Parkinson DiseasePhase 2NCT03103399
Efficacy and Tolerability of Nebicapone in Parkinson's Disease Patients With "Wearingoff" Phenomenon
A Phase 2 study testing Comtan®, Nebicapone and Levodopa/DDCI in people with Parkinson Disease, run by Bial - Portela C S.A..
Trial summary
The purpose of this study was to investigate the effect on the "wearing-off" phenomenon of 3 different doses of nebicapone (NEB 50 mg, 100 mg and 150 mg), compared with entacapone and placebo when dministered concomitantly with existing treatment with levodopa plus a dopa decarboxylase inhibitor (DDCI: carbidopa or… Read more about this study
- Who is it for?
- Ages 30 to 80 years
- Conditions the study is for
- Parkinson Disease
- What is being tested?
- Comtan®, Nebicapone and Levodopa/DDCI
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 254 participants
- Where
- No sites listed yet
- Study dates
- 26 Sep 2006to 21 Sep 2007
- 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 30 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- At Visit V1 (screening), patients had to be/have:
- Ability to comprehend and willingness to sign an informed consent form
- Aged 30 to 80 years, inclusive
- Diagnosis of idiopathic Parkinson's disease according to the Brain Bank Clinical Diagnosis Criteria of the UK Parkinson's Disease Society [Hughes et al, 1992]
- Disease severity less than Stage 5 (modified Hoehn \& Yahr staging) while during the "off" time
- Treated with levodopa plus DDCI for at least 1 year with clear clinical improvement
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- Treated with 4 to 8 (inclusive) daily doses of standard levodopa plus DDCI (bedtime dose of a slow-release formulation is permitted)
- Stable regimen of levodopa plus DDCI and other anti Parkinson drugs for at least 4 weeks before screening
- Signs of end-of-dose "wearing-off" phenomenon (end-of-dose deterioration) with average total daily "off" time while awake of at least 1.5 hours excluding the early morning pre first dose "off" period despite optimal anti Parkinson therapy, determined subjectively and objectively (observations of the investigator) for a minimum of 2 months before screening
- Ability to keep reliable diaries of motor fluctuations (alone or with family/caregiver assistance)
- Patient must be amenorrhoeic for at least 1 year or surgically sterile for at least 6 months before screening. In case of women of childbearing potential, patient must be using double-barrier contraceptive method.
- At Visit V2 (entry to Period 1), patients had to have the results of laboratory tests acceptable by the investigator (not clinically relevant for the well being of the patient or for the purpose of the study).
- At Visit V3 (randomisation), patients had to have:
- At least 80% treatment medication (levodopa/DDCI plus investigational product) compliance with the recommended dosage regimen during Period 1
- Self-rating diary charts filled in in accordance with the diary chart instructions; less than 3 errors per day are allowed
- Average of at least 1.5 "off" hours per day (excluding the early morning pre first dose "off" period) on the 3 day diaries, filled in on the 3 days preceding Visit V3, according to the self-rating diary charts completed during Period 1
Who cannot join
- At Visit V1 (screening), patients were not to be/have:
- Non-idiopathic Parkinson's disease (atypical parkinsonism, symptomatic parkinsonism, Parkinson-plus syndrome)
- Dyskinesia disability score more than 3 in the Unified Parkinson's Disease Rating Scale (UPDRS) IV.A item 33
- Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criterion for dementia
- Major depressive episode within the 6 months before screening
- Treatment with entacapone, tolcapone, neuroleptics, antidepressants (except serotonin-specific reuptake inhibitors or imipraminics [desipramine, imipramine, clomipramine and amitriptyline]), monoamine oxidase inhibitors (except selegiline up to 10 mg/day in oral formulation or 1.25 mg/day in buccal absorption formulation or rasagiline up to 1 mg/day), or antiemetics (except domperidone) within the 3 months before screening
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- Treatment with apomorphine within the previous month before screening
- Dosage change of concomitant anti Parkinson medication within 4 weeks of screening
- Any investigational product within the 3 months (or within 5 half-lives, whichever is longer) before screening
- A psychiatric or any medical condition that might place the patient at increased risk or interfere with assessment
- A clinically relevant electrocardiogram (ECG) abnormality
- A history or current evidence of heart disease, including but not limited to myocardial infarction, angina, congestive heart failure and cardiac arrhythmia
- Phaeochromocytoma
- Known hypersensitivity to the ingredients of products used
- Unstable concomitant disease being treated with changing doses of medication
- History or current evidence of any relevant disease in the context of this study, i.e. with respect to the safety of the patient or related to the study conditions, e.g. that may influence the absorption or metabolism (e.g. hepatic impairment) of the investigational drug
- Any abnormality in the liver enzymes above 2 times the upper limit of the normal range
About this study
Official title: A Multicentre, Double-blind, Randomised, Active- and Placebo-controlled Trial to Investigate the Efficacy and Tolerability of Nebicapone in Parkinson's Disease Patients With "Wearingoff" Phenomenon Treated With Levodopa/Carbidopa or Levodopa/Benserazide
The purpose of this study was to investigate the effect on the "wearing-off" phenomenon of 3 different doses of nebicapone (NEB 50 mg, 100 mg and 150 mg), compared with entacapone and placebo when dministered concomitantly with existing treatment with levodopa plus a dopa decarboxylase inhibitor (DDCI: carbidopa or benserazide).
Read the detailed description
The study was conducted in 40 sites in Europe and South America: Argentina (6); Austria (2); Brazil (5); France (1); Hungary (4); Poland (7); Portugal (2); Romania (7); and Ukraine (6).
Multicentre study with a screening visit (Visit V1), a single-blind placebo run-in period of 1 or 2 weeks (Period 1, Visits V2 to V3), and an 8-week randomised, double-blind, activeand placebo-controlled, parallel-group (5 groups) treatment period (Period 2, Visits V3 to V7). In Hungary only: a 1-week tapering-off period was added by amendment #1HU. The dosage of nebicapone was to be tapered off stepwise during 6 days. This period was to end with a follow-up Visit V8.
- Conditions
- Parkinson Disease
- Being tested
- Comtan®, Nebicapone, Levodopa/DDCI, Placebo
- Medical subject headings
- Parkinson Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Comtan®Drug
Also called entacapone
200 mg entacapone were to be taken concomitantly with each levodopa/DDCI dose.
NebicaponeDrug
Also called BIA 3-202
50 mg, 100 mg and 150 mg doses of nebicapone were to be taken concomitantly with each levodopa/DDCI dose.
Levodopa/DDCIDrug
Also called Levodopa plus a dopa decarboxylase inhibitor (DDCI: carbidopa or benserazide)
Prior to the study, all patients were to have been receiving levodopa/DDCI therapy for at least 1 year with clear clinical improvement. At entry to the study, patients were to be receiving levodopa/DDCI therapy of at least 4 but not more than 8 (inclusive) standard daily doses.
All patients were to continue receiving levodopa/DDCI during the study. Levodopa and DDCI were prescribed by the investigators and purchased locally by patients.
PlaceboDrug
Also called placebo tablets
Administered orally as encapsulated tablets, which were identical in appearance to the study drugs
| Study group | Role | What they receive |
|---|---|---|
| 50 mg nebicapone | Experimental | At Visit V2, patients received a supply of a placebo to take concomitantly with each levodopa/DDCI dose for the duration of the run-in period (Period 1). At the end of Period 1, patients were randomised to receive 50 mg of the study treatment in addition to their levodopa/DDCI therapy for the duration of the double-blind (Period 2) Receives: Drug: Nebicapone; Drug: Levodopa/DDCI; Drug: Placebo |
| 100 mg nebicapone | Experimental | At Visit V2, patients received a supply of a placebo to take concomitantly with each levodopa/DDCI dose for the duration of the run-in period (Period 1). At the end of Period 1, patients were randomised to receive 100 mg of the study treatment in addition to their levodopa/DDCI therapy for the duration of the double-blind (Period 2) Receives: Drug: Nebicapone; Drug: Levodopa/DDCI; Drug: Placebo |
| 150 mg nebicapone | Experimental | At Visit V2, patients received a supply of a placebo to take concomitantly with each levodopa/DDCI dose for the duration of the run-in period (Period 1). At the end of Period 1, patients were randomised to receive 150 mg of the study treatment in addition to their levodopa/DDCI therapy for the duration of the double-blind (Period 2) Receives: Drug: Nebicapone; Drug: Levodopa/DDCI; Drug: Placebo |
| 200 mg entacapone | Active comparator | At Visit V2, patients received a supply of a placebo to take concomitantly with each levodopa/DDCI dose for the duration of the run-in period (Period 1). At the end of Period 1, patients were randomised to receive 200 mg of entacapone (Comtan®) in addition to their levodopa/DDCI therapy for the duration of the double-blind (Period 2) Receives: Drug: Comtan®; Drug: Levodopa/DDCI; Drug: Placebo |
| Placebo | Placebo comparator | At Visit V2, patients received a supply of a placebo to take concomitantly with each levodopa/DDCI dose for the duration of the run-in period (Period 1). At the end of Period 1, patients were randomised to receive study treatment matching placebo tablets in addition to their levodopa/DDCI therapy for the duration of the double-blind (Period 2) Receives: Drug: Levodopa/DDCI; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline in absolute "off" time (time with poor mobility or complete immobility) at Visit V7
Baseline values for all efficacy variables were the values from Visit V3, and change from baseline refers to absolute change from baseline at Visit 7 (end of the 8-week treatment period)
Measured: 8 weeks
Secondary outcomes (2)
Proportion of "off" time responders
"off" time responders are defined as patients with a reduction of at least 1 hour in absolute "off" time since baseline (Visit V3).
