Parkinson DiseasePhase 2LDCD-001NCT02763137
Intermittent Oral Administration vs. Semi-continuous Intra-oral Administration of Levodopa/Carbidopa in Fluctuating Parkinsonian Patients
A Phase 2 study testing Standard LD/CD and Semi continuous intra-oral administration of LD/CD in people with Parkinson Disease, run by IRCCS San Raffaele Roma at 1 site in Italy.
Trial summary
This is a phase IIa study to assess the safety, tolerability, plasma pharmacokinetics and efficacy of intermittent oral administration of standard levodopa/carbidopa (LD/CD) vs.semi-continuous intra-oral administration of levodopa/carbidopa in patients with advanced Parkinson's disease (PD) who suffer motor… Read more about this study
- Who is it for?
- Ages 35 to 75 years
- Conditions the study is for
- Parkinson Disease
- What is being tested?
- Standard LD/CD and Semi continuous intra-oral administration of LD/CD
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteItaly
- Study dates
- 30 Jul 2014to Oct 2015
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 35 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- PD diagnosis consistent with United Kingdom Brain Bank Criteria
- Good response to levodopa with at least 2 hours of wearing off episodes in judgment of investigator
- Stable doses of levodopa plus/minus other dopaminergic therapy (minimum of 4 weeks for each drug)
- Mini Mental Score Examination (MMSE): score > 26
- Capable of providing informed consent
- No clinically significant medical, psychiatric or laboratory abnormalities in the judgment of the investigator.
Show all 9Show fewer
- No history of psychosis or hallucinations in the past 6 months
- Women who are capable of child bearing must have a negative urine pregnancy test at screening visit and use an adequate contraceptive method throughout the study.
- Approval for entry into the study by an enrolment steering committee
Who cannot join
- Atypical or secondary parkinsonism
- Severe dyskinesia that might interfere with study performance in judgment of investigator
- Patient receiving duodopa, apomorphine infusion or Deep Brain Stimulation (DBS)
- Dysphagia or sialorrhea that might interfere with administration of study intervention
- Any relevant medical, surgical, or psychiatric condition, laboratory value, or concomitant medication which, in the opinion of the Investigator, would interfere with performing a pharmacokinetic study or would interfere with drug absorption.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase IIa Study to Assess the Safety, Tolerability, Plasma Pharmacokinetics and Efficacy of Intermittent Oral Administration of Standard Levodopa/Carbidopa vs. Semi-continuous Intra-oral Administration of Levodopa/Carbidopa in Patients With Advanced Parkinson's Disease Who Suffer Motor Fluctuations
This is a phase IIa study to assess the safety, tolerability, plasma pharmacokinetics and efficacy of intermittent oral administration of standard levodopa/carbidopa (LD/CD) vs.semi-continuous intra-oral administration of levodopa/carbidopa in patients with advanced Parkinson's disease (PD) who suffer motor fluctuations.The objective of this study is to assess the plasma pharmacokinetics (PK) of continuous intra-oral administration of LD/CD vs. intermittent administration of standard oral LD/CD. For purposes of this study continuous intra-oral administration of LD/CD is defined as oral administration of LD/CD at 5-10 minute intervals.
Secondary objectives are to assess the safety and tolerability of continuous intra-oral administration of LD/CD and the effect on PD motor function of continuous intra-oral administration of LD/CD vs. intermittent administration of standard oral LD/CD.
Read the detailed description
18 PD subjects with motor fluctuations on stable doses of standard levodopa/carbidopa +/- other dopaminergic therapy who meet entry criteria and sign an Institutional Ethical Committee approved informed consent will participate in this study. The study will be conducted at the San Raffaele IRCCS in Rome, Italy.
