Trial Outcomes & Findings for A Study of ACP-196 (Acalabrutinib) in Subjects With Relapsed/Refractory CLL and Intolerant of Ibrutinib Therapy (NCT NCT02717611)

NCT ID: NCT02717611

Last Updated: 2026-01-08

Results Overview

The overall response rate (ORR) of ACP-196 (acalabrutinib) in subjects with relapsed / refractory CLL who are intolerant of ibrutinib therapy. ORR is defined as the proportion of subjects achieving a best overall response (BOR) of either complete remission (CR), complete remission with incomplete bone marrow recovery (CRi), nodular partial remission (nPR), or partial remission (PR) at or before initiation of subsequent anticancer therapy. ORR will be analyzed per investigator's assessment.

• Recruitment status: ACTIVE_NOT_RECRUITING
• Study phase: PHASE2
• Target enrollment: 60 participants
• Primary outcome timeframe: From date of the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to approximately 4 years and 7 months). 1 cycle = 28 days
• Results posted on: 2026-01-08

Participant Flow

For the ACE-CL-208 program, Study Terminated by Sponsor refers to the following: Patients receiving treatment benefits will continue to be provided with study medication in the Post Final Analysis Management of the trial. Sponsor has terminated further data collection for analysis and reporting

Participant milestones

Measure	Acalabrutinib Acalabrutinib 100 mg BID
Overall Study STARTED	60
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	60

Reasons for withdrawal

Measure	Acalabrutinib Acalabrutinib 100 mg BID
Overall Study Death	13
Overall Study Withdrawal by Subject	6
Overall Study Active, not recruiting	40
Overall Study Complicating disease	1

Baseline Characteristics

A Study of ACP-196 (Acalabrutinib) in Subjects With Relapsed/Refractory CLL and Intolerant of Ibrutinib Therapy

Baseline characteristics by cohort

Measure	Acalabrutinib n=60 Participants Acalabrutinib 100 mg BID
Age, Continuous	69.2 Years STANDARD_DEVIATION 9.4 • n=18 Participants
Sex: Female, Male Female	22 Participants n=18 Participants
Sex: Female, Male Male	38 Participants n=18 Participants
Race/Ethnicity, Customized Hispanic or Latino	2 Participants n=18 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	54 Participants n=18 Participants
Race/Ethnicity, Customized Not Reported	2 Participants n=18 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=18 Participants
Race/Ethnicity, Customized Asian	0 Participants n=18 Participants
Race/Ethnicity, Customized Black or African American	1 Participants n=18 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=18 Participants
Race/Ethnicity, Customized White	56 Participants n=18 Participants
Race/Ethnicity, Customized Other	1 Participants n=18 Participants
Region of Enrollment United States	49 Participants n=18 Participants
Region of Enrollment Europe	11 Participants n=18 Participants

PRIMARY outcome

Timeframe: From date of the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to approximately 4 years and 7 months). 1 cycle = 28 days

Population: All Treated Population

The overall response rate (ORR) of ACP-196 (acalabrutinib) in subjects with relapsed / refractory CLL who are intolerant of ibrutinib therapy.

ORR is defined as the proportion of subjects achieving a best overall response (BOR) of either complete remission (CR), complete remission with incomplete bone marrow recovery (CRi), nodular partial remission (nPR), or partial remission (PR) at or before initiation of subsequent anticancer therapy. ORR will be analyzed per investigator's assessment.

Outcome measures

Measure	Acalabrutinib n=60 Participants Acalabrutinib 100 mg BID
The Overall Response Rate (ORR) of ACP-196 (Acalabrutinib)	70.0 Percentage of participants Interval 56.8 to 81.2

SECONDARY outcome

Timeframe: From the date of the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years).

Population: All Treated Population

The progression-free survival of ACP-196 (acalabrutinib) in subjects with relapsed / refractory CLL who are intolerant of ibrutinib therapy.

PFS is calculated as date of disease progression or death (censoring date for censored subjects) - first dose date + 1.

