Trial Outcomes & Findings for Investigate the Safety and Tolerability of Olaparib Tablet in Japanese Patients With Advanced Solid Malignancies (NCT NCT01813474)

Last Updated: 2018-01-16

Results Overview

An adverse event is the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. This was recorded if it happend from the start dose to 30 days after the last of study drug.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

23 participants

Primary outcome timeframe

From the start dose to 30 days after the last dose of study drug

Results posted on

2018-01-16

Participant Flow

First patient enrolled on 25 March 2013. Last patient enrolled on 31 October 2013. Data cut off on 31 July 2014.

A total of 28 participants gave informed consent to join this study. Five participants were screen failures so that 23 participants were assigned and received study treatment

Participant milestones

Participant milestones
Measure	200 mg Bid, Dose Escalation Part Olaparib tablet 200 mg bid, 400 mg/day, dose escalation part	300 mg Bid, Dose Escalation Part Olaparib table 300 mg bid, 600 mg/day, dose escalation part	300 mg Bid, Expansion Part Olaparib tablet 300 mg bid, 600 mg/day, expansion part
Overall Study STARTED	4	7	12
Overall Study COMPLETED	1	0	1
Overall Study NOT COMPLETED	3	7	11

Reasons for withdrawal

Reasons for withdrawal
Measure	200 mg Bid, Dose Escalation Part Olaparib tablet 200 mg bid, 400 mg/day, dose escalation part	300 mg Bid, Dose Escalation Part Olaparib table 300 mg bid, 600 mg/day, dose escalation part	300 mg Bid, Expansion Part Olaparib tablet 300 mg bid, 600 mg/day, expansion part
Overall Study Withdrawal by Subject	0	0	1
Overall Study Adverse Event	1	1	0
Overall Study Lack of Efficacy	2	6	9
Overall Study Death	0	0	1

Baseline Characteristics

Investigate the Safety and Tolerability of Olaparib Tablet in Japanese Patients With Advanced Solid Malignancies

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	200 mg Bid, Dose Escalation Part n=4 Participants Olaparib tablet 200 mg bid, 400 mg/day, dose escalation part	300 mg Bid, Dose Escalation Part n=7 Participants Olaparib table 300 mg bid, 600 mg/day, dose escalation part	300 mg Bid, Expansion Part n=12 Participants Olaparib tablet 300 mg bid, 600 mg/day, expansion part	Total n=23 Participants Total of all reporting groups
Age, Continuous	42.0 Years STANDARD_DEVIATION 8.68 • n=99 Participants	55.4 Years STANDARD_DEVIATION 8.98 • n=107 Participants	57.3 Years STANDARD_DEVIATION 12.43 • n=206 Participants	54.1 Years STANDARD_DEVIATION 11.94 • n=7 Participants
Sex: Female, Male Sex · Female	4 Participants n=99 Participants	4 Participants n=107 Participants	7 Participants n=206 Participants	15 Participants n=7 Participants
Sex: Female, Male Sex · Male	0 Participants n=99 Participants	3 Participants n=107 Participants	5 Participants n=206 Participants	8 Participants n=7 Participants
Primary tumour location Breast	1 Participants n=99 Participants	1 Participants n=107 Participants	3 Participants n=206 Participants	5 Participants n=7 Participants
Primary tumour location Colorectal	0 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants	1 Participants n=7 Participants
Primary tumour location Lung	0 Participants n=99 Participants	1 Participants n=107 Participants	2 Participants n=206 Participants	3 Participants n=7 Participants
Primary tumour location Peritoneum	0 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants	1 Participants n=7 Participants
Primary tumour location Pancreas	0 Participants n=99 Participants	1 Participants n=107 Participants	0 Participants n=206 Participants	1 Participants n=7 Participants
Primary tumour location Ovary	0 Participants n=99 Participants	2 Participants n=107 Participants	2 Participants n=206 Participants	4 Participants n=7 Participants
Primary tumour location Uterus	1 Participants n=99 Participants	1 Participants n=107 Participants	0 Participants n=206 Participants	2 Participants n=7 Participants
Primary tumour location Cervix	2 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	2 Participants n=7 Participants
Primary tumour location Colon	0 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants	1 Participants n=7 Participants
Primary tumour location Gastric Antrum	0 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants	1 Participants n=7 Participants
Primary tumour location Other	0 Participants n=99 Participants	1 Participants n=107 Participants	1 Participants n=206 Participants	2 Participants n=7 Participants

PRIMARY outcome

Timeframe: From the start dose to 30 days after the last dose of study drug

Outcome measures

Outcome measures
Measure	200 mg Bid, Dose Escalation Part n=4 Participants Olaparib tablet 200 mg bid, 400 mg/day, dose escalation part	300 mg Bid, Dose Escalation Part n=7 Participants Olaparib table 300 mg bid, 600 mg/day, dose escalation part	300 mg Bid, Expansion Part n=12 Participants Olaparib tablet 300 mg bid, 600 mg/day, expansion part
Number of Participants With Adverse Events At least 1 Adverse Events (AE)	4 Participants	7 Participants	10 Participants
Number of Participants With Adverse Events At least 1 AE of CTCAE Grade 3 or higher	1 Participants	3 Participants	1 Participants
Number of Participants With Adverse Events At least 1 Serious Adverse Events (SAE)	1 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From the start dose to 28 days after the first dose of study drug

Population: All patients in only the dose escalation part who received olaparib and completed the safety follow-up through the dose-limiting toxicity (DLT) evaluation period (28 days), or who experienced a DLT.

Dose Limiting Toxicities were defined as study specific events that is determined to be possibly or probably related to olaparib (as determined by the investigator) and occurring during the first cycle of treatment (28 days after the first dose), irrespective of whether the toxicity resolved.

Outcome measures

Outcome measures
Measure	200 mg Bid, Dose Escalation Part n=3 Participants Olaparib tablet 200 mg bid, 400 mg/day, dose escalation part	300 mg Bid, Dose Escalation Part n=6 Participants Olaparib table 300 mg bid, 600 mg/day, dose escalation part	300 mg Bid, Expansion Part Olaparib tablet 300 mg bid, 600 mg/day, expansion part
Number of Participants With Dose Limiting Toxicities	0 Participants	0 Participants	—

SECONDARY outcome

Timeframe: Day 1: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours at post-dose

Population: Dose escalation part only

Outcome measures

Outcome measures
Measure	200 mg Bid, Dose Escalation Part n=4 Participants Olaparib tablet 200 mg bid, 400 mg/day, dose escalation part	300 mg Bid, Dose Escalation Part n=7 Participants Olaparib table 300 mg bid, 600 mg/day, dose escalation part	300 mg Bid, Expansion Part Olaparib tablet 300 mg bid, 600 mg/day, expansion part
Cmax Following Single Dosing	6.697 μg/mL Geometric Coefficient of Variation 95.69	7.743 μg/mL Geometric Coefficient of Variation 34.76	—

SECONDARY outcome

Timeframe: Day 15: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours at post-dose

Population: Dose escalation part only. Two participants (1 in 200 mg bid and 1 in 300 mg bid) had no PK data due to early discontinuation prior to Day 15.

Outcome measures

Outcome measures
Measure	200 mg Bid, Dose Escalation Part n=3 Participants Olaparib tablet 200 mg bid, 400 mg/day, dose escalation part	300 mg Bid, Dose Escalation Part n=6 Participants Olaparib table 300 mg bid, 600 mg/day, dose escalation part	300 mg Bid, Expansion Part Olaparib tablet 300 mg bid, 600 mg/day, expansion part
Cmax Following Multiple Dosing	7.668 μg/mL Geometric Coefficient of Variation 46.93	8.434 μg/mL Geometric Coefficient of Variation 35.05	—

SECONDARY outcome

Timeframe: Day 1: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours at post-dose

Population: Dose escalation part only

Outcome measures

Outcome measures
Measure	200 mg Bid, Dose Escalation Part n=4 Participants Olaparib tablet 200 mg bid, 400 mg/day, dose escalation part	300 mg Bid, Dose Escalation Part n=7 Participants Olaparib table 300 mg bid, 600 mg/day, dose escalation part	300 mg Bid, Expansion Part Olaparib tablet 300 mg bid, 600 mg/day, expansion part
Tmax Following Single Dosing	2.00 hour Full Range 95.69 • Interval 1.0 to 3.0	1.98 hour Full Range 34.76 • Interval 1.0 to 3.0	—

SECONDARY outcome

Timeframe: Day 15: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours at post-dose

Population: Dose escalation part only. Two participants (1 in 200 mg bid and 1 in 300 mg bid) had no PK data due to early discontinuation prior to Day 15.

Outcome measures

Outcome measures
Measure	200 mg Bid, Dose Escalation Part n=3 Participants Olaparib tablet 200 mg bid, 400 mg/day, dose escalation part	300 mg Bid, Dose Escalation Part n=6 Participants Olaparib table 300 mg bid, 600 mg/day, dose escalation part	300 mg Bid, Expansion Part Olaparib tablet 300 mg bid, 600 mg/day, expansion part
Tmax Following Multiple Dosing	1.50 hour Full Range 46.93 • Interval 1.0 to 3.0	3.00 hour Full Range 35.05 • Interval 1.5 to 3.93	—

SECONDARY outcome

Timeframe: Day 1: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours at post-dose

Population: Dose escalation part only. One participant in 200 mg bid had no AUC data because AUC was not calculable for this participant.

Outcome measures

Outcome measures
Measure	200 mg Bid, Dose Escalation Part n=3 Participants Olaparib tablet 200 mg bid, 400 mg/day, dose escalation part	300 mg Bid, Dose Escalation Part n=7 Participants Olaparib table 300 mg bid, 600 mg/day, dose escalation part	300 mg Bid, Expansion Part Olaparib tablet 300 mg bid, 600 mg/day, expansion part
AUC Following Single Dosing	61.97 μg*h/mL Geometric Coefficient of Variation 473.4	46.21 μg*h/mL Geometric Coefficient of Variation 64.64	—

SECONDARY outcome

Timeframe: Day 15: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours at post-dose

Population: Dose escalation part only. Two participants (1 in 200 mg bid and 1 in 300 mg bid) had no PK data due to early discontinuation prior to Day 15.

Outcome measures

Outcome measures
Measure	200 mg Bid, Dose Escalation Part n=3 Participants Olaparib tablet 200 mg bid, 400 mg/day, dose escalation part	300 mg Bid, Dose Escalation Part n=6 Participants Olaparib table 300 mg bid, 600 mg/day, dose escalation part	300 mg Bid, Expansion Part Olaparib tablet 300 mg bid, 600 mg/day, expansion part
AUC at Steady State Following Multiple Dosing	36.50 μg*h/mL Geometric Coefficient of Variation 71.94	52.34 μg*h/mL Geometric Coefficient of Variation 68.17	—

Adverse Events

200 mg Bid, Dose Escalation Part

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

300 mg Bid, Dose Escalation Part

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

300 mg Bid, Expansion Part

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	200 mg Bid, Dose Escalation Part n=4 participants at risk Olaparib tablet 200 mg bid, 400 mg/day, dose escalation part	300 mg Bid, Dose Escalation Part n=7 participants at risk Olaparib table 300 mg bid, 600 mg/day, dose escalation part	300 mg Bid, Expansion Part n=12 participants at risk Olaparib tablet 300 mg bid, 600 mg/day, expansion part
Gastrointestinal disorders Ileus	25.0% 1/4 • Number of events 1 • Through treatment and 30-day follow-up period, an average of about 4 months.	0.00% 0/7 • Through treatment and 30-day follow-up period, an average of about 4 months.	0.00% 0/12 • Through treatment and 30-day follow-up period, an average of about 4 months.

Other adverse events

Additional Information

Medical Director

AstraZeneca

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	200 mg Bid, Dose Escalation Part n=4 participants at risk Olaparib tablet 200 mg bid, 400 mg/day, dose escalation part	300 mg Bid, Dose Escalation Part n=7 participants at risk Olaparib table 300 mg bid, 600 mg/day, dose escalation part	300 mg Bid, Expansion Part n=12 participants at risk Olaparib tablet 300 mg bid, 600 mg/day, expansion part
Infections and infestations Nasopharyngitis	25.0% 1/4 • Through treatment and 30-day follow-up period, an average of about 4 months.	0.00% 0/7 • Through treatment and 30-day follow-up period, an average of about 4 months.	8.3% 1/12 • Through treatment and 30-day follow-up period, an average of about 4 months.
Infections and infestations Paronychia	0.00% 0/4 • Through treatment and 30-day follow-up period, an average of about 4 months.	14.3% 1/7 • Through treatment and 30-day follow-up period, an average of about 4 months.	0.00% 0/12 • Through treatment and 30-day follow-up period, an average of about 4 months.
Infections and infestations Pneumonia	0.00% 0/4 • Through treatment and 30-day follow-up period, an average of about 4 months.	0.00% 0/7 • Through treatment and 30-day follow-up period, an average of about 4 months.	8.3% 1/12 • Through treatment and 30-day follow-up period, an average of about 4 months.
Infections and infestations Pyelonephritis	25.0% 1/4 • Through treatment and 30-day follow-up period, an average of about 4 months.	0.00% 0/7 • Through treatment and 30-day follow-up period, an average of about 4 months.	0.00% 0/12 • Through treatment and 30-day follow-up period, an average of about 4 months.
Infections and infestations Upper respiratory tract infection	0.00% 0/4 • Through treatment and 30-day follow-up period, an average of about 4 months.	0.00% 0/7 • Through treatment and 30-day follow-up period, an average of about 4 months.	8.3% 1/12 • Through treatment and 30-day follow-up period, an average of about 4 months.
Blood and lymphatic system disorders Anaemia	0.00% 0/4 • Through treatment and 30-day follow-up period, an average of about 4 months.	57.1% 4/7 • Through treatment and 30-day follow-up period, an average of about 4 months.	16.7% 2/12 • Through treatment and 30-day follow-up period, an average of about 4 months.
Blood and lymphatic system disorders Neutropenia	0.00% 0/4 • Through treatment and 30-day follow-up period, an average of about 4 months.	14.3% 1/7 • Through treatment and 30-day follow-up period, an average of about 4 months.	0.00% 0/12 • Through treatment and 30-day follow-up period, an average of about 4 months.
Metabolism and nutrition disorders Decreased appetite	0.00% 0/4 • Through treatment and 30-day follow-up period, an average of about 4 months.	57.1% 4/7 • Through treatment and 30-day follow-up period, an average of about 4 months.	25.0% 3/12 • Through treatment and 30-day follow-up period, an average of about 4 months.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/4 • Through treatment and 30-day follow-up period, an average of about 4 months.	14.3% 1/7 • Through treatment and 30-day follow-up period, an average of about 4 months.	0.00% 0/12 • Through treatment and 30-day follow-up period, an average of about 4 months.
Psychiatric disorders Anxiety	0.00% 0/4 • Through treatment and 30-day follow-up period, an average of about 4 months.	14.3% 1/7 • Through treatment and 30-day follow-up period, an average of about 4 months.	0.00% 0/12 • Through treatment and 30-day follow-up period, an average of about 4 months.
Nervous system disorders Dizziness	0.00% 0/4 • Through treatment and 30-day follow-up period, an average of about 4 months.	14.3% 1/7 • Through treatment and 30-day follow-up period, an average of about 4 months.	0.00% 0/12 • Through treatment and 30-day follow-up period, an average of about 4 months.
Nervous system disorders Dysgeusia	0.00% 0/4 • Through treatment and 30-day follow-up period, an average of about 4 months.	14.3% 1/7 • Through treatment and 30-day follow-up period, an average of about 4 months.	0.00% 0/12 • Through treatment and 30-day follow-up period, an average of about 4 months.
Nervous system disorders Headache	25.0% 1/4 • Through treatment and 30-day follow-up period, an average of about 4 months.	0.00% 0/7 • Through treatment and 30-day follow-up period, an average of about 4 months.	0.00% 0/12 • Through treatment and 30-day follow-up period, an average of about 4 months.
Eye disorders Erythema of eyelid	0.00% 0/4 • Through treatment and 30-day follow-up period, an average of about 4 months.	14.3% 1/7 • Through treatment and 30-day follow-up period, an average of about 4 months.	0.00% 0/12 • Through treatment and 30-day follow-up period, an average of about 4 months.
Eye disorders Eye pruritus	0.00% 0/4 • Through treatment and 30-day follow-up period, an average of about 4 months.	14.3% 1/7 • Through treatment and 30-day follow-up period, an average of about 4 months.	0.00% 0/12 • Through treatment and 30-day follow-up period, an average of about 4 months.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/4 • Through treatment and 30-day follow-up period, an average of about 4 months.	14.3% 1/7 • Through treatment and 30-day follow-up period, an average of about 4 months.	0.00% 0/12 • Through treatment and 30-day follow-up period, an average of about 4 months.
Respiratory, thoracic and mediastinal disorders Dysaesthesia pharynx	25.0% 1/4 • Through treatment and 30-day follow-up period, an average of about 4 months.	14.3% 1/7 • Through treatment and 30-day follow-up period, an average of about 4 months.	0.00% 0/12 • Through treatment and 30-day follow-up period, an average of about 4 months.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/4 • Through treatment and 30-day follow-up period, an average of about 4 months.	14.3% 1/7 • Through treatment and 30-day follow-up period, an average of about 4 months.	0.00% 0/12 • Through treatment and 30-day follow-up period, an average of about 4 months.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/4 • Through treatment and 30-day follow-up period, an average of about 4 months.	14.3% 1/7 • Through treatment and 30-day follow-up period, an average of about 4 months.	8.3% 1/12 • Through treatment and 30-day follow-up period, an average of about 4 months.
Gastrointestinal disorders Constipation	0.00% 0/4 • Through treatment and 30-day follow-up period, an average of about 4 months.	28.6% 2/7 • Through treatment and 30-day follow-up period, an average of about 4 months.	33.3% 4/12 • Through treatment and 30-day follow-up period, an average of about 4 months.
Gastrointestinal disorders Diarrhoea	0.00% 0/4 • Through treatment and 30-day follow-up period, an average of about 4 months.	28.6% 2/7 • Through treatment and 30-day follow-up period, an average of about 4 months.	16.7% 2/12 • Through treatment and 30-day follow-up period, an average of about 4 months.
Gastrointestinal disorders Duodenitis	0.00% 0/4 • Through treatment and 30-day follow-up period, an average of about 4 months.	14.3% 1/7 • Through treatment and 30-day follow-up period, an average of about 4 months.	0.00% 0/12 • Through treatment and 30-day follow-up period, an average of about 4 months.
Gastrointestinal disorders Dyspepsia	0.00% 0/4 • Through treatment and 30-day follow-up period, an average of about 4 months.	28.6% 2/7 • Through treatment and 30-day follow-up period, an average of about 4 months.	8.3% 1/12 • Through treatment and 30-day follow-up period, an average of about 4 months.
Gastrointestinal disorders Gastritis	0.00% 0/4 • Through treatment and 30-day follow-up period, an average of about 4 months.	0.00% 0/7 • Through treatment and 30-day follow-up period, an average of about 4 months.	8.3% 1/12 • Through treatment and 30-day follow-up period, an average of about 4 months.
Gastrointestinal disorders Nausea	25.0% 1/4 • Through treatment and 30-day follow-up period, an average of about 4 months.	85.7% 6/7 • Through treatment and 30-day follow-up period, an average of about 4 months.	25.0% 3/12 • Through treatment and 30-day follow-up period, an average of about 4 months.
Gastrointestinal disorders Stomatitis	0.00% 0/4 • Through treatment and 30-day follow-up period, an average of about 4 months.	14.3% 1/7 • Through treatment and 30-day follow-up period, an average of about 4 months.	0.00% 0/12 • Through treatment and 30-day follow-up period, an average of about 4 months.
Gastrointestinal disorders Toothache	25.0% 1/4 • Through treatment and 30-day follow-up period, an average of about 4 months.	0.00% 0/7 • Through treatment and 30-day follow-up period, an average of about 4 months.	0.00% 0/12 • Through treatment and 30-day follow-up period, an average of about 4 months.
Gastrointestinal disorders Vomiting	0.00% 0/4 • Through treatment and 30-day follow-up period, an average of about 4 months.	14.3% 1/7 • Through treatment and 30-day follow-up period, an average of about 4 months.	8.3% 1/12 • Through treatment and 30-day follow-up period, an average of about 4 months.
Hepatobiliary disorders Hepatic function abnormal	0.00% 0/4 • Through treatment and 30-day follow-up period, an average of about 4 months.	0.00% 0/7 • Through treatment and 30-day follow-up period, an average of about 4 months.	8.3% 1/12 • Through treatment and 30-day follow-up period, an average of about 4 months.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	0.00% 0/4 • Through treatment and 30-day follow-up period, an average of about 4 months.	14.3% 1/7 • Through treatment and 30-day follow-up period, an average of about 4 months.	0.00% 0/12 • Through treatment and 30-day follow-up period, an average of about 4 months.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/4 • Through treatment and 30-day follow-up period, an average of about 4 months.	14.3% 1/7 • Through treatment and 30-day follow-up period, an average of about 4 months.	0.00% 0/12 • Through treatment and 30-day follow-up period, an average of about 4 months.
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/4 • Through treatment and 30-day follow-up period, an average of about 4 months.	0.00% 0/7 • Through treatment and 30-day follow-up period, an average of about 4 months.	8.3% 1/12 • Through treatment and 30-day follow-up period, an average of about 4 months.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/4 • Through treatment and 30-day follow-up period, an average of about 4 months.	0.00% 0/7 • Through treatment and 30-day follow-up period, an average of about 4 months.	8.3% 1/12 • Through treatment and 30-day follow-up period, an average of about 4 months.
Musculoskeletal and connective tissue disorders Back pain	25.0% 1/4 • Through treatment and 30-day follow-up period, an average of about 4 months.	0.00% 0/7 • Through treatment and 30-day follow-up period, an average of about 4 months.	0.00% 0/12 • Through treatment and 30-day follow-up period, an average of about 4 months.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/4 • Through treatment and 30-day follow-up period, an average of about 4 months.	14.3% 1/7 • Through treatment and 30-day follow-up period, an average of about 4 months.	0.00% 0/12 • Through treatment and 30-day follow-up period, an average of about 4 months.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/4 • Through treatment and 30-day follow-up period, an average of about 4 months.	14.3% 1/7 • Through treatment and 30-day follow-up period, an average of about 4 months.	0.00% 0/12 • Through treatment and 30-day follow-up period, an average of about 4 months.
Renal and urinary disorders Proteinuria	0.00% 0/4 • Through treatment and 30-day follow-up period, an average of about 4 months.	28.6% 2/7 • Through treatment and 30-day follow-up period, an average of about 4 months.	0.00% 0/12 • Through treatment and 30-day follow-up period, an average of about 4 months.
General disorders Fatigue	0.00% 0/4 • Through treatment and 30-day follow-up period, an average of about 4 months.	14.3% 1/7 • Through treatment and 30-day follow-up period, an average of about 4 months.	16.7% 2/12 • Through treatment and 30-day follow-up period, an average of about 4 months.
General disorders Malaise	0.00% 0/4 • Through treatment and 30-day follow-up period, an average of about 4 months.	28.6% 2/7 • Through treatment and 30-day follow-up period, an average of about 4 months.	16.7% 2/12 • Through treatment and 30-day follow-up period, an average of about 4 months.
General disorders Oedema	0.00% 0/4 • Through treatment and 30-day follow-up period, an average of about 4 months.	14.3% 1/7 • Through treatment and 30-day follow-up period, an average of about 4 months.	0.00% 0/12 • Through treatment and 30-day follow-up period, an average of about 4 months.
General disorders Pyrexia	0.00% 0/4 • Through treatment and 30-day follow-up period, an average of about 4 months.	14.3% 1/7 • Through treatment and 30-day follow-up period, an average of about 4 months.	0.00% 0/12 • Through treatment and 30-day follow-up period, an average of about 4 months.
Investigations Alanine aminotransferase increased	0.00% 0/4 • Through treatment and 30-day follow-up period, an average of about 4 months.	14.3% 1/7 • Through treatment and 30-day follow-up period, an average of about 4 months.	8.3% 1/12 • Through treatment and 30-day follow-up period, an average of about 4 months.
Investigations Aspartate aminotransferase increased	0.00% 0/4 • Through treatment and 30-day follow-up period, an average of about 4 months.	14.3% 1/7 • Through treatment and 30-day follow-up period, an average of about 4 months.	8.3% 1/12 • Through treatment and 30-day follow-up period, an average of about 4 months.
Investigations Blood creatinine increased	0.00% 0/4 • Through treatment and 30-day follow-up period, an average of about 4 months.	14.3% 1/7 • Through treatment and 30-day follow-up period, an average of about 4 months.	8.3% 1/12 • Through treatment and 30-day follow-up period, an average of about 4 months.
Investigations Grip strength decreased	0.00% 0/4 • Through treatment and 30-day follow-up period, an average of about 4 months.	14.3% 1/7 • Through treatment and 30-day follow-up period, an average of about 4 months.	0.00% 0/12 • Through treatment and 30-day follow-up period, an average of about 4 months.
Investigations Lymphocyte count decreased	0.00% 0/4 • Through treatment and 30-day follow-up period, an average of about 4 months.	14.3% 1/7 • Through treatment and 30-day follow-up period, an average of about 4 months.	0.00% 0/12 • Through treatment and 30-day follow-up period, an average of about 4 months.
Investigations Neutrophil count decreased	0.00% 0/4 • Through treatment and 30-day follow-up period, an average of about 4 months.	28.6% 2/7 • Through treatment and 30-day follow-up period, an average of about 4 months.	16.7% 2/12 • Through treatment and 30-day follow-up period, an average of about 4 months.
Investigations Platelet count decreased	0.00% 0/4 • Through treatment and 30-day follow-up period, an average of about 4 months.	14.3% 1/7 • Through treatment and 30-day follow-up period, an average of about 4 months.	0.00% 0/12 • Through treatment and 30-day follow-up period, an average of about 4 months.
Investigations White blood cell count decreased	0.00% 0/4 • Through treatment and 30-day follow-up period, an average of about 4 months.	42.9% 3/7 • Through treatment and 30-day follow-up period, an average of about 4 months.	16.7% 2/12 • Through treatment and 30-day follow-up period, an average of about 4 months.
Injury, poisoning and procedural complications Contusion	0.00% 0/4 • Through treatment and 30-day follow-up period, an average of about 4 months.	0.00% 0/7 • Through treatment and 30-day follow-up period, an average of about 4 months.	8.3% 1/12 • Through treatment and 30-day follow-up period, an average of about 4 months.
Injury, poisoning and procedural complications Procedural pain	0.00% 0/4 • Through treatment and 30-day follow-up period, an average of about 4 months.	14.3% 1/7 • Through treatment and 30-day follow-up period, an average of about 4 months.	0.00% 0/12 • Through treatment and 30-day follow-up period, an average of about 4 months.