Trial Outcomes & Findings for A Trial Comparing Gemcitabine With and Without IMM-101 in Advanced Pancreatic Cancer (NCT NCT01303172)

Last Updated: 2021-11-10

Results Overview

A clinically relevant deleterious effect of IMM-101 on safety and tolerability profiles was judged by: * Local and systemic toxicities. * Number, type and degree of toxicities as measured by the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) v4.0. Adverse events were collected from time of Informed Consent to 30 days post last dose of study medication IMM-101 does not appear to confer an incremental safety burden beyond that associated with chemotherapy and the disease itself. No new safety signals were identified from this study. The numbers of SAEs by preferred term were low, such that no trends could be inferred from these data and no significant SAEs attributable to IMM 101 were observed.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

110 participants

Primary outcome timeframe

From time of Informed Consent to 30 days post last dose of study medication

Results posted on

2021-11-10

Participant Flow

Participant milestones

Participant milestones
Measure	Gemcitabine Plus IMM-101 Patients in the experimental arm received IMM-101 in addition to Gemcitabine (Gem). The treatment regimen with IMM-101 was every 2 weeks for the first 3 doses followed by a rest of 4 weeks then every 2 weeks for the next 3 doses followed by every 4 weeks thereafter. For patients in the experimental group, GEM was initiated at least 14 days after first dose of IMM-101. GEM plus IMM-101 was offered until intolerable toxicity or withdrawal from the study up to a maximum of 12 cycles (i.e. approximately 48 weeks). IMM-101: IMM-101 is a suspension of heat-killed whole cell M. obuense in borate-buffered saline. A single 0.1 mL intradermal injection of IMM-101 (10 mg/mL)will be administered every 2 weeks for the first 3 doses followed by a rest of 4 weeks then every 2 weeks for the next 3 doses followed by every 4 weeks thereafter. Chemotherapy plus IMM-101 will be offered until intolerable toxicity or withdrawal from the study up to a maximum of 12 cycles of GEM. Patients who completed the Main Study and who provided informed consent were eligible to participate in a long term treatment Sub-Study where all patients received IMM-101.	Gemcitabine Monotherapy Patients in the control arm received normal standard of care - up to 12 cycles of Gemcitabine. Dosing of Gemcitabine was as per the normal prescribing information for pancreatic cancer. Gemcitabine was administered intravenously at 1000 mg/m2 over 30 minutes once weekly for 3 consecutive weeks out of every 4 weeks until intolerable toxicity or withdrawal from the study up to a maximum of 12 cycles (i.e. approximately 48 weeks). Dosage reduction with each cycle or within each cycle was applied based upon the grade of Gemcitabine-related toxicity experienced by the patient using centre's standard protocol. Patients who completed the Main Study and who provided informed consent were eligible to participate in a long term treatment Sub-Study where all patients received IMM-101.
Overall Study STARTED	75	35
Overall Study COMPLETED	12	1
Overall Study NOT COMPLETED	63	34

Reasons for withdrawal

Reasons for withdrawal
Measure	Gemcitabine Plus IMM-101 Patients in the experimental arm received IMM-101 in addition to Gemcitabine (Gem). The treatment regimen with IMM-101 was every 2 weeks for the first 3 doses followed by a rest of 4 weeks then every 2 weeks for the next 3 doses followed by every 4 weeks thereafter. For patients in the experimental group, GEM was initiated at least 14 days after first dose of IMM-101. GEM plus IMM-101 was offered until intolerable toxicity or withdrawal from the study up to a maximum of 12 cycles (i.e. approximately 48 weeks). IMM-101: IMM-101 is a suspension of heat-killed whole cell M. obuense in borate-buffered saline. A single 0.1 mL intradermal injection of IMM-101 (10 mg/mL)will be administered every 2 weeks for the first 3 doses followed by a rest of 4 weeks then every 2 weeks for the next 3 doses followed by every 4 weeks thereafter. Chemotherapy plus IMM-101 will be offered until intolerable toxicity or withdrawal from the study up to a maximum of 12 cycles of GEM. Patients who completed the Main Study and who provided informed consent were eligible to participate in a long term treatment Sub-Study where all patients received IMM-101.	Gemcitabine Monotherapy Patients in the control arm received normal standard of care - up to 12 cycles of Gemcitabine. Dosing of Gemcitabine was as per the normal prescribing information for pancreatic cancer. Gemcitabine was administered intravenously at 1000 mg/m2 over 30 minutes once weekly for 3 consecutive weeks out of every 4 weeks until intolerable toxicity or withdrawal from the study up to a maximum of 12 cycles (i.e. approximately 48 weeks). Dosage reduction with each cycle or within each cycle was applied based upon the grade of Gemcitabine-related toxicity experienced by the patient using centre's standard protocol. Patients who completed the Main Study and who provided informed consent were eligible to participate in a long term treatment Sub-Study where all patients received IMM-101.
Overall Study Physician Decision	9	6
Overall Study Adverse Event	5	2
Overall Study Withdrawal by Subject	4	2
Overall Study Death	20	7
Overall Study Lack of Efficacy	25	17

Baseline Characteristics

A Trial Comparing Gemcitabine With and Without IMM-101 in Advanced Pancreatic Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Experimental n=75 Participants Gemcitabine plus IMM-101	Control n=35 Participants Gemcitabine monotherapy	Total n=110 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	28 Participants n=5 Participants	16 Participants n=7 Participants	44 Participants n=5 Participants
Age, Categorical >=65 years	47 Participants n=5 Participants	19 Participants n=7 Participants	66 Participants n=5 Participants
Age, Continuous	68 years n=5 Participants	66 years n=7 Participants	67 years n=5 Participants
Sex: Female, Male Female	37 Participants n=5 Participants	14 Participants n=7 Participants	51 Participants n=5 Participants
Sex: Female, Male Male	38 Participants n=5 Participants	21 Participants n=7 Participants	59 Participants n=5 Participants
Race/Ethnicity, Customized White	74 Participants n=5 Participants	33 Participants n=7 Participants	107 Participants n=5 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Other	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Unknown	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment Cyprus	3 participants n=5 Participants	3 participants n=7 Participants	6 participants n=5 Participants
Region of Enrollment Ireland	1 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants
Region of Enrollment United Kingdom	25 participants n=5 Participants	9 participants n=7 Participants	34 participants n=5 Participants
Region of Enrollment Italy	14 participants n=5 Participants	9 participants n=7 Participants	23 participants n=5 Participants
Region of Enrollment Spain	32 participants n=5 Participants	13 participants n=7 Participants	45 participants n=5 Participants

PRIMARY outcome

Timeframe: From time of Informed Consent to 30 days post last dose of study medication

Population: The safety analysis set included all randomised patients who received at least one dose of the study drug. One patient in the Gemcitabine plus IMM-101 group was withdrawn prior to administration of study treatment due to a worsening of his physical condition.

Outcome measures

Outcome measures
Measure	Experimental n=74 Participants Gemcitabine plus IMM-101	Control n=35 Participants Gemcitabine monotherapy
Safety and Tolerability. With Treatment Emergent Adverse Events (TEAEs)	73 participants	35 participants
Safety and Tolerability. Withdrawn due to a TEAE	4 participants	0 participants
Safety and Tolerability. With TEAEs related to IMM-101	43 participants	0 participants
Safety and Tolerability. With Treatment Emergent Serious Adverse Events (TESAEs)	38 participants	10 participants
Safety and Tolerability. With Treatment Emergent Serious Adverse Events (TESAEs) related to IMM-101	7 participants	0 participants

SECONDARY outcome

Timeframe: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 1 year (or longer in the case of patients who entered the long term treatment sub-study, up to 5 years).

Population: The Intent To Treat analysis set included all randomised patients.

