A Safety and Efficacy Study of Oral Tapentadol Extended-Release in Japanese Participants

• Sponsor: Janssen Pharmaceutical K.K. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01309386
• Collaborator: (none)
• Enrollment: 100
• Locations: 25
• Arms: 2
• Duration (Months): 17
• Patients Per Site: 4
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the conversion rate based on the number of participants achieving pain control and safety within 1 week after switching the opioid (morphine-like medications) analgesics (drug used to control pain), when tapentadol extended-release (ER) (JNS024ER) is orally administered to participants treated with around-the-clock opioid analgesics, for their moderate to severe (very serious, life threatening) chronic (lasting a long time) malignant (cancerous) tumor-related (a mass in a specific area) cancer (abnormal tissue that grows and spreads in the body) pain.

Condition or Disease	Intervention/Treatment	Phase
Neoplasms	Drug: Tapentadol ER; Drug: Morphine SR	Phase 3

Detailed Description

This is a randomized (study drug assigned by chance), open-label (a medical research study in which participants and researchers are told which treatments the participants are receiving, "unblinded"), parallel-arm (participants receive 1 of 2 possible interventions during the same time frame throughout the study), optimal dose-titration, multicenter (when more than one hospital or medical school team work on a medical research study) study evaluating the conversion rate based on the number of participants achieving pain control and safety within 1 week after switching from an ongoing around-the-clock opioid analgesic (morphine sustained-release [SR], oxycodone controlled-release, or fentanyl transdermal) to tapentadol ER or morphine SR, for their moderate to severe chronic, malignant tumor-related cancer pain. The study consists of 2 periods: 1 to 2 week screening period, followed by 8-week open-label treatment period. During the study period, participants will be hospitalized or outpatient. However, it is preferable to be hospitalized 1 week before and 1 week after to evaluate efficacy before and after switching opioids for securing participants' safety. At Day 1, participants will receive either tapentadol ER or morphine SR twice daily. During the treatment period, the dose of the study drug will be titrated to the participant's optimal dose. The participants will receive either tapentadol ER or morphine SR twice daily for 8 weeks. The maximum dose allowed for tapentadol ER will be 500 milligram (mg) daily or morphine SR 140 mg daily throughout the study. Efficacy is primarily evaluated using pain intensity score on an 11 point Numerical Rating Scale (an 11-point NRS is used to measure the pain level where 0=no pain to 10=pain as bad as you can imagine). Participants' safety will also be monitored.

Study Design

• Study Type: Interventional
• Actual Enrollment: 100 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized, Open-Label, Parallel-Arm, Optimal Dose-Titration, Multicenter Study to Evaluate the Safety and Efficacy of Oral JNS024 Extended-Release (ER) in Japanese Subjects Treated With Around-the-Clock Opioid Analgesics for Their Moderate to Severe Chronic Malignant Tumor- Related Cancer Pain
• Study Start Date: Aug 1, 2010
• Actual Primary Completion Date: Jan 1, 2012
• Actual Study Completion Date: Jan 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tapentadol ER Tapentadol extended-release (ER) (JNS024ER) oral tablets 100 to 400 milligram (mg) daily for 8 weeks (maximum dose could be up to 500 mg daily), as per Investigator's discretion.	Drug: Tapentadol ER; Tapentadol ER 100 to 400 milligram (mg) orally daily for 8 weeks (maximum up to 500 mg daily), as per Investigator's discretion.
Active Comparator: Morphine SR Morphine sustained-release (SR) oral tablets 30 to 120 mg daily for 8 weeks (maximum dose could be up to 140 mg daily), as per Investigator's discretion.	Drug: Morphine SR; Morphine SR 30 to 120 mg orally daily for 8 weeks (maximum up to 140 mg daily), as per Investigator's discretion.

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Who Achieved Pain Control [Week 1]

   Pain control was considered to be achieved for participants who met both of the following criteria for any consecutive 3 days during the first week of treatment period: a) Change from baseline of mean 24 hour numerical rating scale (NRS) (an 11-point NRS is used to measure the pain level where 0=no pain to 10=pain as bad as you can imagine) score less than +1.5, and b) when the frequency of rescue medication was twice or less per day.

Secondary Outcome Measures

1. Change From Baseline in Numerical Rating Scale (NRS) at Week 1, 2, 3, 4, 5, 6, 7 and 8 [Baseline, Week 1, 2, 3, 4, 5, 6, 7, 8]

   Average pain intensity was assessed using an 11-point NRS to measure the pain level for the past 24-hours where 0=no pain to 10=pain as bad as you can imagine.

2. Number of Participants Who Discontinued Study Treatment Due to Lack of Efficacy [Baseline up to Week 8]

   Number of participants who discontinued the treatment due to lack of efficacy were assessed throughout the study.

3. Number of Participants With Patient Global Impression of Change (PGIC) [Week 1, 4 and 8]

   The PGIC is a single-item questionnaire designed to provide an overall assessment of treatment from the participant's perspective since the start of the study. It is measured on a 7-point scale, where 1=very much improved and 7=very much worse. A participant is considered a responder if they have a response of "very much improved" or "much improved".

4. Total Number of Days of Rescue Medication Over Time [Baseline up to Week 8]

   Total number of days of rescue medication over time were assessed. Rescue medications are medicines that are administered to the participants when the efficacy of the study drug is not satisfactory, or the effect of the study drug is too great and is likely to cause a hazard to the participant, or to manage an emergency situation. Supplemental analgesics (drug used to control pain) were used as rescue medication.

5. Number of Doses of Rescue Medication Over Time [Baseline up to Week 8]

   Number of doses of rescue medication over time were assessed. Rescue medications are medicines that are administered to the participants when the efficacy of the study drug is not satisfactory, or the effect of the study drug is too great and is likely to cause a hazard to the participant, or to manage an emergency situation. Supplemental analgesics (drug used to control pain) were used as rescue medication.

6. Average Change From Baseline in Amount of Rescue Medication Over Time [Baseline, Week 1, 2, 3, 4, 5, 6, 7, 8]

   Rescue medications are medicines that are administered to the participants when the efficacy of the study drug is not satisfactory, or the effect of the study drug is too great and is likely to cause a hazard to the participant, or to manage an emergency situation. Supplemental analgesics (drug used to control pain) were used as rescue medication. Average amount was the averages of all doses recorded during the baseline period or during each week (Week 1, 2, 3, 4, 5, 6, 7 and 8).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Participants with documented clinical diagnosis (determination of the cause of a medical problem) of any type of cancer (abnormal tissue that grows and spreads in the body)

• Participants with mean 24-hour Numerical Rating Scale (NRS) score (11-point NRS used to measure the pain level for the past 24-hours where 0=no pain to 10=pain as bad as you can imagine) during 3 days (Day -4 to Day -2) before randomization (study drug assigned by chance) less than 4.0

• Women must be post-menopausal, surgically sterile, or before entry and throughout the study practicing an effective method of birth control

• Participants using immediate-release (IR) morphine hydrochloride (HCl) or oxycodone HCl hydrate as rescue medication (rescue medications are medicines that may be administered to the participants when the efficacy of the study drug is not satisfactory, or the effect of the study drug is too great and is likely to cause a hazard to the participant, or to manage an emergency situation) for breakthrough pain

• Participants treated with around-the-clock opioid (morphine-like medications) therapy for moderate to severe (very serious, life threatening) chronic (lasting a long time), malignant (cancerous) tumor-related (a mass in a specific area) cancer (abnormal tissue that grows and spreads in the body) pain using one of the following opioid analgesics (drug used to control pain) before randomization: morphine SR tablet less than or equal to 120 milligram (mg) per day, oxycodone hydrochloride controlled release (CR) tablet: 15 mg to 80 mg per day, durotep MT (fentanyl transdermal [through the skin] matrix) patch less than or equal to 8.4 mg per patch, fentos tape less than or equal to 4 mg per tape, or oneduro patch less than or equal to 3.4 mg per patch

Exclusion Criteria:

• Participants with complicated uncontrolled/clinically significant arrhythmia (uneven heart beat)

• Participants who had received rescue doses 3 times or more daily within 3 days (Day -4 to Day -2) before the randomization

• History of surgery intended for the cure of the primary disease or for the treatment of cancer pain within 28 days before screening

• Participants who had application of radiotherapy (treatment of cancer using x-rays), nerve block, or stimulation analgesia within 7 days before screening

• Participants with known allergies (over sensitivity to a substance), hypersensitivity, or intolerance to opioid analgesics or its excipients

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Chiba		Japan
2		Hamamatsu		Japan
3		Ibaraki		Japan
4		Kanagawa		Japan
5		Katsushika		Japan
6		Kobe		Japan
7		Kumamoto		Japan
8		Matsumoto-City		Japan
9		Matsumoto		Japan
10		Matsuyama N/A		Japan
11		Matsuyama		Japan
12		Nagasaki		Japan
13		Nagoya		Japan
14		Nishinomiya		Japan
15		Ohmura		Japan
16		Ohta		Japan
17		Osaka		Japan
18		Saga		Japan
19		Sapporo		Japan
20		Tokyo		Japan
21		Toyama		Japan
22		Toyohashi N/A		Japan
23		Toyohashi		Japan
24		Utsunomiya		Japan
25		Yokohama		Japan

Sponsors and Collaborators

• Janssen Pharmaceutical K.K.

Investigators

• Study Director: Janssen Pharmaceutical K.K. Clinical Trial, Janssen Pharmaceutical K.K.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Janssen Pharmaceutical K.K.
• ClinicalTrials.gov Identifier: NCT01309386
• Other Study ID Numbers: CR017326; JNS024ER-JPN-C03
• First Posted: Mar 7, 2011
• Last Update Posted: Mar 13, 2013
• Last Verified: Feb 1, 2013

• Keywords provided by Janssen Pharmaceutical K.K.: Tapentadol; Tumor related pain; Opioid; Cancer related pain; Morphine
• Additional relevant MeSH terms: Morphine; Tapentadol

Study Results

Participant Flow

Arm/Group Title	Tapentadol ER	Morphine SR
Arm/Group Description	Tapentadol extended-release (ER) (JNS024ER) oral tablets 100 to 400 milligram (mg) daily for 8 weeks (maximum dose could be up to 500 mg daily), as per Investigator's discretion.	Morphine sustained-release (SR) oral tablets 30 to 120 mg daily for 8 weeks (maximum dose could be up to 140 mg daily), as per Investigator's discretion.
Period Title: Overall Study
STARTED	50	50
COMPLETED	28	29
NOT COMPLETED	22	21

Baseline Characteristics

Arm/Group Title	Tapentadol ER	Morphine SR	Total
Arm/Group Description	Tapentadol extended-release (ER) (JNS024ER) oral tablets 100 to 400 milligram (mg) daily for 8 weeks (maximum dose could be up to 500 mg daily), as per Investigator's discretion.	Morphine sustained-release (SR) oral tablets 30 to 120 mg daily for 8 weeks (maximum dose could be up to 140 mg daily), as per Investigator's discretion.	Total of all reporting groups
Overall Participants	50	50	100
Age, Customized (Number) [Number]
Less than 65 years	23 (8.5) 46%	25 (9.97) 50%	48 48%
More than or equal to 65 years	27 54%	25 50%	52 52%
Sex: Female, Male (Count of Participants)
Female	25 50%	23 46%	48 48%
Male	25 50%	27 54%	52 52%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Who Achieved Pain Control
Description	Pain control was considered to be achieved for participants who met both of the following criteria for any consecutive 3 days during the first week of treatment period: a) Change from baseline of mean 24 hour numerical rating scale (NRS) (an 11-point NRS is used to measure the pain level where 0=no pain to 10=pain as bad as you can imagine) score less than +1.5, and b) when the frequency of rescue medication was twice or less per day.
Time Frame	Week 1

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) population included all participants who were randomly assigned, received at least 1 dose of study drug and had post-baseline efficacy data.

Arm/Group Title	Tapentadol ER	Morphine SR
Arm/Group Description	Tapentadol extended-release (ER) (JNS024ER) oral tablets 100 to 400 milligram (mg) daily for 8 weeks (maximum dose could be up to 500 mg daily), as per Investigator's discretion.	Morphine sustained-release (SR) oral tablets 30 to 120 mg daily for 8 weeks (maximum dose could be up to 140 mg daily), as per Investigator's discretion.
Measure Participants	50	50
Number (95% Confidence Interval) [Percentage of Participants]	84.0 168%	98.0 196%

2. Secondary Outcome

Title	Change From Baseline in Numerical Rating Scale (NRS) at Week 1, 2, 3, 4, 5, 6, 7 and 8
Description	Average pain intensity was assessed using an 11-point NRS to measure the pain level for the past 24-hours where 0=no pain to 10=pain as bad as you can imagine.
Time Frame	Baseline, Week 1, 2, 3, 4, 5, 6, 7, 8

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) population included all participants who were randomly assigned, received at least 1 dose of study drug and had post-baseline efficacy data. Here 'n' signifies those participants evaluable for this measure at the specified time point for each arm group, respectively.

Arm/Group Title	Tapentadol ER	Morphine SR
Arm/Group Description	Tapentadol extended-release (ER) (JNS024ER) oral tablets 100 to 400 milligram (mg) daily for 8 weeks (maximum dose could be up to 500 mg daily), as per Investigator's discretion.	Morphine sustained-release (SR) oral tablets 30 to 120 mg daily for 8 weeks (maximum dose could be up to 140 mg daily), as per Investigator's discretion.
Measure Participants	50	50
Change at Week 1 (n = 50, 50)	0.4 (0.92)	-0.2 (0.84)
Change at Week 2 (n = 45, 44)	0.3 (1.11)	-0.3 (0.75)
Change at Week 3 (n= 41, 41)	0.1 (0.90)	-0.1 (1.03)
Change at Week 4 (n = 38, 37)	0.1 (0.90)	-0.3 (0.95)
Change at Week 5 (n = 36, 34)	0.1 (0.92)	-0.1 (1.22)
Change at Week 6 (n = 36, 32)	0.2 (0.97)	0.1 (1.43)
Change at Week 7 (n = 34, 29)	0.1 (1.00)	0.1 (1.05)
Change at Week 8 (n = 29, 29)	0.0 (0.92)	0.0 (1.21)

3. Secondary Outcome

Title	Number of Participants Who Discontinued Study Treatment Due to Lack of Efficacy
Description	Number of participants who discontinued the treatment due to lack of efficacy were assessed throughout the study.
Time Frame	Baseline up to Week 8

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) population included all participants who were randomly assigned, received at least 1 dose of study drug and had post-baseline efficacy data.

Arm/Group Title	Tapentadol ER	Morphine SR
Arm/Group Description	Tapentadol extended-release (ER) (JNS024ER) oral tablets 100 to 400 milligram (mg) daily for 8 weeks (maximum dose could be up to 500 mg daily), as per Investigator's discretion.	Morphine sustained-release (SR) oral tablets 30 to 120 mg daily for 8 weeks (maximum dose could be up to 140 mg daily), as per Investigator's discretion.
Measure Participants	50	50
Number [Participants]	3 6%	1 2%

4. Secondary Outcome

Title	Number of Participants With Patient Global Impression of Change (PGIC)
Description	The PGIC is a single-item questionnaire designed to provide an overall assessment of treatment from the participant's perspective since the start of the study. It is measured on a 7-point scale, where 1=very much improved and 7=very much worse. A participant is considered a responder if they have a response of "very much improved" or "much improved".
Time Frame	Week 1, 4 and 8

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) population; here 'N' signifies those participants evaluable for this outcome measure and 'n' signifies those participants evaluable for this measure at the specified time point for each arm group, respectively.

Arm/Group Title	Tapentadol ER	Morphine SR
Arm/Group Description	Tapentadol extended-release (ER) (JNS024ER) oral tablets 100 to 400 milligram (mg) daily for 8 weeks (maximum dose could be up to 500 mg daily), as per Investigator's discretion.	Morphine sustained-release (SR) oral tablets 30 to 120 mg daily for 8 weeks (maximum dose could be up to 140 mg daily), as per Investigator's discretion.
Measure Participants	48	48
Week 1 (very much improved) (n=48,48)	1 2%	2 4%
Week 1 (much improved) (n=48,48)	1 2%	4 8%
Week 1 (minimally improved) (n=48,48)	11 22%	7 14%
Week 1 (not changed) (n=48,48)	24 48%	29 58%
Week 1 (minimally worse) (n=48,48)	9 18%	6 12%
Week 1 (much worse) (n=48,48)	2 4%	0 0%
Week 1 (very much worse) (n=48,48)	0 0%	0 0%
Week 4 (very much improved) (n=37,37)	1 2%	3 6%
Week 4 (much improved) (n=37,37)	2 4%	5 10%
Week 4 (minimally improved) (n=37,37)	9 18%	7 14%
Week 4 (not changed) (n=37,37)	22 44%	19 38%
Week 4 (minimally worse) (n=37,37)	3 6%	3 6%
Week 4 (much worse) (n=37,37)	0 0%	0 0%
Week 4 (very much worse) (n=37,37)	0 0%	0 0%
Week 8 (very much improved) (n=28,28)	0 0%	3 6%
Week 8 (much improved) (n=28,28)	3 6%	2 4%
Week 8 (minimally improved) (n=28,28)	8 16%	4 8%
Week 8 (not changed) (n=28,28)	15 30%	13 26%
Week 8 (minimally worse) (n=28,28)	2 4%	4 8%
Week 8 (much worse) (n=28,28)	0 0%	2 4%
Week 8 (very much worse) (n=28,28)	0 0%	0 0%

5. Secondary Outcome

Title	Total Number of Days of Rescue Medication Over Time
Description	Total number of days of rescue medication over time were assessed. Rescue medications are medicines that are administered to the participants when the efficacy of the study drug is not satisfactory, or the effect of the study drug is too great and is likely to cause a hazard to the participant, or to manage an emergency situation. Supplemental analgesics (drug used to control pain) were used as rescue medication.
Time Frame	Baseline up to Week 8

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) population included all participants who were randomly assigned, received at least 1 dose of study drug and had post-baseline efficacy data.

Arm/Group Title	Tapentadol ER	Morphine SR
Arm/Group Description	Tapentadol extended-release (ER) (JNS024ER) oral tablets 100 to 400 milligram (mg) daily for 8 weeks (maximum dose could be up to 500 mg daily), as per Investigator's discretion.	Morphine sustained-release (SR) oral tablets 30 to 120 mg daily for 8 weeks (maximum dose could be up to 140 mg daily), as per Investigator's discretion.
Measure Participants	50	50
Mean (Standard Deviation) [Days]	15.9 (19.58)	9.2 (12.76)

6. Secondary Outcome

Title	Number of Doses of Rescue Medication Over Time
Description	Number of doses of rescue medication over time were assessed. Rescue medications are medicines that are administered to the participants when the efficacy of the study drug is not satisfactory, or the effect of the study drug is too great and is likely to cause a hazard to the participant, or to manage an emergency situation. Supplemental analgesics (drug used to control pain) were used as rescue medication.
Time Frame	Baseline up to Week 8

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) population included all participants who were randomly assigned, received at least 1 dose of study drug and had post-baseline efficacy data.

Arm/Group Title	Tapentadol ER	Morphine SR
Arm/Group Description	Tapentadol extended-release (ER) (JNS024ER) oral tablets 100 to 400 milligram (mg) daily for 8 weeks (maximum dose could be up to 500 mg daily), as per Investigator's discretion.	Morphine sustained-release (SR) oral tablets 30 to 120 mg daily for 8 weeks (maximum dose could be up to 140 mg daily), as per Investigator's discretion.
Measure Participants	50	50
Mean (Standard Deviation) [Morphine-equivalent doses]	0.7 (0.89)	0.4 (0.53)

7. Secondary Outcome

Title	Average Change From Baseline in Amount of Rescue Medication Over Time
Description	Rescue medications are medicines that are administered to the participants when the efficacy of the study drug is not satisfactory, or the effect of the study drug is too great and is likely to cause a hazard to the participant, or to manage an emergency situation. Supplemental analgesics (drug used to control pain) were used as rescue medication. Average amount was the averages of all doses recorded during the baseline period or during each week (Week 1, 2, 3, 4, 5, 6, 7 and 8).
Time Frame	Baseline, Week 1, 2, 3, 4, 5, 6, 7, 8

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) population included all participants who were randomly assigned, received at least 1 dose of study drug and had post-baseline efficacy data.

Arm/Group Title	Tapentadol ER	Morphine SR
Arm/Group Description	Tapentadol extended-release (ER) (JNS024ER) oral tablets 100 to 400 milligram (mg) daily for 8 weeks (maximum dose could be up to 500 mg daily), as per Investigator's discretion.	Morphine sustained-release (SR) oral tablets 30 to 120 mg daily for 8 weeks (maximum dose could be up to 140 mg daily), as per Investigator's discretion.
Measure Participants	50	50
Mean (Standard Deviation) [Milligram (mg)]	3.02 (8.303)	-0.15 (5.038)

Adverse Events

Arm/Group Title	Tapentadol ER		Morphine SR
Arm/Group Description	Tapentadol extended-release (ER) (JNS024ER) oral tablets 100 to 400 milligram (mg) daily for 8 weeks (maximum dose could be up to 500 mg daily), as per Investigator's discretion.		Morphine sustained-release (SR) oral tablets 30 to 120 mg daily for 8 weeks (maximum dose could be up to 140 mg daily), as per Investigator's discretion.
All Cause Mortality
	Tapentadol ER		Morphine SR
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Tapentadol ER		Morphine SR
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/50 (32%)		16/50 (32%)
Gastrointestinal disorders
Vomiting	1/50 (2%)		3/50 (6%)
Gastrointestinal perforation	1/50 (2%)		0/50 (0%)
Stomatitis	0/50 (0%)		1/50 (2%)
General disorders
Disease progression	10/50 (20%)		10/50 (20%)
Condition aggravated	0/50 (0%)		1/50 (2%)
Malaise	1/50 (2%)		0/50 (0%)
Hepatobiliary disorders
Cholangitis	1/50 (2%)		0/50 (0%)
Infections and infestations
Pneumonia	1/50 (2%)		0/50 (0%)
Urinary tract infection	1/50 (2%)		0/50 (0%)
Injury, poisoning and procedural complications
Fall	2/50 (4%)		0/50 (0%)
Metabolism and nutrition disorders
Decreased appetite	1/50 (2%)		1/50 (2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain	1/50 (2%)		1/50 (2%)
Gastric cancer	1/50 (2%)		0/50 (0%)
Nervous system disorders
Dyskinesia	1/50 (2%)		0/50 (0%)
Subarachnoid haemorrhage	1/50 (2%)		0/50 (0%)
Reproductive system and breast disorders
Genital haemorrhage	0/50 (0%)		1/50 (2%)
Other (Not Including Serious) Adverse Events
	Tapentadol ER		Morphine SR
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	43/50 (86%)		44/50 (88%)
Blood and lymphatic system disorders
Anaemia	4/50 (8%)		1/50 (2%)
Leukopenia	2/50 (4%)		1/50 (2%)
Thrombocytopenia	2/50 (4%)		1/50 (2%)
Bone marrow failure	0/50 (0%)		1/50 (2%)
Cardiac disorders
Angina pectoris	1/50 (2%)		0/50 (0%)
Ear and labyrinth disorders
Motion sickness	1/50 (2%)		0/50 (0%)
Eye disorders
Diabetic retinopathy	0/50 (0%)		1/50 (2%)
Diplopia	1/50 (2%)		0/50 (0%)
Visual impairment	1/50 (2%)		0/50 (0%)
Gastrointestinal disorders
Constipation	6/50 (12%)		10/50 (20%)
Nausea	7/50 (14%)		7/50 (14%)
Vomiting	2/50 (4%)		11/50 (22%)
Diarrhoea	3/50 (6%)		4/50 (8%)
Stomatitis	2/50 (4%)		1/50 (2%)
Abdominal pain upper	0/50 (0%)		1/50 (2%)
Cheilitis	0/50 (0%)		1/50 (2%)
Gastric ulcer	1/50 (2%)		0/50 (0%)
Hiatus hernia	1/50 (2%)		0/50 (0%)
Lip dry	1/50 (2%)		0/50 (0%)
Pancreatitis	0/50 (0%)		1/50 (2%)
Periodontitis	0/50 (0%)		1/50 (2%)
Toothache	1/50 (2%)		0/50 (0%)
General disorders
Pyrexia	3/50 (6%)		4/50 (8%)
Disease progression	9/50 (18%)		8/50 (16%)
Chest pain	0/50 (0%)		1/50 (2%)
Feeling abnormal	1/50 (2%)		0/50 (0%)
Catheter site haemorrhage	1/50 (2%)		0/50 (0%)
Catheter site pain	1/50 (2%)		0/50 (0%)
Catheter site swelling	1/50 (2%)		0/50 (0%)
Malaise	3/50 (6%)		0/50 (0%)
Hepatobiliary disorders
Hepatic function abnormal	1/50 (2%)		1/50 (2%)
Cholangitis	1/50 (2%)		0/50 (0%)
Infections and infestations
Nasopharyngitis	1/50 (2%)		1/50 (2%)
Pneumonia	1/50 (2%)		1/50 (2%)
Bacteraemia	0/50 (0%)		1/50 (2%)
Cellulitis	0/50 (0%)		1/50 (2%)
Oral candidiasis	1/50 (2%)		0/50 (0%)
Paronychia	1/50 (2%)		0/50 (0%)
Rhinitis	1/50 (2%)		0/50 (0%)
Upper respiratory tract infection	0/50 (0%)		1/50 (2%)
Injury, poisoning and procedural complications
Fall	2/50 (4%)		1/50 (2%)
Post gastric surgery syndrome	0/50 (0%)		1/50 (2%)
Tooth fracture	0/50 (0%)		1/50 (2%)
Post procedural haematuria	0/50 (0%)		1/50 (2%)
Investigations
Gamma-glutamyltransferase increased	1/50 (2%)		4/50 (8%)
Alanine aminotransferase increased	0/50 (0%)		2/50 (4%)
Aspartate aminotransferase increased	0/50 (0%)		2/50 (4%)
Blood creatine phosphokinase increased	1/50 (2%)		1/50 (2%)
Blood lactate dehydrogenase increased	1/50 (2%)		1/50 (2%)
Blood triglycerides increased	1/50 (2%)		1/50 (2%)
Glucose urine present	0/50 (0%)		2/50 (4%)
Neutrophil count increased	0/50 (0%)		2/50 (4%)
Platelet count decreased	1/50 (2%)		1/50 (2%)
Protein urine present	0/50 (0%)		2/50 (4%)
Blood urea increased	0/50 (0%)		1/50 (2%)
Differential white blood cell count abnormal	0/50 (0%)		1/50 (2%)
Blood urine present	1/50 (2%)		0/50 (0%)
Haemoglobin decreased	0/50 (0%)		1/50 (2%)
White blood cell count decreased	1/50 (2%)		0/50 (0%)
Platelet count increased	0/50 (0%)		1/50 (2%)
Urine output decreased	1/50 (2%)		0/50 (0%)
Blood alkaline phosphatase increased	1/50 (2%)		2/50 (4%)
Weight decreased	0/50 (0%)		1/50 (2%)
Metabolism and nutrition disorders
Hyperkalaemia	1/50 (2%)		0/50 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/50 (2%)		1/50 (2%)
Back pain	1/50 (2%)		0/50 (0%)
Lumbar spinal stenosis	0/50 (0%)		1/50 (2%)
Periarthritis	0/50 (0%)		1/50 (2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to liver	1/50 (2%)		0/50 (0%)
Metastases to skin	1/50 (2%)		0/50 (0%)
Nervous system disorders
Somnolence	8/50 (16%)		10/50 (20%)
Headache	1/50 (2%)		4/50 (8%)
Dizziness	2/50 (4%)		1/50 (2%)
Lethargy	2/50 (4%)		0/50 (0%)
Neuropathy peripheral	2/50 (4%)		0/50 (0%)
Autonomic nervous system imbalance	1/50 (2%)		0/50 (0%)
Depressed level of consciousness	0/50 (0%)		1/50 (2%)
Dysgeusia	1/50 (2%)		0/50 (0%)
Hypoaesthesia	1/50 (2%)		0/50 (0%)
Muscle contractions involuntary	1/50 (2%)		0/50 (0%)
Slow response to stimuli	0/50 (0%)		1/50 (2%)
Vocal cord paralysis	1/50 (2%)		0/50 (0%)
Psychiatric disorders
Insomnia	4/50 (8%)		0/50 (0%)
Delirium	0/50 (0%)		1/50 (2%)
Generalised anxiety disorder	0/50 (0%)		1/50 (2%)
Senile psychosis	1/50 (2%)		0/50 (0%)
Adjustment disorder	1/50 (2%)		0/50 (0%)
Renal and urinary disorders
Haematuria	1/50 (2%)		1/50 (2%)
Proteinuria	0/50 (0%)		2/50 (4%)
Chromaturia	1/50 (2%)		0/50 (0%)
Dysuria	0/50 (0%)		1/50 (2%)
Hydronephrosis	1/50 (2%)		0/50 (0%)
Urobilinuria	0/50 (0%)		1/50 (2%)
Reproductive system and breast disorders
Benign prostatic hyperplasia	1/50 (2%)		0/50 (0%)
Vaginal discharge	1/50 (2%)		0/50 (0%)
Respiratory, thoracic and mediastinal disorders
Epistaxis	2/50 (4%)		0/50 (0%)
Dyspnoea	0/50 (0%)		1/50 (2%)
Sputum increased	0/50 (0%)		1/50 (2%)
Oropharyngeal pain	0/50 (0%)		1/50 (2%)
Skin and subcutaneous tissue disorders
Pruritus	1/50 (2%)		4/50 (8%)
Decubitus ulcer	2/50 (4%)		1/50 (2%)
Rash	0/50 (0%)		3/50 (6%)
Erythema	1/50 (2%)		1/50 (2%)
Alopecia	1/50 (2%)		0/50 (0%)
Dermatitis contact	1/50 (2%)		0/50 (0%)
Skin disorder	0/50 (0%)		1/50 (2%)
Skin erosion	1/50 (2%)		0/50 (0%)
Urticaria	1/50 (2%)		0/50 (0%)
Pruritus generalised	1/50 (2%)		0/50 (0%)
Vascular disorders
Hypertension	0/50 (0%)		1/50 (2%)
Hypotension	0/50 (0%)		1/50 (2%)
Orthostatic hypotension	0/50 (0%)		1/50 (2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The disclosure restriction on PI is that the sponsor can review results communications prior to public release and can embargo communications regarding results for a period as the sponsor requires.