Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 3 of 15 for:    glutamate | Parkinson

Efficacy Phase IIa Study of CVXL-0107 in Advanced Parkinson's Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02641054
Recruitment Status : Completed
First Posted : December 29, 2015
Last Update Posted : July 24, 2017
Sponsor:
Information provided by (Responsible Party):
CleveXel Pharma

Brief Summary:
CVXL-0107 a glutamate release inhibitor, has shown evidence of antiparkinsonian and antidyskinetic activity in a macaque model and has shown a significant effect on the UPDRS-III (Movement Disorder Society - Unified Parkinson's Disease Rating Scale) while "ON", as well as an increase of "ON-time" without dyskinesia or without troublesome dyskinesia in a previous phase 2a proof of concept study. This study will confirm the efficacy of CVXL-0107 in combination with optimal dose of levodopa on motor symptoms of Parkinson's disease (PD) .

Condition or disease Intervention/treatment Phase
Idiopathic Parkinson Disease Drug: CVXL-0107 Drug: Placebo Drug: Levodopa Phase 2

Detailed Description:
Phase IIa study, 1:1 randomized, double blind placebo- controlled, with cross-over. Each volunteer patient will be randomly assigned to receive CVXL-0107 or placebo as add-on PD therapy and crossed-over to the other arm in the second sequence of the study. They will be assessed during an acute levodopa challenge test with one intake of the study drug or placebo with a supra-optimal dose of levodopa after 2 weeks of daily treatment with the same study drug or placebo. Patients will be cross-overed to the other treatment and reassessed during a second acute levodopa challenge test after 2 weeks of daily treatment with the study drug or the placebo. The study will evaluate the anti-PD and the anti-dyskinesia efficacy of CVXL-0107 as measured by MDS-UPDRS part III (Movement Disorder Society - Unified Parkinson's Disease Rating Scale) and on levodopa-induced dyskinesia as measured by the AIMS (Abnormal Involuntary Movement Scale).

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 21 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Double-Blind Randomized Placebo-Controlled Cross-Over Phase IIa Trial to Evaluate Efficacy of CVXL-0107 on Parkinson-Related Symptoms and Levodopa-Induced Dyskinesia in Advanced Parkinson's Disease Patients Using a Levodopa Challenge Test
Actual Study Start Date : February 2016
Actual Primary Completion Date : June 2017
Actual Study Completion Date : July 2017

Resource links provided by the National Library of Medicine

Drug Information available for: Levodopa

Arm Intervention/treatment
Experimental: CVXL-0107 then cross-over to placebo

Study drug (CVXL-0107) 4 times per day for 2 weeks on top of usual treatment for Parkinson disease, followed by one challenge test day: one intake of study drug on top of supraoptimal dose of levodopa.

Cross-over to placebo 4 times per day for 2 weeks on top of usual treatment for Parkinson disease, followed by one challenge test day: one intake of placebo on top of supraoptimal dose of levodopa

Drug: CVXL-0107
Drug: Placebo
Drug: Levodopa
Placebo Comparator: Placebo then cross-over to CVXL-0107

Placebo 4 times per day for 2 weeks on top of usual treatment for Parkinson disease, followed by one challenge test day: one intake of placebo on top of supraoptimal dose of levodopa.

Cross-over to study drug (CVXL-0107) 4 times per day for 2 weeks on top of usual treatment for Parkinson disease, followed by one challenge test day: one intake of study drug on top of supraoptimal dose of levodopa

Drug: CVXL-0107
Drug: Placebo
Drug: Levodopa



Primary Outcome Measures :
  1. Change in MDS-UPDRS part III (Movement Disorder Society - Unified Parkinson's Disease Rating Scale Part III) score. [ Time Frame: at visit 3 (day 15= challenge test day) and visit 4 (day 37= challenge test day): at baseline (before L-Dopa administration), then every 20 minutes during the first hour and then every 30 minutes during 5 hours. ]
    CVXL-0107 and placebo

  2. Change in AIMS ( Abnormal Involuntary Movement Scale) score [ Time Frame: at visit 3 (day 15= challenge test day) and visit 4 (day 37 = challenge test day): at baseline (before L-Dopa administration), then every 20 minutes during the first hour and then every 30 minutes during 5 hours ]
    CVXL-0107 and placebo


Secondary Outcome Measures :
  1. Incidence of Clinical Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: at visit 3 (day 14) and visit 4 (day 36) ]
    Physical examination, vital signs

  2. Hematology laboratory safety of CVXL-0107 [ Time Frame: at visit 3 (day 14) and visit 4 (day 36) ]
    complete blood count

  3. Hepatic laboratory safety of CVXL-0107 [ Time Frame: at visit 3 (day 14) and visit 4 (day 36) ]
    aspartate transaminase, alanine transaminase, gamma-glutamyl-transpeptidase, alkaline phosphatase

  4. Area Under the Curve [AUC] of CVXL-0107 concentrations [ Time Frame: at visit 3 (day 15= challenge test day) and visit 4 (day 37= challenge test day) ]
    Blood samples at L-dopa intake and after 20', 40', 60', 90', 120', 240'.

  5. Area Under the Curve [AUC] of levodopa concentrations [ Time Frame: at visit 3 (day 15= challenge test day) and visit 4 (day 37= challenge test day) ]
    Blood samples at L-dopa intake and after 20', 40', 60', 90', 120', 240'.

  6. Assessment of total daily "ON" time in Patients Diaries [ Time Frame: During 3 days, prior to visit 3 (days 11-13) and prior to visit 4 (days 33, 34, 35) ]
    Total "ON-time"

  7. Assessment of daily "ON" time without dyskinesia in Patients Diaries [ Time Frame: During 3 days; prior to visit 3 (days 11-13) and prior to visit 4 (days 33, 34, 35) ]
    "ON-time" without dyskinesia



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   40 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Signed written Informed Consent
  2. Male and female patient aged 40 -75 years
  3. Clinical diagnosis of idiopathic PD according to the UK Parkinson's Disease Society Brain Bank Clinical Diagnosis Criteria
  4. Advanced PD with clear daily motor fluctuations and dyskinesia with optimal levodopa-based therapy
  5. At least 2 hours in "OFF" state per day including morning OFF
  6. Predictable "OFF" in the morning on awakening prior to receiving morning dose of levodopa
  7. During an acute levodopa challenge test : Motor improvement of at least 30% on the MDS-UPDRS part III and AIMS score ≥ 1 at least two time points
  8. Patient with dyskinesia: MDS-UPDRS items 4.1 ("time spent with dyskinesia") and 4.2 ("functional impact of dyskinesia") scores ≥ 1 at Screening
  9. Hoehn and Yahr stages of 2-4 in the "OFF" state at Screening
  10. Stable doses and regimens of antiparkinsonian medications for at least the last month prior to randomization (levodopa, dopamine agonists and selective monoamine oxidase type B inhibitors (selegiline, rasagiline))
  11. Anti-PD therapy intended to remain constant throughout the course of the study
  12. Normal platelets count
  13. Mini-mental state examination (MMSE)≥24 at Screening
  14. PD patient treated by DBS can be included if surgery occurred at least one year before the study
  15. Patient with health insurance
  16. Female of childbearing potential with an effective contraception

Exclusion Criteria:

  1. Any relevant neurologic or psychiatric disease, except idiopathic PD
  2. Any secondary causes for Parkinsonism or other neurodegenerative disorder with Parkinsonism symptoms
  3. Any neurosurgical intervention for PD planned during the study period
  4. Neuroleptics and any D2-receptor antagonists within the last 3 months before Screening
  5. Amantadine, Riluzole, dextromethorphan, apomorphine continuous infusion (pump), morphine, or memantine, during the last month before screening and during the study duration
  6. History of psychosis or treatment with any antipsychotic drugs within the last 2 years
  7. History of seizure or epilepsy, or treatment with anticonvulsant drugs within the last year
  8. Any clinically significant unstable medical illness in the last month before randomization (e.g. unstable angina, unstable vascular disease etc)
  9. Anti-cancer treatment within the 3 months before Screening
  10. Treatment with anticoagulant drugs
  11. Any clinically significant renal (serum creatinine level ≥1.5x ULN or dialysis) or hepatic (liver enzyme values≥2x ULN) disease
  12. Any clinically significant condition that may compromise the safety of patient or the conduct of the study protocol according to Investigators' opinion.
  13. Known genetic disorder of human UDP-glucuronosyltransferase
  14. Participation in another trial with any investigational product within the last month before randomization or intake of any investigational product
  15. Pregnant, breastfeeding or lactating female

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02641054


Locations
Layout table for location information
France
Clevexel Pharma
Maisons-Alfort, France, 94700
Sponsors and Collaborators
CleveXel Pharma
Investigators
Layout table for investigator information
Principal Investigator: Jean-Christophe Corvol, MD, PhD CIC-Neurologie, bâtiment ICM, Hôpital Pitié-Salpêtrière, 47/83 Bd de l'Hôpital, 75013 Paris, France

Layout table for additonal information
Responsible Party: CleveXel Pharma
ClinicalTrials.gov Identifier: NCT02641054     History of Changes
Other Study ID Numbers: CT-CVXL-0107-01
First Posted: December 29, 2015    Key Record Dates
Last Update Posted: July 24, 2017
Last Verified: July 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Layout table for MeSH terms
Parkinson Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Levodopa
Antiparkinson Agents
Anti-Dyskinesia Agents
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs