A Study of Sativex® for Pain Relief in Patients With Adva... | NCT00530764

Status Module

Name	Class
Quintiles, Inc.	INDUSTRY

Oversight Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Sativex Low Dose	Experimental	Range of 1 to 4 sprays per day. Each actuation of oromucosal spray delivers 2.7mg delta-9-tetrahydrocannabinol (THC) and 2.5mg cannabidiol (CBD). Thus maximum daily dose is 10.8mg THC and 10mg CBD.	Drug: Sativex Low Dose
Sativex Medium Dose	Experimental	Range of 6 to 10 sprays per day. Each actuation of oromucosal spray delivers 2.7mg delta-9-tetrahydrocannabinol (THC) and 2.5mg cannabidiol (CBD). Thus maximum daily dose is 27mg THC and 25mg CBD.	Drug: Sativex Medium Dose
Sativex High Dose	Experimental	Range of 11 to 16 sprays per day. Each actuation of oromucosal spray delivers 2.7mg delta-9-tetrahydrocannabinol (THC) and 2.5mg cannabidiol (CBD). Thus maximum daily dose is 43.2mg THC and 40mg CBD.	Drug: Sativex High Dose
Placebo	No Intervention	Range of 1-16 sprays per day of placebo spray.

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Sativex Low Dose	Drug	Range of 1 to 4 sprays per day. Each actuation of oromucosal spray delivers 2.7mg delta-9-tetrahydrocannabinol (THC) and 2.5mg cannabidiol (CBD). Thus maximum daily dose is 10.8mg THC and 10mg CBD.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Patients With at Least 30% Improvement in Numerical Rating Scale (NRS) Average Pain Score From Baseline	A positive 30% pain response is defined as a reduction of at least 30% in the mean NRS average pain score from baseline to week 5 (last 3 days). 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 due to cancer. The average pain NRS was completed at the same time each day, i.e. bedtime in the evening.	5 Weeks: Baseline (first 3 days) - Week 5 (last 3 days)

Secondary Outcomes

Measure	Description	Time Frame
Change in Cumulative Average Pain Response Curves	The cumulative response to treatment is the percentage changes from baseline in the mean NRS pain score as defined as the 30% response. The 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 due to cancer.

Eligibility Module

Facility	Status	City	State	ZIP	Country	Contacts
Cancer Care Center of Tuscaloosa		Tuscaloosa	Alabama	35406	United States
Desert Oasis Cancer Center

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
22483680	Result	Portenoy RK, Ganae-Motan ED, Allende S, Yanagihara R, Shaiova L, Weinstein S, McQuade R, Wright S, Fallon MT. Nabiximols for opioid-treated cancer patients with poorly-controlled chronic pain: a randomized, placebo-controlled, graded-dose trial. J Pain. 2012 May;13(5):438-49. doi: 10.1016/j.jpain.2012.01.003. Epub 2012 Apr 5.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Sativex High Dose Group	Range of 11 to 16 sprays per day. Each actuation of oromucosal spray delivers 2.7mg delta-9-tetrahydrocannabinol (THC) and 2.5mg cannabidiol (CBD). Thus maximum daily dose is 43.2mg THC and 40mg CBD.
FG001	Sativex Medium Dose Group

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Sativex High Dose Group	Range of 11 to 16 sprays per day. Each actuation of oromucosal spray delivers 2.7mg delta-9-tetrahydrocannabinol (THC) and 2.5mg cannabidiol (CBD). Thus maximum daily dose is 43.2mg THC and 40mg CBD.
BG001	Sativex Medium Dose Group	Range of 6 to 10 sprays per day. Each actuation of oromucosal spray delivers 2.7mg delta-9-tetrahydrocannabinol (THC) and 2.5mg cannabidiol (CBD). Thus maximum daily dose is 27mg THC and 25mg CBD.
BG002	Sativex Low Dose Group	Range of 1 to 4 sprays per day. Each actuation of oromucosal spray delivers 2.7mg delta-9-tetrahydrocannabinol (THC) and 2.5mg cannabidiol (CBD). Thus maximum daily dose is 10.8mg THC and 10mg CBD.
BG003	Placebo	Range of 1-16 sprays per day of placebo spray
BG004	Total	Total of all reporting groups

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Patients With at Least 30% Improvement in Numerical Rating Scale (NRS) Average Pain Score From Baseline

A positive 30% pain response is defined as a reduction of at least 30% in the mean NRS average pain score from baseline to week 5 (last 3 days). 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 due to cancer. The average pain NRS was completed at the same time each day, i.e. bedtime in the evening.

Posted

Number

Participants

5 Weeks: Baseline (first 3 days) - Week 5 (last 3 days)

ID	Title	Description
OG000	Sativex High Dose Group	Range of 11 to 16 sprays per day. Each actuation of oromucosal spray delivers 2.7mg delta-9-tetrahydrocannabinol (THC) and 2.5mg cannabidiol (CBD). Thus maximum daily dose is 43.2mg THC and 40mg CBD.
OG001	Sativex Medium Dose Group	Range of 6 to 10 sprays per day. Each actuation of oromucosal spray delivers 2.7mg delta-9-tetrahydrocannabinol (THC) and 2.5mg cannabidiol (CBD). Thus maximum daily dose is 27mg THC and 25mg CBD.
OG002	Sativex Low Dose Group	Range of 1 to 4 sprays per day. Each actuation of oromucosal spray delivers 2.7mg delta-9-tetrahydrocannabinol (THC) and 2.5mg cannabidiol (CBD). Thus maximum daily dose is 10.8mg THC and 10mg CBD.
OG003	Placebo	Range of 1-16 sprays per day of placebo spray

Units	Counts
Participants	OG00090 OG00187 OG00291 OG003

Title

Denominators

Categories

Title	Measurements
	OG00022(0.46 to 1.76) OG00126(0.62 to 2.28) OG00230(0.72 to 2.60) OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG002 OG003	The proportions of responders were compared between the treatment groups using logistic regression with region and treatment groups as factors. The null hypothesis was that there was no difference between each of the Sativex treatment groups and placebo. The estimated response rates, odds ratios, 95% CIs for the odds ratios and p-values were presented.	Regression, Logistic		0.33		Odds Ratio (OR)	1.37			2-Sided	95	0.72	2.60				No	Superiority or Other

Secondary

Change in Cumulative Average Pain Response Curves

The cumulative response to treatment is the percentage changes from baseline in the mean NRS pain score as defined as the 30% response.

The 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 due to cancer.

Posted

Median

Inter-Quartile Range

Percent Change

Baseline to end of treatment (Week 5)

ID	Title	Description
OG000	Sativex High Dose Group	Range of 11 to 16 sprays per day. Each actuation of oromucosal spray delivers 2.7mg delta-9-tetrahydrocannabinol (THC) and 2.5mg cannabidiol (CBD). Thus maximum daily dose is 43.2mg THC and 40mg CBD.
OG001	Sativex Medium Dose Group	Range of 6 to 10 sprays per day. Each actuation of oromucosal spray delivers 2.7mg delta-9-tetrahydrocannabinol (THC) and 2.5mg cannabidiol (CBD). Thus maximum daily dose is 27mg THC and 25mg CBD.
OG002	Sativex Low Dose Group	Range of 1 to 4 sprays per day. Each actuation of oromucosal spray delivers 2.7mg delta-9-tetrahydrocannabinol (THC) and 2.5mg cannabidiol (CBD). Thus maximum daily dose is 10.8mg THC and 10mg CBD.

Secondary

Change in Mean Daily NRS Pain Score (Average Pain).

The average pain NRS was complete 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 due to cancer. A negative value indicates an improvement in pain score from baseline.

Posted

Mean

Standard Deviation

Points on scale

5 Weeks: Baseline (first 3 days) - End of Treatment (last 3 days of week 5)

ID	Title	Description
OG000	Sativex High Dose	Range of 11 to 16 sprays per day. Each actuation of oromucosal spray delivers 2.7mg delta-9-tetrahydrocannabinol (THC) and 2.5mg cannabidiol (CBD). Thus maximum daily dose is 43.2mg THC and 40mg CBD.
OG001	Sativex Medium Dose	Range of 6 to 10 sprays per day. Each actuation of oromucosal spray delivers 2.7mg delta-9-tetrahydrocannabinol (THC) and 2.5mg cannabidiol (CBD). Thus maximum daily dose is 27mg THC and 25mg CBD.
OG002	Sativex Low Dose	Range of 1 to 4 sprays per day. Each actuation of oromucosal spray delivers 2.7mg delta-9-tetrahydrocannabinol (THC) and 2.5mg cannabidiol (CBD). Thus maximum daily dose is 10.8mg THC and 10mg CBD.

Secondary

Change in Mean Daily NRS Pain Score (Worst Pain).

The worst 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 worst 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 due to cancer. A negative value indicates an improvement in worst pain score from baseline.

Posted

Mean

Standard Deviation

Points on scale

5 Weeks: Baseline (first 3 days) - End of Treatment (last 3 days of week 5)

ID	Title	Description
OG000	Sativex High Dose	Range of 11 to 16 sprays per day. Each actuation of oromucosal spray delivers 2.7mg delta-9-tetrahydrocannabinol (THC) and 2.5mg cannabidiol (CBD). Thus maximum daily dose is 43.2mg THC and 40mg CBD.
OG001	Sativex Medium Dose	Range of 6 to 10 sprays per day. Each actuation of oromucosal spray delivers 2.7mg delta-9-tetrahydrocannabinol (THC) and 2.5mg cannabidiol (CBD). Thus maximum daily dose is 27mg THC and 25mg CBD.
OG002	Sativex Low Dose	Range of 1 to 4 sprays per day. Each actuation of oromucosal spray delivers 2.7mg delta-9-tetrahydrocannabinol (THC) and 2.5mg cannabidiol (CBD). Thus maximum daily dose is 10.8mg THC and 10mg CBD.

Secondary

Change in Sleep Disruption NRS

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.

Posted

Mean

Standard Deviation

Points on scale

5 Weeks: Baseline - End of Treatment (Last 3 days of Week 5)

ID	Title	Description
OG000	Sativex High Dose Group	Range of 11 to 16 sprays per day. Each actuation of oromucosal spray delivers 2.7mg delta-9-tetrahydrocannabinol (THC) and 2.5mg cannabidiol (CBD). Thus maximum daily dose is 43.2mg THC and 40mg CBD.
OG001	Sativex Medium Dose Group	Range of 6 to 10 sprays per day. Each actuation of oromucosal spray delivers 2.7mg delta-9-tetrahydrocannabinol (THC) and 2.5mg cannabidiol (CBD). Thus maximum daily dose is 27mg THC and 25mg CBD.
OG002	Sativex Low Dose Group	Range of 1 to 4 sprays per day. Each actuation of oromucosal spray delivers 2.7mg delta-9-tetrahydrocannabinol (THC) and 2.5mg cannabidiol (CBD). Thus maximum daily dose is 10.8mg THC and 10mg CBD.

Secondary

Change in Brief Pain Inventory - Short Form (BPI-SF)

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.

Posted

Mean

Standard Deviation

Score on scale

Baseline (Visit 2) and End of Treatment (End of Week 5 or premature termination)

ID	Title	Description
OG000	Sativex High Dose Group	Range of 11 to 16 sprays per day. Each actuation of oromucosal spray delivers 2.7mg delta-9-tetrahydrocannabinol (THC) and 2.5mg cannabidiol (CBD). Thus maximum daily dose is 43.2mg THC and 40mg CBD.
OG001	Sativex Medium Dose Group	Range of 6 to 10 sprays per day. Each actuation of oromucosal spray delivers 2.7mg delta-9-tetrahydrocannabinol (THC) and 2.5mg cannabidiol (CBD). Thus maximum daily dose is 27mg THC and 25mg CBD.
OG002	Sativex Low Dose Group	Range of 1 to 4 sprays per day. Each actuation of oromucosal spray delivers 2.7mg delta-9-tetrahydrocannabinol (THC) and 2.5mg cannabidiol (CBD). Thus maximum daily dose is 10.8mg THC and 10mg CBD.