Subjects who successfully complete the screening activities to confirm eligibility and are approved by an enrollment steering committee will be admitted to hospital on the evening of day 1 to undergo baseline evaluations. Standard oral levodopa/carbidopa (LD/CD) medication will be stopped at midnight. On day 2, a standardized low protein breakfast will be provided and treatment will be initiated with their usual dose of standard oral LD/CD. All subsequent doses will be administered at their pre-baseline dosing intervals; other anti-parkinson medications will not be stopped and will be maintained at their usual dose. If rescue therapy is required, treatment with apomorphine sc will be administered as a first preference. Plasma levels of levodopa and metabolites will be measured over the course of the ensuing 8 hours. Physicians will assess motor status (off, on without dyskinesia, or on with dyskinesia) at 30-minute intervals throughout the 8-hour observation period and perform UPDRS motor exams at 0, 2, 4, and 8 hours. Patients will then resume their standard oral LD/CD anti-parkinsonian medications (if any), which will be stopped at midnight. On day 3 subjects will receive continuous intra-oral administration of standard LD/CD at a dose equal to the total dose of standard oral LD/CD that they would normally consume over the time course of the study period. For the purposes of this study continuous intra-oral administration will refer to oral dosing at 5-10 minute intervals. To achieve this, the drug will be chopped and administered with water so that the same total dose of levodopa that would normally be taken intermittently will be divided up and administered as small doses at 5-10 minute intervals. Patients will undergo all of the same PK blood sampling as on Day 2. If the patient is taking Stalevo, a dose of entacapone will be administered at the usual time intervals that Stalevo otherwise would have been taken. Patients will then resume their standard oral LD/CD anti-parkinsonian medication (if any), which will be stopped at midnight. On Day 4 of the study subjects will receive their first LD/CD dose orally, and the balance of the total dose they would normally take over the next 8 hours by way of continuous intra-oral administration of LD/CD over the course of the 8 hour study period. If taking Stalevo, entacapone will be administered by itself at the time Stalevo would normally have been taken.
Physicians will assess motor status (off, on without dyskinesia, or on with dyskinesia) at 30-minute intervals throughout the continuous intra-oral administration and perform UPDRS motor exams at 0, 2, 4, and 8 hours. At the completion of the study, patients will be discharged from the clinic on their standard medication. Patients will return on day 18 for a safety evaluation.
- Conditions
- Parkinson Disease
- Being tested
- Standard LD/CD, Semi continuous intra-oral administration of 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.
Standard LD/CDDrug
Also called Sinemet 25 mg/100 mg at patient's usual dose and frequency
LD/CD will be administered at patient's usual dose and frequency during 8 hours interval
Semi continuous intra-oral administration of LD/CDDrug
Also called Sinemet 25 mg/100 mg administered at 5-10 minutes intervals
Semi continuous intra-oral administration of standard LD/CD at a dose equal to the total dose of standard oral LD/CD that patients would normally consume over 8 hours period.
| Study group | Role | What they receive |
|---|---|---|
| Standard LD/CD | Active comparator | Standard LD/CD administered at patient's usual dose and frequency Receives: Drug: Standard LD/CD |
| Semi continuous intra-oral administration of LD/CD | Experimental | Semi continuous intra-oral administration of LD/CD at a dose equivalent to the patient's regular dose of standard LD/CD Receives: Drug: Semi continuous intra-oral administration of LD/CD |
What is being measured
The primary outcome is the main question the study is designed to answer.
Variability in the observed plasma concentration of levodopa as assessed with the fluctuation index (Fluctuation index= (Maximum Plasma Concentration (Cmax)-Minimum Plasma Concentration (Cmin))/Concentration average)
Change in fluctuation index between intermittent administration (Day 2) and intra-oral administration (Day 3)
Measured: Change in fluctuation index between Day 2 and Day 3
Secondary outcomes (3)
Assess the safety and tolerability of continuous intra-oral administration of LD/CD: Adverse Events
Record of any adverse event
Measured: From Day 1 to Day 18
Assess the effect on number of hours of "off" time of continuous intra-oral administration of LD/CD vs. intermittent administration of standard oral LD/CD
Measured: Change in number of hours of "off" time between Day 2 and Day 3
Assess the effect on UPDRS of continuous intra-oral administration of LD/CD vs. intermittent administration of standard oral LD/CD
Measured: Change in UPDRS between Day 2 and Day 3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 May 2016 (estimated)
- Study start30 Jul 2014
- Primary completionOct 2015
- Study completionOct 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Parkinson DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- IRCCS San Raffaele Roma
- Sponsor type
- University, hospital or other
- Collaborators
- SynAgile Corporation
- Responsible party
- Sponsor
- Investigators
- FABRIZIO STOCCHI, PROFESSOR, Principal investigator, IRCCS San Raffaele
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02763137
- Sponsor's protocol ID
- RP 12/14
- Acronym
- LDCD-001
- Status last verified
- Oct 2022
- First submitted
- 26 Apr 2016
- Last updated
- 10 Apr 2024
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: Publication on peer-reviewed journal
Publications
Stocchi F, Vacca L, Ruggieri S, Olanow CW. Intermittent vs continuous levodopa administration in patients with advanced Parkinson disease: a clinical and pharmacokinetic study. Arch Neurol. 2005 Jun;62(6):905-10. doi: 10.1001/archneur.62.6.905.
PubMed 15956161
Study at a glance
From the registry record, last updated by the sponsor on 10 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase IIa Study to Assess the Safety, Tolerability, Plasma Pharmacokinetics and Efficacy of Intermittent Oral Administration of Standard Levodopa/Carbidopa vs. Semi-continuous Intra-oral Administration of Levodopa/Carbidopa in Patients With Advanced Parkinson's Disease Who Suffer Motor Fluctuations
- ClinicalTrials.gov ID
- NCT02763137
- Acronym / sponsor ID
- LDCD-001 / RP 12/14
- Conditions
- Parkinson Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- IRCCS San Raffaele RomaUniversity, hospital or other
- Collaborators
- SynAgile Corporation
- Study start
- 30 Jul 2014 (actual)
- Primary completion
- Oct 2015 (actual)
- Study completion
- Oct 2015 (actual)
- First posted
- 5 May 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a phase IIa study to assess the safety, tolerability, plasma pharmacokinetics and efficacy of intermittent oral administration of standard levodopa/carbidopa (LD/CD) vs.semi-continuous intra-oral administration of levodopa/carbidopa in patients with advanced Parkinson's disease (PD) who suffer motor fluctuations.The objective of this study is to assess the plasma pharmacokinetics (PK) of continuous intra-oral administration of LD/CD vs. intermittent administration of standard oral LD/CD. For purposes of this study continuous intra-oral administration of LD/CD is defined as oral administration of LD/CD at 5-10 minute intervals.
Secondary objectives are to assess the safety and tolerability of continuous intra-oral administration of LD/CD and the effect on PD motor function of continuous intra-oral administration of LD/CD vs. intermittent administration of standard oral LD/CD.
Detailed description
18 PD subjects with motor fluctuations on stable doses of standard levodopa/carbidopa +/- other dopaminergic therapy who meet entry criteria and sign an Institutional Ethical Committee approved informed consent will participate in this study. The study will be conducted at the San Raffaele IRCCS in Rome, Italy.
Subjects who successfully complete the screening activities to confirm eligibility and are approved by an enrollment steering committee will be admitted to hospital on the evening of day 1 to undergo baseline evaluations. Standard oral levodopa/carbidopa (LD/CD) medication will be stopped at midnight. On day 2, a standardized low protein breakfast will be provided and treatment will be initiated with their usual dose of standard oral LD/CD. All subsequent doses will be administered at their pre-baseline dosing intervals; other anti-parkinson medications will not be stopped and will be maintained at their usual dose. If rescue therapy is required, treatment with apomorphine sc will be administered as a first preference. Plasma levels of levodopa and metabolites will be measured over the course of the ensuing 8 hours. Physicians will assess motor status (off, on without dyskinesia, or on with dyskinesia) at 30-minute intervals throughout the 8-hour observation period and perform UPDRS motor exams at 0, 2, 4, and 8 hours. Patients will then resume their standard oral LD/CD anti-parkinsonian medications (if any), which will be stopped at midnight. On day 3 subjects will receive continuous intra-oral administration of standard LD/CD at a dose equal to the total dose of standard oral LD/CD that they would normally consume over the time course of the study period. For the purposes of this study continuous intra-oral administration will refer to oral dosing at 5-10 minute intervals. To achieve this, the drug will be chopped and administered with water so that the same total dose of levodopa that would normally be taken intermittently will be divided up and administered as small doses at 5-10 minute intervals. Patients will undergo all of the same PK blood sampling as on Day 2. If the patient is taking Stalevo, a dose of entacapone will be administered at the usual time intervals that Stalevo otherwise would have been taken. Patients will then resume their standard oral LD/CD anti-parkinsonian medication (if any), which will be stopped at midnight. On Day 4 of the study subjects will receive their first LD/CD dose orally, and the balance of the total dose they would normally take over the next 8 hours by way of continuous intra-oral administration of LD/CD over the course of the 8 hour study period. If taking Stalevo, entacapone will be administered by itself at the time Stalevo would normally have been taken.
Physicians will assess motor status (off, on without dyskinesia, or on with dyskinesia) at 30-minute intervals throughout the continuous intra-oral administration and perform UPDRS motor exams at 0, 2, 4, and 8 hours. At the completion of the study, patients will be discharged from the clinic on their standard medication. Patients will return on day 18 for a safety evaluation.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard LD/CD | Active comparator | Drug: Standard LD/CDStandard LD/CD administered at patient's usual dose and frequency |
| Semi continuous intra-oral administration of LD/CD | Experimental | Drug: Semi continuous intra-oral administration of LD/CDSemi continuous intra-oral administration of LD/CD at a dose equivalent to the patient's regular dose of standard LD/CD |
Who may qualify
- Ages
- 35 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- PD diagnosis consistent with United Kingdom Brain Bank Criteria
- Good response to levodopa with at least 2 hours of wearing off episodes in judgment of investigator
- Stable doses of levodopa plus/minus other dopaminergic therapy (minimum of 4 weeks for each drug)
- Mini Mental Score Examination (MMSE): score > 26
- Capable of providing informed consent
Key exclusion criteria (5 listed)
- Atypical or secondary parkinsonism
- Severe dyskinesia that might interfere with study performance in judgment of investigator
- Patient receiving duodopa, apomorphine infusion or Deep Brain Stimulation (DBS)
- Dysphagia or sialorrhea that might interfere with administration of study intervention
- Any relevant medical, surgical, or psychiatric condition, laboratory value, or concomitant medication which, in the opinion of the Investigator, would interfere with performing a pharmacokinetic study or would interfere with drug absorption.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Standard LD/CDAlso: Sinemet 25 mg/100 mg at patient's usual dose and frequencyLD/CD will be administered at patient's usual dose and frequency during 8 hours interval | Drug | Standard LD/CD |
| Semi continuous intra-oral administration of LD/CDAlso: Sinemet 25 mg/100 mg administered at 5-10 minutes intervalsSemi continuous intra-oral administration of standard LD/CD at a dose equal to the total dose of standard oral LD/CD that patients would normally consume over 8 hours period. | Drug | Semi continuous intra-oral administration of LD/CD |
Primary outcome
Variability in the observed plasma concentration of levodopa as assessed with the fluctuation index (Fluctuation index= (Maximum Plasma Concentration (Cmax)-Minimum Plasma Concentration (Cmin))/Concentration average)
Time frame: Change in fluctuation index between Day 2 and Day 3
Change in fluctuation index between intermittent administration (Day 2) and intra-oral administration (Day 3)
3 secondary outcomes
Assess the safety and tolerability of continuous intra-oral administration of LD/CD: Adverse Events
Time frame: From Day 1 to Day 18
Assess the effect on number of hours of "off" time of continuous intra-oral administration of LD/CD vs. intermittent administration of standard oral LD/CD
Time frame: Change in number of hours of "off" time between Day 2 and Day 3
Assess the effect on UPDRS of continuous intra-oral administration of LD/CD vs. intermittent administration of standard oral LD/CD
Time frame: Change in UPDRS between Day 2 and Day 3
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Apr 2024.
- Results publication: PubMed 15956161Stocchi F, Vacca L, Ruggieri S, Olanow CW. Intermittent vs continuous levodopa administration in patients with advanced Parkinson disease: a clinical and pharmacokinetic study. Arch Neurol. 2005 Jun;62(6):905-10. doi: 10.1001/archneur.62.6.905.
- Individual participant dataSharing planned: Yes. Publication on peer-reviewed journal
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
FABRIZIO STOCCHI, PROFESSOR principal investigator
IRCCS San Raffaele
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Standard LD/CD and Semi continuous intra-oral administration of LD/CD in people with Parkinson Disease, run by IRCCS San Raffaele Roma at 1 site in Italy.
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 9 inclusion and 5 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 10 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Variability in the observed plasma concentration of levodopa as assessed with the fluctuation index (Fluctuation index= (Maximum Plasma Concentration (Cmax)-Minimum Plasma Concentration (Cmin))/Concentration average) (time frame: Change in fluctuation index between Day 2 and Day 3). 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 NCT02763137, 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 10 Apr 2024.