Sativex® for Relieving Persistent Pain in Participants Wi... | NCT01262651

ID	Type	Description	Link
2009-016064-36	EudraCT Number

Status Module

Name	Class
Otsuka Pharmaceutical Development & Commercialization, Inc.	INDUSTRY

Oversight Module

Description 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
Nabiximols	Experimental	Nabiximols was self-administered by participants as a 100 microliter (μL) oromucosal spray in the morning and evening, up to a maximum of 10 sprays per day for 5 weeks. Nabiximols oromucosal spray contained delta-9-tetrahydrocannabinol (THC) (27 milligram [mg]/milliliter [mL]):cannabidiol (CBD) (25 mg/mL), in ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring. Each 100 μL actuation delivered 2.7 mg THC and 2.5 mg CBD.	Drug: Nabiximols
Placebo (GA-0034)	Placebo Comparator	Placebo Comparator: Placebo (GA-0034) Placebo was self-administered by participants as a 100 μL oromucosal spray in the morning and evening, up to a maximum of 10 sprays per day for 5 weeks. Placebo oromucosal spray contained ethanol: propylene glycol (50:50)	Drug: Placebo (GA-0034)

Name	Type	Description	Arm Group Labels	Other Names
Nabiximols	Drug		Nabiximols	Sativex®
Placebo (GA-0034)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percent Improvement From Baseline In Mean NRS Average Pain At End Of Treatment	Participants indicated level of pain in the last 24 hours on an 11-point Numerical Rating Scale (NRS), where a score of 0 was "no pain" and 10 was "pain as bad as you can imagine". Baseline = mean score from first day of 3-day eligibility period through to the day before first dose of study drug. End of Treatment = mean score over last (up to) 7 days to the final pain score at End of Treatment or up until Day 35, whichever is earlier, or final score available (prematurely terminated). Percentage improvement from baseline (Imp%) was calculated as: Imp% = (Baseline pain NRS mean - End of Treatment pain NRS mean)/Baseline pain NRS mean * 100. For participants who died or withdrew due to disease progression, Imp% values were used. For participants who died or withdrew unrelated to disease progression before end of Week 5 (no diary data from Day 33 onwards), Imp% was zero for participants whose Imp% value was positive and it was Imp% for participants whose Imp% value was not positive.	Baseline, End of Treatment (Day 36)

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline In Mean NRS Average Pain At End Of Treatment	Participants indicated the level of pain experienced in the last 24 hours on an 11-point NRS, where a score of 0 indicated "no pain" and a score of 10 indicated "pain as bad as you can imagine." Change in mean NRS average pain was calculated as: End of Treatment NRS average pain score - Baseline NRS average pain score. A negative value indicates an improvement in average pain score from Baseline.

Eligibility Module

Eligibility Criteria

Inclusion Criteria (abbreviated):

The participant had advanced cancer for which there was no known curative therapy
The participant had a clinical diagnosis of cancer related pain, which was not wholly alleviated with their current optimized opioid treatment
The participant received an optimized maintenance dose of Step 3 opioid therapy, preferably with a sustained release preparation, but also allowing a regular maintenance dose of around the clock use of immediate release preparations
The participant received a daily maintenance dose Step 3 opioid therapy of less than or equal to a total daily opioid dose of 500 mg/day of morphine equivalence (including maintenance and break-through opioids)
The participant was using no more than one type of break-through opioid analgesia

Exclusion Criteria (abbreviated):

The participant had any planned clinical interventions that would have affected their pain (for example, chemotherapy or radiation therapy where, in the clinical judgment of the investigator, these would be expected to affect pain)
The participant was using or had used cannabis or cannabinoid-based medications within 30 days of study entry and is unwilling to abstain for the duration of the study
The participant had experienced myocardial infarction or clinically significant cardiac dysfunction within the last 12 months or had a cardiac disorder that, in the opinion of the investigator, would have put the participant at risk of a clinically significant arrhythmia or myocardial infarction
The participant had significantly impaired renal function
The participant had significantly impaired hepatic function
Female participants of child-bearing potential and male participants whose partner was of child-bearing potential, unless willing to ensure that they or their partner used effective contraception, for example, oral contraception, double barrier, intra-uterine device, during the study and for 3 months thereafter (however, a male condom was not to be used in conjunction with a female condom as this may not have proven effective)

