Trial Outcomes & Findings for Efficacy and Safety of BIA 9-1067 in Idiopathic Parkinson's Disease Patients. (NCT NCT01227655)
NCT ID: NCT01227655
Last Updated: 2015-10-19
Results Overview
Efficacy of 2 BIA 9-1067 (25 mg, and 50 mg) compared with placebo, when administered with the existing treatment of L-DOPA plus a DDCI (DOPA decarboxylase inhibitor), in patients with PD and end-of-dose motor fluctuations. The primary efficacy variable will be the change from baseline in absolute OFF-time at the end of the DB period.
COMPLETED
PHASE3
427 participants
14-15 weeks
2015-10-19
Participant Flow
Participant milestones
| Measure |
BIA 9-1067 25 mg
BIA 9-1067 once daily (QD).
|
BIA 9-1067 50 mg
BIA 9-1067 once daily (QD).
|
Placebo
Placebo: comparator
|
|---|---|---|---|
|
Overall Study
STARTED
|
129
|
154
|
144
|
|
Overall Study
Safety Set
|
125
|
150
|
136
|
|
Overall Study
Full Analysis Set
|
125
|
147
|
135
|
|
Overall Study
COMPLETED
|
118
|
128
|
130
|
|
Overall Study
NOT COMPLETED
|
11
|
26
|
14
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Efficacy and Safety of BIA 9-1067 in Idiopathic Parkinson's Disease Patients.
Baseline characteristics by cohort
| Measure |
BIA 9-1067 25 mg
n=125 Participants
BIA 9-1067 once daily (QD).
|
BIA 9-1067 50 mg
n=147 Participants
BIA 9-1067 once daily (QD).
|
Placebo
n=135 Participants
Placebo: comparator
|
Total
n=407 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Customized
<70 years
|
96 participants
n=5 Participants
|
96 participants
n=7 Participants
|
107 participants
n=5 Participants
|
299 participants
n=4 Participants
|
|
Age, Customized
≥70 years
|
29 participants
n=5 Participants
|
51 participants
n=7 Participants
|
28 participants
n=5 Participants
|
108 participants
n=4 Participants
|
|
Sex: Female, Male
Female
|
82 Participants
n=5 Participants
|
89 Participants
n=7 Participants
|
71 Participants
n=5 Participants
|
242 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
43 Participants
n=5 Participants
|
58 Participants
n=7 Participants
|
64 Participants
n=5 Participants
|
165 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: 14-15 weeksEfficacy of 2 BIA 9-1067 (25 mg, and 50 mg) compared with placebo, when administered with the existing treatment of L-DOPA plus a DDCI (DOPA decarboxylase inhibitor), in patients with PD and end-of-dose motor fluctuations. The primary efficacy variable will be the change from baseline in absolute OFF-time at the end of the DB period.
Outcome measures
| Measure |
BIA 9-1067 25 mg
n=125 Participants
BIA 9-1067 once daily (QD).
|
BIA 9-1067 50 mg
n=147 Participants
BIA 9-1067 once daily (QD).
|
Placebo
n=135 Participants
Placebo: comparator
|
|---|---|---|---|
|
Efficacy of 2 BIA 9-1067 (25 mg, and 50 mg) Compared With Placebo, When Administered With the Existing Treatment of L-DOPA Plus a DDCI (DOPA Decarboxylase Inhibitor)
|
-102.8 minutes
Standard Deviation 159.42
|
-124.0 minutes
Standard Deviation 178.23
|
-64.5 minutes
Standard Deviation 155.35
|
SECONDARY outcome
Timeframe: 14-15 weeksTotal UPDRS SCORE (I, II (ON), and III) Change from Baseline to Endpoint * UPDRS I evaluation of mentation, behavior, and mood * UPDRS 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 * UPDRS III clinician-scored monitored motor evaluation The UPDRS I, II and III scores and subscores are calculated as the sum of all individual items. If one or two items in a scale are missing, they will be imputed with the mean of the non-missing items of that scale. Subscale has 0-4 ratings, where 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe The final cumulative score will range from 0 (no disability) to 199 (total disability).
Outcome measures
| Measure |
BIA 9-1067 25 mg
n=125 Participants
BIA 9-1067 once daily (QD).
|
BIA 9-1067 50 mg
n=147 Participants
BIA 9-1067 once daily (QD).
|
Placebo
n=135 Participants
Placebo: comparator
|
|---|---|---|---|
|
UPDRS (Unified Parkinson's Disease Rating Scale) Sections I (ON), II (ON and OFF), and III (ON)
Endpoint
|
26.6 units on a scale
Standard Deviation 16.40
|
28.7 units on a scale
Standard Deviation 18.11
|
28.1 units on a scale
Standard Deviation 16.78
|
|
UPDRS (Unified Parkinson's Disease Rating Scale) Sections I (ON), II (ON and OFF), and III (ON)
Baseline
|
30.8 units on a scale
Standard Deviation 16.88
|
31.7 units on a scale
Standard Deviation 17.55
|
31.5 units on a scale
Standard Deviation 17.00
|
SECONDARY outcome
Timeframe: 14-15 weeksThe Parkinson's disease Sleep Scale (PDSS) is a specific scale for the assessment of sleep disturbances in subjects with PD. The PDSS score is calculated as the sum of all single items. If one or two items are missing, they will be imputed with the mean of the non-missing items. If three or more items are missing, no imputation will be done and the score will be set to missing. Subscale has 0-10 ratings, where 0 = severe and 10 = normal The PDSS total score is a sum score of all 15 questions and ranges from 0 to 150, with lower scores meaning more disability.
Outcome measures
| Measure |
BIA 9-1067 25 mg
n=123 Participants
BIA 9-1067 once daily (QD).
|
BIA 9-1067 50 mg
n=147 Participants
BIA 9-1067 once daily (QD).
|
Placebo
n=135 Participants
Placebo: comparator
|
|---|---|---|---|
|
Parkinson's Disease Sleep Scale (PDSS)
Baseline
|
95.75 units on a scale
Standard Deviation 28.026
|
102.62 units on a scale
Standard Deviation 25.116
|
101.76 units on a scale
Standard Deviation 26.729
|
|
Parkinson's Disease Sleep Scale (PDSS)
Visit 7
|
98.79 units on a scale
Standard Deviation 25.280
|
103.25 units on a scale
Standard Deviation 26.752
|
105.39 units on a scale
Standard Deviation 28.643
|
|
Parkinson's Disease Sleep Scale (PDSS)
Visit 5
|
97.99 units on a scale
Standard Deviation 26.196
|
103.05 units on a scale
Standard Deviation 26.437
|
107.11 units on a scale
Standard Deviation 26.987
|
SECONDARY outcome
Timeframe: 14-15 weeksThe Non-motor Symptoms Scale (NMSS) consists of 30 questions, covering 9 dimensions, whereby each item is scored for severity and frequency: Severity None 0 Mild (symptoms present but causes little distress) 1 Moderate (some distress or disturbance to subject) 2 Severe (major source of distress or disturbance to subject) 3 Frequency Rarely (\<1/wk) 1 Often (1/wk) 2 Frequent (several times per week) 3 Very Frequent (daily or all the time) 4 The product of frequency and severity is calculated for each item and each dimension score is defined as the sum of the frequency\*severity of the respective items. If frequency or severity of a single item is missing, the domain score will not be calculated. The NMSS total score is defined as the sum of all domain scores. The NMSS total score is calculated by adding all domain scores (0-360), and lower scores mean less disability.
Outcome measures
| Measure |
BIA 9-1067 25 mg
n=125 Participants
BIA 9-1067 once daily (QD).
|
BIA 9-1067 50 mg
n=147 Participants
BIA 9-1067 once daily (QD).
|
Placebo
n=135 Participants
Placebo: comparator
|
|---|---|---|---|
|
Non-motor Symptoms Scale (NMSS)
Baseline
|
38.2 units on a scale
Standard Deviation 29.40
|
36.7 units on a scale
Standard Deviation 30.88
|
38.2 units on a scale
Standard Deviation 33.37
|
|
Non-motor Symptoms Scale (NMSS)
Visit 5
|
33.7 units on a scale
Standard Deviation 26.30
|
33.2 units on a scale
Standard Deviation 27.95
|
33.5 units on a scale
Standard Deviation 31.18
|
|
Non-motor Symptoms Scale (NMSS)
Visit 7
|
35.0 units on a scale
Standard Deviation 29.88
|
31.5 units on a scale
Standard Deviation 28.47
|
31.6 units on a scale
Standard Deviation 29.88
|
Adverse Events
BIA 9-1067 25 mg
BIA 9-1067 50 mg
Placebo
Serious adverse events
| Measure |
BIA 9-1067 25 mg
n=125 participants at risk
BIA 9-1067 once daily (QD).
|
BIA 9-1067 50 mg
n=150 participants at risk
BIA 9-1067 once daily (QD).
