Trial Outcomes & Findings for Pharmacokinetics and Safety of ORF Tablets in Pediatric Patients (NCT NCT01160614)

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

30 participants

Primary outcome timeframe

Up to 24 hours

Results posted on

2012-10-15

Participant Flow

First Patient First Visit: 18-Aug-2010; Last Patient Last Visit: 16-Aug-2011. The study was conducted at 11 sites in the United States and Australia.

Pediatric patients who were anticipated to have pain requiring opioid analgesia.

Participant milestones

Participant milestones
Measure	6 to < 12 Years Children aged 6 to \< 12 Years received ORF Tablets (10 mg, 15 mg or 20 mg taken every 12 hours). Study treatment could have lasted from 12 hours (single dose) to 72 hours (5 doses).	≥ 12 to ≤ 16 Years Children aged ≥ 12 to ≤ 16 Years received ORF Tablets (10 mg, 15 mg or 20 mg taken every 12 hours). Study treatment could have lasted from 12 hours (single dose) to 72 hours (5 doses).
Overall Study STARTED	5	25
Overall Study COMPLETED	5	23
Overall Study NOT COMPLETED	0	2

Reasons for withdrawal

Reasons for withdrawal
Measure	6 to < 12 Years Children aged 6 to \< 12 Years received ORF Tablets (10 mg, 15 mg or 20 mg taken every 12 hours). Study treatment could have lasted from 12 hours (single dose) to 72 hours (5 doses).	≥ 12 to ≤ 16 Years Children aged ≥ 12 to ≤ 16 Years received ORF Tablets (10 mg, 15 mg or 20 mg taken every 12 hours). Study treatment could have lasted from 12 hours (single dose) to 72 hours (5 doses).
Overall Study Withdrawal by Subject	0	2

Baseline Characteristics

Pharmacokinetics and Safety of ORF Tablets in Pediatric Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	6 to < 12 Years n=5 Participants Children aged 6 to \< 12 Years received ORF Tablets (10 mg, 15 mg or 20 mg taken every 12 hours). Study treatment could have lasted from 12 hours (single dose) to 72 hours (5 doses).	≥ 12 to ≤ 16 Years n=25 Participants Children aged ≥ 12 to ≤ 16 Years received ORF Tablets (10 mg, 15 mg or 20 mg taken every 12 hours). Study treatment could have lasted from 12 hours (single dose) to 72 hours (5 doses).	Total n=30 Participants Total of all reporting groups
Age Continuous	10.6 Years STANDARD_DEVIATION 0.9 • n=5 Participants	14.1 Years STANDARD_DEVIATION 1.6 • n=7 Participants	13.5 Years STANDARD_DEVIATION 2.0 • n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	14 Participants n=7 Participants	17 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	11 Participants n=7 Participants	13 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) White	4 Participants n=5 Participants	21 Participants n=7 Participants	25 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 24 hours

Population: The full analysis population for PK (N = 30) was defined as patients who received at least 1 dose of oral study drug and had at least 1 valid quantifiable PK metric

Outcome measures

Outcome measures
Measure	6 to < 12 Years (10 mg ORF) n=1 Participants Children from 6 to \< 12 years received a single dose of 10 mg ORF	6 to < 12 Years (15 mg ORF) n=1 Participants Children from 6 to \< 12 years received a single dose of 15 mg ORF	6 to < 12 Years (20 mg ORF) n=1 Participants Children from 6 to \< 12 years received a single dose of 20 mg ORF	≥ 12 to ≤ 16 Years (10 mg ORF) n=2 Participants Children from ≥ 12 to ≤ 16 years received a single dose of 10 mg ORF	≥ 12 to ≤ 16 Years (15 mg ORF) n=5 Participants Children from ≥ 12 to ≤ 16 years received a single dose of 15 mg ORF	≥ 12 to ≤ 16 Years (20 mg ORF) n=8 Participants Children from ≥ 12 to ≤ 16 years received a single dose of 20 mg ORF. One patient took a single dose of ORF 30 mg and is included in this dose level.
Single-dose PK Metric: Area Under the Plasma Concentration-time Curve From Hour 0 to the Last Measurable Plasma Concentration [AUCt]	129.2 ng*h/mL Standard Deviation NA Standard deviation not calculable since there was only 1 patient in this group	121.1 ng*h/mL Standard Deviation NA Standard deviation not calculable since there was only 1 patient in this group	272.2 ng*h/mL Standard Deviation NA Standard deviation not calculable since there was only 1 patient in this group	85.5 ng*h/mL Standard Deviation 39.3	193.0 ng*h/mL Standard Deviation 149.4	264.4 ng*h/mL Standard Deviation 128.1

