Efficacy and Tolerability of Nebicapone in Parkinson's Disease Patients With "Wearingoff" Phenomenon

March 31, 2017 updated by: Bial - Portela C S.A.

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).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
254

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

30 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

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
  • 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

Exclusion Criteria:

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
  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: 50 mg nebicapone
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)
Drug: Nebicapone
50 mg, 100 mg and 150 mg doses of nebicapone were to be taken concomitantly with each levodopa/DDCI dose.
Other Names:
  • BIA 3-202
Drug: Levodopa/DDCI

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.

Other Names:
  • Levodopa plus a dopa decarboxylase inhibitor (DDCI: carbidopa or benserazide)
Drug: Placebo
Administered orally as encapsulated tablets, which were identical in appearance to the study drugs
Other Names:
  • placebo tablets
Experimental: 100 mg nebicapone
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)
Drug: Nebicapone
50 mg, 100 mg and 150 mg doses of nebicapone were to be taken concomitantly with each levodopa/DDCI dose.
Other Names:
  • BIA 3-202
Drug: Levodopa/DDCI

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.

Other Names:
  • Levodopa plus a dopa decarboxylase inhibitor (DDCI: carbidopa or benserazide)
Drug: Placebo
Administered orally as encapsulated tablets, which were identical in appearance to the study drugs
Other Names:
  • placebo tablets
Experimental: 150 mg nebicapone
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)
Drug: Nebicapone
50 mg, 100 mg and 150 mg doses of nebicapone were to be taken concomitantly with each levodopa/DDCI dose.
Other Names:
  • BIA 3-202
Drug: Levodopa/DDCI

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.

Other Names:
  • Levodopa plus a dopa decarboxylase inhibitor (DDCI: carbidopa or benserazide)
Drug: Placebo
Administered orally as encapsulated tablets, which were identical in appearance to the study drugs
Other Names:
  • placebo tablets
Active Comparator: 200 mg entacapone
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)
Drug: Levodopa/DDCI

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.

Other Names:
  • Levodopa plus a dopa decarboxylase inhibitor (DDCI: carbidopa or benserazide)
Drug: Placebo
Administered orally as encapsulated tablets, which were identical in appearance to the study drugs
Other Names:
  • placebo tablets
Drug: Comtan®
200 mg entacapone were to be taken concomitantly with each levodopa/DDCI dose.
Other Names:
  • entacapone
Placebo Comparator: Placebo
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)
Drug: Levodopa/DDCI

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.

Other Names:
  • Levodopa plus a dopa decarboxylase inhibitor (DDCI: carbidopa or benserazide)
Drug: Placebo
Administered orally as encapsulated tablets, which were identical in appearance to the study drugs
Other Names:
  • placebo tablets

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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)
8 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Proportion of "off" time responders
Time Frame: 8 weeks
"off" time responders are defined as patients with a reduction of at least 1 hour in absolute "off" time since baseline (Visit V3).
8 weeks
Proportion of "on" time responders
Time Frame: 8 weeks
"on" time responders are defined as patients with an increase of at least 1 hour in absolute total "on" time since baseline (Visit V3).
8 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Bial - Portela C S.A.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 26, 2006

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 21, 2007

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 21, 2007

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 28, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 31, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 6, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 6, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 31, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • BIA-3202-202

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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