Efficacy of Levodopa/Carbidopa/Entacapone vs Levodopa/Carbidopa in Parkinson's Disease Patients With Early Wearing-off

Parkinson's Disease Clinical Trial

Official title:

A 3-month, Multi-center, Double-blind, Randomized Study to Evaluate the Efficacy of Levodopa/Carbidopa/Entacapone vs Levodopa/Carbidopa in Parkinson's Disease Patients With Impairment of Activities of Daily Living and Early Wearing-off With Levodopa

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00391898
• Other study ID #: CELC200AES03
• Status: Completed
• Phase: Phase 4
• First received: October 24, 2006
• Last updated: February 16, 2011
• Start date: October 2006
• Est. completion date: June 2008

Study information

• Verified date: February 2011
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Agencia Española del Medicamento y Productos Sanitarios. Ministerio de Sanidad y Consumo
• Study type: Interventional

Clinical Trial Summary

The study evaluated the efficacy of levodopa/carbidopa/entacapone vs levodopa/carbidopa in patients with Parkinson's disease and early wearing-off with levodopa

Recruitment information / eligibility

• Status: Completed
• Enrollment: 95
• Est. completion date: June 2008
• Est. primary completion date: June 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 30 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Male and female patients ages = 30 and = 80 years old.

2. A clinical diagnosis of idiopathic Parkinson's disease.

3. Taking a stable dose of levodopa/carbidopa (= 300 and = 600mg) for a period of at least 1 month prior to study entry.

4. Must be using any of the following levodopa/carbidopa standard formulation levodopa/carbidopa 100/25mg dose in any intake of the day.

• 1 full tablet, and/or

• 1½ tablets The patient can also be using, for a period of at least 1 month prior to study entry, 1 tablet of the controlled release formulation of levodopa/carbidopa 100/25 mg (marketed in Spain as Sinemet Plus retard) or 1 tablet the controlled release formulation of levodopa/carbidopa 200/50 mg (marketed in Spain as Sinemet retard) in each intake, at different doses.

5. Must have early end-of-dose wearing-off defined by >= 2 or <=7 positive responses to the QUICK questionnaire.

6. Must have a minimum UPDRS part II (ADL) score of 9.

7. Patients without dyskinesia or with mild dyskinesia.

8. Female patients must be either post-menopausal or using one or more acceptable methods of contraception.

9. Must be capable of satisfying the requirements of the protocol and must be willing and able to give informed consent according to legal requirements.

Exclusion Criteria:

1. Previous or current use of entacapone.

2. History, signs, or symptoms suggesting the diagnosis of secondary or atypical parkinsonism.

3. Unstable Parkinson's disease patients.

4. Patients who experience severe dyskinesia.

5. The following levodopa/carbidopa doses and strengths are not permitted:

• Patients taking ½ tablet of standard formulation levodopa/carbidopa 100/25

• Patients taking standard formulation levodopa/carbidopa 100/10 or 250/25

• Patients taking fewer than 3 or more than 6 daily intakes of standard formulation levodopa/carbidopa 100/25 (fewer than 300mg or more than 600mg of levodopa)

6. Patients with hallucinations or psychiatric diseases related to levodopa or dopamine agonists intake. Patients with major depression.

7. Female patients who are pregnant, trying to become pregnant or nursing (lactating) an infant.

8. Concomitant treatment with MAO-inhibitors (except selegiline up to 10mg/day), rotigotine or neuroleptics, within 60 days prior to the screening visit.

9. Patients with a previous history of Neuroleptic Malignant Syndrome (NMS) and/or non-traumatic rhabdomyolysis.

10. Participated in another trial of an investigational drug/device within the last 30 days prior to study entry.

11. Patients who have a history of poor compliance or are in the Investigator's judgment unlikely to comply with medical regimens or study requirements.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Parkinson Disease
• Parkinson's Disease

Intervention

Drug:
• Levodopa/carbidopa/entacapone
Patients were instructed to take the study medication at the same hours and the same levodopa dose they were taking prior to enrollment in this study. Levodopa/carbidopa/entacapone was available in 2 oral dosage forms: 100/25/200 or 150/37.5/200 mg encapsulated tablets.
• Levodopa/carbidopa
Patients were instructed to take the study medication at the same hours and the same levodopa dose they were taking prior to enrollment in this study. Levodopa/carbidopa was available in 2 oral dosage forms: One or one and one-half 100/25 mg encapsulated tablets.

Locations

Country	Name	City	State
Spain	Hospital Universitario Principe de Asturias	Alcalá de Henares, Madrid
Spain	Fundación Hospital de Alcorcón	Alcorcón (Madrid
Spain	Hospital General de Alicante	Alicante
Spain	Centro Médico Teknon	Barcelona
Spain	Corporació Sanitària Parc Taulí Sabadell	Barcelona
Spain	Hospital Clínic i Provincial de Barcelona	Barcelona
Spain	Hospital de la Santa Creu i de Sant Pau	Barcelona
Spain	Hospital Vall d'Hebron	Barcelona
Spain	Hospital General Yagüe	Burgos
Spain	Hospital Universitario Virgen de las Nieves	Granada
Spain	Hospital Universitari Bellvitge Princeps d'Espanya	L'Hospitalet de Llobregat , Barcelona
Spain	Hospital Juan Canalejo	La Coruña
Spain	Clínica Ruber	Madrid
Spain	Fundación Jiménez Díaz	Madrid
Spain	Hospital 12 de Octubre	Madrid
Spain	Hospital Clínico San Carlos	Madrid
Spain	Hospital General Universitario Gregorio Marañon	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Universitaria de Navarra	Pamplona
Spain	Policlínica Gipuzkoa	San Sebastian
Spain	Hospital General de Catalunya	Sant Cugat del Valles, Barcelona
Spain	Hospital Universitario Virgen del Rocio	Sevilla
Spain	Hospital Mutua de Terrassa	Terrassa, Barcelona
Spain	Hospital Clínico Universitario de Valencia	Valencia
Spain	Hospital Gral. de Valencia	Valencia
Spain	Hospital Universitario de la Fe	Valencia

Sponsors (1)

Lead Sponsor	Collaborator
Novartis

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in the Unified Parkinson's Disease Rating Scale (UPDRS) Part II (Activities of Daily Living [ADL]) Score From Baseline to Month 3	The UPDRS is a standardized assessment scale used to measure a patient's disease state. It is completed by a blinded rater. There are 6 parts to the UPDRS. Part II (items 5-17; total score 0-52, calculated as the sum of the individual items) measures the patient's activities of daily living. A lower total score indicates greater symptom control. A negative change score indicates improvement.	Baseline to end of study (Month 3)	No
Secondary	Change in the UPDRS Part I (Mentation, Behavior, and Mood) Score From Baseline to Month 3	The UPDRS is a standardized assessment scale used to measure a patient's disease state. It is completed by a blinded rater. There are 6 parts to the UPDRS. Part I (items 1-4; total score 0-16, calculated as the sum of the individual items) measures the patient's mentation, mood and behavior. A lower total score indicates greater symptom control. A negative change score indicates improvement.	Baseline to end of study (Month 3)	No
Secondary	Change in the UPDRS Part III (Motor Function) Score From Baseline to Month 3	The UPDRS is a standardized assessment scale used to measure a patient's disease state. It is completed by a blinded rater. There are 6 parts to the UPDRS. Part III (items 18-31; total score 0-56, calculated as the sum of the individual items) measures the patient's motor function. A lower total score indicates greater symptom control. A negative change score indicates improvement.	Baseline to end of study (Month 3)	No
Secondary	Change in the UPDRS Part IV (Complications of Therapy) Score From Baseline to Month 3	Part IV of the UPDRS measures complications the patient may be experiencing with therapy and was only collected at and after the visit at which the first dyskinesia or episode of wearing-off was recorded. Part IV is composed of 3 sections and 11 items: A (32-35, dyskinesia), B (36-39, clinical fluctuations, C (40-42, other complications) (total score 0-23, calculated as the sum of the individual items). A lower total score indicates greater symptom control. A negative change score indicates improvement.	Baseline to end of study (Month 3)	No
Secondary	Change in the 39-item Parkinson's Disease Questionnaire (PDQ-39) Total Score From Baseline to Month 3	The PDQ-39 is an instrument used to assess quality of life in individuals with Parkinson's disease. The questionnaire provides scores on eight scales: Mobility, activities of daily living, emotions, stigma, social support, cognitions, communication, and bodily discomfort. Questions are scored on a 5-point Likert scale ranging from 1 (never) to 3 (sometimes) to 5 (always). The total score can range from 39 to 195. A lower score indicates better quality of life. A positive change score indicates an improvement.	Baseline to end of study (Month 3)	No
Secondary	Patient and Investigator Global Evaluation of the Patient	Both the patient and the investigator made an evaluation of the change in the patient's condition by rating the condition of the patient at the end of the study compared to patient's condition at baseline. The rating was made on a scale ranging from -3 to +3: (-3: Very much improved, -2: much improved, -1: mild improvement, 0: no change, +1: mild deterioration, +2: much deterioration, +3: very much deterioration). A negative score indicates improvement.	Baseline to end of study (Month 3)	No
Secondary	Change on the QUICK Questionnaire (QQ) Score From Baseline to Month 3	The QQ is a self-administered questionnaire that includes 19 wearing-off (WO) symptoms (motor and non-motor). A positive answer to each of the 19 symptoms is given by patients if they presented with a symptom and the symptom disappeared after the next drug dose. Two positive answers are diagnostic of wearing-off (WO). A negative change score indicates improvement.	Baseline to end of study (Month 3)	No