PRIMARY outcome

Timeframe: Up to 24 hours

Due to insufficient sampling, AUCinf was not estimated.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Up to 24 hours

Population: The full analysis population for PK (N = 30) was defined as patients who received at least 1 dose of oral study drug and had at least 1 valid quantifiable PK metric

Outcome measures

Outcome measures
Measure	6 to < 12 Years (10 mg ORF) n=1 Participants Children from 6 to \< 12 years received a single dose of 10 mg ORF	6 to < 12 Years (15 mg ORF) n=1 Participants Children from 6 to \< 12 years received a single dose of 15 mg ORF	6 to < 12 Years (20 mg ORF) n=1 Participants Children from 6 to \< 12 years received a single dose of 20 mg ORF	≥ 12 to ≤ 16 Years (10 mg ORF) n=2 Participants Children from ≥ 12 to ≤ 16 years received a single dose of 10 mg ORF	≥ 12 to ≤ 16 Years (15 mg ORF) n=5 Participants Children from ≥ 12 to ≤ 16 years received a single dose of 15 mg ORF	≥ 12 to ≤ 16 Years (20 mg ORF) n=8 Participants Children from ≥ 12 to ≤ 16 years received a single dose of 20 mg ORF. One patient took a single dose of ORF 30 mg and is included in this dose level.
Single-dose PK Metric: Maximum Observed Plasma Concentration (Cmax)	12.3 ng/mL Standard Deviation NA Standard deviation not calculable since there was only 1 patient in this group	16.6 ng/mL Standard Deviation NA Standard deviation not calculable since there was only 1 patient in this group	21.9 ng/mL Standard Deviation NA Standard deviation not calculable since there was only 1 patient in this group	8.3 ng/mL Standard Deviation 1.9	26.6 ng/mL Standard Deviation 16.0	26.2 ng/mL Standard Deviation 7.9

PRIMARY outcome

Timeframe: Up to 24 hours

Population: The full analysis population for PK (N = 30) was defined as patients who received at least 1 dose of oral study drug and had at least 1 valid quantifiable PK metric

Outcome measures

Outcome measures
Measure	6 to < 12 Years (10 mg ORF) n=1 Participants Children from 6 to \< 12 years received a single dose of 10 mg ORF	6 to < 12 Years (15 mg ORF) n=1 Participants Children from 6 to \< 12 years received a single dose of 15 mg ORF	6 to < 12 Years (20 mg ORF) n=1 Participants Children from 6 to \< 12 years received a single dose of 20 mg ORF	≥ 12 to ≤ 16 Years (10 mg ORF) n=2 Participants Children from ≥ 12 to ≤ 16 years received a single dose of 10 mg ORF	≥ 12 to ≤ 16 Years (15 mg ORF) n=5 Participants Children from ≥ 12 to ≤ 16 years received a single dose of 15 mg ORF	≥ 12 to ≤ 16 Years (20 mg ORF) n=8 Participants Children from ≥ 12 to ≤ 16 years received a single dose of 20 mg ORF. One patient took a single dose of ORF 30 mg and is included in this dose level.
Single-dose PK Metric: Time to Maximum Plasma Concentration (Tmax)	6 hour (h) Interval 6.0 to 6.0	3 hour (h) Full Range NA • Interval 3.0 to 3.0	12 hour (h) Full Range NA • Interval 12.0 to 12.0	5.3 hour (h) Full Range 1.011 • Interval 4.6 to 6.0	3 hour (h) Full Range 1.26 • Interval 1.5 to 4.5	6 hour (h) Full Range 6.663 • Interval 4.4 to 24.1

PRIMARY outcome

Timeframe: Up to 24 hours

Due to insufficient sampling, Lamda z was not estimated.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Up to 24 hours

Due to insufficient sampling, t1/2z was not estimated.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Up to 24 hours

Due to insufficient sampling, tlag was not estimated.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Up to 12 hours

Population: The full analysis population for PK (N = 30) was defined as patients who received at least 1 dose of oral study drug and had at least 1 valid quantifiable PK metric

Outcome measures

Outcome measures
Measure	6 to < 12 Years (10 mg ORF) n=2 Participants Children from 6 to \< 12 years received a single dose of 10 mg ORF	6 to < 12 Years (15 mg ORF) n=2 Participants Children from 6 to \< 12 years received a single dose of 15 mg ORF	6 to < 12 Years (20 mg ORF) n=1 Participants Children from 6 to \< 12 years received a single dose of 20 mg ORF	≥ 12 to ≤ 16 Years (10 mg ORF) n=4 Participants Children from ≥ 12 to ≤ 16 years received a single dose of 10 mg ORF	≥ 12 to ≤ 16 Years (15 mg ORF) n=8 Participants Children from ≥ 12 to ≤ 16 years received a single dose of 15 mg ORF	≥ 12 to ≤ 16 Years (20 mg ORF) n=9 Participants Children from ≥ 12 to ≤ 16 years received a single dose of 20 mg ORF. One patient took a single dose of ORF 30 mg and is included in this dose level.
Single- and Multiple-dose PK Metric: Mean Area Under the Plasma Concentration During Each Dosing Interval-time Curve From Hour 0 to 12 Hours of the First Dose of ORF (AUC 0-12)	67.5 ng*h/mL Standard Deviation 29.1	114.5 ng*h/mL Standard Deviation 9.4	112.8 ng*h/mL Standard Deviation NA Standard deviation not calculable since there was only 1 patient in this group	82.5 ng*h/mL Standard Deviation 13.4	139.0 ng*h/mL Standard Deviation 105.2	174.2 ng*h/mL Standard Deviation 112.7

PRIMARY outcome

Timeframe: Up to 12 hours

Population: The full analysis population for PK (N = 30) was defined as patients who received at least 1 dose of oral study drug and had at least 1 valid quantifiable PK metric

Outcome measures

Outcome measures
Measure	6 to < 12 Years (10 mg ORF) n=2 Participants Children from 6 to \< 12 years received a single dose of 10 mg ORF	6 to < 12 Years (15 mg ORF) n=2 Participants Children from 6 to \< 12 years received a single dose of 15 mg ORF	6 to < 12 Years (20 mg ORF) n=1 Participants Children from 6 to \< 12 years received a single dose of 20 mg ORF	≥ 12 to ≤ 16 Years (10 mg ORF) n=5 Participants Children from ≥ 12 to ≤ 16 years received a single dose of 10 mg ORF	≥ 12 to ≤ 16 Years (15 mg ORF) n=9 Participants Children from ≥ 12 to ≤ 16 years received a single dose of 15 mg ORF	≥ 12 to ≤ 16 Years (20 mg ORF) n=11 Participants Children from ≥ 12 to ≤ 16 years received a single dose of 20 mg ORF. One patient took a single dose of ORF 30 mg and is included in this dose level.
Single- and Multiple-dose PK Metric: Maximum Observed Plasma Concentration From Hour 0 to 12 Hours of the First Dose of ORF (Cmax 0-12)	9.4 ng/mL Standard Deviation 4.2	23.5 ng/mL Standard Deviation 9.8	21.9 ng/mL Standard Deviation NA Standard deviation not calculable since there was only 1 patient in this group	10.0 ng/mL Standard Deviation 2.3	21.8 ng/mL Standard Deviation 14.2	25.1 ng/mL Standard Deviation 14.2

PRIMARY outcome

Timeframe: Up to 12 hours

Population: The full analysis population for PK (N = 30) was defined as patients who received at least 1 dose of oral study drug and had at least 1 valid quantifiable PK metric

Outcome measures

Outcome measures
Measure	6 to < 12 Years (10 mg ORF) n=2 Participants Children from 6 to \< 12 years received a single dose of 10 mg ORF	6 to < 12 Years (15 mg ORF) n=2 Participants Children from 6 to \< 12 years received a single dose of 15 mg ORF	6 to < 12 Years (20 mg ORF) n=1 Participants Children from 6 to \< 12 years received a single dose of 20 mg ORF	≥ 12 to ≤ 16 Years (10 mg ORF) n=5 Participants Children from ≥ 12 to ≤ 16 years received a single dose of 10 mg ORF	≥ 12 to ≤ 16 Years (15 mg ORF) n=9 Participants Children from ≥ 12 to ≤ 16 years received a single dose of 15 mg ORF	≥ 12 to ≤ 16 Years (20 mg ORF) n=11 Participants Children from ≥ 12 to ≤ 16 years received a single dose of 20 mg ORF. One patient took a single dose of ORF 30 mg and is included in this dose level.
Single- and Multiple-dose PK Metric: Time to Maximum Plasma Concentration From Hour 0 to 12 Hours of the First Dose of ORF (Tmax 0-12)	9 h Full Range 4.243 • Interval 6.0 to 12.0	7.3 h Full Range 6.131 • Interval 3.0 to 11.7	12 h Full Range NA • Interval 12.0 to 12.0	4.6 h Full Range 3.526 • Interval 2.8 to 12.0	4.5 h Full Range 3.036 • Interval 1.5 to 12.0	6 h Full Range 2.931 • Interval 3.3 to 11.9

PRIMARY outcome

Timeframe: Up to 12 hours

Due to insufficient sampling, tlag 0-12 was not estimated.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Adverse events (AEs) & serious adverse events (SAEs) were reported from start of study participation through the period beyond study completion (AEs) & through 30 days following last study drug dose, or until last study visit, whichever was later (SAEs).

Population: The safety population (N = 30) was defined as the group of patients who received study drug

Outcome measures

Outcome measures
Measure	6 to < 12 Years (10 mg ORF) n=5 Participants Children from 6 to \< 12 years received a single dose of 10 mg ORF	6 to < 12 Years (15 mg ORF) n=25 Participants Children from 6 to \< 12 years received a single dose of 15 mg ORF	6 to < 12 Years (20 mg ORF) Children from 6 to \< 12 years received a single dose of 20 mg ORF	≥ 12 to ≤ 16 Years (10 mg ORF) Children from ≥ 12 to ≤ 16 years received a single dose of 10 mg ORF	≥ 12 to ≤ 16 Years (15 mg ORF) Children from ≥ 12 to ≤ 16 years received a single dose of 15 mg ORF	≥ 12 to ≤ 16 Years (20 mg ORF) Children from ≥ 12 to ≤ 16 years received a single dose of 20 mg ORF. One patient took a single dose of ORF 30 mg and is included in this dose level.
The Number of Patients With Adverse Events as a Measure of Safety Death	0 participants	0 participants	—	—	—	—
The Number of Patients With Adverse Events as a Measure of Safety Serious Adverse Event (SAE)	0 participants	1 participants	—	—	—	—
The Number of Patients With Adverse Events as a Measure of Safety Any TEAE reported in ≥ 5% of participants	5 participants	16 participants	—	—	—	—

SECONDARY outcome

Timeframe: Up to 72 hours if all 5 doses were administered

Population: The full analysis population for PK (N = 30) was defined as patients who received at least 1 dose of oral study drug and had at least 1 valid quantifiable PK metric

Outcome measures

Outcome measures
Measure	6 to < 12 Years (10 mg ORF) n=1 Participants Children from 6 to \< 12 years received a single dose of 10 mg ORF	6 to < 12 Years (15 mg ORF) n=1 Participants Children from 6 to \< 12 years received a single dose of 15 mg ORF	6 to < 12 Years (20 mg ORF) Children from 6 to \< 12 years received a single dose of 20 mg ORF	≥ 12 to ≤ 16 Years (10 mg ORF) n=3 Participants Children from ≥ 12 to ≤ 16 years received a single dose of 10 mg ORF	≥ 12 to ≤ 16 Years (15 mg ORF) n=4 Participants Children from ≥ 12 to ≤ 16 years received a single dose of 15 mg ORF	≥ 12 to ≤ 16 Years (20 mg ORF) n=3 Participants Children from ≥ 12 to ≤ 16 years received a single dose of 20 mg ORF. One patient took a single dose of ORF 30 mg and is included in this dose level.
Multiple-dose PK Metric: Minimum Observed Plasma Concentration Just Prior to the Next Dose (Cmin)	15.5 ng/mL Standard Deviation NA Standard deviation not calculable since there was only 1 patient in this group	17.3 ng/mL Standard Deviation NA Standard deviation not calculable since there was only 1 patient in this group	—	4.8 ng/mL Standard Deviation 1.9	11.9 ng/mL Standard Deviation 6.9	19.1 ng/mL Standard Deviation 2.7

Adverse Events

6 to < 12 Years

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

≥ 12 to ≤ 16 Years

Serious events: 1 serious events

Other events: 16 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	6 to < 12 Years n=5 participants at risk Children aged 6 to \< 12 Years received ORF Tablets (10 mg, 15 mg or 20 mg taken every 12 hours). Study treatment could have lasted from 12 hours (single dose) to 72 hours (5 doses).	≥ 12 to ≤ 16 Years n=25 participants at risk Children aged ≥ 12 to ≤ 16 Years received ORF Tablets (10 mg, 15 mg or 20 mg taken every 12 hours). Study treatment could have lasted from 12 hours (single dose) to 72 hours (5 doses).
General disorders Medical device complication	0.00% 0/5 • Adverse events (AEs) & serious adverse events (SAEs) were reported from start of study participation through the period beyond study completion (AEs) & through 30 days following last study drug dose, or until last study visit, whichever was later (SAEs). AEs were learned of through spontaneous reports or patient interview.	4.0% 1/25 • Number of events 1 • Adverse events (AEs) & serious adverse events (SAEs) were reported from start of study participation through the period beyond study completion (AEs) & through 30 days following last study drug dose, or until last study visit, whichever was later (SAEs). AEs were learned of through spontaneous reports or patient interview.

Other adverse events

Additional Information

Medical Services

Purdue Pharma L.P.

