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This is a multi-center, randomized, double-blind, placebo-controlled, 2-arm, parallel group study to evaluate the efficacy and safety of ADS-5102 extended release (ER) capsules, an investigational formulation of amantadine, dosed once nightly at bedtime for the treatment of levodopa induced dyskinesia (LID) in subjects with Parkinson's disease (PD). The novel pharmacokinetic profile of ADS-5102 is expected to achieve i) maximal concentrations in the early morning through mid-day, when LID can be troublesome, and ii) lower concentrations in the evening, potentially reducing the negative impact of amantadine on sleep. This pharmacokinetic profile could enable higher doses to be tolerated with a once-nightly ER formulation than can be tolerated with an immediate-release formulation. The once-nightly dosing regimen may also provide enhanced convenience and compliance.
In a previous clinical study, ADS-5102 met its primary endpoint; LID was significantly reduced as measured by the change in UDysRS score over 8 weeks vs. placebo.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ADS-5102 | Experimental | ADS-5102 (amantadine HCl extended release) |
|
| Placebo | Placebo Comparator | Placebo |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ADS-5102 | Drug | Oral capsules to be administered once nightly at bedtime, for 25 weeks |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in the Unified Dyskinesia Rating Scale (UDysRS) Score at Week 12 | The UDysRS is a dyskinesia rating scale from 0-104; it evaluates involuntary movements associated with PD. A higher score indicates more severe PD. The UDysRS was measured at Baseline and Weeks 2, 8, 12, 18, and 24. | Baseline to Week 12 |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in the Unified Dyskinesia Rating Scale (UDysRS) Score at Week 24 | The UDysRS is a dyskinesia rating scale from 0-104; it evaluates involuntary movements associated with PD. A higher score indicates more severe PD. The UDysRS was measured at Baseline and Weeks 2, 8, 12, 18, and 24. | Baseline to Week 24 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials Director | Adamas Pharmaceuticals, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Birmingham | Alabama | 35233 | United States | |||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34024025 | Derived | Hauser RA, Mehta SH, Kremens D, Chernick D, Formella AE. Effects of Gocovri (Amantadine) Extended-Release Capsules on Motor Aspects of Experiences of Daily Living in People with Parkinson's Disease and Dyskinesia. Neurol Ther. 2021 Dec;10(2):739-751. doi: 10.1007/s40120-021-00256-1. Epub 2021 May 22. | |
| 33864229 | Derived |
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All randomized subjects who received ≥ 1 dose of study drug (123) were included in the Safety Analysis Population (60 placebo, 63 ADS-5102); all randomized subjects who received ≥ 1 dose of study drug and provided ≥ 1 postbaseline efficacy assessment (121) were included in the Modified Intent-to-Treat (MITT) population (58 placebo, 63 ADS-5102).
126 Participants with Parkinson's disease (PD) and Levodopa-induced Dyskinesia (LID) were randomized at 41 study sites in the United States and Canada. The first subject was randomized on 20 May 2014 and the last subject completed on 18 November 2015.
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | Placebo: oral capsules administered once nightly at bedtime for 25 weeks |
| FG001 | ADS-5102 (340 mg) | 340 mg dose of ADS-5102 (amantadine hydrochloride [HCl] extended release): oral capsules administered once nightly at bedtime for 25 weeks |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Placebo | Other | Oral capsules to be administered once nightly at bedtime, for 25 weeks |
|
| Change in the Standardized PD Home Diary (ON Time Without Troublesome Dyskinesia, ON Time With Troublesome Dyskinesia, OFF Time) |
A PD home diary was used to score 5 different conditions in 30-minute intervals: ASLEEP, OFF, ON (ie, had adequate control of PD symptoms) without dyskinesia, ON with non-troublesome dyskinesia, and ON with troublesome dyskinesia. The results were based on 2 consecutive 24-hour diaries taken prior to the day of randomization and prior to the Week 2, 8, 12, 18, and 24 visits. |
| Baseline (BL) to Week 12 (W12) and Week 24 (W24) |
| Change in the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Combined Score (Parts I, II, and III) | The MDS-UPDRS Parts I, II, and III examined non-motor experiences of daily living, motor experiences of daily living, and motor examination, respectively. Each Part contains items or questions that were each rated on a scale from 0 (normal) to 4 (severe). The Combined Parts I, II, and III (representing the sum of the individual scores from Parts I, II, and III) has a scale range of 0-236. Higher scores, whether for individual Parts or the sum of the combined Parts, indicate more severe PD. | Baseline (BL) to Week 12 (W12) and Week 24 (W24) |
| Clinician's Global Impression of Change (CGI-C) in Overall PD Symptoms | The CGI-C consisted of a single question that assessed the investigator's global impression of the subject's change from Baseline in overall PD symptoms, including but not limited to LID. The CGI-C required that the investigator rate the extent to which the subject's PD had improved or worsened (from marked worsening to marked improvement). The CGI-C was assessed at Baseline and Weeks 2, 8, 12, 18, and 24. | Baseline to Week 12 and Week 24 |
| Phoenix |
| Arizona |
| 85013 |
| United States |
| Scottsdale | Arizona | 85259 | United States |
| Sun City | Arizona | 85351 | United States |
| Fountain Valley | California | 92708 | United States |
| Pasadena | California | 91105 | United States |
| Reseda | California | 91335 | United States |
| Sacramento | California | 95817 | United States |
| Torrance | California | 90505 | United States |
| Ventura | California | 93003 | United States |
| Aurora | Colorado | 80045 | United States |
| Manchester | Connecticut | 06040 | United States |
| Boca Raton | Florida | 33486 | United States |
| Gainesville | Florida | 32607 | United States |
| Naples | Florida | 34102 | United States |
| Port Charlotte | Florida | 33980 | United States |
| Sunrise | Florida | 33351 | United States |
| Tampa | Florida | 33613 | United States |
| Weston | Florida | 33331 | United States |
| Atlanta | Georgia | 30329 | United States |
| Chicago | Illinois | 60612 | United States |
| Des Moines | Iowa | 50309 | United States |
| Kansas City | Kansas | 66160 | United States |
| Bingham Farms | Michigan | 48025 | United States |
| West Bloomfield | Michigan | 48322 | United States |
| Golden Valley | Minnesota | 55427 | United States |
| St Louis | Missouri | 63110 | United States |
| Albany | New York | 12208 | United States |
| Commack | New York | 11725 | United States |
| New York | New York | 10003 | United States |
| New York | New York | 10016 | United States |
| New York | New York | 10029 | United States |
| Raleigh | North Carolina | 27607 | United States |
| Cincinnati | Ohio | 45219 | United States |
| Cleveland | Ohio | 44195 | United States |
| Toledo | Ohio | 43614 | United States |
| Tulsa | Oklahoma | 74136 | United States |
| Philadelphia | Pennsylvania | 19107 | United States |
| Dallas | Texas | 75390 | United States |
| Houston | Texas | 77030-1 | United States |
| Houston | Texas | 77030-2 | United States |
| Kirkland | Washington | 98034 | United States |
| Milwaukee | Wisconsin | 53233 | United States |
| Edmonton | Alberta | T6G 2B7 | Canada |
| Toronto | Ontario | M5T 2S8 | Canada |
| Regina | Saskatchewan | S4T 1A5 | Canada |
| Mehta SH, Pahwa R, Tanner CM, Hauser RA, Johnson R. Effects of Gocovri (Amantadine) Extended Release Capsules on Non-Motor Symptoms in Patients with Parkinson's Disease and Dyskinesia. Neurol Ther. 2021 Jun;10(1):307-320. doi: 10.1007/s40120-021-00246-3. Epub 2021 Apr 17. |
| 29532440 | Derived | Elmer LW, Juncos JL, Singer C, Truong DD, Criswell SR, Parashos S, Felt L, Johnson R, Patni R. Pooled Analyses of Phase III Studies of ADS-5102 (Amantadine) Extended-Release Capsules for Dyskinesia in Parkinson's Disease. CNS Drugs. 2018 Apr;32(4):387-398. doi: 10.1007/s40263-018-0498-4. |
| 28604926 | Derived | Pahwa R, Tanner CM, Hauser RA, Isaacson SH, Nausieda PA, Truong DD, Agarwal P, Hull KL, Lyons KE, Johnson R, Stempien MJ. ADS-5102 (Amantadine) Extended-Release Capsules for Levodopa-Induced Dyskinesia in Parkinson Disease (EASE LID Study): A Randomized Clinical Trial. JAMA Neurol. 2017 Aug 1;74(8):941-949. doi: 10.1001/jamaneurol.2017.0943. |
| Received Study Drug |
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
Safety Analysis Population
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | Placebo: oral capsules administered once nightly at bedtime for 25 weeks |
| BG001 | ADS-5102 (340 mg) | 340 mg dose of ADS-5102 (amantadine HCl extended release): oral capsules administered once nightly at bedtime for 25 weeks |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Unified Dyskinesia Rating Scale (UDysRS) | The UDysRS is a dyskinesia rating scale that evaluates involuntary movements associated with PD; the UDysRS consists of the following sub-parts: IA, IB, IIA, IIB, III, and IV. The total score is the sum of all individual sub-parts, and scores for this measure can range from 0-104. The total objective score is the sum of Part III (which measures objective impairment) and Part IV (which measures objective disability), and scores for this measure can range from 0-44. For both the total score and total objective score, a higher score indicates more severe PD. | Mean | Standard Deviation | units on a scale |
| ||||||||||||||
| PD Home Diary | A PD home diary was used to score 5 different conditions in 30-minute intervals: ASLEEP, OFF, ON (ie, had adequate control of PD symptoms) without dyskinesia, ON with non-troublesome dyskinesia, and ON with troublesome dyskinesia. | Mean | Standard Deviation | hours |
| ||||||||||||||
| Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) | The MDS-UPDRS Parts I, II, III, and IV examined non-motor experiences of daily living, motor experiences of daily living, motor examination, and motor complications, respectively. Each Part contains items/questions, each rated on a scale from 0 (normal) to 4 (severe). The range of total scores for each Part is as follows: Part I, 0-52; Part II, 0-52; Part III, 0-132; Part IV, 0-24. Combined Parts I, II, and III is the sum of scores from Parts I, II, and III and has a scale range of 0-236. Parts 4.1 and 4.2 each has a scale range of 0-4. Higher scores indicate more severe PD. | For Part I and combined Parts I, II, and III, in the placebo group, the data is based on 59 patients only. | Mean | Standard Deviation | units on a scale |
| |||||||||||||
| Time Since PD Diagnosis | Mean | Standard Deviation | years |
| |||||||||||||||
| Duration of Levodopa Treatment | Mean | Standard Deviation | years |
| |||||||||||||||
| Duration of LID | Mean | Standard Deviation | years |
| |||||||||||||||
| Hoehn and Yahr Stage | The Hoehn and Yahr scale, from 1-5, describes the patient's PD progression. The higher the score the more severe the symptoms of PD. | Mean | Standard Deviation | units on a scale |
| ||||||||||||||
| Subjects taking Antiparkinson Medication | Patients may have been taking more than 1 antiparkinson medication at Baseline | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change From Baseline in the Unified Dyskinesia Rating Scale (UDysRS) Score at Week 12 | The UDysRS is a dyskinesia rating scale from 0-104; it evaluates involuntary movements associated with PD. A higher score indicates more severe PD. The UDysRS was measured at Baseline and Weeks 2, 8, 12, 18, and 24. | MITT population | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline to Week 12 |
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| Secondary | Change From Baseline in the Unified Dyskinesia Rating Scale (UDysRS) Score at Week 24 | The UDysRS is a dyskinesia rating scale from 0-104; it evaluates involuntary movements associated with PD. A higher score indicates more severe PD. The UDysRS was measured at Baseline and Weeks 2, 8, 12, 18, and 24. | MITT population | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline to Week 24 |
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| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change in the Standardized PD Home Diary (ON Time Without Troublesome Dyskinesia, ON Time With Troublesome Dyskinesia, OFF Time) | A PD home diary was used to score 5 different conditions in 30-minute intervals: ASLEEP, OFF, ON (ie, had adequate control of PD symptoms) without dyskinesia, ON with non-troublesome dyskinesia, and ON with troublesome dyskinesia. The results were based on 2 consecutive 24-hour diaries taken prior to the day of randomization and prior to the Week 2, 8, 12, 18, and 24 visits. | MITT population | Posted | Least Squares Mean | Standard Error | hours | Baseline (BL) to Week 12 (W12) and Week 24 (W24) |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change in the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Combined Score (Parts I, II, and III) | The MDS-UPDRS Parts I, II, and III examined non-motor experiences of daily living, motor experiences of daily living, and motor examination, respectively. Each Part contains items or questions that were each rated on a scale from 0 (normal) to 4 (severe). The Combined Parts I, II, and III (representing the sum of the individual scores from Parts I, II, and III) has a scale range of 0-236. Higher scores, whether for individual Parts or the sum of the combined Parts, indicate more severe PD. | MITT population | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline (BL) to Week 12 (W12) and Week 24 (W24) |
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| Secondary | Clinician's Global Impression of Change (CGI-C) in Overall PD Symptoms | The CGI-C consisted of a single question that assessed the investigator's global impression of the subject's change from Baseline in overall PD symptoms, including but not limited to LID. The CGI-C required that the investigator rate the extent to which the subject's PD had improved or worsened (from marked worsening to marked improvement). The CGI-C was assessed at Baseline and Weeks 2, 8, 12, 18, and 24. | MITT population | Posted | Count of Participants | Participants | Baseline to Week 12 and Week 24 |
|
|
Baseline through Week 25
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Placebo: oral capsules administered once nightly at bedtime for 25 weeks | 0 | 60 | 3 | 60 | 36 | 60 |
| EG001 | ADS-5102 (340 mg) | 340 mg dose of ADS-5102 (amantadine HCl extended release): oral capsules administered once nightly at bedtime for 25 weeks | 1 | 63 | 7 | 63 | 56 | 63 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hip fracture | Injury, poisoning and procedural complications | MedDRA (17.0) | Systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDRA (17.0) | Systematic Assessment |
| |
| Humerus fracture | Injury, poisoning and procedural complications | MedDRA (17.0) | Systematic Assessment |
| |
| Presyncope | Nervous system disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Subdural haematoma | Injury, poisoning and procedural complications | MedDRA (17.0) | Systematic Assessment |
| |
| Small intestinal obstruction | Gastrointestinal disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA (17.0) | Systematic Assessment |
| |
| ON and OFF phenomenon | Nervous system disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Encephalopathy | Nervous system disorders | MedDRA (17.0) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hallucination, any type | Psychiatric disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Hallucination, visual | Psychiatric disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Hallucination, auditory | Psychiatric disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Dry mouth | Gastrointestinal disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA (17.0) | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA (17.0) | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA (17.0) | Systematic Assessment |
| |
| Livedo reticularis | Skin and subcutaneous tissue disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Abnormal dreams | Psychiatric disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Balance disorder | Nervous system disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA (17.0) | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA (17.0) | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (17.0) | Systematic Assessment |
|
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Head, Regulatory Affairs | Adamas Pharmaceuticals, Inc. | +1 (510) 450-3500 | drugsafety@adamaspharma.com |
| ID | Term |
|---|---|
| D020820 | Dyskinesias |
| D010300 | Parkinson Disease |
| D020734 | Parkinsonian Disorders |
| ID | Term |
|---|---|
| D009069 | Movement Disorders |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D001480 | Basal Ganglia Diseases |
| D001927 | Brain Diseases |
| D000080874 | Synucleinopathies |
| D019636 | Neurodegenerative Diseases |
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| Between 18 and 65 years |
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| >=65 years |
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| Total Objective Score (Parts III, IV) |
|
|
|
| Off |
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| ON without Troublesome Dyskinesia |
|
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| ON with Troublesome Dyskinesia |
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| Part II |
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| Part III |
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| Combined Parts I, II, and III |
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| Part IV |
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| Part IV, Item 4.1 |
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| Part IV, Item 4.2 |
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| Dopamine Agonist |
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| MAO Inhibitors |
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| COMT Inhibitor |
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| Anticholinergics |
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| Moderate Improvement |
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| Minimal Improvement |
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| No Change |
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| Minimal Worsening |
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| Moderate Worsening |
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| Marked Worsening |
|