Outcome measures

Measure	Acalabrutinib n=60 Participants Acalabrutinib 100 mg BID
Progression-Free Survival	NA Months Interval 33.7 to not estimable; insufficient number of participants with events

SECONDARY outcome

Timeframe: From the date of the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years)

Population: All Treated Population

The duration of response of ACP-196 (acalabrutinib) in subjects with relapsed / refractory CLL who are intolerant of ibrutinib therapy.

DOR is calculated as date of disease progression or death (censoring date for censored subjects) - date of achieving the first CR, CRi, nPR, or PR + 1.

Outcome measures

Measure	Acalabrutinib n=60 Participants Acalabrutinib 100 mg BID
Duration of Response	NA Months Interval 29.9 to not estimable; insufficient number of participants with events

SECONDARY outcome

Timeframe: From date of the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years)

Population: All Treated Population

The time to next treatment of ACP-196 (acalabrutinib) in subjects with relapsed / refractory CLL who are intolerant of ibrutinib therapy.

TTNT is defined as the time from date of first acalabrutinib treatment to date of institution of subsequent anticancer therapy for CLL or death due to any cause, whichever comes first. Subjects who do not have the above specified events prior to the data cutoff date will be censored at the date of last visit. TTNT will be calculated as follows:

(Earlier date of institution of subsequent anticancer therapy for CLL or date of death due to any cause) - date of first dose + 1. For censored subjects, date of last visit will replace earlier date of use of subsequent anticancer therapy for CLL or date of death due to any cause in the calculation.

Outcome measures

Measure	Acalabrutinib n=60 Participants Acalabrutinib 100 mg BID
Time-to-Next Treatment	44.0 Months Interval 27.4 to not estimable; insufficient number of participants with events

SECONDARY outcome

Timeframe: From date of the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years).

Population: All Treated Population

The overall survival of ACP-319 (acalabrutinib) in subjects with relapsed/refractory CLL who are intolerant of ibrutinib therapy

Outcome measures

Measure	Acalabrutinib n=60 Participants Acalabrutinib 100 mg BID
Overall Survival	NA Months not estimable; insufficient number of participants with events

Adverse Events

Acalabrutinib

Serious events: 32 serious events

Other events: 60 other events

Deaths: 13 deaths

Serious adverse events

Measure	Acalabrutinib n=60 participants at risk Acalabrutinib 100 mg BID
Blood and lymphatic system disorders Anaemia	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Cardiac disorders Atrial fibrillation	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Cardiac disorders Cardiac failure congestive	3.3% 2/60 • Number of events 2 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Cardiac disorders Ventricular fibrillation	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Gastrointestinal disorders Diarrhoea	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Gastrointestinal disorders Inguinal hernia	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
General disorders Gait disturbance	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
General disorders Influenza like illness	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
General disorders Injection site haemorrhage	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
General disorders Non-cardiac chest pain	3.3% 2/60 • Number of events 4 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
General disorders Pyrexia	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Infections and infestations Bronchopulmonary aspergillosis	3.3% 2/60 • Number of events 2 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Infections and infestations Cellulitis	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Infections and infestations Clostridium difficile colitis	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Infections and infestations Diverticulitis	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Infections and infestations Lower respiratory tract infection	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Infections and infestations Pneumonia	11.7% 7/60 • Number of events 8 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Infections and infestations Pneumonia mycoplasmal	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Infections and infestations Pneumonia respiratory syncytial viral	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Infections and infestations Pneumonia viral	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Infections and infestations Pulmonary sepsis	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Infections and infestations Respiratory tract infection	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Infections and infestations Sepsis	5.0% 3/60 • Number of events 3 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Injury, poisoning and procedural complications Hip fracture	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Injury, poisoning and procedural complications Respiratory fume inhalation disorder	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Injury, poisoning and procedural complications Spinal fracture	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Injury, poisoning and procedural complications Splenic rupture	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Investigations Transaminases increased	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Metabolism and nutrition disorders Hyponatraemia	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Musculoskeletal and connective tissue disorders Arthralgia	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Musculoskeletal and connective tissue disorders Lumbar spinal stenosis	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Chronic myelomonocytic leukaemia	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastrointestinal adenocarcinoma	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant melanoma in situ	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Nervous system disorders Cerebrovascular accident	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Nervous system disorders Dizziness	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Nervous system disorders Dysarthria	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Nervous system disorders Encephalopathy	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Nervous system disorders Syncope	5.0% 3/60 • Number of events 3 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Psychiatric disorders Confusional state	1.7% 1/60 • Number of events 2 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Renal and urinary disorders Haematuria	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Renal and urinary disorders Renal tubular necrosis	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	1.7% 1/60 • Number of events 2 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Respiratory, thoracic and mediastinal disorders Dyspnoea	3.3% 2/60 • Number of events 2 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Vascular disorders Hypertension	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.

Other adverse events

Measure	Acalabrutinib n=60 participants at risk Acalabrutinib 100 mg BID
Gastrointestinal disorders Oesophagitis	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Gastrointestinal disorders Oral blood blister	1.7% 1/60 • Number of events 2 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Eye disorders Ocular hyperaemia	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Eye disorders Retinal tear	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Eye disorders Retinopathy	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Eye disorders Vision blurred	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Eye disorders Vitreous floaters	3.3% 2/60 • Number of events 2 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Eye disorders Vitreous haemorrhage	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Gastrointestinal disorders Abdominal discomfort	6.7% 4/60 • Number of events 4 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Gastrointestinal disorders Abdominal distension	5.0% 3/60 • Number of events 3 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Gastrointestinal disorders Abdominal pain	11.7% 7/60 • Number of events 8 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Gastrointestinal disorders Abdominal pain lower	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Gastrointestinal disorders Ascites	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Gastrointestinal disorders Barrett's oesophagus	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Gastrointestinal disorders Cheilitis	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Gastrointestinal disorders Colitis	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Gastrointestinal disorders Constipation	16.7% 10/60 • Number of events 12 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Gastrointestinal disorders Dental caries	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Gastrointestinal disorders Diarrhoea	53.3% 32/60 • Number of events 50 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Gastrointestinal disorders Dry mouth	8.3% 5/60 • Number of events 5 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Gastrointestinal disorders Dyspepsia	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Gastrointestinal disorders Dysphagia	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Gastrointestinal disorders Enterocolitis	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Gastrointestinal disorders Gastric polyps	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Gastrointestinal disorders Gastritis	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Gastrointestinal disorders Gastrointestinal haemorrhage	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Gastrointestinal disorders Gastrooesophageal reflux disease	6.7% 4/60 • Number of events 4 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Gastrointestinal disorders Haematochezia	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Gastrointestinal disorders Haemorrhoids	3.3% 2/60 • Number of events 2 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Gastrointestinal disorders Hiatus hernia	3.3% 2/60 • Number of events 2 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Gastrointestinal disorders Large intestine polyp	6.7% 4/60 • Number of events 4 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Gastrointestinal disorders Nausea	25.0% 15/60 • Number of events 16 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Investigations Weight decreased	6.7% 4/60 • Number of events 7 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Investigations Weight increased	13.3% 8/60 • Number of events 10 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Blood and lymphatic system disorders Anaemia	16.7% 10/60 • Number of events 25 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Blood and lymphatic system disorders Eosinophilia	1.7% 1/60 • Number of events 2 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Blood and lymphatic system disorders Increased tendency to bruise	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Blood and lymphatic system disorders Iron deficiency anaemia	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Blood and lymphatic system disorders Leukocytosis	3.3% 2/60 • Number of events 2 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Blood and lymphatic system disorders Lymph node pain	3.3% 2/60 • Number of events 3 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Blood and lymphatic system disorders Lymphocytosis	6.7% 4/60 • Number of events 5 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Blood and lymphatic system disorders Neutropenia	15.0% 9/60 • Number of events 18 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Eye disorders Dry eye	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Blood and lymphatic system disorders Pancytopenia	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Blood and lymphatic system disorders Polycythaemia	1.7% 1/60 • Number of events 2 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Blood and lymphatic system disorders Spontaneous haemorrhage	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Blood and lymphatic system disorders Thrombocytopenia	6.7% 4/60 • Number of events 7 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Cardiac disorders Arrhythmia	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Cardiac disorders Atrial fibrillation	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Cardiac disorders Atrial flutter	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Cardiac disorders Cardiac arrest	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Cardiac disorders Cardiac failure congestive	3.3% 2/60 • Number of events 2 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Cardiac disorders Cardiomyopathy	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Cardiac disorders Cardiorenal syndrome	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Cardiac disorders Extrasystoles	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Cardiac disorders Left ventricular dysfunction	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Cardiac disorders Mitral valve incompetence	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Cardiac disorders Palpitations	3.3% 2/60 • Number of events 2 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Cardiac disorders Sinus bradycardia	3.3% 2/60 • Number of events 3 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Cardiac disorders Sinus tachycardia	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Cardiac disorders Tachycardia	