A Phase 1/2, Open-Label, Dose Escalation, Safety and Tolerability Study of INCB050465 and Itacitinib in Subjects With Previously Treated B-Cell Malignancies (CITADEL-101)

• ClinicalTrials.gov Identifier: NCT02018861
• Recruitment Status: Completed
• First Posted: December 23, 2013
• Results First Posted: June 28, 2022
• Last Update Posted: June 28, 2022
• Sponsor: Incyte Corporation
• Information provided by (Responsible Party): Incyte Corporation

• Study Type: Interventional
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: B-Cell Malignancies
• Interventions: Drug: Parsaclisib; Drug: Itacitinib; Drug: Rituximab; Drug: Ifosfamide; Drug: Carboplatin; Drug: Etoposide
• Enrollment: 88

Participant Flow

Recruitment Details

This study was conducted at 13 study centers in the United States.

Pre-assignment Details

This was a 4-part study. Part 1 parsaclisib monotherapy dose escalation determined the recommended dose(s) (RDs) to explore. Part 2 evaluated the combination of parsaclisib and itacitinib to determine the RDs. Part 3 expansion further evaluated the RDs of parsaclisib as monotherapy and in combination with itacitinib in disease cohorts. Part 6 consisted of a safety assessment of parsaclisib in combination with the chemotherapy regimen R-ICE (rituximab, ifosfamide, carboplatin, and etoposide).

Arm/Group Title	Parsaclisib 5 mg QD	Parsaclisib 10 mg QD	Parsaclisib 15 mg QD	Parsaclisib 20 mg QD	Parsaclisib 30 mg QD	Parsaclisib 45 mg QD	Parsaclisib 20 mg + Itacitinib 300 mg	Parsaclisib 30 mg + Itacitinib 300 mg	Parsaclisib 15 mg QD + R-ICE	Parsaclisib 20 mg QD + R-ICE
Arm/Group Description	Participants self-administered parsaclisib 5 milligrams (mg) as an oral tablet once a day (QD) in 21-day treatment cycles.	Participants self-administered parsaclisib 10 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 15 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 20 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 30 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 45 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 20 mg as oral tablets QD and itacitinib 300 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 30 mg as oral tablets QD and itacitinib 300 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 15 mg as oral tablets QD in 21-day treatment cycles. R-ICE was a standard-of-care chemotherapy combination administered at the following doses: rituximab 375 milligrams per meters squared (mg/m^2) intravenously (IV) on Day 1 and Day 2 of Cycle 1 and on Day 1 of Cycles 2 and 3, ifosfamide 5000 mg/m^2 IV on Day 3 of each cycle, carboplatin area under the curve (AUC) = 5 (maximum dose 800 mg) IV on Day 3 of each cycle, and etoposide 100 mg/m^2 or at doses consistent with institutional practice with approval from the medical monitor on Days 3 and 5 of each cycle. Each cycle was 21 days in duration.	Participants self-administered parsaclisib 20 mg as oral tablets QD in 21-day treatment cycles. R-ICE was a standard-of-care chemotherapy combination administered at the following doses: rituximab 375 mg/m^2 IV on Day 1 and Day 2 of Cycle 1 and on Day 1 of Cycles 2 and 3, ifosfamide 5000 mg/m^2 IV on Day 3 of each cycle, carboplatin AUC = 5 (maximum dose 800 mg) IV on Day 3 of each cycle, and etoposide 100 mg/m^2 or at doses consistent with institutional practice with approval from the medical monitor on Days 3 and 5 of each cycle. Each cycle was 21 days in duration.
Period Title: Parsaclisib Monotherapy: 21-day Cycles
Started	1	3	3	34	27	4	0	0	0	0
Completed	0	0	0	4	0	0	0	0	0	0
Not Completed	1	3	3	30	27	4	0	0	0	0
Reason Not Completed
Adverse Event	0	2	1	6	4	1	0	0	0	0
Withdrawal by Subject	0	0	0	1	1	0	0	0	0	0
Disease Progression	0	1	1	13	18	1	0	0	0	0
Death	1	0	0	3	1	0	0	0	0	0
Lost to Follow-up	0	0	1	1	0	0	0	0	0	0
Non-compliance with Study Treatment	0	0	0	0	1	0	0	0	0	0
Physician Decision	0	0	0	4	1	2	0	0	0	0
Unknown or Not Reported	0	0	0	2	1	0	0	0	0	0
Period Title: Parsaclisib + Itacitinib; 21-day Cycles
Started	0	0	0	0	0	0	8	3	0	0
Completed	0	0	0	0	0	0	0	0	0	0
Not Completed	0	0	0	0	0	0	8	3	0	0
Reason Not Completed
Disease Progression	0	0	0	0	0	0	5	2	0	0
Unknown or Not Reported	0	0	0	0	0	0	3	1	0	0
Period Title: Parsaclisib + R-ICE; 21-day Cycles
Started	0	0	0	0	0	0	0	0	4	1
Completed	0	0	0	0	0	0	0	0	1	1
Not Completed	0	0	0	0	0	0	0	0	3	0
Reason Not Completed
Physician Decision	0	0	0	0	0	0	0	0	1	0
Disease Progression	0	0	0	0	0	0	0	0	1	0
Adverse Event	0	0	0	0	0	0	0	0	1	0

Baseline Characteristics

Arm/Group Title		Parsaclisib 5 mg QD	Parsaclisib 10 mg QD	Parsaclisib 15 mg QD	Parsaclisib 20 mg QD	Parsaclisib 30 mg QD	Parsaclisib 45 mg QD	Parsaclisib 20 mg + Itacitinib 300 mg	Parsaclisib 30 mg + Itacitinib 300 mg	Parsaclisib 15 mg QD + R-ICE	Parsaclisib 20 mg QD + R-ICE	Total
Arm/Group Description		Participants self-administered parsaclisib 5 milligrams (mg) as an oral tablet once a day (QD) in 21-day treatment cycles.	Participants self-administered parsaclisib 10 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 15 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 20 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 30 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 45 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 20 mg as oral tablets QD and itacitinib 300 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 30 mg as oral tablets QD and itacitinib 300 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 15 mg as oral tablets QD in 21-day treatment cycles. R-ICE was a standard-of-care chemotherapy combination administered at the following doses: rituximab 375 milligrams per meters squared (mg/m^2) intravenously (IV) on Day 1 and Day 2 of Cycle 1 and on Day 1 of Cycles 2 and 3, ifosfamide 5000 mg/m^2 IV on Day 3 of each cycle, carboplatin area under the curve (AUC) = 5 (maximum dose 800 mg) IV on Day 3 of each cycle, and etoposide 100 mg/m^2 or at doses consistent with institutional practice with approval from the medical monitor on Days 3 and 5 of each cycle. Each cycle was 21 days in duration.	Participants self-administered parsaclisib 20 mg as oral tablets QD in 21-day treatment cycles. R-ICE was a standard-of-care chemotherapy combination administered at the following doses: rituximab 375 mg/m^2 IV on Day 1 and Day 2 of Cycle 1 and on Day 1 of Cycles 2 and 3, ifosfamide 5000 mg/m^2 IV on Day 3 of each cycle, carboplatin AUC = 5 (maximum dose 800 mg) IV on Day 3 of each cycle, and etoposide 100 mg/m^2 or at doses consistent with institutional practice with approval from the medical monitor on Days 3 and 5 of each cycle. Each cycle was 21 days in duration.	Total of all reporting groups
Overall Number of Baseline Participants		1	3	3	34	27	4	8	3	4	1	88
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	1 participants	3 participants	3 participants	34 participants	27 participants	4 participants	8 participants	3 participants	4 participants	1 participants	88 participants
		NA [1] (NA)	69.0 (16.52)	63.3 (9.45)	62.4 (16.48)	63.7 (11.81)	66.8 (8.77)	64.6 (17.15)	51.7 (27.02)	62.3 (8.26)	NA [1] (NA)	63.3 (14.44)
		[1] Due to low participant enrollment in this arm, data are not being reported, as doing so may risk participant identification.
Sex/Gender, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	1 participants	3 participants	3 participants	34 participants	27 participants	4 participants	8 participants	3 participants	4 participants	1 participants	88 participants
Female		NA [1]	NA [1]	NA [1]	12	14	NA [1]	NA [1]	NA [1]	NA [1]	NA [1]	38
Male		NA [1]	NA [1]	NA [1]	22	13	NA [1]	NA [1]	NA [1]	NA [1]	NA [1]	50
		[1] Due to low participant enrollment in this arm, data are not being reported, as doing so may risk participant identification.
Race/Ethnicity, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	1 participants	3 participants	3 participants	34 participants	27 participants	4 participants	8 participants	3 participants	4 participants	1 participants	88 participants
Black or African American		NA [1]	NA [1]	NA [1]	4	4	NA [1]	NA [1]	NA [1]	NA [1]	NA [1]	9
White		NA [1]	NA [1]	NA [1]	25	21	NA [1]	NA [1]	NA [1]	NA [1]	NA [1]	70
Unknown or Not Reported		NA [1]	NA [1]	NA [1]	5	2	NA [1]	NA [1]	NA [1]	NA [1]	NA [1]	9
		[1] Due to low participant enrollment in this arm, data are not being reported, as doing so may risk participant identification.

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Description	An adverse event (AE) is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after a participant provides informed consent. Abnormal laboratory values or test results occurring after informed consent constitute AEs only if they induce clinical signs or symptoms, are considered clinically meaningful, require therapy (e.g., hematologic abnormality that requires transfusion), or require changes in the study drug(s). A TEAE is defined as an event that was reported for the first time, or the worsening of a pre-existing event, after the first dose of study drug.
Time Frame	Up to approximately 53 months (4.4 years)

Outcome Measure Data

Analysis Population Description

Safety Population: all participants enrolled in the study who received at least 1 dose of parsaclisib, itacitinib, rituximab, ifosfamide, carboplatin, and/or etoposide

Arm/Group Title	Parsaclisib 5 mg QD	Parsaclisib 10 mg QD	Parsaclisib 15 mg QD	Parsaclisib 20 mg QD	Parsaclisib 30 mg QD	Parsaclisib 45 mg QD	Parsaclisib 20 mg + Itacitinib 300 mg	Parsaclisib 30 mg + Itacitinib 300 mg	Parsaclisib 15 mg QD + R-ICE	Parsaclisib 20 mg QD + R-ICE
Arm/Group Description:	Participants self-administered parsaclisib 5 milligrams (mg) as an oral tablet once a day (QD) in 21-day treatment cycles.	Participants self-administered parsaclisib 10 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 15 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 20 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 30 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 45 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 20 mg as oral tablets QD and itacitinib 300 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 30 mg as oral tablets QD and itacitinib 300 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 15 mg as oral tablets QD in 21-day treatment cycles. R-ICE was a standard-of-care chemotherapy combination administered at the following doses: rituximab 375 milligrams per meters squared (mg/m^2) intravenously (IV) on Day 1 and Day 2 of Cycle 1 and on Day 1 of Cycles 2 and 3, ifosfamide 5000 mg/m^2 IV on Day 3 of each cycle, carboplatin area under the curve (AUC) = 5 (maximum dose 800 mg) IV on Day 3 of each cycle, and etoposide 100 mg/m^2 or at doses consistent with institutional practice with approval from the medical monitor on Days 3 and 5 of each cycle. Each cycle was 21 days in duration.	Participants self-administered parsaclisib 20 mg as oral tablets QD in 21-day treatment cycles. R-ICE was a standard-of-care chemotherapy combination administered at the following doses: rituximab 375 mg/m^2 IV on Day 1 and Day 2 of Cycle 1 and on Day 1 of Cycles 2 and 3, ifosfamide 5000 mg/m^2 IV on Day 3 of each cycle, carboplatin AUC = 5 (maximum dose 800 mg) IV on Day 3 of each cycle, and etoposide 100 mg/m^2 or at doses consistent with institutional practice with approval from the medical monitor on Days 3 and 5 of each cycle. Each cycle was 21 days in duration.
Overall Number of Participants Analyzed	1	3	3	34	27	4	8	3	4	1
Measure Type: Count of Participants; Unit of Measure: Participants
	1 100.0%	3 100.0%	3 100.0%	32 94.1%	25 92.6%	4 100.0%	6 75.0%	3 100.0%	4 100.0%	1 100.0%

2. Secondary Outcome

Title	Part 1: Overall Response Rate (Percentage of Participants With Complete Response [CR] and Partial Response [PR]) Based on International Workshop on Chronic Lymphocytic Leukemia (IWCLL) Criteria for Chronic Lymphocytic Leukemia (CLL) for CLL Participants
Description	CR: (a) peripheral blood lymphocytes <4 x 10^9/Liter (L); (b) no significant lymphadenopathy and lymph nodes <1.5 centimeters (cm) in longest diameter; (c) no splenomegaly/hepatomegaly; (d) no disease-related constitutional symptoms; (e) neutrophils ≥1.5 x 10^9/L; (f) platelets ≥100 x 10^9/L; (g) hemoglobin ≥11.0 grams/deciliter (g/dL) (without transfusion); (h) minimal residual disease assessment; (i) normocellular marrow, with no CLL cells/no B-lymphoid nodules. PR (improvement in ≥2 Group A parameters and ≥1 Group B parameter if previously abnormal. If only 1 parameter of both Groups A and B was abnormal before therapy, only 1 needs to improve): Group A: (a) decrease of ≥50% (from Baseline) in lymph nodes, liver/spleen size, and circulating lymphocyte count; (b) any constitutional symptoms. Group B: (a) platelets ≥100 x 10^9/L or increase ≥50% over Baseline; (b) hemoglobin ≥11 g/dL or increase ≥50% over Baseline; (c) presence of CLL cells or B-lymphoid nodules.
Time Frame	Up to approximately 53 months (4.4 years)

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Population: all participants with CLL enrolled in the study who received at least 1 dose of parsaclisib, itacitinib, rituximab, ifosfamide, carboplatin, and/or etoposide. Confidence intervals were calculated based on the exact method for binomial distributions.

Arm/Group Title	Parsaclisib 5 mg QD	Parsaclisib 10 mg QD	Parsaclisib 15 mg QD	Parsaclisib 20 mg QD	Parsaclisib 30 mg QD	Parsaclisib 45 mg QD
Arm/Group Description:	Participants self-administered parsaclisib 5 milligrams (mg) as an oral tablet once a day (QD) in 21-day treatment cycles.	Participants self-administered parsaclisib 10 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 15 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 20 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 30 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 45 mg as oral tablets QD in 21-day treatment cycles.
Overall Number of Participants Analyzed	0	1	0	1	3	1
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
		0.0; (0.0 to 97.5)		0.0; (0.0 to 97.5)	66.7; (9.4 to 99.2)	0.0; (0.0 to 97.5)

3. Secondary Outcome

Title	Part 2: Overall Response Rate (Percentage of Participants With CR and PR) Based on IWCLL Criteria for CLL for Participants With CLL
Description	CR: (a) peripheral blood lymphocytes <4 x 10^9/L; (b) no significant lymphadenopathy and lymph nodes <1.5 cm in longest diameter; (c) no splenomegaly/hepatomegaly; (d) no disease-related constitutional symptoms; (e) neutrophils ≥1.5 x 10^9/L; (f) platelets ≥100 x 10^9/L; (g) hemoglobin ≥11.0 g/dL (without transfusion); (h) minimal residual disease assessment; (i) normocellular marrow, with no CLL cells/no B-lymphoid nodules. PR (improvement in ≥2 Group A parameters and ≥1 Group B parameter if previously abnormal. If only 1 parameter of both Groups A and B was abnormal before therapy, only 1 needs to improve): Group A: (a) decrease of ≥50% (from Baseline) in lymph nodes, liver/spleen size, and circulating lymphocyte count; (b) any constitutional symptoms. Group B: (a) platelets ≥100 x 10^9/L or increase ≥50% over Baseline; (b) ≥11 g/dL or increase ≥50% over Baseline; (c) presence of CLL cells or B-lymphoid nodules.
Time Frame	Up to approximately 44 months (3.7 years)

Outcome Measure Data

Analysis Population Description

ITT Population: all participants with CLL. Confidence intervals were calculated based on the exact method for binomial distributions.

Arm/Group Title	Parsaclisib 20 mg + Itacitinib 300 mg	Parsaclisib 30 mg + Itacitinib 300 mg
Arm/Group Description:	Participants self-administered parsaclisib 20 mg as oral tablets QD and itacitinib 300 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 30 mg as oral tablets QD and itacitinib 300 mg as oral tablets QD in 21-day treatment cycles.
Overall Number of Participants Analyzed	1	0
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	100.0; (2.5 to 100.0)

4. Secondary Outcome

Title	Part 6: Overall Response Rate (Percentage of Participants With CR and PR) Based on IWCLL Criteria for CLL for Participants With CLL
Description	CR: (a) peripheral blood lymphocytes <4 x 10^9/L; (b) no significant lymphadenopathy and lymph nodes <1.5 cm in longest diameter; (c) no splenomegaly/hepatomegaly; (d) no disease-related constitutional symptoms; (e) neutrophils ≥1.5 x 10^9/L; (f) platelets ≥100 x 10^9/L; (g) hemoglobin ≥11.0 g/dL (without transfusion); (h) minimal residual disease assessment; (i) normocellular marrow, with no CLL cells/no B-lymphoid nodules. PR (improvement in ≥2 Group A parameters and ≥1 Group B parameter if previously abnormal. If only 1 parameter of both Groups A and B was abnormal before therapy, only 1 needs to improve): Group A: (a) decrease of ≥50% (from Baseline) in lymph nodes, liver/spleen size, and circulating lymphocyte count; (b) any constitutional symptoms. Group B: (a) platelets ≥100 x 10^9/L or increase ≥50% over Baseline; (b) ≥11 g/dL or increase ≥50% over Baseline; (c) presence of CLL cells or B-lymphoid nodules.
Time Frame	Up to approximately 4 months

Outcome Measure Data

Analysis Population Description

ITT Population: all participants with CLL

Arm/Group Title	Parsaclisib 15 mg QD + R-ICE	Parsaclisib 20 mg QD + R-ICE
Arm/Group Description:	Participants self-administered parsaclisib 15 mg as oral tablets QD in 21-day treatment cycles. R-ICE was a standard-of-care chemotherapy combination administered at the following doses: rituximab 375 milligrams per meters squared (mg/m^2) intravenously (IV) on Day 1 and Day 2 of Cycle 1 and on Day 1 of Cycles 2 and 3, ifosfamide 5000 mg/m^2 IV on Day 3 of each cycle, carboplatin area under the curve (AUC) = 5 (maximum dose 800 mg) IV on Day 3 of each cycle, and etoposide 100 mg/m^2 or at doses consistent with institutional practice with approval from the medical monitor on Days 3 and 5 of each cycle. Each cycle was 21 days in duration.	Participants self-administered parsaclisib 20 mg as oral tablets QD in 21-day treatment cycles. R-ICE was a standard-of-care chemotherapy combination administered at the following doses: rituximab 375 mg/m^2 IV on Day 1 and Day 2 of Cycle 1 and on Day 1 of Cycles 2 and 3, ifosfamide 5000 mg/m^2 IV on Day 3 of each cycle, carboplatin AUC = 5 (maximum dose 800 mg) IV on Day 3 of each cycle, and etoposide 100 mg/m^2 or at doses consistent with institutional practice with approval from the medical monitor on Days 3 and 5 of each cycle. Each cycle was 21 days in duration.
Overall Number of Participants Analyzed	0	0

No data displayed because Outcome Measure has zero total analyzed.

5. Secondary Outcome

Title	Part 1: ORR Based on the VIth International Workshop on Waldenström Macroglobulinemia (WM) Response Assessment for Participants With WM
Description	ORR: sum of participants achieving minor response (MR), PR, very good partial response (VGPR), and CR. CR: (a) no serum monoclonal IgM protein by immunofixation; (b) normal serum IgM level; (c) complete resolution of extramedullary disease, i.e., lymphadenopathy/splenomegaly if present at Baseline (BL); (d) morphologically normal bone marrow aspirate and trephine biopsy. VGPR: (a) detectable monoclonal IgM protein; (b) ≥90% reduction in serum IgM level from BL; (c) complete resolution of extramedullary disease, i.e., lymphadenopathy/splenomegaly if present at BL; (d) no new signs/symptoms of active disease. PR: (a) detectable monoclonal IgM protein; (b) ≥50% but <90% reduction in serum IgM level from BL; (c) reduction in extramedullary disease, i.e., lymphadenopathy/splenomegaly if present at BL; (d) no new signs/symptoms of active disease. MR: (a) detectable monoclonal IgM protein; (b) ≥25% but <50% reduction in serum IgM level from BL; (d) no new signs/symptoms of active disease.
Time Frame	Up to approximately 53 months (4.4 years)

Outcome Measure Data

Analysis Population Description

ITT Population: all participants with WM. Confidence intervals were calculated based on the exact method for binomial distributions.

Arm/Group Title	Parsaclisib 5 mg QD	Parsaclisib 10 mg QD	Parsaclisib 15 mg QD	Parsaclisib 20 mg QD	Parsaclisib 30 mg QD	Parsaclisib 45 mg QD
Arm/Group Description:	Participants self-administered parsaclisib 5 milligrams (mg) as an oral tablet once a day (QD) in 21-day treatment cycles.	Participants self-administered parsaclisib 10 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 15 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 20 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 30 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 45 mg as oral tablets QD in 21-day treatment cycles.
Overall Number of Participants Analyzed	0	0	0	1	0	0
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
				100.0; (2.5 to 100.0)

6. Secondary Outcome

Title	Part 2: ORR Based on the VIth International Workshop on WM Response Assessment for Participants With WM
Description	ORR: sum of participants achieving MR, PR, VGPR, and CR. CR: (a) no serum monoclonal IgM protein by immunofixation; (b) normal serum IgM level; (c) complete resolution of extramedullary disease, i.e., lymphadenopathy/splenomegaly if present at BL; (d) morphologically normal bone marrow aspirate and trephine biopsy. VGPR: (a) detectable monoclonal IgM protein; (b) ≥90% reduction in serum IgM level from BL; (c) complete resolution of extramedullary disease, i.e., lymphadenopathy/splenomegaly if present at BL; (d) no new signs/symptoms of active disease. PR: (a) detectable monoclonal IgM protein; (b) ≥50% but <90% reduction in serum IgM level from BL; (c) reduction in extramedullary disease, i.e., lymphadenopathy/splenomegaly if present at BL; (d) no new signs/symptoms of active disease. MR: (a) detectable monoclonal IgM protein; (b) ≥25% but <50% reduction in serum IgM level from BL; (d) no new signs/symptoms of active disease.
Time Frame	Up to approximately 44 months (3.7 years)

Outcome Measure Data

Analysis Population Description

ITT Population: all participants with WM. Confidence intervals were calculated based on the exact method for binomial distributions.

Arm/Group Title	Parsaclisib 20 mg + Itacitinib 300 mg	Parsaclisib 30 mg + Itacitinib 300 mg
Arm/Group Description:	Participants self-administered parsaclisib 20 mg as oral tablets QD and itacitinib 300 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 30 mg as oral tablets QD and itacitinib 300 mg as oral tablets QD in 21-day treatment cycles.
Overall Number of Participants Analyzed	0	0

No data displayed because Outcome Measure has zero total analyzed.

7. Secondary Outcome

Title	Part 6: ORR Based on the VIth International Workshop on WM Response Assessment for Participants With WM
Description	ORR: sum of participants achieving MR, PR, VGPR, and CR. CR: (a) no serum monoclonal IgM protein by immunofixation; (b) normal serum IgM level; (c) complete resolution of extramedullary disease, i.e., lymphadenopathy/splenomegaly if present at BL; (d) morphologically normal bone marrow aspirate and trephine biopsy. VGPR: (a) detectable monoclonal IgM protein; (b) ≥90% reduction in serum IgM level from BL; (c) complete resolution of extramedullary disease, i.e., lymphadenopathy/splenomegaly if present at BL; (d) no new signs/symptoms of active disease. PR: (a) detectable monoclonal IgM protein; (b) ≥50% but <90% reduction in serum IgM level from BL; (c) reduction in extramedullary disease, i.e., lymphadenopathy/splenomegaly if present at BL; (d) no new signs/symptoms of active disease. MR: (a) detectable monoclonal IgM protein; (b) ≥25% but <50% reduction in serum IgM level from BL; (d) no new signs/symptoms of active disease.
Time Frame	Up to approximately 4 months

Outcome Measure Data

Analysis Population Description

ITT Population: all participants with WM

Arm/Group Title	Parsaclisib 15 mg QD + R-ICE	Parsaclisib 20 mg QD + R-ICE
Arm/Group Description:	Participants self-administered parsaclisib 15 mg as oral tablets QD in 21-day treatment cycles. R-ICE was a standard-of-care chemotherapy combination administered at the following doses: rituximab 375 milligrams per meters squared (mg/m^2) intravenously (IV) on Day 1 and Day 2 of Cycle 1 and on Day 1 of Cycles 2 and 3, ifosfamide 5000 mg/m^2 IV on Day 3 of each cycle, carboplatin area under the curve (AUC) = 5 (maximum dose 800 mg) IV on Day 3 of each cycle, and etoposide 100 mg/m^2 or at doses consistent with institutional practice with approval from the medical monitor on Days 3 and 5 of each cycle. Each cycle was 21 days in duration.	Participants self-administered parsaclisib 20 mg as oral tablets QD in 21-day treatment cycles. R-ICE was a standard-of-care chemotherapy combination administered at the following doses: rituximab 375 mg/m^2 IV on Day 1 and Day 2 of Cycle 1 and on Day 1 of Cycles 2 and 3, ifosfamide 5000 mg/m^2 IV on Day 3 of each cycle, carboplatin AUC = 5 (maximum dose 800 mg) IV on Day 3 of each cycle, and etoposide 100 mg/m^2 or at doses consistent with institutional practice with approval from the medical monitor on Days 3 and 5 of each cycle. Each cycle was 21 days in duration.
Overall Number of Participants Analyzed	0	0

No data displayed because Outcome Measure has zero total analyzed.

8. Secondary Outcome

Title	Part 1: ORR (Sum of Participants With CR and PR) Based on the Revised Response Criteria for Hodgkin's Lymphoma (HL) and Non-Hodgkin's Lymphoma (NHL), Using Positron Emission Tomography-computed Tomography (PET-CT) and CT
Description	CR, PET-CT: (a) complete metabolic response (MR); (b) lymph nodes and extralymphatic sites (LNs/ELSs): score 1, 2, or 3, with/without residual mass; (c) no new lesions (NNLs); (d) no evidence of fluorodeoxyglucose-avid disease in marrow. CT: complete radiologic response: (a) regression of target nodes/nodal masses to ≤ 1.5 cm in longest transverse lesion diameter; (b) no ELSs of disease; (c) absence of nonmeasured lesions; (d) regression to normal organ size; (e) NNLs; (f) normal morphological bone marrow. PR, PET-CT: (a) partial MR; (b) LNs/ELSs: score 4 or 5, with reduced uptake compared with Baseline and residual mass of any size; (c) NNLs; (d) residual uptake higher than uptake in normal marrow but reduced compared with Baseline. CT: partial remission: (a) LNs/ELSs: ≥ 50% decrease in the sum of the product of the perpendicular diameters for multiple lesions of up to 6 target measurable sites; (b) spleen must have regressed by > 50% in length beyond normal; (c) NNLs.
Time Frame	Up to approximately 53 months (4.4 years)

Outcome Measure Data

Analysis Population Description

ITT Population: all participants with the indicated types of HL and NHL. Confidence intervals were calculated based on the exact method for binomial distributions.

Arm/Group Title		Parsaclisib 5 mg QD	Parsaclisib 10 mg QD	Parsaclisib 15 mg QD	Parsaclisib 20 mg QD	Parsaclisib 30 mg QD	Parsaclisib 45 mg QD
Arm/Group Description:		Participants self-administered parsaclisib 5 milligrams (mg) as an oral tablet once a day (QD) in 21-day treatment cycles.	Participants self-administered parsaclisib 10 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 15 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 20 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 30 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 45 mg as oral tablets QD in 21-day treatment cycles.
Overall Number of Participants Analyzed		1	2	3	32	24	3
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
Diffuse large B-cell lymphoma	Number Analyzed	1 participants	1 participants	2 participants	11 participants	6 participants	2 participants
		0.0; (0.0 to 97.5)	0.0; (0.0 to 97.5)	50.0; (1.3 to 98.7)	36.4; (10.9 to 69.2)	16.7; (0.4 to 64.1)	50.0; (1.3 to 98.7)
Follicular lymphoma	Number Analyzed	0 participants	1 participants	1 participants	7 participants	5 participants	0 participants
			100.0; (2.5 to 100.0)	100.0; (2.5 to 100.0)	85.7; (42.1 to 99.6)	40.0; (5.3 to 85.3)
Mantle cell lymphoma	Number Analyzed	0 participants	0 participants	0 participants	6 participants	2 participants	1 participants
					66.7; (22.3 to 95.7)	100.0; (15.8 to 100.0)	0.0; (0.0 to 97.5)
Marginal zone lymphoma	Number Analyzed	0 participants	0 participants	0 participants	0 participants	1 participants	0 participants
						0.0; (0.0 to 97.5)
Extranodal marginal zone lymphoma of mucosa-associated lymphatic tissue	Number Analyzed	0 participants	0 participants	0 participants	2 participants	0 participants	0 participants
					50.0; (1.3 to 98.7)
Nodal marginal zone B-cell lymphoma	Number Analyzed	0 participants	0 participants	0 participants	1 participants	3 participants	0 participants
					100.0; (2.5 to 100.0)	100.0; (29.2 to 100.0)
Splenic marginal zone lymphoma	Number Analyzed	0 participants	0 participants	0 participants	1 participants	1 participants	0 participants
					100.0; (2.5 to 100.0)	100.0; (2.5 to 100.0)
Classical Hodgkin's lymphoma	Number Analyzed	0 participants	0 participants	0 participants	4 participants	5 participants	0 participants
					50.0; (6.8 to 93.2)	0.0; (0.0 to 52.2)
Nodular lymphocytic-predominant Hodgkin's lymphoma	Number Analyzed	0 participants	0 participants	0 participants	0 participants	1 participants	0 participants
						0.0; (0.0 to 97.5)

9. Secondary Outcome

Title	Part 2: ORR (Sum of Participants With CR and PR) Based on the Revised Response Criteria for HL and NHL, Using PET-CT and CT
Description	CR, PET-CT: (a) complete MR; (b) LNs/ELSs: score 1, 2, or 3, with/without residual mass; (c) NNLs; (d) no evidence of fluorodeoxyglucose-avid disease in marrow. CT: complete radiologic response: (a) regression of target nodes/nodal masses to ≤ 1.5 cm in longest transverse lesion diameter; (b) no ELSs of disease; (c) absence of nonmeasured lesions; (d) regression to normal organ size; (e) NNLs; (f) normal morphological bone marrow. PR, PET-CT: (a) partial MR; (b) LNs/ELSs: score 4 or 5, with reduced uptake compared with Baseline and residual mass of any size; (c) NNLs; (d) residual uptake higher than uptake in normal marrow but reduced compared with Baseline. CT: partial remission: (a) LNs/ELSs: ≥ 50% decrease in the sum of the product of the perpendicular diameters for multiple lesions of up to 6 target measurable sites; (b) spleen must have regressed by > 50% in length beyond normal; (c) NNLs.
Time Frame	Up to approximately 44 months (3.7 years)

Outcome Measure Data

Analysis Population Description

ITT Population: all participants with the indicated types of HL and NHL. Confidence intervals were calculated based on the exact method for binomial distributions.

Arm/Group Title		Parsaclisib 20 mg + Itacitinib 300 mg	Parsaclisib 30 mg + Itacitinib 300 mg
Arm/Group Description:		Participants self-administered parsaclisib 20 mg as oral tablets QD and itacitinib 300 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 30 mg as oral tablets QD and itacitinib 300 mg as oral tablets QD in 21-day treatment cycles.
Overall Number of Participants Analyzed		7	3
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
Diffuse large B-cell lymphoma	Number Analyzed	3 participants	3 participants
		0.0; (0.0 to 70.8)	0.0; (0.0 to 70.8)
Follicular lymphoma	Number Analyzed	1 participants	0 participants
		0.0; (0.0 to 97.5)
Mantle cell lymphoma	Number Analyzed	1 participants	0 participants
		100.0; (2.5 to 100.0)
Marginal zone lymphoma	Number Analyzed	0 participants	0 participants
Extranodal marginal zone lymphoma of mucosa-associated lymphatic tissue	Number Analyzed	0 participants	0 participants
Nodal marginal zone B-cell lymphoma	Number Analyzed	0 participants	0 participants
Splenic marginal zone lymphoma	Number Analyzed	0 participants	0 participants
Classical Hodgkin's lymphoma	Number Analyzed	2 participants	0 participants
		50.0; (1.3 to 98.7)
Nodular lymphocytic-predominant Hodgkin's lymphoma	Number Analyzed	0 participants	0 participants

10. Secondary Outcome

Title	Part 6: ORR (Sum of Participants With CR and PR) Based on the Revised Response Criteria for HL and NHL, Using PET-CT and CT
Description	CR, PET-CT: (a) complete MR; (b) LNs/ELSs: score 1, 2, or 3, with/without residual mass; (c) NNLs; (d) no evidence of fluorodeoxyglucose-avid disease in marrow. CT: complete radiologic response: (a) regression of target nodes/nodal masses to ≤ 1.5 cm in longest transverse lesion diameter; (b) no ELSs of disease; (c) absence of nonmeasured lesions; (d) regression to normal organ size; (e) NNLs; (f) normal morphological bone marrow. PR, PET-CT: (a) partial MR; (b) LNs/ELSs: score 4 or 5, with reduced uptake compared with Baseline and residual mass of any size; (c) NNLs; (d) residual uptake higher than uptake in normal marrow but reduced compared with Baseline. CT: partial remission: (a) LNs/ELSs: ≥ 50% decrease in the sum of the product of the perpendicular diameters for multiple lesions of up to 6 target measurable sites; (b) spleen must have regressed by > 50% in length beyond normal; (c) NNLs.
Time Frame	Up to approximately 4 months

Outcome Measure Data

Analysis Population Description

ITT Population: all participants with the indicated types of HL and NHL

Arm/Group Title		Parsaclisib 15 mg QD + R-ICE	Parsaclisib 20 mg QD + R-ICE
Arm/Group Description:		Participants self-administered parsaclisib 15 mg as oral tablets QD in 21-day treatment cycles. R-ICE was a standard-of-care chemotherapy combination administered at the following doses: rituximab 375 milligrams per meters squared (mg/m^2) intravenously (IV) on Day 1 and Day 2 of Cycle 1 and on Day 1 of Cycles 2 and 3, ifosfamide 5000 mg/m^2 IV on Day 3 of each cycle, carboplatin area under the curve (AUC) = 5 (maximum dose 800 mg) IV on Day 3 of each cycle, and etoposide 100 mg/m^2 or at doses consistent with institutional practice with approval from the medical monitor on Days 3 and 5 of each cycle. Each cycle was 21 days in duration.	Participants self-administered parsaclisib 20 mg as oral tablets QD in 21-day treatment cycles. R-ICE was a standard-of-care chemotherapy combination administered at the following doses: rituximab 375 mg/m^2 IV on Day 1 and Day 2 of Cycle 1 and on Day 1 of Cycles 2 and 3, ifosfamide 5000 mg/m^2 IV on Day 3 of each cycle, carboplatin AUC = 5 (maximum dose 800 mg) IV on Day 3 of each cycle, and etoposide 100 mg/m^2 or at doses consistent with institutional practice with approval from the medical monitor on Days 3 and 5 of each cycle. Each cycle was 21 days in duration.
Overall Number of Participants Analyzed		4	1
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
Diffuse large B-cell lymphoma	Number Analyzed	4 participants	1 participants
		50.0 [1]; (NA to NA)	100.0 [1]; (NA to NA)
Follicular lymphoma	Number Analyzed	0 participants	0 participants
Mantle cell lymphoma	Number Analyzed	0 participants	0 participants
Marginal zone lymphoma	Number Analyzed	0 participants	0 participants
Extranodal marginal zone lymphoma of mucosa-associated lymphatic tissue	Number Analyzed	0 participants	0 participants
Nodal marginal zone B-cell lymphoma	Number Analyzed	0 participants	0 participants
Splenic marginal zone lymphoma	Number Analyzed	0 participants	0 participants
Classical Hodgkin's lymphoma	Number Analyzed	0 participants	0 participants
Nodular lymphocytic-predominant Hodgkin's lymphoma	Number Analyzed	0 participants	0 participants

[1]

Summary statistics are not available due to the small sample size in Part 6.

11. Secondary Outcome

Title	Cmax of Itacitinib in Combination With Parsaclisib
Description	Cmax is defined as the maximum observed plasma or serum concentration of itacitinib.
Time Frame	Cycle 1 Day 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK)/Pharmacodynamics (PD) Population: participants in the ITT/Safety Population who had PK/PD data. Data from the parsaclisib 20 mg + itacitinib 300 mg and the parsaclisib 30 mg + itacitinib 300 mg arms were pooled for analysis because all participants received 300 mg itacitinib and there is no drug-drug interaction between parsaclisib and itacitinib to affect the PK of either drug.

Arm/Group Title	Parsaclisib 20/30 mg + Itacitinib 300 mg
Arm/Group Description:	Participants self-administered parsaclisib 20 mg or 30 mg as oral tablets QD and itacitinib 300 mg as oral tablets QD in 21-day treatment cycles.
Overall Number of Participants Analyzed	7
Mean (Standard Deviation); Unit of Measure: nanomoles (nmol)
	887 (404)

12. Secondary Outcome

Title	Tmax of Itacitinib in Combination With Parsaclisib
Description	tmax is defined as the time to the maximum concentration of itacitinib.
Time Frame	Cycle 1 Day 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose

Outcome Measure Data

Analysis Population Description

PK/PD Population. Data from the parsaclisib 20 mg + itacitinib 300 mg and the parsaclisib 30 mg + itacitinib 300 mg arms were pooled for analysis because all participants received 300 mg itacitinib and there is no drug-drug interaction between parsaclisib and itacitinib to affect the PK of either drug.

Arm/Group Title	Parsaclisib 20/30 mg + Itacitinib 300 mg
Arm/Group Description:	Participants self-administered parsaclisib 20 or 30 mg as oral tablets QD and itacitinib 300 mg as oral tablets QD in 21-day treatment cycles.
Overall Number of Participants Analyzed	7
Median (Full Range); Unit of Measure: hours
	2.0; (1.0 to 4.0)

13. Secondary Outcome

Title	Cmin of Itacitinib in Combination With Parsaclisib
Description	Cmin is defined as the minimum observed plasma or serum concentration over the dose interval of itacitinib.
Time Frame	Cycle 1 Day 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose

Outcome Measure Data

Analysis Population Description

PK/PD Population. Data from the parsaclisib 20 mg + itacitinib 300 mg and the parsaclisib 30 mg + itacitinib 300 mg arms were pooled for analysis because all participants received 300 mg itacitinib and there is no drug-drug interaction between parsaclisib and itacitinib to affect the PK of either drug.

Arm/Group Title	Parsaclisib 20/30 mg + Itacitinib 300 mg
Arm/Group Description:	Participants self-administered parsaclisib 20 or 30 mg as oral tablets QD and itacitinib 300 mg as oral tablets QD in 21-day treatment cycles.
Overall Number of Participants Analyzed	7
Mean (Standard Deviation); Unit of Measure: nmol
	32.8 (32.5)

14. Secondary Outcome

Title	AUC0-t of Itacitinib in Combination With Parsaclisib
Description	AUC0-t is defined as the area under the plasma or serum concentration-time curve from time = 0 to the last measurable concentration at time = t of itacitinib.
Time Frame	Cycle 1 Day 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose

Outcome Measure Data

Analysis Population Description

PK/PD Population. Data from the parsaclisib 20 mg + itacitinib 300 mg and the parsaclisib 30 mg + itacitinib 300 mg arms were pooled for analysis because all participants received 300 mg itacitinib and there is no drug-drug interaction between parsaclisib and itacitinib to affect the PK of either drug.

Arm/Group Title	Parsaclisib 20/30 mg + Itacitinib 300 mg
Arm/Group Description:	Participants self-administered parsaclisib 20 or 30 mg as oral tablets QD and itacitinib 300 mg as oral tablets QD in 21-day treatment cycles.
Overall Number of Participants Analyzed	7
Mean (Standard Deviation); Unit of Measure: hours (hr)*nmol/L
	6450 (3780)

15. Secondary Outcome

Title	AUC0-τ of Itacitinib in Combination With Parsaclisib
Description	AUC0-τ is defined as the area under the steady-state plasma or serum concentration-time curve over 1 dose interval (i.e., from hour 0 to 12 for once every 12 hours [q12h] administration or from hour 0 to 24 for once every 24 hours [q24h] administration) of itacitinib.
Time Frame	Cycle 1 Day 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose

Outcome Measure Data

Analysis Population Description

PK/PD Population. Data from the parsaclisib 20 mg + itacitinib 300 mg and the parsaclisib 30 mg + itacitinib 300 mg arms were pooled for analysis because all participants received 300 mg itacitinib and there is no drug-drug interaction between parsaclisib and itacitinib to affect the PK of either drug.

Arm/Group Title	Parsaclisib 20/30 mg + Itacitinib 300 mg
Arm/Group Description:	Participants self-administered parsaclisib 20 or 30 mg as oral tablets QD and itacitinib 300 mg as oral tablets QD in 21-day treatment cycles.
Overall Number of Participants Analyzed	7
Mean (Standard Deviation); Unit of Measure: hr*nmol/L
	6450 (13780)

16. Secondary Outcome

Title	Parts 1 and 2: Cmax of Parsaclisib as Monotherapy and in Combination With Itacitinib
Description	Cmax is defined as the maximum observed plasma or serum concentration of parsaclisib. PK samples collected in Part 2, the combination dose escalation study, and in Part 3, Cohort E expansion group, were analyzed for both parsaclisib and itacitinib.
Time Frame	Cycle 1 Days 1 and 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose

Outcome Measure Data

Analysis Population Description

PK/PD Population. Only participants with available data were analyzed. In the combination therapy arms, data are reported for the Part 3 Cohort E population (participants with B-cell malignancies).

Arm/Group Title		Parsaclisib 5 mg QD	Parsaclisib 10 mg QD	Parsaclisib 15 mg QD	Parsaclisib 20 mg QD	Parsaclisib 30 mg QD	Parsaclisib 45 mg QD	Parsaclisib 20 mg + Itacitinib 300 mg	Parsaclisib 30 mg + Itacitinib 300 mg
Arm/Group Description:		Participants self-administered parsaclisib 5 milligrams (mg) as an oral tablet once a day (QD) in 21-day treatment cycles.	Participants self-administered parsaclisib 10 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 15 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 20 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 30 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 45 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 20 mg as oral tablets QD and itacitinib 300 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 30 mg as oral tablets QD and itacitinib 300 mg as oral tablets QD in 21-day treatment cycles.
Overall Number of Participants Analyzed		1	3	3	4	4	4	8	3
Mean (Standard Deviation); Unit of Measure: nmol
Cycle 1 Day 1	Number Analyzed	1 participants	3 participants	3 participants	4 participants	4 participants	4 participants	8 participants	3 participants
		354 [1] (NA)	791 (502)	808 (316)	1270 (655)	3270 (775)	4010 (1400)	1740 (1010)	2040 (338)
Cycle 1 Day 15	Number Analyzed	1 participants	3 participants	3 participants	4 participants	3 participants	4 participants	8 participants	3 participants
		690 [1] (NA)	856 (449)	1310 (290)	1280 (437)	3310 (682)	5530 (3210)	2390 (1480)	2500 (973)

[1]

Standard deviation was not calculated for a single participant.

17. Secondary Outcome

Title	Parts 1 and 2: Tmax of Parsaclisib as Monotherapy and in Combination With Itacitinib
Description	tmax is defined as the time to the maximum concentration of parsaclisib. PK samples collected in Part 2, the combination dose escalation study, and in Part 3, Cohort E expansion group, were analyzed for both parsaclisib and itacitinib.
Time Frame	Cycle 1 Days 1 and 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose

Outcome Measure Data

Analysis Population Description

PK/PD Population. Only participants with available data were analyzed. In the combination therapy arms, data are reported for the Part 3 Cohort E population (participants with B-cell malignancies).

Arm/Group Title		Parsaclisib 5 mg QD	Parsaclisib 10 mg QD	Parsaclisib 15 mg QD	Parsaclisib 20 mg QD	Parsaclisib 30 mg QD	Parsaclisib 45 mg QD	Parsaclisib 20 mg + Itacitinib 300 mg	Parsaclisib 30 mg + Itacitinib 300 mg
Arm/Group Description:		Participants self-administered parsaclisib 5 milligrams (mg) as an oral tablet once a day (QD) in 21-day treatment cycles.	Participants self-administered parsaclisib 10 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 15 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 20 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 30 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 45 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 20 mg as oral tablets QD and itacitinib 300 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 30 mg as oral tablets QD and itacitinib 300 mg as oral tablets QD in 21-day treatment cycles.
Overall Number of Participants Analyzed		1	3	3	4	4	4	8	3
Median (Full Range); Unit of Measure: hours
Cycle 1 Day 1	Number Analyzed	1 participants	3 participants	3 participants	4 participants	4 participants	4 participants	8 participants	3 participants
		2.0; (2.0 to 2.0)	1.0; (0.5 to 2.0)	1.0; (1.0 to 2.0)	1.0; (0.5 to 2.0)	0.5; (0.5 to 1.0)	1.0; (0.5 to 2.0)	1.0; (0.5 to 1.0)	1.0; (1.0 to 1.0)
Cycle 1 Day 15	Number Analyzed	1 participants	3 participants	3 participants	4 participants	3 participants	4 participants	8 participants	3 participants
		0.5; (0.5 to 0.5)	1.0; (0.5 to 1.0)	1.0; (1.0 to 1.0)	1.0; (0.5 to 1.0)	0.5; (0.5 to 2.0)	0.5; (0.5 to 1.0)	1.0; (0.5 to 2.0)	1.0; (0.5 to 1.0)

18. Secondary Outcome

Title	Parts 1 and 2: Cmin of Parsaclisib as Monotherapy and in Combination With Itacitinib
Description	Cmin is defined as the minimum observed plasma or serum concentration over the dose interval of parsaclisib. PK samples collected in Part 2, the combination dose escalation study, and in Part 3, Cohort E expansion group, were analyzed for both parsaclisib and itacitinib.
Time Frame	Cycle 1 Days 1 and 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose

Outcome Measure Data

Analysis Population Description

PK/PD Population. Only participants with available data were analyzed. In the combination therapy arms, data are reported for the Part 3 Cohort E population (participants with B-cell malignancies).

Arm/Group Title		Parsaclisib 5 mg QD	Parsaclisib 10 mg QD	Parsaclisib 15 mg QD	Parsaclisib 20 mg QD	Parsaclisib 30 mg QD	Parsaclisib 45 mg QD	Parsaclisib 20 mg + Itacitinib 300 mg	Parsaclisib 30 mg + Itacitinib 300 mg
Arm/Group Description:		Participants self-administered parsaclisib 5 milligrams (mg) as an oral tablet once a day (QD) in 21-day treatment cycles.	Participants self-administered parsaclisib 10 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 15 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 20 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 30 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 45 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 20 mg as oral tablets QD and itacitinib 300 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 30 mg as oral tablets QD and itacitinib 300 mg as oral tablets QD in 21-day treatment cycles.
Overall Number of Participants Analyzed		1	3	3	4	4	4	8	3
Mean (Standard Deviation); Unit of Measure: nmol
Cycle 1 Day 1	Number Analyzed	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants
Cycle 1 Day 15	Number Analyzed	1 participants	3 participants	3 participants	4 participants	3 participants	4 participants	8 participants	3 participants
		127 [1] (NA)	104 (46)	156 (99.8)	178 (141)	295 (83.1)	864 (690)	515 (652)	341 (278)

[1]

Standard deviation was not calculated for a single participant.

19. Secondary Outcome

Title	Parts 1 and 2: AUC0-t of Parsaclisib as Monotherapy and in Combination With Itacitinib
Description	AUC0-t is defined as the area under the plasma or serum concentration-time curve from time = 0 to the last measurable concentration at time = t of parsaclisib. PK samples collected in Part 2, the combination dose escalation study, and in Part 3, Cohort E expansion group, were analyzed for both parsaclisib and itacitinib.
Time Frame	Cycle 1 Days 1 and 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose

Outcome Measure Data

Analysis Population Description

PK/PD Population. Only participants with available data were analyzed. In the combination therapy arms, data are reported for the Part 3 Cohort E population (participants with B-cell malignancies).

Arm/Group Title		Parsaclisib 5 mg QD	Parsaclisib 10 mg QD	Parsaclisib 15 mg QD	Parsaclisib 20 mg QD	Parsaclisib 30 mg QD	Parsaclisib 45 mg QD	Parsaclisib 20 mg + Itacitinib 300 mg	Parsaclisib 30 mg + Itacitinib 300 mg
Arm/Group Description:		Participants self-administered parsaclisib 5 milligrams (mg) as an oral tablet once a day (QD) in 21-day treatment cycles.	Participants self-administered parsaclisib 10 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 15 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 20 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 30 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 45 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 20 mg as oral tablets QD and itacitinib 300 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 30 mg as oral tablets QD and itacitinib 300 mg as oral tablets QD in 21-day treatment cycles.
Overall Number of Participants Analyzed		1	3	3	4	4	4	8	3
Mean (Standard Deviation); Unit of Measure: hr*nmol/L
Cycle 1 Day 1	Number Analyzed	1 participants	3 participants	3 participants	4 participants	4 participants	4 participants	8 participants	3 participants
		2110 [1] (NA)	3260 (1460)	3730 (678)	5990 (2650)	13300 (2480)	16800 (4880)	7540 (3370)	10400 (1330)
Cycle 1 Day 15	Number Analyzed	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants

[1]

Standard deviation was not calculated for a single participant.

20. Secondary Outcome

Title	Parts 1 and 2: AUC0-τ of Parsaclisib as Monotherapy and in Combination With Itacitinib
Description	AUC0-τ is defined as the area under the steady-state plasma or serum concentration-time curve over 1 dose interval (i.e., from hour 0 to 12 for q12h administration or from hour 0 to 24 for q24h administration) of parsaclisib. PK samples collected in Part 2, the combination dose escalation study, and in Part 3, Cohort E expansion group, were analyzed for both parsaclisib and itacitinib.
Time Frame	Cycle 1 Days 1 and 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose

Outcome Measure Data

Analysis Population Description

PK/PD Population. Only participants with available data were analyzed. In the combination therapy arms, data are reported for the Part 3 Cohort E population (participants with B-cell malignancies).

Arm/Group Title		Parsaclisib 5 mg QD	Parsaclisib 10 mg QD	Parsaclisib 15 mg QD	Parsaclisib 20 mg QD	Parsaclisib 30 mg QD	Parsaclisib 45 mg QD	Parsaclisib 20 mg + Itacitinib 300 mg	Parsaclisib 30 mg + Itacitinib 300 mg
Arm/Group Description:		Participants self-administered parsaclisib 5 milligrams (mg) as an oral tablet once a day (QD) in 21-day treatment cycles.	Participants self-administered parsaclisib 10 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 15 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 20 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 30 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 45 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 20 mg as oral tablets QD and itacitinib 300 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 30 mg as oral tablets QD and itacitinib 300 mg as oral tablets QD in 21-day treatment cycles.
Overall Number of Participants Analyzed		1	3	3	4	4	4	8	3
Mean (Standard Deviation); Unit of Measure: hr*nmol/L
Cycle 1 Day 1	Number Analyzed	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants
Cycle 1 Day 15	Number Analyzed	1 participants	3 participants	3 participants	4 participants	4 participants	4 participants	8 participants	3 participants
		7130 [1] (NA)	6910 (2330)	11100 (6310)	11900 (5110)	24800 (2140)	47700 (30500)	22400 (17100)	22900 (10700)

[1]

Standard deviation was not calculated for a single participant.

21. Secondary Outcome

Title	Part 3: Cmax of Parsaclisib Monotherapy
Description	Cmax is defined as the maximum observed plasma or serum concentration of parsaclisib. PK samples for parsaclisib monotherapy were collected and analyzed from the Part 3 dose expansion (different participant populations). Cohort A: B-cell malignancies; Cohort B: Hodgkin's lymphoma; Cohort C: diffuse large B-cell lymphoma; Cohort D: indolent lymphoma.
Time Frame	Cycle 1 Days 1 and 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose

Outcome Measure Data

Analysis Population Description

PK/PD Population. Only participants with available data were analyzed.

Arm/Group Title		Parsaclisib 5 mg QD	Parsaclisib 10 mg QD	Parsaclisib 15 mg QD	Parsaclisib 20 mg QD	Parsaclisib 30 mg QD	Parsaclisib 45 mg QD
Arm/Group Description:		Participants self-administered parsaclisib 5 milligrams (mg) as an oral tablet once a day (QD) in 21-day treatment cycles.	Participants self-administered parsaclisib 10 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 15 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 20 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 30 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 45 mg as oral tablets QD in 21-day treatment cycles.
Overall Number of Participants Analyzed		0	0	0	30	23	0
Mean (Standard Deviation); Unit of Measure: nmol
Cycle 1 Day 1, Cohort A	Number Analyzed	0 participants	0 participants	0 participants	17 participants	8 participants	0 participants
					1550 (544)	2350 (944)
Cycle 1 Day 15, Cohort A	Number Analyzed	0 participants	0 participants	0 participants	15 participants	9 participants	0 participants
					1720 (492)	2390 (648)
Cycle 1 Day 1, Cohort B	Number Analyzed	0 participants	0 participants	0 participants	1 participants	6 participants	0 participants
					1200 [1] (NA)	1720 (925)
Cycle 1 Day 15, Cohort B	Number Analyzed	0 participants	0 participants	0 participants	1 participants	6 participants	0 participants
					1930 [1] (NA)	2260 (784)
Cycle 1 Day 1, Cohort C	Number Analyzed	0 participants	0 participants	0 participants	9 participants	4 participants	0 participants
					1760 (772)	1760 (534)
Cycle 1 Day 15, Cohort C	Number Analyzed	0 participants	0 participants	0 participants	8 participants	4 participants	0 participants
					2060 (682)	3920 (1320)
Cycle 1 Day 1, Cohort D	Number Analyzed	0 participants	0 participants	0 participants	3 participants	4 participants	0 participants
					1760 (580)	2500 (279)
Cycle 1 Day 15, Cohort D	Number Analyzed	0 participants	0 participants	0 participants	3 participants	4 participants	0 participants
					1600 (378)	2990 (783)

[1]

Standard deviation was not calculated for a single participant.

22. Secondary Outcome

Title	Part 3: Tmax of Parsaclisib Monotherapy
Description	tmax is defined as the time to the maximum concentration of parsaclisib. PK samples for parsaclisib monotherapy were collected and analyzed from the Part 3 dose expansion (different participant populations). Cohort A: B-cell malignancies; Cohort B: Hodgkin's lymphoma; Cohort C: diffuse large B-cell lymphoma; Cohort D: indolent lymphoma.
Time Frame	Cycle 1 Days 1 and 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose

Outcome Measure Data

Analysis Population Description

PK/PD Population. Only participants with available data were analyzed.

Arm/Group Title		Parsaclisib 5 mg QD	Parsaclisib 10 mg QD	Parsaclisib 15 mg QD	Parsaclisib 20 mg QD	Parsaclisib 30 mg QD	Parsaclisib 45 mg QD
Arm/Group Description:		Participants self-administered parsaclisib 5 milligrams (mg) as an oral tablet once a day (QD) in 21-day treatment cycles.	Participants self-administered parsaclisib 10 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 15 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 20 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 30 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 45 mg as oral tablets QD in 21-day treatment cycles.
Overall Number of Participants Analyzed		0	0	0	30	23	0
Median (Full Range); Unit of Measure: hours
Cycle 1 Day 1, Cohort A	Number Analyzed	0 participants	0 participants	0 participants	17 participants	8 participants	0 participants
					0.5; (0.5 to 4.0)	1.0; (0.5 to 2.0)
Cycle 1 Day 15, Cohort A	Number Analyzed	0 participants	0 participants	0 participants	15 participants	9 participants	0 participants
					1.0; (0.5 to 1.0)	1.0; (0.5 to 2.0)
Cycle 1 Day 1, Cohort B	Number Analyzed	0 participants	0 participants	0 participants	1 participants	6 participants	0 participants
					2.0; (2.0 to 2.0)	1.5; (0.5 to 2.0)
Cycle 1 Day 15, Cohort B	Number Analyzed	0 participants	0 participants	0 participants	1 participants	6 participants	0 participants
					0.5; (0.5 to 0.5)	0.75; (0.5 to 8.0)
Cycle 1 Day 1, Cohort C	Number Analyzed	0 participants	0 participants	0 participants	9 participants	4 participants	0 participants
					0.5; (0.5 to 4.0)	1.0; (0.5 to 2.0)
Cycle 1 Day 15, Cohort C	Number Analyzed	0 participants	0 participants	0 participants	8 participants	4 participants	0 participants
					1.0; (0.5 to 1.0)	0.5; (0.5 to 0.5)
Cycle 1 Day 1, Cohort D	Number Analyzed	0 participants	0 participants	0 participants	3 participants	4 participants	0 participants
					1.0; (0.5 to 1.0)	0.75; (0.5 to 1.0)
Cycle 1 Day 15, Cohort D	Number Analyzed	0 participants	0 participants	0 participants	3 participants	4 participants	0 participants
					0.5; (0.5 to 1.0)	1.0; (0.5 to 1.0)

23. Secondary Outcome

Title	Part 3: Cmin of Parsaclisib Monotherapy
Description	Cmin is defined as the minimum observed plasma or serum concentration over the dose interval of parsaclisib. PK samples for parsaclisib monotherapy were collected and analyzed from the Part 3 dose expansion (different participant populations). Cohort A: B-cell malignancies; Cohort B: Hodgkin's lymphoma; Cohort C: diffuse large B-cell lymphoma; Cohort D: indolent lymphoma.
Time Frame	Cycle 1 Days 1 and 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose

Outcome Measure Data

Analysis Population Description

PK/PD Population. Only participants with available data were analyzed.

Arm/Group Title		Parsaclisib 5 mg QD	Parsaclisib 10 mg QD	Parsaclisib 15 mg QD	Parsaclisib 20 mg QD	Parsaclisib 30 mg QD	Parsaclisib 45 mg QD
Arm/Group Description:		Participants self-administered parsaclisib 5 milligrams (mg) as an oral tablet once a day (QD) in 21-day treatment cycles.	Participants self-administered parsaclisib 10 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 15 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 20 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 30 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 45 mg as oral tablets QD in 21-day treatment cycles.
Overall Number of Participants Analyzed		0	0	0	30	23	0
Mean (Standard Deviation); Unit of Measure: nmol
Cycle 1 Day 1, Cohort A	Number Analyzed	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants
Cycle 1 Day 15, Cohort A	Number Analyzed	0 participants	0 participants	0 participants	15 participants	9 participants	0 participants
					214 (171)	281 (137)
Cycle 1 Day 1, Cohort B	Number Analyzed	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants
Cycle 1 Day 15, Cohort B	Number Analyzed	0 participants	0 participants	0 participants	1 participants	6 participants	0 participants
					395 [1] (NA)	296 (177)
Cycle 1 Day 1, Cohort C	Number Analyzed	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants
Cycle 1 Day 15, Cohort C	Number Analyzed	0 participants	0 participants	0 participants	8 participants	4 participants	0 participants
					197 (79.6)	477 (137)
Cycle 1 Day 1, Cohort D	Number Analyzed	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants
Cycle 1 Day 15, Cohort D	Number Analyzed	0 participants	0 participants	0 participants	3 participants	4 participants	0 participants
					202 (161)	421 (365)

[1]

Standard deviation was not calculated for a single participant.

24. Secondary Outcome

Title	Part 3: AUC0-t of Parsaclisib Monotherapy
Description	AUC0-t is defined as the area under the plasma or serum concentration-time curve from time = 0 to the last measurable concentration at time = t of of parsaclisib. PK samples for parsaclisib monotherapy were collected and analyzed from the Part 3 dose expansion (different participant populations). Cohort A: B-cell malignancies; Cohort B: Hodgkin's lymphoma; Cohort C: diffuse large B-cell lymphoma; Cohort D: indolent lymphoma.
Time Frame	Cycle 1 Days 1 and 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose

Outcome Measure Data

Analysis Population Description

PK/PD Population. Only participants with available data were analyzed.

Arm/Group Title		Parsaclisib 5 mg QD	Parsaclisib 10 mg QD	Parsaclisib 15 mg QD	Parsaclisib 20 mg QD	Parsaclisib 30 mg QD	Parsaclisib 45 mg QD
Arm/Group Description:		Participants self-administered parsaclisib 5 milligrams (mg) as an oral tablet once a day (QD) in 21-day treatment cycles.	Participants self-administered parsaclisib 10 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 15 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 20 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 30 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 45 mg as oral tablets QD in 21-day treatment cycles.
Overall Number of Participants Analyzed		0	0	0	30	23	0
Mean (Standard Deviation); Unit of Measure: hr*nmol/L
Cycle 1 Day 1, Cohort A	Number Analyzed	0 participants	0 participants	0 participants	17 participants	8 participants	0 participants
					6530 (2280)	10700 (4150)
Cycle 1 Day 15, Cohort A	Number Analyzed	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants
Cycle 1 Day 1, Cohort B	Number Analyzed	0 participants	0 participants	0 participants	1 participants	6 participants	0 participants
					7010 [1] (NA)	8430 (3560)
Cycle 1 Day 15, Cohort B	Number Analyzed	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants
Cycle 1 Day 1, Cohort C	Number Analyzed	0 participants	0 participants	0 participants	9 participants	4 participants	0 participants
					7110 (2760)	12000 (3230)
Cycle 1 Day 15, Cohort C	Number Analyzed	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants
Cycle 1 Day 1, Cohort D	Number Analyzed	0 participants	0 participants	0 participants	3 participants	4 participants	0 participants
					7230 (2530)	9970 (1260)
Cycle 1 Day 15, Cohort D	Number Analyzed	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants

[1]

Standard deviation was not calculated for a single participant.

25. Secondary Outcome

Title	Part 3: AUC0-τ of Parsaclisib Monotherapy
Description	AUC0-τ is defined as the area under the steady-state plasma or serum concentration-time curve over 1 dose interval (i.e., from hour 0 to 12 for once every 12 hours [q12h] administration or from hour 0 to 24 for once every 24 hours [q24h] administration) of parsaclisib. PK samples for parsaclisib monotherapy were collected and analyzed from the Part 3 dose expansion (different participant populations). Cohort A: B-cell malignancies; Cohort B: Hodgkin's lymphoma; Cohort C: diffuse large B-cell lymphoma; Cohort D: indolent lymphoma.
Time Frame	Cycle 1 Days 1 and 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose

Outcome Measure Data

Analysis Population Description

PK/PD Population. Only participants with available data were analyzed.

Arm/Group Title		Parsaclisib 5 mg QD	Parsaclisib 10 mg QD	Parsaclisib 15 mg QD	Parsaclisib 20 mg QD	Parsaclisib 30 mg QD	Parsaclisib 45 mg QD
Arm/Group Description:		Participants self-administered parsaclisib 5 milligrams (mg) as an oral tablet once a day (QD) in 21-day treatment cycles.	Participants self-administered parsaclisib 10 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 15 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 20 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 30 mg as oral tablets QD in 21-day treatment cycles.	Participants self-administered parsaclisib 45 mg as oral tablets QD in 21-day treatment cycles.
Overall Number of Participants Analyzed		0	0	0	30	23	0
Mean (Standard Deviation); Unit of Measure: hr*nmol/L
Cycle 1 Day 1, Cohort A	Number Analyzed	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants
Cycle 1 Day 15, Cohort A	Number Analyzed	0 participants	0 participants	0 participants	15 participants	9 participants	0 participants
					12600 (5170)	19500 (6020)
Cycle 1 Day 1, Cohort B	Number Analyzed	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants
Cycle 1 Day 15, Cohort B	Number Analyzed	0 participants	0 participants	0 participants	1 participants	6 participants	0 participants
					17900 [1] (NA)	20100 (6640)
Cycle 1 Day 1, Cohort C	Number Analyzed	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants
Cycle 1 Day 15, Cohort C	Number Analyzed	0 participants	0 participants	0 participants	8 participants	4 participants	0 participants
					14200 (4600)	28000 (4310)
Cycle 1 Day 1, Cohort D	Number Analyzed	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants
Cycle 1 Day 15, Cohort D	Number Analyzed	0 participants	0 participants	0 participants	3 participants	4 participants	0 participants
					13600 (7270)	25200 (8820)

[1]

Standard deviation was not calculated for a single participant.

Adverse Events

Time Frame	Up to approximately 53 months (4.4 years)
Adverse Event Reporting Description	Treatment-emergent adverse events (TEAEs), defined as events that were reported for the first time, or the worsening of a pre-existing event, after the first dose of study drug, are reported for the Safety Population, defined as all participants enrolled in the study who received at least 1 dose of parsaclisib, itacitinib, rituximab, ifosfamide, carboplatin, and/or etoposide.
Arm/Group Title	Parsaclisib 5 mg QD		Parsaclisib 10 mg QD		Parsaclisib 15 mg QD		Parsaclisib 20 mg QD		Parsaclisib 30 mg QD		Parsaclisib 45 mg QD		Parsaclisib 20 mg + Itacitinib 300 mg		Parsaclisib 30 mg + Itacitinib 300 mg		Parsaclisib 15 mg QD + R-ICE		Parsaclisib 20 mg QD + R-ICE		Total
Arm/Group Description	Participants self-administered parsaclisib 5 milligrams (mg) as an oral tablet once a day (QD) in 21-day treatment cycles.		Participants self-administered parsaclisib 10 mg as oral tablets QD in 21-day treatment cycles.		Participants self-administered parsaclisib 15 mg as oral tablets QD in 21-day treatment cycles.		Participants self-administered parsaclisib 20 mg as oral tablets QD in 21-day treatment cycles.		Participants self-administered parsaclisib 30 mg as oral tablets QD in 21-day treatment cycles.		Participants self-administered parsaclisib 45 mg as oral tablets QD in 21-day treatment cycles.		Participants self-administered parsaclisib 20 mg as oral tablets QD and itacitinib 300 mg as oral tablets QD in 21-day treatment cycles.		Participants self-administered parsaclisib 30 mg as oral tablets QD and itacitinib 300 mg as oral tablets QD in 21-day treatment cycles.		Participants self-administered parsaclisib 15 mg as oral tablets QD in 21-day treatment cycles. R-ICE was a standard-of-care chemotherapy combination administered at the following doses: rituximab 375 milligrams per meters squared (mg/m^2) intravenously (IV) on Day 1 and Day 2 of Cycle 1 and on Day 1 of Cycles 2 and 3, ifosfamide 5000 mg/m^2 IV on Day 3 of each cycle, carboplatin area under the curve (AUC) = 5 (maximum dose 800 mg) IV on Day 3 of each cycle, and etoposide 100 mg/m^2 or at doses consistent with institutional practice with approval from the medical monitor on Days 3 and 5 of each cycle. Each cycle was 21 days in duration.		Participants self-administered parsaclisib 20 mg as oral tablets QD in 21-day treatment cycles. R-ICE was a standard-of-care chemotherapy combination administered at the following doses: rituximab 375 mg/m^2 IV on Day 1 and Day 2 of Cycle 1 and on Day 1 of Cycles 2 and 3, ifosfamide 5000 mg/m^2 IV on Day 3 of each cycle, carboplatin AUC = 5 (maximum dose 800 mg) IV on Day 3 of each cycle, and etoposide 100 mg/m^2 or at doses consistent with institutional practice with approval from the medical monitor on Days 3 and 5 of each cycle. Each cycle was 21 days in duration.		All participants in all treatment arms combined.
All-Cause Mortality
	Parsaclisib 5 mg QD		Parsaclisib 10 mg QD		Parsaclisib 15 mg QD		Parsaclisib 20 mg QD		Parsaclisib 30 mg QD		Parsaclisib 45 mg QD		Parsaclisib 20 mg + Itacitinib 300 mg		Parsaclisib 30 mg + Itacitinib 300 mg		Parsaclisib 15 mg QD + R-ICE		Parsaclisib 20 mg QD + R-ICE		Total
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	1/1 (100.00%)		0/3 (0.00%)		0/3 (0.00%)		3/34 (8.82%)		1/27 (3.70%)		0/4 (0.00%)		0/8 (0.00%)		0/3 (0.00%)		0/4 (0.00%)		0/1 (0.00%)		5/88 (5.68%)
Serious Adverse Events
	Parsaclisib 5 mg QD		Parsaclisib 10 mg QD		Parsaclisib 15 mg QD		Parsaclisib 20 mg QD		Parsaclisib 30 mg QD		Parsaclisib 45 mg QD		Parsaclisib 20 mg + Itacitinib 300 mg		Parsaclisib 30 mg + Itacitinib 300 mg		Parsaclisib 15 mg QD + R-ICE		Parsaclisib 20 mg QD + R-ICE		Total
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/1 (100.00%)		2/3 (66.67%)		1/3 (33.33%)		14/34 (41.18%)		12/27 (44.44%)		2/4 (50.00%)		0/8 (0.00%)		2/3 (66.67%)		1/4 (25.00%)		1/1 (100.00%)		36/88 (40.91%)
Blood and lymphatic system disorders
Anaemia † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/34 (0.00%)	0	1/27 (3.70%)	1	0/4 (0.00%)	0	0/8 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/1 (0.00%)	0	1/88 (1.14%)	1
Febrile neutropenia † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/34 (2.94%)	1	0/27 (0.00%)	0	0/4 (0.00%)	0	0/8 (0.00%)	0	0/3 (0.00%)	0	1/4 (25.00%)	1	0/1 (0.00%)	0	2/88 (2.27%)	2
Leukocytosis † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/34 (0.00%)	0	1/27 (3.70%)	1	0/4 (0.00%)	0	0/8 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/1 (0.00%)	0	1/88 (1.14%)	1
Cardiac disorders
Atrial flutter † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/34 (0.00%)	0	0/27 (0.00%)	0	0/4 (0.00%)	0	0/8 (0.00%)	0	0/3 (0.00%)	0	1/4 (25.00%)	2	0/1 (0.00%)	0	1/88 (1.14%)	2
Ventricular tachycardia † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	1/34 (2.94%)	1	0/27 (0.00%)	0	0/4 (0.00%)	0	0/8 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/1 (0.00%)	0	2/88 (2.27%)	2
Gastrointestinal disorders
Abdominal pain † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	2/34 (5.88%)	2	0/27 (0.00%)	0	0/4 (0.00%)	0	0/8 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/1 (0.00%)	0	2/88 (2.27%)	2
Anal incontinence † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/34 (0.00%)	0	1/27 (3.70%)	1	0/4 (0.00%)	0	0/8 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/1 (0.00%)	0	1/88 (1.14%)	1
Colitis † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	4/34 (11.76%)	5	0/27 (0.00%)	0	0/4 (0.00%)	0	0/8 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/1 (0.00%)	0	4/88 (4.55%)	5
Diarrhoea † 1	0/1 (0.00%)	0	1/3 (33.33%)	1	1/3 (33.33%)	1	1/34 (2.94%)	1	3/27 (11.11%)	3	0/4 (0.00%)	0	0/8 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/1 (0.00%)	0	6/88 (6.82%)	6
Gastritis erosive † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/34 (0.00%)	0	1/27 (3.70%)	1	0/4 (0.00%)	0	0/8 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/1 (0.00%)	0	1/88 (1.14%)	1
General disorders
Gait disturbance † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/34 (2.94%)	1	0/27 (0.00%)	0	0/4 (0.00%)	0	0/8 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/1 (0.00%)	0	1/88 (1.14%)	1
Pyrexia † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	2/34 (5.88%)	2	1/27 (3.70%)	1	1/4 (25.00%)	1	0/8 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/1 (0.00%)	0	4/88 (4.55%)	4
Infections and infestations
Bacteraemia † 1	0/1 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/34 (0.00%)	0	1/27 (3.70%)	1	0/4 (0.00%)	0	0/8 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/1 (0.00%)	0	2/88 (2.27%)	2
Bronchitis † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/34 (2.94%)	1	1/27 (3.70%)	1	0/4 (0.00%)	0	0/8 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/1 (0.00%)	0	2/88 (2.27%)	2
Cytomegalovirus colitis † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/34 (2.94%)	1	0/27 (0.00%)	0	0/4 (0.00%)	0	0/8 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/1 (0.00%)	0	1/88 (1.14%)	1
Escherichia bacteraemia † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/34 (2.94%)	1	0/27 (0.00%)	0	0/4 (0.00%)	0	0/8 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/1 (0.00%)	0	1/88 (1.14%)	1
Klebsiella bacteraemia † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/34 (0.00%)	0	0/27 (0.00%)	0	1/4 (25.00%)	1	0/8 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/1 (0.00%)	0	1/88 (1.14%)	1
Pneumonia † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/34 (2.94%)	1	0/27 (0.00%)	0	1/4 (25.00%)	2	0/8 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/1 (0.00%)	0	2/88 (2.27%)	3
Sepsis † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	3/34 (8.82%)	3	0/27 (0.00%)	0	0/4 (0.00%)	0	0/8 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/1 (0.00%)	0	3/88 (3.41%)	3
Urinary tract infection † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/34 (0.00%)	0	1/27 (3.70%)	1	1/4 (25.00%)	1	0/8 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/1 (0.00%)	0	2/88 (2.27%)	2
Injury, poisoning and procedural complications
Fall † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/34 (0.00%)	0	1/27 (3.70%)	1	0/4 (0.00%)	0	0/8 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/1 (0.00%)	0	1/88 (1.14%)	1
Hip fracture † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/34 (0.00%)	0	1/27 (3.70%)	1	0/4 (0.00%)	0	0/8 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/1 (0.00%)	0	1/88 (1.14%)	1
Investigations
White blood cell count decreased † 1	1/1 (100.00%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/34 (0.00%)	0	0/27 (0.00%)	0	0/4 (0.00%)	0	0/8 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/1 (0.00%)	0	1/88 (1.14%)	1
Metabolism and nutrition disorders
Dehydration † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/34 (2.94%)	1	0/27 (0.00%)	0	0/4 (0.00%)	0	0/8 (0.00%)	0	1/3 (33.33%)	1	0/4 (0.00%)	0	0/1 (0.00%)	0	2/88 (2.27%)	2
Hypercalcaemia † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/34 (0.00%)	0	1/27 (3.70%)	1	0/4 (0.00%)	0	0/8 (0.00%)	0	1/3 (33.33%)	2	0/4 (0.00%)	0	0/1 (0.00%)	0	2/88 (2.27%)	3
Musculoskeletal and connective tissue disorders
Muscular weakness † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/34 (0.00%)	0	1/27 (3.70%)	1	0/4 (0.00%)	0	0/8 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/1 (0.00%)	0	1/88 (1.14%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant pleural effusion † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/34 (0.00%)	0	1/27 (3.70%)	2	0/4 (0.00%)	0	0/8 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/1 (0.00%)	0	1/88 (1.14%)	2
Nervous system disorders
Encephalopathy † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/34 (0.00%)	0	0/27 (0.00%)	0	0/4 (0.00%)	0	0/8 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	1/1 (100.00%)	1	1/88 (1.14%)	1
Syncope † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/34 (2.94%)	1	1/27 (3.70%)	1	0/4 (0.00%)	0	0/8 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/1 (0.00%)	0	2/88 (2.27%)	2
Psychiatric disorders
Confusional state † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/34 (0.00%)	0	1/27 (3.70%)	1	0/4 (0.00%)	0	0/8 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/1 (0.00%)	0	1/88 (1.14%)	1
Mental status changes † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/34 (0.00%)	0	1/27 (3.70%)	1	0/4 (0.00%)	0	0/8 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/1 (0.00%)	0	1/88 (1.14%)	1
Renal and urinary disorders
Acute kidney injury † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/34 (0.00%)	0	1/27 (3.70%)	1	0/4 (0.00%)	0	0/8 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/1 (0.00%)	0	1/88 (1.14%)	1
Renal tubular necrosis † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/34 (0.00%)	0	1/27 (3.70%)	1	0/4 (0.00%)	0	0/8 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/1 (0.00%)	0	1/88 (1.14%)	1
Urinary incontinence † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/34 (0.00%)	0	1/27 (3.70%)	1	0/4 (0.00%)	0	0/8 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/1 (0.00%)	0	1/88 (1.14%)	1
Respiratory, thoracic and mediastinal disorders
Cough † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/34 (2.94%)	1	0/27 (0.00%)	0	0/4 (0.00%)	0	0/8 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/1 (0.00%)	0	1/88 (1.14%)	1
Pleural effusion † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/34 (2.94%)	2	1/27 (3.70%)	1	0/4 (0.00%)	0	0/8 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/1 (0.00%)	0	2/88 (2.27%)	3
Pneumonitis † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/34 (0.00%)	0	0/27 (0.00%)	0	0/4 (0.00%)	0	0/8 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/1 (0.00%)	0	1/88 (1.14%)	1
Pulmonary oedema † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/34 (0.00%)	0	0/27 (0.00%)	0	0/4 (0.00%)	0	0/8 (0.00%)	0	0/3 (0.00%)	0	1/4 (25.00%)	1	0/1 (0.00%)	0	1/88 (1.14%)	1
Respiratory failure † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/34 (2.94%)	1	1/27 (3.70%)	1	0/4 (0.00%)	0	0/8 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/1 (0.00%)	0	2/88 (2.27%)	2
Skin and subcutaneous tissue disorders
Dermatitis exfoliative † 1	0/1 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/34 (0.00%)	0	1/27 (3.70%)	1	0/4 (0.00%)	0	0/8 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/1 (0.00%)	0	2/88 (2.27%)	2
Vascular disorders
Hypotension † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/34 (0.00%)	0	2/27 (7.41%)	2	0/4 (0.00%)	0	0/8 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/1 (0.00%)	0	3/88 (3.41%)	3
1 Term from vocabulary, MedDRA 23.1; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Parsaclisib 5 mg QD		Parsaclisib 10 mg QD		Parsaclisib 15 mg QD		Parsaclisib 20 mg QD		Parsaclisib 30 mg QD		Parsaclisib 45 mg QD		Parsaclisib 20 mg + Itacitinib 300 mg		Parsaclisib 30 mg + Itacitinib 300 mg		Parsaclisib 15 mg QD + R-ICE		Parsaclisib 20 mg QD + R-ICE		Total
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/1 (100.00%)		3/3 (100.00%)		3/3 (100.00%)		32/34 (94.12%)		24/27 (88.89%)		4/4 (100.00%)		6/8 (75.00%)		3/3 (100.00%)		4/4 (100.00%)		1/1 (100.00%)		81/88 (92.05%)
Blood and lymphatic system disorders
Anaemia † 1	1/1 (100.00%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	5/34 (14.71%)	8	4/27 (14.81%)	5	0/4 (0.00%)	0	0/8 (0.00%)	0	0/3 (0.00%)	0	4/4 (100.00%)	4	1/1 (100.00%)	1	15/88 (17.05%)	19
Neutropenia † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	7/34 (20.59%)	10	7/27 (25.93%)	16	1/4 (25.00%)	1	1/8 (12.50%)	2	0/3 (0.00%)	0	3/4 (75.00%)	6	1/1 (100.00%)	1	20/88 (22.73%)	36
Polycythaemia † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/34 (0.00%)	0	0/27 (0.00%)	0	1/4 (25.00%)	1	0/8 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/1 (0.00%)	0	1/88 (1.14%)	1
Thrombocytopenia † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	7/34 (20.59%)	12	5/27 (18.52%)	6	0/4 (0.00%)	0	0/8 (0.00%)	0	0/3 (0.00%)	0	3/4 (75.00%)	9	1/1 (100.00%)	2	17/88 (19.32%)	30
Cardiac disorders
Atrial fibrillation † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/34 (0.00%)	0	0/27 (0.00%)	0	0/4 (0.00%)	0	0/8 (0.00%)	0	0/3 (0.00%)	0	1/4 (25.00%)	1	0/1 (0.00%)	0	1/88 (1.14%)	1
Bradycardia † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/34 (2.94%)	1	0/27 (0.00%)	0	0/4 (0.00%)	0	1/8 (12.50%)	1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/1 (0.00%)	0	2/88 (2.27%)	2
Palpitations † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/34 (0.00%)	0	3/27 (11.11%)	3	0/4 (0.00%)	0	0/8 (0.00%)	0	0/3 (0.00%)	0	1/4 (25.00%)	1	0/1 (0.00%)	0	4/88 (4.55%)	4
Sinus tachycardia † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/34 (0.00%)	0	0/27 (0.00%)	0	0/4 (0.00%)	0	0/8 (0.00%)	0	0/3 (0.00%)	0	1/4 (25.00%)	1	0/1 (0.00%)	0	1/88 (1.14%)	1
Supraventricular tachycardia † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/34 (2.94%)	1	0/27 (0.00%)	0	0/4 (0.00%)	0	0/8 (0.00%)	0	0/3 (0.00%)	0	1/4 (25.00%)	1	0/1 (0.00%)	0	2/88 (2.27%)	2
Tachycardia † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	2/34 (5.88%)	2	4/27 (14.81%)	5	0/4 (0.00%)	0	2/8 (25.00%)	2	0/3 (0.00%)	0	1/4 (25.00%)	1	0/1 (0.00%)	0	9/88 (10.23%)	10
Ear and labyrinth disorders
Cerumen impaction † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	2/34 (5.88%)	2	0/27 (0.00%)	0	0/4 (0.00%)	0	0/8 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/1 (0.00%)	0	2/88 (2.27%)	2
Deafness † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	2/34 (5.88%)	2	0/27 (0.00%)	0	0/4 (0.00%)	0	0/8 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/1 (0.00%)	0	2/88 (2.27%)	2
Middle ear inflammation † 1	0/1 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/34 (0.00%)	0	0/27 (0.00%)	0	0/4 (0.00%)	0	0/8 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/1 (0.00%)	0	1/88 (1.14%)	1
Tinnitus † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/34 (0.00%)	0	1/27 (3.70%)	1	0/4 (0.00%)	0	0/8 (0.00%)	0	0/3 (0.00%)	0	1/4 (25.00%)	2	0/1 (0.00%)	0	2/88 (2.27%)	3
Vertigo † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/34 (0.00%)	0	0/27 (0.00%)	0	0/4 (0.00%)	0	1/8 (12.50%)	1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/1 (0.00%)	0	1/88 (1.14%)	1
Eye disorders
Eye irritation † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/34 (0.00%)	0	0/27 (0.00%)	0	0/4 (0.00%)	0	0/8 (0.00%)	0	0/3 (0.00%)	0	1/4 (25.00%)	1	0/1 (0.00%)	0	1/88 (1.14%)	1
Lacrimation increased † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/34 (0.00%)	0	0/27 (0.00%)	0	0/4 (0.00%)	0	1/8 (12.50%)	1	1/3 (33.33%)	1	0/4 (0.00%)	0	0/1 (0.00%)	0	2/88 (2.27%)	2
Gastrointestinal disorders
Abdominal discomfort † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	3	0/34 (0.00%)	0	1/27 (3.70%)	1	0/4 (0.00%)	0	0/8 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/1 (0.00%)	0	2/88 (2.27%)	4
Abdominal distension † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/34 (0.00%)	0	2/27 (7.41%)	2	0/4 (0.00%)	0	1/8 (12.50%)	1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/1 (0.00%)	0	3/88 (3.41%)	3
Abdominal pain † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	5/34 (14.71%)	6	6/27 (22.22%)	6	0/4 (0.00%)	0	1/8 (12.50%)	1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/1 (0.00%)	0	12/88 (13.64%)	13
Abdominal pain upper † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	2/34 (5.88%)	2	0/27 (0.00%)	0	1/4 (25.00%)	1	0/8 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/1 (0.00%)	0	3/88 (3.41%)	3
Abdominal tenderness † 1	0/1 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/34 (0.00%)	0	0/27 (0.00%)	0	0/4 (0.00%)	0	0/8 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/1 (0.00%)	0	1/88 (1.14%)	1
Constipation † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	3/34 (8.82%)	3	9/27 (33.33%)	9	0/4 (0.00%)	0	0/8 (0.00%)	0	1/3 (33.33%)	1	1/4 (25.00%)	1	1/1 (100.00%)	1	16/88 (18.18%)	16
Diarrhoea † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	14/34 (41.18%)	19	11/27 (40.74%)	16	1/4 (25.00%)	1	2/8 (25.00%)	3	1/3 (33.33%)	1	1/4 (25.00%)	1	0/1 (0.00%)	0	31/88 (35.23%)	42
Dry mouth † 1	0/1 (0.00%)	0	1/3 (33.33%)	1	1/3 (33.33%)	1	0/34 (0.00%)	0	0/27 (0.00%)	0	0/4 (0.00%)	0	0/8 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/1 (0.00%)	0	2/88 (2.27%)	2
Dyspepsia † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/34 (0.00%)	0	0/27 (0.00%)	0	0/4 (0.00%)	0	1/8 (12.50%)	1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/1 (0.00%)	0	1/88 (1.14%)	1
Dysphagia † 1	0/1 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/34 (0.00%)	0	0/27 (0.00%)	0	0/4 (0.00%)	0	0/8 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/1 (0.00%)	0	1/88 (1.14%)	1
Gastrointestinal disorder † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/34 (0.00%)	0	0/27 (0.00%)	0	1/4 (25.00%)	1	0/8 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/1 (0.00%)	0	1/88 (1.14%)	1
Haemorrhoids † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/34 (2.94%)	1	0/27 (0.00%)	0	0/4 (0.00%)	0	0/8 (0.00%)	0	1/3 (33.33%)	1	0/4 (0.00%)	0	0/1 (0.00%)	0	2/88 (2.27%)	2
Nausea † 1	1/1 (100.00%)	1	1/3 (33.33%)	1	2/3 (66.67%)	2	9/34 (26.47%)	10	12/27 (44.44%)	15	1/4 (25.00%)	1	3/8 (37.50%)	3	2/3 (66.67%)	2	1/4 (25.00%)	1	0/1 (0.00%)	0	32/88 (36.36%)	36
Oral pain † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/34 (2.94%)	1	0/27 (0.00%)	0	0/4 (0.00%)	0	0/8 (0.00%)	0	0/3 (0.00%)	0	1/4 (25.00%)	1	0/1 (0.00%)	0	2/88 (2.27%)	2
Stomatitis † 1	1/1 (100.00%)	1	1/3 (33.33%)	1	0/3 (0.00%)	0	0/34 (0.00%)	0	3/27 (11.11%)	3	1/4 (25.00%)	1	0/8 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	1/1 (100.00%)	1	7/88 (7.95%)	7
Toothache † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/34 (2.94%)	1	0/27 (0.00%)	0	1/4 (25.00%)	1	0/8 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/1 (0.00%)	0	2/88 (2.27%)	2
Vomiting † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	2/3 (66.67%)	2	4/34 (11.76%)	4	11/27 (40.74%)	11	0/4 (0.00%)	0	1/8 (12.50%)	1	2/3 (66.67%)	3	0/4 (0.00%)	0	1/1 (100.00%)	1	21/88 (23.86%)	22
General disorders
Asthenia † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	2/34 (5.88%)	2	2/27 (7.41%)	2	0/4 (0.00%)	0	0/8 (0.00%)	0	1/3 (33.33%)	1	0/4 (0.00%)	0	0/1 (0.00%)	0	5/88 (5.68%)	5
Chills † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	5/34 (14.71%)	6	4/27 (14.81%)	4	0/4 (0.00%)	0	0/8 (0.00%)	0	0/3 (0.00%)	0	1/4 (25.00%)	1	0/1 (0.00%)	0	10/88 (11.36%)	11
Fatigue † 1	0/1 (0.00%)	0	1/3 (33.33%)	1	1/3 (33.33%)	1	11/34 (32.35%)	12	9/27 (33.33%)	9	1/4 (25.00%)	1	5/8 (62.50%)	6	1/3 (33.33%)	1	1/4 (25.00%)	1	0/1 (0.00%)	0	30/88 (34.09%)	32
Malaise † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/34 (0.00%)	0	0/27 (0.00%)	0	0/4 (0.00%)	0	1/8 (12.50%)	1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/1 (0.00%)	0	1/88 (1.14%)	1
Oedema peripheral † 1	0/1 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	5/34 (14.71%)	5	4/27 (14.81%)	4	0/4 (0.00%)	0	1/8 (12.50%)	2	0/3 (0.00%)	0	1/4 (25.00%)	2	0/1 (0.00%)	0	12/88 (13.64%)	14
Pain † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/34 (2.94%)	1	2/27 (7.41%)	3	0/4 (0.00%)	0	1/8 (12.50%)	1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/1 (0.00%)	0	4/88 (4.55%)	5
Peripheral swelling † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	2/34 (5.88%)	2	3/27 (11.11%)	3	0/4 (0.00%)	0	0/8 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/1 (0.00%)	0	5/88 (5.68%)	5
Pyrexia † 1	0/1 (0.00%)	0	2/3 (66.67%)	2	0/3 (0.00%)	0	6/34 (17.65%)	8	2/27 (7.41%)	5	0/4 (0.00%)	0	1/8 (12.50%)	1	0/3 (0.00%)	0	1/4 (25.00%)	1	0/1 (0.00%)	0	12/88 (13.64%)	17
Hepatobiliary disorders
Hepatic steatosis † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/34 (0.00%)	0	0/27 (0.00%)	0	0/4 (0.00%)	0	1/8 (12.50%)	1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/1 (0.00%)	0	1/88 (1.14%)	1
Immune system disorders
Drug hypersensitivity † 1	0/1 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/34 (0.00%)	0	1/27 (3.70%)	1	0/4 (0.00%)	0	0/8 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/1 (0.00%)	0	2/88 (2.27%)	2
Seasonal allergy † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	2/34 (5.88%)	2	1/27 (3.70%)	1	0/4 (0.00%)	0	0/8 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/1 (0.00%)	0	3/88 (3.41%)	3
Infections and infestations
Bronchitis † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	2/34 (5.88%)	2	2/27 (7.41%)	2	0/4 (0.00%)	0	0/8 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/1 (0.00%)	0	4/88 (4.55%)	4
Candida infection † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/34 (2.94%)	2	3/27 (11.11%)	3	0/4 (0.00%)	0	0/8 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/1 (0.00%)	0	4/88 (4.55%)	5
Device related infection † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/34 (0.00%)	0	0/27 (0.00%)	0	0/4 (0.00%)	0	0/8 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	1/1 (100.00%)	1	1/88 (1.14%)	1
Herpes zoster † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	2/34 (5.88%)	2	1/27 (3.70%)	1	0/4 (0.00%)	0	1/8 (12.50%)	1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/1 (0.00%)	0	5/88 (5.68%)	5
Influenza † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/34 (0.00%)	0	0/27 (0.00%)	0	0/4 (0.00%)	0	0/8 (0.00%)	0	0/3 (0.00%)	0	1/4 (25.00%)	1	0/1 (0.00%)	0	1/88 (1.14%)	1
Nasopharyngitis † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/34 (0.00%)	0	2/27 (7.41%)	2	0/4 (0.00%)	0	0/8 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/1 (0.00%)	0	3/88 (3.41%)	3
Oral herpes † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/34 (0.00%)	0	0/27 (0.00%)	0	0/4 (0.00%)	0	2/8 (25.00%)	4	0/3 (0.00%)	0	0/4 (0.00%)	0	0/1 (0.00%)	0	2/88 (2.27%)	4
Pneumonia † 1	0/1 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	3/34 (8.82%)	3	3/27 (11.11%)	3	0/4 (0.00%)	0	0/8 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/1 (0.00%)	0	7/88 (7.95%)	7
Sinusitis † 1	0/1 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	1/34 (2.94%)	2	3/27 (11.11%)	3	0/4 (0.00%)	0	1/8 (12.50%)	1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/1 (0.00%)	0	6/88 (6.82%)	7
Upper respiratory tract infection † 1	0/1 (0.00%)	0	2/3 (66.67%)	2	1/3 (33.33%)	3	3/34 (8.82%)	4	4/27 (14.81%)	4	1/4 (25.00%)	1	3/8 (37.50%)	7	0/3 (0.00%)	0	0/4 (0.00%)	0	0/1 (0.00%)	0	14/88 (15.91%)	21
Urinary tract infection † 1	0/1 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	3/34 (8.82%)	3	2/27 (7.41%)	6	0/4 (0.00%)	0	0/8 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/1 (0.00%)	0	6/88 (6.82%)	10
Wound infection bacterial † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/34 (0.00%)	0	0/27 (0.00%)	0	0/4 (0.00%)	0	0/8 (0.00%)	0	0/3 (0.00%)	0	1/4 (25.00%)	1	0/1 (0.00%)	0	1/88 (1.14%)	1
Wound infection pseudomonas † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/34 (0.00%)	0	0/27 (0.00%)	0	0/4 (0.00%)	0	0/8 (0.00%)	0	0/3 (0.00%)	0	1/4 (25.00%)	1	0/1 (0.00%)	0	1/88 (1.14%)	1
Injury, poisoning and procedural complications
Contusion † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	2/34 (5.88%)	3	1/27 (3.70%)	1	0/4 (0.00%)	0	0/8 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/1 (0.00%)	0	3/88 (3.41%)	4
Fall † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	2/34 (5.88%)	3	2/27 (7.41%)	2	1/4 (25.00%)	1	0/8 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/1 (0.00%)	0	5/88 (5.68%)	6
Wound † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/34 (2.94%)	1	0/27 (0.00%)	0	0/4 (0.00%)	0	1/8 (12.50%)	1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/1 (0.00%)	0	2/88 (2.27%)	2
Investigations
Alanine aminotransferase increased † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	5/34 (14.71%)	5	2/27 (7.41%)	3	0/4 (0.00%)	0	1/8 (12.50%)	1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/1 (0.00%)	0	8/88 (9.09%)	9
Aspartate aminotransferase increased † 1	0/1 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	6/34 (17.65%)	11	3/27 (11.11%)	4	0/4 (0.00%)	0