Phone: 888-726-7535, option 1

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Measure	6 to < 12 Years n=5 participants at risk Children aged 6 to \< 12 Years received ORF Tablets (10 mg, 15 mg or 20 mg taken every 12 hours). Study treatment could have lasted from 12 hours (single dose) to 72 hours (5 doses).	≥ 12 to ≤ 16 Years n=25 participants at risk Children aged ≥ 12 to ≤ 16 Years received ORF Tablets (10 mg, 15 mg or 20 mg taken every 12 hours). Study treatment could have lasted from 12 hours (single dose) to 72 hours (5 doses).
Gastrointestinal disorders Constipation	20.0% 1/5 • Adverse events (AEs) & serious adverse events (SAEs) were reported from start of study participation through the period beyond study completion (AEs) & through 30 days following last study drug dose, or until last study visit, whichever was later (SAEs). AEs were learned of through spontaneous reports or patient interview.	24.0% 6/25 • Adverse events (AEs) & serious adverse events (SAEs) were reported from start of study participation through the period beyond study completion (AEs) & through 30 days following last study drug dose, or until last study visit, whichever was later (SAEs). AEs were learned of through spontaneous reports or patient interview.
Gastrointestinal disorders Nausea	20.0% 1/5 • Adverse events (AEs) & serious adverse events (SAEs) were reported from start of study participation through the period beyond study completion (AEs) & through 30 days following last study drug dose, or until last study visit, whichever was later (SAEs). AEs were learned of through spontaneous reports or patient interview.	12.0% 3/25 • Adverse events (AEs) & serious adverse events (SAEs) were reported from start of study participation through the period beyond study completion (AEs) & through 30 days following last study drug dose, or until last study visit, whichever was later (SAEs). AEs were learned of through spontaneous reports or patient interview.
Gastrointestinal disorders Vomiting	40.0% 2/5 • Adverse events (AEs) & serious adverse events (SAEs) were reported from start of study participation through the period beyond study completion (AEs) & through 30 days following last study drug dose, or until last study visit, whichever was later (SAEs). AEs were learned of through spontaneous reports or patient interview.	20.0% 5/25 • Adverse events (AEs) & serious adverse events (SAEs) were reported from start of study participation through the period beyond study completion (AEs) & through 30 days following last study drug dose, or until last study visit, whichever was later (SAEs). AEs were learned of through spontaneous reports or patient interview.
Investigations Oxygen saturation decreased	0.00% 0/5 • Adverse events (AEs) & serious adverse events (SAEs) were reported from start of study participation through the period beyond study completion (AEs) & through 30 days following last study drug dose, or until last study visit, whichever was later (SAEs). AEs were learned of through spontaneous reports or patient interview.	8.0% 2/25 • Adverse events (AEs) & serious adverse events (SAEs) were reported from start of study participation through the period beyond study completion (AEs) & through 30 days following last study drug dose, or until last study visit, whichever was later (SAEs). AEs were learned of through spontaneous reports or patient interview.
Investigations Respiratory rate decreased	20.0% 1/5 • Adverse events (AEs) & serious adverse events (SAEs) were reported from start of study participation through the period beyond study completion (AEs) & through 30 days following last study drug dose, or until last study visit, whichever was later (SAEs). AEs were learned of through spontaneous reports or patient interview.	16.0% 4/25 • Adverse events (AEs) & serious adverse events (SAEs) were reported from start of study participation through the period beyond study completion (AEs) & through 30 days following last study drug dose, or until last study visit, whichever was later (SAEs). AEs were learned of through spontaneous reports or patient interview.
Skin and subcutaneous tissue disorders Erythema	20.0% 1/5 • Adverse events (AEs) & serious adverse events (SAEs) were reported from start of study participation through the period beyond study completion (AEs) & through 30 days following last study drug dose, or until last study visit, whichever was later (SAEs). AEs were learned of through spontaneous reports or patient interview.	0.00% 0/25 • Adverse events (AEs) & serious adverse events (SAEs) were reported from start of study participation through the period beyond study completion (AEs) & through 30 days following last study drug dose, or until last study visit, whichever was later (SAEs). AEs were learned of through spontaneous reports or patient interview.
Skin and subcutaneous tissue disorders Pruritus	20.0% 1/5 • Adverse events (AEs) & serious adverse events (SAEs) were reported from start of study participation through the period beyond study completion (AEs) & through 30 days following last study drug dose, or until last study visit, whichever was later (SAEs). AEs were learned of through spontaneous reports or patient interview.	8.0% 2/25 • Adverse events (AEs) & serious adverse events (SAEs) were reported from start of study participation through the period beyond study completion (AEs) & through 30 days following last study drug dose, or until last study visit, whichever was later (SAEs). AEs were learned of through spontaneous reports or patient interview.
Skin and subcutaneous tissue disorders Rash	0.00% 0/5 • Adverse events (AEs) & serious adverse events (SAEs) were reported from start of study participation through the period beyond study completion (AEs) & through 30 days following last study drug dose, or until last study visit, whichever was later (SAEs). AEs were learned of through spontaneous reports or patient interview.	8.0% 2/25 • Adverse events (AEs) & serious adverse events (SAEs) were reported from start of study participation through the period beyond study completion (AEs) & through 30 days following last study drug dose, or until last study visit, whichever was later (SAEs). AEs were learned of through spontaneous reports or patient interview.
