E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment of levodopa-induced dyskinesia in subjects with Parkinson's disease |
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E.1.1.1 | Medical condition in easily understood language |
Treatment of drug induced abnormal movements in Parkinson's disease |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10013916 |
E.1.2 | Term | Dyskinesia |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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). |
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E.2.2 | Secondary objectives of the trial |
To evaluate duration of ADS-5102 effect on dyskinesia as assessed by the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), Part IV To evaluate clinical progression of Parkinson’s disease as assessed by MDS-UPDRS, Combined Score, Parts I, II, and III |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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. Male or female subjects between 30 and 85 years of age, inclusive 3. Subject has undergone deep brain stimulation procedure prior to start of this study (14 July 2014) 4. Ambulatory or ambulatory-aided (e.g. walker or cane) ability while ON, such that the subject can complete study assessments 5. 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 6. 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 7. 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 8. Parkinson’s disease, per UK Parkinson's Disease Society (UKPDS) Brain Bank Clinical Diagnostic Criteria |
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E.4 | Principal 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 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&/orALT>2 ULN GFR < 50 mL/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 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 30d prior to screening Treatment with an investigational biologic 6 m prior to screening Possible treatment with restricted medication Current/planned participation in another trial
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E.5 End points |
E.5.1 | Primary end point(s) |
The following safety assessments will be performed during the study: AEs Safety-related study drug discontinuations Vital signs Safety laboratory tests |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary outcome measure is the change from baseline to Week 52, 64, 76, 88, 100, 103 |
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E.5.2 | Secondary end point(s) |
The following efficacy assessment will be performed during the study: Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The secondary outcome measures are changes from baseline to Week 52, 64, 76, 88, 100, 103 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 0 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 29 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |