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Safety and Efficacy Study of Tozadenant to Treat End of Dose Wearing Off in Parkinson's Patients (TOZ-PD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02453386
Recruitment Status : Terminated (New Safety Information)
First Posted : May 25, 2015
Results First Posted : March 26, 2019
Last Update Posted : April 3, 2019
Sponsor:
Information provided by (Responsible Party):
Biotie Therapies Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Idiopathic Parkinson's Disease
Interventions Drug: tozadenant
Drug: placebo
Enrollment 449
Recruitment Details This study was conducted at 80 sites in 7 countries. Planned patient enrollment numbers were achieved, but the study and the tozadenant development program were terminated prior to study completion by all patients, based on an unexpected emerging safety signal as discussed in the safety sections of this report.
Pre-assignment Details  
Arm/Group Title Tozadenant 60 mg BID Tozadenant 120 mg BID Placebo BID
Hide Arm/Group Description During Part A, patients took two (2) tablets, one 60 mg tozadenant and one placebo, by mouth BID for a total of four (4) tablets per day. During Part A, patients took two (2) tablets of 60 mg tozadenant, by mouth BID for a total of four (4) tablets per day. During Part A, patients took two (2) tablets of placebo, by mouth BID for a total of four (4) tablets per day.
Period Title: Overall Study
Started 151 149 149
Completed 102 100 108
Not Completed 49 49 41
Reason Not Completed
Adverse Event             22             30             15
Protocol Violation             1             0             1
Withdrawal by Subject             10             9             9
Sponsor Terminated Study             14             8             11
Subject Terminated by Sponsor             1             1             1
Sponsor Terminated by Investigator             0             1             2
Lost to Follow-up             0             0             1
Other             1             0             1
Arm/Group Title Tozadenant 60 mg BID Tozadenant 120 mg BID Placebo BID Total
Hide Arm/Group Description During Part A, patients took two (2) tablets, one 60 mg tozadenant and one placebo, by mouth BID for a total of four (4) tablets per day. During Part A, patients took two (2) tablets of 60 mg tozadenant, by mouth BID for a total of four (4) tablets per day. During Part A, patients took two (2) tablets of placebo, by mouth BID for a total of four (4) tablets per day. Total of all reporting groups
Overall Number of Baseline Participants 151 149 149 449
Hide Baseline Analysis Population Description
The 449 patients who were randomized in the study comprised the ITT set.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 151 participants 149 participants 149 participants 449 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
73
  48.3%
61
  40.9%
66
  44.3%
200
  44.5%
>=65 years
78
  51.7%
88
  59.1%
83
  55.7%
249
  55.5%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 151 participants 149 participants 149 participants 449 participants
64.1  (8.68) 65.1  (7.57) 65.0  (8.29) 64.7  (8.19)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 151 participants 149 participants 149 participants 449 participants
Female
51
  33.8%
49
  32.9%
48
  32.2%
148
  33.0%
Male
100
  66.2%
100
  67.1%
101
  67.8%
301
  67.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 151 participants 149 participants 149 participants 449 participants
Hispanic or Latino
5
   3.3%
5
   3.4%
5
   3.4%
15
   3.3%
Not Hispanic or Latino
146
  96.7%
144
  96.6%
144
  96.6%
434
  96.7%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 151 participants 149 participants 149 participants 449 participants
American Indian or Alaska Native
1
   0.7%
1
   0.7%
0
   0.0%
2
   0.4%
Asian
2
   1.3%
2
   1.3%
3
   2.0%
7
   1.6%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
2
   1.3%
0
   0.0%
2
   0.4%
White
148
  98.0%
144
  96.6%
146
  98.0%
438
  97.6%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 151 participants 149 participants 149 participants 449 participants
Canada 5 5 5 15
Austria 3 3 2 8
United States 69 69 69 207
Czechia 22 22 22 66
Italy 20 19 20 59
Germany 19 19 19 57
Spain 13 12 12 37
Weight at Screening  
Mean (Standard Deviation)
Unit of measure:  Kilograms
Number Analyzed 151 participants 149 participants 149 participants 449 participants
78.74  (15.725) 80.42  (16.576) 79.35  (14.436) 79.50  (15.585)
1.Primary Outcome
Title Change From Baseline to Week 24 in the Number of Hours Per Day Spent in OFF Time
Hide Description Awake time in OFF state (hr) is the average of maximum of 3 days diary. The primary efficacy endpoint was the change from baseline to Week 24 in OFF time, where OFF time in the Hauser Parkinson's Disease Home Diary (PD) was averaged over 3 days prior to the study visit. During Screening and through Part A of the study, the Hauser Parkinson's Disease Home Diary (PD) was completed on specified days directly preceding the scheduled study visits/assessments. Motor activity was recorded as OFF, ON (mobility improved), or asleep time. Patients were asked to record ON time according to dyskinesia categories "without dyskinesia", "with non troublesome dyskinesia" or "with troublesome dyskinesia". Patients (and/or caregivers) were trained to complete the PD diary to record their status at half hourly intervals as OFF, ON without dyskinesia, ON with non troublesome dyskinesia, ON with troublesome dyskinesia, or asleep.
Time Frame Baseline to 24 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Modified Intent-to-Treat (mITT) population
Arm/Group Title Placebo BID Tozadenant 60 mg BID Tozadenant 120 mg BID
Hide Arm/Group Description:
Two placebo tablets BID
One 60 mg tozadenant tablet BID plus 1 Placebo
Two 60 mg tozadenant tablets BID
Overall Number of Participants Analyzed 145 144 145
Mean (Standard Deviation)
Unit of Measure: hours
Baseline Number Analyzed 145 participants 144 participants 145 participants
6.34  (1.986) 6.00  (1.970) 6.25  (2.337)
Week 2 Number Analyzed 145 participants 143 participants 145 participants
-0.725  (2.0018) -1.100  (2.1188) -1.409  (2.3957)
Week 6 Number Analyzed 139 participants 139 participants 134 participants
-0.817  (2.0993) -1.112  (2.2903) -1.879  (2.2866)
Week 12 Number Analyzed 130 participants 128 participants 122 participants
-0.962  (2.2186) -1.460  (2.3689) -1.919  (2.2008)
Week 18 Number Analyzed 119 participants 117 participants 113 participants
0.860  (2.4246) -1.020  (2.5886) -1.742  (2.6855)
Week 24 Number Analyzed 108 participants 104 participants 104 participants
-0.958  (2.2725) -0.835  (2.9730) -1.789  (2.4802)
2.Secondary Outcome
Title Change in Good ON Time From Baseline to Week 24
Hide Description

The first key secondary efficacy endpoint was the change from baseline to Week 24 in good ON which was defined as ON without dyskinesia or ON with non-troublesome dyskinesia.

Awake Time in Good ON State (hr) is the average of a maximum of 3 days diary. Patients were asked to record ON time according to dyskinesia categories "without dyskinesia", "with non troublesome dyskinesia" or "with troublesome dyskinesia" . Patients (and/or caregivers) were trained to complete the PD diary to record their status at half hourly intervals as OFF, ON without dyskinesia, ON with non troublesome dyskinesia, ON with troublesome dyskinesia, or asleep. For patients with missing baseline or baseline was measured post-dose, screening was used as baseline in the calculation of change from baseline.

Time Frame Baseline to 24 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Modified Intent-to-Treat (mITT) population
Arm/Group Title Placebo Tozadenant 60 mg BID 120 mg Tozadanent
Hide Arm/Group Description:
One placebo BID
One 60 mg tozadenant tablet BID plus 1 Placebo
Two 60 mg tozadenant tablets BID
Overall Number of Participants Analyzed 145 144 145
Mean (Standard Deviation)
Unit of Measure: hours
Baseline Number Analyzed 145 participants 144 participants 145 participants
9.58  (2.266) 9.92  (2.217) 9.51  (2.554)
Week 2 Number Analyzed 145 participants 143 participants 145 participants
0.790  (2.2778) 1.145  (2.1291) 1.397  (2.5102)
Week 6 Number Analyzed 139 participants 139 participants 134 participants
0.812  (2.4177) 1.002  (2.4533) 1.650  (2.2538)
Week 12 Number Analyzed 130 participants 128 participants 122 participants
0.777  (2.4300) 1.307  (2.7051) 1.830  (2.2870)
Week 18 Number Analyzed 119 participants 117 participants 113 participants
0.709  (2.6284) 0.903  (2.6297) 1.553  (2.6138)
Week 24 Number Analyzed 108 participants 104 participants 104 participants
1.011  (2.5470) 0.705  (3.1219) 1.689  (2.7335)
3.Secondary Outcome
Title Change in Unified Parkinson's Disease Rating Scale (UPDRS) Part II Activities of Daily Living (ADL) Subscale + Part III Motor Function
Hide Description

The Unified Parkinson's Disease Rating Scale (UPDRS) is a scale to monitor Parkinson's Disease related disability and impairment. The scale itself has 4 components are titled; (1) nonmotor experiences of daily living (13 items), (2) motor experiences of daily living (13 items), (3) motor examination (18 items), and (4) motor complications (six items). Each subscale now has 0-4 ratings, where 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. In this outcome measure we are evaluating Part II and Part III.

Part II: self-evaluation of the activities of daily life (ADLs) including speech, swallowing, handwriting, dressing, hygiene, falling, salivating, turning in bed, walking, and cutting food Part III: clinician-scored monitored motor evaluation Range of score is 0 - 160: 0 meaning less impact and Higher score indicates greater impact of PD symptoms.

Time Frame Baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population (Modified Intent-to-Treat) - all safety set patients who had valid diaries at baseline and had valid diaries on at least 1 post-baseline visit.
Arm/Group Title Placebo Tozadenant 60 mg Tozadenant 120 mg
Hide Arm/Group Description:
One Placebo BID
One 60 mg tozadenant tablet BID plus 1 Placebo
Two 60 mg tozadenant tablets BID
Overall Number of Participants Analyzed 145 144 145
Mean (Standard Deviation)
Unit of Measure: score on a scale
Baseline Number Analyzed 140 participants 141 participants 143 participants
33.2  (12.14) 31.3  (12.18) 32.3  (12.08)
Week 2 Number Analyzed 143 participants 141 participants 142 participants
-3.16  (5.931) -3.43  (6.611) -3.96  (5.924)
Week 6 Number Analyzed 136 participants 138 participants 131 participants
-3.53  (6.375) -2.82  (7.223) -4.31  (6.362)
Week 12 Number Analyzed 130 participants 127 participants 118 participants
-3.02  (8.385) -3.64  (7.393) -4.38  (6.602)
Week 18 Number Analyzed 118 participants 113 participants 111 participants
-3.35  (7.934) -3.63  (7.958) -3.83  (7.150)
Week 24 Number Analyzed 108 participants 103 participants 106 participants
-2.80  (8.183) -2.54  (8.584) -3.68  (7.853)
4.Secondary Outcome
Title Change From Baseline to Week 24 in the ON State in Unified Parkinson's Disease Rating Scale (UPDRS) Part IIl
Hide Description Change from Baseline to Week 24 in the Unified Parkinson's Disease Rating Scale (UPDRS) Parts III Motor Function (motor subscale) total scores. Each subscale has 0-4 ratings, where 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. Range of score is 0 - 108. Higher scores indicate greater impact of PD symptoms. Unified Parkinson's Disease Rating Scale (UPDRS) in the ON state was measured at a time representative of the ON state in that patient, not in "best" ON. Unified Parkinson's Disease Rating Scale Part III in OFF was not evaluated.
Time Frame Baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population (Modified Intent-to-Treat) - all safety set patients who had valid diaries at baseline and had valid diaries on at least 1 post-baseline visit.
Arm/Group Title Placebo Tozadenant 60 mg Tozadenant 120 mg
Hide Arm/Group Description:
One Placebo BID
One 60 mg tozadenant tablet BID plus 1 Placebo
Two 60 mg tozadenant tablets BID
Overall Number of Participants Analyzed 145 144 145
Mean (Standard Deviation)
Unit of Measure: score on a scale
Baseline Number Analyzed 140 participants 141 participants 143 participants
20.9  (8.80) 19.8  (8.58) 20.5  (8.71)
Week 2 Number Analyzed 143 participants 141 participants 142 participants
-2.13  (4.828) -2.35  (5.144) -2.83  (4.613)
Week 6 Number Analyzed 136 participants 138 participants 131 participants
-2.29  (5.011) -2.18  (5.476) -2.76  (5.423)
Week 12 Number Analyzed 130 participants 127 participants 118 participants
-2.31  (6.276) -2.69  (5.822) -3.19  (5.356)
Week 18 Number Analyzed 118 participants 113 participants 111 participants
-2.46  (6.112) -2.64  (6.303) -2.95  (5.572)
Week 24 Number Analyzed 108 participants 103 participants 106 participants
-2.15  (6.363) -2.13  (6.822) -2.93  (6.048)
5.Other Pre-specified Outcome
Title Global Assessments of Improvement: Clinical Global Impression of Improvement (CGI-I) Week 24
Hide Description For the Clinical Global Impression of Improvement (CGI-I), the investigator or rater is asked to rate the patient's total improvement, whether or not in his or her judgment it is due entirely to drug treatment, based on a 1-7 point weighted scale ranging from "very much improved" (1) to "very much worse" (7). A zero score is assigned if the score is not assessed. Scale: 1 = Very much improved, 2 = Much improved, 3 = Minimally improved, 4 = No change, 5 = Minimally worse, 6 = Much worse, 7 = Very much worse. Tables show Treatment vs Placebo.
Time Frame At Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population (Modified Intent-to-Treat) - all safety set patients who had valid diaries at baseline and had valid diaries on at least 1 post-baseline visit. Patients were accounted for in the treatment group to which they were originally randomized.
Arm/Group Title Placebo Tozadenant 60 mg Tozadanent 120 mg
Hide Arm/Group Description:
One Placebo
One 60 mg tozadenant tablet BID plus 1 Placebo
Two 60 mg tozadenant tablets BID
Overall Number of Participants Analyzed 145 144 145
Mean (Standard Deviation)
Unit of Measure: score on a scale
Week 2 Number Analyzed 145 participants 144 participants 144 participants
3.5  (0.80) 3.4  (0.87) 3.2  (0.85)
Week 6 Number Analyzed 138 participants 138 participants 133 participants
3.4  (0.86) 3.3  (0.96) 3.2  (0.93)
Week 12 Number Analyzed 132 participants 129 participants 122 participants
3.5  (0.98) 3.3  (1.01) 3.2  (0.92)
Week 18 Number Analyzed 120 participants 117 participants 114 participants
3.5  (1.04) 3.5  (0.92) 3.2  (0.97)
Week 24 Number Analyzed 111 participants 106 participants 107 participants
3.5  (0.92) 3.5  (1.07) 3.2  (0.98)
6.Other Pre-specified Outcome
Title Patient Global Impression of Improvement (PGI-I) Week 24
Hide Description

For the Patient Global Impression of Improvement (PG-I), the patient is asked to rate the total improvement of their Parkinson's Disease, whether or not in the patient's judgment it is due entirely to drug treatment, based on a 1-7 point weighted scale. "very much improved" (1) to "very much worse" (7). A zero score is assigned if the score is not assessed.

Scale: 1 = Normal, not at all ill, 2 = Borderline ill, 3 = Mildly ill, 4 = Moderately ill, 5 = Markedly ill, 6 = Severly ill, 7 = Among the most extremely ill.

Tables show Treatment vs Placebo.

Time Frame At Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population (Modified Intent-to-Treat) - all safety set patients who had valid diaries at baseline and had valid diaries on at least 1 post-baseline visit. Patients were accounted for in the treatment group to which they were originally randomized.
Arm/Group Title Placebo Tozadenant 60 mg Tozadenant 120 mg
Hide Arm/Group Description:
One Placebo
One 60 mg tozadenant tablet BID plus 1 Placebo
Two 60 mg tozadenant tablets BID
Overall Number of Participants Analyzed 145 144 145
Mean (Standard Deviation)
Unit of Measure: score on a scale
Week 2 Number Analyzed 145 participants 144 participants 144 participants
3.6  (0.90) 3.3  (1.02) 3.1  (1.00)
Week 6 Number Analyzed 138 participants 140 participants 134 participants
3.5  (0.92) 3.4  (1.22) 3.1  (1.02)
Week 12 Number Analyzed 132 participants 129 participants 122 participants
3.5  (1.16) 3.5  (1.21) 3.1  (1.13)
Week 18 Number Analyzed 120 participants 117 participants 114 participants
3.6  (1.03) 3.6  (1.13) 3.2  (1.08)
Week 24 Number Analyzed 111 participants 106 participants 107 participants
3.6  (1.14) 3.6  (1.21) 3.4  (1.14)
Time Frame 24 Weeks
Adverse Event Reporting Description The Adverse Events was based on the Safety Set Population (SS). The SS included 447 of the 449 (ITT Population) randomized patients as two patients who were randomized were not dosed.
 
Arm/Group Title Tozadenant 60 mg BID Tozadenant 120 mg BID Placebo BID
Hide Arm/Group Description

Part A (double-blind phase)

During Part A, patients took two (2) tablets, one 60 mg tozadenant and one placebo, by mouth BID for a total of four (4) tablets per day.

Part A (double-blind phase)

During Part A, patients took two (2) tablets of 60 mg tozadenant, by mouth BID for a total of four (4) tablets per day.

Part A (double-blind phase)

During Part A, patients took two (2) tablets of placebo, by mouth BID for a total of four (4) tablets per day.

All-Cause Mortality
Tozadenant 60 mg BID Tozadenant 120 mg BID Placebo BID
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/150 (0.67%)   1/149 (0.67%)   1/148 (0.68%) 
Hide Serious Adverse Events
Tozadenant 60 mg BID Tozadenant 120 mg BID Placebo BID
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   13/150 (8.67%)   12/149 (8.05%)   15/148 (10.14%) 
Blood and lymphatic system disorders       
Iron deficiency anaemia  1  1/150 (0.67%)  0/149 (0.00%)  0/148 (0.00%) 
Cardiac disorders       
Angina pectoris  1  0/150 (0.00%)  0/149 (0.00%)  1/148 (0.68%) 
Atrial flutter  1  0/150 (0.00%)  1/149 (0.67%)  0/148 (0.00%) 
Myocardial infarction  1  1/150 (0.67%)  0/149 (0.00%)  0/148 (0.00%) 
Torsade de pointes  1  0/150 (0.00%)  1/149 (0.67%)  0/148 (0.00%) 
Gastrointestinal disorders       
Colitis ischaemic  1  1/150 (0.67%)  0/149 (0.00%)  0/148 (0.00%) 
Inguinal hernia  1  1/150 (0.67%)  0/149 (0.00%)  0/148 (0.00%) 
Pancreatitis  1  0/150 (0.00%)  1/149 (0.67%)  0/148 (0.00%) 
General disorders       
Asthenia  1  1/150 (0.67%)  0/149 (0.00%)  0/148 (0.00%) 
Gait disturbance  1  1/150 (0.67%)  0/149 (0.00%)  0/148 (0.00%) 
Infections and infestations       
Appendicitis  1  1/150 (0.67%)  0/149 (0.00%)  0/148 (0.00%) 
Bronchitis  1  1/150 (0.67%)  0/149 (0.00%)  0/148 (0.00%) 
Pneumonia  1  0/150 (0.00%)  0/149 (0.00%)  1/148 (0.68%) 
Septic shock  1  0/150 (0.00%)  1/149 (0.67%)  0/148 (0.00%) 
Urinary tract infection  1  0/150 (0.00%)  0/149 (0.00%)  1/148 (0.68%) 
Injury, poisoning and procedural complications       
Burns third degree  1  0/150 (0.00%)  0/149 (0.00%)  1/148 (0.68%) 
Face injury  1  1/150 (0.67%)  0/149 (0.00%)  0/148 (0.00%) 
Fall  1  1/150 (0.67%)  0/149 (0.00%)  0/148 (0.00%) 
Femur fracture  1  1/150 (0.67%)  0/149 (0.00%)  0/148 (0.00%) 
Fractured sacrum  1  0/150 (0.00%)  1/149 (0.67%)  0/148 (0.00%) 
Hip fracture  1  1/150 (0.67%)  0/149 (0.00%)  0/148 (0.00%) 
Pubis fracture  1  0/150 (0.00%)  1/149 (0.67%)  1/148 (0.68%) 
Respiratory fume inhalation disorder  1  0/150 (0.00%)  0/149 (0.00%)  1/148 (0.68%) 
Rib fracture  1  0/150 (0.00%)  1/149 (0.67%)  0/148 (0.00%) 
Musculoskeletal and connective tissue disorders       
Cervical spinal stenosis  1  0/150 (0.00%)  0/149 (0.00%)  1/148 (0.68%) 
Intervertebral disc protrusion  1  0/150 (0.00%)  0/149 (0.00%)  1/148 (0.68%) 
Lumbar spinal stenosis  1  0/150 (0.00%)  0/149 (0.00%)  2/148 (1.35%) 
Muscle spasm  1  1/150 (0.67%)  0/149 (0.00%)  0/148 (0.00%) 
Muscular weakness  1  0/150 (0.00%)  0/149 (0.00%)  1/148 (0.68%) 
Osteoarthritis  1  1/150 (0.67%)  0/149 (0.00%)  0/148 (0.00%) 
Spinal column stenosis  1  0/150 (0.00%)  0/149 (0.00%)  1/148 (0.68%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Thyroid adenoma  1  1/150 (0.67%)  0/149 (0.00%)  0/148 (0.00%) 
Nervous system disorders       
Aphasia  1  0/150 (0.00%)  1/149 (0.67%)  0/148 (0.00%) 
Carotid artery occlusion  1  0/150 (0.00%)  0/149 (0.00%)  1/148 (0.68%) 
Carpal tunnel syndrome  1  0/150 (0.00%)  1/149 (0.67%)  0/148 (0.00%) 
Cerebrovascular accident  1  0/150 (0.00%)  1/149 (0.67%)  0/148 (0.00%) 
Dyskinesia  1  1/150 (0.67%)  0/149 (0.00%)  0/148 (0.00%) 
Intracranial aneurysm  1  0/150 (0.00%)  0/149 (0.00%)  1/148 (0.68%) 
Parkinson's disease  1  2/150 (1.33%)  0/149 (0.00%)  1/148 (0.68%) 
Psychiatric disorders       
Confusional state  1  0/150 (0.00%)  1/149 (0.67%)  0/148 (0.00%) 
Delirium  1  0/150 (0.00%)  1/149 (0.67%)  0/148 (0.00%) 
Hallucination, visual  1  0/150 (0.00%)  2/149 (1.34%)  0/148 (0.00%) 
Renal and urinary disorders       
Anuria  1  0/150 (0.00%)  0/149 (0.00%)  1/148 (0.68%) 
Calculus ureteric  1  1/150 (0.67%)  0/149 (0.00%)  0/148 (0.00%) 
Reproductive system and breast disorders       
Erectile dysfunction  1  1/150 (0.67%)  0/149 (0.00%)  0/148 (0.00%) 
Vascular disorders       
Accelerated hypertension  1  0/150 (0.00%)  0/149 (0.00%)  1/148 (0.68%) 
Hypertension  1  0/150 (0.00%)  1/149 (0.67%)  0/148 (0.00%) 
1
Term from vocabulary, MedDRA 19.1, 20.0,
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
Tozadenant 60 mg BID Tozadenant 120 mg BID Placebo BID
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   115/150 (76.67%)   111/149 (74.50%)   111/148 (75.00%) 
Gastrointestinal disorders       
Constipation  1  15/150 (10.00%)  8/149 (5.37%)  2/148 (1.35%) 
Dry Mouth  1  2/150 (1.33%)  4/149 (2.68%)  0/148 (0.00%) 
Nausea  1  8/150 (5.33%)  13/149 (8.72%)  6/148 (4.05%) 
General disorders       
Fatigue  1  7/150 (4.67%)  4/149 (2.68%)  2/148 (1.35%) 
Infections and infestations       
Nasopharyngitis  1  7/150 (4.67%)  5/149 (3.36%)  10/148 (6.76%) 
Urinary Tract Infection  1  4/150 (2.67%)  9/149 (6.04%)  4/148 (2.70%) 
Upper respiratory tract infection  1  6/150 (4.00%)  1/149 (0.67%)  7/148 (4.73%) 
Injury, poisoning and procedural complications       
Contusion  1  0/150 (0.00%)  5/149 (3.36%)  1/148 (0.68%) 
Fall  1  22/150 (14.67%)  13/149 (8.72%)  9/148 (6.08%) 
Investigations       
Blood creatine phosphokinase increased  1  4/150 (2.67%)  6/149 (4.03%)  3/148 (2.03%) 
Weight decreased  1  4/150 (2.67%)  2/149 (1.34%)  0/148 (0.00%) 
White Blood cell count decreased  1  2/150 (1.33%)  0/149 (0.00%)  4/148 (2.70%) 
Musculoskeletal and connective tissue disorders       
Back pain  1  4/150 (2.67%)  7/149 (4.70%)  8/148 (5.41%) 
Myalgia  1  4/150 (2.67%)  2/149 (1.34%)  0/148 (0.00%) 
Pain in extremity  1  5/150 (3.33%)  3/149 (2.01%)  6/148 (4.05%) 
Arthralgia  1  3/150 (2.00%)  2/149 (1.34%)  6/148 (4.05%) 
Musculoskeletal pain  1  4/150 (2.67%)  0/149 (0.00%)  1/148 (0.68%) 
Nervous system disorders       
Dizziness  1  7/150 (4.67%)  7/149 (4.70%)  9/148 (6.08%) 
Somnolence  1  5/150 (3.33%)  8/149 (5.37%)  5/148 (3.38%) 
Sudden onset of sleep  1  7/150 (4.67%)  7/149 (4.70%)  4/148 (2.70%) 
Dyskinesia  1  22/150 (14.67%)  22/149 (14.77%)  13/148 (8.78%) 
Parkinson's disease  1  11/150 (7.33%)  3/149 (2.01%)  7/148 (4.73%) 
Headache  1  3/150 (2.00%)  2/149 (1.34%)  5/148 (3.38%) 
Psychiatric disorders       
Anxiety  1  5/150 (3.33%)  2/149 (1.34%)  3/148 (2.03%) 
Hallucination, visual  1  8/150 (5.33%)  8/149 (5.37%)  2/148 (1.35%) 
Insomnia  1  9/150 (6.00%)  9/149 (6.04%)  9/148 (6.08%) 
Confusional state  1  2/150 (1.33%)  4/149 (2.68%)  1/148 (0.68%) 
Disorientation  1  4/150 (2.67%)  0/149 (0.00%)  0/148 (0.00%) 
Renal and urinary disorders       
Micturition urgency  1  3/150 (2.00%)  4/149 (2.68%)  0/148 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Cough  1  1/150 (0.67%)  4/149 (2.68%)  2/148 (1.35%) 
Vascular disorders       
Flushing  1  1/150 (0.67%)  4/149 (2.68%)  1/148 (0.68%) 
Hypertension  1  5/150 (3.33%)  3/149 (2.01%)  3/148 (2.03%) 
1
Term from vocabulary, MedDRA 19.1, 20.0,
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding the study results for a period up to 30 days from the date the communication is submitted to the sponsor. The sponsor shall have the right to defer proposed publication an additional 60 days from the end of the review period. The sponsor cannot require changes to the communication and cannot unilaterally extend the embargo.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Christopher Kenney, Senior Vice President - Medical Affairs
Organization: Acorda Therapeutics
Phone: 914-326-5775
EMail: ckenney@acorda.com
Layout table for additonal information
Responsible Party: Biotie Therapies Inc.
ClinicalTrials.gov Identifier: NCT02453386    
Other Study ID Numbers: TOZ-CL05
2014-005630-60 ( EudraCT Number )
First Submitted: May 21, 2015
First Posted: May 25, 2015
Results First Submitted: January 31, 2019
Results First Posted: March 26, 2019
Last Update Posted: April 3, 2019