E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10013113 |
E.1.2 | Term | Disease Parkinson's |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To investigate the effect of three single oral doses of BIA 9-1067 (25 mg, 50 mg and 100 mg) on the levodopa pharmacokinetics when administered in combination with immediate release levodopa/carbidopa 100 mg/25 mg or levodopa/benserazide 100 mg/25 mg in Parkinson’s Disease (PD) patients.
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E.2.2 | Secondary objectives of the trial |
To investigate: - tolerability and safety of three single oral doses of BIA 9-1067 (25 mg, 50 mg and 100 mg) when co-administered with immediate release levodopa/carbidopa 100 mg/25 mg or levodopa/benserazide 100 mg/25 mg in PD patients. - effect of three single oral doses of BIA 9-1067 (25 mg, 50 mg and 100 mg) on the motor response to immediate release levodopa/carbidopa 100 mg/25 mg or levodopa/benserazide 100 mg/25 mg in PD patients with end-of-dose deterioration. - effect of three single oral doses of BIA 9-1067 (25 mg, 50 mg and 100 mg) on the erythrocyte soluble catechol-O-methyltransferase (S-COMT) activity when co-administered with immediate release levodopa/carbidopa 100 mg/25 mg or levodopa/benserazide 100 mg/25 mg in PD patients. - pharmacokinetics of three single oral doses of BIA 9-1067 (25 mg, 50 mg and 100 mg) when co-administered with immediate release levodopa/carbidopa 100 mg/25 mg or levodopa/benserazide 100 mg/25 mg in PD patients.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 levodopa/carbidopa 100/25 mg or levodopa/benserazide 100/25 mg 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 patient or for the purpose of the study); able and willing to give written informed consent.
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E.4 | Principal 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 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 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 patient (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 patient’s ability to comply with the study protocol.
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E.5 End points |
E.5.1 | Primary end point(s) |
To investigate the effect of three single oral doses of BIA 9-1067 (25 mg, 50 mg and 100 mg) on the levodopa pharmacokinetics, the Cmax, AUC 0-t and AUC 0-infinite of parameters of levodopa, 3-OMD, BIA 9-1067 and BIA 9-1079 will be the primary variables |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 2 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |