Trial Outcomes & Findings for Study of Lanreotide Autogel 120 mg in Patients With Non-functioning Entero- Pancreatic Endocrine Tumour (NCT NCT00842348)

NCT ID: NCT00842348

Last Updated: 2022-10-12

Results Overview

Adverse events (AEs) that were ongoing from Study 726 at the time of entry into Study 729 were transcribed into the case report form (CRF) for Study 729 with a start date corresponding to the original report of this AE in Study 726. All new AEs that started after the last visit in Study 726 (i.e. irrespective of whether the AE had onset before or after giving informed consent for Study 729) were recorded Study 729. An AE was considered as a treatment emergent adverse event (TEAE) for Study 729 if: * It was not present prior to receiving the first dose of study treatment in Study 729; or, * It was present prior to receiving the first dose of study treatment in Study 729 but the intensity increased after the first dose of study treatment in Study 729. Adverse event data are presented in the AE section.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 89 participants
• Primary outcome timeframe: Throughout the study until the completion/early discontinuation visit.
• Results posted on: 2022-10-12

Participant Flow

There were 26 active sites across 10 countries in Study 729; however, only 24 recruited patients. The study was initiated in February 2009 and was completed in December 2015.

Participant milestones

Measure	Lanreotide Autogel Patients who received lanreotide 120 mg (Autogel formulation) in the preceding double blind (DB) study (Study 2-55-52030-726) and who continued to receive lanreotide 120 mg (Autogel formulation) in the open label study.	Placebo Patients who received placebo in the preceding DB study (Study 2-55-52030-726) and who received lanreotide 120 mg (Autogel formulation) in the open label study.
Patients Randomised in Study 726 STARTED	101	103
Patients Randomised in Study 726 COMPLETED	42	47
Patients Randomised in Study 726 NOT COMPLETED	59	56
Study 729 STARTED	42	47
Study 729 COMPLETED	16	9
Study 729 NOT COMPLETED	26	38

Reasons for withdrawal

Measure	Lanreotide Autogel Patients who received lanreotide 120 mg (Autogel formulation) in the preceding double blind (DB) study (Study 2-55-52030-726) and who continued to receive lanreotide 120 mg (Autogel formulation) in the open label study.	Placebo Patients who received placebo in the preceding DB study (Study 2-55-52030-726) and who received lanreotide 120 mg (Autogel formulation) in the open label study.
Patients Randomised in Study 726 Did not enter Study 729	59	56
Study 729 Disease progression/death	19	30
Study 729 Adverse Event	1	1
Study 729 Protocol Violation	1	1
Study 729 Withdrawal by Subject	2	4
Study 729 Due to Sponsor stopping the study	1	1
Study 729 Due to non-availability of IP	0	1
Study 729 Sponsor's decision	1	0
Study 729 Surgical resection	1	0

Baseline Characteristics

Study of Lanreotide Autogel 120 mg in Patients With Non-functioning Entero- Pancreatic Endocrine Tumour

Baseline characteristics by cohort

Measure	Lanreotide Autogel n=42 Participants Patients who received lanreotide 120 mg (Autogel formulation) in the preceding DB study (Study 2-55-52030-726) and who continued to receive lanreotide 120 mg (Autogel formulation) in the open label study.	Placebo n=47 Participants Patients who received placebo in the preceding DB study (Study 2-55-52030-726) and who received lanreotide 120 mg (Autogel formulation) in the open label study.	Total n=89 Participants Total of all reporting groups
Age, Continuous	64.8 years STANDARD_DEVIATION 10.8 • n=5 Participants	61.3 years STANDARD_DEVIATION 10.2 • n=7 Participants	62.9 years STANDARD_DEVIATION 10.6 • n=5 Participants
Sex: Female, Male Female	23 Participants n=5 Participants	22 Participants n=7 Participants	45 Participants n=5 Participants
Sex: Female, Male Male	19 Participants n=5 Participants	25 Participants n=7 Participants	44 Participants n=5 Participants
Race/Ethnicity, Customized Asian	0 participants n=5 Participants	3 participants n=7 Participants	3 participants n=5 Participants
Race/Ethnicity, Customized Black or African American	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Race/Ethnicity, Customized Caucasian/White	41 participants n=5 Participants	44 participants n=7 Participants	85 participants n=5 Participants

PRIMARY outcome

Timeframe: Throughout the study until the completion/early discontinuation visit.

Population: Safety population: all patients who received at least one dose of lanreotide Autogel in Study 729.