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Cardiac disorders Ventricular arrhythmia	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Ear and labyrinth disorders Ear discomfort	3.3% 2/60 • Number of events 2 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Ear and labyrinth disorders Ear pain	3.3% 2/60 • Number of events 2 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Ear and labyrinth disorders Hypoacusis	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Ear and labyrinth disorders Middle ear effusion	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Ear and labyrinth disorders Tinnitus	6.7% 4/60 • Number of events 4 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Ear and labyrinth disorders Vertigo	5.0% 3/60 • Number of events 3 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Endocrine disorders Goitre	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Endocrine disorders Hyperparathyroidism	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Endocrine disorders Thyroid mass	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Eye disorders Cataract	3.3% 2/60 • Number of events 2 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Eye disorders Conjunctival haemorrhage	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Gastrointestinal disorders Oral pain	1.7% 1/60 • Number of events 2 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Gastrointestinal disorders Stomatitis	6.7% 4/60 • Number of events 6 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Gastrointestinal disorders Toothache	3.3% 2/60 • Number of events 2 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Gastrointestinal disorders Umbilical hernia	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Gastrointestinal disorders Varices oesophageal	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Gastrointestinal disorders Vomiting	10.0% 6/60 • Number of events 7 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
General disorders Asthenia	3.3% 2/60 • Number of events 2 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
General disorders Chest pain	3.3% 2/60 • Number of events 2 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
General disorders Chills	10.0% 6/60 • Number of events 6 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
General disorders Cyst	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
General disorders Fatigue	25.0% 15/60 • Number of events 21 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
General disorders Feeling cold	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
General disorders Gait disturbance	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
General disorders Hypothermia	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
General disorders Inflammation	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
General disorders Influenza like illness	11.7% 7/60 • Number of events 7 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
General disorders Localised oedema	8.3% 5/60 • Number of events 7 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
General disorders Malaise	5.0% 3/60 • Number of events 3 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
General disorders Non-cardiac chest pain	8.3% 5/60 • Number of events 6 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
General disorders Oedema	5.0% 3/60 • Number of events 3 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
General disorders Oedema peripheral	16.7% 10/60 • Number of events 12 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
General disorders Pain	5.0% 3/60 • Number of events 3 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
General disorders Peripheral swelling	5.0% 3/60 • Number of events 3 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
General disorders Pyrexia	20.0% 12/60 • Number of events 17 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Hepatobiliary disorders Cholangitis	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Hepatobiliary disorders Cholelithiasis	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Hepatobiliary disorders Portal hypertension	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Immune system disorders Drug hypersensitivity	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Immune system disorders Hypersensitivity	3.3% 2/60 • Number of events 2 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Immune system disorders Hypogammaglobulinaemia	3.3% 2/60 • Number of events 2 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Immune system disorders Immunodeficiency	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Infections and infestations Bronchiolitis	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Infections and infestations Bronchitis	6.7% 4/60 • Number of events 4 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Infections and infestations Cellulitis	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Infections and infestations Chronic sinusitis	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Infections and infestations Clostridium difficile colitis	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Infections and infestations Clostridium difficile infection	5.0% 3/60 • Number of events 5 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Infections and infestations Conjunctivitis	3.3% 2/60 • Number of events 2 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Infections and infestations Diverticulitis	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Infections and infestations Ear infection	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Infections and infestations Enterocolitis infectious	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Infections and infestations Escherichia bacteraemia	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Infections and infestations Folliculitis	3.3% 2/60 • Number of events 2 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Infections and infestations Gastroenteritis	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Infections and infestations Gingivitis	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Infections and infestations Helicobacter infection	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Infections and infestations Hepatitis b reactivation	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Infections and infestations Herpes zoster	3.3% 2/60 • Number of events 2 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Infections and infestations Hordeolum	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Infections and infestations Infected bite	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Infections and infestations Influenza	3.3% 2/60 • Number of events 2 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Infections and infestations Kidney infection	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Infections and infestations Localised infection	1.7% 1/60 • Number of events 2 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Infections and infestations Lower respiratory tract infection	3.3% 2/60 • Number of events 8 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Infections and infestations Nail infection	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Infections and infestations Nasopharyngitis	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Infections and infestations Onychomycosis	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Infections and infestations Oral fungal infection	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Infections and infestations Oral herpes	3.3% 2/60 • Number of events 3 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Infections and infestations Otitis media	5.0% 3/60 • Number of events 6 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Infections and infestations Pneumonia	13.3% 8/60 • Number of events 13 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Infections and infestations Pseudomonas infection	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Infections and infestations Pyelitis	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Infections and infestations Pyelonephritis	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Infections and infestations Pyuria	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Infections and infestations Respiratory tract infection	1.7% 1/60 • Number of events 5 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Infections and infestations Rhinitis	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Infections and infestations Rhinovirus infection	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Infections and infestations Sinusitis	15.0% 9/60 • Number of events 16 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Infections and infestations Skin infection	5.0% 3/60 • Number of events 3 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Infections and infestations Strongyloidiasis	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Infections and infestations Tinea infection	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Infections and infestations Tooth infection	3.3% 2/60 • Number of events 2 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Infections and infestations Upper respiratory tract infection	33.3% 20/60 • Number of events 34 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Infections and infestations Urinary tract infection	13.3% 8/60 • Number of events 17 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Infections and infestations Vulvovaginal mycotic infection	3.3% 2/60 • Number of events 5 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Injury, poisoning and procedural complications Ankle fracture	1.7% 1/60 • Number of events 3 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Injury, poisoning and procedural complications Aortic pseudoaneurysm	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Injury, poisoning and procedural complications Arthropod bite	3.3% 2/60 • Number of events 2 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Injury, poisoning and procedural complications Contusion	43.3% 26/60 • Number of events 32 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Injury, poisoning and procedural complications Eye contusion	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Injury, poisoning and procedural complications Face injury	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Injury, poisoning and procedural complications Fall	15.0% 9/60 • Number of events 19 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Injury, poisoning and procedural complications Ligament sprain	3.3% 2/60 • Number of events 3 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Injury, poisoning and procedural complications Limb injury	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Injury, poisoning and procedural complications Lower limb fracture	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Injury, poisoning and procedural complications Mouth injury	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Injury, poisoning and procedural complications Patella fracture	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Injury, poisoning and procedural complications Post procedural haemorrhage	3.3% 2/60 • Number of events 2 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Injury, poisoning and procedural complications Postoperative hypertension	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Injury, poisoning and procedural complications Procedural pain	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Injury, poisoning and procedural complications Rib fracture	3.3% 2/60 • Number of events 2 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Injury, poisoning and procedural complications Road traffic accident	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Injury, poisoning and procedural complications Scratch	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Injury, poisoning and procedural complications Skin abrasion	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Injury, poisoning and procedural complications Skin laceration	5.0% 3/60 • Number of events 3 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Injury, poisoning and procedural complications Spinal fracture	3.3% 2/60 • Number of events 3 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Injury, poisoning and procedural complications Subdural haematoma	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Injury, poisoning and procedural complications Sunburn	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Injury, poisoning and procedural complications Thermal burn	1.7% 1/60 • Number of events 2 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Injury, poisoning and procedural complications Transfusion reaction	1.7% 1/60 • Number of events 3 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Injury, poisoning and procedural complications Wrist fracture	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Investigations Alanine aminotransferase increased	5.0% 3/60 • Number of events 6 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Investigations Anticonvulsant drug level increased	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Investigations Blood creatinine increased	3.3% 2/60 • Number of events 2 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Investigations Blood phosphorus decreased	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Investigations Cardiac murmur	3.3% 2/60 • Number of events 2 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Investigations Liver function test abnormal	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Investigations Liver function test increased	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Investigations Lymphocyte count decreased	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Investigations Lymphocyte count increased	10.0% 6/60 • Number of events 7 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Investigations Neutrophil count decreased	11.7% 7/60 • Number of events 10 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Investigations Platelet count decreased	10.0% 6/60 • Number of events 8 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Investigations Prostatic specific antigen increased	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Investigations Transaminases increased	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Metabolism and nutrition disorders Decreased appetite	8.3% 5/60 • Number of events 8 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Metabolism and nutrition disorders Fluid overload	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Metabolism and nutrition disorders Folate deficiency	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Metabolism and nutrition disorders Hyperglycaemia	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Metabolism and nutrition disorders Hyperkalaemia	6.7% 4/60 • Number of events 4 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Metabolism and nutrition disorders Hyperlipidaemia	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Metabolism and nutrition disorders Hyperuricaemia	3.3% 2/60 • Number of events 2 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Metabolism and nutrition disorders Hypocalcaemia	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Metabolism and nutrition disorders Hypoglycaemia	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Metabolism and nutrition disorders Hypokalaemia	5.0% 3/60 • Number of events 6 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Metabolism and nutrition disorders Hypomagnesaemia	3.3% 2/60 • Number of events 2 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Metabolism and nutrition disorders Hyponatraemia	8.3% 5/60 • Number of events 13 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Metabolism and nutrition disorders Hypophosphataemia	3.3% 2/60 • Number of events 2 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Metabolism and nutrition disorders Hypovolaemia	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Metabolism and nutrition disorders Increased appetite	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Metabolism and nutrition disorders Iron deficiency	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Metabolism and nutrition disorders Vitamin d deficiency	3.3% 2/60 • Number of events 2 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Musculoskeletal and connective tissue disorders Arthralgia	23.3% 14/60 • Number of events 17 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Musculoskeletal and connective tissue disorders Arthritis	6.7% 4/60 • Number of events 5 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Musculoskeletal and connective tissue disorders Back pain	20.0% 12/60 • Number of events 18 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Musculoskeletal and connective tissue disorders Bone lesion	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Musculoskeletal and connective tissue disorders Bone pain	3.3% 2/60 • Number of events 2 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Musculoskeletal and connective tissue disorders Diastasis recti abdominis	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Musculoskeletal and connective tissue disorders Groin pain	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Musculoskeletal and connective tissue disorders Intervertebral disc degeneration	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Musculoskeletal and connective tissue disorders Joint range of motion decreased	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Musculoskeletal and connective tissue disorders Joint swelling	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Musculoskeletal and connective tissue disorders Muscle spasms	8.3% 5/60 • Number of events 7 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	11.7% 7/60 • Number of events 8 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Musculoskeletal and connective tissue disorders Myalgia	8.3% 5/60 • Number of events 6 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Musculoskeletal and connective tissue disorders Neck pain	5.0% 3/60 • Number of events 3 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Musculoskeletal and connective tissue disorders Osteoarthritis	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Musculoskeletal and connective tissue disorders Osteoporosis	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Musculoskeletal and connective tissue disorders Osteosclerosis	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Musculoskeletal and connective tissue disorders Pain in extremity	10.0% 6/60 • Number of events 9 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Musculoskeletal and connective tissue disorders Plantar fasciitis	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Musculoskeletal and connective tissue disorders Scoliosis	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Musculoskeletal and connective tissue disorders Spinal osteoarthritis	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Musculoskeletal and connective tissue disorders Synovial cyst	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Musculoskeletal and connective tissue disorders Tendon disorder	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Acanthoma	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	8.3% 5/60 • Number of events 7 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Dysplastic naevus	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Endometrial cancer	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Haemangioma of bone	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Haemangioma of skin	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lentigo maligna	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Melanocytic naevus	1.7% 1/60 • Number of events 2 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Seborrhoeic keratosis	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Skin papilloma	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of lung	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of skin	8.3% 5/60 • Number of events 10 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour flare	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Nervous system disorders Arachnoid cyst	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Nervous system disorders Carpal tunnel syndrome	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Nervous system disorders Disturbance in attention	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Nervous system disorders Dizziness	31.7% 19/60 • Number of events 26 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Nervous system disorders Headache	43.3% 26/60 • Number of events 29 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Nervous system disorders Hypersomnia	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Nervous system disorders Hypoaesthesia	8.3% 5/60 • Number of events 5 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Nervous system disorders Lethargy	3.3% 2/60 • Number of events 2 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Nervous system disorders Memory impairment	3.3% 2/60 • Number of events 2 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Nervous system disorders Migraine	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Nervous system disorders Migraine with aura	3.3% 2/60 • Number of events 2 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Nervous system disorders Neuralgia	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Nervous system disorders Neuropathy peripheral	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Nervous system disorders Paraesthesia	5.0% 3/60 • Number of events 3 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Nervous system disorders Peripheral sensory neuropathy	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Nervous system disorders Sciatica	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Nervous system disorders Sensory loss	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Nervous system disorders Sinus headache	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Nervous system disorders Syncope	3.3% 2/60 • Number of events 3 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Nervous system disorders Tremor	6.7% 4/60 • Number of events 4 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Psychiatric disorders Adjustment disorder with depressed mood	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Psychiatric disorders Anxiety	3.3% 2/60 • Number of events 2 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Psychiatric disorders Depression	11.7% 7/60 • Number of events 8 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Psychiatric disorders Insomnia	10.0% 6/60 • Number of events 6 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Psychiatric disorders Nightmare	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Psychiatric disorders Sleep disorder	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Renal and urinary disorders Acute kidney injury	1.7% 1/60 • Number of events 2 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Renal and urinary disorders Chronic kidney disease	1.7% 1/60 • Number of events 2 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Renal and urinary disorders Dysuria	3.3% 2/60 • Number of events 3 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Renal and urinary disorders Glomerulosclerosis	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Renal and urinary disorders Haematuria	13.3% 8/60 • Number of events 9 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Renal and urinary disorders Micturition urgency	3.3% 2/60 • Number of events 2 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Renal and urinary disorders Nephrolithiasis	3.3% 2/60 • Number of events 2 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Renal and urinary disorders Nocturia	6.7% 4/60 • Number of events 6 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Renal and urinary disorders Pollakiuria	8.3% 5/60 • Number of events 5 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Renal and urinary disorders Renal impairment	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Renal and urinary disorders Stress urinary incontinence	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Renal and urinary disorders Urinary incontinence	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Renal and urinary disorders Urinary retention	5.0% 3/60 • Number of events 3 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Reproductive system and breast disorders Adnexa uteri cyst	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Reproductive system and breast disorders Prostatic obstruction	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Reproductive system and breast disorders Spermatocele	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Reproductive system and breast disorders Vaginal haemorrhage	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Respiratory, thoracic and mediastinal disorders Apnoea	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Respiratory, thoracic and mediastinal disorders Asthma	1.7% 1/60 • Number of events 3 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Respiratory, thoracic and mediastinal disorders Bronchiectasis	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Respiratory, thoracic and mediastinal disorders Bronchitis chronic	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Respiratory, thoracic and mediastinal disorders Cough	31.7% 19/60 • Number of events 25 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Respiratory, thoracic and mediastinal disorders Dyspnoea	18.3% 11/60 • Number of events 11 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	3.3% 2/60 • Number of events 3 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Respiratory, thoracic and mediastinal disorders Epistaxis	6.7% 4/60 • Number of events 6 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Respiratory, thoracic and mediastinal disorders Haemoptysis	5.0% 3/60 • Number of events 4 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Respiratory, thoracic and mediastinal disorders Hiccups	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Respiratory, thoracic and mediastinal disorders Laryngeal inflammation	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Respiratory, thoracic and mediastinal disorders Nasal congestion	11.7% 7/60 • Number of events 8 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	6.7% 4/60 • Number of events 5 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Respiratory, thoracic and mediastinal disorders Pleural effusion	5.0% 3/60 • Number of events 4 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Respiratory, thoracic and mediastinal disorders Productive cough	5.0% 3/60 • Number of events 3 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Respiratory, thoracic and mediastinal disorders Pulmonary mass	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Respiratory, thoracic and mediastinal disorders Respiratory failure	3.3% 2/60 • Number of events 2 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	6.7% 4/60 • Number of events 4 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	3.3% 2/60 • Number of events 2 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Respiratory, thoracic and mediastinal disorders Sinus congestion	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Respiratory, thoracic and mediastinal disorders Sleep apnoea syndrome	3.3% 2/60 • Number of events 2 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Respiratory, thoracic and mediastinal disorders Sputum discoloured	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Respiratory, thoracic and mediastinal disorders Upper-airway cough syndrome	15.0% 9/60 • Number of events 11 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Respiratory, thoracic and mediastinal disorders Wheezing	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Skin and subcutaneous tissue disorders Acne	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Skin and subcutaneous tissue disorders Actinic keratosis	3.3% 2/60 • Number of events 2 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Skin and subcutaneous tissue disorders Alopecia	3.3% 2/60 • Number of events 2 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Skin and subcutaneous tissue disorders Blister	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Skin and subcutaneous tissue disorders Blood blister	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Skin and subcutaneous tissue disorders Cold sweat	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Skin and subcutaneous tissue disorders Dermal cyst	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Skin and subcutaneous tissue disorders Dermatitis acneiform	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Skin and subcutaneous tissue disorders Dry skin	6.7% 4/60 • Number of events 4 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Skin and subcutaneous tissue disorders Ecchymosis	8.3% 5/60 • Number of events 5 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Skin and subcutaneous tissue disorders Hyperhidrosis	10.0% 6/60 • Number of events 8 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Skin and subcutaneous tissue disorders Hyperkeratosis	3.3% 2/60 • Number of events 2 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Skin and subcutaneous tissue disorders Hypertrichosis	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Skin and subcutaneous tissue disorders Ingrown hair	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Skin and subcutaneous tissue disorders Night sweats	13.3% 8/60 • Number of events 11 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Skin and subcutaneous tissue disorders Onychoclasis	3.3% 2/60 • Number of events 2 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Skin and subcutaneous tissue disorders Petechiae	8.3% 5/60 • Number of events 6 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Skin and subcutaneous tissue disorders Precancerous skin lesion	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Skin and subcutaneous tissue disorders Pruritus	10.0% 6/60 • Number of events 7 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Skin and subcutaneous tissue disorders Purpura	5.0% 3/60 • Number of events 3 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Skin and subcutaneous tissue disorders Rash	20.0% 12/60 • Number of events 13 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Skin and subcutaneous tissue disorders Rash erythematous	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Skin and subcutaneous tissue disorders Rash maculo-papular	5.0% 3/60 • Number of events 5 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Skin and subcutaneous tissue disorders Skin discolouration	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Skin and subcutaneous tissue disorders Skin exfoliation	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Skin and subcutaneous tissue disorders Skin haemorrhage	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Skin and subcutaneous tissue disorders Skin hyperpigmentation	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Skin and subcutaneous tissue disorders Skin lesion	11.7% 7/60 • Number of events 8 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Skin and subcutaneous tissue disorders Skin mass	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Skin and subcutaneous tissue disorders Transient acantholytic dermatosis	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Vascular disorders Aortic stenosis	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Vascular disorders Deep vein thrombosis	3.3% 2/60 • Number of events 2 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Vascular disorders Haematoma	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Vascular disorders Hot flush	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Vascular disorders Hypertension	13.3% 8/60 • Number of events 10 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Vascular disorders Hypotension	8.3% 5/60 • Number of events 5 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Vascular disorders Intermittent claudication	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Vascular disorders Lymphoedema	3.3% 2/60 • Number of events 3 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Vascular disorders Peripheral coldness	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.
Vascular disorders Thrombophlebitis superficial	1.7% 1/60 • Number of events 1 • From first dose of study drug until 30 days post last dose through study completion. An average of 5 years.

Additional Information

Global Clinical Lead

Acerta Pharma

Phone: 1-877-240-9479

Email: information.center@astrazeneca.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: LTE60