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
28923526	Background	Lichtman AH, Lux EA, McQuade R, Rossetti S, Sanchez R, Sun W, Wright S, Kornyeyeva E, Fallon MT. Results of a Double-Blind, Randomized, Placebo-Controlled Study of Nabiximols Oromucosal Spray as an Adjunctive Therapy in Advanced Cancer Patients with Chronic Uncontrolled Pain. J Pain Symptom Manage. 2018 Feb;55(2):179-188.e1. doi: 10.1016/j.jpainsymman.2017.09.001. Epub 2017 Sep 18.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Nabiximols	Nabiximols was self-administered by participants as a 100 microliter (μL) oromucosal spray in the morning and evening, up to a maximum of 10 sprays per day, for 5 weeks. Nabiximols oromucosal spray contained delta-9-tetrahydrocannabinol (THC) (27 milligram [mg]/milliliter [mL]):cannabidiol (CBD) (25 mg/mL), in ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring. Each 100 μL actuation delivered 2.7 mg THC and 2.5 mg CBD.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Nabiximols	Nabiximols was self-administered by participants as a 100 μL oromucosal spray in the morning and evening, up to a maximum of 10 sprays per day, for 5 weeks. Nabiximols oromucosal spray contained THC (27 mg/mL):CBD (25 mg/mL), in ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring. Each 100 μL actuation delivered 2.7 mg THC and 2.5 mg CBD.
BG001	Placebo (GA-0034)	Placebo was self-administered by participants as a 100 μL oromucosal spray in the morning and evening, up to a maximum of 10 sprays per day, for 5 weeks. Placebo oromucosal spray contained ethanol: propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring and colorings.
BG002	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

Percent Improvement From Baseline In Mean NRS Average Pain At End Of Treatment

Participants indicated level of pain in the last 24 hours on an 11-point Numerical Rating Scale (NRS), where a score of 0 was "no pain" and 10 was "pain as bad as you can imagine". Baseline = mean score from first day of 3-day eligibility period through to the day before first dose of study drug. End of Treatment = mean score over last (up to) 7 days to the final pain score at End of Treatment or up until Day 35, whichever is earlier, or final score available (prematurely terminated).

Percentage improvement from baseline (Imp%) was calculated as:

Imp% = (Baseline pain NRS mean - End of Treatment pain NRS mean)/Baseline pain NRS mean * 100.

For participants who died or withdrew due to disease progression, Imp% values were used. For participants who died or withdrew unrelated to disease progression before end of Week 5 (no diary data from Day 33 onwards), Imp% was zero for participants whose Imp% value was positive and it was Imp% for participants whose Imp% value was not positive.

The ITT Population included all participants who were randomized, received at least 1 dose of study drug, and had at least 1 efficacy endpoint. Participants were analyzed according to the treatment group they were randomized to.

Posted

Median

Inter-Quartile Range

percent improvement

Baseline, End of Treatment (Day 36)

ID	Title	Description
OG000	Nabiximols	Nabiximols was self-administered by participants as a 100 μL oromucosal spray in the morning and evening, up to a maximum of 10 sprays per day, for 5 weeks. Nabiximols oromucosal spray contained THC (27 mg/mL):CBD (25 mg/mL), in ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring. Each 100 μL actuation delivered 2.7 mg THC and 2.5 mg CBD.
OG001	Placebo (GA-0034)	Placebo was self-administered by participants as a 100 μL oromucosal spray in the morning and evening, up to a maximum of 10 sprays per day, for 5 weeks. Placebo oromucosal spray contained ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring and colorings.

Units	Counts
Participants	OG000199 OG001198

Title

Denominators

Categories

Title	Measurements
	OG00010.7(0.0 to 30.0) OG0014.5(-2.9 to 25.7)

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
OG000 OG001		Wilcoxon (Mann-Whitney)		0.0854		Median Difference (Final Values)	3.41			2-Sided	95	0.00	8.16					Superiority

Secondary

Change From Baseline In Mean NRS Average Pain At End Of Treatment

Participants indicated the level of pain experienced in the last 24 hours on an 11-point NRS, where a score of 0 indicated "no pain" and a score of 10 indicated "pain as bad as you can imagine." Change in mean NRS average pain was calculated as: End of Treatment NRS average pain score - Baseline NRS average pain score.

A negative value indicates an improvement in average pain score from Baseline.

ITT Population included all participants who receive at least 1 dose of study drug, and had at least 1 efficacy endpoint. Participants were analyzed according to the treatment group they were randomized to.

Posted

Mean

Standard Deviation

units on a scale

Baseline, End Of Treatment (Day 36)

ID	Title	Description
OG000	Nabiximols	Nabiximols was self-administered by participants as a 100 μL oromucosal spray in the morning and evening, up to a maximum of 10 sprays per day, for 5 weeks. Nabiximols oromucosal spray contained THC (27 mg/mL):CBD (25 mg/mL), in ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring. Each 100 μL actuation delivered 2.7 mg THC and 2.5 mg CBD.
OG001	Placebo (GA-0034)	Placebo was self-administered by participants as a 100 μL oromucosal spray in the morning and evening, up to a maximum of 10 sprays per day, for 5 weeks. Placebo oromucosal spray contained ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring and colorings.

Secondary

Change From Baseline In Mean NRS Worst Pain At End Of Treatment

Participants indicated the level of worst pain experienced in the last 24 hours on an 11-point NRS, where a score of 0 indicated "no pain" and a score of 10 indicated "pain as bad as you can imagine." Change in mean NRS worst pain was calculated as: End of Treatment NRS worst pain score - Baseline NRS worst pain score.

A negative value indicates an improvement in worst pain score from Baseline.

Posted

Mean

Standard Deviation

units on a scale

Baseline, End of Treatment (Day 36)

ID	Title	Description
OG000	Nabiximols	Nabiximols was self-administered by participants as a 100 μL oromucosal spray in the morning and evening, up to a maximum of 10 sprays per day, for 5 weeks. Nabiximols oromucosal spray contained THC (27 mg/mL):CBD (25 mg/mL), in ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring. Each 100 μL actuation delivered 2.7 mg THC and 2.5 mg CBD.
OG001	Placebo (GA-0034)	Placebo was self-administered by participants as a 100 μL oromucosal spray in the morning and evening, up to a maximum of 10 sprays per day, for 5 weeks. Placebo oromucosal spray contained ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring and colorings.

Secondary

Change From Baseline In Mean Sleep Disruption NRS At End Of Treatment

Participants indicated the level of sleep disruption experienced in the last 24 hours on an 11-point NRS, where a score of 0 indicated "did not disrupt sleep" and a score of 10 indicated "completely disrupted (unable to sleep at all)." Change in mean sleep disruption NRS was calculated as: End of Treatment sleep disruption NRS score - Baseline sleep disruption NRS score.

A negative value indicates an improvement in sleep disruption score from Baseline.

Posted

Mean

Standard Deviation

units on a scale

Baseline, End of Treatment (Day 36)

ID	Title	Description
OG000	Nabiximols	Nabiximols was self-administered by participants as a 100 μL oromucosal spray in the morning and evening, up to a maximum of 10 sprays per day, for 5 weeks. Nabiximols oromucosal spray contained THC (27 mg/mL):CBD (25 mg/mL), in ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring. Each 100 μL actuation delivered 2.7 mg THC and 2.5 mg CBD.
OG001	Placebo (GA-0034)	Placebo was self-administered by participants as a 100 μL oromucosal spray in the morning and evening, up to a maximum of 10 sprays per day, for 5 weeks. Placebo oromucosal spray contained ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring and colorings.

Secondary

Subject Global Impression Of Change At Last Visit (Up To Day 36)

The Subject Global Impression of Change (SGIC) was used to assess the overall status of the participant related to their cancer pain, with the markers "very much improved, much improved, slightly improved, no change, slightly worse, much worse, or very much worse". The SGIC was assessed at Day 36 or at which a participant's last evaluation was performed, such as in the case of early termination. Last visit refers to the last visit that a participant completed the assessment; this could be either Day 22 or Day 36.

Posted

Count of Participants

Participants

Last Visit (up to Day 36)

ID	Title	Description
OG000	Nabiximols	Nabiximols was self-administered by participants as a 100 μL oromucosal spray in the morning and evening, up to a maximum of 10 sprays per day, for 5 weeks. Nabiximols oromucosal spray contained THC (27 mg/mL):CBD (25 mg/mL), in ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring. Each 100 μL actuation delivered 2.7 mg THC and 2.5 mg CBD.
OG001	Placebo (GA-0034)	Placebo was self-administered by participants as a 100 μL oromucosal spray in the morning and evening, up to a maximum of 10 sprays per day, for 5 weeks. Placebo oromucosal spray contained ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring and colorings.

