Back to resultsA Clinical Study of Efficacy, Safety, Tolerability and PK of ND0612H in Subjects With Advanced Parkinson's Disease
Primary Purpose
Parkinson's Disease
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
ND0612 (Levodopa/Carbidopa solution)
ND0612 (Levodopa/Carbidopa solution) + morning oral IR-LD/CD
Sponsored by
About this trial
This is an interventional treatment trial for Parkinson's Disease
Eligibility Criteria
Inclusion Criteria:
- Male and female PD subjects of any race aged 30 to 80 years who sign an Institutional Review Board/Ethics Committee (IRB/EC)-approved informed consent form (ICF).
- PD diagnosis consistent with the UK Brain Bank Criteria.
- Modified Hoehn & Yahr scale in "ON" state of stage ≤3.
- Taking at least 4 doses/day of LD (or at least 3 doses/day of Rytary) and taking, or have attempted to take, at least 2 other classes of anti-PD medications in a therapeutic dose for at least 30 consecutive days each.
- Subjects must be stable on their anti-PD medications for at least 30 days before Day 1.
- Subjects may have had prior exposure to SC apomorphine injections/infusion but must have stopped administration at least 4 weeks before the screening visit. Treatment with apomorphine is prohibited during the entire ND0612H treatment period.
- Must have a minimum of 2.5 hrs of "OFF" time per day with predictable early morning "OFF" periods as estimated by the subject.
- Must have predictable and well defined early morning "OFF" periods with a good response to LD for treatment of the early morning "OFF" in the judgement of the investigator.
- Mini Mental State Examination (MMSE) score >26.
- No clinically significant medical, psychiatric or laboratory abnormalities which the investigator judges would be unsafe or non-compliant in the study.
- Female subjects must be surgically sterile, postmenopausal (defined as cessation of menses for at least 1 year), or willing to practice a highly effective method of contraception. All female participants must be non-lactating and non-pregnant and have a negative urine pregnancy test at Screening and at Baseline. Female subjects of childbearing potential must practice a highly effective method of contraception (e.g., oral contraceptives, a barrier method of birth control [e.g., condoms with contraceptive foams, diaphragms with contraceptive jelly], intrauterine devices, partner with vasectomy), 1 month before enrollment, for the duration of the study, and 3 months after the last dose of study drug.
- Willingness and ability to comply with study requirements
Exclusion Criteria:
- Atypical or secondary parkinsonism.
- Acute psychosis or hallucinations in past 6 months.
- Any relevant medical, surgical, or psychiatric condition, laboratory value, or concomitant medication which, in the opinion of the Investigator or the eligibility reviewer, makes the subject unsuitable for study entry or potentially unable to complete all aspects of the study.
- Prior neurosurgical procedure for PD, or duodopa treatment.
- Subjects with a history of drug abuse or alcoholism within the past 12 months.
- Clinically significant ECG rhythm abnormalities.
- Renal or liver dysfunction that may alter drug metabolism including: serum creatinine >1.3 mg/dL, serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2 x upper limit of normal (ULN), total serum bilirubin >2.5 mg/dL.
- Subjects who are not willing to operate the pump system.
Sites / Locations
- Northwestern University
- QUEST Research Institute
- University of Cincinnati
- Medical University Innsbruck
- Rabin Medical Center
- Chaim Sheba Medical Center
- Sourasky Medical Center
- University Foundation
- AOU Pisa
- IRCCS San Raffaele Pisana
- Fondazione Ospedale San Camillo - I.R.C.C.S.
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
ND0612 (Levodopa/Carbidopa solution) Dosing Regimen 1
ND0612 (Levodopa/Carbidopa solution) Dosing Regimen 2
Arm Description
Dosing Regimen 1 of ND0612 (Levodopa/Carbidopa solution) continuous SC infusion over 24 hours.
Dosing Regimen 2 of ND0612 (Levodopa/Carbidopa solution) continuous SC infusion over 14 hours. Infusion started at wake-up time supplemented with an oral IR LD/CD tablet.
Outcomes
Primary Outcome Measures
Change in Daily "OFF" Time
Based on Parkinson's disease symptom assessment, "ON" time is when there is good response to medication and few symptoms. "OFF" time is when no there is no response to medication and significant motor symptoms. An "ON/OFF" Log was completed by a blinded rater starting before the first dose of LD/DDI and following the first dose at 30 min intervals for 8 hrs. The changes in "OFF" time as hours (normalized to 16 hrs of awake time) during the 8 hrs of data collection were estimated. Negative change from baseline for "OFF" time indicates improvement.
Secondary Outcome Measures
The Percentage of Subjects With Full "ON" at Approximately 08:00 and Approximately 09:00, as Determined by the Subject
Based on Parkinson's disease symptom assessment, "ON" time is when there is good response to medication and few symptoms. "OFF" time is when no there is no response to medication and significant motor symptoms. Subjects were asked to indicate when exactly in their opinion they had turned to full "ON" (i.e. an "ON" response comparable to the "ON" response to standard oral LD/DDI treatment). Higher percentage of subjects with full "ON" on Day 28 indicates improvement.
Change in Daily "Good ON" Time as Assessed by a Blinded Rater
Based on Parkinson's disease symptom assessment, "ON" time is when there is good response to medication and few symptoms. "OFF" time is when no there is no response to medication and significant motor symptoms. "Good ON" time means "ON" time without troublesome dyskinesia (involuntary muscle movement), defined as the sum of "ON" time without dyskinesia and "ON" time with non-troublesome dyskinesia. An "ON/OFF" Log was completed by a blinded rater starting before the first dose of LD/DDI and following the first dose at 30 min intervals for 8 hrs. Daily total scores were normalized to 16 hours of awake time. Positive change from baseline for "ON" time without dyskinesia and for "Good ON" time, and a negative change in "ON" time with moderate or severe (troublesome) dyskinesia indicates improvement.
Change in Morning UPDRS Part III (Motor) Scores
The Unified Parkinson's Disease Rating Scale (UPDRS) is an Investigator-used rating tool to follow the longitudinal course of Parkinson's disease. UPDRS part III (motor) score is calculated as the sum of the individual UPDRS items 18-31, each of which are measured on a 5-point scale (i.e., 0 is normal and 4 indicates a severe abnormality). UPDRS part III was done as a motor examination on Day 1 before the first dose of standard oral LD/DDI and at the same time on Day 28. The range of score values is from 0 to 132. Higher scores correlate with greater motor impairment.
Change in UPDRS Part II (ADL) Scores
The Unified Parkinson's disease rating scale (UPDRS) is an Investigator-used rating tool to follow the longitudinal course of Parkinson's disease. The UPDRS Part II (activity of daily living) score was calculated as the sum of the individual UPDRS items 5-17. The Part II score is the sum of the answers to the 13 questions that comprise Part II, each of which are measured on a 5-point scale (i.e., 0 is normal and 4 indicates a severe abnormality). The range of score values is from 0 to 52. Higher scores correlate with greater impairments for daily activities.
CGI-Improvement (CGI-I) Score as Assessed by Investigator
Global improvement was rated by the investigator or designee using Clinical Global Impression of Improvement (CGI-I). The CGI-I employs a 7-point scale with 1 being "very much improved" and 7 being "very much worse" for improvement rating.
Change in PDSS-2 Total Score
The quality of night sleep was rated by the subjects using the Parkinson's Disease Sleep Scale (PDSS)-2, which includes questions addressing 15 commonly reported symptoms associated with sleep disturbance in PD. Each question is assessed from 0 (Always) to 10 (Never). The total score values range from 0 to 150. Higher scores indicate a lower quality of sleep, i.e., a reduction in the score indicates an improvement in sleep quality.
Change in PDQ-39 Summary Index and the 8-dimension Scores
Subjects were requested to rate their quality of life using the Quality of Life in Parkinson's Disease (PDQ)-39, a 39-item, self-administered questionnaire with 8 discrete dimensions (mobility, activities of daily living, emotional well-being, stigma, social support, cognition, communication, and bodily discomfort.). The PDQ-39 Summary Index is the sum of the dimension scores divided by the number of dimensions. The total score values range from 0 to 100%. Higher scores indicate a worse quality of life.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02577523
Brief Title
A Clinical Study of Efficacy, Safety, Tolerability and PK of ND0612H in Subjects With Advanced Parkinson's Disease
Official Title
A Multicenter, Parallel-group, Rater-blinded, Randomized Clinical Study Investigating the Efficacy, Safety, Tolerability and Pharmacokinetics of 2 Dosing Regimens of ND0612H [ ] in Subjects With Advanced Parkinson's Disease
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Completed
Study Start Date
December 29, 2015 (Actual)
Primary Completion Date
December 20, 2016 (Actual)
Study Completion Date
January 31, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
NeuroDerm Ltd.
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is a multicenter, parallel-group, rater-blinded, randomized clinical study in subjects with advanced PD investigating the efficacy, PK, safety and tolerability of continuous SC infusion of 2 dosing regimens of ND0612H, a solution of LD/CD delivered via a pump system as a continuous SC infusion, compared to standard oral LD/CD. After screening, subjects will undergo 1 day of standard oral LD/CD inpatient dosing followed by 2 days of inpatient treatment with 1 of 2 randomly allocated (1:1 randomization ratio) dosing regimens of ND0612H continuous SC infusion. Subjects will then continue on a maintenance dose of the assigned ND0612H dosing regimen for the next 25 days. A safety visit will be performed 4 weeks after the last SC administration of the study drug for a total of about 2.5 months of participation for each subject enrolled into the trial.
Detailed Description
This phase IIa randomized, controlled, parallel-group study will be conducted in 36 subjects with advanced PD who are treated with oral LD/CD at a stable dose and have predictable morning "OFF" periods and at least 2.5 hrs of daily "OFF" periods. The study will investigate the efficacy, PK, safety and tolerability of continuous SC infusion of 2 dosing regimens of ND0612H. Regimen 1 will employ continuous infusion for 24 hrs using a low infusion rate at night and a higher rate at daytime with supplemental administration of oral immediate release (IR) LD/CD in the mornings. During the inpatient period of about 3 days, the site staff will manage the administration and replacement of the infusions. On Day 4 subjects will be discharged home after they and their study partners have received training on the administration of the infusion. Subjects will then continue on a maintenance dose of the assigned ND0612 dosing regimen for the next 25 days. A safety visit will be performed 4 weeks after the last SC administration of the study drug.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Parkinson's Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
38 (Actual)
8. Arms, Groups, and Interventions
Arm Title
ND0612 (Levodopa/Carbidopa solution) Dosing Regimen 1
Arm Type
Experimental
Arm Description
Dosing Regimen 1 of ND0612 (Levodopa/Carbidopa solution) continuous SC infusion over 24 hours.
Arm Title
ND0612 (Levodopa/Carbidopa solution) Dosing Regimen 2
Arm Type
Experimental
Arm Description
Dosing Regimen 2 of ND0612 (Levodopa/Carbidopa solution) continuous SC infusion over 14 hours. Infusion started at wake-up time supplemented with an oral IR LD/CD tablet.
Intervention Type
Drug
Intervention Name(s)
ND0612 (Levodopa/Carbidopa solution)
Other Intervention Name(s)
Regimen 1 - 24-hr infusion
Intervention Description
The total daily dose of levodopa/carbidopa 720/90 mg. Device: CRONO TWIN pump system.
Intervention Type
Drug
Intervention Name(s)
ND0612 (Levodopa/Carbidopa solution) + morning oral IR-LD/CD
Other Intervention Name(s)
Regimen 2 - 14-hr infusion
Intervention Description
The total daily dose levodopa/carbidopa from ND0612 538/67 mg. Morning dose of oral IR-LD/CD 150/15 mg. Device: CRONO TWIN pump system.
Primary Outcome Measure Information:
Title
Change in Daily "OFF" Time
Description
Based on Parkinson's disease symptom assessment, "ON" time is when there is good response to medication and few symptoms. "OFF" time is when no there is no response to medication and significant motor symptoms. An "ON/OFF" Log was completed by a blinded rater starting before the first dose of LD/DDI and following the first dose at 30 min intervals for 8 hrs. The changes in "OFF" time as hours (normalized to 16 hrs of awake time) during the 8 hrs of data collection were estimated. Negative change from baseline for "OFF" time indicates improvement.
Time Frame
Baseline to Day 28
Secondary Outcome Measure Information:
Title
The Percentage of Subjects With Full "ON" at Approximately 08:00 and Approximately 09:00, as Determined by the Subject
Description
Based on Parkinson's disease symptom assessment, "ON" time is when there is good response to medication and few symptoms. "OFF" time is when no there is no response to medication and significant motor symptoms. Subjects were asked to indicate when exactly in their opinion they had turned to full "ON" (i.e. an "ON" response comparable to the "ON" response to standard oral LD/DDI treatment). Higher percentage of subjects with full "ON" on Day 28 indicates improvement.
Time Frame
Baseline to Day 28
Title
Change in Daily "Good ON" Time as Assessed by a Blinded Rater
Description
Based on Parkinson's disease symptom assessment, "ON" time is when there is good response to medication and few symptoms. "OFF" time is when no there is no response to medication and significant motor symptoms. "Good ON" time means "ON" time without troublesome dyskinesia (involuntary muscle movement), defined as the sum of "ON" time without dyskinesia and "ON" time with non-troublesome dyskinesia. An "ON/OFF" Log was completed by a blinded rater starting before the first dose of LD/DDI and following the first dose at 30 min intervals for 8 hrs. Daily total scores were normalized to 16 hours of awake time. Positive change from baseline for "ON" time without dyskinesia and for "Good ON" time, and a negative change in "ON" time with moderate or severe (troublesome) dyskinesia indicates improvement.
Time Frame
Baseline to Day 28
Title
Change in Morning UPDRS Part III (Motor) Scores
Description
The Unified Parkinson's Disease Rating Scale (UPDRS) is an Investigator-used rating tool to follow the longitudinal course of Parkinson's disease. UPDRS part III (motor) score is calculated as the sum of the individual UPDRS items 18-31, each of which are measured on a 5-point scale (i.e., 0 is normal and 4 indicates a severe abnormality). UPDRS part III was done as a motor examination on Day 1 before the first dose of standard oral LD/DDI and at the same time on Day 28. The range of score values is from 0 to 132. Higher scores correlate with greater motor impairment.
Time Frame
Baseline to Day 28
Title
Change in UPDRS Part II (ADL) Scores
Description
The Unified Parkinson's disease rating scale (UPDRS) is an Investigator-used rating tool to follow the longitudinal course of Parkinson's disease. The UPDRS Part II (activity of daily living) score was calculated as the sum of the individual UPDRS items 5-17. The Part II score is the sum of the answers to the 13 questions that comprise Part II, each of which are measured on a 5-point scale (i.e., 0 is normal and 4 indicates a severe abnormality). The range of score values is from 0 to 52. Higher scores correlate with greater impairments for daily activities.
Time Frame
Baseline to Day 28
Title
CGI-Improvement (CGI-I) Score as Assessed by Investigator
Description
Global improvement was rated by the investigator or designee using Clinical Global Impression of Improvement (CGI-I). The CGI-I employs a 7-point scale with 1 being "very much improved" and 7 being "very much worse" for improvement rating.
Time Frame
Baseline to Day 28
Title
Change in PDSS-2 Total Score
Description
The quality of night sleep was rated by the subjects using the Parkinson's Disease Sleep Scale (PDSS)-2, which includes questions addressing 15 commonly reported symptoms associated with sleep disturbance in PD. Each question is assessed from 0 (Always) to 10 (Never). The total score values range from 0 to 150. Higher scores indicate a lower quality of sleep, i.e., a reduction in the score indicates an improvement in sleep quality.
Time Frame
Baseline to Day 27
Title
Change in PDQ-39 Summary Index and the 8-dimension Scores
Description
Subjects were requested to rate their quality of life using the Quality of Life in Parkinson's Disease (PDQ)-39, a 39-item, self-administered questionnaire with 8 discrete dimensions (mobility, activities of daily living, emotional well-being, stigma, social support, cognition, communication, and bodily discomfort.). The PDQ-39 Summary Index is the sum of the dimension scores divided by the number of dimensions. The total score values range from 0 to 100%. Higher scores indicate a worse quality of life.
Time Frame
Baseline to Day 27
10. Eligibility
Sex
All
Minimum Age & Unit of Time
30 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male and female PD subjects of any race aged 30 to 80 years who sign an Institutional Review Board/Ethics Committee (IRB/EC)-approved informed consent form (ICF).
PD diagnosis consistent with the UK Brain Bank Criteria.
Modified Hoehn & Yahr scale in "ON" state of stage ≤3.
Taking at least 4 doses/day of LD (or at least 3 doses/day of Rytary) and taking, or have attempted to take, at least 2 other classes of anti-PD medications in a therapeutic dose for at least 30 consecutive days each.
Subjects must be stable on their anti-PD medications for at least 30 days before Day 1.
Subjects may have had prior exposure to SC apomorphine injections/infusion but must have stopped administration at least 4 weeks before the screening visit. Treatment with apomorphine is prohibited during the entire ND0612H treatment period.
Must have a minimum of 2.5 hrs of "OFF" time per day with predictable early morning "OFF" periods as estimated by the subject.
Must have predictable and well defined early morning "OFF" periods with a good response to LD for treatment of the early morning "OFF" in the judgement of the investigator.
Mini Mental State Examination (MMSE) score >26.
No clinically significant medical, psychiatric or laboratory abnormalities which the investigator judges would be unsafe or non-compliant in the study.
Female subjects must be surgically sterile, postmenopausal (defined as cessation of menses for at least 1 year), or willing to practice a highly effective method of contraception. All female participants must be non-lactating and non-pregnant and have a negative urine pregnancy test at Screening and at Baseline. Female subjects of childbearing potential must practice a highly effective method of contraception (e.g., oral contraceptives, a barrier method of birth control [e.g., condoms with contraceptive foams, diaphragms with contraceptive jelly], intrauterine devices, partner with vasectomy), 1 month before enrollment, for the duration of the study, and 3 months after the last dose of study drug.
Willingness and ability to comply with study requirements
Exclusion Criteria:
Atypical or secondary parkinsonism.
Acute psychosis or hallucinations in past 6 months.
Any relevant medical, surgical, or psychiatric condition, laboratory value, or concomitant medication which, in the opinion of the Investigator or the eligibility reviewer, makes the subject unsuitable for study entry or potentially unable to complete all aspects of the study.
Prior neurosurgical procedure for PD, or duodopa treatment.
Subjects with a history of drug abuse or alcoholism within the past 12 months.
Clinically significant ECG rhythm abnormalities.
Renal or liver dysfunction that may alter drug metabolism including: serum creatinine >1.3 mg/dL, serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2 x upper limit of normal (ULN), total serum bilirubin >2.5 mg/dL.
Subjects who are not willing to operate the pump system.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Laurence Salin, MD
Organizational Affiliation
NeuroDerm Ltd.
Official's Role
Study Director
Facility Information:
Facility Name
Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
QUEST Research Institute
City
Farmington Hills
State/Province
Michigan
ZIP/Postal Code
48334
Country
United States
Facility Name
University of Cincinnati
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45219
Country
United States
Facility Name
Medical University Innsbruck
City
Innsbruck
ZIP/Postal Code
A- 4060
Country
Austria
Facility Name
Rabin Medical Center
City
Petah Tikva
ZIP/Postal Code
4941492
Country
Israel
Facility Name
Chaim Sheba Medical Center
City
Ramat Gan
ZIP/Postal Code
56520
Country
Israel
Facility Name
Sourasky Medical Center
City
Tel Aviv
ZIP/Postal Code
64239
Country
Israel
Facility Name
University Foundation
City
Chieti
ZIP/Postal Code
66100
Country
Italy
Facility Name
AOU Pisa
City
Pisa
ZIP/Postal Code
56126
Country
Italy
Facility Name
IRCCS San Raffaele Pisana
City
Rome
ZIP/Postal Code
00163
Country
Italy
Facility Name
Fondazione Ospedale San Camillo - I.R.C.C.S.
City
Venice
ZIP/Postal Code
30126
Country
Italy
12. IPD Sharing Statement
Citations:
PubMed Identifier
33164945
Citation
Olanow CW, Espay AJ, Stocchi F, Ellenbogen AL, Leinonen M, Adar L, Case RJ, Orenbach SF, Yardeni T, Oren S, Poewe W; 006 study group. Continuous Subcutaneous Levodopa Delivery for Parkinson's Disease: A Randomized Study. J Parkinsons Dis. 2021;11(1):177-186. doi: 10.3233/JPD-202285.
Results Reference
result
Learn more about this trial
A Clinical Study of Efficacy, Safety, Tolerability and PK of ND0612H in Subjects With Advanced Parkinson's Disease
We'll reach out to this number within 24 hrs