Nervous system disorders Dizziness	40.0% 2/5 • Adverse events (AEs) & serious adverse events (SAEs) were reported from start of study participation through the period beyond study completion (AEs) & through 30 days following last study drug dose, or until last study visit, whichever was later (SAEs). AEs were learned of through spontaneous reports or patient interview.	4.0% 1/25 • Adverse events (AEs) & serious adverse events (SAEs) were reported from start of study participation through the period beyond study completion (AEs) & through 30 days following last study drug dose, or until last study visit, whichever was later (SAEs). AEs were learned of through spontaneous reports or patient interview.
Nervous system disorders Headache	20.0% 1/5 • Adverse events (AEs) & serious adverse events (SAEs) were reported from start of study participation through the period beyond study completion (AEs) & through 30 days following last study drug dose, or until last study visit, whichever was later (SAEs). AEs were learned of through spontaneous reports or patient interview.	4.0% 1/25 • Adverse events (AEs) & serious adverse events (SAEs) were reported from start of study participation through the period beyond study completion (AEs) & through 30 days following last study drug dose, or until last study visit, whichever was later (SAEs). AEs were learned of through spontaneous reports or patient interview.
Nervous system disorders Sedation	20.0% 1/5 • Adverse events (AEs) & serious adverse events (SAEs) were reported from start of study participation through the period beyond study completion (AEs) & through 30 days following last study drug dose, or until last study visit, whichever was later (SAEs). AEs were learned of through spontaneous reports or patient interview.	0.00% 0/25 • Adverse events (AEs) & serious adverse events (SAEs) were reported from start of study participation through the period beyond study completion (AEs) & through 30 days following last study drug dose, or until last study visit, whichever was later (SAEs). AEs were learned of through spontaneous reports or patient interview.
General disorders Pyrexia	0.00% 0/5 • Adverse events (AEs) & serious adverse events (SAEs) were reported from start of study participation through the period beyond study completion (AEs) & through 30 days following last study drug dose, or until last study visit, whichever was later (SAEs). AEs were learned of through spontaneous reports or patient interview.	12.0% 3/25 • Adverse events (AEs) & serious adverse events (SAEs) were reported from start of study participation through the period beyond study completion (AEs) & through 30 days following last study drug dose, or until last study visit, whichever was later (SAEs). AEs were learned of through spontaneous reports or patient interview.
Blood and lymphatic system disorders Anaemia	20.0% 1/5 • Adverse events (AEs) & serious adverse events (SAEs) were reported from start of study participation through the period beyond study completion (AEs) & through 30 days following last study drug dose, or until last study visit, whichever was later (SAEs). AEs were learned of through spontaneous reports or patient interview.	4.0% 1/25 • Adverse events (AEs) & serious adverse events (SAEs) were reported from start of study participation through the period beyond study completion (AEs) & through 30 days following last study drug dose, or until last study visit, whichever was later (SAEs). AEs were learned of through spontaneous reports or patient interview.
Renal and urinary disorders Urinary retention	20.0% 1/5 • Adverse events (AEs) & serious adverse events (SAEs) were reported from start of study participation through the period beyond study completion (AEs) & through 30 days following last study drug dose, or until last study visit, whichever was later (SAEs). AEs were learned of through spontaneous reports or patient interview.	4.0% 1/25 • Adverse events (AEs) & serious adverse events (SAEs) were reported from start of study participation through the period beyond study completion (AEs) & through 30 days following last study drug dose, or until last study visit, whichever was later (SAEs). AEs were learned of through spontaneous reports or patient interview.
Injury, poisoning and procedural complications Scratch	20.0% 1/5 • Adverse events (AEs) & serious adverse events (SAEs) were reported from start of study participation through the period beyond study completion (AEs) & through 30 days following last study drug dose, or until last study visit, whichever was later (SAEs). AEs were learned of through spontaneous reports or patient interview.	0.00% 0/25 • Adverse events (AEs) & serious adverse events (SAEs) were reported from start of study participation through the period beyond study completion (AEs) & through 30 days following last study drug dose, or until last study visit, whichever was later (SAEs). AEs were learned of through spontaneous reports or patient interview.
Injury, poisoning and procedural complications Seroma	20.0% 1/5 • Adverse events (AEs) & serious adverse events (SAEs) were reported from start of study participation through the period beyond study completion (AEs) & through 30 days following last study drug dose, or until last study visit, whichever was later (SAEs). AEs were learned of through spontaneous reports or patient interview.	0.00% 0/25 • Adverse events (AEs) & serious adverse events (SAEs) were reported from start of study participation through the period beyond study completion (AEs) & through 30 days following last study drug dose, or until last study visit, whichever was later (SAEs). AEs were learned of through spontaneous reports or patient interview.