Secondary

Physician Global Impression Of Change At Last Visit (Up To Day 36)

The Physician Global Impression of Change (PGIC) was used by the treating physician (investigator/sub-investigator) to assess if there was any change in the general functional abilities of the participant since prior to commencement of study medication, with the markers: "Very much worse, Much worse, Slightly worse, No change, Slightly improved, Much improved, Very much improved". Last visit refers to the last visit that a participant completed the assessment; this could be either Day 22 or Day 36.

Posted

Count of Participants

Participants

Last Visit (up to Day 36)

ID	Title	Description
OG000	Nabiximols	Nabiximols was self-administered by participants as a 100 μL oromucosal spray in the morning and evening, up to a maximum of 10 sprays per day, for 5 weeks. Nabiximols oromucosal spray contained THC (27 mg/mL):CBD (25 mg/mL), in ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring. Each 100 μL actuation delivered 2.7 mg THC and 2.5 mg CBD.
OG001	Placebo (GA-0034)	Placebo was self-administered by participants as a 100 μL oromucosal spray in the morning and evening, up to a maximum of 10 sprays per day, for 5 weeks. Placebo oromucosal spray contained ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring and colorings.

Secondary

Patient Satisfaction Questionnaire At Last Visit (Up To Day 36)

The Patient Satisfaction Questionnaire (PSQ) was used to assess level of satisfaction of the participant with the study drug, with the markers "Extremely satisfied, Very satisfied, Slightly satisfied, Neutral, Slightly dissatisfied, Very dissatisfied, Extremely dissatisfied". Last visit refers to the last visit that a participant completed the assessment; this could be either Day 22 or Day 36.

Posted

Count of Participants

Participants

Last Visit (up to Day 36)

ID	Title	Description
OG000	Nabiximols	Nabiximols was self-administered by participants as a 100 μL oromucosal spray in the morning and evening, up to a maximum of 10 sprays per day, for 5 weeks. Nabiximols oromucosal spray contained THC (27 mg/mL):CBD (25 mg/mL), in ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring. Each 100 μL actuation delivered 2.7 mg THC and 2.5 mg CBD.
OG001	Placebo (GA-0034)	Placebo was self-administered by participants as a 100 μL oromucosal spray in the morning and evening, up to a maximum of 10 sprays per day, for 5 weeks. Placebo oromucosal spray contained ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring and colorings.

Secondary

Change From Baseline In Daily Total Opioid Use (Morphine Equivalent) At End Of Treatment

The total daily opioid use (in morphine equivalence) was the sum of morphine equivalents of daily maintenance dose and break-through dose.

Change in daily total opioid use was calculated as: End of Treatment daily total opioid use - Baseline daily total opioid use.

A negative value indicates a decrease in use from Baseline.

Posted

Mean

Standard Deviation

mg (morphine equivalent)

Baseline, End of Treatment (Day 36)

ID	Title	Description
OG000	Nabiximols	Nabiximols was self-administered by participants as a 100 μL oromucosal spray in the morning and evening, up to a maximum of 10 sprays per day, for 5 weeks. Nabiximols oromucosal spray contained THC (27 mg/mL):CBD (25 mg/mL), in ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring. Each 100 μL actuation delivered 2.7 mg THC and 2.5 mg CBD.
OG001	Placebo (GA-0034)	Placebo was self-administered by participants as a 100 μL oromucosal spray in the morning and evening, up to a maximum of 10 sprays per day, for 5 weeks. Placebo oromucosal spray contained ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring and colorings.

Secondary

Change From Baseline In Daily Maintenance Opioid Dose (Morphine Equivalent) At End of Treatment

The prescribed daily quantity of opioid maintenance dose was calculated as the product of dose per use and daily frequency of use. Participants were asked: "Have you used your maintenance dose painkiller today as prescribed?" If the participant answered "No" to the question, the daily opioid maintenance dose usage on that day was set to 0.

Change in daily maintenance opioid dose was calculated as: End of Treatment daily maintenance opioid dose - Baseline daily maintenance opioid dose.

