Trial Outcomes & Findings for A Dose-finding Study for SPM 962 in Advanced Parkinson's Disease Patients (NCT NCT01628848)

NCT ID: NCT01628848

Last Updated: 2014-03-19

Results Overview

Mean change (LOCF) from baseline in UPDRS Part 3 sum score at 12 weeks after dosing. UPDRS is a scale for monitoring Parkinson's Disease-related disability and impairment. The UPDRS consists of the following four sub-scales. Part 1: Mentation, Part 2: Activities of Daily Living, Part 3: Motor, Part 4: Complications. Part 3 assesses 14 items. Each item is scored from 0 (normal) to 4 (severe). The sum score serves as the sub-scale score. A higher score indicates a greater severity of symptoms. Thus a decrease in the scores means improvement.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

174 participants

Primary outcome timeframe

baseline, 12 weeks after dosing

Results posted on

2014-03-19

Participant Flow

Participant milestones

Participant milestones
Measure
SPM 962
SPM 962 transdermal patch
Placebo
Placebo transdermal patch
Overall Study
STARTED
87
87
Overall Study
COMPLETED
75
73
Overall Study
NOT COMPLETED
12
14

Reasons for withdrawal

Reasons for withdrawal
Measure
SPM 962
SPM 962 transdermal patch
Placebo
Placebo transdermal patch
Overall Study
Adverse Event
9
7
Overall Study
Lack of Efficacy
0
4
Overall Study
Withdrawal by Subject
0
2
Overall Study
Physician Decision
3
1

Baseline Characteristics

A Dose-finding Study for SPM 962 in Advanced Parkinson's Disease Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
SPM 962
n=86 Participants
SPM 962 transdermal patch
Placebo
n=86 Participants
Placebo transdermal patch
Total
n=172 Participants
Total of all reporting groups
Age, Categorical
<=18 years
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Age, Categorical
Between 18 and 65 years
24 Participants
n=5 Participants
26 Participants
n=7 Participants
50 Participants
n=5 Participants
Age, Categorical
>=65 years
62 Participants
n=5 Participants
60 Participants
n=7 Participants
122 Participants
n=5 Participants
Age, Continuous
67.0 years
STANDARD_DEVIATION 6.8 • n=5 Participants
66.8 years
STANDARD_DEVIATION 8.3 • n=7 Participants
66.9 years
STANDARD_DEVIATION 7.5 • n=5 Participants
Sex: Female, Male
Female
52 Participants
n=5 Participants
42 Participants
n=7 Participants
94 Participants
n=5 Participants
Sex: Female, Male
Male
34 Participants
n=5 Participants
44 Participants
n=7 Participants
78 Participants
n=5 Participants
Region of Enrollment
Japan
87 participants
n=5 Participants
87 participants
n=7 Participants
174 participants
n=5 Participants

PRIMARY outcome

Timeframe: baseline, 12 weeks after dosing

Population: Full analysis set (FAS), last observation carried forward (LOCF)

Mean change (LOCF) from baseline in UPDRS Part 3 sum score at 12 weeks after dosing. UPDRS is a scale for monitoring Parkinson's Disease-related disability and impairment. The UPDRS consists of the following four sub-scales. Part 1: Mentation, Part 2: Activities of Daily Living, Part 3: Motor, Part 4: Complications. Part 3 assesses 14 items. Each item is scored from 0 (normal) to 4 (severe). The sum score serves as the sub-scale score. A higher score indicates a greater severity of symptoms. Thus a decrease in the scores means improvement.

Outcome measures

Outcome measures
Measure
SPM 962
n=86 Participants
SPM 962 transdermal patch
Placebo
n=86 Participants
Placebo transdermal patch
Unified Parkinson's Disease Rating Scale (UPDRS) Part 3 Sum Score
-10.1 Scores on a scale
Standard Deviation 9.0
-4.4 Scores on a scale
Standard Deviation 7.4

SECONDARY outcome

Timeframe: baseline, 12 weeks after dosing

Population: FAS, LOCF

Mean change (LOCF) from baseline in UPDRS Part 2 sum score (average scores of on state and off state) at 12 weeks after dosing. Mean change (LOCF) from baseline in UPDRS Part 2 sum score (average score of on state and off state) at 12 weeks after dosing. UPDRS sub-scale Part 2 assesses 13 items. Each item is scored from 0 (normal) to 4 (severe). The sum score serves as the sub-scale score. A higher score indicates a greater severity of symptoms. Thus a decrease in the scores means improvement.

Outcome measures

Outcome measures
Measure
SPM 962
n=86 Participants
SPM 962 transdermal patch
Placebo
n=86 Participants
Placebo transdermal patch
UPDRS Part 2 Sum Score (Average Score of on State and Off State)
-3.8 Scores on a scale
Standard Deviation 3.6
-1.6 Scores on a scale
Standard Deviation 2.6

SECONDARY outcome

Timeframe: baseline, 12 weeks after dosing

Population: FAS subjects with measurable off time data at baseline, LOCF

Mean change (LOCF) from baseline in off time at 12 weeks after dosing.

Outcome measures

Outcome measures
Measure
SPM 962
n=54 Participants
SPM 962 transdermal patch
Placebo
n=56 Participants
Placebo transdermal patch
Off Time
-2.1 Hours
Standard Deviation 3.1
-0.7 Hours
Standard Deviation 2.8

SECONDARY outcome

Timeframe: Baseline, 12 weeks after dosing

Population: FAS, LOCF

Effective rate (percentage of subjects with 20% or 30% decrease) (LOCF) in UPDRS Part 3 sum score at 12 weeks after dosing.

Outcome measures

Outcome measures
Measure
SPM 962
n=86 Participants
SPM 962 transdermal patch
Placebo
n=86 Participants
Placebo transdermal patch
Effective Rate in UPDRS Part 3 Sum Score
Subjects with ≥30% decrease
64.0 Percentage of participants
Interval 53.8 to 74.1
29.1 Percentage of participants
Interval 19.5 to 38.7
Effective Rate in UPDRS Part 3 Sum Score
Subjects with ≥20% decrease
73.3 Percentage of participants
Interval 63.9 to 82.6
43.0 Percentage of participants
Interval 32.6 to 53.5

SECONDARY outcome

Timeframe: Baseline, 12 weeks after dosing

Population: FAS, LOCF

Mean change (LOCF) from baseline in UPDRS Part 1 sum score at 12 weeks after dosing. UPDRS sub-scale Part 1 assesses 4 items. Each item is scored from 0 (normal) to 4 (severe). The sum score serves as the sub-scale score. A higher score indicates a greater severity of symptoms. Thus a decrease in the scores means improvement.

Outcome measures

Outcome measures
Measure
SPM 962
n=86 Participants
SPM 962 transdermal patch
Placebo
n=86 Participants
Placebo transdermal patch
UPDRS Part 1 Sum Score
-0.15 Scores on a scale
Standard Deviation 1.34
-0.12 Scores on a scale
Standard Deviation 0.79

SECONDARY outcome

Timeframe: Baseline, 12 weeks after dosing.

Population: FAS subjects with measurable off time data at baseline, LOCF

Effective rate (percentage of subjects with 20% or 30% decrease) (LOCF) in off time at 12 weeks after dosing.

Outcome measures

Outcome measures
Measure
SPM 962
n=54 Participants
SPM 962 transdermal patch
Placebo
n=56 Participants
Placebo transdermal patch
Effective Rate in Off Time
Subjects with ≥20% decrease
63.0 Percentage of participants
Interval 50.1 to 75.8
46.4 Percentage of participants
Interval 33.4 to 59.5
Effective Rate in Off Time
Subjects with ≥30% decrease
51.9 Percentage of participants
Interval 38.5 to 65.2
37.5 Percentage of participants
Interval 24.8 to 50.2

SECONDARY outcome

Timeframe: Baseline, 12 weeks after dosing

Population: FAS, LOCF

Mean change (LOCF) from baseline in UPDRS Part 2 sum score (on state) at 12 weeks after dosing. UPDRS sub-scale Part 2 assesses 13 items. Each item is scored from 0 (normal) to 4 (severe). The sum score serves as the sub-scale score. A higher score indicates a greater severity of symptoms. Thus a decrease in the scores means improvement.

Outcome measures

Outcome measures
Measure
SPM 962
n=86 Participants
SPM 962 transdermal patch
Placebo
n=86 Participants
Placebo transdermal patch
UPDRS Part 2 Sum Score (on State)
-3.0 Scores on a scale
Standard Deviation 3.7
-1.2 Scores on a scale
Standard Deviation 2.6

SECONDARY outcome

Timeframe: Baseline, 12 weeks after dosing

Population: FAS, LOCF

Mean change (LOCF) from baseline in UPDRS Part 2 sum score (off state) at 12 weeks after dosing. UPDRS sub-scale Part 2 assesses 13 items. Each item is scored from 0 (normal) to 4 (severe). The sum score serves as the sub-scale score. A higher score indicates a greater severity of symptoms. Thus a decrease in the scores means improvement.

Outcome measures

Outcome measures
Measure
SPM 962
n=55 Participants
SPM 962 transdermal patch
Placebo
n=59 Participants
Placebo transdermal patch
UPDRS Part 2 Sum Score (Off State)
-4.6 Scores on a scale
Standard Deviation 4.5
-1.9 Scores on a scale
Standard Deviation 3.6

SECONDARY outcome

Timeframe: Baseline, 12 weeks after dosing

Population: FAS, LOCF

Mean change (LOCF) from baseline in UPDRS Part 4 sum score at 12 weeks after dosing. UPDRS sub-scale Part 4 assesses 11 items. Each item is scored from 0 (normal) to 4 (severe). The sum score serves as the sub-scale score. A higher score indicates a greater severity of symptoms. Thus a decrease in the scores means improvement.

Outcome measures

Outcome measures
Measure
SPM 962
n=86 Participants
SPM 962 transdermal patch
Placebo
n=85 Participants
Placebo transdermal patch
UPDRS Part 4 Sum Score
-0.40 Scores on a scale
Standard Deviation 1.73
-0.22 Scores on a scale
Standard Deviation 1.21

SECONDARY outcome

Timeframe: Baseline, 12 weeks after dosing

Population: FAS, LOCF

Mean change (LOCF) from baseline in total of UPDRS Part 2 sum score (average score of on state and off state), and UPDRS Part 3 sum score at 12 weeks after dosing. UPDRS sub-scale Part 2 assesses 13 items and Part 3 assesses 14 items. Each item is scored from 0 (normal) to 4 (severe). The sum score serves as the sub-scale score. A higher score indicates a greater severity of symptoms. Thus a decrease in the scores means improvement.

Outcome measures

Outcome measures
Measure
SPM 962
n=86 Participants
SPM 962 transdermal patch
Placebo
n=86 Participants
Placebo transdermal patch
Total of UPDRS Part 2 Sum Score (Average Score of on State and Off State) and UPDRS Part 3 Sum Score
-14.0 Scores on a scale
Standard Deviation 11.4
-6.0 Scores on a scale
Standard Deviation 9.3

SECONDARY outcome

Timeframe: Baseline, 12 weeks after dosing

Population: FAS, LOCF

Mean change (LOCF) from baseline in total of UPDRS Part 1 sum score, UPDRS Part 2 sum score (average score of on state and off state), UPDRS Part 3 sum score, and UPDRS Part 4 sum score at 12 weeks after dosing. UPDRS sub-scale Part 1, 2, 3, and 4 assess 4, 13, 14, and 11 items respectively. Each item is scored from 0 (normal) to 4 (severe). The sum score serves as the sub-scale score. A higher score indicates a greater severity of symptoms. Thus a decrease in the scores means improvement.

Outcome measures

Outcome measures
Measure
SPM 962
n=86 Participants
SPM 962 transdermal patch
Placebo
n=86 Participants
Placebo transdermal patch
Total of UPDRS Part 1 Sum Score, UPDRS Part 2 Sum Score (Average Score of on State and Off State), UPDRS Part 3 Sum Score, and UPDRS Part 4 Sum Score.
-14.6 Scores on a scale
Standard Deviation 11.9
-6.4 Scores on a scale
Standard Deviation 10.1

SECONDARY outcome

Timeframe: Baseline, 12 weeks after dosing

Population: FAS, LOCF

Mean change (LOCF) from baseline in the Modified Hoehn \& Yahr Severity of Illness at 12 weeks after dosing. The Modified Hoehn \& Yahr criteria are measured on the following 8-point scale for staging: 0, No signs of disease; 1, Unilateral disease; 1.5, Unilateral plus axial involvement; 2, Bilateral disease without impairment of balance; 2.5, Mild bilateral disease with recovery on pull test; 3, Mild to moderate bilateral disease, some postural instability, physically independent 4, Severe disability, still able to walk or stand unassisted; and 5, Wheelchair bound or bedridden unless aided.

Outcome measures

Outcome measures
Measure
SPM 962
n=86 Participants
SPM 962 transdermal patch
Placebo
n=86 Participants
Placebo transdermal patch
The Modified Hoehn & Yahr Severity of Illness
Increased
1.2 Percentage of participants
4.7 Percentage of participants
The Modified Hoehn & Yahr Severity of Illness
Not changed
61.6 Percentage of participants
80.0 Percentage of participants
The Modified Hoehn & Yahr Severity of Illness
Decreased
37.2 Percentage of participants
15.3 Percentage of participants

Adverse Events

SPM 962

Serious events: 3 serious events
Other events: 80 other events
Deaths: 0 deaths

Placebo

Serious events: 3 serious events
Other events: 59 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
SPM 962
n=87 participants at risk
SPM 962 transdermal patch
Placebo
n=87 participants at risk
Placebo transdermal patch
Blood and lymphatic system disorders
Anaemia
1.1%
1/87 • Number of events 1 • 14 weeks
0.00%
0/87 • 14 weeks
Gastrointestinal disorders
Hernia Inguinal
0.00%
0/87 • 14 weeks
1.1%
1/87 • Number of events 1 • 14 weeks
General disorders
Malaise
1.1%
1/87 • Number of events 1 • 14 weeks
0.00%
0/87 • 14 weeks
Infections and infestations
Arthritis Bacterial
0.00%
0/87 • 14 weeks
1.1%
1/87 • Number of events 1 • 14 weeks
Infections and infestations
Gastroenteritis
0.00%
0/87 • 14 weeks
1.1%
1/87 • Number of events 1 • 14 weeks
Investigations
Blood Creatine Phosphokinase Increased
1.1%
1/87 • Number of events 1 • 14 weeks
0.00%
0/87 • 14 weeks
Nervous system disorders
Consciousness Loss
0.00%
0/87 • 14 weeks
1.1%
1/87 • Number of events 1 • 14 weeks
Nervous system disorders
Neuroleptic Malignant
1.1%
1/87 • Number of events 1 • 14 weeks
0.00%
0/87 • 14 weeks
Psychiatric disorders
Delusion
1.1%
1/87 • Number of events 1 • 14 weeks
0.00%
0/87 • 14 weeks
Psychiatric disorders
Hallucination, Auditory
1.1%
1/87 • Number of events 1 • 14 weeks
0.00%
0/87 • 14 weeks

Other adverse events

Other adverse events
Measure
SPM 962
n=87 participants at risk
SPM 962 transdermal patch
Placebo
n=87 participants at risk
Placebo transdermal patch
Blood and lymphatic system disorders
Anaemia
3.4%
3/87 • Number of events 3 • 14 weeks
1.1%
1/87 • Number of events 1 • 14 weeks
Gastrointestinal disorders
Nausea
19.5%
17/87 • Number of events 17 • 14 weeks
5.7%
5/87 • Number of events 8 • 14 weeks
Gastrointestinal disorders
Constipation
10.3%
9/87 • Number of events 9 • 14 weeks
1.1%
1/87 • Number of events 1 • 14 weeks
Gastrointestinal disorders
Vomiting
10.3%
9/87 • Number of events 10 • 14 weeks
1.1%
1/87 • Number of events 1 • 14 weeks
Gastrointestinal disorders
Gastric Ulcer
4.6%
4/87 • Number of events 4 • 14 weeks
0.00%
0/87 • 14 weeks
Gastrointestinal disorders
Diarrhoea
3.4%
3/87 • Number of events 4 • 14 weeks
1.1%
1/87 • Number of events 1 • 14 weeks
General disorders
Application Site Reaction
50.6%
44/87 • Number of events 46 • 14 weeks
18.4%
16/87 • Number of events 21 • 14 weeks
General disorders
Application Site Erythema
9.2%
8/87 • Number of events 14 • 14 weeks
4.6%
4/87 • Number of events 5 • 14 weeks
General disorders
Application Site Pruritus
5.7%
5/87 • Number of events 5 • 14 weeks
4.6%
4/87 • Number of events 4 • 14 weeks
General disorders
Feeling Abnormal
3.4%
3/87 • Number of events 3 • 14 weeks
1.1%
1/87 • Number of events 1 • 14 weeks
Infections and infestations
Nasopharyngitis
20.7%
18/87 • Number of events 20 • 14 weeks
14.9%
13/87 • Number of events 19 • 14 weeks
Infections and infestations
Cystitis
2.3%
2/87 • Number of events 2 • 14 weeks
3.4%
3/87 • Number of events 3 • 14 weeks
Injury, poisoning and procedural complications
Fall
6.9%
6/87 • Number of events 6 • 14 weeks
8.0%
7/87 • Number of events 7 • 14 weeks
Injury, poisoning and procedural complications
Contusion
5.7%
5/87 • Number of events 5 • 14 weeks
3.4%
3/87 • Number of events 4 • 14 weeks
Injury, poisoning and procedural complications
Excoriation
1.1%
1/87 • Number of events 1 • 14 weeks
4.6%
4/87 • Number of events 4 • 14 weeks
Investigations
Blood Creatine Phosphokinase Increased
6.9%
6/87 • Number of events 6 • 14 weeks
3.4%
3/87 • Number of events 3 • 14 weeks
Metabolism and nutrition disorders
Anorexia
6.9%
6/87 • Number of events 6 • 14 weeks
0.00%
0/87 • 14 weeks
Metabolism and nutrition disorders
Decreased Appetite
4.6%
4/87 • Number of events 6 • 14 weeks
1.1%
1/87 • Number of events 1 • 14 weeks
Musculoskeletal and connective tissue disorders
Back Pain
3.4%
3/87 • Number of events 3 • 14 weeks
4.6%
4/87 • Number of events 4 • 14 weeks
Nervous system disorders
Dyskinesia
13.8%
12/87 • Number of events 13 • 14 weeks
8.0%
7/87 • Number of events 7 • 14 weeks
Nervous system disorders
Dizziness
8.0%
7/87 • Number of events 8 • 14 weeks
2.3%
2/87 • Number of events 2 • 14 weeks
Nervous system disorders
Dizziness Postural
8.0%
7/87 • Number of events 7 • 14 weeks
1.1%
1/87 • Number of events 2 • 14 weeks
Nervous system disorders
Headache
5.7%
5/87 • Number of events 5 • 14 weeks
2.3%
2/87 • Number of events 2 • 14 weeks
Psychiatric disorders
Somnolence
13.8%
12/87 • Number of events 12 • 14 weeks
1.1%
1/87 • Number of events 1 • 14 weeks
Psychiatric disorders
Hallucination Visual
9.2%
8/87 • Number of events 10 • 14 weeks
2.3%
2/87 • Number of events 2 • 14 weeks
Psychiatric disorders
Hallucination
3.4%
3/87 • Number of events 3 • 14 weeks
3.4%
3/87 • Number of events 3 • 14 weeks
Psychiatric disorders
Insomnia
3.4%
3/87 • Number of events 3 • 14 weeks
3.4%
3/87 • Number of events 3 • 14 weeks
Respiratory, thoracic and mediastinal disorders
Upper Respiratory Tract Inflammation
1.1%
1/87 • Number of events 1 • 14 weeks
3.4%
3/87 • Number of events 3 • 14 weeks

Additional Information

Director of Clinical Research and Development

Otsuka Pharmaceutical Co., Ltd.

Phone: +81-3-6131-7366

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place