Trial Outcomes & Findings for An Interventional Study to Compare the Efficacy and Tolerability With Targin® in Non-malignant Chronic Pain (GLORY) (NCT NCT01811186)

NCT ID: NCT01811186

Last Updated: 2017-03-10

Results Overview

To assess the drop-out rate caused by adverse event\* after 6 weeks treatment

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

261 participants

Primary outcome timeframe

6 weeks

Results posted on

2017-03-10

Participant Flow

Safety set: 261 patients were enrolled. ITT set was 258, 3 patients of the 261 patients deviated from inclusion/exclusion criteria.

Participant milestones

Participant milestones
Measure	Start Oxycodone/Naloxone 10/5mg b.i.d. Start oxycodone/naloxone 10/5mg b.i.d. titration-\>20/10mg b.i.d.-\>30/15mg b.i.d-\>40/20mg b.i.d.	Start Oxycodone/Naloxone 5/2.5mg b.i.d Start oxycodone/naloxone 5/2.5mg b.i.d-\>10/5mg b.i.d. titration-\>20/10mg b.i.d.-\>30/15mg b.i.d-\>40/20mg b.i.d.
Overall Study STARTED	132	126
Overall Study COMPLETED	61	64
Overall Study NOT COMPLETED	71	62

Reasons for withdrawal

Reasons for withdrawal
Measure	Start Oxycodone/Naloxone 10/5mg b.i.d. Start oxycodone/naloxone 10/5mg b.i.d. titration-\>20/10mg b.i.d.-\>30/15mg b.i.d-\>40/20mg b.i.d.	Start Oxycodone/Naloxone 5/2.5mg b.i.d Start oxycodone/naloxone 5/2.5mg b.i.d-\>10/5mg b.i.d. titration-\>20/10mg b.i.d.-\>30/15mg b.i.d-\>40/20mg b.i.d.
Overall Study Adverse Event	54	38
Overall Study Protocol Violation	5	6
Overall Study Withdrawal by Subject	5	10
Overall Study Lack of Efficacy	3	6
Overall Study Lost to Follow-up	4	2

Baseline Characteristics

An Interventional Study to Compare the Efficacy and Tolerability With Targin® in Non-malignant Chronic Pain (GLORY)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Start Oxycodone/Naloxone 10/5mg b.i.d n=132 Participants Start oxycodone/naloxone 10/5mg b.i.d. titration-\>20/10mg b.i.d.-\>30/15mg b.i.d-\>40/20mg b.i.d.	Start Oxycodone/Naloxone 5/2.5mg b.i.d n=126 Participants Start oxycodone/naloxone 5/2.5mg b.i.d titration-\> 10/5mg b.i.d.-\>20/10mg b.i.d.-\>30/15mg b.i.d-\>40/20mg b.i.d.	Total n=258 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	77 Participants n=5 Participants	64 Participants n=7 Participants	141 Participants n=5 Participants
Age, Categorical >=65 years	55 Participants n=5 Participants	62 Participants n=7 Participants	117 Participants n=5 Participants
Age, Continuous	60.63 years STANDARD_DEVIATION 9.69 • n=5 Participants	61.15 years STANDARD_DEVIATION 11.94 • n=7 Participants	60.88 years STANDARD_DEVIATION 10.83 • n=5 Participants
Sex: Female, Male Female	81 Participants n=5 Participants	84 Participants n=7 Participants	165 Participants n=5 Participants
Sex: Female, Male Male	51 Participants n=5 Participants	42 Participants n=7 Participants	93 Participants n=5 Participants
Region of Enrollment Korea, Republic of	132 participants n=5 Participants	126 participants n=7 Participants	258 participants n=5 Participants

PRIMARY outcome

Timeframe: 6 weeks

Population: Intent to treat analysis set: 258 patients (Last Observation Carried Forward)

To assess the drop-out rate caused by adverse event\* after 6 weeks treatment

Outcome measures

Outcome measures
Measure	Start Oxycodone/Naloxone 10/5mg b.i.d. n=132 Participants Start oxycodone/naloxone 10/5mg b.i.d. titration-\>20/10mg b.i.d.-\>30/15mg b.i.d-\>40/20mg b.i.d	Start Oxycodone/Naloxone 5/2.5mg b.i.d. n=126 Participants Start oxycodone/naloxone 5/2.5mg b.i.d-\>10/5mg b.i.d. titration-\>20/10mg b.i.d.-\>30/15mg b.i.d-\>40/20mg b.i.d.
Drop-out Rate Caused by Adverse Event After 6 Weeks Treatment	40.91 percentage of participants	30.16 percentage of participants

SECONDARY outcome

Timeframe: 1 week

Population: Intent to treat analysis set: 258(Last observation Carried Forward)

The drop-out rate due to an adverse event after treatment (1 week) by treatment arm were summarized and presented as frequency and percentage, and the inter-group difference were compared by using a Chi-square test or Fisher's exact test.

Outcome measures

Outcome measures
Measure	Start Oxycodone/Naloxone 10/5mg b.i.d. n=132 Participants Start oxycodone/naloxone 10/5mg b.i.d. titration-\>20/10mg b.i.d.-\>30/15mg b.i.d-\>40/20mg b.i.d	Start Oxycodone/Naloxone 5/2.5mg b.i.d. n=126 Participants Start oxycodone/naloxone 5/2.5mg b.i.d-\>10/5mg b.i.d. titration-\>20/10mg b.i.d.-\>30/15mg b.i.d-\>40/20mg b.i.d.
The Drop-out Rate Due to an Adverse Event After 1 Week Treatment With the Study Drug.	28.79 percentage of participants	19.84 percentage of participants

SECONDARY outcome

Timeframe: 6 weeks

Population: ITT analysis set: 258

Change in numeric rating scales (NRS) such as score for average pain levels over the previous 24 hours, from baseline to 6weeks. NRS score was measured from 0 (No pain) to 10(worst pain imaginable).

Outcome measures

Outcome measures
Measure	Start Oxycodone/Naloxone 10/5mg b.i.d. n=132 Participants Start oxycodone/naloxone 10/5mg b.i.d. titration-\>20/10mg b.i.d.-\>30/15mg b.i.d-\>40/20mg b.i.d	Start Oxycodone/Naloxone 5/2.5mg b.i.d. n=126 Participants Start oxycodone/naloxone 5/2.5mg b.i.d-\>10/5mg b.i.d. titration-\>20/10mg b.i.d.-\>30/15mg b.i.d-\>40/20mg b.i.d.
The Change of Pain Intensity Scores(NRS) From Baseline After 6 Weeks Treatment With the Study.	-1.62 units on a scale Standard Deviation 1.90	-1.48 units on a scale Standard Deviation 1.82

SECONDARY outcome

Timeframe: 6 weeks

Population: ITT analysis set.

EQ-5D to measure of health related quality of life should be answered as one of 3 levels about current condition for 5 dimensions and was calculated total average by giving a weighting on 3 level of answers (EQ-5D levels into 'no problems' (level 1) and 'problems' (level 2 and 3)). Table of scores by each level for EQ-5D items: mobility(level 1=0, level2=0.069,level 3=0.314), self care(level 1=0, level2=0.104,level 3=0.214), usual activities(level 1=0, level2=0.036,level 3=0.094), pain/discomfort (level 1=0, level2=0.,level 3=0.386) and anxiety/depression(level 1=0, level2=0.071,level 3=0.2) \*EQ-5D Total = 1 - 0.081 - (the score of the each level) - 0.269 (if at least one of level 3 presents) EQ-5D total score could be 0.919 in maximum and -0.594 in minimum if case all index indicates the level 3. So, if EQ-5D total score closed by "1" means that the healthy condition and high quality of life.

Outcome measures

Outcome measures
Measure	Start Oxycodone/Naloxone 10/5mg b.i.d. n=61 Participants Start oxycodone/naloxone 10/5mg b.i.d. titration-\>20/10mg b.i.d.-\>30/15mg b.i.d-\>40/20mg b.i.d	Start Oxycodone/Naloxone 5/2.5mg b.i.d. n=64 Participants Start oxycodone/naloxone 5/2.5mg b.i.d-\>10/5mg b.i.d. titration-\>20/10mg b.i.d.-\>30/15mg b.i.d-\>40/20mg b.i.d.
Change of Quality of Life (EQ-5D) Score After 6 Weeks Treatment With the Study Drug	0.14 units on a scale Standard Deviation 0.26	0.07 units on a scale Standard Deviation 0.22

SECONDARY outcome

Timeframe: 6 weeks

Population: ITT analysis set: 171. Last visit(Visit 5) data was handled as LOCF. However, Missing Number as visit 3 for assessment of Investigator's overall satisfaction after 6 weeks treatment with the study drug was Group A = 50, Group B=37.

Investigator's overall satisfaction after treatment (6 weeks) (Clinical Global Impression of Change Scale(CGIC) 7 point scale) by treatment arm were summarized and presented as frequency and proportion, and the inter-group difference were compared by using a Chi-square test or Fisher's exact test.

Outcome measures

Outcome measures
Measure	Start Oxycodone/Naloxone 10/5mg b.i.d. n=82 Participants Start oxycodone/naloxone 10/5mg b.i.d. titration-\>20/10mg b.i.d.-\>30/15mg b.i.d-\>40/20mg b.i.d	Start Oxycodone/Naloxone 5/2.5mg b.i.d. n=89 Participants Start oxycodone/naloxone 5/2.5mg b.i.d-\>10/5mg b.i.d. titration-\>20/10mg b.i.d.-\>30/15mg b.i.d-\>40/20mg b.i.d.
Assessment of Investigator's Overall Satisfaction After 6 Weeks Treatment With the Study Drug Very much improved	2 participants	2 participants
Assessment of Investigator's Overall Satisfaction After 6 Weeks Treatment With the Study Drug Much improved	27 participants	30 participants
Assessment of Investigator's Overall Satisfaction After 6 Weeks Treatment With the Study Drug Minimally improved	48 participants	43 participants
Assessment of Investigator's Overall Satisfaction After 6 Weeks Treatment With the Study Drug No change	5 participants	14 participants
Assessment of Investigator's Overall Satisfaction After 6 Weeks Treatment With the Study Drug Minimally worse	0 participants	0 participants
Assessment of Investigator's Overall Satisfaction After 6 Weeks Treatment With the Study Drug Much worse	0 participants	0 participants
Assessment of Investigator's Overall Satisfaction After 6 Weeks Treatment With the Study Drug very much worse	0 participants	0 participants

SECONDARY outcome

Timeframe: 6weeks

At each visit, the subject assessed the overall satisfaction for efficacy by using the 7 point scale of Patient Global Impression of Change Scale(PGIC).

Outcome measures

Outcome measures
Measure	Start Oxycodone/Naloxone 10/5mg b.i.d. n=82 Participants Start oxycodone/naloxone 10/5mg b.i.d. titration-\>20/10mg b.i.d.-\>30/15mg b.i.d-\>40/20mg b.i.d	Start Oxycodone/Naloxone 5/2.5mg b.i.d. n=89 Participants Start oxycodone/naloxone 5/2.5mg b.i.d-\>10/5mg b.i.d. titration-\>20/10mg b.i.d.-\>30/15mg b.i.d-\>40/20mg b.i.d.
Assessment of Subject's Overall Satisfaction After 6 Weeks Treatment With the Study Drug Very much improved	2 participants	2 participants
Assessment of Subject's Overall Satisfaction After 6 Weeks Treatment With the Study Drug Much improved	24 participants	28 participants
Assessment of Subject's Overall Satisfaction After 6 Weeks Treatment With the Study Drug Minimally improved	44 participants	42 participants
Assessment of Subject's Overall Satisfaction After 6 Weeks Treatment With the Study Drug No change	11 participants	16 participants
Assessment of Subject's Overall Satisfaction After 6 Weeks Treatment With the Study Drug Minimally worse	0 participants	1 participants
Assessment of Subject's Overall Satisfaction After 6 Weeks Treatment With the Study Drug Much worse	1 participants	0 participants
Assessment of Subject's Overall Satisfaction After 6 Weeks Treatment With the Study Drug Very much worse	0 participants	0 participants

Adverse Events

Start Oxycodone/Naloxone 10/5mg b.i.d

Serious events: 0 serious events

Other events: 115 other events

Deaths: 0 deaths

Start Oxycodone/Naloxone 5/2.5mg b.i.d

Serious events: 2 serious events

Other events: 104 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Start Oxycodone/Naloxone 10/5mg b.i.d n=133 participants at risk Start oxycodone/naloxone 10/5mg b.i.d. titration-\>20/10mg b.i.d.-\>30/15mg b.i.d-\>40/20mg b.i.d.	Start Oxycodone/Naloxone 5/2.5mg b.i.d n=128 participants at risk Start oxycodone/naloxone 5/2.5mg b.i.d titration-\> 10/5mg b.i.d.-\>20/10mg b.i.d.-\>30/15mg b.i.d-\>40/20mg b.i.d.
Gastrointestinal disorders Duodenal stenosis	0.00% 0/133 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.	0.78% 1/128 • Number of events 1 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.
General disorders Inflammation	0.00% 0/133 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.	0.78% 1/128 • Number of events 1 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.
Injury, poisoning and procedural complications Femoral neck fracture	0.00% 0/133 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.	0.78% 1/128 • Number of events 1 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.

Other adverse events

Additional Information

Hoseong Lee

Asan Medical Center

Phone: 82-2-3010-3521

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Start Oxycodone/Naloxone 10/5mg b.i.d n=133 participants at risk Start oxycodone/naloxone 10/5mg b.i.d. titration-\>20/10mg b.i.d.-\>30/15mg b.i.d-\>40/20mg b.i.d.	Start Oxycodone/Naloxone 5/2.5mg b.i.d n=128 participants at risk Start oxycodone/naloxone 5/2.5mg b.i.d titration-\> 10/5mg b.i.d.-\>20/10mg b.i.d.-\>30/15mg b.i.d-\>40/20mg b.i.d.
Gastrointestinal disorders Nausea	39.1% 52/133 • Number of events 55 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.	35.9% 46/128 • Number of events 53 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.
Gastrointestinal disorders Constipation	18.0% 24/133 • Number of events 26 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.	16.4% 21/128 • Number of events 21 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.
Gastrointestinal disorders vomiting	20.3% 27/133 • Number of events 27 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.	12.5% 16/128 • Number of events 16 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.
Gastrointestinal disorders Dyspepsia	3.8% 5/133 • Number of events 5 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.	1.6% 2/128 • Number of events 2 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.
Gastrointestinal disorders Dry mouth	2.3% 3/133 • Number of events 3 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.	1.6% 2/128 • Number of events 2 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.
Gastrointestinal disorders Abdominal pain lower	0.00% 0/133 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.	0.78% 1/128 • Number of events 1 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.
Gastrointestinal disorders Diarrhoea	0.75% 1/133 • Number of events 1 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.	0.00% 0/128 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.
Gastrointestinal disorders Duodenal stenosis	0.00% 0/133 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.	0.78% 1/128 • Number of events 1 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.
Nervous system disorders Dizziness	24.1% 32/133 • Number of events 34 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.	22.7% 29/128 • Number of events 29 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.
Nervous system disorders Somnolence	15.8% 21/133 • Number of events 22 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.	20.3% 26/128 • Number of events 27 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.
Nervous system disorders Headache	11.3% 15/133 • Number of events 16 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.	6.2% 8/128 • Number of events 10 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.
Nervous system disorders Paraesthesia	1.5% 2/133 • Number of events 2 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.	1.6% 2/128 • Number of events 2 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.
Nervous system disorders Mental impairment	0.00% 0/133 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.	1.6% 2/128 • Number of events 2 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.
Nervous system disorders Dysaesthesia	0.75% 1/133 • Number of events 1 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.	0.00% 0/128 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.
Nervous system disorders Essential tremor	0.00% 0/133 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.	0.78% 1/128 • Number of events 1 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.
Nervous system disorders Lethargy	0.00% 0/133 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.	0.78% 1/128 • Number of events 1 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.
Skin and subcutaneous tissue disorders Pruritus	15.0% 20/133 • Number of events 21 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.	13.3% 17/128 • Number of events 17 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.
Skin and subcutaneous tissue disorders Urticaria	5.3% 7/133 • Number of events 7 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.	0.00% 0/128 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.
