Parkinson's Disease
Conditions
Keywords
Parkinson's Disease, BIA 9-1067
Brief summary
The purpose of this study is to investigate the effect of BIA 9-1067 on the levodopa pharmacokinetics when administered in combination with immediate release levodopa/carbidopa or levodopa/benserazide in Parkinson's Disease (PD) patients.
Detailed description
This was a three-centre, double-blind, randomised, placebo-controlled, crossover study with four consecutive single-dose treatment periods in PD patients treated with immediate release 100 mg/25 mg levodopa/carbidopa or 100 mg/25 mg levodopa/benserazide
Interventions
DRUGBIA 9-1067
BIA 9-1067 - 25 mg single-dose
DRUGPlacebo
single-dose
Levodopa 100 mg Carbidopa 25 mg
Levodopa 100 mg Benzerazide 25 mg
Sponsors
Bial - Portela C S.A.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
30 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Male or female of non-childbearing potential (by reason of surgery or postmenopausal); * Aged between 30 and 75 years, inclusive; * A diagnosis of PD according to the UK PDS Brain Bank diagnostic criteria (bradykinesia and at least one of the following: muscular rigidity, rest tremor and postural instability); * Predictable signs of end-of-dose deterioration despite optimal levodopa/carbidopa or levodopa/benserazide therapy; * Been treated with a stable regimen of 3 to 8 doses of standard release 100 mg/25 mg levodopa/carbidopa or 100 mg/25 mg levodopa/benserazide per day within at least 1 week prior to randomisation; * Modified Hoehn and Yahr stage of less than 5 in the off-state; * Mean duration of OFF stage ≥ 1.5 h during waking hours (based on historical information); * Concomitant anti-Parkinsonian medication (other than apomorphine, entacapone or tolcapone) in stable doses for at least 4 weeks prior to randomisation; * Results of clinical laboratory tests acceptable by the investigator (not clinically significant for the well-being of the subject or for the purpose of the study); * Able and willing to give written informed consent.
Exclusion criteria
* Non-idiopathic parkinsonism (atypical parkinsonism, symptomatic parkinsonism, Parkinson-plus syndrome); * Treated with levodopa/carbidopa or levodopa/benserazide in a 10:1 ratio, or with levodopa/carbidopa in a controlled-release formulation; * Treated with entacapone, tolcapone, neuroleptics, antidepressants (except serotonin-specific reuptake inhibitors or imipramines \[desipramine, imipramine, clomipramine and amitriptyline\]), 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 4 weeks prior to randomisation; * Treated with apomorphine within 7 days prior to randomisation; * Treated with any investigational product within 2 months prior to randomisation (or within 5 half-lives, whichever is longer); * A psychiatric or any medical condition that might place him/her at increased risk or interfere with assessments; * Known hypersensitivity to any of the ingredients of the investigational products; * A history of abuse of alcohol, drugs or medications within the last 2 years; * A clinically relevant ECG abnormality; * A history or current evidence of heart disease, including but not limited to myocardial infarction, angina, congestive heart failure and cardiac arrhythmia; * Unstable concomitant disease being treated with changing doses of medication; * A history or current evidence of any relevant disease in the context of this study, i.e., with respect to the safety of the subject (e.g., hepatic or renal impairment) or related to the study conditions; * A test positive for the human immunodeficiency viruses (HIV) 1 or 2 antibodies, or hepatitis B surface antigen (HBsAg), or hepatitis C antibody (HCVAb); * Donated blood or received blood or blood products within the 6 months prior to randomisation; * Pregnant, breast-feeding or of childbearing potential; * Other condition or circumstance that, in the opinion of the investigator, may compromise the subject's ability to comply with the study protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax - Maximum Plasma Concentration Day 3 | Day 3 | Cmax - Maximum plasma concentration (ng/mL) |
| Tmax = Time to Cmax Day 3 | Day 3 | tmax = time to Cmax (values are median) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUC0-6 - Area Under the Plasma Concentration-time Curve From Time 0 to 6 Hours Post-dose (Day 3) | Day 3 | AUC0-6 - area under the plasma concentration-time curve from time 0 to 6 hours post-dose (ng.h/mL) |
Countries
Portugal, Romania, Ukraine
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Overall Study The study was to consist of four consecutive treatment periods, corresponding to the 4 different treatment options (25 mg, 50 mg and 100 mg BIA 9-1067or Placebo).According to randomisation, subjects were to receive, in a double-blind manner, 25, 50 and 100 mg BIA 9-1067 or Placebo at 4 separate treatment periods. Each subject were to receive each of the three BIA 9-1067 doses and Placebo in a random sequence with a 3:1 ratio (BIA 9-1067: Placebo) per treatment period. | 10 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Overall Study |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 6 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 10 | 6 / 10 | 7 / 10 | 3 / 9 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 | 0 / 10 | 0 / 9 |
Outcome results
Primary
Cmax - Maximum Plasma Concentration Day 3
Cmax - Maximum plasma concentration (ng/mL)
Time frame: Day 3
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Cmax - Maximum Plasma Concentration Day 3 | Cmax (levodopa) | 2103 ng/ml | Standard Deviation 48.4 |
| Placebo | Cmax - Maximum Plasma Concentration Day 3 | Cmax (BIA 9-067) | NA ng/ml | — |
| Placebo | Cmax - Maximum Plasma Concentration Day 3 | Cmax (3-OMD) | 3996 ng/ml | Standard Deviation 50.5 |
| BIA 9-1067 25 mg | Cmax - Maximum Plasma Concentration Day 3 | Cmax (levodopa) | 2112 ng/ml | Standard Deviation 49.6 |
| BIA 9-1067 25 mg | Cmax - Maximum Plasma Concentration Day 3 | Cmax (BIA 9-067) | 320 ng/ml | Standard Deviation 57.2 |
| BIA 9-1067 25 mg | Cmax - Maximum Plasma Concentration Day 3 | Cmax (3-OMD) | 4193 ng/ml | Standard Deviation 42.4 |
| BIA 9-1067 50 mg | Cmax - Maximum Plasma Concentration Day 3 | Cmax (3-OMD) | 4284 ng/ml | Standard Deviation 49.2 |
| BIA 9-1067 50 mg | Cmax - Maximum Plasma Concentration Day 3 | Cmax (levodopa) | 2366 ng/ml | Standard Deviation 44 |
| BIA 9-1067 50 mg | Cmax - Maximum Plasma Concentration Day 3 | Cmax (BIA 9-067) | 590 ng/ml | Standard Deviation 41.5 |
| BIA 9-1067 100 mg | Cmax - Maximum Plasma Concentration Day 3 | Cmax (levodopa) | 2657 ng/ml | Standard Deviation 32.5 |
| BIA 9-1067 100 mg | Cmax - Maximum Plasma Concentration Day 3 | Cmax (BIA 9-067) | 816 ng/ml | Standard Deviation 35.5 |
| BIA 9-1067 100 mg | Cmax - Maximum Plasma Concentration Day 3 | Cmax (3-OMD) | 4085 ng/ml | Standard Deviation 60.4 |
Primary
Tmax = Time to Cmax Day 3
tmax = time to Cmax (values are median)
Time frame: Day 3
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Tmax = Time to Cmax Day 3 | Tmax (levodopa) | 0.5 hours |
| Placebo | Tmax = Time to Cmax Day 3 | Tmax (BIA 9-067) | NA hours |
| Placebo | Tmax = Time to Cmax Day 3 | Tmax (3-OMD) | 2.00 hours |
| BIA 9-1067 25 mg | Tmax = Time to Cmax Day 3 | Tmax (levodopa) | 1.0 hours |
| BIA 9-1067 25 mg | Tmax = Time to Cmax Day 3 | Tmax (BIA 9-067) | 2.00 hours |
| BIA 9-1067 25 mg | Tmax = Time to Cmax Day 3 | Tmax (3-OMD) | 1.75 hours |
| BIA 9-1067 50 mg | Tmax = Time to Cmax Day 3 | Tmax (3-OMD) | 2.50 hours |
| BIA 9-1067 50 mg | Tmax = Time to Cmax Day 3 | Tmax (levodopa) | 0.5 hours |
| BIA 9-1067 50 mg | Tmax = Time to Cmax Day 3 | Tmax (BIA 9-067) | 2.00 hours |
| BIA 9-1067 100 mg | Tmax = Time to Cmax Day 3 | Tmax (levodopa) | 0.5 hours |
| BIA 9-1067 100 mg | Tmax = Time to Cmax Day 3 | Tmax (BIA 9-067) | 2.00 hours |
| BIA 9-1067 100 mg | Tmax = Time to Cmax Day 3 | Tmax (3-OMD) | 1.75 hours |
Secondary
AUC0-6 - Area Under the Plasma Concentration-time Curve From Time 0 to 6 Hours Post-dose (Day 3)
AUC0-6 - area under the plasma concentration-time curve from time 0 to 6 hours post-dose (ng.h/mL)
Time frame: Day 3
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | AUC0-6 - Area Under the Plasma Concentration-time Curve From Time 0 to 6 Hours Post-dose (Day 3) | AUC0-6 (BIA 9-1067) | NA ng.h/mL | — |
| Placebo | AUC0-6 - Area Under the Plasma Concentration-time Curve From Time 0 to 6 Hours Post-dose (Day 3) | AUC0-6 (3-OMD) | 22334 ng.h/mL | Standard Deviation 51.1 |
| Placebo | AUC0-6 - Area Under the Plasma Concentration-time Curve From Time 0 to 6 Hours Post-dose (Day 3) | AUC0-6 (levodopa) | 3958 ng.h/mL | Standard Deviation 46.7 |
| BIA 9-1067 25 mg | AUC0-6 - Area Under the Plasma Concentration-time Curve From Time 0 to 6 Hours Post-dose (Day 3) | AUC0-6 (BIA 9-1067) | 776 ng.h/mL | Standard Deviation 60.1 |
| BIA 9-1067 25 mg | AUC0-6 - Area Under the Plasma Concentration-time Curve From Time 0 to 6 Hours Post-dose (Day 3) | AUC0-6 (levodopa) | 4545 ng.h/mL | Standard Deviation 61.4 |
| BIA 9-1067 25 mg | AUC0-6 - Area Under the Plasma Concentration-time Curve From Time 0 to 6 Hours Post-dose (Day 3) | AUC0-6 (3-OMD) | 22026 ng.h/mL | Standard Deviation 44.3 |
| BIA 9-1067 50 mg | AUC0-6 - Area Under the Plasma Concentration-time Curve From Time 0 to 6 Hours Post-dose (Day 3) | AUC0-6 (levodopa) | 4580 ng.h/mL | Standard Deviation 36.5 |
| BIA 9-1067 50 mg | AUC0-6 - Area Under the Plasma Concentration-time Curve From Time 0 to 6 Hours Post-dose (Day 3) | AUC0-6 (3-OMD) | 23515 ng.h/mL | Standard Deviation 50 |
| BIA 9-1067 50 mg | AUC0-6 - Area Under the Plasma Concentration-time Curve From Time 0 to 6 Hours Post-dose (Day 3) | AUC0-6 (BIA 9-1067) | 1694 ng.h/mL | Standard Deviation 34.6 |
| BIA 9-1067 100 mg | AUC0-6 - Area Under the Plasma Concentration-time Curve From Time 0 to 6 Hours Post-dose (Day 3) | AUC0-6 (BIA 9-1067) | 2647 ng.h/mL | Standard Deviation 51.4 |
| BIA 9-1067 100 mg | AUC0-6 - Area Under the Plasma Concentration-time Curve From Time 0 to 6 Hours Post-dose (Day 3) | AUC0-6 (3-OMD) | 22200 ng.h/mL | Standard Deviation 61.4 |
| BIA 9-1067 100 mg | AUC0-6 - Area Under the Plasma Concentration-time Curve From Time 0 to 6 Hours Post-dose (Day 3) | AUC0-6 (levodopa) | 5440 ng.h/mL | Standard Deviation 46.4 |