Trial Outcomes & Findings for Study of Ibrutinib in Combination With Rituximab in Previously Untreated Subjects With Follicular Lymphoma (NCT NCT01980654)
NCT ID: NCT01980654
Last Updated: 2019-04-16
Results Overview
Number of subjects achieving the best overall responses of CR or PR prior to the initiation of the next line of antineoplastic therapy as assessed by investigator per the Cheson et al, 2007 criteria. Target lesions are measured by CT, unless MRI is used as the assessment modality for lesions in anatomical locations not amenable to CT. CR is defined as the disappearance of all evidence of disease. PR is defined as \>=50% decrease in the sum of the product of the diameters of up to 6 largest dominant masses.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
80 participants
Primary outcome timeframe
Subjects in Arm 1 will have imaging assessments every 12 weeks for the first 8 assessments, then every 24 weeks. Subjects in Arm 2 will have imaging assessments starting at week 9, then every 12 weeks for 8 assessments, then every 24 weeks.
Results posted on
2019-04-16
Participant Flow
Participant milestones
| Measure |
Main Study Arm 1
Subjects enrolled into this arm will receive ibrutinib continuously until disease progression or unacceptable toxicity. In addition, subjects will receive rituximab once weekly for four doses for the first four weeks of study treatment.
Ibrutinib: All subjects will receive 560 mg of Ibrutinib orally.
rituximab: All subjects will receive rituximab 375 mg/m2 intravenously
|
Exploratory Study Arm 2
Subjects enrolled into this arm will receive ibrutinib continuously as a single agent for the first eight weeks, then ibrutinib concurrently with rituximab once weekly for four doses. After the rituximab treatment, subjects will receive ibrutinib continuously until disease progression or unacceptable toxicity.
Ibrutinib: All subjects will receive 560 mg of Ibrutinib orally.
rituximab: All subjects will receive rituximab 375 mg/m2 intravenously
|
|---|---|---|
|
Overall Study
STARTED
|
60
|
20
|
|
Overall Study
COMPLETED
|
60
|
20
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Study of Ibrutinib in Combination With Rituximab in Previously Untreated Subjects With Follicular Lymphoma
Baseline characteristics by cohort
| Measure |
Main Study Arm 1
n=60 Participants
Subjects enrolled into this arm will receive ibrutinib continuously until disease progression or unacceptable toxicity. In addition, subjects will receive rituximab once weekly for four doses for the first four weeks of study treatment.
Ibrutinib: All subjects will receive 560 mg of Ibrutinib orally.
rituximab: All subjects will receive rituximab 375 mg/m2 intravenously
|
Exploratory Study Arm 2
n=20 Participants
Subjects enrolled into this arm will receive ibrutinib continuously as a single agent for the first eight weeks, then ibrutinib concurrently with rituximab once weekly for four doses. After the rituximab treatment, subjects will receive ibrutinib continuously until disease progression or unacceptable toxicity.
Ibrutinib: All subjects will receive 560 mg of Ibrutinib orally.
rituximab: All subjects will receive rituximab 375 mg/m2 intravenously
|
Total
n=80 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
42 Participants
n=93 Participants
|
12 Participants
n=4 Participants
|
54 Participants
n=27 Participants
|
|
Age, Categorical
>=65 years
|
18 Participants
n=93 Participants
|
8 Participants
n=4 Participants
|
26 Participants
n=27 Participants
|
|
Age, Continuous
|
58.0 years
n=93 Participants
|
55.0 years
n=4 Participants
|
58.0 years
n=27 Participants
|
|
Sex: Female, Male
Female
|
32 Participants
n=93 Participants
|
8 Participants
n=4 Participants
|
40 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
28 Participants
n=93 Participants
|
12 Participants
n=4 Participants
|
40 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
3 Participants
n=93 Participants
|
3 Participants
n=4 Participants
|
6 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
57 Participants
n=93 Participants
|
17 Participants
n=4 Participants
|
74 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
2 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
3 Participants
n=27 Participants
|
|
Race (NIH/OMB)
White
|
56 Participants
n=93 Participants
|
18 Participants
n=4 Participants
|
74 Participants
n=27 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
|
Region of Enrollment
United States
|
60 participants
n=93 Participants
|
20 participants
n=4 Participants
|
80 participants
n=27 Participants
|
|
Baseline B-Symptoms
B-Symptoms present prior to first dose
|
4 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
4 Participants
n=27 Participants
|
|
Baseline B-Symptoms
B-Symptoms absent
|
56 Participants
n=93 Participants
|
20 Participants
n=4 Participants
|
76 Participants
n=27 Participants
|
|
Baseline Eastern Cooperative Oncology Group (ECOG) Score
Baseline ECOG Score = 0
|
47 Participants
n=93 Participants
|
12 Participants
n=4 Participants
|
59 Participants
n=27 Participants
|
|
Baseline Eastern Cooperative Oncology Group (ECOG) Score
Baseline ECOG Score = 1
|
13 Participants
n=93 Participants
|
8 Participants
n=4 Participants
|
21 Participants
n=27 Participants
|
PRIMARY outcome
Timeframe: Subjects in Arm 1 will have imaging assessments every 12 weeks for the first 8 assessments, then every 24 weeks. Subjects in Arm 2 will have imaging assessments starting at week 9, then every 12 weeks for 8 assessments, then every 24 weeks.Number of subjects achieving the best overall responses of CR or PR prior to the initiation of the next line of antineoplastic therapy as assessed by investigator per the Cheson et al, 2007 criteria. Target lesions are measured by CT, unless MRI is used as the assessment modality for lesions in anatomical locations not amenable to CT. CR is defined as the disappearance of all evidence of disease. PR is defined as \>=50% decrease in the sum of the product of the diameters of up to 6 largest dominant masses.
Outcome measures
| Measure |
Main Study Arm 1
n=60 Participants
Subjects enrolled into this arm will receive ibrutinib continuously until disease progression or unacceptable toxicity. In addition, subjects will receive rituximab once weekly for four doses for the first four weeks of study treatment.
Ibrutinib: All subjects will receive 560 mg of Ibrutinib orally.
rituximab: All subjects will receive rituximab 375 mg/m2 intravenously
|
Exploratory Study Arm 2
n=20 Participants
Subjects enrolled into this arm will receive ibrutinib continuously as a single agent for the first eight weeks, then ibrutinib concurrently with rituximab once weekly for four doses. After the rituximab treatment, subjects will receive ibrutinib continuously until disease progression or unacceptable toxicity.
Ibrutinib: All subjects will receive 560 mg of Ibrutinib orally.
rituximab: All subjects will receive rituximab 375 mg/m2 intravenously
|
|---|---|---|
|
Overall Response Rate (ORR): Proportion of Subjects Achieving the Best Overall Responses of Complete Response (CR) or Partial Response (PR)
|
51 Participants
|
15 Participants
|
SECONDARY outcome
Timeframe: Up to 45 monthsDOR is defined as the interval between the date of the first documented response (CR, PR) and the date of the first documented evidence of progressive disease (PD) or death. DOR will be analyzed for the subjects who achieve an overall response during the duration of study.
Outcome measures
| Measure |
Main Study Arm 1
n=51 Participants
Subjects enrolled into this arm will receive ibrutinib continuously until disease progression or unacceptable toxicity. In addition, subjects will receive rituximab once weekly for four doses for the first four weeks of study treatment.
Ibrutinib: All subjects will receive 560 mg of Ibrutinib orally.
rituximab: All subjects will receive rituximab 375 mg/m2 intravenously
|
Exploratory Study Arm 2
n=15 Participants
Subjects enrolled into this arm will receive ibrutinib continuously as a single agent for the first eight weeks, then ibrutinib concurrently with rituximab once weekly for four doses. After the rituximab treatment, subjects will receive ibrutinib continuously until disease progression or unacceptable toxicity.
Ibrutinib: All subjects will receive 560 mg of Ibrutinib orally.
rituximab: All subjects will receive rituximab 375 mg/m2 intravenously
|
|---|---|---|
|
Duration of Response (DOR)
|
NA months
Interval 30.1602 to
The median DOR was not reached so 95% Confidence Interval is not applicable.
|
NA months
Interval 24.6078 to
The median DOR was not reached so 95% Confidence Interval is not applicable.
|
SECONDARY outcome
Timeframe: Up to 45 monthsPFS is defined as the time interval between the date of the first dose and the date of the earliest occurrence of PD or death due to any cause, whichever occurs first. PD is characterized by any new lesion or increase by \>=50% of previously involved sites from nadir.
Outcome measures
| Measure |
Main Study Arm 1
n=60 Participants
Subjects enrolled into this arm will receive ibrutinib continuously until disease progression or unacceptable toxicity. In addition, subjects will receive rituximab once weekly for four doses for the first four weeks of study treatment.
Ibrutinib: All subjects will receive 560 mg of Ibrutinib orally.
rituximab: All subjects will receive rituximab 375 mg/m2 intravenously
|
Exploratory Study Arm 2
n=20 Participants
Subjects enrolled into this arm will receive ibrutinib continuously as a single agent for the first eight weeks, then ibrutinib concurrently with rituximab once weekly for four doses. After the rituximab treatment, subjects will receive ibrutinib continuously until disease progression or unacceptable toxicity.
Ibrutinib: All subjects will receive 560 mg of Ibrutinib orally.
rituximab: All subjects will receive rituximab 375 mg/m2 intravenously
|
|---|---|---|
|
Progression Free Survival (PFS)
|
41.922 months
Interval 31.6057 to 41.922
|
NA months
Interval 23.4908 to
The median PFS was not reached so 95% Confidence Interval is not applicable.
|
SECONDARY outcome
Timeframe: Up to 45 monthsSubjects will be followed for survival information up to three years after the last dose of study treatment, until new treatment or death, whichever occurs first. OS is defined as the duration of time from the date of the first dose to the date of death from any cause.
Outcome measures
| Measure |
Main Study Arm 1
n=60 Participants
Subjects enrolled into this arm will receive ibrutinib continuously until disease progression or unacceptable toxicity. In addition, subjects will receive rituximab once weekly for four doses for the first four weeks of study treatment.
Ibrutinib: All subjects will receive 560 mg of Ibrutinib orally.
rituximab: All subjects will receive rituximab 375 mg/m2 intravenously
|
Exploratory Study Arm 2
n=20 Participants
Subjects enrolled into this arm will receive ibrutinib continuously as a single agent for the first eight weeks, then ibrutinib concurrently with rituximab once weekly for four doses. After the rituximab treatment, subjects will receive ibrutinib continuously until disease progression or unacceptable toxicity.
Ibrutinib: All subjects will receive 560 mg of Ibrutinib orally.
rituximab: All subjects will receive rituximab 375 mg/m2 intravenously
|
|---|---|---|
|
Overall Survival (OS)
|
41.922 months
The 95% Confidence Interval is not applicable because the median OS was estimated based on time to event data. The 95% confidence limit cannot be estimated.
|
NA months
The median OS was not reached so 95% Confidence Interval is not applicable.
|
SECONDARY outcome
Timeframe: Up to 45 monthsFrequency, severity, and relatedness of treatment-emergent adverse events (AEs) Frequency of treatment-emergent AEs requiring discontinuation of study drug or dose reductions
Outcome measures
| Measure |
Main Study Arm 1
n=60 Participants
Subjects enrolled into this arm will receive ibrutinib continuously until disease progression or unacceptable toxicity. In addition, subjects will receive rituximab once weekly for four doses for the first four weeks of study treatment.
Ibrutinib: All subjects will receive 560 mg of Ibrutinib orally.
rituximab: All subjects will receive rituximab 375 mg/m2 intravenously
|
Exploratory Study Arm 2
n=20 Participants
Subjects enrolled into this arm will receive ibrutinib continuously as a single agent for the first eight weeks, then ibrutinib concurrently with rituximab once weekly for four doses. After the rituximab treatment, subjects will receive ibrutinib continuously until disease progression or unacceptable toxicity.
Ibrutinib: All subjects will receive 560 mg of Ibrutinib orally.
rituximab: All subjects will receive rituximab 375 mg/m2 intravenously
|
|---|---|---|
|
Number of Participants With Treatment-emergent Adverse Events
Subjects with any treatment-emergent AE
|
60 Participants
|
20 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events
Subjects with any treatment-emergent AE Grade >=3
|
39 Participants
|
14 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events
Subjects with any treatment-related AE
|
59 Participants
|
20 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events
Subjects with any treatment-related AE Grade >=3
|
29 Participants
|
14 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events
Subjects with any Ibrutinib-related AE
|
57 Participants
|
20 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events
Subjects with any Ibrutinib-related AE Grade >=3
|
29 Participants
|
14 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events
Subjects with any Rituximab-related AE
|
50 Participants
|
17 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events
Subjects with any Rituximab-related AE Grade >=3
|
11 Participants
|
7 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events
TEAE leading to ibrutinib dose reduction
|
9 Participants
|
5 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events
TEAE Grade >=3 leading to Ibrutinib dose reduction
|
6 Participants
|
4 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events
TEAE leading to witholding Rituximab
|
1 Participants
|
1 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events
TEAE Grade >=3 leading to witholding Rituximab
|
1 Participants
|
1 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events
TEAE leading to discontinuation of Ibrutinib
|
14 Participants
|
2 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events
TEAE Grade >=3 leading to discontinuation of Ibrut
|
11 Participants
|
1 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events
TEAE leading to discontinuation of Rituximab
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events
TEAE Grade >=3 leading to discontinuation of Ritux
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events
Subjects with any TE Serious Adverse Event (SAE)
|
14 Participants
|
6 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events
Subjects with any TE SAE Grade >=3
|
13 Participants
|
5 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events
Ibrutinib-related SAEs
|
6 Participants
|
4 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events
Ibrutinib-related SAEs Grade >=3
|
6 Participants
|
4 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events
Rituximab-related SAEs
|
2 Participants
|
2 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events
Rituximab-related SAEs Grade >=3
|
2 Participants
|
2 Participants
|
Adverse Events
Main Study Arm 1
Serious events: 14 serious events
Other events: 60 other events
Deaths: 4 deaths
Exploratory Study Arm 2
Serious events: 6 serious events
Other events: 20 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Main Study Arm 1
n=60 participants at risk
Subjects enrolled into this arm will receive ibrutinib continuously until disease progression or unacceptable toxicity. In addition, subjects will receive rituximab once weekly for four doses for the first four weeks of study treatment.
Ibrutinib: All subjects will receive 560 mg of Ibrutinib orally.
rituximab: All subjects will receive rituximab 375 mg/m2 intravenously
|
Exploratory Study Arm 2
n=20 participants at risk
Subjects enrolled into this arm will receive ibrutinib continuously as a single agent for the first eight weeks, then ibrutinib concurrently with rituximab once weekly for four doses. After the rituximab treatment, subjects will receive ibrutinib continuously until disease progression or unacceptable toxicity.
Ibrutinib: All subjects will receive 560 mg of Ibrutinib orally.
rituximab: All subjects will receive rituximab 375 mg/m2 intravenously
|
|---|---|---|
|
Blood and lymphatic system disorders
Eosinophilia
|
1.7%
1/60 • Number of events 1 • 3 years, 9 months
|
0.00%
0/20 • 3 years, 9 months
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
1.7%
1/60 • Number of events 1 • 3 years, 9 months
|
0.00%
0/20 • 3 years, 9 months
|
|
Cardiac disorders
Atrial fibrillation
|
1.7%
1/60 • Number of events 1 • 3 years, 9 months
|
0.00%
0/20 • 3 years, 9 months
|
|
Cardiac disorders
Cardiac failure
|
1.7%
1/60 • Number of events 1 • 3 years, 9 months
|
0.00%
0/20 • 3 years, 9 months
|
|
Cardiac disorders
Pericardial effusion
|
1.7%
1/60 • Number of events 1 • 3 years, 9 months
|
0.00%
0/20 • 3 years, 9 months
|
|
Cardiac disorders
Ventricular tachycardia
|
1.7%
1/60 • Number of events 2 • 3 years, 9 months
|
0.00%
0/20 • 3 years, 9 months
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/60 • 3 years, 9 months
|
10.0%
2/20 • Number of events 2 • 3 years, 9 months
|
|
Gastrointestinal disorders
Abdominal pain
|
1.7%
1/60 • Number of events 1 • 3 years, 9 months
|
0.00%
0/20 • 3 years, 9 months
|
|
Gastrointestinal disorders
Oesophageal achalasia
|
1.7%
1/60 • Number of events 2 • 3 years, 9 months
|
0.00%
0/20 • 3 years, 9 months
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
0.00%
0/60 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
General disorders
Pyrexia
|
3.3%
2/60 • Number of events 2 • 3 years, 9 months
|
15.0%
3/20 • Number of events 3 • 3 years, 9 months
|
|
General disorders
Death
|
3.3%
2/60 • Number of events 2 • 3 years, 9 months
|
0.00%
0/20 • 3 years, 9 months
|
|
General disorders
Chest pain
|
1.7%
1/60 • Number of events 1 • 3 years, 9 months
|
0.00%
0/20 • 3 years, 9 months
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/60 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Infections and infestations
Pneumonia
|
3.3%
2/60 • Number of events 3 • 3 years, 9 months
|
10.0%
2/20 • Number of events 2 • 3 years, 9 months
|
|
Infections and infestations
Urinary tract infection
|
1.7%
1/60 • Number of events 2 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Infections and infestations
Bronchitis
|
1.7%
1/60 • Number of events 1 • 3 years, 9 months
|
0.00%
0/20 • 3 years, 9 months
|
|
Infections and infestations
Clostridium difficile colitis
|
0.00%
0/60 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Infections and infestations
Influenza
|
0.00%
0/60 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Infections and infestations
Sepsis
|
1.7%
1/60 • Number of events 1 • 3 years, 9 months
|
0.00%
0/20 • 3 years, 9 months
|
|
Metabolism and nutrition disorders
Dehydration
|
1.7%
1/60 • Number of events 1 • 3 years, 9 months
|
0.00%
0/20 • 3 years, 9 months
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
1.7%
1/60 • Number of events 1 • 3 years, 9 months
|
0.00%
0/20 • 3 years, 9 months
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
1.7%
1/60 • Number of events 1 • 3 years, 9 months
|
0.00%
0/20 • 3 years, 9 months
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
1.7%
1/60 • Number of events 1 • 3 years, 9 months
|
0.00%
0/20 • 3 years, 9 months
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
1.7%
1/60 • Number of events 1 • 3 years, 9 months
|
0.00%
0/20 • 3 years, 9 months
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/60 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Musculoskeletal and connective tissue disorders
Tendonitis
|
0.00%
0/60 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Fallopian tube cancer
|
1.7%
1/60 • Number of events 1 • 3 years, 9 months
|
0.00%
0/20 • 3 years, 9 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung adenocarcinoma
|
0.00%
0/60 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Nervous system disorders
Cerebral artery stenosis
|
1.7%
1/60 • Number of events 1 • 3 years, 9 months
|
0.00%
0/20 • 3 years, 9 months
|
|
Nervous system disorders
Headache
|
1.7%
1/60 • Number of events 1 • 3 years, 9 months
|
0.00%
0/20 • 3 years, 9 months
|
|
Nervous system disorders
Transient ischaemic attack
|
1.7%
1/60 • Number of events 2 • 3 years, 9 months
|
0.00%
0/20 • 3 years, 9 months
|
|
Nervous system disorders
Vascular encephalopathy
|
1.7%
1/60 • Number of events 1 • 3 years, 9 months
|
0.00%
0/20 • 3 years, 9 months
|
|
Renal and urinary disorders
Acute kidney injury
|
0.00%
0/60 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
1.7%
1/60 • Number of events 2 • 3 years, 9 months
|
0.00%
0/20 • 3 years, 9 months
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/60 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
1.7%
1/60 • Number of events 1 • 3 years, 9 months
|
0.00%
0/20 • 3 years, 9 months
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
1.7%
1/60 • Number of events 1 • 3 years, 9 months
|
0.00%
0/20 • 3 years, 9 months
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema
|
1.7%
1/60 • Number of events 1 • 3 years, 9 months
|
0.00%
0/20 • 3 years, 9 months
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
1.7%
1/60 • Number of events 1 • 3 years, 9 months
|
0.00%
0/20 • 3 years, 9 months
|
Other adverse events
| Measure |
Main Study Arm 1
n=60 participants at risk
Subjects enrolled into this arm will receive ibrutinib continuously until disease progression or unacceptable toxicity. In addition, subjects will receive rituximab once weekly for four doses for the first four weeks of study treatment.
Ibrutinib: All subjects will receive 560 mg of Ibrutinib orally.
rituximab: All subjects will receive rituximab 375 mg/m2 intravenously
|
Exploratory Study Arm 2
n=20 participants at risk
Subjects enrolled into this arm will receive ibrutinib continuously as a single agent for the first eight weeks, then ibrutinib concurrently with rituximab once weekly for four doses. After the rituximab treatment, subjects will receive ibrutinib continuously until disease progression or unacceptable toxicity.
Ibrutinib: All subjects will receive 560 mg of Ibrutinib orally.
rituximab: All subjects will receive rituximab 375 mg/m2 intravenously
|
|---|---|---|
|
Blood and lymphatic system disorders
Neutropenia
|
15.0%
9/60 • Number of events 11 • 3 years, 9 months
|
15.0%
3/20 • Number of events 3 • 3 years, 9 months
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
13.3%
8/60 • Number of events 13 • 3 years, 9 months
|
10.0%
2/20 • Number of events 2 • 3 years, 9 months
|
|
Blood and lymphatic system disorders
Increased tendency to bruise
|
6.7%
4/60 • Number of events 4 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Blood and lymphatic system disorders
Anaemia
|
5.0%
3/60 • Number of events 4 • 3 years, 9 months
|
0.00%
0/20 • 3 years, 9 months
|
|
Cardiac disorders
Atrial fibrillation
|
8.3%
5/60 • Number of events 5 • 3 years, 9 months
|
0.00%
0/20 • 3 years, 9 months
|
|
Cardiac disorders
Cardiac flutter
|
1.7%
1/60 • Number of events 1 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Cardiac disorders
Sinus bradycardia
|
0.00%
0/60 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Cardiac disorders
Tachycardia
|
0.00%
0/60 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Congenital, familial and genetic disorders
Gilbert's syndrome
|
0.00%
0/60 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Ear and labyrinth disorders
Ear pain
|
1.7%
1/60 • Number of events 1 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Ear and labyrinth disorders
Tinnitus
|
0.00%
0/60 • 3 years, 9 months
|
10.0%
2/20 • Number of events 2 • 3 years, 9 months
|
|
Ear and labyrinth disorders
Conductive deafness
|
0.00%
0/60 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Ear and labyrinth disorders
Ear haemorrhage
|
0.00%
0/60 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Endocrine disorders
Hypothyroidism
|
3.3%
2/60 • Number of events 2 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Eye disorders
Dry eye
|
25.0%
15/60 • Number of events 24 • 3 years, 9 months
|
20.0%
4/20 • Number of events 7 • 3 years, 9 months
|
|
Eye disorders
Vision blurred
|
13.3%
8/60 • Number of events 13 • 3 years, 9 months
|
30.0%
6/20 • Number of events 10 • 3 years, 9 months
|
|
Eye disorders
Lacrimation increased
|
5.0%
3/60 • Number of events 4 • 3 years, 9 months
|
30.0%
6/20 • Number of events 8 • 3 years, 9 months
|
|
Eye disorders
Eye irritation
|
6.7%
4/60 • Number of events 4 • 3 years, 9 months
|
5.0%
1/20 • Number of events 2 • 3 years, 9 months
|
|
Eye disorders
Eye pruritus
|
1.7%
1/60 • Number of events 1 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Eye disorders
Diplopia
|
0.00%
0/60 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Gastrointestinal disorders
Diarrhoea
|
56.7%
34/60 • Number of events 78 • 3 years, 9 months
|
60.0%
12/20 • Number of events 30 • 3 years, 9 months
|
|
Gastrointestinal disorders
Nausea
|
48.3%
29/60 • Number of events 68 • 3 years, 9 months
|
50.0%
10/20 • Number of events 22 • 3 years, 9 months
|
|
Gastrointestinal disorders
Constipation
|
26.7%
16/60 • Number of events 32 • 3 years, 9 months
|
30.0%
6/20 • Number of events 12 • 3 years, 9 months
|
|
Gastrointestinal disorders
Vomiting
|
26.7%
16/60 • Number of events 30 • 3 years, 9 months
|
30.0%
6/20 • Number of events 7 • 3 years, 9 months
|
|
Gastrointestinal disorders
Stomatitis
|
16.7%
10/60 • Number of events 33 • 3 years, 9 months
|
55.0%
11/20 • Number of events 35 • 3 years, 9 months
|
|
Gastrointestinal disorders
Abdominal pain
|
20.0%
12/60 • Number of events 13 • 3 years, 9 months
|
20.0%
4/20 • Number of events 4 • 3 years, 9 months
|
|
Gastrointestinal disorders
Dyspepsia
|
13.3%
8/60 • Number of events 10 • 3 years, 9 months
|
15.0%
3/20 • Number of events 3 • 3 years, 9 months
|
|
Gastrointestinal disorders
Dry mouth
|
6.7%
4/60 • Number of events 4 • 3 years, 9 months
|
20.0%
4/20 • Number of events 4 • 3 years, 9 months
|
|
Gastrointestinal disorders
Flatulence
|
8.3%
5/60 • Number of events 5 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
8.3%
5/60 • Number of events 5 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Gastrointestinal disorders
Haemorrhoids
|
3.3%
2/60 • Number of events 3 • 3 years, 9 months
|
15.0%
3/20 • Number of events 3 • 3 years, 9 months
|
|
Gastrointestinal disorders
Abdominal pain upper
|
6.7%
4/60 • Number of events 6 • 3 years, 9 months
|
0.00%
0/20 • 3 years, 9 months
|
|
Gastrointestinal disorders
Gingival bleeding
|
6.7%
4/60 • Number of events 6 • 3 years, 9 months
|
0.00%
0/20 • 3 years, 9 months
|
|
Gastrointestinal disorders
Abdominal discomfort
|
3.3%
2/60 • Number of events 2 • 3 years, 9 months
|
5.0%
1/20 • Number of events 11 • 3 years, 9 months
|
|
Gastrointestinal disorders
Abdominal distension
|
3.3%
2/60 • Number of events 2 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Gastrointestinal disorders
Haematochezia
|
3.3%
2/60 • Number of events 2 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Gastrointestinal disorders
Chapped lips
|
1.7%
1/60 • Number of events 1 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Gastrointestinal disorders
Barrett's oesophagus
|
0.00%
0/60 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Gastrointestinal disorders
Haemorrhoidal haemorrhage
|
0.00%
0/60 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Gastrointestinal disorders
Hypoaesthesia oral
|
0.00%
0/60 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Gastrointestinal disorders
Lip discolouration
|
0.00%
0/60 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Gastrointestinal disorders
Lip ulceration
|
0.00%
0/60 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Gastrointestinal disorders
Toothache
|
0.00%
0/60 • 3 years, 9 months
|
5.0%
1/20 • Number of events 5 • 3 years, 9 months
|
|
General disorders
Fatigue
|
68.3%
41/60 • Number of events 108 • 3 years, 9 months
|
75.0%
15/20 • Number of events 30 • 3 years, 9 months
|
|
General disorders
Pyrexia
|
25.0%
15/60 • Number of events 20 • 3 years, 9 months
|
20.0%
4/20 • Number of events 5 • 3 years, 9 months
|
|
General disorders
Chills
|
16.7%
10/60 • Number of events 12 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
General disorders
Oedema peripheral
|
15.0%
9/60 • Number of events 13 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
General disorders
Peripheral swelling
|
8.3%
5/60 • Number of events 7 • 3 years, 9 months
|
20.0%
4/20 • Number of events 9 • 3 years, 9 months
|
|
General disorders
Chest pain
|
6.7%
4/60 • Number of events 4 • 3 years, 9 months
|
10.0%
2/20 • Number of events 2 • 3 years, 9 months
|
|
General disorders
Pain
|
6.7%
4/60 • Number of events 4 • 3 years, 9 months
|
10.0%
2/20 • Number of events 2 • 3 years, 9 months
|
|
General disorders
Chest discomfort
|
6.7%
4/60 • Number of events 4 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
General disorders
Swelling
|
3.3%
2/60 • Number of events 3 • 3 years, 9 months
|
10.0%
2/20 • Number of events 4 • 3 years, 9 months
|
|
General disorders
Malaise
|
5.0%
3/60 • Number of events 4 • 3 years, 9 months
|
0.00%
0/20 • 3 years, 9 months
|
|
General disorders
Unevaluable event
|
0.00%
0/60 • 3 years, 9 months
|
10.0%
2/20 • Number of events 2 • 3 years, 9 months
|
|
General disorders
Feeling hot
|
0.00%
0/60 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
General disorders
Gait disturbance
|
0.00%
0/60 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
General disorders
Generalised oedema
|
0.00%
0/60 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
5.0%
3/60 • Number of events 5 • 3 years, 9 months
|
10.0%
2/20 • Number of events 2 • 3 years, 9 months
|
|
Hepatobiliary disorders
Hepatic function abnormal
|
3.3%
2/60 • Number of events 4 • 3 years, 9 months
|
5.0%
1/20 • Number of events 7 • 3 years, 9 months
|
|
Immune system disorders
Drug hypersensitivity
|
5.0%
3/60 • Number of events 3 • 3 years, 9 months
|
0.00%
0/20 • 3 years, 9 months
|
|
Infections and infestations
Upper respiratory tract infection
|
21.7%
13/60 • Number of events 16 • 3 years, 9 months
|
35.0%
7/20 • Number of events 12 • 3 years, 9 months
|
|
Infections and infestations
Urinary tract infection
|
21.7%
13/60 • Number of events 28 • 3 years, 9 months
|
25.0%
5/20 • Number of events 7 • 3 years, 9 months
|
|
Infections and infestations
Sinusitis
|
11.7%
7/60 • Number of events 8 • 3 years, 9 months
|
25.0%
5/20 • Number of events 10 • 3 years, 9 months
|
|
Infections and infestations
Conjunctivitis
|
6.7%
4/60 • Number of events 4 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Infections and infestations
Folliculitis
|
3.3%
2/60 • Number of events 3 • 3 years, 9 months
|
10.0%
2/20 • Number of events 2 • 3 years, 9 months
|
|
Infections and infestations
Herpes zoster
|
6.7%
4/60 • Number of events 5 • 3 years, 9 months
|
0.00%
0/20 • 3 years, 9 months
|
|
Infections and infestations
Onychomycosis
|
3.3%
2/60 • Number of events 2 • 3 years, 9 months
|
10.0%
2/20 • Number of events 2 • 3 years, 9 months
|
|
Infections and infestations
Tooth infection
|
5.0%
3/60 • Number of events 3 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Infections and infestations
Cystitis
|
0.00%
0/60 • 3 years, 9 months
|
15.0%
3/20 • Number of events 5 • 3 years, 9 months
|
|
Infections and infestations
Influenza
|
3.3%
2/60 • Number of events 2 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Infections and infestations
Oral herpes
|
3.3%
2/60 • Number of events 2 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Infections and infestations
Pneumonia
|
5.0%
3/60 • Number of events 5 • 3 years, 9 months
|
0.00%
0/20 • 3 years, 9 months
|
|
Infections and infestations
Viral upper respiratory tract infection
|
5.0%
3/60 • Number of events 3 • 3 years, 9 months
|
0.00%
0/20 • 3 years, 9 months
|
|
Infections and infestations
Clostridium difficile infection
|
0.00%
0/60 • 3 years, 9 months
|
10.0%
2/20 • Number of events 2 • 3 years, 9 months
|
|
Infections and infestations
Dacryocanaliculitis
|
1.7%
1/60 • Number of events 1 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Infections and infestations
Ear infection
|
1.7%
1/60 • Number of events 1 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Infections and infestations
Localised infection
|
1.7%
1/60 • Number of events 1 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Infections and infestations
Pharyngitis
|
1.7%
1/60 • Number of events 1 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Infections and infestations
Bacterial vaginosis
|
0.00%
0/60 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Infections and infestations
Cellulitis
|
0.00%
0/60 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Infections and infestations
Eye infection
|
0.00%
0/60 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Infections and infestations
Prostate infection
|
0.00%
0/60 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Infections and infestations
Bronchitis
|
11.7%
7/60 • Number of events 9 • 3 years, 9 months
|
0.00%
0/20 • 3 years, 9 months
|
|
Infections and infestations
Respiratory tract infection viral
|
0.00%
0/60 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Infections and infestations
Rhinitis
|
0.00%
0/60 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Infections and infestations
Streptococcal infection
|
0.00%
0/60 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Infections and infestations
Tinea cruris
|
0.00%
0/60 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Infections and infestations
Tinea pedis
|
0.00%
0/60 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Infections and infestations
Vulvovaginal mycotic infection
|
0.00%
0/60 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Infections and infestations
Wound infection staphylococcal
|
0.00%
0/60 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Injury, poisoning and procedural complications
Infusion related reaction
|
23.3%
14/60 • Number of events 16 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Injury, poisoning and procedural complications
Contusion
|
8.3%
5/60 • Number of events 8 • 3 years, 9 months
|
10.0%
2/20 • Number of events 2 • 3 years, 9 months
|
|
Injury, poisoning and procedural complications
Fall
|
5.0%
3/60 • Number of events 3 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Injury, poisoning and procedural complications
Laceration
|
5.0%
3/60 • Number of events 4 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Injury, poisoning and procedural complications
Skin abrasion
|
5.0%
3/60 • Number of events 3 • 3 years, 9 months
|
0.00%
0/20 • 3 years, 9 months
|
|
Injury, poisoning and procedural complications
Arthropod sting
|
0.00%
0/60 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Injury, poisoning and procedural complications
Road traffic accident
|
0.00%
0/60 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Investigations
Aspartate aminotransferase increased
|
6.7%
4/60 • Number of events 4 • 3 years, 9 months
|
5.0%
1/20 • Number of events 2 • 3 years, 9 months
|
|
Investigations
Alanine aminotransferase increased
|
5.0%
3/60 • Number of events 4 • 3 years, 9 months
|
5.0%
1/20 • Number of events 3 • 3 years, 9 months
|
|
Investigations
Blood bilirubin increased
|
1.7%
1/60 • Number of events 1 • 3 years, 9 months
|
5.0%
1/20 • Number of events 2 • 3 years, 9 months
|
|
Investigations
Blood pressure increased
|
0.00%
0/60 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Investigations
Low density lipoprotein increased
|
0.00%
0/60 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Investigations
White blood cell count increased
|
0.00%
0/60 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
10.0%
6/60 • Number of events 7 • 3 years, 9 months
|
20.0%
4/20 • Number of events 4 • 3 years, 9 months
|
|
Metabolism and nutrition disorders
Decreased appetite
|
11.7%
7/60 • Number of events 9 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Metabolism and nutrition disorders
Hyperuricaemia
|
8.3%
5/60 • Number of events 5 • 3 years, 9 months
|
0.00%
0/20 • 3 years, 9 months
|
|
Metabolism and nutrition disorders
Dehydration
|
5.0%
3/60 • Number of events 3 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
3.3%
2/60 • Number of events 2 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
5.0%
3/60 • Number of events 3 • 3 years, 9 months
|
0.00%
0/20 • 3 years, 9 months
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
5.0%
3/60 • Number of events 3 • 3 years, 9 months
|
0.00%
0/20 • 3 years, 9 months
|
|
Metabolism and nutrition disorders
Abnormal loss of weight
|
0.00%
0/60 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Metabolism and nutrition disorders
Hypernatraemia
|
0.00%
0/60 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Metabolism and nutrition disorders
Polydipsia
|
0.00%
0/60 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
33.3%
20/60 • Number of events 38 • 3 years, 9 months
|
45.0%
9/20 • Number of events 20 • 3 years, 9 months
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
33.3%
20/60 • Number of events 27 • 3 years, 9 months
|
15.0%
3/20 • Number of events 5 • 3 years, 9 months
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
26.7%
16/60 • Number of events 22 • 3 years, 9 months
|
25.0%
5/20 • Number of events 8 • 3 years, 9 months
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
13.3%
8/60 • Number of events 13 • 3 years, 9 months
|
10.0%
2/20 • Number of events 2 • 3 years, 9 months
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
11.7%
7/60 • Number of events 10 • 3 years, 9 months
|
10.0%
2/20 • Number of events 3 • 3 years, 9 months
|
|
Musculoskeletal and connective tissue disorders
Joint swelling
|
6.7%
4/60 • Number of events 8 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
5.0%
3/60 • Number of events 5 • 3 years, 9 months
|
0.00%
0/20 • 3 years, 9 months
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
1.7%
1/60 • Number of events 1 • 3 years, 9 months
|
10.0%
2/20 • Number of events 2 • 3 years, 9 months
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
1.7%
1/60 • Number of events 1 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal stiffness
|
1.7%
1/60 • Number of events 1 • 3 years, 9 months
|
5.0%
1/20 • Number of events 2 • 3 years, 9 months
|
|
Musculoskeletal and connective tissue disorders
Tendonitis
|
1.7%
1/60 • Number of events 1 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
0.00%
0/60 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Seborrhoeic keratosis
|
3.3%
2/60 • Number of events 2 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Nervous system disorders
Headache
|
31.7%
19/60 • Number of events 27 • 3 years, 9 months
|
25.0%
5/20 • Number of events 10 • 3 years, 9 months
|
|
Nervous system disorders
Dizziness
|
21.7%
13/60 • Number of events 18 • 3 years, 9 months
|
45.0%
9/20 • Number of events 19 • 3 years, 9 months
|
|
Nervous system disorders
Paraesthesia
|
15.0%
9/60 • Number of events 20 • 3 years, 9 months
|
40.0%
8/20 • Number of events 19 • 3 years, 9 months
|
|
Nervous system disorders
Memory impairment
|
15.0%
9/60 • Number of events 13 • 3 years, 9 months
|
25.0%
5/20 • Number of events 9 • 3 years, 9 months
|
|
Nervous system disorders
Hypoaesthesia
|
5.0%
3/60 • Number of events 3 • 3 years, 9 months
|
5.0%
1/20 • Number of events 2 • 3 years, 9 months
|
|
Nervous system disorders
Cognitive disorder
|
5.0%
3/60 • Number of events 3 • 3 years, 9 months
|
0.00%
0/20 • 3 years, 9 months
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
5.0%
3/60 • Number of events 4 • 3 years, 9 months
|
0.00%
0/20 • 3 years, 9 months
|
|
Nervous system disorders
Tremor
|
3.3%
2/60 • Number of events 2 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Nervous system disorders
Migraine
|
1.7%
1/60 • Number of events 1 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Nervous system disorders
Restless legs syndrome
|
1.7%
1/60 • Number of events 1 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Nervous system disorders
Dyskinesia
|
0.00%
0/60 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Nervous system disorders
Syncope
|
0.00%
0/60 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Psychiatric disorders
Anxiety
|
15.0%
9/60 • Number of events 9 • 3 years, 9 months
|
0.00%
0/20 • 3 years, 9 months
|
|
Psychiatric disorders
Insomnia
|
13.3%
8/60 • Number of events 10 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Psychiatric disorders
Depression
|
5.0%
3/60 • Number of events 3 • 3 years, 9 months
|
0.00%
0/20 • 3 years, 9 months
|
|
Renal and urinary disorders
Haematuria
|
6.7%
4/60 • Number of events 4 • 3 years, 9 months
|
0.00%
0/20 • 3 years, 9 months
|
|
Renal and urinary disorders
Pollakiuria
|
3.3%
2/60 • Number of events 2 • 3 years, 9 months
|
10.0%
2/20 • Number of events 2 • 3 years, 9 months
|
|
Renal and urinary disorders
Dysuria
|
1.7%
1/60 • Number of events 2 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Renal and urinary disorders
Hydronephrosis
|
0.00%
0/60 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Renal and urinary disorders
Nocturia
|
0.00%
0/60 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Renal and urinary disorders
Polyuria
|
0.00%
0/60 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Reproductive system and breast disorders
Vulvovaginal dryness
|
0.00%
0/60 • 3 years, 9 months
|
10.0%
2/20 • Number of events 2 • 3 years, 9 months
|
|
Reproductive system and breast disorders
Benign prostatic hyperplasia
|
0.00%
0/60 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Reproductive system and breast disorders
Dyspareunia
|
0.00%
0/60 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Reproductive system and breast disorders
Vulvovaginal erythema
|
0.00%
0/60 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Reproductive system and breast disorders
Vulvovaginal pain
|
0.00%
0/60 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
33.3%
20/60 • Number of events 26 • 3 years, 9 months
|
30.0%
6/20 • Number of events 9 • 3 years, 9 months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
20.0%
12/60 • Number of events 23 • 3 years, 9 months
|
20.0%
4/20 • Number of events 8 • 3 years, 9 months
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
16.7%
10/60 • Number of events 11 • 3 years, 9 months
|
25.0%
5/20 • Number of events 6 • 3 years, 9 months
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
8.3%
5/60 • Number of events 9 • 3 years, 9 months
|
10.0%
2/20 • Number of events 4 • 3 years, 9 months
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
10.0%
6/60 • Number of events 9 • 3 years, 9 months
|
0.00%
0/20 • 3 years, 9 months
|
|
Respiratory, thoracic and mediastinal disorders
Sinus congestion
|
5.0%
3/60 • Number of events 4 • 3 years, 9 months
|
10.0%
2/20 • Number of events 2 • 3 years, 9 months
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
3.3%
2/60 • Number of events 2 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Respiratory, thoracic and mediastinal disorders
Throat irritation
|
0.00%
0/60 • 3 years, 9 months
|
10.0%
2/20 • Number of events 2 • 3 years, 9 months
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
0.00%
0/60 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Respiratory, thoracic and mediastinal disorders
Nasal discomfort
|
0.00%
0/60 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngeal oedema
|
0.00%
0/60 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
30.0%
18/60 • Number of events 32 • 3 years, 9 months
|
40.0%
8/20 • Number of events 10 • 3 years, 9 months
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
11.7%
7/60 • Number of events 7 • 3 years, 9 months
|
15.0%
3/20 • Number of events 3 • 3 years, 9 months
|
|
Skin and subcutaneous tissue disorders
Onychoclasis
|
13.3%
8/60 • Number of events 9 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
11.7%
7/60 • Number of events 12 • 3 years, 9 months
|
10.0%
2/20 • Number of events 2 • 3 years, 9 months
|
|
Skin and subcutaneous tissue disorders
Rash erythematous
|
11.7%
7/60 • Number of events 9 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Skin and subcutaneous tissue disorders
Petechiae
|
10.0%
6/60 • Number of events 13 • 3 years, 9 months
|
0.00%
0/20 • 3 years, 9 months
|
|
Skin and subcutaneous tissue disorders
Ecchymosis
|
6.7%
4/60 • Number of events 6 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Skin and subcutaneous tissue disorders
Nail disorder
|
5.0%
3/60 • Number of events 3 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Skin and subcutaneous tissue disorders
Night sweats
|
6.7%
4/60 • Number of events 4 • 3 years, 9 months
|
0.00%
0/20 • 3 years, 9 months
|
|
Skin and subcutaneous tissue disorders
Rash
|
3.3%
2/60 • Number of events 3 • 3 years, 9 months
|
10.0%
2/20 • Number of events 3 • 3 years, 9 months
|
|
Skin and subcutaneous tissue disorders
Skin fissures
|
3.3%
2/60 • Number of events 2 • 3 years, 9 months
|
10.0%
2/20 • Number of events 3 • 3 years, 9 months
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
5.0%
3/60 • Number of events 3 • 3 years, 9 months
|
0.00%
0/20 • 3 years, 9 months
|
|
Skin and subcutaneous tissue disorders
Eczema
|
3.3%
2/60 • Number of events 3 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Skin and subcutaneous tissue disorders
Erythema
|
3.3%
2/60 • Number of events 3 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Skin and subcutaneous tissue disorders
Ingrowing nail
|
3.3%
2/60 • Number of events 2 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Skin and subcutaneous tissue disorders
Rash macular
|
3.3%
2/60 • Number of events 3 • 3 years, 9 months
|
5.0%
1/20 • Number of events 2 • 3 years, 9 months
|
|
Skin and subcutaneous tissue disorders
Acne
|
1.7%
1/60 • Number of events 1 • 3 years, 9 months
|
5.0%
1/20 • Number of events 2 • 3 years, 9 months
|
|
Skin and subcutaneous tissue disorders
Actinic keratosis
|
1.7%
1/60 • Number of events 1 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Skin and subcutaneous tissue disorders
Dermatitis acneiform
|
1.7%
1/60 • Number of events 1 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Skin and subcutaneous tissue disorders
Rosacea
|
1.7%
1/60 • Number of events 1 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Skin and subcutaneous tissue disorders
Skin hyperpigmentation
|
1.7%
1/60 • Number of events 1 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Skin and subcutaneous tissue disorders
Dermatitis allergic
|
0.00%
0/60 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Skin and subcutaneous tissue disorders
Eczema nummular
|
0.00%
0/60 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Skin and subcutaneous tissue disorders
Exfoliative rash
|
0.00%
0/60 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Skin and subcutaneous tissue disorders
Koilonychia
|
0.00%
0/60 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Skin and subcutaneous tissue disorders
Nail discolouration
|
0.00%
0/60 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Skin and subcutaneous tissue disorders
Pyoderma gangrenosum
|
0.00%
0/60 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Skin and subcutaneous tissue disorders
Scab
|
0.00%
0/60 • 3 years, 9 months
|
5.0%
1/20 • Number of events 1 • 3 years, 9 months
|
|
Vascular disorders
Hypertension
|
16.7%
10/60 • Number of events 12 • 3 years, 9 months
|
10.0%
2/20 • Number of events 3 • 3 years, 9 months
|
|
Vascular disorders
Hot flush
|
6.7%
4/60 • Number of events 4 • 3 years, 9 months
|
0.00%
0/20 • 3 years, 9 months
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60