Overall and progression free survival

Outcome measures

Outcome measures
Measure	Experimental n=75 Participants Gemcitabine plus IMM-101	Control n=35 Participants Gemcitabine monotherapy
Survival Overall Survival	6.7 Months Interval 5.4 to 7.5	5.6 Months Interval 3.2 to 7.2
Survival Progression Free Survival	4.1 Months Interval 3.3 to 4.8	2.4 Months Interval 2.1 to 4.0

SECONDARY outcome

Population: The Intent To Treat analysis set included all randomised patients.

A clinically relevant improvement Overall Response Rate (ORR). Overall response rate was defined as the percentage of patients with a complete response or partial response as assessed by RECIST v1.1 criteria.

Outcome measures

Outcome measures
Measure	Experimental n=75 Participants Gemcitabine plus IMM-101	Control n=35 Participants Gemcitabine monotherapy
Overall Response Rate (ORR). Complete Response	0 participants	0 participants
Overall Response Rate (ORR). Partial Response	8 participants	1 participants

SECONDARY outcome

Population: The subgroup of patients with metastatic disease at baseline was the largest and accounted for 80.0% of patients in the ITT analysis set.

Overall and progression free survival in metastatic patients only

Outcome measures

Outcome measures
Measure	Experimental n=64 Participants Gemcitabine plus IMM-101	Control n=28 Participants Gemcitabine monotherapy
Overall Survival in Metastatic Patients Only	7.0 Months Interval 5.5 to 9.0	4.4 Months Interval 2.8 to 6.5

Adverse Events

Experimental

Serious events: 36 serious events

Other events: 73 other events

Deaths: 22 deaths

Control

Serious events: 10 serious events

Other events: 35 other events

Deaths: 7 deaths

Serious adverse events

Other adverse events

Additional Information

Chief Medical Officer

Immodulon Therapeutics Ltd

Phone: +44 (0) 20 3137 6346

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Serious adverse events
Measure	Experimental n=75 participants at risk Gemcitabine plus IMM-101	Control n=35 participants at risk Gemcitabine monotherapy
Infections and infestations Biliary sepsis	5.3% 4/75 • Number of events 6 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	0.00% 0/35 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
Infections and infestations Infection	4.0% 3/75 • Number of events 3 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	0.00% 0/35 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
Infections and infestations Pneumonia	4.0% 3/75 • Number of events 3 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	0.00% 0/35 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
Infections and infestations Sepsis	1.3% 1/75 • Number of events 1 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	2.9% 1/35 • Number of events 2 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
Infections and infestations Lower respiratory tract infection	2.7% 2/75 • Number of events 2 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	0.00% 0/35 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
Infections and infestations Urinary tract infection	2.7% 2/75 • Number of events 2 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	0.00% 0/35 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
Infections and infestations Biliary tract infection	1.3% 1/75 • Number of events 1 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	0.00% 0/35 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
Infections and infestations Clostridium difficile colitis	1.3% 1/75 • Number of events 3 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	0.00% 0/35 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
Infections and infestations Device related infection	1.3% 1/75 • Number of events 1 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	0.00% 0/35 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
Infections and infestations Gastroenteritis	1.3% 1/75 • Number of events 1 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	0.00% 0/35 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
Infections and infestations Liver abscess	1.3% 1/75 • Number of events 1 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	0.00% 0/35 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
Infections and infestations Lung infection	1.3% 1/75 • Number of events 1 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	0.00% 0/35 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
Infections and infestations Septic shock	0.00% 0/75 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	2.9% 1/35 • Number of events 1 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
Infections and infestations Urinary tract infection fungal	1.3% 1/75 • Number of events 1 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	0.00% 0/35 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
Gastrointestinal disorders Abdominal pain	5.3% 4/75 • Number of events 4 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	0.00% 0/35 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
Gastrointestinal disorders Ascites	4.0% 3/75 • Number of events 4 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	0.00% 0/35 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
Gastrointestinal disorders Vomiting	4.0% 3/75 • Number of events 3 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	0.00% 0/35 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
Gastrointestinal disorders Intestinal obstruction	1.3% 1/75 • Number of events 1 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	2.9% 1/35 • Number of events 1 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
Gastrointestinal disorders Gastrointestinal hemorrhage	1.3% 1/75 • Number of events 1 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	0.00% 0/35 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
Gastrointestinal disorders Diarrhea	0.00% 0/75 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	2.9% 1/35 • Number of events 1 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
Gastrointestinal disorders Large intestine perforation	1.3% 1/75 • Number of events 1 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	0.00% 0/35 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
Gastrointestinal disorders Pancreatic duct stenosis	1.3% 1/75 • Number of events 1 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	0.00% 0/35 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
Gastrointestinal disorders Small intestine perforation	0.00% 0/75 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	2.9% 1/35 • Number of events 1 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	1.3% 1/75 • Number of events 1 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	0.00% 0/35 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
General disorders Disease progression	4.0% 3/75 • Number of events 3 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	5.7% 2/35 • Number of events 2 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
General disorders Pyrexia	5.3% 4/75 • Number of events 4 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	2.9% 1/35 • Number of events 1 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
General disorders Chest pain	1.3% 1/75 • Number of events 1 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	0.00% 0/35 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
General disorders Fatigue	1.3% 1/75 • Number of events 1 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	0.00% 0/35 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
General disorders General physical health deterioration	1.3% 1/75 • Number of events 1 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	0.00% 0/35 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
General disorders Mucosal inflammation	1.3% 1/75 • Number of events 1 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	0.00% 0/35 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
General disorders Sudden death	0.00% 0/75 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	2.9% 1/35 • Number of events 1 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
Nervous system disorders Cerebral infarction	1.3% 1/75 • Number of events 1 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	2.9% 1/35 • Number of events 1 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
Nervous system disorders Cerebellar infarction	1.3% 1/75 • Number of events 1 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	0.00% 0/35 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
Nervous system disorders Convulsion	1.3% 1/75 • Number of events 1 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	0.00% 0/35 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
Nervous system disorders IVth nerve paralysis	0.00% 0/75 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	2.9% 1/35 • Number of events 1 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
Nervous system disorders Nerve root compression	1.3% 1/75 • Number of events 1 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	0.00% 0/35 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
Nervous system disorders Peroneal nerve palsy	1.3% 1/75 • Number of events 1 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	0.00% 0/35 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
Nervous system disorders Syncope	1.3% 1/75 • Number of events 1 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	0.00% 0/35 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
Metabolism and nutrition disorders Decreased appetite	1.3% 1/75 • Number of events 1 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	0.00% 0/35 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
Metabolism and nutrition disorders Dehydration	0.00% 0/75 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	2.9% 1/35 • Number of events 1 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.

Other adverse events
Measure	Experimental n=75 participants at risk Gemcitabine plus IMM-101	Control n=35 participants at risk Gemcitabine monotherapy
Gastrointestinal disorders Abdominal pain	46.7% 35/75 • Number of events 56 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	31.4% 11/35 • Number of events 22 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
Gastrointestinal disorders Diarrhoea	44.0% 33/75 • Number of events 65 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	40.0% 14/35 • Number of events 27 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
Gastrointestinal disorders Nausea	44.0% 33/75 • Number of events 59 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	37.1% 13/35 • Number of events 26 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
Gastrointestinal disorders Constipation	41.3% 31/75 • Number of events 42 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	31.4% 11/35 • Number of events 21 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
Gastrointestinal disorders Vomiting	29.3% 22/75 • Number of events 34 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	40.0% 14/35 • Number of events 19 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
Gastrointestinal disorders Stomatitis	10.7% 8/75 • Number of events 11 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	11.4% 4/35 • Number of events 8 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
Gastrointestinal disorders Ascites	9.3% 7/75 • Number of events 13 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	8.6% 3/35 • Number of events 3 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
Gastrointestinal disorders Abdominal distension	8.0% 6/75 • Number of events 7 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	8.6% 3/35 • Number of events 3 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
Gastrointestinal disorders Abdominal pain upper	12.0% 9/75 • Number of events 15 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	0.00% 0/35 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
Gastrointestinal disorders Dyspepsia	9.3% 7/75 • Number of events 9 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	5.7% 2/35 • Number of events 2 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
Gastrointestinal disorders Abdominal discomfort	8.0% 6/75 • Number of events 8 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	0.00% 0/35 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
Gastrointestinal disorders Gastrooesophageal reflux	8.0% 6/75 • Number of events 8 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	0.00% 0/35 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
Gastrointestinal disorders Malabsorption	5.3% 4/75 • Number of events 6 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	0.00% 0/35 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
Gastrointestinal disorders Rectal haemorrhage	5.3% 4/75 • Number of events 4 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	0.00% 0/35 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
General disorders Asthenia	45.3% 34/75 • Number of events 77 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	34.3% 12/35 • Number of events 46 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
General disorders Fatigue	25.3% 19/75 • Number of events 50 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	28.6% 10/35 • Number of events 24 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
General disorders Pyrexia	24.0% 18/75 • Number of events 30 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	5.7% 2/35 • Number of events 2 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
General disorders Oedema peripheral	16.0% 12/75 • Number of events 22 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	20.0% 7/35 • Number of events 9 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
Gastrointestinal disorders Mucosal inflammation	8.0% 6/75 • Number of events 8 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	2.9% 1/35 • Number of events 1 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
General disorders Pain	6.7% 5/75 • Number of events 6 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	5.7% 2/35 • Number of events 2 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
General disorders Chills	8.0% 6/75 • Number of events 7 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	0.00% 0/35 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
General disorders Injection site reaction	6.7% 5/75 • Number of events 8 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	0.00% 0/35 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
General disorders Injection site pain	5.3% 4/75 • Number of events 6 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	0.00% 0/35 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
General disorders Oedema	5.3% 4/75 • Number of events 6 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	0.00% 0/35 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
Metabolism and nutrition disorders Decreased appetite	44.0% 33/75 • Number of events 45 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	31.4% 11/35 • Number of events 24 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
Metabolism and nutrition disorders Vitamin D deficiency	9.3% 7/75 • Number of events 7 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	2.9% 1/35 • Number of events 1 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
Metabolism and nutrition disorders Hypokalaemia	2.7% 2/75 • Number of events 3 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	8.6% 3/35 • Number of events 5 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
Blood and lymphatic system disorders Anaemia	30.7% 23/75 • Number of events 40 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	25.7% 9/35 • Number of events 14 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
Blood and lymphatic system disorders Neutropenia	21.3% 16/75 • Number of events 48 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	28.6% 10/35 • Number of events 24 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
Blood and lymphatic system disorders Thrombocytopenia	14.7% 11/75 • Number of events 21 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	20.0% 7/35 • Number of events 13 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
Blood and lymphatic system disorders Leukopenia	5.3% 4/75 • Number of events 24 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	8.6% 3/35 • Number of events 9 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
Investigations Weight decrased	18.7% 14/75 • Number of events 17 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	2.9% 1/35 • Number of events 1 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
Investigations Platelet count decrased	9.3% 7/75 • Number of events 24 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	20.0% 7/35 • Number of events 14 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
Investigations Alanine aminotransferase increased	8.0% 6/75 • Number of events 15 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	5.7% 2/35 • Number of events 2 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
Investigations Neutrophil count decreased	6.7% 5/75 • Number of events 8 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	5.7% 2/35 • Number of events 3 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
Investigations Blood bilirubin increased	6.7% 5/75 • Number of events 12 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	2.9% 1/35 • Number of events 1 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
Investigations WBC count deceased	2.7% 2/75 • Number of events 7 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	11.4% 4/35 • Number of events 7 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
Investigations Aspartate aminotransferase increased	5.3% 4/75 • Number of events 11 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	2.9% 1/35 • Number of events 1 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
Investigations Blood alkaline phosphatase increased	5.3% 4/75 • Number of events 11 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	2.9% 1/35 • Number of events 2 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
Investigations Haemoglobin deceased	4.0% 3/75 • Number of events 10 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.	5.7% 2/35 • Number of events 3 • Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.