Trial Outcomes & Findings for A Study of Sativex® for Pain Relief of Peripheral Neuropathic Pain, Associated With Allodynia (NCT NCT00710554)

Last Updated: 2023-05-03

Results Overview

The peripheral neuropathic pain NRS was completed at the same time each day, i.e. bedtime in the evening. The patient was asked "on a scale of '0 to 10', please indicate the number that best describes your pain or average pain in the last 24 hours" where 0 = no pain and 10 = pain as bad as you can imagine. No pain relates to the time prior to the onset of pain. A negative value indicates an improvement in pain score from baseline.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

246 participants

Primary outcome timeframe

Day 7 to Day 98

Results posted on

2023-05-03

Participant Flow

Participant milestones

Participant milestones
Measure	Sativex Each actuation delivered 100 μl (THC 2.7 mg and CBD 2.5 mg) up to a maximum of 24 actuations in any 24 hour period.	Placebo Each 100 ul actuation delivered the excipients plus colorants, up to a maximum of 24 actuations in any 24 hour period.
Overall Study STARTED	128	118
Overall Study COMPLETED	79	94
Overall Study NOT COMPLETED	49	24

Reasons for withdrawal

Reasons for withdrawal
Measure	Sativex Each actuation delivered 100 μl (THC 2.7 mg and CBD 2.5 mg) up to a maximum of 24 actuations in any 24 hour period.	Placebo Each 100 ul actuation delivered the excipients plus colorants, up to a maximum of 24 actuations in any 24 hour period.
Overall Study Adverse Event	24	7
Overall Study Withdrawal by Subject	7	3
Overall Study Lost to Follow-up	7	1
Overall Study Lack of Efficacy	11	12
Overall Study Receiving radiotherapy - prostate cancer	0	1

Baseline Characteristics

A Study of Sativex® for Pain Relief of Peripheral Neuropathic Pain, Associated With Allodynia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sativex n=128 Participants Each actuation delivered 100 μl (THC 2.7 mg and CBD 2.5 mg) up to a maximum of 24 actuations in any 24 hour period.	Placebo n=118 Participants Each 100 ul actuation delivered the excipients plus colorants, up to a maximum of 24 actuations in any 24 hour period.	Total n=246 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	91 Participants n=5 Participants	88 Participants n=7 Participants	179 Participants n=5 Participants
Age, Categorical >=65 years	37 Participants n=5 Participants	30 Participants n=7 Participants	67 Participants n=5 Participants
Age, Continuous	57.6 years STANDARD_DEVIATION 14.38 • n=5 Participants	57 years STANDARD_DEVIATION 14.07 • n=7 Participants	57.3 years STANDARD_DEVIATION 14.21 • n=5 Participants
Sex: Female, Male Female	85 Participants n=5 Participants	65 Participants n=7 Participants	150 Participants n=5 Participants
Sex: Female, Male Male	43 Participants n=5 Participants	53 Participants n=7 Participants	96 Participants n=5 Participants
Region of Enrollment United Kingdom	74 participants n=5 Participants	72 participants n=7 Participants	146 participants n=5 Participants
Region of Enrollment Belgium	8 participants n=5 Participants	7 participants n=7 Participants	15 participants n=5 Participants
Region of Enrollment Canada	3 participants n=5 Participants	2 participants n=7 Participants	5 participants n=5 Participants
Region of Enrollment Czech Republic	35 participants n=5 Participants	32 participants n=7 Participants	67 participants n=5 Participants
Region of Enrollment Romania	8 participants n=5 Participants	5 participants n=7 Participants	13 participants n=5 Participants

PRIMARY outcome

Timeframe: Day 7 to Day 98

Population: The efficacy analyses were conducted on data from all subjects who were randomised, received at least one dose of study medication and yielded on-treatment efficacy data.

Outcome measures

Outcome measures
Measure	Sativex n=77 Participants Each actuation delivered 100 μl (THC 2.7 mg and CBD 2.5 mg) up to a maximum of 24 actuations in any 24 hour period.	Placebo n=92 Participants Each 100 ul actuation delivered the excipients plus colorants, up to a maximum of 24 actuations in any 24 hour period.
Change From Baseline in Mean Peripheral Neuropathic Pain on a 0-10 Numerical Rating Scale (NRS) Score at the End of Treatment (15 Weeks)	-1.36 units on a scale Standard Deviation 2.02	-0.84 units on a scale Standard Deviation 1.86

SECONDARY outcome

Timeframe: Day 7 to Day 98

Population: The primary population for the analysis of efficacy was the full analysis set, which included all randomised subjects who received at least one dose of test treatment and had on-treatment efficacy data.

The NPS score is 0-100 sum of 10 individual pain scores (0-10 NRS, 0= no pain to 10 = most pain imaginable). A negative change from baseline indicates an improvement in pain.

Outcome measures

Outcome measures
Measure	Sativex n=78 Participants Each actuation delivered 100 μl (THC 2.7 mg and CBD 2.5 mg) up to a maximum of 24 actuations in any 24 hour period.	Placebo n=93 Participants Each 100 ul actuation delivered the excipients plus colorants, up to a maximum of 24 actuations in any 24 hour period.
Change From Baseline in Neuropathic Pain Scale Score at the End of Treatment (15 Weeks)	-11.57 units on a scale Standard Deviation 16.15	-7.19 units on a scale Standard Deviation 19.65

SECONDARY outcome

Timeframe: Day 7 to Day 98

The sleep disruption NRS was completed at the same time each day, i.e. bedtime in the evening. The patient was asked "on a scale of '0 to 10', please indicate how your pain disrupted your sleep last night?" where 0 = did not disrupt sleep and 10 = completely disrupted (unable to sleep at all). A negative value indicates an improvement in sleep disruption score from baseline.

Outcome measures

Outcome measures
Measure	Sativex n=81 Participants Each actuation delivered 100 μl (THC 2.7 mg and CBD 2.5 mg) up to a maximum of 24 actuations in any 24 hour period.	Placebo n=86 Participants Each 100 ul actuation delivered the excipients plus colorants, up to a maximum of 24 actuations in any 24 hour period.
Change From Baseline in Sleep Quality 0-10 Numerical Rating Scale Scores at the End of Treatment (15 Weeks)	-2.0 units on a scale Standard Deviation 2.70	-1.2 units on a scale Standard Deviation 2.38

SECONDARY outcome

Timeframe: Day 7 and Day 98

Dynamic allodynia was assessed by stroking the skin over the affected area five times with a standardised brush, designed specifically for sensory testing at 5 s intervals, and recording the pain severity on a 0-10 point scale (0= no pain to 10 = most pain imaginable). All strokes were of the same length, minimum 2 cm. Each dynamic allodynia score was calculated as the average of the five strokes.A negative change from baseline indicates an improvement in score.

Outcome measures

Outcome measures
Measure	Sativex n=112 Participants Each actuation delivered 100 μl (THC 2.7 mg and CBD 2.5 mg) up to a maximum of 24 actuations in any 24 hour period.	Placebo n=102 Participants Each 100 ul actuation delivered the excipients plus colorants, up to a maximum of 24 actuations in any 24 hour period.
Change in Baseline Mean Dynamic Allodynia Test Score at the End of Treatment (15 Weeks)	-1.1 units on a scale Standard Deviation 2.16	-1.0 units on a scale Standard Deviation 2.49

SECONDARY outcome

Timeframe: Day 7 and Day 98

Punctate allodynia was measured using an in-house built pressure algometer comprising a strain gauge connected to a metal filament with a diameter of 1 mm and blunt tip at baseline and end of study. The filament was manually directed against the skin at an angle of 90 degrees and a steadily increasing pressure applied until the patient verbally indicated that they perceived pain (punctate pressure pain threshold). Patients were asked to verbally rate the intensity of the pain elicited, choosing a number between 0 (no pain)and 10 (most intense pain imaginable).

