Study Evaluating the Efficacy and Safety of Subcutaneous Methylnaltrexone (MOA-728) for the Treatment of Opioid-Induced-Constipation

• Sponsor: Bausch Health Americas, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00936884
• Collaborator: Progenics Pharmaceuticals, Inc. (Industry)
• Enrollment: 50
• Locations: 6
• Arms: 3
• Duration (Months): 52
• Patients Per Site: 8.3
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The primary purpose of this study is to evaluate the safety, efficacy, and tolerability of subcutaneous (injection beneath the skin) MOA-728 versus placebo in adult Asian subjects with opioid-induced constipation associated with advanced illness (ie, a terminal illness such as incurable cancer or other end-stage disease) or chronic nonmalignant pain.

Condition or Disease	Intervention/Treatment	Phase
Constipation	Drug: Methylnaltrexone; Drug: Placebo	Phase 3

Detailed Description

Subjects received subcutaneous methylnaltrexone (also referred to as MOA-728 or MNTX) or placebo every other day beginning on Day 1 up to a maximum of 7 doses during the 2-week double-blind period.

Inclusion criteria for this study included subjects with advanced illness or subjects with chronic nonmalignant pain. The actual study population included only subjects with cancer-related advanced illness.

All subjects who completed the double-blind treatment phase of this study could elect to receive methylnaltrexone during a 12-week open-label extension study, provided eligibility criteria were met. Subjects who did not continue in the open-label extension study had a follow-up visit 2 weeks after their last dose of test article.

Study Design

• Study Type: Interventional
• Actual Enrollment: 50 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, And Parallel-Group Study Of Subcutaneous Methylnaltrexone (MOA-728) For The Treatment Of Opioid-Induced Constipation In Adult Subjects
• Study Start Date: Jul 1, 2009
• Actual Primary Completion Date: Nov 1, 2013
• Actual Study Completion Date: Nov 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Methylnaltrexone double-blind Methylnaltrexone once every other day.	Drug: Methylnaltrexone; Subjects received 0.6 mL (12 mg) every other day if weight ≥ 62kg; 0.4 mL (8 mg) every other day if weight between 38 and < 62 kg; or 0.0075 mL/kg (0.15 mg/kg) every other day if weight between 27 and <38 kg. Study duration: 2 weeks double-blind period (MNTX treatments) followed by 12 weeks open-label extension period (MNTX treatments).; Other Names: MOA-728 MNTX
Placebo Comparator: Placebo Placebo once every other day.	Drug: Placebo; Subjects received matching placebo injections. Study duration: 2 weeks double-blind period (placebo treatments) followed by 12 weeks open-label extension period (MNTX treatments).
Other: Methylnaltrexone open-label Subjects who completed the double-blind period had the option to receive methylnaltrexone once every other day during a 12-week, open-label extension period.	Drug: Methylnaltrexone; Subjects received 0.6 mL (12 mg) every other day if weight ≥ 62kg; 0.4 mL (8 mg) every other day if weight between 38 and < 62 kg; or 0.0075 mL/kg (0.15 mg/kg) every other day if weight between 27 and <38 kg. Study duration: 2 weeks double-blind period (MNTX treatments) followed by 12 weeks open-label extension period (MNTX treatments).; Other Names: MOA-728 MNTX

Outcome Measures

Primary Outcome Measures

1. The Proportion of Subjects Having a Rescue-free Bowel Movement (RFBM) Within 4 Hours After the First Injection. [Up to 4 hours after the first injection]

   There were 2 co-primary endpoints for this study. This measurement is the first of the 2 co-primary endpoints. This endpoint measures the percentage of patients who had an RFBM within 4 hours after the first dose of test article during the double-blind period; data are expressed as percentages of patients for the MNTX and placebo groups. To qualify as rescue free, the bowel movement could not occur within 6 hours after a rectal intervention (ie, rectal suppository, enema, manual disimpaction). Note that efficacy results (primary and secondary outcomes) are presented for the double-blind period only. Therefore, no efficacy results are presented for the open-label period.

2. The Proportion of Subjects Having a Rescue-free Bowel Movement (RFBM) Within 4 Hours After Each Dose During Double-blind Period. [Within 4 Hours After Each Dose During the 2 weeks Double-Blind Period]

   This measurement is the second of the 2 co-primary endpoints. This endpoint measures the percentage of patients who had an RFBM within 4 hours after each dose of test article during the double-blind period; data are expressed as percentages of patients by dose (first, second, third, fourth, etc.) for the MNTX and placebo groups. The definition of RFBM is described above (see first co-primary endpoint).

Secondary Outcome Measures

1. Percentage of Injections Resulting in RFBM Within 4 Hours After Test Article Administration. [Within 4 Hours After Each Dose During the 2 weeks Double-Blind Period]

   This endpoint measures the percentage of injections resulting in RFBMs within 4 hours after test article administration during the double-blind period. The percentage of injections resulting in RFBMs is calculated for each patient and then data are expressed as the mean (± standard deviation) percentage for the MNTX and placebo groups. The definition of RFBM is described above (see first co-primary endpoint).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Men and women who are at least 18 years of age, and who have a diagnosis of advanced illness with anticipated life expectancy >= 1 month;

• Is receiving a regular dose of opioids for the control of pain;

• Has a diagnosis of opioid induced constipation;

• Is on a stable laxative regimen.

Exclusion Criteria:

• Has a known or suspected mechanical gastrointestinal obstruction, or any potential non-opioid cause of bowel dysfunction contributed to constipation;

• Has evidence of current fecal impaction;

• Has evidence of active diverticulitis, or peritonitis, or a history of bowel surgery within 30 days before test article administration;

• Has a body weight less than 27 kg

• Has any major illness/condition that, in the investigator's judgment, will substantially increase the risk associated with the subject's participation in and completion of the study, or could preclude the evaluation of the subject's response.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Koyang-shi	Kyounggi-do	Korea, Republic of	410-719
2		Seoul		Korea, Republic of	135-710
3		Seoul		Korea, Republic of	137-701
4		Seoul		Korea, Republic of	152-703
5		Tainan		Taiwan	70428
6		Taipei TOC		Taiwan	100

Sponsors and Collaborators

• Bausch Health Americas, Inc.
• Progenics Pharmaceuticals, Inc.

Investigators

• Study Director: Enoch Bortey, Bausch Health Americas, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Bausch Health Americas, Inc.
• ClinicalTrials.gov Identifier: NCT00936884
• Other Study ID Numbers: 3200K1-3361; B2541004
• First Posted: Jul 10, 2009
• Last Update Posted: Jan 2, 2020
• Last Verified: Dec 1, 2019

• Keywords provided by Bausch Health Americas, Inc.: Opioid Induced Constipation
• Additional relevant MeSH terms: Constipation; Opioid-Induced Constipation; Methylnaltrexone

Study Results

Participant Flow

Arm/Group Title	Methylnaltrexone Double-blind	Placebo	Methylnaltrexone Open-label
Arm/Group Description	Methylnaltrexone once every other day.	Placebo once every other day.	Subjects who completed the double-blind period had the option to receive methylnaltrexone once every other day during a 12-week, open-label extension period.
Period Title: Double-blind
STARTED	25	25	0
COMPLETED	13	18	0
NOT COMPLETED	12	7	0
Period Title: Double-blind
STARTED	0	0	31
COMPLETED	0	0	12
NOT COMPLETED	0	0	19

Baseline Characteristics

Arm/Group Title	Methylnaltrexone Double-blind	Placebo	Total
Arm/Group Description	Methylnaltrexone once every other day. Subjects received 0.6 mL (12 mg) every other day if weight ≥ 62kg; 0.4 mL (8 mg) every other day if weight between 38 and < 62 kg; or 0.0075 mL/kg (0.15 mg/kg) every other day if weight between 27 and <38 kg.	Placebo once every other day. Subjects received matching placebo injections.	Total of all reporting groups
Overall Participants	25	25	50
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	18 72%	13 52%	31 62%
>=65 years	7 28%	12 48%	19 38%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58.5 (11.68)	62.1 (14.23)	60.3 (13.01)
Sex: Female, Male (Count of Participants)
Female	14 56%	11 44%	25 50%
Male	11 44%	14 56%	25 50%
Eastern Cooperative Oncology Group Score (Count of Participants)
0 - Fully active	0 0%	1 4%	1 2%
1 - Restricted in strenuous activity	3 12%	4 16%	7 14%
2 - Unable to work	6 24%	5 20%	11 22%
3 - Limited self-care	16 64%	15 60%	31 62%
Hospitalization Status at Screening Period (participants) [Number]
Yes	12 48%	8 32%	20 40%
No	13 52%	17 68%	30 60%
Underlying Advanced Illness - Cancer-related illness (Count of Participants)
Count of Participants [Participants]	25 100%	25 100%	50 100%
Weight (Count of Participants)
< 38 kg	2 8%	0 0%	2 4%
38 - < 62 kg	17 68%	20 80%	37 74%
≥62 kg	6 24%	4 16%	10 20%
Missing	0 0%	1 4%	1 2%

Outcome Measures

1. Primary Outcome

Title	The Proportion of Subjects Having a Rescue-free Bowel Movement (RFBM) Within 4 Hours After the First Injection.
Description	There were 2 co-primary endpoints for this study. This measurement is the first of the 2 co-primary endpoints. This endpoint measures the percentage of patients who had an RFBM within 4 hours after the first dose of test article during the double-blind period; data are expressed as percentages of patients for the MNTX and placebo groups. To qualify as rescue free, the bowel movement could not occur within 6 hours after a rectal intervention (ie, rectal suppository, enema, manual disimpaction). Note that efficacy results (primary and secondary outcomes) are presented for the double-blind period only. Therefore, no efficacy results are presented for the open-label period.
Time Frame	Up to 4 hours after the first injection

Outcome Measure Data

Analysis Population Description

Although 25 patients in the MNTX group and 24 in the placebo group received study drug, 24 and 23 patients, respectively, had ≥ 1 post baseline diary assessment and were analyzed for efficacy.

Arm/Group Title	Methylnaltrexone Double-blind	Placebo
Arm/Group Description	Methylnaltrexone once every other day. Subjects received 0.6 mL (12 mg) every other day if weight ≥ 62kg; 0.4 mL (8 mg) every other day if weight between 38 and < 62 kg; or 0.0075 mL/kg (0.15 mg/kg) every other day if weight between 27 and <38 kg.	Placebo once every other day. Subjects received matching placebo injections.
Measure Participants	24	23
Number [percentage of participants]	79.2 316.8%	4.3 17.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Methylnaltrexone Double-blind, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Comparison of the MNTX group and the placebo group in the proportion of subjects having a RFBM within 4 hours after the first injection was performed by using a 2-sided Cochran-Mantel-Haenszel Chi square test at the alpha level of 0.025.
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	83.60
	Confidence Interval	(2-Sided) 97.5%; 6.50 to 1074.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Percentage of Injections Resulting in RFBM Within 4 Hours After Test Article Administration.
Description	This endpoint measures the percentage of injections resulting in RFBMs within 4 hours after test article administration during the double-blind period. The percentage of injections resulting in RFBMs is calculated for each patient and then data are expressed as the mean (± standard deviation) percentage for the MNTX and placebo groups. The definition of RFBM is described above (see first co-primary endpoint).
Time Frame	Within 4 Hours After Each Dose During the 2 weeks Double-Blind Period

Outcome Measure Data

Analysis Population Description

Although 25 patients in the MNTX group and 24 in the placebo group received study drug, 24 and 23 patients, respectively, had ≥ 1 post baseline diary assessment and were analyzed for efficacy.

Arm/Group Title	Methylnaltrexone Double-blind	Placebo
Arm/Group Description	Methylnaltrexone once every other day. Subjects received 0.6 mL (12 mg) every other day if weight ≥ 62kg; 0.4 mL (8 mg) every other day if weight between 38 and < 62 kg; or 0.0075 mL/kg (0.15 mg/kg) every other day if weight between 27 and <38 kg.	Placebo once every other day. Subjects received matching placebo injections.
Measure Participants	24	23
Mean (Standard Deviation) [percentage of injections]	61.61 (36.520)	4.97 (22.203)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Methylnaltrexone Double-blind, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Comparison of the MNTX group and the placebo group was based on ANOVA model with the proportion of injections resulting in RFBM within 4 hours during the double-blind period as the dependent variable and the treatment group as the fixed effect. .
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	56.64
	Confidence Interval	(2-Sided) 97.5%; 40.62 to 72.66
	Parameter Dispersion	Type: Value:
	Estimation Comments	Estimated value is the difference in least squared means for MNTX vs. placebo (MNTX minus placebo). Based on the ANOVA model, there is 97.5% confidence that the difference between MNTX and placebo falls between the lower and upper limits presented.

3. Primary Outcome

Title	The Proportion of Subjects Having a Rescue-free Bowel Movement (RFBM) Within 4 Hours After Each Dose During Double-blind Period.
Description	This measurement is the second of the 2 co-primary endpoints. This endpoint measures the percentage of patients who had an RFBM within 4 hours after each dose of test article during the double-blind period; data are expressed as percentages of patients by dose (first, second, third, fourth, etc.) for the MNTX and placebo groups. The definition of RFBM is described above (see first co-primary endpoint).
Time Frame	Within 4 Hours After Each Dose During the 2 weeks Double-Blind Period

Outcome Measure Data

Analysis Population Description

Although 25 patients in the MNTX group and 24 in the placebo group received study drug, 24 and 23 patients, respectively, had ≥ 1 post baseline diary assessment and were analyzed for efficacy.

Arm/Group Title	Methylnaltrexone Double-blind	Placebo
Arm/Group Description	Methylnaltrexone once every other day. Subjects received 0.6 mL (12 mg) every other day if weight ≥ 62kg; 0.4 mL (8 mg) every other day if weight between 38 and < 62 kg; or 0.0075 mL/kg (0.15 mg/kg) every other day if weight between 27 and <38 kg.	Placebo once every other day. Subjects received matching placebo injections.
Measure Participants	24	23
RFBM post second DB injection	61.9 247.6%	8.7 34.8%
RFBM post third DB injection	52.6 210.4%	8.7 34.8%
RFBM post fourth DB injection	38.9 155.6%	8.7 34.8%
RFBM post fifth DB injection	56.3 225.2%	4.5 18%
RFBM post sixth DB injection	43.8 175.2%	0 0%
RFBM post seventh DB injection	43.8 175.2%	0 0%
RFBM post eighth DB injection	57.1 228.4%	7.7 30.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Methylnaltrexone Double-blind, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	Comparison of the MNTX group and the placebo group in the proportion of subjects having a RFBM within 4 hours after each injection was performed by using a 2-sided Cochran-Mantel-Haenszel Chi square test at the alpha level of 0.025.
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	23.38
	Confidence Interval	(2-Sided) 97.5%; 10.91 to 50.14
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Adverse events were collected over the 2-week double-blind period and over the 12-week open-label period.
Adverse Event Reporting Description	Adverse events were collected by non-systematic (patient reports) and systematic methods (investigator examinations and lab tests). For both adverse events tables, a subject reporting more than one adverse event for a particular MedDRA preferred term or system organ class was counted only once for that MedDRA preferred term or system organ class.
Arm/Group Title	Methylnaltrexone Double-blind		Placebo		Methylnaltrexone Open-label
Arm/Group Description	Methylnaltrexone once every other day. Subjects received 0.6 mL (12 mg) every other day if weight ≥ 62kg; 0.4 mL (8 mg) every other day if weight between 38 and < 62 kg; or 0.0075 mL/kg (0.15 mg/kg) every other day if weight between 27 and <38 kg.		Placebo once every other day. Subjects received matching placebo injections.		Subjects who completed the double-blind period had the option to receive methylnaltrexone once every other day during a 12-week, open-label extension period.
All Cause Mortality
	Methylnaltrexone Double-blind		Placebo		Methylnaltrexone Open-label
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Methylnaltrexone Double-blind		Placebo		Methylnaltrexone Open-label
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/25 (48%)		8/24 (33.3%)		21/31 (67.7%)
Blood and lymphatic system disorders
Leukopenia	1/25 (4%)		0/24 (0%)		0/31 (0%)
Gastrointestinal disorders
Abdominal distension	1/25 (4%)		0/24 (0%)		1/31 (3.2%)
Abdominal pain	0/25 (0%)		1/24 (4.2%)		2/31 (6.5%)
Nausea	1/25 (4%)		0/24 (0%)		1/31 (3.2%)
Vomiting	1/25 (4%)		0/24 (0%)		1/31 (3.2%)
Abdominal discomfort	0/25 (0%)		0/24 (0%)		1/31 (3.2%)
Ascites	0/25 (0%)		0/24 (0%)		1/31 (3.2%)
Diarrhea	0/25 (0%)		0/24 (0%)		1/31 (3.2%)
Gingival bleeding	0/25 (0%)		0/24 (0%)		1/31 (3.2%)
Melena	0/25 (0%)		0/24 (0%)		1/31 (3.2%)
General disorders
Asthenia	1/25 (4%)		2/24 (8.3%)		9/31 (29%)
Disease progression	0/25 (0%)		0/24 (0%)		2/31 (6.5%)
Malignant neoplasm progression	0/25 (0%)		1/24 (4.2%)		1/31 (3.2%)
Chest discomfort	1/25 (4%)		0/24 (0%)		0/31 (0%)
Feeling cold	0/25 (0%)		0/24 (0%)		1/31 (3.2%)
Non-cardiac chest pain	0/25 (0%)		0/24 (0%)		1/31 (3.2%)
Pain	0/25 (0%)		0/24 (0%)		1/31 (3.2%)
Pyrexia	0/25 (0%)		0/24 (0%)		1/31 (3.2%)
Hepatobiliary disorders
Hepatic failure	0/25 (0%)		0/24 (0%)		1/31 (3.2%)
Infections and infestations
Herpes zoster	1/25 (4%)		0/24 (0%)		0/31 (0%)
Metabolism and nutrition disorders
Decreased appetite	0/25 (0%)		0/24 (0%)		4/31 (12.9%)
Musculoskeletal and connective tissue disorders
Muscular weakness	1/25 (4%)		0/24 (0%)		0/31 (0%)
Back pain	0/25 (0%)		0/24 (0%)		1/31 (3.2%)
Pain in extremity	0/25 (0%)		0/24 (0%)		1/31 (3.2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant neoplasm progression	4/25 (16%)		5/24 (20.8%)		9/31 (29%)
Mesothelioma malignant advanced	1/25 (4%)		0/24 (0%)		0/31 (0%)
Metastatic gastric cancer	0/25 (0%)		0/24 (0%)		1/31 (3.2%)
Nervous system disorders
Somnolence	1/25 (4%)		0/24 (0%)		2/31 (6.5%)
Diplegia	1/25 (4%)		0/24 (0%)		0/31 (0%)
Hepatic encephalopathy	1/25 (4%)		0/24 (0%)		0/31 (0%)
Syncope	1/25 (4%)		0/24 (0%)		0/31 (0%)
Headache	0/25 (0%)		0/24 (0%)		1/31 (3.2%)
Renal and urinary disorders
Dysuria	0/25 (0%)		1/24 (4.2%)		2/31 (6.5%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/25 (4%)		2/24 (8.3%)		1/31 (3.2%)
Pulmonary embolism	1/25 (4%)		1/24 (4.2%)		1/31 (3.2%)
Pneumonia aspiration	1/25 (4%)		0/24 (0%)		0/31 (0%)
Hemoptysis	0/25 (0%)		0/24 (0%)		1/31 (3.2%)
Sputum increased	0/25 (0%)		0/24 (0%)		1/31 (3.2%)
Other (Not Including Serious) Adverse Events
	Methylnaltrexone Double-blind		Placebo		Methylnaltrexone Open-label
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/25 (64%)		18/24 (75%)		25/31 (80.6%)
Blood and lymphatic system disorders
Anemia	1/25 (4%)		3/24 (12.5%)		4/31 (12.9%)
Gastrointestinal disorders
Abdominal distension	2/25 (8%)		2/24 (8.3%)		3/31 (9.7%)
Abdominal pain	4/25 (16%)		1/24 (4.2%)		2/31 (6.5%)
Ascites	4/25 (16%)		3/24 (12.5%)		2/31 (6.5%)
Diarrhoea	1/25 (4%)		2/24 (8.3%)		4/31 (12.9%)
Nausea	1/25 (4%)		2/24 (8.3%)		2/31 (6.5%)
Vomiting	2/25 (8%)		1/24 (4.2%)		3/31 (9.7%)
General disorders
Asthenia	0/25 (0%)		1/24 (4.2%)		9/31 (29%)
Edema	0/25 (0%)		1/24 (4.2%)		3/31 (9.7%)
Edema peripheral	3/25 (12%)		0/24 (0%)		3/31 (9.7%)
Fatigue	0/25 (0%)		2/24 (8.3%)		0/31 (0%)
Pain	2/25 (8%)		0/24 (0%)		1/31 (3.2%)
Pyrexia	3/25 (12%)		1/24 (4.2%)		1/31 (3.2%)
Hepatobiliary disorders
Jaundice	1/25 (4%)		2/24 (8.3%)		1/31 (3.2%)
Infections and infestations
Urinary tract infection	1/25 (4%)		0/24 (0%)		2/31 (6.5%)
Metabolism and nutrition disorders
Decreased appetite	2/25 (8%)		1/24 (4.2%)		7/31 (22.6%)
Hypoalbuminemia	0/25 (0%)		0/24 (0%)		3/31 (9.7%)
Musculoskeletal and connective tissue disorders
Back pain	2/25 (8%)		0/24 (0%)		2/31 (6.5%)
Musculoskeletal pain	1/25 (4%)		0/24 (0%)		2/31 (6.5%)
Pain in extremity	1/25 (4%)		0/24 (0%)		3/31 (9.7%)
Nervous system disorders
Dizziness	3/25 (12%)		1/24 (4.2%)		1/31 (3.2%)
Headache	0/25 (0%)		1/24 (4.2%)		2/31 (6.5%)
Somnolence	2/25 (8%)		1/24 (4.2%)		2/31 (6.5%)
Psychiatric disorders
Delirium	1/25 (4%)		0/24 (0%)		2/31 (6.5%)
Insomnia	0/25 (0%)		0/24 (0%)		2/31 (6.5%)
Renal and urinary disorders
Dysuria	4/25 (16%)		3/24 (12.5%)		1/31 (3.2%)
Respiratory, thoracic and mediastinal disorders
Cough	0/25 (0%)		2/24 (8.3%)		3/31 (9.7%)
Dyspnea	2/25 (8%)		1/24 (4.2%)		3/31 (9.7%)
Productive cough	1/25 (4%)		0/24 (0%)		2/31 (6.5%)
Skin and subcutaneous tissue disorders
Hyperhidrosis	2/25 (8%)		0/24 (0%)		1/31 (3.2%)
Vascular disorders
Hypotension	1/25 (4%)		2/24 (8.3%)		1/31 (3.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.