A clinical trial to see if ADS-5102 is safe in people with drug induced abnormal movements in Parkinson's disease

Phase 1

• Conditions: Treatment of levodopa-induced dyskinesia in subjects with Parkinson's disease; MedDRA version: 18.0Level: PTClassification code 10013916Term: DyskinesiaSystem Organ Class: 10029205 - Nervous system disorders; Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

• Registration Number: EUCTR2014-003739-20-ES
• Lead Sponsor: Adamas Pharmaceuticals, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2015-02-16
• Last Update Posted: 30 April 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

Group 1: Current Adamas LID study subjects
Below are the inclusion criteria subjects who are continuing directly into ADS-AMT-PD302 without a time gap between their Adamas LID efficacy study and ADS-AMT-PD302:
1. Signed a current IRB/REB/IEC-approved informed consent form
2. Completed study visits per protocol in a previous Adamas efficacy study
3. Ambulatory or ambulatory-aided (e.g. walker or cane) ability while ON, such that the subject can complete study assessments
4. Knowledgeable and reliable caregiver/study partner, if appropriate, to accompany the subject to study visits and assist in completion of study assessments, as needed and allowed
5. History of peak dose dyskinesia that might benefit from specific dyskinesia treatment in the judgment of the subject and clinical investigator
6. On a stable regimen of antiparkinson?s medications, including a levodopa preparation administered not less than three times daily

Group 2: Previous Adamas LID study subjects
Below are the inclusion criteria for subjects who participated in a previous Adamas efficacy study evaluating ADS-5102 in LID and will enter ADS-AMT-PD302 with a time gap:
1. Signed a current IRB/REB/IEC-approved informed consent form
2. Completed study visits per protocol in a previous Adamas efficacy study
3. Ambulatory or ambulatory-aided (e.g. walker or cane) ability while ON, such that the subject can complete study assessments
4. Knowledgeable and reliable caregiver/study partner, if appropriate, to accompany the subject to study visits and assist in completion of study instruments, as needed and allowed
5. Peak dose dyskinesia during Screening that might benefit from specific dyskinesia treatment in the judgment of the subject and clinical investigator OR a history of peak dose dyskinesia that is currently being managed by amantadine treatment
6. On a stable regimen of antiparkinson?s medications at least 30 days prior to screening, including a levodopa preparation administered not less than three times daily
7. Parkinson?s disease, per UK Parkinson's Disease Society (UKPDS) Brain Bank Clinical Diagnostic Criteria

Group 3: Non Adamas LID study subjects ? with prior DBS
Below are the eligibility criteria for subjects who would have been deemed ineligible for participation in previous or current Adamas efficacy studies due to having undergone deep brain stimulation:
1. Signed a current IRB/REB/IEC-approved informed consent form
2. Subject has undergone deep brain stimulation procedure prior to start of this study (14 July 2014)
3. Ambulatory or ambulatory-aided (e.g. walker or cane) ability while ON, such that the subject can complete study assessments
4. Knowledgeable and reliable caregiver/study partner, if appropriate, to accompany the subject to study visits and assist in completion of study instruments, as needed and allowed
5. Peak dose dyskinesia during Screening that might benefit from specific dyskinesia treatment in the judgment of the subject and clinical investigator OR a history of peak dose dyskinesia that is currently being managed by amantadine treatment
6. On a stable regimen of antiparkinson?s medications at least 30 days prior to screening, including a levodopa preparation administered not less than three times daily
7. Parkinson?s disease, per UK Parkinson's Disease Society (UKPDS) Brain Bank Clinical Diagnostic Criteria
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subje

Exclusion Criteria

Group 1 Current Adamas subjects
Discontinued due to ADS-5102-AEs
H&Y Stage 5
Presence of orthostatic hypotension
GFR < 50 mL/min/1.73m2
Female is pregnant or lactating
Sexually active female, not sterile or 2 y postmenopausal, or will not use highly effective hormonal contraception, with a barrier, from screening to least 4 weeks post-treatment
Possible treatment with restricted medication
Planned participation in another trial
Group 2 Previous Adamas subjects
Discontinued due to ADS-5102-AEs
History of neurosurgery related to PD, Except DBS
History of other neurological disease that would affect motor function or cognition
Current sensory impairments impairing assessment completion or untreated angle closure glaucoma
History of alcohol or substance dependence or abuse seizures, stroke or TIA since completion in previous Adamas trial
History of MI, or NYHA Functional Classification of Heart Failure Class 3 or 4 since completion of participation in previous Adamas trial
Any clinically significant ECG other than isolated PVCs or first degree AV block
History of cancer since completion in previous Adamas trial
MMSE<24 during screening
H&Y Stage 5
Presence of an acute or chronic major psychiatric disorder or symptom (e.g. suicidal ideation) that would affect ability to complete assessments
Presence of orthostatic hypotension
Any of the following results at screening:
?Hb<10g/dL
?WBC<3.0x1e9/L
?Neutrophils<1.5x1e9/L
?Lymphocytes<0.5x1e9/L
?Platelets<100x1e9/L
?AST &/or ALT>2 ULN
GFR<50mL/min/1.73m2
Can?t swallow oral capsules or GI malabsorption
Female is pregnant or lactating
Sexually active female, not sterile or 2 y postmenopausal, or will not use highly effective hormonal contraception, with a barrier, from screening to least 4 weeks post-treatment
Inability to tolerate amantadine or history of suicidal ideation or suicide attempt during prior amantadine use
History of hypersensitivity or allergic reaction to amantadine, rimantidine, or memantine, or to any of the excipients used in the study medication
Received live attenuated influenza vaccine within 2 weeks prior to enrolment
Current treatment with carbonic anhydrase inhibitors, sodium bicarbonate, or urinary acidification agents, quinine, quinidine, triamterene, or trimethoprim
Current treatment with medications that act primarily by blocking dopamine receptors & current treatment with medications that prolong the QT interval & known risk of torsades de pointes
Treatment with an investigational drug (other than ADS-5102) within 30 days prior to screening
Treatment with an investigational biologic 6 m to screening
Possible treatment with restricted medication
Current/planned participation in another trial
Group 3 Non Adamas Subjects ? with prior DBS
History of neurosurgery related to PD, except DBS
History of other neurological disease that would affect motor function/cognition
Current sensory impairments impairing assessment completion or untreated angle closure glaucoma
History of alcohol or substance dependence or abuse, seizures, stroke or TIA within 2 y prior to screening
History of MI, or NYHA Functional Classification of Heart Failure Class 3 or 4 within 2 y prior to screening
Any clinically significant ECG abnormalities other than isolated PVCs or first degree AV block
History of cancer within 5 y of screening
MMSE score <24 in screening
H&Y Stage 5
Presence of an acute or chronic major psychiatric disorder or symptom (e.g. suicidal ideation) that would affect ability to com

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the safety and tolerability of ADS-5102 oral capsules, an extended release formulation of amantadine, administered at a dose of 340 mg once nightly at bedtime for the treatment of levodopa induced dyskinesia (LID) in subjects with Parkinson?s disease (PD).;Secondary Objective: To evaluate duration of ADS-5102 effect on dyskinesia as assessed by the Unified Parkinson?s Disease Rating Scale (MDS-UPDRS), Part IV<br>To evaluate clinical progression of Parkinson?s disease as assessed by MDS-UPDRS, Combined Score, Parts I, II, and III;Primary end point(s): The following safety assessments will be performed during the study:<br>? AEs<br>? Safety-related study drug discontinuations<br>? Vital signs<br>? Safety laboratory tests;Timepoint(s) of evaluation of this end point: The primary outcome measure is the change from baseline to Week 52

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): The following efficacy assessment will be performed during the study:<br>? Unified Parkinson?s Disease Rating Scale (MDS-UPDRS);Timepoint(s) of evaluation of this end point: The secondary outcome measures are changes from baseline to Week 52