Outcome measures

Outcome measures
Measure	Sativex n=112 Participants Each actuation delivered 100 μl (THC 2.7 mg and CBD 2.5 mg) up to a maximum of 24 actuations in any 24 hour period.	Placebo n=106 Participants Each 100 ul actuation delivered the excipients plus colorants, up to a maximum of 24 actuations in any 24 hour period.
Change in Baseline Mean Punctate Allodynia Test Scores at the End of Treatment (15 Weeks)	0.2 units on a scale Standard Deviation 0.78	0.3 units on a scale Standard Deviation 1.08

SECONDARY outcome

Timeframe: Day 98

A 7-point Likert-type scale was used, with the question: 'Please assess the status of your pain due to peripheral neuropathy since entry into the study using the scale below' with the markers "very much improved, much improved, slightly improved, no change, slightly worse, much worse or very much worse". At Visit 2 (Baseline) patients wrote a brief description of their pain caused by peripheral neuropathy which was used at end of treatment to aid their memory regarding their symptoms at study start. For each of above markers the number of participants were reported.

Outcome measures

Outcome measures
Measure	Sativex n=117 Participants Each actuation delivered 100 μl (THC 2.7 mg and CBD 2.5 mg) up to a maximum of 24 actuations in any 24 hour period.	Placebo n=111 Participants Each 100 ul actuation delivered the excipients plus colorants, up to a maximum of 24 actuations in any 24 hour period.
Subject Global Impression of Change Very much improved	8 participants	4 participants
Subject Global Impression of Change Much improved	16 participants	10 participants
Subject Global Impression of Change Slightly improved	38 participants	24 participants
Subject Global Impression of Change No change	44 participants	66 participants
Subject Global Impression of Change Slightly worse	9 participants	4 participants
Subject Global Impression of Change Much worse	2 participants	3 participants

SECONDARY outcome

Timeframe: Day 7 and Day 98

The BPI-SF is a 14-item questionnaire that asks patients to rate pain over the prior week and the degree to which it interferes with activities on a 0 to 10 scale, where 0=no pain and 10=pain as bad as you can imagine. Severity is measured as worst pain, least pain, average pain, and pain right now. The severity composite score was calculated as the arithmetic mean of the four severity items(range 0-10). The minimum value is zero and maximum is 10. A higher score represents a poor outcome.

Outcome measures

Outcome measures
Measure	Sativex n=114 Participants Each actuation delivered 100 μl (THC 2.7 mg and CBD 2.5 mg) up to a maximum of 24 actuations in any 24 hour period.	Placebo n=105 Participants Each 100 ul actuation delivered the excipients plus colorants, up to a maximum of 24 actuations in any 24 hour period.
Change From Baseline in Brief Pain Inventory (Short Form) Scores at the End of Treatment	-0.9 units on a scale Standard Deviation 1.69	-0.6 units on a scale Standard Deviation 1.90

SECONDARY outcome

Timeframe: Day 7 and Day 98

The EQ-5D questionnaire provided two outcomes:(1)A weighted health state index visual analogue scale (VAS); (2) A self-rated health status VAS. EQ-5D Health Status VAS Scale: 0 = worst health state imaginable to 100 = best health state imaginable. An increase in score indicates an improvement in condition.The weighted health state index used the same VAS as above but was calculated for each assessment without imputation to account for missing values i.e., if one or more individual items was missing then the whole index was missing.

Outcome measures

Outcome measures
Measure	Sativex n=113 Participants Each actuation delivered 100 μl (THC 2.7 mg and CBD 2.5 mg) up to a maximum of 24 actuations in any 24 hour period.	Placebo n=107 Participants Each 100 ul actuation delivered the excipients plus colorants, up to a maximum of 24 actuations in any 24 hour period.
Change From Baseline in Quality of Life EuroQol 5-D (Health Status Index) Score at the End of Treatment (15 Weeks)	0.037 units on a scale Standard Deviation 0.187	0.044 units on a scale Standard Deviation 0.214

SECONDARY outcome

Timeframe: Day 7 and Day 98

Outcome measures

Outcome measures
Measure	Sativex n=111 Participants Each actuation delivered 100 μl (THC 2.7 mg and CBD 2.5 mg) up to a maximum of 24 actuations in any 24 hour period.	Placebo n=105 Participants Each 100 ul actuation delivered the excipients plus colorants, up to a maximum of 24 actuations in any 24 hour period.
Change From Baseline in Quality of Life EuroQol 5-D (Health Status Visual Analogue Scale) Score at the End of Treatment (15 Weeks)	3.7 units on a scale Standard Deviation 20.6	2.5 units on a scale Standard Deviation 21.2

SECONDARY outcome

Timeframe: Days 0-7 and Days 92-98

Use of break through medication was recorded daily during the study as the number of paracetamol tablets taken. The change in mean daily quantities of tablets used was calculated from baseline to the last seven days of treatment.

Outcome measures

Outcome measures
Measure	Sativex n=77 Participants Each actuation delivered 100 μl (THC 2.7 mg and CBD 2.5 mg) up to a maximum of 24 actuations in any 24 hour period.	Placebo n=92 Participants Each 100 ul actuation delivered the excipients plus colorants, up to a maximum of 24 actuations in any 24 hour period.
Change From Baseline in the Use of Rescue Analgesia at the End Treatment (15 Weeks)	-0.99 number of tablets Standard Deviation 2.20	-0.47 number of tablets Standard Deviation 2.08

SECONDARY outcome

Timeframe: 19 weeks

Population: All subjects were included in this analysis.

The number of subjects that reported an adverse event in this study is presented.

Outcome measures

Outcome measures
Measure	Sativex n=128 Participants Each actuation delivered 100 μl (THC 2.7 mg and CBD 2.5 mg) up to a maximum of 24 actuations in any 24 hour period.	Placebo n=118 Participants Each 100 ul actuation delivered the excipients plus colorants, up to a maximum of 24 actuations in any 24 hour period.
Incidence of Adverse Events as a Measure of Subject's Safety.	109 participants	83 participants

Adverse Events

Sativex

Serious events: 10 serious events

Other events: 109 other events

Deaths: 0 deaths

Placebo

Serious events: 6 serious events

Other events: 83 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Mr Richard Potts, Clinical Operations Director

GW Pharma Ltd.

Phone: 0044 1223 266800

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee GW will coordinate the dissemination of data from this study and may solicit input and assistance from the principal investigator. All publications, for example manuscripts, abstracts, oral/slide presentations or book chapters based on this study, must be submitted to GW for corporate review before release.
Publication restrictions are in place

Restriction type: OTHER

Measure	Sativex n=128 participants at risk Each actuation delivered 100 μl (THC 2.7 mg and CBD 2.5 mg) up to a maximum of 24 actuations in any 24 hour period.	Placebo n=118 participants at risk Each 100 ul actuation delivered the excipients plus colorants, up to a maximum of 24 actuations in any 24 hour period.
Infections and infestations Bronchopneumonia	0.78% 1/128 • All adverse events occurring from the time of consent to post study follow up i.e. 19 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	0.00% 0/118 • All adverse events occurring from the time of consent to post study follow up i.e. 19 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
Infections and infestations Infective Exacerbation of Chronic Obstructive Airway Disease	0.78% 1/128 • All adverse events occurring from the time of consent to post study follow up i.e. 19 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	0.00% 0/118 • All adverse events occurring from the time of consent to post study follow up i.e. 19 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
Infections and infestations Pneumonia	0.78% 1/128 • All adverse events occurring from the time of consent to post study follow up i.e. 19 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	0.00% 0/118 • All adverse events occurring from the time of consent to post study follow up i.e. 19 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
Infections and infestations Subcutaneous Abscess	0.78% 1/128 • All adverse events occurring from the time of consent to post study follow up i.e. 19 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	0.00% 0/118 • All adverse events occurring from the time of consent to post study follow up i.e. 19 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
Infections and infestations Urinary Tract Infection	0.78% 1/128 • All adverse events occurring from the time of consent to post study follow up i.e. 19 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	0.00% 0/118 • All adverse events occurring from the time of consent to post study follow up i.e. 19 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
Nervous system disorders Transient Ischaemic Attack	0.78% 1/128 • All adverse events occurring from the time of consent to post study follow up i.e. 19 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	0.00% 0/118 • All adverse events occurring from the time of consent to post study follow up i.e. 19 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
Nervous system disorders Coma	0.00% 0/128 • All adverse events occurring from the time of consent to post study follow up i.e. 19 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	0.85% 1/118 • All adverse events occurring from the time of consent to post study follow up i.e. 19 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
Nervous system disorders Dizziness	0.00% 0/128 • All adverse events occurring from the time of consent to post study follow up i.e. 19 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	0.85% 1/118 • All adverse events occurring from the time of consent to post study follow up i.e. 19 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
Nervous system disorders Loss of Consciousness	0.00% 0/128 • All adverse events occurring from the time of consent to post study follow up i.e. 19 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	0.85% 1/118 • All adverse events occurring from the time of consent to post study follow up i.e. 19 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast Cancer Stage II	0.78% 1/128 • All adverse events occurring from the time of consent to post study follow up i.e. 19 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	0.00% 0/118 • All adverse events occurring from the time of consent to post study follow up i.e. 19 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant Melanoma	0.78% 1/128 • All adverse events occurring from the time of consent to post study follow up i.e. 19 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	0.00% 0/118 • All adverse events occurring from the time of consent to post study follow up i.e. 19 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm Malignant	0.78% 1/128 • All adverse events occurring from the time of consent to post study follow up i.e. 19 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	0.00% 0/118 • All adverse events occurring from the time of consent to post study follow up i.e. 19 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
Cardiac disorders Myocardial Infarction	0.78% 1/128 • All adverse events occurring from the time of consent to post study follow up i.e. 19 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	0.00% 0/118 • All adverse events occurring from the time of consent to post study follow up i.e. 19 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
Gastrointestinal disorders Inguinal Hernia	0.78% 1/128 • All adverse events occurring from the time of consent to post study follow up i.e. 19 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	0.00% 0/118 • All adverse events occurring from the time of consent to post study follow up i.e. 19 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
Gastrointestinal disorders Enterovesical Fistula	0.00% 0/128 • All adverse events occurring from the time of consent to post study follow up i.e. 19 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	0.85% 1/118 • All adverse events occurring from the time of consent to post study follow up i.e. 19 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
General disorders Chest Pain	0.78% 1/128 • All adverse events occurring from the time of consent to post study follow up i.e. 19 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	0.00% 0/118 • All adverse events occurring from the time of consent to post study follow up i.e. 19 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
Injury, poisoning and procedural complications Head Injury	0.00% 0/128 • All adverse events occurring from the time of consent to post study follow up i.e. 19 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	0.85% 1/118 • All adverse events occurring from the time of consent to post study follow up i.e. 19 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
Injury, poisoning and procedural complications Joint Dislocation	0.00% 0/128 • All adverse events occurring from the time of consent to post study follow up i.e. 19 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	0.85% 1/118 • All adverse events occurring from the time of consent to post study follow up i.e. 19 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
Injury, poisoning and procedural complications Lumbar Vertebral fracture	0.00% 0/128 • All adverse events occurring from the time of consent to post study follow up i.e. 19 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	0.85% 1/118 • All adverse events occurring from the time of consent to post study follow up i.e. 19 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
Injury, poisoning and procedural complications Road Traffic Accident	0.00% 0/128 • All adverse events occurring from the time of consent to post study follow up i.e. 19 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	0.85% 1/118 • All adverse events occurring from the time of consent to post study follow up i.e. 19 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
Injury, poisoning and procedural complications Soft Tissue Injury	0.00% 0/128 • All adverse events occurring from the time of consent to post study follow up i.e. 19 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	0.85% 1/118 • All adverse events occurring from the time of consent to post study follow up i.e. 19 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
Vascular disorders Deep Vein Thrombosis	0.00% 0/128 • All adverse events occurring from the time of consent to post study follow up i.e. 19 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	0.85% 1/118 • All adverse events occurring from the time of consent to post study follow up i.e. 19 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
Vascular disorders Hypotension	0.00% 0/128 • All adverse events occurring from the time of consent to post study follow up i.e. 19 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	0.85% 1/118 • All adverse events occurring from the time of consent to post study follow up i.e. 19 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
Musculoskeletal and connective tissue disorders Groin Pain	0.00% 0/128 • All adverse events occurring from the time of consent to post study follow up i.e. 19 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	0.85% 1/118 • All adverse events occurring from the time of consent to post study follow up i.e. 19 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.