Adverse events (AEs) that were ongoing from Study 726 at the time of entry into Study 729 were transcribed into the case report form (CRF) for Study 729 with a start date corresponding to the original report of this AE in Study 726. All new AEs that started after the last visit in Study 726 (i.e. irrespective of whether the AE had onset before or after giving informed consent for Study 729) were recorded Study 729.

An AE was considered as a treatment emergent adverse event (TEAE) for Study 729 if:

• It was not present prior to receiving the first dose of study treatment in Study 729; or,
• It was present prior to receiving the first dose of study treatment in Study 729 but the intensity increased after the first dose of study treatment in Study 729.

Adverse event data are presented in the AE section.

Outcome measures

Measure	Lanreotide Autogel n=42 Participants Patients who received lanreotide 120 mg (Autogel formulation) in the preceding DB study (Study 2-55-52030-726) and who continued to receive lanreotide 120 mg (Autogel formulation) in the open label study.	Placebo n=47 Participants Patients who received placebo in the preceding double DB study (Study 2-55-52030-726) and who received lanreotide 120 mg (Autogel formulation) in the open label study.	Total n=89 Participants All patients treated with Lanreotide 120 mg (Autogel formulation) in the open label study.
Adverse Events	40 participants with any TEAEs	46 participants with any TEAEs	86 participants with any TEAEs

SECONDARY outcome

Timeframe: Throughout the study (every 24 weeks and at completion/withdrawal visit)

Population: Intention-to-treat (ITT) population: all patients randomised in the original protocol Study 726 (regardless of whether they continued into the extension Study 729). The ITT population was analysed using patients as randomised in Study 726.

The time from randomisation in Study 726 to the first occurrence of either disease progression (measured using Response Evaluation Criteria In Solid Tumours [RECIST] criteria) or death in Study 726 or in Study 729, or equivalently, the Progression Free Survival (PFS) time.

Tumour assessments for the placebo group after switching to open label lanreotide Autogel were excluded for the purpose of this analysis. Estimation of the median was based on the Kaplan-Meier method.

Outcome measures

Measure	Lanreotide Autogel n=101 Participants Patients who received lanreotide 120 mg (Autogel formulation) in the preceding DB study (Study 2-55-52030-726) and who continued to receive lanreotide 120 mg (Autogel formulation) in the open label study.	Placebo n=103 Participants Patients who received placebo in the preceding double DB study (Study 2-55-52030-726) and who received lanreotide 120 mg (Autogel formulation) in the open label study.	Total All patients treated with Lanreotide 120 mg (Autogel formulation) in the open label study.
Progression Free Survival (PFS): Kaplan-Meier Estimate	154.14 weeks Interval 123.57 to 237.43	72.00 weeks Interval 48.43 to 84.57	—

