Levodopa Benserazide Generic Formulation Versus the Originator

NCT02741947 | Completed Phase 4 DMC

• 1 other identifier: RP 13/12
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

The trial was an experimental two-centers, randomized, double-blind, two-sequence, non-inferiority cross-over study. Screened subjects already treated with Levodopa/Benserazide (LDB) (Madopar®) who agreed to participate in the study entered a 4 weeks period if not on stable regimen of Madopar® (run-in period). Following the run-in period, there were two maintenance periods of 4 weeks each, for a total duration of 8 weeks. Patients were assigned randomly (1:1) by a computerized randomization system to one of two formulation sequences maintaining the dose stabilized during the run in:

• generic-originator
• originator-generic At the end of maintenance period 1, the patients in each formulation group underwent an overnight switch to the same dose of the alternative formulation. The dose was kept stable during the whole length of trial. Clinical evaluations were performed at the end of each period. The tablets were encapsulated to maintain the blindness. A pharmacokinetic study with a fixed dose (100+25 mg) was performed in a sub-population of 14 subjects. Population: out-patients with a diagnosis of idiopathic Parkinson's disease for at least 5 years, receiving L-dopa/benserazide. The total duration of the trial was approximately 8 weeks for patient divided in two maintenance periods of 4 weeks each.

Conditions

Parkinson Disease

Keywords

Parkinson; Therapeutic Equivalence; Levodopa

Outcome Measures

Primary Outcomes (2)

• Change in bioequivalence in the total Area Under the Curve (AUC-t) between the generic levodopa/benserazide and the originator.

  AUC-t: area under the curve within first and last observed point

  end of maintenance period 1 and maintenance period 2 (each period of 4 weeks)

• Change in therapeutic equivalence measured with the Unified Parkinson's Disease rating scale part III between the generic levodopa/benserazide and the originator.

  A difference of -3 points on the UPDRS motor score be the margin for non-inferiority

  end of maintenance period 1 and maintenance period 2 (each period of 4 weeks)

Secondary Outcomes (4)

• Change in Patient Clinical Global Impression - Global Improvement scale between the generic levodopa/benserazide and the originator.

  end of maintenance period 1 and maintenance period 2 (each period of 4 weeks)

• Change in bioequivalence in minimum concentration (Cmin) between the generic levodopa/benserazide and the originator.

  end of maintenance period 1 and maintenance period 2 (each period of 4 weeks)

• Change in bioequivalence in time to maximum concentration (Tmax) after the last dose between the generic levodopa/benserazide and the originator.

  end of maintenance period 1 and maintenance period 2 (each period of 4 weeks)

• Change in bioequivalence in the half life (t 1/2) after the last dose between the generic levodopa/benserazide and the originator.

  end of maintenance period 1 and maintenance period 2 (each period of 4 weeks)

Study Arms (2)

Levodopa Benserazide Madopar

ACTIVE COMPARATOR

Madopar 100+25mg and 200+50mg, tablet, tid e qid, for four weeks

Drug: Levodopa Benserazide Madopar

Levodopa Benserazide Teva Italia

EXPERIMENTAL

Levodopa Benserazide Teva Italia100+25mg and 200+50mg, tablet, tid e qid, for four weeks

Drug: Levodopa Benserazide Teva Italia

Interventions

Levodopa Benserazide Madopar DRUG

Madopar 100+25mg and 200+50mg, tablet, tid e qid, for four weeks

Levodopa Benserazide Madopar

Levodopa Benserazide Teva Italia DRUG

Levodopa benserazide Teva 100+25mg and 200+50mg, tablet, tid e qid, for four weeks

Levodopa Benserazide Teva Italia

Eligibility Criteria

• Age: 30 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Out-patients with a diagnosis of idiopathic Parkinson's disease for at least 5 years, receiving L-dopa/benserazide, were enrolled to participate into the study. The patients were recruited within the patient population using the hospitals out-patients clinics.
• Subject must be ≥30 and ≤75 years of age, of either sex and of any race.
• Diagnosis of Parkinson's disease
• Subjects 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.
• Fragile population was included in the trial (Elderly 65-74 years and over 75 years).

You may not qualify if:

• 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 rhabdomyolysis
• Subjects in therapy with Catechol-O-methyltransferase-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

Sponsors & Collaborators

• IRCCS San Raffaele Roma: lead
• Agenzia Italiana del Farmaco: collaborator

Study Sites (1)

Irccs San Raffaele Pisana

Rome, 00163, Italy

Location

Related Publications (3)

• Stocchi F, Jenner P, Obeso JA. When do levodopa motor fluctuations first appear in Parkinson's disease? Eur Neurol. 2010;63(5):257-66. doi: 10.1159/000300647. Epub 2010 Mar 24.

  PMID: 20332641 RESULT

• Olanow CW, Agid Y, Mizuno Y, Albanese A, Bonuccelli U, Damier P, De Yebenes J, Gershanik O, Guttman M, Grandas F, Hallett M, Hornykiewicz O, Jenner P, Katzenschlager R, Langston WJ, LeWitt P, Melamed E, Mena MA, Michel PP, Mytilineou C, Obeso JA, Poewe W, Quinn N, Raisman-Vozari R, Rajput AH, Rascol O, Sampaio C, Stocchi F. Levodopa in the treatment of Parkinson's disease: current controversies. Mov Disord. 2004 Sep;19(9):997-1005. doi: 10.1002/mds.20243.

  PMID: 15372588 RESULT

• Stocchi F. The levodopa wearing-off phenomenon in Parkinson's disease: pharmacokinetic considerations. Expert Opin Pharmacother. 2006 Jul;7(10):1399-407. doi: 10.1517/14656566.7.10.1399.

  PMID: 16805724 RESULT

MeSH Terms

Conditions

Parkinson Disease

Interventions

benserazide, levodopa drug combination

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Study Officials

• FABRIZIO STOCCHI, PROFESSOR

  IRCCS San Raffaele

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 31, 2016
• First Posted: April 18, 2016
• Study Start: April 1, 2014
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: April 10, 2024

Record last verified: 2016-04

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)