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

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

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01634243

Enrollment

Registered

2012-07-06

Start date

2005-01-31

Completion date

2006-05-31

Last updated

2014-03-19

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Parkinson's Disease

Keywords

SPM 962, rotigotine, Parkinson's disease

Brief summary

The primary objective of this trial is to establish the maximum maintenance dose of SPM 962 in patients with Parkinson's disease in a multi-center, uncontrolled, open-label study by conducting safety evaluation of each patient following once-daily transdermal doses of SPM 962 within a range of 4.5 to 36.0 mg. (The administration period will consist of a standard 8-week dose-titration period, 4-week dose-maintenance period, and a dose de-escalation period) Exploratory evaluation of each patient's maintenance dose will also be conducted with attention to patient safety. The relationship of pharmacokinetics, safety, and efficacy will also be examined.

Interventions

DRUGSPM 962

SPM 962 transdermal patch once a daily up to 36.0 mg/day

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

30 Years to 79 Years

Healthy volunteers

Inclusion criteria

* For subject with early and advanced Parkinson's disease * Subject diagnosed as having Parkinson's disease in accordance with Diagnostic Criteria established by the Research Committee of MHLW-specified Intractable Neurodegenerative Diseases (1995). * Subject is 30 and more and less than 80 years of age at the time of informed consent. * Gender and inpatient-outpatient status are not specified. * For subject with early Parkinson's disease * Hoehn & Yahr stage 3 or less. * Subject who has not taken L-dopa within 28 days prior to initial administration of SPM 962. * For subject with dvanced Parkinson's disease * Hoehn & Yahr stage 2-4. * Subject is on a stable dose of L-dopa with no change in daily dose or dosing regimen for at least 7 days prior to the initial treatment of SPM 962. * Subject has any of the following problematic symptoms; 1) Wearing off phenomenon 2) On and off phenomenon 3) Not well controlled with L-dopa due to adverse effect 4) Weakening of L-dopa efficacy.

Exclusion criteria

* Subject is on other dopamine agonist treatment within 7 days prior to the initial treatment. Subject is on cabergoline treatment within 14 days prior to the initial treatment. * Subject has psychiatric symptoms, e.g. confusion, hallucination, delusion, excitation, delirium, abnormal behavior. * Subject has orthostatic hypotension. * Subject has a history of epilepsy, convulsion and other. * Subject has a complication of serious cardiac disorder or has the history. * Subject has arrhythmia and treated with class 1a antiarrhythmic drugs (e.g. quinidine, procainamide etc.) or class 3 antiarrhythmic drugs (e.g. amiodarone, sotalol etc.). * At screening and baseline, subject develops serious ECG abnormality. Subjects has QTc-interval \>450 msec at screening. Subject has QTc-interval \>450 msec in males and \>470 msec in females at baseline. * Subject has congenital long QT syndrome. * Subject has hypokalaemia. * Subject has a total bilirubin \>= 3.0 mg/dL or AST(GOT) or ALT(GPT) greater than 2.5 times of the upper limit of the reference range (or \>= 100 IU/L). * Subject has BUN \>= 25 mg/dL or serum creatinine \>= 2.0 mg/dl. * Subject has a history of allergic reaction to topical agents such as transdermal patch. * Subject is pregnant or nursing or woman who plans pregnancy during the trial. * Subject is receiving therapy with prohibited drug specified in the study protocol. * Subject has a history of pallidotomy, thalamotomy, deep brain stimulation or fetal tissue transplant. * Subject has dementia. * Subject is unable to give consent. * Subject is participating in another trial of an investigational drug or done so within 6 months prior to the initial treatment. * Investigator judges that subject is inappropriate as a study subject with other reasons.

Design outcomes

Primary

Measure	Time frame	Description
Maintenance Dose of the SPM962	Up to 12 weeks after dosing	The maintenance dose of the SPM 962 was examined based on the safety and efficacy.

Secondary

Measure	Time frame	Description
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	baseline, 12 weeks after dosing	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.
UPDRS Part 3 Sum Score for Advanced Parkinson's Disease With Concomitant L-dopa Therapy	baseline, 12 weeks after dosing	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.
UPDRS Part 2 Sum Score for Early Parkinson's Disease Without Concomitant L-dopa Therapy	Baseline, 12 weeks after dosing	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.
UPDRS Part 3 Sum Score for Early Parkinson's Disease Without Concomitant L-dopa Therapy	Baseline, 12 weeks after dosing	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.
Incidence and Severity of Adverse Events, Vital Signs, and Laboratory Parameters	Up to 12 weeks after dosing	Incidence and severity of adverse events, vital signs, and laboratory parameters following the initiation of study treatment.
UPDRS Part 2 Sum Score (Off State) for Advanced Parkinson's Disease With Concomitant L-dopa Therapy.	Baseline, 12 weeks after dosing	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.
UPDRS Part 2 Sum Score (Average Score of on State and Off State) for Advanced Parkinson's Disease With Concomitant L-dopa Therapy	Baseline, 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.
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	Baseline, 12 weeks after dosing	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.
Off Time for Advanced Parkinson's Disease With Concomitant L-dopa Therapy	Baseline, 12 weeks after dosing	Mean change (LOCF) from baseline in off time at 12 weeks after dosing.
UPDRS Part 2 Sum Score (on State) for Advanced Parkinson's Disease With Concomitant L-dopa Therapy.	Baseline, 12 weeks after dosing	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.

Countries

Japan

Participant flow

Participants by arm

Arm	Count
Early-stage Parkinson's Disease	21
Advanced Parkinson's Disease	43
Total	64

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	5	5
Overall Study	Lack of Efficacy	1	0

Baseline characteristics

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

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	20 / 21	41 / 43
serious Total, serious adverse events	1 / 21	3 / 43

Outcome results

Primary

Maintenance Dose of the SPM962

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

Time frame: Up to 12 weeks after dosing

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

Arm	Measure	Group	Value (NUMBER)
Early-stage Parkinson's Disease	Maintenance Dose of the SPM962	4.5 mg	0 participants
Early-stage Parkinson's Disease	Maintenance Dose of the SPM962	9.0 mg	0 participants
Early-stage Parkinson's Disease	Maintenance Dose of the SPM962	13.5 mg	0 participants
Early-stage Parkinson's Disease	Maintenance Dose of the SPM962	18.0 mg	3 participants
Early-stage Parkinson's Disease	Maintenance Dose of the SPM962	22.5 mg	2 participants
Early-stage Parkinson's Disease	Maintenance Dose of the SPM962	27.0 mg	2 participants
Early-stage Parkinson's Disease	Maintenance Dose of the SPM962	31.5 mg	2 participants
Early-stage Parkinson's Disease	Maintenance Dose of the SPM962	36.0 mg	8 participants
Advanced Parkinson's Disease	Maintenance Dose of the SPM962	36.0 mg	8 participants
Advanced Parkinson's Disease	Maintenance Dose of the SPM962	4.5 mg	0 participants
Advanced Parkinson's Disease	Maintenance Dose of the SPM962	22.5 mg	9 participants
Advanced Parkinson's Disease	Maintenance Dose of the SPM962	9.0 mg	1 participants
Advanced Parkinson's Disease	Maintenance Dose of the SPM962	31.5 mg	3 participants
Advanced Parkinson's Disease	Maintenance Dose of the SPM962	13.5 mg	5 participants
Advanced Parkinson's Disease	Maintenance Dose of the SPM962	27.0 mg	9 participants
Advanced Parkinson's Disease	Maintenance Dose of the SPM962	18.0 mg	5 participants

Secondary

Incidence and Severity of Adverse Events, Vital Signs, and Laboratory Parameters

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

Time frame: Up to 12 weeks after dosing

Population: Safety analysis set

Arm	Measure	Group	Value (NUMBER)
Early-stage Parkinson's Disease	Incidence and Severity of Adverse Events, Vital Signs, and Laboratory Parameters	Treatment-related AEs	19 participants
Early-stage Parkinson's Disease	Incidence and Severity of Adverse Events, Vital Signs, and Laboratory Parameters	Death	0 participants
Early-stage Parkinson's Disease	Incidence and Severity of Adverse Events, Vital Signs, and Laboratory Parameters	Severe AEs	1 participants
Early-stage Parkinson's Disease	Incidence and Severity of Adverse Events, Vital Signs, and Laboratory Parameters	AEs related to laboratory parameters	7 participants
Early-stage Parkinson's Disease	Incidence and Severity of Adverse Events, Vital Signs, and Laboratory Parameters	SAEs	1 participants
Early-stage Parkinson's Disease	Incidence and Severity of Adverse Events, Vital Signs, and Laboratory Parameters	Discontinuation due to AEs related to labs	0 participants
Early-stage Parkinson's Disease	Incidence and Severity of Adverse Events, Vital Signs, and Laboratory Parameters	Discontinuation due to AEs	5 participants
Early-stage Parkinson's Disease	Incidence and Severity of Adverse Events, Vital Signs, and Laboratory Parameters	Clinically significant QTc prolongation	0 participants
Early-stage Parkinson's Disease	Incidence and Severity of Adverse Events, Vital Signs, and Laboratory Parameters	Any AEs	20 participants
Advanced Parkinson's Disease	Incidence and Severity of Adverse Events, Vital Signs, and Laboratory Parameters	Clinically significant QTc prolongation	0 participants
Advanced Parkinson's Disease	Incidence and Severity of Adverse Events, Vital Signs, and Laboratory Parameters	Any AEs	41 participants
Advanced Parkinson's Disease	Incidence and Severity of Adverse Events, Vital Signs, and Laboratory Parameters	Treatment-related AEs	36 participants
Advanced Parkinson's Disease	Incidence and Severity of Adverse Events, Vital Signs, and Laboratory Parameters	SAEs	3 participants
Advanced Parkinson's Disease	Incidence and Severity of Adverse Events, Vital Signs, and Laboratory Parameters	Severe AEs	1 participants
Advanced Parkinson's Disease	Incidence and Severity of Adverse Events, Vital Signs, and Laboratory Parameters	Discontinuation due to AEs	5 participants
Advanced Parkinson's Disease	Incidence and Severity of Adverse Events, Vital Signs, and Laboratory Parameters	Death	0 participants
Advanced Parkinson's Disease	Incidence and Severity of Adverse Events, Vital Signs, and Laboratory Parameters	AEs related to laboratory parameters	8 participants
Advanced Parkinson's Disease	Incidence and Severity of Adverse Events, Vital Signs, and Laboratory Parameters	Discontinuation due to AEs related to labs	1 participants

Secondary

Off Time for Advanced Parkinson's Disease With Concomitant L-dopa Therapy

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

Time frame: Baseline, 12 weeks after dosing

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

Arm	Measure	Value (MEAN)	Dispersion
Advanced Parkinson's Disease	Off Time for Advanced Parkinson's Disease With Concomitant L-dopa Therapy	-1.98 Hours	Standard Deviation 1.3

Secondary

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

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.

Time frame: baseline, 12 weeks after dosing

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

Arm	Measure	Value (MEAN)	Dispersion
Early-stage Parkinson's Disease	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

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

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.

Time frame: Baseline, 12 weeks after dosing