EASE LID 3: Efficacy and Safety Study of ADS-5102 in PD Patients With Levodopa-Induced Dyskinesia

• Sponsor: Adamas Pharmaceuticals, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02274766
• Collaborator: (none)
• Enrollment: 77
• Locations: 51
• Arms: 2
• Duration (Months): 17.3
• Patients Per Site: 1.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is a multi-center, randomized, double-blind, placebo-controlled, 2-arm, parallel group study to evaluate the efficacy and safety of ADS-5102 extended release (ER) capsules, an investigational formulation of amantadine, dosed once nightly at bedtime for the treatment of levodopa-induced dyskinesia (LID) in subjects with Parkinson's disease (PD). The novel pharmacokinetic profile of ADS-5102 is expected to achieve i) maximal concentrations in the early morning through mid-day, when LID can be troublesome, and ii) lower concentrations in the evening, potentially reducing the negative impact of amantadine on sleep. This pharmacokinetic profile could enable higher doses to be tolerated with a once-nightly ER formulation than can be tolerated with an immediate-release formulation. The once-nightly dosing regimen may also provide enhanced convenience and compliance.

In a previous clinical study, ADS-5102 met its primary endpoint; LID was significantly reduced as measured by the change in UDysRS score over 8 weeks vs. placebo.

Condition or Disease	Intervention/Treatment	Phase
Dyskinesia; Levodopa-Induced Dyskinesia (LID); Parkinson's Disease (PD)	Drug: ADS-5102; Other: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 77 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: ADS-5102 (Amantadine HCl) Extended Release Efficacy and Safety Study in Parkinson's Disease Patients With Levodopa-Induced Dyskinesia (EASE LID 3 Study)
• Study Start Date: Oct 1, 2014
• Actual Primary Completion Date: Mar 10, 2016
• Actual Study Completion Date: Mar 10, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ADS-5102 (amantadine HCl extended release) ADS-5102 (amantadine HCl extended release)	Drug: ADS-5102; Oral capsules to be administered once nightly at bedtime, for 13 weeks.; Other Names: amantadine HCl extended release
Placebo Comparator: Placebo Placebo	Other: Placebo; Oral capsules to be administered once nightly at bedtime, for 13 weeks.

Outcome Measures

Primary Outcome Measures

1. Change in the Unified Dyskinesia Rating Scale (UDysRS) Total Score [Baseline to Week 12]

   The UDysRS is a dyskinesia rating scale from 0-104; it evaluates involuntary movements associated with PD. A higher score indicates more severe PD. The UDysRS was measured at Baseline and Weeks 2, 4, 8, and 12.

Secondary Outcome Measures

1. Change in the Standardized PD Home Diary (ON Time Without Dyskinesia, ON Time With Troublesome Dyskinesia, OFF Time) [Baseline to Week 12]

   A PD home diary was used to score 5 different conditions in 30-minute intervals: ASLEEP, OFF, ON (ie, had adequate control of PD symptoms) without dyskinesia, ON with non-troublesome dyskinesia, and ON with troublesome dyskinesia. The results were based on 2 consecutive 24-hour diaries taken prior to the day of randomization and prior to the Week 2, 4, 8, and 12 visits.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 30 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Signed a current IRB/REB/IEC-approved informed consent form;

• Parkinson's disease, per UK Parkinson's Disease Society (UKPDS) Brain Bank Clinical Diagnostic Criteria;

• On a stable regimen of antiparkinson's medications for at least 30 days prior to screening, including a levodopa preparation administered not less than three times daily, and willing to continue the same doses and regimens during study participation;

• Following diary training, the subject is willing and able to understand and complete the 24-hour PD home diary (trained caregiver/study partner assistance allowed);

• Any other current and allowed prescription/non-prescription medications and/or nutritional supplements taken regularly must have been at a stable dose and regimen for at least 30 days prior to screening, and subject must be willing to continue the same doses and regimens during study participation (this criterion does not apply to medications that are being taken pre-study only on an as-needed basis);

