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Parkinson's DiseasePhase 2NCT02577523

A Clinical Study of Efficacy, Safety, Tolerability and PK of ND0612H in Subjects With Advanced Parkinson's Disease

A Phase 2 study testing ND0612 (Levodopa/Carbidopa solution) and ND0612 (Levodopa/Carbidopa solution) + morning oral IR-LD/CD in people with Parkinson's Disease, run by NeuroDerm Ltd. at 11 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 30 to 80 years
Conditions the study is for
Parkinson's Disease
What is being tested?
ND0612 (Levodopa/Carbidopa solution) and ND0612 (Levodopa/Carbidopa solution) + morning oral IR-LD/CD
Could I receive a placebo?
No, everyone receives an active treatment
How many people
38 participants
Where
11 sitesin 4 countries
Study dates
29 Dec 2015to 31 Jan 2017
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 30 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
Show all 12Show fewer
  • 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

Who cannot join

  • 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.

Trial locations and contacts

11 sites in 4 countries.

11 sites in 4 countries

Italy4 sites

  • University Foundation

    Chieti, 66100

  • AOU Pisa

    Pisa, 56126

  • IRCCS San Raffaele Pisana

    Rome, 00163

  • Fondazione Ospedale San Camillo - I.R.C.C.S.

    Venice, 30126

Other trials in Italy

United States3 sites

  • Northwestern University

    Chicago, Illinois, 60611

  • University of Cincinnati

    Cincinnati, Ohio, 45219

  • QUEST Research Institute

    Farmington Hills, Michigan, 48334

Other trials in United States

Israel3 sites

  • Rabin Medical Center

    Petah Tikva, 4941492

  • Chaim Sheba Medical Center

    Ramat Gan, 56520

  • Sourasky Medical Center

    Tel Aviv, 64239

Other trials in Israel

Austria1 site

  • Medical University Innsbruck

    Innsbruck, A- 4060

Other trials in Austria

About this study

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

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.

Read the 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.

Being tested
ND0612 (Levodopa/Carbidopa solution), ND0612 (Levodopa/Carbidopa solution) + morning oral IR-LD/CD
Medical subject headings
Parkinson Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ND0612 (Levodopa/Carbidopa solution)Drug

    Also called Regimen 1 - 24-hr infusion

    The total daily dose of levodopa/carbidopa 720/90 mg. Device: CRONO TWIN pump system.

  • ND0612 (Levodopa/Carbidopa solution) + morning oral IR-LD/CDDrug

    Also called Regimen 2 - 14-hr infusion

    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.

Study groups in NCT02577523
Study groupRoleWhat they receive
ND0612 (Levodopa/Carbidopa solution) Dosing Regimen 1ExperimentalDosing Regimen 1 of ND0612 (Levodopa/Carbidopa solution) continuous SC infusion over 24 hours.
Receives: Drug: ND0612 (Levodopa/Carbidopa solution)
ND0612 (Levodopa/Carbidopa solution) Dosing Regimen 2ExperimentalDosing 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.
Receives: Drug: ND0612 (Levodopa/Carbidopa solution) + morning oral IR-LD/CD

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Baseline to Day 28

Secondary outcomes (7)

  1. 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.

    Measured: Baseline to Day 28

  2. 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.

    Measured: Baseline to Day 28

  3. 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.

    Measured: Baseline to Day 28

  4. 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.

    Measured: Baseline to Day 28

  5. 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.

    Measured: Baseline to Day 28

  6. 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.

    Measured: Baseline to Day 27

  7. 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.

    Measured: Baseline to Day 27

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Oct 2015 (estimated)
  2. Study start29 Dec 2015
  3. Primary completion20 Dec 2016
  4. Study completion31 Jan 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
38 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02577523
Sponsor's protocol ID
ND0612H-006
Status last verified
May 2023
First submitted
6 Oct 2015
Last updated
25 May 2023
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 33164945

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing ND0612 (Levodopa/Carbidopa solution) and ND0612 (Levodopa/Carbidopa solution) + morning oral IR-LD/CD in people with Parkinson's Disease, run by NeuroDerm Ltd. at 11 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 May 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in Italy, United States, Israel, Austria. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 Mar 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Daily "OFF" Time (time frame: Baseline to Day 28). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02577523, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 May 2023.

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