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

• ClinicalTrials.gov Identifier: NCT00391898
• Recruitment Status: Completed
• First Posted: October 25, 2006
• Results First Posted: March 15, 2011
• Last Update Posted: March 15, 2011
• Sponsor: Novartis
• Information provided by: Novartis

Study Description

Brief 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

Condition or disease	Intervention/treatment	Phase
Parkinson's Disease	Drug: Levodopa/carbidopa/entacapone; Drug: Levodopa/carbidopa	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 95 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• 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
• Study Start Date: October 2006
• Actual Primary Completion Date: June 2008
• Actual Study Completion Date: June 2008

Arms and Interventions

Arm	Intervention/treatment
Experimental: Levodopa/carbidopa/entacapone	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.
Active Comparator: Levodopa/carbidopa	Drug: 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.

Outcome Measures

Primary Outcome Measures :

1. Change in the Unified Parkinson's Disease Rating Scale (UPDRS) Part II (Activities of Daily Living [ADL]) Score From Baseline to Month 3 [ Time Frame: Baseline to end of study (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.

Secondary Outcome Measures :

1. Change in the UPDRS Part I (Mentation, Behavior, and Mood) Score From Baseline to Month 3 [ Time Frame: Baseline to end of study (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.
2. Change in the UPDRS Part III (Motor Function) Score From Baseline to Month 3 [ Time Frame: Baseline to end of study (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.
3. Change in the UPDRS Part IV (Complications of Therapy) Score From Baseline to Month 3 [ Time Frame: Baseline to end of study (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.
4. Change in the 39-item Parkinson's Disease Questionnaire (PDQ-39) Total Score From Baseline to Month 3 [ Time Frame: Baseline to end of study (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.
5. Patient and Investigator Global Evaluation of the Patient [ Time Frame: Baseline to end of study (Month 3) ]
   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.
6. Change on the QUICK Questionnaire (QQ) Score From Baseline to Month 3 [ Time Frame: Baseline to end of study (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.

Eligibility Criteria

• Ages Eligible for Study: 30 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

Spain

Hospital Universitario Principe de Asturias

Alcalá de Henares, Madrid, Spain, 28805

Fundación Hospital de Alcorcón

Alcorcón (Madrid, Spain, 28922

Hospital General de Alicante

Alicante, Spain, 03010

Centro Médico Teknon

Barcelona, Spain, 08022

Hospital de la Santa Creu i de Sant Pau

Barcelona, Spain, 08025

Hospital Vall d'Hebron

Barcelona, Spain, 08025

Hospital Clínic i Provincial de Barcelona

Barcelona, Spain, 08036

Corporació Sanitària Parc Taulí Sabadell

Barcelona, Spain, 08208

Hospital General Yagüe

Burgos, Spain, 09005

Hospital Universitario Virgen de las Nieves

Granada, Spain, 18012

Hospital Universitari Bellvitge Princeps d'Espanya

L'Hospitalet de Llobregat , Barcelona, Spain, 08907

Hospital Juan Canalejo

La Coruña, Spain, 15002

Clínica Ruber

Madrid, Spain, 28006

Hospital General Universitario Gregorio Marañon

Madrid, Spain, 28007

Fundación Jiménez Díaz

Madrid, Spain, 28040

Hospital Clínico San Carlos

Madrid, Spain, 28040

Hospital 12 de Octubre

Madrid, Spain, 28041

Hospital Universitario La Paz

Madrid, Spain, 28046

Universitaria de Navarra

Pamplona, Spain, 31008

Policlínica Gipuzkoa

San Sebastian, Spain, 20009

Hospital General de Catalunya

Sant Cugat del Valles, Barcelona, Spain, 08195

Hospital Universitario Virgen del Rocio

Sevilla, Spain, 41013

Hospital Mutua de Terrassa

Terrassa, Barcelona, Spain, 08221

Hospital Universitario de la Fe

Valencia, Spain, 46009

Hospital Clínico Universitario de Valencia

Valencia, Spain, 46010

Hospital Gral. de Valencia

Valencia, Spain, 46014

Sponsors and Collaborators

Novartis

Investigators

• Principal Investigator: Eduard Tolosa-Sarró, Dr.; Hospital Clínic i Provincial de Barcelona

More Information

• Responsible Party: External Affairs, Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00391898 History of Changes
• Other Study ID Numbers: CELC200AES03
• First Posted: October 25, 2006
• Results First Posted: March 15, 2011
• Last Update Posted: March 15, 2011
• Last Verified: February 2011

Keywords provided by Novartis:

Parkinson's disease, adults, levodopa/carbidopa/entacapone, wearing-off, activities of daily living

Additional relevant MeSH terms:

Parkinson Disease; Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Neurodegenerative Diseases; Levodopa; Carbidopa; Entacapone; Antiparkinson Agents; Anti-Dyskinesia Agents; Dopamine Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs; Aromatic Amino Acid Decarboxylase Inhibitors; Enzyme Inhibitors; Catechol O-Methyltransferase Inhibitors