Exclusion Criteria:

• History of neurosurgical intervention related to Parkinson's disease (e.g. deep brain stimulation);

• History of seizures within 2 years prior to screening;

• History of stroke or TIA within 2 years prior to screening;

• History of cancer within 5 years prior to screening, with the following exceptions: adequately treated non-melanomatous skin cancers, localized bladder cancer, non-metastatic prostate cancer, in situ cervical cancer, or other definitively treated cancer that is considered cured;

• Presence of cognitive impairment, as evidenced by a Mini-Mental Status Examination (MMSE) score of less than 24 during screening;

• If female, is pregnant or lactating;

• If a sexually active female, is not surgically sterile or at least 2 years post-menopausal, or does not agree to utilize an effective method of contraception from screening through at least 4 weeks after the completion of study treatment, using one of the following: barrier methods (diaphragm or partner using condoms plus use of spermicidal jelly or foam, preferably double-barrier methods); oral or implanted hormonal contraceptive; intrauterine device (IUD); or vasectomized male partner;

• Treatment with an investigational drug or device within 30 days prior to screening;

• Treatment with an investigational biologic within 6 months prior to screening;

• Current participation in another clinical trial;

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Fountain Valley	California	United States	92708
2		Sunnyvale	California	United States	94085
3		Boca Raton	Florida	United States	33486
4		Jacksonville	Florida	United States	32209
5		Port Charlotte	Florida	United States	33980
6		Sunrise	Florida	United States	33351
7		Tampa	Florida	United States	33612
8		Atlanta	Georgia	United States	30329
9		Chicago	Illinois	United States	60611
10		Kansas City	Kansas	United States	66160
11		Baltimore	Maryland	United States	21287
12		Elkridge	Maryland	United States	21075
13		Boston	Massachusetts	United States	02114
14		West Bloomfield	Michigan	United States	48322
15		Greensboro	North Carolina	United States	27405
16		Raleigh	North Carolina	United States	27607
17		Tulsa	Oklahoma	United States	74136
18		Roanoke	Virginia	United States	24018
19		Kirkland	Washington	United States	98034
20		Morgantown	West Virginia	United States	26506
21		Milwaukee	Wisconsin	United States	53233
22		Innsbruck		Austria	6020
23		Vienna		Austria	1080
24		Vienna		Austria	1220
25		Bordeaux		France	33076
26		Bron		France	69677
27		Clermont Ferrand		France	63003
28		Lille		France	59037
29		Marseille		France	13385
30		Montpellier		France	34295
31		Poitier		France	86021
32		Rennes		France	35033
33		Rouen		France	76031
34		Strasbourg		France	67098
35		Toulouse		France	31059
36		München	Bayern	Germany	80804
37		München	Bayern	Germany	81675
38		Beelitz-Heilstätten	Brandenburg	Germany	14547
39		Göttingen	Niedersachsen	Germany	37075
40		Leipzig	Sachsen	Germany	04103
41		Gera	Thüringen	Germany	07751
42		Stadtroda	Thüringen	Germany	07646
43		Berlin		Germany	12163
44		Berlin		Germany	13353
45		Hamburg		Germany	22291
46		Kassel		Germany	34128
47		Marburg		Germany	35043
48		Barcelona		Spain	08028
49		Barcelona		Spain	08035
50		Barcelona		Spain	08036
51		Barcelona		Spain	08041

Sponsors and Collaborators

• Adamas Pharmaceuticals, Inc.

Investigators

• Study Director: Clinical Trials Director, Adamas Pharmaceuticals, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Adamas Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT02274766
• Other Study ID Numbers: ADS-AMT-PD304
• First Posted: Oct 24, 2014
• Last Update Posted: Jan 10, 2018
• Last Verified: Jan 1, 2018

• Keywords provided by Adamas Pharmaceuticals, Inc.: Levodopa-Induced Dyskinesia; LID; Parkinsonism; Parkinson's Disease
• Additional relevant MeSH terms: Parkinson Disease; Dyskinesias; Amantadine

Study Results

Participant Flow

Recruitment Details	77 subjects with Parkinson's disease (PD) and Levodopa-induced Dyskinesia (LID) were randomized at 32 study sites in the United States, Germany, France, Spain, and Austria. The first subject was randomized on 23 October 2014 and the last subject completed on 10 March 2016.
Pre-assignment Detail	All randomized subjects who received ≥ 1 dose of study drug and provided ≥ 1 postbaseline efficacy assessment (75) were included in both the Safety Analysis Population and the Modified Intent-to-Treat (MITT) population (with 38 subjects in the placebo group and 37 in the ADS-5102 group).

Arm/Group Title	Placebo	ADS-5102 (Amantadine HCl Extended Release)
Arm/Group Description	Placebo: oral capsules administered once nightly at bedtime for 13 weeks	340 mg dose of ADS-5102 (amantadine hydrochloride [HCl] extended release): oral capsules administered once nightly at bedtime for 13 weeks
Period Title: Overall Study
STARTED	39	38
Received Study Drug	38	37
COMPLETED	35	29
NOT COMPLETED	4	9

Baseline Characteristics

Arm/Group Title	Placebo	ADS-5102 (Amantadine HCl Extended Release)	Total
Arm/Group Description	Placebo: oral capsules administered once nightly at bedtime for 13 weeks	340 mg dose of ADS-5102 (amantadine HCl extended release): oral capsules administered once nightly at bedtime for 13 weeks	Total of all reporting groups
Overall Participants	38	37	75
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	15 39.5%	16 43.2%	31 41.3%
>=65 years	23 60.5%	21 56.8%	44 58.7%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.9 (9.08)	64.7 (9.66)	64.8 (9.31)
Sex: Female, Male (Count of Participants)
Female	18 47.4%	18 48.6%	36 48%
Male	20 52.6%	19 51.4%	39 52%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	5 13.5%	5 6.7%
Not Hispanic or Latino	38 100%	32 86.5%	70 93.3%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	38 100%	36 97.3%	74 98.7%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	1 2.7%	1 1.3%
Region of Enrollment (Count of Participants)
United States	8 21.1%	15 40.5%	23 30.7%
Europe	30 78.9%	22 59.5%	52 69.3%
Unified Dyskinesia Rating Scale (UDysRS) (units on a scale) [Mean (Standard Deviation) ]
Total Score	41.2 (10.32)	40.2 (13.06)	40.7 (11.68)
Total Objective Score (Parts III, IV)	15.9 (7.00)	18.1 (7.99)	17.0 (7.53)
PD Home Diary (hours) [Mean (Standard Deviation) ]
ON time without troublesome dyskinesia	7.79 (3.249)	8.77 (2.457)	8.27 (2.909)
ON time with troublesome dyskinesia	6.02 (3.353)	4.71 (2.509)	5.37 (3.020)
OFF time	1.98 (1.687)	2.62 (2.015)	2.30 (1.871)
Asleep time	8.21 (1.643)	7.91 (1.502)	8.06 (1.572)
Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) (units on a scale) [Mean (Standard Deviation) ]
Part I	9.9 (4.86)	11.3 (5.87)	10.6 (5.39)
Part II	14.8 (6.06)	14.1 (6.15)	14.4 (6.07)
Part III	21.4 (10.22)	21.2 (9.24)	21.3 (9.68)
Combined Parts I, II, and III	46.1 (17.00)	46.6 (14.76)	46.3 (15.83)
Part IV	11.1 (2.40)	9.8 (2.78)	10.5 (2.66)
Part IV, Item 4.1	2.8 (0.94)	2.2 (0.81)	2.5 (0.92)
Part IV, Item 4.2	2.5 (0.51)	2.5 (0.61)	2.5 (0.55)
Time Since PD Diagnosis (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	10.71 (4.265)	10.40 (5.105)	10.55 (4.669)
Duration of Levodopa Treatment (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	8.54 (4.845)	7.69 (4.121)	8.12 (4.493)
Duration of LID (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	3.98 (2.566)	3.78 (3.160)	3.88 (2.857)
Hoehn and Yahr Stage (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	2.4 (0.55)	2.1 (0.60)	2.2 (0.59)
Subjects taking Antiparkinson Medication (Count of Participants)
Levodopa	38 100%	37 100%	75 100%
Dopamine Agonists	25 65.8%	21 56.8%	46 61.3%
MAO Inhibitors	20 52.6%	17 45.9%	37 49.3%
COMT Inhibitors	1 2.6%	3 8.1%	4 5.3%
Anticholinergics	2 5.3%	0 0%	2 2.7%

