CLINICAL AND PHARMACOLOGICAL STUDY TO EVALUATE THE THERAPEUTIC EQUIVALENCE AND BIOEQUIVALENCE OF LEVODOPA BENSERAZIDE GENERIC FORMULATION (TEVA ITALIA) VERSUS THE ORIGINATOR (MADOPAR®)

• Register: EUCTR
• Last refreshed on: 11 April 2016
• Main ID: EUCTR2012-001245-40-IT
• Date of registration: 17/05/2013
• Prospective Registration: Yes
• Public title: CLINICAL AND PHARMACOLOGICAL STUDY TO EVALUATE THE THERAPEUTIC EQUIVALENCE AND BIOEQUIVALENCE OF LEVODOPA BENSERAZIDE GENERIC FORMULATION (TEVA ITALIA) VERSUS THE ORIGINATOR (MADOPAR®)
• Scientific title: CLINICAL AND PHARMACOKINETICS STUDY TO EVALUATE THE THERAPEUTIC EQUIVALENCE AND BIOEQUIVALENCE OF LEVODOPA BENSERAZIDE GENERIC FORMULATION (TEVA ITALIA) VERSUS THE ORIGINATOR (MADOPAR®)
• Date of first enrolment: 05/06/2013
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-001245-40
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: yes Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: Originator versus generic drug Number of treatment arms in the trial: 2

Countries of recruitment

Italy

Key inclusion & exclusion criteria

Inclusion criteria:
Population: 60 out-patients with a diagnosis of idiopathic Parkinson's disease for at least 5 years, receiving L-dopa, will be enrolled to participate into the study. The study will be performed in hospital setting using the facilities of the clinical trial centre in both sites involved in the study. The patients will be recruited within the patient population using the hospitals out-patients clinics. Recruitment timing will be 12 months.
Inclusion Criteria:
° Subject must be >=30 and <=75 years of age, of either sex and of any race.
° Diagnosis of Parkinson's disease
° Subjects must be in Hoehn and Yahr stages 2 to 4.
° Subject must have good response to levodopa (>=30% improvement in the UPDRS score).
° Subject must have been on a stable regimen of L-dopa for at least 4 month before Screening.
° A female subject must be postmenopausal, or sterile or use a medically accepted method of contraception.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 30
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30

Exclusion criteria:
° Atypical Parkinsonism
° Subjects with very severe motor fluctuations and/or dyskinesias.
° Significant internal-medicine or psychiatric diseases.
° Subject's clinical laboratory tests outside the normal ranges.
° History of previous rabdomiolysis.
° Subjects in therapy with COMT-inhibitor.
° Subjects who participated in any other clinical trial in the 4 months before the screening.
° Any subject who is pregnant or breastfeeding.
° Subjects demented or not able to give informed consent to trial



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

PARKINSON'S DISEASE
MedDRA version: 16.0 Level: LLT Classification code 10013113 Term: Disease Parkinson's System Organ Class: 100000004852

Intervention(s)

Trade Name: Madopar 200+50 mg
Pharmaceutical Form: Tablet

Trade Name: LEVODOPA / BENSERAZIDE 200 + 50 MG
Pharmaceutical Form: Tablet

Primary Outcome(s)

Primary end point(s): Change in UPDRS scores has been used as a primary outcome in a large number of clinical trial. In the present study part III (motor score) will be used as the primary outcome because the motor part is more sensitive to immediate changes and score all the motor symptoms of PD. The bioequivalence will be evaluated with the pharmacokinetic study taking the total Area Under the Curve (AUC) as the primary parameter.

Main Objective: The primary objective of the study will be achieved if non-inferiority in improving motor symptoms (therapeutic equivalence) and bioequivalence in the primary pharmacokinetic parameters (total Area Under the Curve) of the generic levodopa/benserazide compared with originator will be demonstrated. The therapeutic equivalence will be measured with the Unified Parkinson's Disease rating scale (UPDRS) part III (total motor score). A reduction in UPDRS motor score indicates an improvement in the motor symptoms of Parkinson's disease. The bioequivalence will be assessed with the pharmacokinetic study taking the total Area Under the Curve (AUC) as the primary parameter.

Timepoint(s) of evaluation of this end point: At the end of the study

Secondary Objective: Secondary clinical endpoints will the proportion of patients with a score of 1 or 2 (‘very much improved' or ‘much improved') on the Patient Clinical Global Impression - Global Improvement (CGI-I) scale. Secondary PK endpoints will be the bioequivalence in the following parameters: minimum concentration (Cmin), maximum concentration (Cmax), time to maximum concentration (Tmax) and the half life (t 1/2) after the last dose.

Secondary Outcome(s)

Secondary end point(s): Secondary PK endpoints will be the bioequivalence in the following parameters: minimum concentration (Cmin), Maximum concentration (Cmax), time to maximum concentration (Tmax) and the half life (t 1/2) after the last dose. Secondary clinical endpoints will the proportion of patients with a score of 1 or 2 (‘very much improved' or ‘much improved') on the Patient Clinical Global Impression-Global Improvement (CGI-I) scale and total UPDRS score.

Timepoint(s) of evaluation of this end point: At the end of the study

Secondary ID(s)

FARM9X59Y4