Trial Outcomes & Findings for A Dose-ranging Study for SPM 962 in Parkinson's Disease Patients (NCT NCT01634243)

NCT ID: NCT01634243

Last Updated: 2014-03-19

Results Overview

The maintenance dose of the SPM 962 was examined based on the safety and efficacy.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 64 participants
• Primary outcome timeframe: Up to 12 weeks after dosing
• Results posted on: 2014-03-19

Participant Flow

Participant milestones

Measure	Early-stage Parkinson's Disease Subjects with early Parkinson's disease received SPM 962 transdermal patch	Advanced Parkinson's Disease Subjects with advanced Parkinson's disease received SPM 962 transdermal patch
Overall Study STARTED	21	43
Overall Study COMPLETED	15	38
Overall Study NOT COMPLETED	6	5

Reasons for withdrawal

Measure	Early-stage Parkinson's Disease Subjects with early Parkinson's disease received SPM 962 transdermal patch	Advanced Parkinson's Disease Subjects with advanced Parkinson's disease received SPM 962 transdermal patch
Overall Study Adverse Event	5	5
Overall Study Lack of Efficacy	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Early-stage Parkinson's Disease n=21 Participants	Advanced Parkinson's Disease n=43 Participants	Total n=64 Participants Total of all reporting groups
Age, Continuous	64.3 years STANDARD_DEVIATION 6.9 • n=93 Participants	64.7 years STANDARD_DEVIATION 7.6 • n=4 Participants	64.6 years STANDARD_DEVIATION 7.3 • n=27 Participants
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Age, Categorical Between 18 and 65 years	12 Participants n=93 Participants	20 Participants n=4 Participants	32 Participants n=27 Participants
Age, Categorical >=65 years	9 Participants n=93 Participants	23 Participants n=4 Participants	32 Participants n=27 Participants
Sex: Female, Male Female	12 Participants n=93 Participants	29 Participants n=4 Participants	41 Participants n=27 Participants
Sex: Female, Male Male	9 Participants n=93 Participants	14 Participants n=4 Participants	23 Participants n=27 Participants
Region of Enrollment Japan	21 participants n=93 Participants	43 participants n=4 Participants	64 participants n=27 Participants

PRIMARY outcome

Timeframe: Up to 12 weeks after dosing

Population: Subjects in the safety analysis set who entered the maintenance period

The maintenance dose of the SPM 962 was examined based on the safety and efficacy.

Outcome measures

Measure	Early-stage Parkinson's Disease n=17 Participants Subjects with early Parkinson's disease received SPM 962 transdermal patch	Advanced Parkinson's Disease n=40 Participants Subjects with advanced Parkinson's disease received SPM 962 transdermal patch
Maintenance Dose of the SPM962 13.5 mg	0 participants	5 participants
Maintenance Dose of the SPM962 27.0 mg	2 participants	9 participants
Maintenance Dose of the SPM962 4.5 mg	0 participants	0 participants
Maintenance Dose of the SPM962 9.0 mg	0 participants	1 participants
Maintenance Dose of the SPM962 18.0 mg	3 participants	5 participants
Maintenance Dose of the SPM962 22.5 mg	2 participants	9 participants
Maintenance Dose of the SPM962 31.5 mg	2 participants	3 participants
Maintenance Dose of the SPM962 36.0 mg	8 participants	8 participants

SECONDARY outcome

Timeframe: Up to 12 weeks after dosing

Population: Safety analysis set

Incidence and severity of adverse events, vital signs, and laboratory parameters following the initiation of study treatment.

Outcome measures

Measure	Early-stage Parkinson's Disease n=21 Participants Subjects with early Parkinson's disease received SPM 962 transdermal patch	Advanced Parkinson's Disease n=43 Participants Subjects with advanced Parkinson's disease received SPM 962 transdermal patch
Incidence and Severity of Adverse Events, Vital Signs, and Laboratory Parameters Any AEs	20 participants	41 participants
Incidence and Severity of Adverse Events, Vital Signs, and Laboratory Parameters Treatment-related AEs	19 participants	36 participants
Incidence and Severity of Adverse Events, Vital Signs, and Laboratory Parameters SAEs	1 participants	3 participants
Incidence and Severity of Adverse Events, Vital Signs, and Laboratory Parameters Severe AEs	1 participants	1 participants
Incidence and Severity of Adverse Events, Vital Signs, and Laboratory Parameters Discontinuation due to AEs	5 participants	5 participants
Incidence and Severity of Adverse Events, Vital Signs, and Laboratory Parameters Death	0 participants	0 participants
Incidence and Severity of Adverse Events, Vital Signs, and Laboratory Parameters AEs related to laboratory parameters	7 participants	8 participants
Incidence and Severity of Adverse Events, Vital Signs, and Laboratory Parameters Discontinuation due to AEs related to labs	0 participants	1 participants
Incidence and Severity of Adverse Events, Vital Signs, and Laboratory Parameters Clinically significant QTc prolongation	0 participants	0 participants

SECONDARY outcome

Timeframe: baseline, 12 weeks after dosing

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

Mean change (LOCF) from baseline in Total of UPDRS Part 2 sum score and Part 3 sum 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 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

Measure	Early-stage Parkinson's Disease n=21 Participants Subjects with early Parkinson's disease received SPM 962 transdermal patch	Advanced Parkinson's Disease Subjects with advanced Parkinson's disease received SPM 962 transdermal patch
Total of Unified Parkinson's Disease Rating Scale (UPDRS) Part 2 Sum Score and Part 3 Sum Score for Early Parkinson's Disease Without Concomitant L-dopa Therapy	-8.4 Scores on a scale Standard Deviation 11.2	—

SECONDARY outcome

Timeframe: baseline, 12 weeks after dosing

Population: Efficacy analysis set, LOCF

Mean change (LOCF) from baseline in UPDRS Part 3 sum score at 12 weeks after dosing.

UPDRS sub-scale 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

Measure	Early-stage Parkinson's Disease Subjects with early Parkinson's disease received SPM 962 transdermal patch	Advanced Parkinson's Disease n=43 Participants Subjects with advanced Parkinson's disease received SPM 962 transdermal patch
UPDRS Part 3 Sum Score for Advanced Parkinson's Disease With Concomitant L-dopa Therapy	—	-11.7 Scores on a scale Standard Deviation 10.1

SECONDARY outcome

Timeframe: Baseline, 12 weeks after dosing

Population: Efficacy analysis set, LOCF

Mean change (LOCF) from baseline in UPDRS Part 2 sum score 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

Measure	Early-stage Parkinson's Disease n=21 Participants Subjects with early Parkinson's disease received SPM 962 transdermal patch	Advanced Parkinson's Disease Subjects with advanced Parkinson's disease received SPM 962 transdermal patch
UPDRS Part 2 Sum Score for Early Parkinson's Disease Without Concomitant L-dopa Therapy	-1.5 Scores on a scale Standard Deviation 2.4	—

SECONDARY outcome

Timeframe: Baseline, 12 weeks after dosing

Population: Efficacy analysis set, LOCF

Mean change (LOCF) from baseline in UPDRS Part 3 sum score at 12 weeks after dosing.

UPDRS sub-scale 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

Measure	Early-stage Parkinson's Disease n=21 Participants Subjects with early Parkinson's disease received SPM 962 transdermal patch	Advanced Parkinson's Disease Subjects with advanced Parkinson's disease received SPM 962 transdermal patch
UPDRS Part 3 Sum Score for Early Parkinson's Disease Without Concomitant L-dopa Therapy	-6.9 Scores on a scale Standard Deviation 9.0	—

SECONDARY outcome

Timeframe: Baseline, 12 weeks after dosing

Population: Efficacy analysis set, 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

Measure	Early-stage Parkinson's Disease Subjects with early Parkinson's disease received SPM 962 transdermal patch	Advanced Parkinson's Disease n=43 Participants Subjects with advanced Parkinson's disease received SPM 962 transdermal patch
UPDRS Part 2 Sum Score (on State) for Advanced Parkinson's Disease With Concomitant L-dopa Therapy.	—	-2.6 Scores on a scale Standard Deviation 3.2

SECONDARY outcome

Timeframe: Baseline, 12 weeks after dosing

Population: Efficacy analysis set, 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

Measure	Early-stage Parkinson's Disease Subjects with early Parkinson's disease received SPM 962 transdermal patch	Advanced Parkinson's Disease n=35 Participants Subjects with advanced Parkinson's disease received SPM 962 transdermal patch
UPDRS Part 2 Sum Score (Off State) for Advanced Parkinson's Disease With Concomitant L-dopa Therapy.	—	-4.0 Scores on a scale Standard Deviation 5.2

SECONDARY outcome

Timeframe: Baseline, 12 weeks after dosing

Population: Efficacy analysis set, LOCF

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

Measure	Early-stage Parkinson's Disease Subjects with early Parkinson's disease received SPM 962 transdermal patch	Advanced Parkinson's Disease n=41 Participants Subjects with advanced Parkinson's disease received SPM 962 transdermal patch
UPDRS Part 2 Sum Score (Average Score of on State and Off State) for Advanced Parkinson's Disease With Concomitant L-dopa Therapy	—	-3.2 Scores on a scale Standard Deviation 3.7

SECONDARY outcome

Timeframe: Baseline, 12 weeks after dosing

Population: Efficacy analysis set, LOCF

Mean change (LOCF) from baseline in Total of UPDRS Part 2 sum score (average score of on state and off state) and 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

Measure	Early-stage Parkinson's Disease Subjects with early Parkinson's disease received SPM 962 transdermal patch	Advanced Parkinson's Disease n=41 Participants Subjects with advanced Parkinson's disease received SPM 962 transdermal patch
Total of UPDRS Part 2 Sum Score (Average Score of on State and Off State) and Part 3 Sum Score for Advanced Parkinson's Disease With Concomitant L-dopa Therapy	—	-14.0 Scores on a scale Standard Deviation 11.6

SECONDARY outcome

Timeframe: Baseline, 12 weeks after dosing

Population: Subjects with measurable off time data at baseline and after dosing, LOCF

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

Outcome measures

Measure	Early-stage Parkinson's Disease Subjects with early Parkinson's disease received SPM 962 transdermal patch	Advanced Parkinson's Disease n=43 Participants Subjects with advanced Parkinson's disease received SPM 962 transdermal patch
Off Time for Advanced Parkinson's Disease With Concomitant L-dopa Therapy	—	-1.98 Hours Standard Deviation 1.3

Adverse Events

Early-stage Parkinson's Disease

Serious events: 1 serious events

Other events: 20 other events

Deaths: 0 deaths

Advanced Parkinson's Disease

Serious events: 3 serious events

Other events: 41 other events

Deaths: 0 deaths

Serious adverse events

Measure	Early-stage Parkinson's Disease n=21 participants at risk	Advanced Parkinson's Disease n=43 participants at risk
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Carcinoma Prostate	4.8% 1/21 • Number of events 1 • 5 to 13 weeks depending on maintenance dose	0.00% 0/43 • 5 to 13 weeks depending on maintenance dose
Infections and infestations Pneumonia	0.00% 0/21 • 5 to 13 weeks depending on maintenance dose	2.3% 1/43 • Number of events 1 • 5 to 13 weeks depending on maintenance dose
Psychiatric disorders Abnormal Behaviour	0.00% 0/21 • 5 to 13 weeks depending on maintenance dose	2.3% 1/43 • Number of events 1 • 5 to 13 weeks depending on maintenance dose
Psychiatric disorders Suicide Attempt	0.00% 0/21 • 5 to 13 weeks depending on maintenance dose	2.3% 1/43 • Number of events 1 • 5 to 13 weeks depending on maintenance dose

Other adverse events

Measure	Early-stage Parkinson's Disease n=21 participants at risk	Advanced Parkinson's Disease n=43 participants at risk
Gastrointestinal disorders Nausea	38.1% 8/21 • Number of events 9 • 5 to 13 weeks depending on maintenance dose	20.9% 9/43 • Number of events 10 • 5 to 13 weeks depending on maintenance dose
Gastrointestinal disorders Vomiting	19.0% 4/21 • Number of events 4 • 5 to 13 weeks depending on maintenance dose	11.6% 5/43 • Number of events 8 • 5 to 13 weeks depending on maintenance dose
Gastrointestinal disorders Constipation	14.3% 3/21 • Number of events 3 • 5 to 13 weeks depending on maintenance dose	9.3% 4/43 • Number of events 4 • 5 to 13 weeks depending on maintenance dose
Gastrointestinal disorders Stomatitis	9.5% 2/21 • Number of events 2 • 5 to 13 weeks depending on maintenance dose	0.00% 0/43 • 5 to 13 weeks depending on maintenance dose
General disorders Administration Site Reaction	76.2% 16/21 • Number of events 16 • 5 to 13 weeks depending on maintenance dose	46.5% 20/43 • Number of events 20 • 5 to 13 weeks depending on maintenance dose
General disorders Thirst	9.5% 2/21 • Number of events 2 • 5 to 13 weeks depending on maintenance dose	4.7% 2/43 • Number of events 2 • 5 to 13 weeks depending on maintenance dose
Infections and infestations Nasopharyngitis	28.6% 6/21 • Number of events 6 • 5 to 13 weeks depending on maintenance dose	9.3% 4/43 • Number of events 4 • 5 to 13 weeks depending on maintenance dose
Investigations Blood Urea Increased	14.3% 3/21 • Number of events 3 • 5 to 13 weeks depending on maintenance dose	2.3% 1/43 • Number of events 1 • 5 to 13 weeks depending on maintenance dose
Investigations Blood Creatine Phosphokinase Increased	4.8% 1/21 • Number of events 1 • 5 to 13 weeks depending on maintenance dose	9.3% 4/43 • Number of events 4 • 5 to 13 weeks depending on maintenance dose
Investigations Blood Urine Present	9.5% 2/21 • Number of events 2 • 5 to 13 weeks depending on maintenance dose	4.7% 2/43 • Number of events 2 • 5 to 13 weeks depending on maintenance dose
Metabolism and nutrition disorders Anorexia	9.5% 2/21 • Number of events 2 • 5 to 13 weeks depending on maintenance dose	11.6% 5/43 • Number of events 5 • 5 to 13 weeks depending on maintenance dose
Metabolism and nutrition disorders Decreased Appetite	0.00% 0/21 • 5 to 13 weeks depending on maintenance dose	7.0% 3/43 • Number of events 3 • 5 to 13 weeks depending on maintenance dose
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/21 • 5 to 13 weeks depending on maintenance dose	11.6% 5/43 • Number of events 5 • 5 to 13 weeks depending on maintenance dose
Nervous system disorders Somnolence	19.0% 4/21 • Number of events 5 • 5 to 13 weeks depending on maintenance dose	16.3% 7/43 • Number of events 8 • 5 to 13 weeks depending on maintenance dose
Nervous system disorders Dizziness	14.3% 3/21 • Number of events 4 • 5 to 13 weeks depending on maintenance dose	7.0% 3/43 • Number of events 3 • 5 to 13 weeks depending on maintenance dose
Nervous system disorders Parkinson's Disease	0.00% 0/21 • 5 to 13 weeks depending on maintenance dose	11.6% 5/43 • Number of events 5 • 5 to 13 weeks depending on maintenance dose
Nervous system disorders Dizziness Postural	9.5% 2/21 • Number of events 2 • 5 to 13 weeks depending on maintenance dose	0.00% 0/43 • 5 to 13 weeks depending on maintenance dose
Nervous system disorders Dyskinesia	0.00% 0/21 • 5 to 13 weeks depending on maintenance dose	7.0% 3/43 • Number of events 3 • 5 to 13 weeks depending on maintenance dose
Nervous system disorders hypoesthesia	0.00% 0/21 • 5 to 13 weeks depending on maintenance dose	7.0% 3/43 • Number of events 3 • 5 to 13 weeks depending on maintenance dose
Psychiatric disorders Insomnia	19.0% 4/21 • Number of events 4 • 5 to 13 weeks depending on maintenance dose	9.3% 4/43 • Number of events 4 • 5 to 13 weeks depending on maintenance dose
Psychiatric disorders Hallucination Visual	0.00% 0/21 • 5 to 13 weeks depending on maintenance dose	9.3% 4/43 • Number of events 4 • 5 to 13 weeks depending on maintenance dose
Vascular disorders Orthostatic Hypotension	0.00% 0/21 • 5 to 13 weeks depending on maintenance dose	7.0% 3/43 • Number of events 3 • 5 to 13 weeks depending on maintenance dose

Additional Information

Director of Clinical Research and Development

Otsuka Pharmaceutical Co., Ltd.

Phone: +81-3-6361-7366

Results disclosure agreements

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