Outcome Measures

1. Primary Outcome

Title	Change in the Unified Dyskinesia Rating Scale (UDysRS) Total Score
Description	The UDysRS is a dyskinesia rating scale from 0-104; it evaluates involuntary movements associated with PD. A higher score indicates more severe PD. The UDysRS was measured at Baseline and Weeks 2, 4, 8, and 12.
Time Frame	Baseline to Week 12

Outcome Measure Data

Analysis Population Description

MITT population

Arm/Group Title	Placebo	ADS-5102 (Amantadine HCl Extended Release)
Arm/Group Description	Placebo: oral capsules administered once nightly at bedtime for 13 weeks	340 mg dose of ADS-5102 (amantadine HCl extended release): oral capsules administered once nightly at bedtime for 13 weeks
Measure Participants	38	37
Least Squares Mean (Standard Error) [units on a scale]	-6.3 (2.08)	-20.7 (2.20)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ADS-5102 (Amantadine HCl Extended Release)
	Comments	32 subjects per treatment arm provided 90% power using a 2-sided test at 5% significance.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Linear Mixed Model w/ Repeated Measures
	Comments	Change from baseline is a dependent variable; the baseline value is a continuous covariate
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-14.4
	Confidence Interval	(2-Sided) 95%; -20.4 to -8.3
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.03
	Estimation Comments

2. Secondary Outcome

Title	Change in the Standardized PD Home Diary (ON Time Without Dyskinesia, ON Time With Troublesome Dyskinesia, OFF Time)
Description	A PD home diary was used to score 5 different conditions in 30-minute intervals: ASLEEP, OFF, ON (ie, had adequate control of PD symptoms) without dyskinesia, ON with non-troublesome dyskinesia, and ON with troublesome dyskinesia. The results were based on 2 consecutive 24-hour diaries taken prior to the day of randomization and prior to the Week 2, 4, 8, and 12 visits.
Time Frame	Baseline to Week 12

Outcome Measure Data

Analysis Population Description

MITT population

Arm/Group Title	Placebo	ADS-5102 (Amantadine HCl Extended Release)
Arm/Group Description	Placebo: oral capsules administered once nightly at bedtime for 13 weeks	340 mg dose of ADS-5102 (amantadine HCl extended release): oral capsules administered once nightly at bedtime for 13 weeks
Measure Participants	38	37
Change in ON time without troublesome dyskinesia	2.05 (0.526)	3.95 (0.562)
Change in ON time with troublesome dyskinesia	-2.47 (0.436)	-3.61 (0.468)
Change in OFF time	0.61 (0.313)	-0.49 (0.336)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ADS-5102 (Amantadine HCl Extended Release)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0168
	Comments	Change from Baseline in ON time without troublesome dyskinesia.
	Method	Linear Mixed Model w/ Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	1.90
	Confidence Interval	(2-Sided) 95%; 0.35 to 3.45
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.775
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	ADS-5102 (Amantadine HCl Extended Release)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0853
	Comments	Change from Baseline in ON time with troublesome dyskinesia.
	Method	Linear Mixed Model w/ Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-1.13
	Confidence Interval	(2-Sided) 95%; -2.42 to 0.16
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.648
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	ADS-5102 (Amantadine HCl Extended Release)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0199
	Comments	Change from Baseline in OFF time.
	Method	Linear Mixed Model w/ Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-1.10
	Confidence Interval	(2-Sided) 95%; -2.02 to -0.18
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.461
	Estimation Comments

Adverse Events

Time Frame	Baseline through Week 13
Arm/Group Title	Placebo		ADS-5102 (Amantadine HCl Extended Release)
Arm/Group Description	Placebo: oral capsules administered once nightly at bedtime for 13 weeks		340 mg dose of ADS-5102 (amantadine HCl extended release): oral capsules administered once nightly at bedtime for 13 weeks
All Cause Mortality
	Placebo		ADS-5102 (Amantadine HCl Extended Release)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/38 (0%)		0/37 (0%)
Serious Adverse Events
	Placebo		ADS-5102 (Amantadine HCl Extended Release)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/38 (0%)		4/37 (10.8%)
Cardiac disorders
Cardio-respiratory arrest	0/38 (0%)		1/37 (2.7%)
Gastrointestinal disorders
Constipation	0/38 (0%)		1/37 (2.7%)
Injury, poisoning and procedural complications
Laceration	0/38 (0%)		1/37 (2.7%)
Nervous system disorders
Transient ischaemic attack	0/38 (0%)		1/37 (2.7%)
Dysaesthesia	0/38 (0%)		1/37 (2.7%)
Psychiatric disorders
Suicide attempt	0/38 (0%)		1/37 (2.7%)
Renal and urinary disorders
Urinary retention	0/38 (0%)		1/37 (2.7%)
Other (Not Including Serious) Adverse Events
	Placebo		ADS-5102 (Amantadine HCl Extended Release)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	19/38 (50%)		31/37 (83.8%)
Cardiac disorders
Arrhythmia	0/38 (0%)		1/37 (2.7%)
Palpitations	1/38 (2.6%)		0/37 (0%)
Ear and labyrinth disorders
Vertigo	1/38 (2.6%)		1/37 (2.7%)
Eye disorders
Cataract	1/38 (2.6%)		1/37 (2.7%)
Photophobia	0/38 (0%)		1/37 (2.7%)
Vision blurred	1/38 (2.6%)		1/37 (2.7%)
Vitreous floaters	1/38 (2.6%)		0/37 (0%)
Visual impairement	0/38 (0%)		1/37 (2.7%)
Gastrointestinal disorders
Dry mouth	1/38 (2.6%)		5/37 (13.5%)
Nausea	1/38 (2.6%)		5/37 (13.5%)
Constipation	0/38 (0%)		2/37 (5.4%)
Abdominal pain	1/38 (2.6%)		1/37 (2.7%)
Abdominal pain upper	0/38 (0%)		1/37 (2.7%)
Dyspepsia	0/38 (0%)		1/37 (2.7%)
Vomiting	0/38 (0%)		1/37 (2.7%)
Salivary hypersecretion	1/38 (2.6%)		0/37 (0%)
Toothache	1/38 (2.6%)		0/37 (0%)
General disorders
Malaise	0/38 (0%)		2/37 (5.4%)
Asthenia	2/38 (5.3%)		1/37 (2.7%)
Gait disturbance	0/38 (0%)		1/37 (2.7%)
Pain	0/38 (0%)		1/37 (2.7%)
Hunger	1/38 (2.6%)		0/37 (0%)
Oedema peripheral	1/38 (2.6%)		0/37 (0%)
Infections and infestations
Nasopharyngitis	3/38 (7.9%)		2/37 (5.4%)
Influenza	0/38 (0%)		1/37 (2.7%)
Urinary tract infection	0/38 (0%)		1/37 (2.7%)
Bronchitis	1/38 (2.6%)		0/37 (0%)
Injury, poisoning and procedural complications
Fall	2/38 (5.3%)		3/37 (8.1%)
Craniocerebral injury	0/38 (0%)		1/37 (2.7%)
Face injury	0/38 (0%)		1/37 (2.7%)
Traumatic haematoma	0/38 (0%)		1/37 (2.7%)
Injury	1/38 (2.6%)		0/37 (0%)
Investigations
Gamma-glutamyltransferase increased	0/38 (0%)		1/37 (2.7%)
Weight increased	0/38 (0%)		1/37 (2.7%)
Glomerular filtration rate decreased	1/38 (2.6%)		0/37 (0%)
Metabolism and nutrition disorders
Decreased appetite	0/38 (0%)		4/37 (10.8%)
Musculoskeletal and connective tissue disorders
Muscle spasms	0/38 (0%)		2/37 (5.4%)
Back pain	2/38 (5.3%)		1/37 (2.7%)
Arthralgia	1/38 (2.6%)		1/37 (2.7%)
Muscle rigidity	0/38 (0%)		1/37 (2.7%)
Myalgia	0/38 (0%)		1/37 (2.7%)
Pain in extremity	0/38 (0%)		1/37 (2.7%)
Intervertebral disc protrusion	1/38 (2.6%)		0/37 (0%)
Joint stiffness	1/38 (2.6%)		0/37 (0%)
Nervous system disorders
Dizziness	1/38 (2.6%)		2/37 (5.4%)
Dystonia	0/38 (0%)		2/37 (5.4%)
Headache	1/38 (2.6%)		2/37 (5.4%)
Somnolence	0/38 (0%)		2/37 (5.4%)
Freezing phenomenon	0/38 (0%)		1/37 (2.7%)
Intracranial venous sinus thrombosis	0/38 (0%)		1/37 (2.7%)
Paraesthesia	0/38 (0%)		1/37 (2.7%)
Parkinson's disease	0/38 (0%)		1/37 (2.7%)
Transverse sinus thrombosis	0/38 (0%)		1/37 (2.7%)
Disturbance in attention	1/38 (2.6%)		0/37 (0%)
Tremor	1/38 (2.6%)		0/37 (0%)
Psychiatric disorders
Insomnia	0/38 (0%)		4/37 (10.8%)
Hallucination (Pooled)	2/38 (5.3%)		3/37 (8.1%)
Apathy	0/38 (0%)		2/37 (5.4%)
Depressed mood	0/38 (0%)		2/37 (5.4%)
Affect lability	0/38 (0%)		1/37 (2.7%)
Anxiety	1/38 (2.6%)		1/37 (2.7%)
Mental status changes	0/38 (0%)		1/37 (2.7%)
Middle insomnia	0/38 (0%)		1/37 (2.7%)
Nervousness	0/38 (0%)		1/37 (2.7%)
Suicidal ideation	0/38 (0%)		1/37 (2.7%)
Confusional state	1/38 (2.6%)		0/37 (0%)
Restlessness	1/38 (2.6%)		0/37 (0%)
Renal and urinary disorders
Dysuria	0/38 (0%)		1/37 (2.7%)
Pollakiuria	0/38 (0%)		1/37 (2.7%)
Nocturia	1/38 (2.6%)		0/37 (0%)
Renal cyst	1/38 (2.6%)		0/37 (0%)
Urinary incontinence	1/38 (2.6%)		0/37 (0%)
Renal impairment	0/38 (0%)		1/37 (2.7%)
Reproductive system and breast disorders
Benign prostatic hyperplasia	0/38 (0%)		2/37 (5.4%)
Erectile dysfunction	0/38 (0%)		1/37 (2.7%)
Respiratory, thoracic and mediastinal disorders
Cough	0/38 (0%)		2/37 (5.4%)
Chronic obstructive pulmonary disease	1/38 (2.6%)		0/37 (0%)
Skin and subcutaneous tissue disorders
Alopecia	0/38 (0%)		1/37 (2.7%)
Skin odour abnormal	0/38 (0%)		1/37 (2.7%)
Vascular disorders
Orthostatic hypotension	0/38 (0%)		4/37 (10.8%)
Jugular vein thrombosis	0/38 (0%)		1/37 (2.7%)
Peripheral coldness	0/38 (0%)		1/37 (2.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.