IMBRUVICA® (ibrutinib) capsules
IMBRUVICA® (ibrutinib) capsules
Table 4: Treatment-Emergent* Decrease of Hemoglobin, Platelets, or Neutrophils
in Patients with CLL/SLL (N=51) in Study 1
Percent of Patients (N=51)
All Grades (%)
Grade 3 or 4 (%)
69
12
53
26
43
0
Platelets Decreased
Neutrophils Decreased
Hemoglobin Decreased
* Based on laboratory measurements per IWCLL criteria and adverse reactions.
Study 2: Adverse reactions and laboratory abnormalities described below in Tables 5 and 6 reflect
exposure to IMBRUVICA with a median duration of 8.6 months and exposure to ofatumumab with a
median of 5.3 months in Study 2 in patients with previously treated CLL/SLL.
Table 5: Adverse Reactions Reported in ≥ 10% of Patients and at Least 2% Greater
in the IMBRUVICA Treated Arm in Patients in Study 2
Body System
Adverse Reaction
Gastrointestinal disorders
Diarrhea
Nausea
Stomatitis*
Constipation
Vomiting
General disorders and
administration site
conditions
Pyrexia
Infections and infestations
Upper respiratory tract
infection
Pneumonia*
Sinusitis*
Urinary tract infection
Skin and subcutaneous
tissue disorders
Rash*
Petechiae
Bruising*
Musculoskeletal and
connective tissue disorders
Musculoskeletal Pain*
Arthralgia
Nervous system disorders
Headache
Dizziness
Injury, poisoning and
procedural complications
Contusion
Eye disorders
Vision blurred
IMBRUVICA
(N=195)
All Grades
Grade 3 or 4
(%)
(%)
Ofatumumab
(N=191)
All Grades
Grade 3 or 4
(%)
(%)
48
26
17
15
14
4
2
1
0
0
18
18
6
9
6
2
0
1
0
1
24
2
15
1
16
1
11
2
15
11
10
10
1
4
13
6
5
9
0
1
24
14
12
3
0
0
13
1
1
0
0
0
28
17
2
1
18
7
1
0
14
11
1
0
6
5
0
0
11
0
3
0
10
0
3
0
Subjects with multiple events for a given ADR term are counted once only for each ADR term.
The system organ class and individual ADR terms are sorted in descending frequency order in the
IMBRUVICA arm.
* Includes multiple ADR terms
Table 6: Treatment-Emergent* Decrease of Hemoglobin, Platelets, or Neutrophils in Study 2
IMBRUVICA
Ofatumumab
(N=195)
(N=191)
All Grades
Grade 3 or 4
All Grades
Grade 3 or 4
(%)
(%)
(%)
(%)
Neutrophils Decreased
51
23
57
26
Platelets Decreased
52
5
45
10
Hemoglobin Decreased
36
0
21
0
* Based on laboratory measurements per IWCLL criteria.
Study 3: Adverse reactions described below in Table 7 reflect exposure to IMBRUVICA with a
median duration of 17.4 months. The median exposure to chlorambucil was 7.1 months in Study 3.
Table 7: Adverse Reactions Reported in ≥ 10% of Patients and at Least 2% Greater
in the IMBRUVICA Treated Arm in Patients in Study 3
Body System
Adverse Reaction
Gastrointestinal disorders
Diarrhea
Stomatitis*
Musculoskeletal and
connective tissue disorders
Musculoskeletal pain*
Arthralgia
Muscle spasms
Eye Disorders
Dry eye
Lacrimation increased
Vision blurred
Visual acuity reduced
IMBRUVICA
(N=135)
All Grades
Grade 3 or 4
(%)
(%)
Chlorambucil
(N=132)
All Grades
Grade 3 or 4
(%)
(%)
42
14
4
1
17
4
0
1
36
16
11
4
1
0
20
7
5
0
1
0
17
13
13
11
0
0
0
0
5
6
8
2
0
0
0
0
Table 7: Adverse Reactions Reported in ≥ 10% of Patients and at Least 2% Greater
in the IMBRUVICA Treated Arm in Patients in Study 3 (continued)
IMBRUVICA
Chlorambucil
(N=135)
(N=132)
All Grades
Grade 3 or 4
All Grades
Grade 3 or 4
Body System
(%)
(%)
(%)
(%)
Adverse Reaction
Skin and subcutaneous
tissue disorders
Rash*
21
4
12
2
Bruising*
19
0
7
0
Infections and infestations
Skin infection*
15
2
3
1
Pneumonia*
14
8
7
4
Urinary tract infections
10
1
8
1
Respiratory, thoracic and
mediastinal disorders
Cough
22
0
15
0
General disorders and
administration site
conditions
Peripheral edema
19
1
9
0
Pyrexia
17
0
14
2
Vascular Disorders
Hypertension*
14
4
1
0
Nervous System Disorders
Headache
12
1
10
2
Subjects with multiple events for a given ADR term are counted once only for each ADR term.
The system organ class and individual ADR terms are sorted in descending frequency order in the
IMBRUVICA arm.
* Includes multiple ADR terms
Study 4: Adverse reactions described below in Table 8 reflect exposure to IMBRUVICA + BR with a
median duration of 14.7 months and exposure to placebo + BR with a median of 12.8 months in Study
4 in patients with previously treated CLL/SLL.
Table 8: Adverse Reactions Reported in at Least 10% of Patients and
at Least 2% Greater in the IMBRUVICA Arm in Patients in Study 4
Body System
Adverse Reaction
Blood and lymphatic
system disorders
Neutropenia*
Thrombocytopenia*
Skin and subcutaneous
tissue disorders
Rash*
Bruising*
Gastrointestinal disorders
Diarrhea
Abdominal Pain
Musculoskeletal and
connective tissue
disorders
Musculoskeletal pain*
Muscle spasms
General disorde