Skin and subcutaneous tissue disorders Erythema	0.00% 0/133 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.	0.78% 1/128 • Number of events 1 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.
Skin and subcutaneous tissue disorders Rash macular	0.75% 1/133 • Number of events 1 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.	0.00% 0/128 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.
General disorders Asthenia	1.5% 2/133 • Number of events 2 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.	3.1% 4/128 • Number of events 4 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.
General disorders Oedema	0.75% 1/133 • Number of events 1 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.	2.3% 3/128 • Number of events 3 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.
General disorders Chest pain	0.75% 1/133 • Number of events 1 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.	1.6% 2/128 • Number of events 2 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.
General disorders Oedema peripheral	1.5% 2/133 • Number of events 2 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.	0.78% 1/128 • Number of events 1 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.
General disorders Inflammation	0.00% 0/133 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.	0.78% 1/128 • Number of events 1 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.
General disorders Pain	0.75% 1/133 • Number of events 1 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.	0.00% 0/128 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.
General disorders Pyrexia	0.75% 1/133 • Number of events 1 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.	0.00% 0/128 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.
Respiratory, thoracic and mediastinal disorders Dysphonia	0.00% 0/133 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.	2.3% 3/128 • Number of events 3 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.75% 1/133 • Number of events 1 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.	1.6% 2/128 • Number of events 2 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/133 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.	1.6% 2/128 • Number of events 2 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/133 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.	0.78% 1/128 • Number of events 1 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.
Psychiatric disorders Insomnia	4.5% 6/133 • Number of events 6 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.	1.6% 2/128 • Number of events 2 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.
Metabolism and nutrition disorders Decreased appetite	3.8% 5/133 • Number of events 5 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.	1.6% 2/128 • Number of events 2 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.
Renal and urinary disorders Dysuria	3.0% 4/133 • Number of events 4 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.	2.3% 3/128 • Number of events 3 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.
Cardiac disorders Palpitations	0.75% 1/133 • Number of events 1 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.	1.6% 2/128 • Number of events 2 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.
Musculoskeletal and connective tissue disorders Bone disorder	0.75% 1/133 • Number of events 1 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.	0.00% 0/128 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.
Musculoskeletal and connective tissue disorders Joint swelling	0.00% 0/133 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.	0.78% 1/128 • Number of events 1 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.
Musculoskeletal and connective tissue disorders Muscle spasms	0.75% 1/133 • Number of events 1 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.	0.00% 0/128 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.
Ear and labyrinth disorders Ear discomfort	0.00% 0/133 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.	0.78% 1/128 • Number of events 1 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.
Ear and labyrinth disorders Tinnitus	0.00% 0/133 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.	0.78% 1/128 • Number of events 1 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.
Infections and infestations Gastroenteritis	0.00% 0/133 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.	0.78% 1/128 • Number of events 1 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.
Infections and infestations Nasopharyngitis	0.75% 1/133 • Number of events 1 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.	0.00% 0/128 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.
Reproductive system and breast disorders Vaginal haemorrhage	0.00% 0/133 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.	1.6% 2/128 • Number of events 2 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.
Eye disorders Eye pain	0.75% 1/133 • Number of events 1 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.	0.00% 0/128 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.
Injury, poisoning and procedural complications Femoral neck fracture	0.00% 0/133 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.	0.78% 1/128 • Number of events 1 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.
Vascular disorders Hyperaemia	0.00% 0/133 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.	0.78% 1/128 • Number of events 1 • Safety set: Safety set included data obtained from all subjects who administered at least one dose of the study drug. Patients were followed by 6 weeks.