Secondary

Change in Patient Assessment of Constipation Quality of Life (PAC-QoL)

The PAC-QoL questionnaire consists of 28 questions divided into the following areas: 4 questions on physical discomfort, 8 questions on psychosocial discomfort, 11 questions on worries/concerns and 5 questions on satisfaction. The PAC-QoL was completed at baseline and then at the end of treatment. An overall score (range 0-4) was calculated at each visit and the difference determined. A positive difference in score represents an improvement.

Posted

Mean

Standard Deviation

Score on scale

Baseline (Visit 2) and End of Treatment (Week 5 or premature termination)

ID	Title	Description
OG000	Sativex High Dose Group	Range of 11 to 16 sprays per day. Each actuation of oromucosal spray delivers 2.7mg delta-9-tetrahydrocannabinol (THC) and 2.5mg cannabidiol (CBD). Thus maximum daily dose is 43.2mg THC and 40mg CBD.
OG001	Sativex Medium Dose Group	Range of 6 to 10 sprays per day. Each actuation of oromucosal spray delivers 2.7mg delta-9-tetrahydrocannabinol (THC) and 2.5mg cannabidiol (CBD). Thus maximum daily dose is 27mg THC and 25mg CBD.
OG002	Sativex Low Dose Group	Range of 1 to 4 sprays per day. Each actuation of oromucosal spray delivers 2.7mg delta-9-tetrahydrocannabinol (THC) and 2.5mg cannabidiol (CBD). Thus maximum daily dose is 10.8mg THC and 10mg CBD.

Secondary

Change in Patient Global Impression of Change - PGIC

A 7-point Likert-type scale was used, with the question: 'Please assess the status of your pain due to cancer 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 cancer which was used at Week 5 to aid their memory regarding their symptoms at study start. For each of above markers the number of participants were reported.

Posted

Number

Participants

End of Week 5

ID	Title	Description
OG000	Sativex High Dose Group	Range of 11 to 16 sprays per day. Each actuation of oromucosal spray delivers 2.7mg delta-9-tetrahydrocannabinol (THC) and 2.5mg cannabidiol (CBD). Thus maximum daily dose is 43.2mg THC and 40mg CBD.
OG001	Sativex Medium Dose Group	Range of 6 to 10 sprays per day. Each actuation of oromucosal spray delivers 2.7mg delta-9-tetrahydrocannabinol (THC) and 2.5mg cannabidiol (CBD). Thus maximum daily dose is 27mg THC and 25mg CBD.
OG002	Sativex Low Dose Group	Range of 1 to 4 sprays per day. Each actuation of oromucosal spray delivers 2.7mg delta-9-tetrahydrocannabinol (THC) and 2.5mg cannabidiol (CBD). Thus maximum daily dose is 10.8mg THC and 10mg CBD.

Secondary

Change in Montgomery Asberg Depression Rating Scale (MADRS)

The MADRS comprises of 10 questions that are completed by the patient to determine their depression level. The MADRS was completed at Visit 2 (Baseline) prior to receiving the study drug and at Visit 4 (Week 5 or premature termination). Each item is scored on a 0-6 scale , where 0=no sadness to 6=extreme and continuous gloom and despondency, and the MADRS score is the sum of the 10 item scores (range 0-60). The higher the score the more severe the depression.

Posted

Mean

Standard Deviation

Score on scale

Baseline and End of Treatment (Week 5 or premature termination)

ID	Title	Description
OG000	Sativex High Dose Group	Range of 11 to 16 sprays per day. Each actuation of oromucosal spray delivers 2.7mg delta-9-tetrahydrocannabinol (THC) and 2.5mg cannabidiol (CBD). Thus maximum daily dose is 43.2mg THC and 40mg CBD.
OG001	Sativex Medium Dose Group	Range of 6 to 10 sprays per day. Each actuation of oromucosal spray delivers 2.7mg delta-9-tetrahydrocannabinol (THC) and 2.5mg cannabidiol (CBD). Thus maximum daily dose is 27mg THC and 25mg CBD.
OG002	Sativex Low Dose Group	Range of 1 to 4 sprays per day. Each actuation of oromucosal spray delivers 2.7mg delta-9-tetrahydrocannabinol (THC) and 2.5mg cannabidiol (CBD). Thus maximum daily dose is 10.8mg THC and 10mg CBD.