Measured: 8 weeks
Proportion of "on" time responders
"on" time responders are defined as patients with an increase of at least 1 hour in absolute total "on" time since baseline (Visit V3).
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Apr 2017
- Study start26 Sep 2006
- Primary completion21 Sep 2007
- Study completion21 Sep 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 254 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bial - Portela C S.A.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03103399
- Sponsor's protocol ID
- BIA-3202-202
- Status last verified
- Mar 2017
- First submitted
- 28 Mar 2017
- Last updated
- 6 Apr 2017
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 6 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicentre, Double-blind, Randomised, Active- and Placebo-controlled Trial to Investigate the Efficacy and Tolerability of Nebicapone in Parkinson's Disease Patients With "Wearingoff" Phenomenon Treated With Levodopa/Carbidopa or Levodopa/Benserazide
- ClinicalTrials.gov ID
- NCT03103399
- Acronym / sponsor ID
- BIA-3202-202
- Conditions
- Parkinson Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 254 participants (actual)
- Lead sponsor
- Bial - Portela C S.A.Industry (pharma, biotech, devices)
- Study start
- 26 Sep 2006 (actual)
- Primary completion
- 21 Sep 2007 (actual)
- Study completion
- 21 Sep 2007 (actual)
- First posted
- 6 Apr 2017 (actual)
- 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.
The purpose of this study was to investigate the effect on the "wearing-off" phenomenon of 3 different doses of nebicapone (NEB 50 mg, 100 mg and 150 mg), compared with entacapone and placebo when dministered concomitantly with existing treatment with levodopa plus a dopa decarboxylase inhibitor (DDCI: carbidopa or benserazide).
Detailed description
The study was conducted in 40 sites in Europe and South America: Argentina (6); Austria (2); Brazil (5); France (1); Hungary (4); Poland (7); Portugal (2); Romania (7); and Ukraine (6).
Multicentre study with a screening visit (Visit V1), a single-blind placebo run-in period of 1 or 2 weeks (Period 1, Visits V2 to V3), and an 8-week randomised, double-blind, activeand placebo-controlled, parallel-group (5 groups) treatment period (Period 2, Visits V3 to V7). In Hungary only: a 1-week tapering-off period was added by amendment #1HU. The dosage of nebicapone was to be tapered off stepwise during 6 days. This period was to end with a follow-up Visit V8.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| 50 mg nebicapone | Experimental | Drug: Nebicapone, Drug: Levodopa/DDCI, Drug: PlaceboAt Visit V2, patients received a supply of a placebo to take concomitantly with each levodopa/DDCI dose for the duration of the run-in period (Period 1). At the end of Period 1, patients were randomised to receive 50 mg of the study treatment in addition to their levodopa/DDCI therapy for the duration of the double-blind (Period 2) |
| 100 mg nebicapone | Experimental | Drug: Nebicapone, Drug: Levodopa/DDCI, Drug: PlaceboAt Visit V2, patients received a supply of a placebo to take concomitantly with each levodopa/DDCI dose for the duration of the run-in period (Period 1). At the end of Period 1, patients were randomised to receive 100 mg of the study treatment in addition to their levodopa/DDCI therapy for the duration of the double-blind (Period 2) |
| 150 mg nebicapone | Experimental | Drug: Nebicapone, Drug: Levodopa/DDCI, Drug: PlaceboAt Visit V2, patients received a supply of a placebo to take concomitantly with each levodopa/DDCI dose for the duration of the run-in period (Period 1). At the end of Period 1, patients were randomised to receive 150 mg of the study treatment in addition to their levodopa/DDCI therapy for the duration of the double-blind (Period 2) |
| 200 mg entacapone | Active comparator | Drug: Comtan®, Drug: Levodopa/DDCI, Drug: PlaceboAt Visit V2, patients received a supply of a placebo to take concomitantly with each levodopa/DDCI dose for the duration of the run-in period (Period 1). At the end of Period 1, patients were randomised to receive 200 mg of entacapone (Comtan®) in addition to their levodopa/DDCI therapy for the duration of the double-blind (Period 2) |
