Associated Chemokines and Cytokines | Granulocyte-colony stimulating factor (G-CSF) | 96.59 percentage of baseline |
| IDL+R to IDL | Overall Change From Baseline in the Plasma Concentrations of Disease-Associated Chemokines and Cytokines | IL-17A | 100 percentage of baseline |
| IDL+R to IDL | Overall Change From Baseline in the Plasma Concentrations of Disease-Associated Chemokines and Cytokines | IL-6 | 100 percentage of baseline |
| IDL+R to IDL | Overall Change From Baseline in the Plasma Concentrations of Disease-Associated Chemokines and Cytokines | IL-8 | 102.59 percentage of baseline |
Secondary
Overall Response Rate (ORR)
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)
Population: Participants in the Full Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IDL+R to IDL | Overall Response Rate (ORR) | 85.5 percentage of participants |
| Placebo+R (PD) to IDL 150 mg | Overall Response Rate (ORR) | 47.6 percentage of participants |
| Placebo+R to IDL 150 mg | Overall Response Rate (ORR) | 68.2 percentage of participants |
Secondary
Overall Survival
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)
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| IDL+R to IDL | Overall Survival | 40.6 months |
| Placebo+R (PD) to IDL 150 mg | Overall Survival | 34.6 months |
Secondary
Plasma Trough (Predose) and Peak (1.5 Hours Postdose) Concentrations of Idelalisib
Time frame: Weeks 4, 12, and 24
Population: 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 | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| IDL+R to IDL | Plasma Trough (Predose) and Peak (1.5 Hours Postdose) Concentrations of Idelalisib | Week 4: Predose | 384.0 ng/mL |
| IDL+R to IDL | Plasma Trough (Predose) and Peak (1.5 Hours Postdose) Concentrations of Idelalisib | Week 4: 1.5 Hours Postdose | 2115.0 ng/mL |
| IDL+R to IDL | Plasma Trough (Predose) and Peak (1.5 Hours Postdose) Concentrations of Idelalisib | Week 12: Predose | 370.0 ng/mL |
| IDL+R to IDL | Plasma Trough (Predose) and Peak (1.5 Hours Postdose) Concentrations of Idelalisib | Week 12: 1.5 Hours Postdose | 2110.0 ng/mL |
| IDL+R to IDL | Plasma Trough (Predose) and Peak (1.5 Hours Postdose) Concentrations of Idelalisib | Week 24: Predose | 307.0 ng/mL |
| IDL+R to IDL | Plasma Trough (Predose) and Peak (1.5 Hours Postdose) Concentrations of Idelalisib | Week 24: 1.5 Hours Postdose | 2270.0 ng/mL |
| Placebo+R (PD) to IDL 150 mg | Plasma Trough (Predose) and Peak (1.5 Hours Postdose) Concentrations of Idelalisib | Week 24: 1.5 Hours Postdose | 5630.0 ng/mL |
| Placebo+R (PD) to IDL 150 mg | Plasma Trough (Predose) and Peak (1.5 Hours Postdose) Concentrations of Idelalisib | Week 12: 1.5 Hours Postdose | 3800.0 ng/mL |
| Placebo+R (PD) to IDL 150 mg | Plasma Trough (Predose) and Peak (1.5 Hours Postdose) Concentrations of Idelalisib | Week 4: Predose | 470.0 ng/mL |
| Placebo+R (PD) to IDL 150 mg | Plasma Trough (Predose) and Peak (1.5 Hours Postdose) Concentrations of Idelalisib | Week 12: Predose | 570.0 ng/mL |
| Placebo+R (PD) to IDL 150 mg | Plasma Trough (Predose) and Peak (1.5 Hours Postdose) Concentrations of Idelalisib | Week 4: 1.5 Hours Postdose | 3940.0 ng/mL |
| Placebo+R (PD) to IDL 150 mg | Plasma Trough (Predose) and Peak (1.5 Hours Postdose) Concentrations of Idelalisib | Week 24: Predose | 637.0 ng/mL |
| Placebo+R to IDL 150 mg | Plasma Trough (Predose) and Peak (1.5 Hours Postdose) Concentrations of Idelalisib | Week 4: 1.5 Hours Postdose | 2580.0 ng/mL |
| Placebo+R to IDL 150 mg | Plasma Trough (Predose) and Peak (1.5 Hours Postdose) Concentrations of Idelalisib | Week 12: Predose | 335.0 ng/mL |
| Placebo+R to IDL 150 mg | Plasma Trough (Predose) and Peak (1.5 Hours Postdose) Concentrations of Idelalisib | Week 12: 1.5 Hours Postdose | 2245.0 ng/mL |
| Placebo+R to IDL 150 mg | Plasma Trough (Predose) and Peak (1.5 Hours Postdose) Concentrations of Idelalisib | Week 24: 1.5 Hours Postdose | 2180.0 ng/mL |
| Placebo+R to IDL 150 mg | Plasma Trough (Predose) and Peak (1.5 Hours Postdose) Concentrations of Idelalisib | Week 24: Predose | 362.0 ng/mL |
| Placebo+R to IDL 150 mg | Plasma Trough (Predose) and Peak (1.5 Hours Postdose) Concentrations of Idelalisib | Week 4: Predose | 301.5 ng/mL |
| Placebo+R to IDL 150 mg | Plasma Trough (Predose) and Peak (1.5 Hours Postdose) Concentrations of Idelalisib | Week 24: Predose | 350.5 ng/mL |
| Placebo+R to IDL 150 mg | Plasma Trough (Predose) and Peak (1.5 Hours Postdose) Concentrations of Idelalisib | Week 24: 1.5 Hours Postdose | 2010.0 ng/mL |
| Placebo+R to IDL 150 mg | Plasma Trough (Predose) and Peak (1.5 Hours Postdose) Concentrations of Idelalisib | Week 4: 1.5 Hours Postdose | 1720.0 ng/mL |
| Placebo+R to IDL 150 mg | Plasma Trough (Predose) and Peak (1.5 Hours Postdose) Concentrations of Idelalisib | Week 12: 1.5 Hours Postdose | 1940.0 ng/mL |
| Placebo+R to IDL 150 mg | Plasma Trough (Predose) and Peak (1.5 Hours Postdose) Concentrations of Idelalisib | Week 4: Predose | 412.0 ng/mL |
| Placebo+R to IDL 150 mg | Plasma Trough (Predose) and Peak (1.5 Hours Postdose) Concentrations of Idelalisib | Week 12: Predose | 298.0 ng/mL |
Secondary
Platelet Response Rate
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)
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| IDL+R to IDL | Platelet Response Rate | 98.0 percentage of participants |
| Placebo+R (PD) to IDL 150 mg | Platelet Response Rate | 73.9 percentage of participants |
| Placebo+R to IDL 150 mg | Platelet Response Rate | 100.0 percentage of participants |
Secondary
Splenomegaly Response Rate
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)
Population: Participants in the Full Analysis Set who had splenomegaly at baseline and at least 1 evaluable postbaseline spleen measurement were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IDL+R to IDL | Splenomegaly Response Rate | 80.3 percentage of participants |
| Placebo+R (PD) to IDL 150 mg | Splenomegaly Response Rate | 47.8 percentage of participants |
| Placebo+R to IDL 150 mg | Splenomegaly Response Rate | 66.7 percentage of participants |
Secondary
Study Drug Compliance as Assessed by the Percentage of Participants Adhering to Treatment
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)
Population: Participants in the Full Analysis Set were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| IDL+R to IDL | Study Drug Compliance as Assessed by the Percentage of Participants Adhering to Treatment | Adherence ≥ 75% | 100.0 percentage of participants |
| IDL+R to IDL | Study Drug Compliance as Assessed by the Percentage of Participants Adhering to Treatment | Adherence < 75% | 0.0 percentage of participants |
| Placebo+R (PD) to IDL 150 mg | Study Drug Compliance as Assessed by the Percentage of Participants Adhering to Treatment | Adherence ≥ 75% | 97.6 percentage of participants |
| Placebo+R (PD) to IDL 150 mg | Study Drug Compliance as Assessed by the Percentage of Participants Adhering to Treatment | Adherence < 75% | 2.4 percentage of participants |
| Placebo+R to IDL 150 mg | Study Drug Compliance as Assessed by the Percentage of Participants Adhering to Treatment | Adherence ≥ 75% | 100.0 percentage of participants |
| Placebo+R to IDL 150 mg | Study Drug Compliance as Assessed by the Percentage of Participants Adhering to Treatment | Adherence < 75% | 0.0 percentage of participants |
Secondary
Time to Response (TTR)
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)
Population: Participants in the Full Analysis Set who achieved a CR or PR were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| IDL+R to IDL | Time to Response (TTR) | 2.1 months |
| Placebo+R (PD) to IDL 150 mg | Time to Response (TTR) | 3.6 months |
| Placebo+R to IDL 150 mg | Time to Response (TTR) | 2.8 months |