|
Placebo
n=136 participants at risk
Placebo: comparator
|
|---|---|---|---|
|
Gastrointestinal disorders
NAUSEA
|
0.00%
0/125
|
0.67%
1/150
|
0.00%
0/136
|
|
Hepatobiliary disorders
CHOLECYSTITIS ACUTE
|
0.00%
0/125
|
0.67%
1/150
|
0.00%
0/136
|
|
Infections and infestations
PNEUMONIA
|
0.00%
0/125
|
0.00%
0/150
|
0.74%
1/136
|
|
Infections and infestations
PYELONEPHRITIS ACUTE
|
0.00%
0/125
|
0.67%
1/150
|
0.00%
0/136
|
|
Injury, poisoning and procedural complications
FALL
|
0.00%
0/125
|
0.67%
1/150
|
0.00%
0/136
|
|
Injury, poisoning and procedural complications
FEMORAL NECK FRACTURE
|
0.00%
0/125
|
0.00%
0/150
|
0.74%
1/136
|
|
Injury, poisoning and procedural complications
HEAD INJURY
|
0.00%
0/125
|
0.67%
1/150
|
0.00%
0/136
|
|
Injury, poisoning and procedural complications
RADIUS FRACTURE
|
0.00%
0/125
|
0.00%
0/150
|
0.74%
1/136
|
|
Investigations
BIOPSY PROSTATE
|
0.00%
0/125
|
0.67%
1/150
|
0.00%
0/136
|
|
Musculoskeletal and connective tissue disorders
OSTEOARTHRITIS
|
0.80%
1/125
|
0.00%
0/150
|
0.00%
0/136
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
BASAL CELL CARCINOMA
|
0.00%
0/125
|
0.67%
1/150
|
0.00%
0/136
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
OVARIAN CANCER
|
0.00%
0/125
|
0.00%
0/150
|
0.74%
1/136
|
|
Nervous system disorders
COGNITIVE DISORDER
|
0.00%
0/125
|
0.00%
0/150
|
0.74%
1/136
|
|
Nervous system disorders
DYSKINESIA
|
0.80%
1/125
|
0.00%
0/150
|
0.00%
0/136
|
|
Psychiatric disorders
DELIRIUM FEBRILE
|
0.00%
0/125
|
0.67%
1/150
|
0.00%
0/136
|
|
Renal and urinary disorders
RENAL FAILURE
|
0.00%
0/125
|
0.00%
0/150
|
0.74%
1/136
|
|
Renal and urinary disorders
RENAL FAILURE ACUTE
|
0.80%
1/125
|
0.00%
0/150
|
0.00%
0/136
|
|
Renal and urinary disorders
URINARY RETENTION
|
0.80%
1/125
|
0.00%
0/150
|
0.00%
0/136
|
|
Reproductive system and breast disorders
CYSTOCELE
|
0.00%
0/125
|
0.67%
1/150
|
0.00%
0/136
|
|
Respiratory, thoracic and mediastinal disorders
PLEURAL EFFUSION
|
0.00%
0/125
|
0.67%
1/150
|
0.00%
0/136
|
|
Respiratory, thoracic and mediastinal disorders
PULMONARY EMBOLISM
|
0.00%
0/125
|
0.67%
1/150
|
0.00%
0/136
|
Other adverse events
| Measure |
BIA 9-1067 25 mg
n=125 participants at risk
BIA 9-1067 once daily (QD).
|
BIA 9-1067 50 mg
n=150 participants at risk
BIA 9-1067 once daily (QD).
|
Placebo
n=136 participants at risk
Placebo: comparator
|
|---|---|---|---|
|
Nervous system disorders
Dyskinesia
|
24.0%
30/125
|
24.0%
36/150
|
8.1%
11/136
|
|
Gastrointestinal disorders
Constipation
|
9.6%
12/125
|
6.7%
10/150
|
1.5%
2/136
|
|
Gastrointestinal disorders
Dry mouth
|
10.4%
13/125
|
4.0%
6/150
|
0.74%
1/136
|
|
Investigations
Blood CPK increased
|
4.0%
5/125
|
8.0%
12/150
|
3.7%
5/136
|
|
Nervous system disorders
Parkinson's disease
|
7.2%
9/125
|
4.0%
6/150
|
5.1%
7/136
|
|
Injury, poisoning and procedural complications
Fall
|
5.6%
7/125
|
4.7%
7/150
|
6.6%
9/136
|
|
Vascular disorders
Hypertension
|
6.4%
8/125
|
4.0%
6/150
|
2.2%
3/136
|
|
Gastrointestinal disorders
Nausea
|
6.4%
8/125
|
3.3%
5/150
|
5.9%
8/136
|
|
Nervous system disorders
Headache
|
4.8%
6/125
|
4.0%
6/150
|
6.6%
9/136
|
|
Psychiatric disorders
Insomnia
|
8.0%
10/125
|
1.3%
2/150
|
2.2%
3/136
|
|
Infections and infestations
Urinary tract infection
|
2.4%
3/125
|
6.0%
9/150
|
1.5%
2/136
|
|
Nervous system disorders
Dizziness
|
3.2%
4/125
|
4.0%
6/150
|
1.5%
2/136
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
4.8%
6/125
|
2.7%
4/150
|
1.5%
2/136
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
4.0%
5/125
|
2.7%
4/150
|
0.74%
1/136
|
|
Nervous system disorders
Somnolence
|
4.8%
6/125
|
2.0%
3/150
|
2.2%
3/136
|
Additional Information
Head of Clinical Research
Bial - Portela & Cª, S.A.
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER