CTRI/2023/04/051973 [Registered on: 25/04/2023] Trial Registered Prospectively
Last Modified On:
22/05/2024
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Single Arm Study
Public Title of Study
Safety and Efficacy of Amantadine Tablets for the Treatment of Parkinsons Disease (A disorder of the central nervous system that affects movement, often including tremors) and Drug-induced Extrapyramidal Reactions (involuntary or uncontrollable movements, tremors, muscle contractions) in Patients
Scientific Title of Study
A Prospective, Multi-centre, Single-arm, Phase IV Study to Assess the Safety and Efficacy of Amantadine Extended Release Tablets for the Treatment of Parkinsons Disease and Drug-induced Extrapyramidal Reactions in Adult Patients
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
ICR/21/017, Version No.1.0; Dated 29/OCT/2021
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Pravin Ghadge
Designation
AVP Head-India Clinical Research
Affiliation
Sun Pharma Laboratories Limited
Address
Sun Pharma Laboratories Limited, Sun House, Plot No. 201 B/1, Western Express Highway, Goregaon (E), Mumbai-400063, Maharashtra, India
Mumbai (Suburban) MAHARASHTRA 400063 India
Phone
02243244324
Fax
02243244343
Email
pravin.ghadge@sunpharma.com
Details of Contact Person Scientific Query
Name
Dr Shruti Saha
Designation
Manager India Clinical Research
Affiliation
Sun Pharma Laboratories Limited
Address
Sun Pharma Laboratories Limited, Sun House, Plot No. 201 B/1, Western Express Highway, Goregaon (E), Mumbai-400063, Maharashtra, India
Mumbai (Suburban) MAHARASHTRA 400063 India
Phone
02243244324
Fax
02243244343
Email
shruti.saha@sunpharma.com
Details of Contact Person Public Query
Name
Vibhawari Waghanna
Designation
Manager – India Clinical Research
Affiliation
Sun Pharma Laboratories Limited
Address
Sun Pharma Laboratories Limited
Sun House, Plot No. 201 B/1, Western Express Highway,
Goregaon (E) Mumbai 400063
Mumbai (Suburban) MAHARASHTRA 400063 India
Phone
02243244324
Fax
02243244343
Email
vibhawari.waghanna@sunpharma.com
Source of Monetary or Material Support
Sun Pharma Laboratories Limited (SPLL)
Primary Sponsor
Name
Sun Pharma Laboratories Limited (SPLL)
Address
Sun House, Plot No. 201 B/1, Western Express Highway,
Goregaon (E), Mumbai 400 063, Maharashtra, India.
City Neurology Centre, Back Side of Gautam Upwan,S8/110 A, Maqbool Alam Rd, Hamrautia, Varanasi, Uttar Pradesh- 221002 Varanasi UTTAR PRADESH
7753936002
drzafar4@gmail.com
Dr K Rakesh
Excel Hospital
Excel Hospital - A Unit Of Bhargava Sai Healthcare 1-5-56/29, Near IG Statue, Old Alwal Medchal,
Secunderabad Medchal Medchal–Malkajgiri Telangana
- 500010 India Medchal TELANGANA
IEC Bangalore Medical College & Research Institute
Approved
IEC Excel Hospital
Approved
IEC GMC & GGH Guntur
Approved
IEC GSVM medical college Kanpur
Approved
IEC Jawahar Lal Nehru Medical College
Approved
IEC Namaste Integrated Services
Approved
IEC Neurological Science
Approved
Leelavati Ethics Committee
Approved
Riddhi Medical Nursing Home IEC
Approved
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: G20||Parkinsons disease,
Intervention / Comparator Agent
Type
Name
Details
Intervention
Amantadine Extended Release Tablets; 129 mg and 193 mg
orally once daily in the morning. The dosage may be increased in weekly intervals to a maximum daily dose of 322 mg (administered as a 129 mg and 193 mg tablet), taken in the morning.
Amantadine ER is not interchangeable with other amantadine immediate- or extended-release products.
For patients unable to tolerate more than 100 mg per day of immediate release amantadine, there is no equivalent dose or dosing regimen of Amantadine ER.
Comparator Agent
Not applicable
Not applicable
Inclusion Criteria
Age From
30.00 Year(s)
Age To
85.00 Year(s)
Gender
Both
Details
Patients of either gender aged between 30 to 85 years both inclusive who agree to provide written informed consent
Patients who can be managed on outpatient basis as per the Investigators judgment
The patient or caregiver must demonstrate the ability to complete an accurate home diary based on training and evaluation during the screening period
Women of childbearing potential must have a negative urine pregnancy test before study entry and agree to use highly effective methods of contraception to prevent pregnancy from study entry till at least two weeks after the last dose of the study medication such contraception may include hormonal birth control eg combined estrogen and progestogen containing oral intravaginal or transdermal or progesterone only oral injectable or implantable hormonal contraception associated with inhibition of ovulation intrauterine devices intrauterine hormone releasing system OR bilateral tubal occlusion vasectomized partner or total sexual abstinence
Note Women with childbearing potential are defined as those who are not surgically sterile bilateral oophorectomy hysterectomy or bilateral tubal ligation or post menopausal Post menopausal woman will be defined as Woman not using hormonal replacement therapy and have had at least twelve continuous months of natural spontaneous amenorrhea and be greater than forty five years of age
Male patients must have had a successful vasectomy confirmed azoospermia or they and their female partners must meet the criteria above ie not of childbearing potential or practicing highly effective contraception throughout the study period No sperm donation is allowed during the study period
Patients with diagnosis of idiopathic Parkinsons disease as per the United Kingdom UK Parkinsons Disease Society Brain Bank criteria
Patients who are on stable dose of anti parkinsonian medications and require additional medications to control PD symptoms Patients should be on stable dose of any anti parkinsonian medications including any levodopa preparation for at least thirty days prior to enrolment and be willing to remain on the same doses throughout the trial
Patients on stable dose of medications before screening such as typical and atypical antipsychotics antidepressants eg SSRIs SNRIs antiemetics eg metoclopramide domperidone levosulpiride or antiepileptic drugs eg valproate phenytoin and experiencing extrapyramidal symptoms such as parkinsonism and or akathisia and or dystonia and or tardive dyskinesia
ExclusionCriteria
Details
Patients having secondary parkinsonian syndrome such as vascular post inflammatory drug induced neoplastic and post traumatic parkinsonism or any atypical parkinsonian syndrome bipolar disorder untreated inadequately treated major depressive disorder Patients on stable dose of selective serotonin reuptake inhibitors or serotonin and norepinephrine reuptake inhibitors for last two months prior to enrolment are eligible schizophrenia or other psychotic disorder history of exposure to a known neurotoxin or any neurological features not consistent with the diagnosis of PD as assessed by the Investigator
History of neurosurgical intervention for treating Parkinsons disease ie pallidotomy or implanted with a deep brain stimulator
Patients taking any medication for the treatment of extrapyramidal reactions within thirty days prior to Screening
Patients with any of the underlying conditions that may cause extrapyramidal symptoms including but not limited to dementia hydrocephalus subdural haemorrhage hypoparathyroidism neurodegeneration and pantothenate kinase associated neurodegeneration
Patients taking amantadine within thirty days prior to screening
Patients with previously documented inability to tolerate amantadine or lack of response to prior amantadine treatment
Patients taking rimantadine for influenza prophylaxis or any other indication memantine or apomorphine within thirty days prior to screening
History of any cancer within five years of screening
Patients who are at imminent risk of suicide or had a suicide attempt within last one year of screening
Patients who have received Live Attenuated Influenza Vaccine within two weeks prior to Screening
Patients who have plans to undergo major elective surgery during the course of the study
Patients with end stage renal disease eGFR less than 15 mL/min/1.73 m2 calculated by MDRD method at the time of screening and enrolment
History of or currently has any of the following clinically significant conditions such as cardiovascular respiratory renal hepatic endocrine or gastrointestinal disease
History or known case of HIV-AIDS hepatitis B and hepatitis C
History of hypersensitivity or allergic reaction to amantadine rimantadine or memantine or to any of the excipients used in the study medication
Participation in other studies involving investigational drugs or surgeries within the last thirty days or investigational biologics within the last 6 months prior to screening
Pregnant or lactating women
Investigator study personnel Sponsor representatives and their first degree relatives
Method of Generating Random Sequence
Not Applicable
Method of Concealment
Not Applicable
Blinding/Masking
Not Applicable
Primary Outcome
Outcome
TimePoints
Proportion of patients with treatment-emergent adverse events (TEAEs)
[Time frame: Throughout the study period]
Secondary Outcome
Outcome
TimePoints
Change from baseline in the MDS-UPDRS PART III score
baseline to Days 14, 28, 56, 70, 77, and 84
Change from baseline in the MDS-UPDRS Parts I, II, and IV score
baseline to Days 14, 28, 56, 70, 77, and 84
Change from baseline in the MDS-UPDRS total Part I II III IV score
baseline to Days 14, 28, 56, 70, 77, and 84
Change from baseline in daily OFF hours
baseline to Days 14, 28, 56, 70, 77, and 84
Change from baseline in daily ON hours with dyskinesia
baseline to Days 14, 28, 56, 70, 77, and 84
Change from baseline in daily ON hours without troublesome dyskinesia
baseline to Days 14, 28, 56, 70, 77, and 84
Change from baseline in daily ON hours with troublesome dyskinesia
baseline to Days 14, 28, 56, 70, 77, and 84
Change from baseline in Quality of life (daily life activities) total score using PD questionnaire-39
baseline to Days 14, 28, 56, 70, 77, and 84
Change from baseline in Extrapyramidal Symptom Rating Scale (ESRS) total score
baseline to Days 7, 14, 28, 35, 42, 49, and 56
Change from baseline in ESRS Part I, II, III & IV Subscores
From baseline to Days 7, 14, 28, 35, 42, 49, and 56
Target Sample Size
Total Sample Size="163" Sample Size from India="163" Final Enrollment numbers achieved (Total)= "163" Final Enrollment numbers achieved (India)="163"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
The patient will be screened only after obtaining written informed consent and will be undergoing various assessments as mentioned in Schedule of Assessment (Appendix I). Screening number will be allotted to every screened patient. At screening visit, the Investigator or his/her designee will provide prospective patient with a detailed description of the study objectives, study participation requirements, as well as potential health risks and benefits associated with study participation. After obtaining written informed consent, study-specific screening [including inclusion and exclusion criteria, medical and medication history, demography, vitals, physical and laboratory examination, 12-Lead Electrocardiogram (ECG), MoCA score (for PD patients), Hoehn and Yahr Rating Scale Staging (for PD patients), and ESRS score (for patients with drug-induced extrapyramidal reactions)] will be performed. Evaluation of concomitant medications and adverse/serious adverse events will be done.
PD patients will be provided with 24-hour PD Home Diary (pre-enrolment) at Screening to record the number of daily asleep hours, daily ON hours without troublesome dyskinesia, and daily ON hours with troublesome dyskinesia, daily ON hours with dyskinesia, and daily OFF hours for 3 consecutive days in the week prior to enrolment (Day 1).
Treatment period
After confirming the eligibility, patients will be enrolled by allotting the enrollment number. The enrolled patients will be given the study drug, Amantadine Extended Release Tablets 129 mg or 193 mg as