Open Label Continuation Treatment Study With Levodopa-Carbidopa Intestinal Gel in Advanced Parkinson's Disease

Phase 3

Completed

Conditions: Advanced Parkinson's Disease

Interventions: Drug: Levodopa-Carbidopa Intestinal Gel (LCIG)
Device: CADD-Legacy® 1400 ambulatory infusion pump
Device: Percutaneous Endoscopic Gastrostomy with jejunal extension tube (PEG-J)

Registration Number: NCT00660673

Lead Sponsor: AbbVie

Brief Summary: The primary objective of this study is to provide continued access to levodopa-carbidopa intestinal gel (LCIG), to participants who have already participated in an open-label efficacy and safety study with the same treatment (Study S187.3.003 \[NCT00360568\] or Study S187.3.004 \[NCT00335153\]).

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: Not specified

Target Recruitment: 262

Inclusion Criteria

The participant should have completed participation in Study S187.3.003 or S187.3.004; and, in the opinion of the Principal Investigator, would benefit from long-term treatment with LCIG.
For Canada, participants will be allowed to participate in the S187.3.005 study with a minimum of 6 months of exposure to LCIG in the S187.3.004 study.
The participant must be able to understand the nature of the study and must provide written informed consent prior to the conduct of any study related procedures. If the participant does not have the capacity to provide informed consent, full informed consent must be obtained from the participant's legally authorized representative. Consenting will be performed according to local regulations.

Exclusion Criteria

Medical, laboratory, psychiatric, or surgical issues deemed by the investigator to be clinically significant and which could interfere with the participant's participation in the study.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Levodopa-Carbidopa Intestinal Gel	CADD-Legacy® 1400 ambulatory infusion pump	Initial dosing is based on the dosing regimen that the participant received during the previous LCIG study. Dosing is individually optimized and can be adjusted at any time during the study as clinically indicated. The total dose/day of LCIG is composed of 3 individually adjusted doses. The morning dose is administered as a bolus infusion, usually 5 to 10 mL (100 to 200 mg levodopa). The maintenance dose is adjustable in steps of 2 mg/hour (0.1 mL/hour), within a range of 1 to 10 mL/hour (20 to 200 mg levodopa/hour) and is usually 2 to 6 mL/hour (40 to 120 mg levodopa/hour). Participants will be allowed to self-administer extra doses of LCIG to address immediate medical needs, normally 0.5 to 2.0 mL. Participants will receive LCIG until it is commercially available.
Levodopa-Carbidopa Intestinal Gel	Percutaneous Endoscopic Gastrostomy with jejunal extension tube (PEG-J)	Initial dosing is based on the dosing regimen that the participant received during the previous LCIG study. Dosing is individually optimized and can be adjusted at any time during the study as clinically indicated. The total dose/day of LCIG is composed of 3 individually adjusted doses. The morning dose is administered as a bolus infusion, usually 5 to 10 mL (100 to 200 mg levodopa). The maintenance dose is adjustable in steps of 2 mg/hour (0.1 mL/hour), within a range of 1 to 10 mL/hour (20 to 200 mg levodopa/hour) and is usually 2 to 6 mL/hour (40 to 120 mg levodopa/hour). Participants will be allowed to self-administer extra doses of LCIG to address immediate medical needs, normally 0.5 to 2.0 mL. Participants will receive LCIG until it is commercially available.
Levodopa-Carbidopa Intestinal Gel	Levodopa-Carbidopa Intestinal Gel (LCIG)	Initial dosing is based on the dosing regimen that the participant received during the previous LCIG study. Dosing is individually optimized and can be adjusted at any time during the study as clinically indicated. The total dose/day of LCIG is composed of 3 individually adjusted doses. The morning dose is administered as a bolus infusion, usually 5 to 10 mL (100 to 200 mg levodopa). The maintenance dose is adjustable in steps of 2 mg/hour (0.1 mL/hour), within a range of 1 to 10 mL/hour (20 to 200 mg levodopa/hour) and is usually 2 to 6 mL/hour (40 to 120 mg levodopa/hour). Participants will be allowed to self-administer extra doses of LCIG to address immediate medical needs, normally 0.5 to 2.0 mL. Participants will receive LCIG until it is commercially available.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Treatment-emergent Adverse Events	From first dose of LCIG in this study up to 30 days after the date of last PEG-J exposure; median duration of treatment was 1178 days, with a maximum of 4217 days (11.5 years).	Treatment-emergent adverse events (TEAEs) are defined as adverse events (AEs) which started on or after the date of the first LCIG Infusion in this study and within 30 days of the date of the last PEG-J exposure. At least possibly drug-related is defined as TEAEs assessed as having a "Possible" or "Probable" or missing relationship to study drug. Serious AEs included any untoward medical occurrence that: * Resulted in death * Was life-threatening * Required inpatient hospitalization or prolongation of an existing hospitalization * Resulted in persistent or significant disability/incapacity * was a congenital anomaly/birth defect The severity of all AEs was characterized as mild, moderate or severe according to the following definitions: * Mild: usually transient and do not interfere with daily activities. * Moderate: low level of inconvenience or concern to the subject, may interfere with daily activities. * Severe: events interrupt the subject's usual daily activity.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Device Complications	From first dose of LCIG in this study up to 30 days after the date of last PEG-J exposure; median duration of treatment was 1178 days.	Device complications include complications with the pump, intestinal tube, PEG-J or stoma.
Number of Participants Who Developed Melanoma	Once per year during the study; median duration of treatment was 1178 days.	A comprehensive assessment for the presence of melanoma was performed at least once a year by a dermatologist.
Number of Participants With Treatment-emergent Adverse Events of Special Interest (TE AESI)	From first dose of LCIG in this study up to 30 days after the date of last PEG-J exposure; median duration of treatment was 1178 days, with a maximum of 4217 days (11.5 years).	Adverse events of special interest (AESIs) were identified using standardized Medical Dictionary for Regulatory Activities (MedDRA) queries (SMQ) or company MedDRA queries (CMQs). The AESI in the following categories were identified on the basis of review of the clinical program and postmarketing observations where the treatment system is commercially available. * Procedure and device associated events * Polyneuropathy, included preferred terms in either the peripheral neuropathy or GuillainBarre syndrome standardized MedDRA query (narrow search), such as polyneuropathy, decreased vibratory sense, peripheral neuropathy, peripheral sensory neuropathy, neuralgia, demyelinating polyneuropathy, and sensory disturbance * Weight loss * Cardiovascular fatalities * Respiratory tract aspiration including aspiration pneumonia/pneumonitis.
Number of Participants With Potentially Clinically Significant Hematology Laboratory Values	Baseline and every 6 months until final visit; median duration of treatment was 1178 days.	A laboratory value was considered potentially clinically significant if it satisfied the pre-specified criteria presented in the table and was also more extreme than the participant's corresponding Baseline value.
Number of Participants With Intense Impulsive Behavior	Baseline (final assessment of the previous open-label LCIG study) and every 6 months until final visit; median duration of treatment was 1178 days.	To monitor for the development of intense impulsive behavior the Minnesota Impulsive Disorder Interview (MIDI) was administered. The MIDI is a semi-structured clinical interview assessing pathological gambling, trichotillomania, kleptomania, pyromania, intermittent explosive disorder, compulsive buying, and compulsive sexual behavior.
Number of Participants With Potentially Clinically Significant Chemistry Laboratory Values	Baseline and every 6 months until final visit; median duration of treatment was 1178 days.	A laboratory value was considered potentially clinically significant if it satisfied the pre-specified criteria presented in the table and was also more extreme than the participant's corresponding baseline value. ULN = upper limit of normal
Number of Participants With Sleep Attacks	Baseline (final assessment period of the previous open-label LCIG study) and every 6 months until final visit; median duration of treatment was 1178 days.	Participants were asked whether they experienced any events in which they fell asleep suddenly or unexpectedly, including while engaged in some activity (e.g., eating/drinking, speaking, or driving) or at rest, with or without any previous warning of sleepiness. If yes, participants were asked if they suffered any "bad" outcome or problem from the falling asleep event.
Number of Participants With Any Suicidal Ideation or Behavior	Every 6 months (beginning with implementation of Protocol Amendment 3) until final visit; median duration of treatment was 1178 days.	The Columbia-Suicide Severity Rating Scale (C-SSRS) was implemented with Protocol Amendment 3 (20 March 2012) in order to assess suicidal behavior and ideation. Suicidal ideation includes the wish to be dead, nonspecific active suicidal thoughts, active ideation without intent to act, active ideation with some intent to act, and active ideation with specific plan or intent. Suicidal behavior includes actual attempts, interrupted attempts, aborted attempts, completed suicide, and preparatory acts or behaviors. The number of participants with affirmative responses on the C-SSRS at any time during the treatment period is reported.
Number of Participants With Potentially Clinically Significant Vital Sign Values	Baseline and every 6 months until final visit; median duration of treatment was 1178 days.	A vital sign value was considered potentially clinically significant if it satisfied the pre-specified criteria presented in the table and was also more extreme than the participant's corresponding Baseline value.
Number of Participants With Vitamin Levels Outside of the Normal Range	Every 6 months (beginning with implementation of Protocol Amendment 2) until final visit; median duration of treatment was 1178 days.	Special tests for vitamin deficiencies (folic acid, vitamin B6, vitamin B12, methylmalonic acid \[MMA\], and homocysteine) were implemented with Protocol Amendment 2 (27 July 2011). The number of participants with vitamin levels outside of the normal range at any time post-baseline is reported for each vitamin tested.
Change in Unified Parkinson's Disease Rating Scale (UPDRS) Part I Score at End of Treatment	Prior to initial LCIG infusion (in the previous study, before the first LCIG infusion), Baseline (final assessment of the previous open-label LCIG study), and end of treatment; median duration of treatment was 1178 days.	The UPDRS is an Investigator-used rating tool to follow the longitudinal course of PD. It is made up of the following sections: I) Mentation, Behavior, and Mood; II) Activities of Daily Living; III) Motor Examinations; IV) Complications of Therapy sections (including dyskinesias). The Part I Score is the sum of the answers to the 4 questions that comprise Part I, each of which are measured on a 5-point scale (0-4). The Part I score ranges from 0-16 and higher scores are associated with more disability. A negative change from Baseline indicates improvement. The UPDRS was implemented with Protocol amendment 4 (December 2013) for participants at US sites only.
Change in Unified Parkinson's Disease Rating Scale (UPDRS) Part IV Dyskinesia Score at End of Treatment	Prior to initial LCIG infusion (in the previous study, before the first LCIG infusion), Baseline (final assessment of the previous open-label LCIG study), and end of treatment; median duration of treatment was 1178 days.	The UPDRS is an Investigator-used rating tool to follow the longitudinal course of PD. It is made up of the following sections: I) Mentation, Behavior, and Mood; II) Activities of Daily Living; III) Motor Examinations; IV) Complications of Therapy sections (including Dyskinesias); and The UPDRS Part IV dyskinesia Score is the sum of Questions 32 (What proportion of the waking day are dyskinesias present?), 33 (How disabling are the dyskinesias? ), and 34 (How painful are the dyskinesias?) on UPDRS Part IV, each of which are measured on a 5-point scale (0-4). The Part IV dyskinesia score ranges from 0 - 12 and higher scores are associated with more disability. A negative change from Baseline indicates improvement. The UPDRS was implemented with Protocol amendment 4 (December 2013) for participants at US sites only.
Number of Participants Receiving Concomitant Anti-Parkinson's Disease Medications by Treatment Year	Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9, Year 10, > Year 10 (maximum time on treatment was approximately 11.5 years).	Participants could use oral levodopa-carbidopa for scheduled or supplemental bedtime/overnight doses after the pump was disconnected for the night, or as rescue medication in case of acute deterioration caused by failure of the LCIG system such as tubes and/or the pump or the onset of an acute illness. The initiation of additional concomitant PD medication was allowed at the discretion of the Investigator if medically indicated.
Change in Unified Parkinson's Disease Rating Scale (UPDRS) Part III Score at End of Treatment	Prior to initial LCIG infusion (in the previous study, before the first LCIG infusion), Baseline (final assessment of the previous open-label LCIG study), and end of treatment; median duration of treatment was 1178 days.	The UPDRS is an Investigator-used rating tool to follow the longitudinal course of PD. It is made up of the following sections: I) Mentation, Behavior, and Mood; II) Activities of Daily Living; III) Motor Examinations; IV) Complications of Therapy sections (including dyskinesias). UPDRS Part III consists of 14 questions. Questions 20 - 26 are multi-part questions in that they are evaluated separately for multiple body parts. Counting each of these assessments leads to a total of 27 answers for Part III. The UPDRS Part III score is the sum of the 27 answers provided to the 14 Part III questions, each of which are measured on a 5-Point scale (0-4). The Part III score ranges from 0-108 and higher scores are associated with more disability. A negative change from Baseline indicates improvement. The UPDRS was implemented with Protocol amendment 4 (December 2013) for participants at US sites only.
Change in Unified Parkinson's Disease Rating Scale (UPDRS) Total Score at End of Treatment	Prior to initial LCIG infusion (in the previous study, before the first LCIG infusion), Baseline (final assessment of the previous open-label LCIG study), and end of treatment; median duration of treatment was 1178 days.	The UPDRS is an Investigator-used rating tool to follow the longitudinal course of PD. It is made up of the following sections: I) Mentation, Behavior, and Mood; II) Activities of Daily Living; III) Motor Examinations; IV) Complications of Therapy sections (including dyskinesias). The UPDRS total score is the sum of the responses to the 31 questions (44 answers) that comprise Parts I - III of the scale. The total score ranges from 0 - 176 with 176 representing the worst (total) disability, and 0 no disability. A negative change from Baseline indicates improvement. The UPDRS was implemented with Protocol amendment 4 (December 2013) for participants at US sites only.
Change in Unified Parkinson's Disease Rating Scale (UPDRS) Part IV Score at End of Treatment	Prior to initial LCIG infusion (in the previous study, before the first LCIG infusion), Baseline (final assessment of the previous open-label LCIG study), and end of treatment; median duration of treatment was 1178 days.	The UPDRS is an Investigator-used rating tool to follow the longitudinal course of PD. It is made up of the following sections: I) Mentation, Behavior, and Mood; II) Activities of Daily Living; III) Motor Examinations; IV) Complications of Therapy sections (including Dyskinesias). The UPDRS Part IV Score is the sum of all answers to the 11 questions that comprise Part IV, 4 of which are measured on a 5-point scale (0 - 4) and 7 which are measured on a 2-point scale (0 - 1). The Part IV score ranges from 0 - 23 with higher scores associated with more disability. A negative change from Baseline indicates improvement. The UPDRS was implemented with Protocol amendment 4 (December 2013) for participants at US sites only.
Change in Parkinson's Disease Questionnaire (PDQ-39) Scores at End of Treatment	Prior to initial LCIG infusion (in the previous study, before the first LCIG infusion), Baseline (final assessment of the previous open-label LCIG study), and end of treatment; median duration of treatment was 1178 days.	The PDQ-39 is a self-administered questionnaire that comprises 39 items addressing the following eight domains of health that patients consider to be adversely affected by the disease: * Mobility (e.g., fear of falling when walking) - 10 questions * Activities of daily living (e.g., difficulty cutting food) - 6 questions * Emotional well-being (e.g., feelings of isolation) - 6 questions * Stigma (e.g., social embarrassment) - 4 questions * Social support - 3 questions * Cognition - 4 questions * Communication - 3 questions * Bodily discomfort - 3 questions Each question is answered on a 5-point scale from 0 (Never) to 4 (Always / Cannot Do At All). Scores are calculated by summing the answers to the questions in the domain and converting to a scale from 0 to 100. Higher scores are associated with the more severe symptoms of the disease such as tremor and stiffness. The PDQ-39 summary index (range 0-100) includes responses to all 39 items. A negative change indicates improvement.
Change in Average Daily "Off" Time Based on the Parkinson's Disease Symptom Diary at End of Treatment	Prior to initial LCIG infusion (in the previous study, before the first LCIG infusion), Baseline (final assessment of the previous open-label LCIG study), and end of treatment; median duration of treatment was 1178 days.	The PD symptom diary asks participants (or their caregivers) to indicate their status upon waking and every 30 minutes during their normal waking time according to the following categories: asleep, "off", "on" without dyskinesia, "on" with non-troublesome dyskinesia, or "on" with troublesome dyskinesia. "Off" time was defined as time when medication had worn off and was no longer providing benefit with regard to mobility, slowness, and stiffness. PD diary times were normalized to a 16-hour waking day and averaged for the 3 days prior to each study visit. A negative change for "off" time indicates improvement. The PD diary assessment was implemented with Protocol amendment 4 (December 2013) for participants at United States (US) sites only.
Change in Average Daily "On" Time With Troublesome Dyskinesia Based on the Parkinson's Disease Symptom Diary at End of Treatment	Prior to initial LCIG infusion (in the previous study, before the first LCIG infusion), Baseline (final assessment of the previous open-label LCIG study), and end of treatment; median duration of treatment was 1178 days.	The PD diary asks participants (or their caregivers) to indicate their status upon waking and every 30 minutes during their normal waking time according to the following categories: asleep, "off", "on" without dyskinesia, "on" with non-troublesome dyskinesia, or "on" with troublesome dyskinesia. "On" time is when medication is providing benefit with regard to mobility, slowness and stiffness. Dyskinesia is involuntary twisting, turning movements which are an effect of medication and occur during "on" time. Troublesome dyskinesia interferes with function or causes meaningful discomfort. PD diary times were normalized to a 16-hour waking day and averaged for the 3 days prior to each study visit. A positive change indicates improvement. The PD diary was implemented with Protocol amendment 4 (December 2013) for participants at US sites only.
Change in Unified Parkinson's Disease Rating Scale (UPDRS) Part II Score at End of Treatment	Prior to initial LCIG infusion (in the previous study, before the first LCIG infusion), Baseline (final assessment of the previous open-label LCIG study), and end of treatment; median duration of treatment was 1178 days.	The UPDRS is an Investigator-used rating tool to follow the longitudinal course of PD. It is made up of the following sections: I) Mentation, Behavior, and Mood; II) Activities of Daily Living; III) Motor Examinations; IV) Complications of Therapy sections (including dyskinesias). The Part II score is the sum of the answers to the 13 questions that comprise Part II, each of which are measured on a 5-point scale (0-4). The Part II score ranges from 0-52 and higher scores are associated with more disability. A negative change from Baseline indicates improvement. The UPDRS was implemented with Protocol amendment 4 (December 2013) for participants at US sites only.
Change in Average Daily "On" Time Without Troublesome Dyskinesia Based on the Parkinson's Disease Symptom Diary at End of Treatment	Prior to initial LCIG infusion (in the previous study, before the first LCIG infusion), Baseline (final assessment of the previous open-label LCIG study), and end of treatment; median duration of treatment was 1178 days.	The PD diary asks participants (or their caregivers) to indicate their status upon waking and every 30 minutes during their normal waking time according to the following categories: asleep, "off", "on" without dyskinesia, "on" with non-troublesome dyskinesia, or "on" with troublesome dyskinesia. "On" time is when medication is providing benefit with regard to mobility, slowness and stiffness. Dyskinesia is involuntary twisting, turning movements which are an effect of medication and occur during "on" time. Non-troublesome dyskinesia does not interfere with function or cause meaningful discomfort. "On" time without troublesome dyskinesia is the sum of "on" time without dyskinesia and "on" time with non-troublesome dyskinesia. PD diary times were normalized to a 16-hour waking day and averaged for the 3 days prior to each study visit. A positive change indicates improvement. The PD diary was implemented with Protocol amendment 4 (December 2013) for participants at US sites only.

Trial Locations

Locations (61): Univ Maryland School Medicine /ID# 49934
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Baltimore, Maryland, United States
Johns Hopkins University /ID# 49937
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Baltimore, Maryland, United States
Charlotte Neurological Service /ID# 49916
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Port Charlotte, Florida, United States
Royal Adelaide Hospital /ID# 50083
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Adelaide, South Australia, Australia
Rush University Medical Center /ID# 49930
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Chicago, Illinois, United States
University of Nebraska Medical Center /ID# 49911
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Omaha, Nebraska, United States
Scientific Research Medical Complex Your Health /ID# 50104
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Kazan, Russian Federation
Military Medical Academy n.a. Kirov /ID# 50103
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Saint Petersburg, Russian Federation
Georgetown University Hospital /ID# 49931
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Washington, District of Columbia, United States
Miejskie Centrum Medyczne im. dr. Karola Jonschera w Lodzi /ID# 50096
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Łódź, Lodzkie, Poland
University of Alabama at Birmingham /ID# 49941
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Birmingham, Alabama, United States
University of Cincinnati /ID# 49914
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Cincinnati, Ohio, United States
Georgia Regents University /ID# 49938
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Augusta, Georgia, United States
University of Alberta /ID# 78476
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Edmonton, Alberta, Canada
Bradenton Research Center, Inc /ID# 49929
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Bradenton, Florida, United States
North Shore University Hospital /ID# 49932
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Manhasset, New York, United States
University of Vermont Medical Center /ID# 49912
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Burlington, Vermont, United States
Toronto Western Hospital /ID# 75913
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Toronto, Ontario, Canada
Columbia Univ Medical Center /ID# 49943
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New York, New York, United States
University of Kentucky Chandler Medical Center /ID# 49940
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Lexington, Kentucky, United States
Colorado Neurological Institute /ID# 49927
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Englewood, Colorado, United States
Louisiana State Univ HSC /ID# 49945
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Shreveport, Louisiana, United States
Fakultni Nemocnice u Svate Anny /ID# 50085
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Brno, Czechia
The Mount Sinai Hospital /ID# 49942
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New York, New York, United States
Austin Hospital /ID# 50082
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Heidelberg, Victoria, Australia
Auckland City Hospital /ID# 50093
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Auckland, New Zealand
University of Florida - Archer /ID# 49935
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Gainesville, Florida, United States
The Research Center of Southern California /ID# 49928
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Encinitas, California, United States
University of South Florida /ID# 49919
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Tampa, Florida, United States
Northwestern University Feinberg School of Medicine /ID# 49944
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Chicago, Illinois, United States
Raleigh Neurology Associates /ID# 49923
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Raleigh, North Carolina, United States
Westmead Hospital /ID# 50081
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Westmead, New South Wales, Australia
Wake Forest Univ HS /ID# 49939
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Winston-Salem, North Carolina, United States
CHUM - Notre-Dame Hospital /ID# 74513
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Montréal, Quebec, Canada
Tel Aviv Sourasky Medical Center /ID# 50089
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Tel-Aviv, Israel
Pardubicka krajska nemocnice, a.s.
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Pardubice, Czechia
Fakultni nemocnice Hradec Kralove /ID# 50088
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Hradec Králové, Czechia
Waikato Hospital /ID# 50091
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Hamilton, Waikato, New Zealand
Vseobecna fakultni nemocnice v Praze /ID# 50086
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Praha, Czechia
Fakultni Nemocnice v Motole /ID# 50084
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Praha, Czechia
Hospitais da Universidade de Coimbra /ID# 50098
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Coimbra, Portugal
Hospital de Santa Maria /ID# 50099
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Lisboa, Portugal
Siriraj Hospital /ID# 50109
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Bangkok, Thailand
Institution of the Russian Academy of Medical Sciences Scientific Centre of Neurology /ID# 50102
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Moscow, Russian Federation
City Clinical Hospital #40 /ID# 50106
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Saint Petersburg, Russian Federation
King Chulalongkorn Mem Hosp /ID# 50108
🇹🇭
Bangkok, Thailand
New Zealand Brain Research Institute/ID# 50090
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Christchurch, New Zealand
Wellington Hospital /ID# 50092
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Wellington, New Zealand
Cleveland Clinic Main Campus /ID# 76173
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Cleveland, Ohio, United States
Froedtert Memorial Lutheran Hospital /ID# 49924
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Milwaukee, Wisconsin, United States
King County Public Hospital /ID# 49917
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Kirkland, Washington, United States
The Parkinson's & Movement Disorder Institute - Fountain Valley /ID# 49915
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Fountain Valley, California, United States
Neurologic Consultants, PA /ID# 49918
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Fort Lauderdale, Florida, United States
University of Florida /ID# 49922
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Jacksonville, Florida, United States
Universtiy of Southern California /ID# 49913
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Los Angeles, California, United States
Washington University-School of Medicine /ID# 49933
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Saint Louis, Missouri, United States
Centro Hospitalar Universitario de Sao Joao, EPE /ID# 50101
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Porto, Portugal
NZOZ Centrum Medyczne HCP /ID# 50094
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Poznań, Wielkopolskie, Poland
I.P. Pavlov First St. Petersburg State Medical University /ID# 50107
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Saint Petersburg, Russian Federation
The Walton Centre NHS Foundation /ID# 50003
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Liverpool, United Kingdom
National Hospital for Neurology & Neurosurgery
🇬🇧
London, United Kingdom