Trial Outcomes & Findings for A Phase 3 Study of DU-176b, Prevention of Venous Thromboembolism in Patients After Total Knee Arthroplasty (NCT NCT01181102)

Last Updated: 2019-03-05

Results Overview

The primary efficacy endpoint was the proportion of subjects who experienced at least one of the thromboembolic events listed below during the period from the start of study treatment to the venography at the end of study treatment. * Lower extremity Deep Vein Thrombosis (DVT) confirmed by unilateral venography at the end of study treatment * Definite diagnosis of symptomatic Pulmonary Embolism (PE) * Symptomatic DVT confirmed before the venography at the end of study treatment The objectives were to verify the non-inferiority of edoxaban to enoxaparin with regard to prevention of venous Thromboembolism (VTE)

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

716 participants

Primary outcome timeframe

2 weeks

Results posted on

2019-03-05

Participant Flow

Participant milestones

Participant milestones
Measure	DU-176b DU-176b oral tablets, 30 mg., taken once daily for 2 weeks edoxaban	Enoxaparin Sodium enoxaparin sodium 20mg(=2000IU)/0.2ml twice daily, subcutaneous injection for 2 weeks enoxaparin sodium
Overall Study STARTED	360	356
Overall Study Safety Analysis Set	354	349
Overall Study Efficacy Analysis Population	299	295
Overall Study COMPLETED	309	310
Overall Study NOT COMPLETED	51	46

Reasons for withdrawal

Reasons for withdrawal
Measure	DU-176b DU-176b oral tablets, 30 mg., taken once daily for 2 weeks edoxaban	Enoxaparin Sodium enoxaparin sodium 20mg(=2000IU)/0.2ml twice daily, subcutaneous injection for 2 weeks enoxaparin sodium
Overall Study Adverse Event	28	26
Overall Study Lack of Efficacy	3	1
Overall Study Lost to Follow-up	2	0
Overall Study Physician Decision	3	1
Overall Study Protocol Violation	5	6
Overall Study Withdrawal by Subject	10	12

Baseline Characteristics

A Phase 3 Study of DU-176b, Prevention of Venous Thromboembolism in Patients After Total Knee Arthroplasty

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	DU-176b n=299 Participants DU-176b oral tablets, 30 mg., taken once daily for 2 weeks edoxaban	Enoxaparin Sodium n=295 Participants enoxaparin sodium 20mg(=2000IU)/0.2ml twice daily, subcutaneous injection for 2 weeks enoxaparin sodium	Total n=594 Participants Total of all reporting groups
Age, Continuous	72.6 years STANDARD_DEVIATION 7.5 • n=5 Participants	72.1 years STANDARD_DEVIATION 7.8 • n=7 Participants	72.4 years STANDARD_DEVIATION 7.6 • n=5 Participants
Sex: Female, Male Female	245 Participants n=5 Participants	229 Participants n=7 Participants	474 Participants n=5 Participants
Sex: Female, Male Male	54 Participants n=5 Participants	66 Participants n=7 Participants	120 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	299 Participants n=5 Participants	295 Participants n=7 Participants	594 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment Taiwan	26 participants n=5 Participants	25 participants n=7 Participants	51 participants n=5 Participants
Region of Enrollment Japan	273 participants n=5 Participants	270 participants n=7 Participants	543 participants n=5 Participants

PRIMARY outcome

Timeframe: 2 weeks

Population: Efficacy Analysis population. 22 (7.4%) - DU-176b 41 (13.9%) - enoxaparin

Outcome measures

Outcome measures
Measure	DU-176b n=299 Participants DU-176b oral tablets, 30 mg., taken once daily for 2 weeks edoxaban	Enoxaparin Sodium n=295 Participants enoxaparin sodium 20mg(=2000IU)/0.2ml twice daily, subcutaneous injection for 2 weeks enoxaparin sodium
Incidence of Subjects With Venous Thromboembolism Events.	7.4 percent of participants with VTE events Interval 4.4 to 10.3	13.9 percent of participants with VTE events Interval 10.0 to 17.8

SECONDARY outcome

Timeframe: 2 weeks

Population: The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment

Outcome measures

Outcome measures
Measure	DU-176b n=354 Participants DU-176b oral tablets, 30 mg., taken once daily for 2 weeks edoxaban	Enoxaparin Sodium n=349 Participants enoxaparin sodium 20mg(=2000IU)/0.2ml twice daily, subcutaneous injection for 2 weeks enoxaparin sodium
Incidence of Major Bleeding or Clinically Relevant Non-major Bleeding.	6.2 percentage of subjects with bleeds Interval 4.1 to 9.2	3.7 percentage of subjects with bleeds Interval 2.2 to 6.3

Adverse Events

DU-176b

Serious events: 10 serious events

Other events: 237 other events

Deaths: 0 deaths

Enoxaparin Sodium

Serious events: 11 serious events

Other events: 256 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Kei Ibusuki, Associate Director

Daiichi Sankyo.,LTD

Phone: 81-90-2732-9505

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee PI shall not publish the results of the Study at any time without the prior written approval of Sponsor.
Publication restrictions are in place

Restriction type: OTHER

Measure	DU-176b n=354 participants at risk DU-176b oral tablets, 30 mg., taken once daily for 2 weeks edoxaban	Enoxaparin Sodium n=349 participants at risk enoxaparin sodium 20mg(=2000IU)/0.2ml twice daily, subcutaneous injection for 2 weeks enoxaparin sodium
Infections and infestations postoperative wound infection	0.28% 1/354 • Number of events 1 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.	0.00% 0/349 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.
Infections and infestations stitch abcess	0.28% 1/354 • Number of events 1 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.	0.00% 0/349 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.
Nervous system disorders carotid artery stenosis	0.00% 0/354 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.	0.29% 1/349 • Number of events 1 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.
Nervous system disorders cerebellar infarction	0.28% 1/354 • Number of events 1 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.	0.00% 0/349 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.
Nervous system disorders convulsion	0.00% 0/354 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.	0.29% 1/349 • Number of events 1 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.
Nervous system disorders syncope	0.00% 0/354 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.	0.29% 1/349 • Number of events 1 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.
Eye disorders retinal artery occlusion	0.00% 0/354 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.	0.29% 1/349 • Number of events 1 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.
Cardiac disorders cyanosis	0.00% 0/354 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.	0.29% 1/349 • Number of events 1 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.
Cardiac disorders myocardial infarction	0.28% 1/354 • Number of events 1 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.	0.00% 0/349 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.
Vascular disorders hypotension	0.00% 0/354 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.	0.29% 1/349 • Number of events 1 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.
Vascular disorders deep vein thrombosis	0.00% 0/354 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.	0.29% 1/349 • Number of events 1 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.
Gastrointestinal disorders gastrointestinal haemorrhage	0.00% 0/354 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.	0.29% 1/349 • Number of events 1 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.
Gastrointestinal disorders melaena	0.28% 1/354 • Number of events 1 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.	0.00% 0/349 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.
Skin and subcutaneous tissue disorders pyoderma gangrenosum	0.00% 0/354 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.	0.29% 1/349 • Number of events 1 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.
Skin and subcutaneous tissue disorders urticaria	0.28% 1/354 • Number of events 1 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.	0.00% 0/349 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.
Musculoskeletal and connective tissue disorders haemarthrosis	0.28% 1/354 • Number of events 1 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.	0.00% 0/349 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.
Musculoskeletal and connective tissue disorders joint contracture	0.00% 0/354 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.	0.29% 1/349 • Number of events 1 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.
General disorders pyrexia	0.00% 0/354 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.	0.29% 1/349 • Number of events 1 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.
Investigations Alanine aminotransferase increased	0.00% 0/354 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.	0.29% 1/349 • Number of events 1 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.
Investigations Aspartate aminotransferase increased	0.00% 0/354 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.	0.29% 1/349 • Number of events 1 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.
Investigations C-reactive protein increased	0.00% 0/354 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.	0.29% 1/349 • Number of events 1 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.
Injury, poisoning and procedural complications Femoral neck fracture	0.00% 0/354 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.	0.29% 1/349 • Number of events 1 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.
Injury, poisoning and procedural complications Lumbar vertebral fracture	0.28% 1/354 • Number of events 1 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.	0.00% 0/349 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.
Injury, poisoning and procedural complications Wound complication	0.28% 1/354 • Number of events 1 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.	0.00% 0/349 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.
Injury, poisoning and procedural complications Ligament rupture	0.28% 1/354 • Number of events 1 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.	0.00% 0/349 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.

Measure	DU-176b n=354 participants at risk DU-176b oral tablets, 30 mg., taken once daily for 2 weeks edoxaban	Enoxaparin Sodium n=349 participants at risk enoxaparin sodium 20mg(=2000IU)/0.2ml twice daily, subcutaneous injection for 2 weeks enoxaparin sodium
Vascular disorders wound haemorrhage	5.1% 18/354 • Number of events 19 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.	2.9% 10/349 • Number of events 10 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.
Skin and subcutaneous tissue disorders Haemorrhage subcutaneous	6.2% 22/354 • Number of events 25 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.	8.0% 28/349 • Number of events 30 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.
Investigations Alanine aminotransferase increased	7.1% 25/354 • Number of events 25 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.	26.9% 94/349 • Number of events 94 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.
Investigations Aspartate aminotransferase increased	3.4% 12/354 • Number of events 12 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.	24.9% 87/349 • Number of events 87 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.
Investigations Gamma-glutamyltransferase increased	9.3% 33/354 • Number of events 33 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.	18.3% 64/349 • Number of events 65 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.
Investigations blood urine present	9.6% 34/354 • Number of events 35 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.	8.9% 31/349 • Number of events 32 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.
Infections and infestations Cystitis	2.3% 8/354 • Number of events 8 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.	1.7% 6/349 • Number of events 6 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.
Infections and infestations Nasopharyngitis	4.5% 16/354 • Number of events 16 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.	4.3% 15/349 • Number of events 15 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.
Skin and subcutaneous tissue disorders rash	2.5% 9/354 • Number of events 9 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.	1.1% 4/349 • Number of events 4 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.
Gastrointestinal disorders Diarrhoea	3.4% 12/354 • Number of events 12 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.	2.9% 10/349 • Number of events 12 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.
Gastrointestinal disorders Vomiting	2.5% 9/354 • Number of events 9 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.	2.0% 7/349 • Number of events 7 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.
Musculoskeletal and connective tissue disorders Haemarthrosis	2.0% 7/354 • Number of events 7 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.	2.0% 7/349 • Number of events 7 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.
Investigations Blood bilirubin increased	4.0% 14/354 • Number of events 14 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.	2.0% 7/349 • Number of events 8 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.
Investigations Blood lactate dehydrogenase increased	1.7% 6/354 • Number of events 6 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.	4.6% 16/349 • Number of events 16 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.
Investigations Blood triglycerides increased	2.5% 9/354 • Number of events 9 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.	1.7% 6/349 • Number of events 6 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.
Investigations Haemoglobin decreased	9.6% 34/354 • Number of events 35 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.	8.9% 31/349 • Number of events 32 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.
Investigations Blood alkaline phosphatase increased	9.6% 34/354 • Number of events 35 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.	8.9% 31/349 • Number of events 32 The Safety Analysis Set was defined as all subjects who were enrolled in the study, but excluded those who had significant GCP violations, who did not receive any doses of the study drug, or who had no safety data after the start of study treatment.