A negative value indicates a decrease in dose from Baseline.

Posted

Mean

Standard Deviation

mg (morphine equivalent)

Baseline, End of Treatment (Day 36)

ID	Title	Description
OG000	Nabiximols	Nabiximols was self-administered by participants as a 100 μL oromucosal spray in the morning and evening, up to a maximum of 10 sprays per day, for 5 weeks. Nabiximols oromucosal spray contained THC (27 mg/mL):CBD (25 mg/mL), in ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring. Each 100 μL actuation delivered 2.7 mg THC and 2.5 mg CBD.
OG001	Placebo (GA-0034)	Placebo was self-administered by participants as a 100 μL oromucosal spray in the morning and evening, up to a maximum of 10 sprays per day, for 5 weeks. Placebo oromucosal spray contained ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring and colorings.

Secondary

Change From Baseline In Daily Break-through Opioid Dose (Morphine Equivalent) At End Of Treatment

Daily break-through opioid dose usage was calculated as the product of prescribed dose per use, and the number of uses per day. If participants took more than 1 different break-through opioid for more than 1 day, the sum of morphine equivalents dose usages for each break-through opioid was calculated for the summary.

Change in daily break-through opioid dose was calculated as: End of Treatment daily break-through opioid dose - Baseline daily break-through opioid dose.

A negative value indicates a decrease in dose from Baseline.

Posted

Mean

Standard Deviation

mg (morphine equivalent)

Baseline, End of Treatment (Day 36)

ID	Title	Description
OG000	Nabiximols	Nabiximols was self-administered by participants as a 100 μL oromucosal spray in the morning and evening, up to a maximum of 10 sprays per day, for 5 weeks. Nabiximols oromucosal spray contained THC (27 mg/mL):CBD (25 mg/mL), in ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring. Each 100 μL actuation delivered 2.7 mg THC and 2.5 mg CBD.
OG001	Placebo (GA-0034)	Placebo was self-administered by participants as a 100 μL oromucosal spray in the morning and evening, up to a maximum of 10 sprays per day, for 5 weeks. Placebo oromucosal spray contained ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring and colorings.

Secondary

Change From Baseline In NRS Constipation At Last Visit (Up To Day 36)

Participants indicated level of constipation on an 11-point NRS, where a score of 0 was "no constipation", and 10 was "constipation as bad as you can imagine." Last visit refers to the last visit that a participant completed the assessment; this could be either Day 22 or Day 36.

Change in NRS constipation score was calculated as: Last Visit NRS constipation score - Baseline NRS constipation score.

A negative value indicates improvement in condition from Baseline.

Posted

Mean

Standard Deviation

units on a scale

Baseline, Last Visit (up to Day 36)

ID	Title	Description
OG000	Nabiximols	Nabiximols was self-administered by participants as a 100 μL oromucosal spray in the morning and evening, up to a maximum of 10 sprays per day, for 5 weeks. Nabiximols oromucosal spray contained THC (27 mg/mL):CBD (25 mg/mL), in ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring. Each 100 μL actuation delivered 2.7 mg THC and 2.5 mg CBD.
OG001	Placebo (GA-0034)	Placebo was self-administered by participants as a 100 μL oromucosal spray in the morning and evening, up to a maximum of 10 sprays per day, for 5 weeks. Placebo oromucosal spray contained ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring and colorings.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Nabiximols	Nabiximols was self-administered by participants as a 100 μL oromucosal spray in the morning and evening, up to a maximum of 10 sprays per day, for 5 weeks. Nabiximols oromucosal spray contained THC (27 mg/mL):CBD (25 mg/mL), in ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring. Each 100 μL actuation delivered 2.7 mg THC and 2.5 mg CBD.			47	199	69	199
EG001	Placebo (GA-0034)	Placebo was self-administered by participants as a 100 μL oromucosal spray in the morning and evening, up to a maximum of 10 sprays per day, for 5 weeks. Placebo oromucosal spray contained ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring and colorings.			43	198	53	198

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Neutropenia	Blood and lymphatic system disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected199 at risk EG0011 affected198 at risk
Pancytopenia	Blood and lymphatic system disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected199 at risk EG0010 affected198 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected199 at risk EG0011 affected198 at risk
Atrial Fibrillation	Cardiac disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected199 at risk EG0010 affected198 at risk
Cardiac Failure Congestive	Cardiac disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected199 at risk EG0010 affected198 at risk
Gastric perforation	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected199 at risk EG0011 affected198 at risk
Gastrointestinal Haemorrhage	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected199 at risk EG0011 affected198 at risk
Ileus	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected199 at risk EG0011 affected198 at risk
Intestinal Obstruction	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected199 at risk EG0012 affected198 at risk
Mouth Haemorrhage	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected199 at risk EG0010 affected198 at risk
Nausea	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected199 at risk EG0011 affected198 at risk
Vomiting	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected199 at risk EG0012 affected198 at risk
Device Occlusion	General disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected199 at risk EG0010 affected198 at risk
Clostridium Difficile Colitis	Infections and infestations	MedDRA 17.0	Systematic Assessment	EG0001 affected199 at risk EG0010 affected198 at risk
Lower Respiratory Tract Infection	Infections and infestations	MedDRA 17.0	Systematic Assessment	EG0003 affected199 at risk EG0010 affected198 at risk
Pneumonia	Infections and infestations	MedDRA 17.0	Systematic Assessment	EG0001 affected199 at risk EG0012 affected198 at risk
Respiratory Tract Infection	Infections and infestations	MedDRA 17.0	Systematic Assessment	EG0001 affected199 at risk EG0010 affected198 at risk
Sepsis	Infections and infestations	MedDRA 17.0	Systematic Assessment	EG0000 affected199 at risk EG0011 affected198 at risk
Urinary Tract Infection	Infections and infestations	MedDRA 17.0	Systematic Assessment	EG0001 affected199 at risk EG0010 affected198 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 17.0	Systematic Assessment	EG0000 affected199 at risk EG0011 affected198 at risk
Electrolyte Imbalance	Metabolism and nutrition disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected199 at risk EG0010 affected198 at risk
Back Pain	Musculoskeletal and connective tissue disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected199 at risk EG0010 affected198 at risk
Cancer Pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 17.0	Systematic Assessment	EG0003 affected199 at risk EG0010 affected198 at risk
Metastases To Central Nervous System	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 17.0	Systematic Assessment	EG0001 affected199 at risk EG0010 affected198 at risk
Neoplasm Progression	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 17.0	Systematic Assessment	EG00031 affected199 at risk EG00128 affected198 at risk
Tumour pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 17.0	Systematic Assessment	EG0000 affected199 at risk EG0011 affected198 at risk
Convulsion	Nervous system disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected199 at risk EG0010 affected198 at risk
Spinal Cord Compression	Nervous system disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected199 at risk EG0011 affected198 at risk
Completed Suicide	Psychiatric disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected199 at risk EG0011 affected198 at risk
Disorientation	Psychiatric disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected199 at risk EG0010 affected198 at risk
Hallucination, Visual	Psychiatric disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected199 at risk EG0010 affected198 at risk
Mental Status Changes	Psychiatric disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected199 at risk EG0011 affected198 at risk
Renal Failure Acute	Renal and urinary disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected199 at risk EG0010 affected198 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected199 at risk EG0010 affected198 at risk
Pleural Effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected199 at risk EG0011 affected198 at risk
Pulmonary Embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected199 at risk EG0010 affected198 at risk
Pulmonary Toxicity	Respiratory, thoracic and mediastinal disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected199 at risk EG0011 affected198 at risk
Deep Vein Thrombosis	Vascular disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected199 at risk EG0011 affected198 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Nausea	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG00031 affected199 at risk EG00120 affected198 at risk
Dizziness	Nervous system disorders	MedDRA 17.0	Systematic Assessment	EG00016 affected199 at risk EG0018 affected198 at risk
Vomiting	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG00015 affected199 at risk EG00111 affected198 at risk
Decreased Appetite	Metabolism and nutrition disorders	MedDRA 17.0	Systematic Assessment	EG00014 affected199 at risk EG00112 affected198 at risk
Constipation	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG00011 affected199 at risk EG00113 affected198 at risk
Fatigue	General disorders	MedDRA 17.0	Systematic Assessment	EG00012 affected199 at risk EG00110 affected198 at risk

Facility	Status	City	State	ZIP	Country	Contacts
		Phoenix	Arizona	85027	United States

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