Adverse Events

Lanreotide Autogel

Serious events: 11 serious events

Other events: 34 other events

Deaths: 0 deaths

Placebo

Serious events: 14 serious events

Other events: 42 other events

Deaths: 0 deaths

Total

Serious events: 25 serious events

Other events: 76 other events

Deaths: 0 deaths

Serious adverse events

Measure	Lanreotide Autogel n=42 participants at risk Patients who received lanreotide 120 mg (Autogel formulation) in the preceding DB study (Study 2-55-52030-726) and who continued to receive lanreotide 120 mg (Autogel formulation) in the open label study.	Placebo n=47 participants at risk Patients who received placebo in the preceding DB study (Study 2-55-52030-726) and who received lanreotide 120 mg (Autogel formulation) in the open label study.	Total n=89 participants at risk All patients treated with lanreotide 120 mg (Autogel formulation) in the open label study.
Gastrointestinal disorders Abdominal adhesions	2.4% 1/42 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	0.00% 0/47 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	1.1% 1/89 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Gastrointestinal disorders Haematochezia	2.4% 1/42 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	0.00% 0/47 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	1.1% 1/89 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Gastrointestinal disorders Ileus	2.4% 1/42 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	0.00% 0/47 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	1.1% 1/89 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Gastrointestinal disorders Lower gastrointestinal haemorrhage	2.4% 1/42 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	0.00% 0/47 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	1.1% 1/89 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Gastrointestinal disorders Abdominal pain	0.00% 0/42 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	8.5% 4/47 • Number of events 5 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	4.5% 4/89 • Number of events 5 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/42 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	4.3% 2/47 • Number of events 2 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	2.2% 2/89 • Number of events 2 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Gastrointestinal disorders Diarrhoea	0.00% 0/42 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	2.1% 1/47 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	1.1% 1/89 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Gastrointestinal disorders Intestinal obstruction	0.00% 0/42 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	2.1% 1/47 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	1.1% 1/89 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Gastrointestinal disorders Pancreatitis	0.00% 0/42 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	2.1% 1/47 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	1.1% 1/89 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/42 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	2.1% 1/47 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	1.1% 1/89 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Gastrointestinal disorders Vomiting	0.00% 0/42 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	2.1% 1/47 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	1.1% 1/89 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Hepatobiliary disorders Cholelithiasis	4.8% 2/42 • Number of events 2 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	0.00% 0/47 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	2.2% 2/89 • Number of events 2 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Nervous system disorders Cerebral infarction	2.4% 1/42 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	0.00% 0/47 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	1.1% 1/89 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Nervous system disorders Stroke in evolution	2.4% 1/42 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	0.00% 0/47 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	1.1% 1/89 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Vascular disorders Hypertension	2.4% 1/42 • Number of events 2 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	0.00% 0/47 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	1.1% 1/89 • Number of events 2 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Eye disorders Retinal vein occlusion	2.4% 1/42 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	0.00% 0/47 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	1.1% 1/89 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Eye disorders Visual impairment	0.00% 0/42 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	2.1% 1/47 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	1.1% 1/89 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
General disorders Fatigue	2.4% 1/42 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	0.00% 0/47 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	1.1% 1/89 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
General disorders Face oedema	0.00% 0/42 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	2.1% 1/47 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	1.1% 1/89 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
General disorders Oedema peripheral	0.00% 0/42 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	2.1% 1/47 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	1.1% 1/89 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
General disorders Sudden death	0.00% 0/42 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	2.1% 1/47 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	1.1% 1/89 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	2.4% 1/42 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	0.00% 0/47 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	1.1% 1/89 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder cancer	0.00% 0/42 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	2.1% 1/47 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	1.1% 1/89 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour necrosis	0.00% 0/42 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	2.1% 1/47 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	1.1% 1/89 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Renal and urinary disorders Prerenal failure	2.4% 1/42 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	0.00% 0/47 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	1.1% 1/89 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Cardiac disorders Atrial fibrillation	0.00% 0/42 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	2.1% 1/47 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	1.1% 1/89 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Cardiac disorders Restrictive cardiomyopathy	0.00% 0/42 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	2.1% 1/47 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	1.1% 1/89 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Infections and infestations Hepatitis viral	0.00% 0/42 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	2.1% 1/47 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	1.1% 1/89 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Infections and infestations Pneumonia	0.00% 0/42 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	2.1% 1/47 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	1.1% 1/89 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Infections and infestations Postoperative wound infection	0.00% 0/42 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	2.1% 1/47 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	1.1% 1/89 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Injury, poisoning and procedural complications Anastomotic stenosis	0.00% 0/42 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	2.1% 1/47 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	1.1% 1/89 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Injury, poisoning and procedural complications Fall	0.00% 0/42 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	2.1% 1/47 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	1.1% 1/89 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Injury, poisoning and procedural complications Incisional hernia	0.00% 0/42 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	2.1% 1/47 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	1.1% 1/89 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Injury, poisoning and procedural complications Post procedural haematoma	0.00% 0/42 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	2.1% 1/47 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	1.1% 1/89 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Injury, poisoning and procedural complications Spinal compression fracture	0.00% 0/42 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	2.1% 1/47 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	1.1% 1/89 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Metabolism and nutrition disorders Decreased appetite	0.00% 0/42 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	2.1% 1/47 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	1.1% 1/89 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Metabolism and nutrition disorders Electrolyte imbalance	0.00% 0/42 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	2.1% 1/47 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	1.1% 1/89 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/42 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	2.1% 1/47 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	1.1% 1/89 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Reproductive system and breast disorders Ovarian cyst	0.00% 0/42 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	2.1% 1/47 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	1.1% 1/89 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/42 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	2.1% 1/47 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	1.1% 1/89 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.

Other adverse events

Measure	Lanreotide Autogel n=42 participants at risk Patients who received lanreotide 120 mg (Autogel formulation) in the preceding DB study (Study 2-55-52030-726) and who continued to receive lanreotide 120 mg (Autogel formulation) in the open label study.	Placebo n=47 participants at risk Patients who received placebo in the preceding DB study (Study 2-55-52030-726) and who received lanreotide 120 mg (Autogel formulation) in the open label study.	Total n=89 participants at risk All patients treated with lanreotide 120 mg (Autogel formulation) in the open label study.
Gastrointestinal disorders Diarrhoea	19.0% 8/42 • Number of events 28 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	31.9% 15/47 • Number of events 25 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	25.8% 23/89 • Number of events 53 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Gastrointestinal disorders Nausea	16.7% 7/42 • Number of events 15 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	12.8% 6/47 • Number of events 11 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	14.6% 13/89 • Number of events 26 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Gastrointestinal disorders Constipation	11.9% 5/42 • Number of events 8 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	8.5% 4/47 • Number of events 6 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	10.1% 9/89 • Number of events 14 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Gastrointestinal disorders Vomiting	16.7% 7/42 • Number of events 8 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	10.6% 5/47 • Number of events 11 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	13.5% 12/89 • Number of events 19 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Gastrointestinal disorders Abdominal pain	16.7% 7/42 • Number of events 7 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	14.9% 7/47 • Number of events 9 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	15.7% 14/89 • Number of events 16 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Gastrointestinal disorders Abdominal discomfort	7.1% 3/42 • Number of events 5 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	4.3% 2/47 • Number of events 3 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	5.6% 5/89 • Number of events 8 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Gastrointestinal disorders Dyspepsia	11.9% 5/42 • Number of events 5 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	4.3% 2/47 • Number of events 4 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	7.9% 7/89 • Number of events 9 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Gastrointestinal disorders Abdominal pain upper	7.1% 3/42 • Number of events 4 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	19.1% 9/47 • Number of events 9 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	13.5% 12/89 • Number of events 13 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Gastrointestinal disorders Abdominal distension	7.1% 3/42 • Number of events 3 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	8.5% 4/47 • Number of events 7 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	7.9% 7/89 • Number of events 10 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Gastrointestinal disorders Steatorrhoea	4.8% 2/42 • Number of events 2 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	10.6% 5/47 • Number of events 5 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	7.9% 7/89 • Number of events 7 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Gastrointestinal disorders Haemorrhoids	0.00% 0/42 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	6.4% 3/47 • Number of events 3 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	3.4% 3/89 • Number of events 3 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Gastrointestinal disorders Rectal haemorrhage	0.00% 0/42 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	8.5% 4/47 • Number of events 4 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	4.5% 4/89 • Number of events 4 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Musculoskeletal and connective tissue disorders Arthralgia	9.5% 4/42 • Number of events 6 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	12.8% 6/47 • Number of events 12 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	11.2% 10/89 • Number of events 18 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Musculoskeletal and connective tissue disorders Back pain	7.1% 3/42 • Number of events 3 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	12.8% 6/47 • Number of events 10 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	10.1% 9/89 • Number of events 13 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Musculoskeletal and connective tissue disorders Neck pain	7.1% 3/42 • Number of events 3 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	2.1% 1/47 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	4.5% 4/89 • Number of events 4 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/42 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	6.4% 3/47 • Number of events 4 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	3.4% 3/89 • Number of events 4 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Musculoskeletal and connective tissue disorders Osteoporosis	0.00% 0/42 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	6.4% 3/47 • Number of events 3 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	3.4% 3/89 • Number of events 3 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Infections and infestations Bronchitis	7.1% 3/42 • Number of events 6 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	14.9% 7/47 • Number of events 7 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	11.2% 10/89 • Number of events 13 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Infections and infestations Upper respiratory tract infection	9.5% 4/42 • Number of events 6 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	2.1% 1/47 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	5.6% 5/89 • Number of events 7 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Infections and infestations Viral infection	9.5% 4/42 • Number of events 5 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	4.3% 2/47 • Number of events 2 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	6.7% 6/89 • Number of events 7 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Infections and infestations Sinusitis	7.1% 3/42 • Number of events 3 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	0.00% 0/47 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	3.4% 3/89 • Number of events 3 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Infections and infestations Urinary tract infection	4.8% 2/42 • Number of events 2 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	10.6% 5/47 • Number of events 6 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	7.9% 7/89 • Number of events 8 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Infections and infestations Nasopharyngitis	2.4% 1/42 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	8.5% 4/47 • Number of events 9 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	5.6% 5/89 • Number of events 10 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Nervous system disorders Dizziness	9.5% 4/42 • Number of events 6 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	4.3% 2/47 • Number of events 2 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	6.7% 6/89 • Number of events 8 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Nervous system disorders Headache	4.8% 2/42 • Number of events 2 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	8.5% 4/47 • Number of events 4 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	6.7% 6/89 • Number of events 6 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Metabolism and nutrition disorders Decreased appetite	9.5% 4/42 • Number of events 5 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	8.5% 4/47 • Number of events 5 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	9.0% 8/89 • Number of events 10 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Metabolism and nutrition disorders Hyperglycaemia	7.1% 3/42 • Number of events 3 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	2.1% 1/47 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	4.5% 4/89 • Number of events 4 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Metabolism and nutrition disorders Diabetes mellitus	4.8% 2/42 • Number of events 2 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	8.5% 4/47 • Number of events 4 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	6.7% 6/89 • Number of events 6 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/42 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	8.5% 4/47 • Number of events 5 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	4.5% 4/89 • Number of events 5 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Investigations Weight decreased	2.4% 1/42 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	6.4% 3/47 • Number of events 5 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	4.5% 4/89 • Number of events 6 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Skin and subcutaneous tissue disorders Rash	11.9% 5/42 • Number of events 6 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	4.3% 2/47 • Number of events 3 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	7.9% 7/89 • Number of events 9 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Skin and subcutaneous tissue disorders Dry skin	7.1% 3/42 • Number of events 5 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	4.3% 2/47 • Number of events 2 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	5.6% 5/89 • Number of events 7 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Skin and subcutaneous tissue disorders Pruritus	2.4% 1/42 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	6.4% 3/47 • Number of events 5 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	4.5% 4/89 • Number of events 6 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
General disorders Fatigue	11.9% 5/42 • Number of events 6 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	8.5% 4/47 • Number of events 6 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	10.1% 9/89 • Number of events 12 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
General disorders Oedema peripheral	7.1% 3/42 • Number of events 4 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	2.1% 1/47 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	4.5% 4/89 • Number of events 5 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
General disorders Injection site pain	2.4% 1/42 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	6.4% 3/47 • Number of events 3 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	4.5% 4/89 • Number of events 4 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
General disorders Asthenia	0.00% 0/42 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	8.5% 4/47 • Number of events 4 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	4.5% 4/89 • Number of events 4 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
General disorders Injection site nodule	0.00% 0/42 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	6.4% 3/47 • Number of events 3 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	3.4% 3/89 • Number of events 3 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
General disorders Pyrexia	0.00% 0/42 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	6.4% 3/47 • Number of events 5 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	3.4% 3/89 • Number of events 5 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Psychiatric disorders Insomnia	9.5% 4/42 • Number of events 5 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	0.00% 0/47 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	4.5% 4/89 • Number of events 5 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Renal and urinary disorders Haematuria	7.1% 3/42 • Number of events 3 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	0.00% 0/47 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	3.4% 3/89 • Number of events 3 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Hepatobiliary disorders Cholelithiasis	16.7% 7/42 • Number of events 10 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	14.9% 7/47 • Number of events 9 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	15.7% 14/89 • Number of events 19 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Vascular disorders Hypertension	9.5% 4/42 • Number of events 4 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	10.6% 5/47 • Number of events 5 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	10.1% 9/89 • Number of events 9 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Vascular disorders Flushing	2.4% 1/42 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	6.4% 3/47 • Number of events 5 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	4.5% 4/89 • Number of events 6 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Respiratory, thoracic and mediastinal disorders Cough	7.1% 3/42 • Number of events 3 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	6.4% 3/47 • Number of events 6 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	6.7% 6/89 • Number of events 9 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	7.1% 3/42 • Number of events 3 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	4.3% 2/47 • Number of events 3 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	5.6% 5/89 • Number of events 6 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/42 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	6.4% 3/47 • Number of events 3 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	3.4% 3/89 • Number of events 3 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Blood and lymphatic system disorders Anaemia	7.1% 3/42 • Number of events 3 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	6.4% 3/47 • Number of events 4 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	6.7% 6/89 • Number of events 7 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.
Injury, poisoning and procedural complications Procedural pain	2.4% 1/42 • Number of events 1 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	6.4% 3/47 • Number of events 6 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.	4.5% 4/89 • Number of events 7 • Adverse events were monitored from the time that the patient withdrew or completed Study 726 until withdrawal in Study 729. Adverse events were elicited by direct, nonleading questioning or by spontaneous reports. Local tolerance AEs were assessed by spontaneous reports. Any local tolerance assessed as present and judged as clinically significant was recorded as an AE in the CRF. Pre-existing conditions that worsened during the study were reported as AEs. Adverse events that were ongoing at the end of Study 726 were recorded and followed during Study 729.

Additional Information

Medical Director, Oncology

Ipsen

Phone: clinical.trials@ipsen.com

Email: clinical.trials@ipsen.com

Results disclosure agreements

• Principal investigator is a sponsor employee The Sponsor required reasonable opportunity to review any abstract, presentation, or paper before the material is submitted for publication or communicated. This also applied to any amendments that are requested by referees or journal editors. The Sponsor committed to comment on the draft documents within a time period agreed in the contractual arrangements between the Sponsor and authors or their institution. Delays were also possible if publication would adversely affect patentability.
• Publication restrictions are in place

Restriction type: OTHER