| Placebo | Placebo comparator | Drug: Levodopa/DDCI, Drug: PlaceboAt Visit V2, patients received a supply of a placebo to take concomitantly with each levodopa/DDCI dose for the duration of the run-in period (Period 1). At the end of Period 1, patients were randomised to receive study treatment matching placebo tablets in addition to their levodopa/DDCI therapy for the duration of the double-blind (Period 2) |
Who may qualify
- Ages
- 30 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Ability to comprehend and willingness to sign an informed consent form
- Aged 30 to 80 years, inclusive
- Diagnosis of idiopathic Parkinson's disease according to the Brain Bank Clinical Diagnosis Criteria of the UK Parkinson's Disease Society [Hughes et al, 1992]
- Disease severity less than Stage 5 (modified Hoehn \& Yahr staging) while during the "off" time
- Treated with levodopa plus DDCI for at least 1 year with clear clinical improvement
Key exclusion criteria (17 listed)
- Non-idiopathic Parkinson's disease (atypical parkinsonism, symptomatic parkinsonism, Parkinson-plus syndrome)
- Dyskinesia disability score more than 3 in the Unified Parkinson's Disease Rating Scale (UPDRS) IV.A item 33
- Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criterion for dementia
- Major depressive episode within the 6 months before screening
- Treatment with entacapone, tolcapone, neuroleptics, antidepressants (except serotonin-specific reuptake inhibitors or imipraminics [desipramine, imipramine, clomipramine and amitriptyline]), monoamine oxidase inhibitors (except selegiline up to 10 mg/day in oral formulation or 1.25 mg/day in buccal absorption formulation or rasagiline up to 1 mg/day), or antiemetics (except domperidone) within the 3 months before screening
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 |
|---|---|---|
| Comtan®Also: entacapone200 mg entacapone were to be taken concomitantly with each levodopa/DDCI dose. | Drug | 200 mg entacapone |
| NebicaponeAlso: BIA 3-20250 mg, 100 mg and 150 mg doses of nebicapone were to be taken concomitantly with each levodopa/DDCI dose. | Drug | 100 mg nebicapone, 150 mg nebicapone, 50 mg nebicapone |
| Levodopa/DDCIAlso: Levodopa plus a dopa decarboxylase inhibitor (DDCI: carbidopa or benserazide)Prior to the study, all patients were to have been receiving levodopa/DDCI therapy for at least 1 year with clear clinical improvement. At entry to the study, patients were to be receiving levodopa/DDCI therapy of at least 4 but not more than 8 (inclusive) standard daily doses. All patients were to continue receiving levodopa/DDCI during the study. Levodopa and DDCI were prescribed by the investigators and purchased locally by patients. | Drug | 100 mg nebicapone, 150 mg nebicapone, 200 mg entacapone, 50 mg nebicapone, Placebo |
| PlaceboAlso: placebo tabletsAdministered orally as encapsulated tablets, which were identical in appearance to the study drugs | Drug | 100 mg nebicapone, 150 mg nebicapone, 200 mg entacapone, 50 mg nebicapone, Placebo |
Primary outcome
Change from baseline in absolute "off" time (time with poor mobility or complete immobility) at Visit V7
Time frame: 8 weeks
Baseline values for all efficacy variables were the values from Visit V3, and change from baseline refers to absolute change from baseline at Visit 7 (end of the 8-week treatment period)
2 secondary outcomes
Proportion of "off" time responders
Time frame: 8 weeks
Proportion of "on" time responders
Time frame: 8 weeks
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 6 Apr 2017.
- Individual participant dataSharing planned: Undecided
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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.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Comtan®, Nebicapone and Levodopa/DDCI in people with Parkinson Disease, run by Bial - Portela C S.A..
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 16 inclusion and 17 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 6 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. 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?
Change from baseline in absolute "off" time (time with poor mobility or complete immobility) at Visit V7 (time frame: 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 6 Apr 2017.