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Sativex High Dose Group	Range of 11 to 16 sprays per day. Each actuation of oromucosal spray delivers 2.7mg delta-9-tetrahydrocannabinol (THC) and 2.5mg cannabidiol (CBD). Thus maximum daily dose is 43.2mg THC and 40mg CBD.	28	90	82	90
EG001	Sativex Medium Dose Group	Range of 6 to 10 sprays per day. Each actuation of oromucosal spray delivers 2.7mg delta-9-tetrahydrocannabinol (THC) and 2.5mg cannabidiol (CBD). Thus maximum daily dose is 27mg THC and 25mg CBD.	18	87	73	87
EG002	Sativex Low Dose Group	Range of 1 to 4 sprays per day. Each actuation of oromucosal spray delivers 2.7mg delta-9-tetrahydrocannabinol (THC) and 2.5mg cannabidiol (CBD). Thus maximum daily dose is 10.8mg THC and 10mg CBD.	35	91	68	91
EG003	Placebo	Range of 1-16 sprays per day of placebo spray	23	91	69	91

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Blood and Lymphatic system disorders	Blood and lymphatic system disorders	MedDRA 10.0	Systematic Assessment		EG0000 affected90 at risk EG0010 affected87 at risk EG0024 affected91 at risk EG0032 affected91 at risk
Cardiac disorders	Cardiac disorders	MedDRA 10.0	Systematic Assessment		EG0000 affected90 at risk EG0010 affected87 at risk EG0020 affected91 at risk EG003
Gastrointestinal disorders	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment		EG0004 affected90 at risk EG0013 affected87 at risk EG0021 affected91 at risk EG003
General Disorders	General disorders	MedDRA 10.0	Systematic Assessment	Any new unfavorable/unintended symptoms, worsening of condition that may/not be considered related to study medication.	EG0004 affected90 at risk EG0011 affected87 at risk EG0024 affected91 at risk EG003
Hepatobiliary disorders	Hepatobiliary disorders	MedDRA 10.0	Systematic Assessment		EG0001 affected90 at risk EG0011 affected87 at risk EG0020 affected91 at risk EG003
Infections and Infestations	Infections and infestations	MedDRA 10.0	Systematic Assessment		EG0002 affected90 at risk EG0015 affected87 at risk EG0024 affected91 at risk EG003
Injury, Poisoning and procedural complications	Injury, poisoning and procedural complications	MedDRA 10.0	Systematic Assessment		EG0000 affected90 at risk EG0011 affected87 at risk EG0021 affected91 at risk EG003
Investigations	Investigations	MedDRA 10.0	Systematic Assessment		EG0001 affected90 at risk EG0010 affected87 at risk EG0020 affected91 at risk EG003
Metabolism and Nutrition disorders	Metabolism and nutrition disorders	MedDRA 10.0	Systematic Assessment		EG0003 affected90 at risk EG0011 affected87 at risk EG0021 affected87 at risk EG003
Musculoskeletal and connective tissue disorders	Musculoskeletal and connective tissue disorders	MedDRA 10.0	Systematic Assessment		EG0000 affected90 at risk EG0010 affected87 at risk EG0020 affected91 at risk EG003
Neoplasms benign, malignant and unspecified (Incl. Cysts and polyps)	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 10.0	Systematic Assessment		EG00013 affected90 at risk EG00112 affected87 at risk EG00226 affected91 at risk EG003
Nervous system disorders	Nervous system disorders	MedDRA 10.0	Systematic Assessment		EG0003 affected90 at risk EG0011 affected87 at risk EG0021 affected91 at risk EG003
Psychiatric disorders	Psychiatric disorders	MedDRA 10.0	Systematic Assessment		EG0002 affected90 at risk EG0011 affected87 at risk EG0021 affected91 at risk EG003
Renal and urinary disorders	Renal and urinary disorders	MedDRA 10.0	Systematic Assessment		EG0004 affected90 at risk EG0010 affected87 at risk EG0020 affected91 at risk EG003
Respiratory, thoracic and mediastinal disorders	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment		EG0001 affected90 at risk EG0011 affected87 at risk EG0021 affected91 at risk EG003
Vascular disorders	Vascular disorders	MedDRA 10.0	Systematic Assessment		EG0003 affected90 at risk EG0010 affected87 at risk EG0020 affected91 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Blood and lymphatic system disorders	Blood and lymphatic system disorders	MedDRA 10.0	Systematic Assessment	EG0009 affected90 at risk EG0018 affected87 at risk EG0029 affected91 at risk EG0037 affected91 at risk
Cardiac disorders	Cardiac disorders	MedDRA 10.0	Systematic Assessment	EG0002 affected90 at risk EG0012 affected87 at risk EG0026 affected91 at risk EG003
Ear and labyrinth disorders	Ear and labyrinth disorders	MedDRA 10.0	Systematic Assessment	EG0004 affected90 at risk EG0014 affected87 at risk EG0020 affected91 at risk EG003
Eye disorders	Eye disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected90 at risk EG0014 affected87 at risk EG0021 affected91 at risk EG003
Gastrointestinal Disorder	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG00047 affected90 at risk EG00142 affected87 at risk EG00236 affected91 at risk EG003
General Disorders	General disorders	MedDRA 10.0	Systematic Assessment	EG00024 affected90 at risk EG00118 affected87 at risk EG00218 affected91 at risk EG003
Hepatobillary Disorders	Hepatobiliary disorders	MedDRA 10.0	Systematic Assessment	EG0002 affected90 at risk EG0011 affected87 at risk EG0020 affected91 at risk EG003
Infections and Infestations	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0008 affected90 at risk EG00115 affected87 at risk EG00211 affected81 at risk EG003
Injury, poisoning and procedural complications	Injury, poisoning and procedural complications	MedDRA 10.0	Systematic Assessment	EG0001 affected90 at risk EG0012 affected87 at risk EG0020 affected91 at risk EG003
Investigations	Investigations	MedDRA 10.0	Systematic Assessment	EG0005 affected90 at risk EG0019 affected87 at risk EG00211 affected91 at risk EG003
Metabolism and nutrition disorders	Metabolism and nutrition disorders	MedDRA 10.0	Systematic Assessment	EG00022 affected90 at risk EG00115 affected87 at risk EG00211 affected91 at risk EG003
Musculoskeletal and connective tissue disorders	Musculoskeletal and connective tissue disorders	MedDRA 10.0	Systematic Assessment	EG0005 affected90 at risk EG00112 affected87 at risk EG0026 affected91 at risk EG003
Neoplasms benign, malignant and unspecified (incl cysts and polyps)	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 10.0	Systematic Assessment	EG00016 affected90 at risk EG00112 affected87 at risk EG00226 affected91 at risk EG003
Nervous system disorders	Nervous system disorders	MedDRA 10.0	Systematic Assessment	EG00044 affected90 at risk EG00139 affected87 at risk EG00226 affected91 at risk EG003
Psychiatric disorders	Psychiatric disorders	MedDRA 10.0	Systematic Assessment	EG00023 affected90 at risk EG00114 affected87 at risk EG00213 affected91 at risk EG003
Renal and urinary disorders	Renal and urinary disorders	MedDRA 10.0	Systematic Assessment	EG0008 affected90 at risk EG0014 affected87 at risk EG0024 affected91 at risk EG003
Respiratory, thoracic and mediastinal disorders	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG0007 affected90 at risk EG0016 affected87 at risk EG00211 affected91 at risk EG003
Skin and subcuraneous tissue disorders	Skin and subcutaneous tissue disorders	MedDRA 10.0	Systematic Assessment	EG0007 affected90 at risk EG0013 affected87 at risk EG0023 affected91 at risk EG003
Surgical and medical procedures	Surgical and medical procedures	MedDRA 10.0	Systematic Assessment	EG0000 affected90 at risk EG0010 affected87 at risk EG0022 affected91 at risk EG003
Vascular Disorders	Vascular disorders	MedDRA 10.0	Systematic Assessment	EG0004 affected90 at risk EG0013 affected87 at risk EG0025 affected91 at risk EG003

ID	Term
D009461	Neurologic Manifestations
D012816	Signs and Symptoms
D013568	Pathological Conditions, Signs and Symptoms