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A 12-week, prospective, multi-center, randomized, double-blind, placebo controlled, Phase 3 study in L-Dopa responsive PD patients with motor fluctuations ("OFF" episodes), designed to determine the efficacy, safety and tolerability of APL-130277.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| APL-130277 | Experimental | APL-130277 sublingual thin film (10 mg, 15 mg, 20 mg, 25 mg, 30 mg and 35 mg) |
|
| Placebo | Placebo Comparator | Matching placebo for APL-130277 sublingual thin film (10 mg, 15 mg, 20 mg, 25 mg, 30 mg and 35 mg) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| APL-130277 | Drug | Use to treat up to 5 "OFF" episodes per day |
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| Measure | Description | Time Frame |
|---|---|---|
| Mean Change From Pre-Dose to 30 Minutes Post-Dose in The Movement Disorders Society Unified Parkinson's Disease Rating Scale Part III Motor Examination (MDS-UPDRS Part III) Score at Maintenance Visit 4 (MV4) - Week 12 | The Motor Function section (Part III) of the MDS-UPDRS was administered by the Investigator, and included 33 scores based on 18-items, each anchored with 5 responses: 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. The scale range was from 0 to 132, with a lower score indicating better motor function and a higher score indicating more severe motor symptoms. The least square mean change in the MDS-UPDRS Part III score from pre-dose to 30 minutes post-dose at MV4 is presented. A negative change from pre-dose indicates an improvement. | At t=0 (just prior to dosing) and t=30 minutes at MV4 (Week 12 of the Maintenance Treatment Phase). |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Patients With a Patient-related Full 'ON' Response Within 30 Minutes at MV4 - Week 12: Predicted Response Rate | A full 'ON' response was defined as a period of time where in the judgment of the patient the medication was providing full benefit with regard to mobility, stiffness, slowness and other PD features comparable to or better than that obtained with their standard dose of oral L-dopa and other anti-parkinsonian medications prior to beginning the study. Patients were asked if they attained a full 'ON' state anytime within 30 minutes of dosing. The predicted response rates are presented and were estimated using a generalized linear mixed model. |
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Inclusion Criteria:
Exclusion Criteria:
A patient will not be eligible for study entry if any of the following exclusion criteria are met:
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| Name | Affiliation | Role |
|---|---|---|
| CNS Medical Director | Sumitomo Pharma America, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Alabama, Birmingham | Birmingham | Alabama | 35233 | United States | ||
| Muhammed Ali Parkinson and Movement Disorder CenterBarrow Neurological |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31818699 | Derived | Olanow CW, Factor SA, Espay AJ, Hauser RA, Shill HA, Isaacson S, Pahwa R, Leinonen M, Bhargava P, Sciarappa K, Navia B, Blum D; CTH-300 Study investigators. Apomorphine sublingual film for off episodes in Parkinson's disease: a randomised, double-blind, placebo-controlled phase 3 study. Lancet Neurol. 2020 Feb;19(2):135-144. doi: 10.1016/S1474-4422(19)30396-5. Epub 2019 Dec 7. |
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The study included a Dose Titration Phase in which individual responses to single doses of APL-130277 (10 - 35 milligram [mg]) were evaluated at 5 mg dose increments to determine the starting dose that achieved a full 'ON' within 45 minutes. Patients were randomized at this dose to APL-130277 or placebo in the 12-week Maintenance Treatment Phase.
Patients with Levodopa (L-dopa) responsive idiopathic Parkinson's Disease (PD) complicated by motor fluctuations ('OFF' episodes) were recruited in 33 study sites in the United States and Canada starting June 2015. Study completed in December 2017. Approval was obtained from the Enrollment Adjudication Committee prior to enrollment of each patient.
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| ID | Title | Description |
|---|---|---|
| FG000 | APL-130277 (Titration) | Patients were titrated to identify the efficacious and tolerable dose of APL-130277. On Titration Visit 1 (TV1), patients presented to the clinic in an 'OFF' state and received 10 mg APL-130277. Patients who responded to 10 mg APL-130277 with a full 'ON' response within 45 minutes of dosing, as assessed by the patient and Investigator, completed the Dose Titration Phase. If a complete 'ON' response was not achieved within 45 minutes of dosing, patients restarted their normal PD medication and returned to the clinic within 3 days for the next TV, to receive the next sequential dose of APL-130277 (15 mg at TV2, 20 mg at TV3, 25 mg at TV4, 30 mg at TV5 and 35 mg at TV6). Patients who achieved a full 'ON' response within 45 minutes at a given dose were randomized to the Maintenance Treatment Phase. Any patients who reached 35 mg at TV6 and did not exhibit a full 'ON' response were discontinued. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Period 1: Dose Titration Phase |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| SAP | No | Yes | No | Statistical Analysis Plan | Nov 2, 2017 | Jun 19, 2020 |
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| Placebo | Drug | placebo |
|
| At t=30 minutes at MV4 (Week 12 of the Maintenance Treatment Phase). |
| Percentage of Patients With a Patient-related Full 'ON' Response Within 30 Minutes That Had a Duration of Effect of at Least 30 Minutes at MV4 - Week 12: Predicted Response Rate | A full 'ON' response was defined as a period of time where in the judgment of the patient the medication was providing full benefit with regard to mobility, stiffness, slowness and other PD features comparable to or better than that obtained with their standard dose of oral L-dopa and other anti-parkinsonian medications prior to beginning the study. The percentage of patients who attained a full 'ON' within 30 minutes of dosing, and whose duration from time when study medication began to have an effect lasted for at least 30 minutes were evaluated. The predicted response rates are presented and were estimated using a generalized linear mixed model. | At MV4 (Week 12 of the Maintenance Treatment Phase). |
| Patient Global Impression of Improvement (PGI-I): Percentage of Patients Who Improved at MV4 - Week 12 | During the PGI-I assessment the patient was asked to answer the question "Since starting study medication, how has your illness changed?" with 1 of the following responses: 1 = very much improved; 2 = much improved; 3 = minimally improved; 4 = no change; 5 = minimally worse; 6 = much worse and 7 = very much worse. The percentage of patients who improved at MV4 (gave responses 1 - 3) are presented. | At MV4 (Week 12 of the Maintenance Treatment Phase). |
| Clinician Global Impression of Improvement (CGI-I): Percentage of Patients Who Improved at MV4 - Week 12 | During the CGI-I assessment the clinician using the question "Compared to his/her condition on baseline, how much has he/she changed?" provided 1 of the following responses: 1 = very much improved; 2 = much improved; 3 = minimally improved; 4 = no change; 5 = minimally worse; 6 = much worse and 7 = very much worse. The percentage of patients who improved at MV4 (responses 1 - 3) are presented. | At MV4 (Week 12 of the Maintenance Treatment Phase). |
| Mean Change From Screening Visit to MV4 (Week 12) in MDS-UPDRS Part II: Motor Aspects of Experience of Daily Living | Part II of the MDS-UPDRS assessed motor experiences of daily living and was self-administered by the patient. The MDS-UPDRS Part II score was calculated as the sum of the individual items of the MDS-UPDRS Part II questionnaire (items 2.1 - 2.13), and was based on 13-items, each anchored with 5 responses: 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. The scale range was from 0 to 52, with a lower score indicating better motor function for daily living and a higher score indicating more severe motor symptoms. The mean change in the MDS-UPDRS Part II score from the screening visit to Week 12 of the Maintenance Treatment Phase is presented. A negative change indicates an improvement. | At Screening Visit and at MV4 (Week 12 of the Maintenance Treatment Phase). |
| Mean Percentage of Instances Where a Full 'ON' Response Was Achieved at 30 Minutes Post-dose on the Home Dosing Diary Entries During the 2 Days Prior to MV4 - Week 12 | Patients self-administered their doses of randomized study medication in order to treat up to 5 'OFF' episodes per day and recorded the time of self-administration and the 'ON'/'OFF' status at 30 minutes post-dose in a home dosing diary. A full 'ON' response was defined as a period of time where in the judgment of the patient the medication was providing full benefit with regard to mobility, stiffness, slowness and other PD features comparable to or better than that obtained with their standard dose of oral L-dopa and other anti-parkinsonian medications prior to beginning the study. The percentage of instances in which a full 'ON' response was achieved at 30 minutes out of all recorded episodes was calculated and is presented, and the mean percentage is presented. | 2 days prior to MV4 (Week 12 of the Maintenance Treatment Phase). |
| Mean Change From Screening Visit to MV4 in the Parkinson's Disease Quality of Life Questionnaire (PDQ-39) Summary Index Score | The PDQ-39 was self-administered by the patient during screening and at each MV. The PDQ-39 assessed the impact of PD on the quality of life in the preceding month using 39-items, each anchored with 5 responses: Never, Occasionally, Sometimes, Often and Always. Items were grouped into 8 scales (Mobility, Activities of daily living, Emotional well-being, Stigma, Social support, Cognitions, Communication and Bodily discomfort) that were scored by expressing summed item scores as a percentage score ranging between 0 and 100. The PDQ-39 summary index score was derived by the sum of the 8 PDQ-39 scale scores divided by 8, yielding a score between 0 and 100. 0 indicates perfect health and 100 indicates worse health as assessed by the measure. A negative change indicates an improvement. | At Screening Visit and at MV4 (Week 12 of the Maintenance Treatment Phase). |
| Mean Change From Pre-Dose to 15 Minutes Post-Dose in the MDS-UPDRS Part III Score at MV4 - Week 12 | The Motor Function section (Part III) of the MDS-UPDRS was administered by the Investigator, and included 33 scores based on 18-items, each anchored with 5 responses: 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. The scale range was from 0 to 132, with a lower score indicating better motor function and a higher score indicating more severe motor symptoms. The mean change in the MDS-UPDRS Part III score from pre-dose to 15 minutes post-dose at MV4 is presented. A negative change indicates an improvement. | At t=0 (just prior to dosing) and t=15 minutes at MV4 (Week 12 of the Maintenance Treatment Phase). |
| Time From Dosing to When Study Medication Provided an Effect at MV4 - Week 12 | The time to effect at MV4 was described using the Kaplan-Meier method, including an estimate of the median time to effect and corresponding 95% confidence interval. | At MV4 (Week 12 of the Maintenance Treatment Phase). |
| Phoenix |
| Arizona |
| United States |
| Movement Disorders Center of Arizona | Scottsdale | Arizona | 85258 | United States |
| Mayo Clinic Arizona | Scottsdale | Arizona | 85259 | United States |
| The Parkinson's and Movement Disorder Institute | Fountain Valley | California | 92708 | United States |
| UC Irvine Health Gottschalk Medical Plaza | Irvine | California | 92697 | United States |
| Keck Medical Center at USC | Los Angeles | California | 90033 | United States |
| The Research Center of Southern California | Oceanside | California | 92056 | United States |
| MedStar Georgetown University Hospital | Washington D.C. | District of Columbia | 20007 | United States |
| Parkinsons Disease and Movement Disorders Center | Boca Raton | Florida | 33486 | United States |
| University of Miami, Miller School of Medicine | Miami | Florida | 33136 | United States |
| Parkinson's Disease Treatment Center of Southwest Florida | Port Charlotte | Florida | 33980 | United States |
| USF Parkinson's Disease and Movement Disorder Center | Tampa | Florida | 33613 | United States |
| Emory University Department of Neurology | Atlanta | Georgia | 30329 | United States |
| Northwestern University | Chicago | Illinois | 60611 | United States |
| Rush University Medical Center | Chicago | Illinois | 60612 | United States |
| Central DuPage Hospital - Neurodegenerative Clinic - Movement Disorders Center | Winfield | Illinois | 60190 | United States |
| Kansas University Medical Center - Department of Neurology | Kansas City | Kansas | 66160 | United States |
| University of Kentucky | Lexington | Kentucky | 40536 | United States |
| Johns Hopkins University | Baltimore | Maryland | 21287 | United States |
| QUEST Research Institute | Farmington Hills | Michigan | 48334 | United States |
| Northern Michigan Neurology | Traverse City | Michigan | 49684 | United States |
| Henry Ford Hospital | West Bloomfield | Michigan | 48322 | United States |
| Columbia University Medical Center - Neurological Institute, Movement Disorders | New York | New York | 10032 | United States |
| Raleigh Neurology Associates, P.A. | Raleigh | North Carolina | 27607 | United States |
| Wake Forest Baptist Health | Winston-Salem | North Carolina | 27157 | United States |
| University of Cincinnati | Cincinnati | Ohio | 45219 | United States |
| Cleveland Clinic | Cleveland | Ohio | 44195 | United States |
| The Movement Disorder Clinic of Oklahoma | Tulsa | Oklahoma | 74136 | United States |
| Jefferson University Hospital Philadelphia | Philadelphia | Pennsylvania | 19107 | United States |
| University of Virginia, Adult Neurology | Charlottesville | Virginia | 22903 | United States |
| Evergreen Health | Kirkland | Washington | 98034 | United States |
| UHN Toronto Western Hospital | Toronto | Ontario | M5T 2S8 | Canada |
| FG001 | Placebo (Maintnance) | Patients who completed the Dose Titration Phase and were randomized in a blinded manner (1:1 ratio) to receive placebo in the 12-week double-blind Maintenance Treatment Phase. Patients self-administered the matching placebo for the strength of treatment determined during the Dose Titration Phase in up to 5 'OFF' episodes per day for 12 weeks in the at-home portion of the study. Patients returned to the clinic in 4-week intervals for safety and efficacy assessments. Patients completed a dosing diary at home for 2 days prior to the scheduled visit. |
| FG002 | APL-130277 (Maintenance) | Patients who completed the Dose Titration Phase and were randomized in a blinded manner (1:1 ratio) to receive APL-130277 in the 12-week double-blind Maintenance Treatment Phase. Patients self-administered the strength of treatment determined during the Dose Titration Phase in up to 5 'OFF' episodes per day for 12 weeks in the at-home portion of the study. Patients returned to the clinic in 4-week intervals for safety and efficacy assessments. Patients completed a dosing diary at home for 2 days prior to the scheduled visit. |
| COMPLETED |
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| NOT COMPLETED |
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| Period 2: Maintenance Treatment Phase |
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo (Maintenance) | Patients who completed the Dose Titration Phase and were randomized in a blinded manner (1:1 ratio) to receive placebo in the 12-week double-blind Maintenance Treatment Phase. Patients self-administered the matching placebo for the strength of treatment determined during the Dose Titration Phase in up to 5 'OFF' episodes per day for 12 weeks in the at-home portion of the study. Patients returned to the clinic in 4-week intervals for safety and efficacy assessments. Patients completed a dosing diary at home for 2 days prior to the scheduled visit. |
| BG001 | APL-130277 (Mainenance) | Patients who completed the Dose Titration Phase and were randomized in a blinded manner (1:1 ratio) to receive APL-130277 in the 12-week double-blind Maintenance Treatment Phase. Patients self-administered the strength of treatment determined during the Dose Titration Phase in up to 5 'OFF' episodes per day for 12 weeks in the at-home portion of the study. Patients returned to the clinic in 4-week intervals for safety and efficacy assessments. Patients completed a dosing diary at home for 2 days prior to the scheduled visit. |
| 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 |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants |
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| Time Since Diagnosis of PD | Mean | Standard Deviation | years |
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| Time Since Motor Fluctuations Started | Mean | Standard Deviation | years |
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| Type of 'OFF' episodes experienced | Number | participants |
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| Number of 'OFF' Episodes Typically Experienced Per Day | Mean | Standard Deviation | "OFF" episodes/day |
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| Length of 'OFF' Episodes | Mean | Standard Deviation | Minutes |
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| ON' State Modified Hoehn and Yahr Score | The Modified Hoehn and Yahr Scale was used to assess the patient's motor function during screening. 0 = Asymptomatic, 1 = Unilateral involvement only, 1.5 = Unilateral and axial involvement, 2 = Bilateral involvement without impairment of balance, 2.5 = Mild bilateral disease with recovery on pull test, 3 = Mild to moderate involvement; some postural instability but physically independent; needs assistance to recover from pull test, 4 = Severe disability; still able to walk or stand unassisted, 5 = Wheelchair bound or bedridden unless aided. | Number | participants |
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| Total Daily L-Dopa Dose | Mean | Standard Deviation | mg |
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| 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 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | Mean Change From Pre-Dose to 30 Minutes Post-Dose in The Movement Disorders Society Unified Parkinson's Disease Rating Scale Part III Motor Examination (MDS-UPDRS Part III) Score at Maintenance Visit 4 (MV4) - Week 12 | The Motor Function section (Part III) of the MDS-UPDRS was administered by the Investigator, and included 33 scores based on 18-items, each anchored with 5 responses: 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. The scale range was from 0 to 132, with a lower score indicating better motor function and a higher score indicating more severe motor symptoms. The least square mean change in the MDS-UPDRS Part III score from pre-dose to 30 minutes post-dose at MV4 is presented. A negative change from pre-dose indicates an improvement. | The modified Intention-To-Treat (mITT) Population consisted of all patients who were randomized and received at least 1 post-randomization dose of study medication (APL-130277 or placebo). Patients were grouped according to the randomized treatment group. Only patients with data available for analysis at the time point are presented. | Posted | Least Squares Mean | Standard Error | Units on a scale | At t=0 (just prior to dosing) and t=30 minutes at MV4 (Week 12 of the Maintenance Treatment Phase). |
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| Secondary | Percentage of Patients With a Patient-related Full 'ON' Response Within 30 Minutes at MV4 - Week 12: Predicted Response Rate | A full 'ON' response was defined as a period of time where in the judgment of the patient the medication was providing full benefit with regard to mobility, stiffness, slowness and other PD features comparable to or better than that obtained with their standard dose of oral L-dopa and other anti-parkinsonian medications prior to beginning the study. Patients were asked if they attained a full 'ON' state anytime within 30 minutes of dosing. The predicted response rates are presented and were estimated using a generalized linear mixed model. | The mITT Population consisted of all patients who were randomized and received at least 1 post-randomization dose of study medication (APL-130277 or placebo). Patients were grouped according to the randomized treatment group. Only patients with data available for analysis at the time point are presented. | Posted | Number | number of participants | At t=30 minutes at MV4 (Week 12 of the Maintenance Treatment Phase). |
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| Secondary | Percentage of Patients With a Patient-related Full 'ON' Response Within 30 Minutes That Had a Duration of Effect of at Least 30 Minutes at MV4 - Week 12: Predicted Response Rate | A full 'ON' response was defined as a period of time where in the judgment of the patient the medication was providing full benefit with regard to mobility, stiffness, slowness and other PD features comparable to or better than that obtained with their standard dose of oral L-dopa and other anti-parkinsonian medications prior to beginning the study. The percentage of patients who attained a full 'ON' within 30 minutes of dosing, and whose duration from time when study medication began to have an effect lasted for at least 30 minutes were evaluated. The predicted response rates are presented and were estimated using a generalized linear mixed model. | The mITT Population consisted of all patients who were randomized and received at least 1 post-randomization dose of study medication (APL-130277 or placebo). Patients were grouped according to the randomized treatment group. Only patients with data available for analysis at the time point are presented. | Posted | Number | number of participants | At MV4 (Week 12 of the Maintenance Treatment Phase). |
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| Secondary | Patient Global Impression of Improvement (PGI-I): Percentage of Patients Who Improved at MV4 - Week 12 | During the PGI-I assessment the patient was asked to answer the question "Since starting study medication, how has your illness changed?" with 1 of the following responses: 1 = very much improved; 2 = much improved; 3 = minimally improved; 4 = no change; 5 = minimally worse; 6 = much worse and 7 = very much worse. The percentage of patients who improved at MV4 (gave responses 1 - 3) are presented. | The mITT Population consisted of all patients who were randomized and received at least 1 post-randomization dose of study medication (APL-130277 or placebo). Patients were grouped according to the randomized treatment group. Only patients with data available for analysis at the time point are presented. | Posted | Number | percentage of participants | At MV4 (Week 12 of the Maintenance Treatment Phase). |
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| Secondary | Clinician Global Impression of Improvement (CGI-I): Percentage of Patients Who Improved at MV4 - Week 12 | During the CGI-I assessment the clinician using the question "Compared to his/her condition on baseline, how much has he/she changed?" provided 1 of the following responses: 1 = very much improved; 2 = much improved; 3 = minimally improved; 4 = no change; 5 = minimally worse; 6 = much worse and 7 = very much worse. The percentage of patients who improved at MV4 (responses 1 - 3) are presented. | The mITT Population consisted of all patients who were randomized and received at least 1 post-randomization dose of study medication (APL-130277 or placebo). Patients were grouped according to the randomized treatment group. Only patients with data available for analysis at the time point are presented. | Posted | Number | percentage of participants | At MV4 (Week 12 of the Maintenance Treatment Phase). |
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| Secondary | Mean Change From Screening Visit to MV4 (Week 12) in MDS-UPDRS Part II: Motor Aspects of Experience of Daily Living | Part II of the MDS-UPDRS assessed motor experiences of daily living and was self-administered by the patient. The MDS-UPDRS Part II score was calculated as the sum of the individual items of the MDS-UPDRS Part II questionnaire (items 2.1 - 2.13), and was based on 13-items, each anchored with 5 responses: 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. The scale range was from 0 to 52, with a lower score indicating better motor function for daily living and a higher score indicating more severe motor symptoms. The mean change in the MDS-UPDRS Part II score from the screening visit to Week 12 of the Maintenance Treatment Phase is presented. A negative change indicates an improvement. | The mITT Population consisted of all patients who were randomized and received at least 1 post-randomization dose of study medication (APL-130277 or placebo). Patients were grouped according to the randomized treatment group. Only patients with data available for analysis at the time point are presented. | Posted | Least Squares Mean | 95% Confidence Interval | units on a scale | At Screening Visit and at MV4 (Week 12 of the Maintenance Treatment Phase). |
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| Secondary | Mean Percentage of Instances Where a Full 'ON' Response Was Achieved at 30 Minutes Post-dose on the Home Dosing Diary Entries During the 2 Days Prior to MV4 - Week 12 | Patients self-administered their doses of randomized study medication in order to treat up to 5 'OFF' episodes per day and recorded the time of self-administration and the 'ON'/'OFF' status at 30 minutes post-dose in a home dosing diary. A full 'ON' response was defined as a period of time where in the judgment of the patient the medication was providing full benefit with regard to mobility, stiffness, slowness and other PD features comparable to or better than that obtained with their standard dose of oral L-dopa and other anti-parkinsonian medications prior to beginning the study. The percentage of instances in which a full 'ON' response was achieved at 30 minutes out of all recorded episodes was calculated and is presented, and the mean percentage is presented. | The mITT Population consisted of all patients who were randomized and received at least 1 post-randomization dose of study medication (APL-130277 or placebo). Patients were grouped according to the randomized treatment group. Only patients with data available for analysis at the time point are presented. | Posted | Least Squares Mean | 95% Confidence Interval | percentage of instnces | 2 days prior to MV4 (Week 12 of the Maintenance Treatment Phase). |
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| Secondary | Mean Change From Screening Visit to MV4 in the Parkinson's Disease Quality of Life Questionnaire (PDQ-39) Summary Index Score | The PDQ-39 was self-administered by the patient during screening and at each MV. The PDQ-39 assessed the impact of PD on the quality of life in the preceding month using 39-items, each anchored with 5 responses: Never, Occasionally, Sometimes, Often and Always. Items were grouped into 8 scales (Mobility, Activities of daily living, Emotional well-being, Stigma, Social support, Cognitions, Communication and Bodily discomfort) that were scored by expressing summed item scores as a percentage score ranging between 0 and 100. The PDQ-39 summary index score was derived by the sum of the 8 PDQ-39 scale scores divided by 8, yielding a score between 0 and 100. 0 indicates perfect health and 100 indicates worse health as assessed by the measure. A negative change indicates an improvement. | The mITT Population consisted of all patients who were randomized and received at least 1 post-randomization dose of study medication (APL-130277 or placebo). Patients were grouped according to the randomized treatment group. Only patients with data available for analysis at the time point are presented. | Posted | Least Squares Mean | 95% Confidence Interval | units on a scale | At Screening Visit and at MV4 (Week 12 of the Maintenance Treatment Phase). |
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| Secondary | Mean Change From Pre-Dose to 15 Minutes Post-Dose in the MDS-UPDRS Part III Score at MV4 - Week 12 | The Motor Function section (Part III) of the MDS-UPDRS was administered by the Investigator, and included 33 scores based on 18-items, each anchored with 5 responses: 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. The scale range was from 0 to 132, with a lower score indicating better motor function and a higher score indicating more severe motor symptoms. The mean change in the MDS-UPDRS Part III score from pre-dose to 15 minutes post-dose at MV4 is presented. A negative change indicates an improvement. | The mITT Population consisted of all patients who were randomized and received at least 1 post-randomization dose of study medication (APL-130277 or placebo). Patients were grouped according to the randomized treatment group. Only patients with data available for analysis at the time point are presented. | Posted | Least Squares Mean | 95% Confidence Interval | units on a scale | At t=0 (just prior to dosing) and t=15 minutes at MV4 (Week 12 of the Maintenance Treatment Phase). |
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| Secondary | Time From Dosing to When Study Medication Provided an Effect at MV4 - Week 12 | The time to effect at MV4 was described using the Kaplan-Meier method, including an estimate of the median time to effect and corresponding 95% confidence interval. | The mITT Population consisted of all patients who were randomized and received at least 1 post-randomization dose of study medication (APL-130277 or placebo). Patients were grouped according to the randomized treatment group. Only patients with data available for analysis at the time point are presented. | Posted | Median | 95% Confidence Interval | Minutes | At MV4 (Week 12 of the Maintenance Treatment Phase). |
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Dose Titration Phase (21 days): all AEs that started on/after the first dose of APL-130277 but before the first dose of study medication during the Maintenance Treatment Phase. Maintenance Treatment Phase (12 weeks): all AEs that started on/after the first dose of study medication during the Maintenance Treatment Phase.
All AEs were collected for each patient. Patients were queried in a non-leading manner, without specific prompting. Treatment emergent AEs are presented for the Dose Titration Phase (APl-130277 [titration]) and for the Maintenance Treatment Phase (APL-130277 [maintenance] and Placebo [maintenance]).
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | APL-130277 (Titration) | Patients were titrated to identify the efficacious and tolerable dose of APL-130277. On Titration Visit 1 (TV1), patients presented to the clinic in an 'OFF' state and received 10 mg APL-130277. Patients who responded to 10 mg APL-130277 with a full 'ON' response within 45 minutes of dosing, as assessed by the patient and Investigator, completed the Dose Titration Phase. If a complete 'ON' response was not achieved within 45 minutes of dosing, patients restarted their normal PD medication and returned to the clinic within 3 days for the next TV, to receive the next sequential dose of APL-130277 (15 mg at TV2, 20 mg at TV3, 25 mg at TV4, 30 mg at TV5 and 35 mg at TV6). Patients who achieved a full 'ON' response within 45 minutes at a given dose were randomized to the Maintenance Treatment Phase. Any patients who reached 35 mg at TV6 and did not exhibit a full 'ON' response were discontinued. | 0 | 141 | 1 | 141 | 60 | 141 |
| EG001 | Placebo (Maintenance) | Patients who completed the Dose Titration Phase and were randomized in a blinded manner (1:1 ratio) to receive placebo in the 12-week double-blind Maintenance Treatment Phase. Patients self-administered the matching placebo for the strength of treatment determined during the Dose Titration Phase in up to 5 'OFF' episodes per day for 12 weeks in the at-home portion of the study. Patients returned to the clinic in 4-week intervals for safety and efficacy assessments. Patients completed a dosing diary at home for 2 days prior to the scheduled visit. | 0 | 55 | 1 | 55 | 12 | 55 |
| EG002 | APL-130277 (Maintenance) | Patients who completed the Dose Titration Phase and were randomized in a blinded manner (1:1 ratio) to receive APL-130277 in the 12-week double-blind Maintenance Treatment Phase. Patients self-administered the strength of treatment determined during the Dose Titration Phase in up to 5 'OFF' episodes per day for 12 weeks in the at-home portion of the study. Patients returned to the clinic in 4-week intervals for safety and efficacy assessments. Patients completed a dosing diary at home for 2 days prior to the scheduled visit. | 1 | 54 | 2 | 54 | 39 | 54 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Staphylococcal infection | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
| |
| Cardiac arrest | Cardiac disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Cardiac failure congestive | Cardiac disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Encephalopathy | Nervous system disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | MedDRA 19.1 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Oral mucosalerythema | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Dry mouth | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Glossodynia | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Lip oedema | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Lip swelling | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Lip ulceration | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Somnolence | Nervous system disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Ageusia | Nervous system disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Oropharyngeal swelling | Respiratory, thoracic and mediastinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Yawning | Respiratory, thoracic and mediastinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Throat irritation | Respiratory, thoracic and mediastinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Chills | General disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA 19.1 | Systematic Assessment |
| |
| Laceration | Injury, poisoning and procedural complications | MedDRA 19.1 | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
| |
| Tooth infection | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
| |
| Squamous cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 19.1 | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Flushing | Vascular disorders | MedDRA 19.1 | Systematic Assessment |
|
In the event the Study is part of a multi-center study, the first publication of the results of the Study shall be made in conjunction with the results of other participating study sites as a multi-center publication; provided however if a multi-center publication is not forthcoming within twenty-four (24) months following completion of the Study at all sites,Institution and Investigator shall be free to publish.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| CNS Medical Director | Sunovion Pharmaceuticals Inc. | 1-866-503-6351 | clinicaltrialdisclosure@sunovion.com |
| SAP_000.pdf |
| Prot | Yes | No | No | Study Protocol | May 6, 2015 | Jun 19, 2020 | Prot_001.pdf |
| ID | Term |
|---|---|
| D010300 | Parkinson Disease |
| ID | Term |
|---|---|
| D020734 | Parkinsonian Disorders |
| D001480 | Basal Ganglia Diseases |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D009069 | Movement Disorders |
| D000080874 | Synucleinopathies |
| D019636 | Neurodegenerative Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D001058 | Apomorphine |
| ID | Term |
|---|---|
| D001060 | Aporphines |
| D044182 | Benzylisoquinolines |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
| D007546 | Isoquinolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
Not provided
Not provided
| Lack of Efficacy |
|
| Death |
|
| >=65 years |
|
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Canada |
|
| Wearing "OFF" |
|
| Delayed "ON" |
|
| Dose Failure |
|
| Sudden :OFF" |
|
| Hoehn and Yahr Score = 1 |
|
| Hoehn and Yahr Score = 1.5 |
|
| Hoehn and Yahr Score = 2 |
|
| Hoehn and Yahr Score = 2.5 |
|
| Hoehn and Yahr Score = 3 |
|
| Hoehn and Yahr Score = 4 |
|
| Hoehn and Yahr Score = 5 |
|
| Missing |
|
| -3.7 |
| Superiority |
| OG001 | APL-130277 (Maintenance) | Patients who completed the Dose Titration Phase and were randomized in a blinded manner (1:1 ratio) to receive APL-130277 in the 12-week double-blind Maintenance Treatment Phase. Patients self-administered the strength of treatment determined during the Dose Titration Phase in up to 5 'OFF' episodes per day for 12 weeks in the at-home portion of the study. Patients returned to the clinic in 4-week intervals for safety and efficacy assessments. Patients completed a dosing diary at home for 2 days prior to the scheduled visit. |
|
|
|
| OG001 | APL-130277 (Maintenance) | Patients who completed the Dose Titration Phase and were randomized in a blinded manner (1:1 ratio) to receive APL-130277 in the 12-week double-blind Maintenance Treatment Phase. Patients self-administered the strength of treatment determined during the Dose Titration Phase in up to 5 'OFF' episodes per day for 12 weeks in the at-home portion of the study. Patients returned to the clinic in 4-week intervals for safety and efficacy assessments. Patients completed a dosing diary at home for 2 days prior to the scheduled visit. |
|
|
|
Patients who completed the Dose Titration Phase and were randomized in a blinded manner (1:1 ratio) to receive APL-130277 in the 12-week double-blind Maintenance Treatment Phase. Patients self-administered the strength of treatment determined during the Dose Titration Phase in up to 5 'OFF' episodes per day for 12 weeks in the at-home portion of the study. Patients returned to the clinic in 4-week intervals for safety and efficacy assessments. Patients completed a dosing diary at home for 2 days prior to the scheduled visit. |
|
|
Patients who completed the Dose Titration Phase and were randomized in a blinded manner (1:1 ratio) to receive APL-130277 in the 12-week double-blind Maintenance Treatment Phase. Patients self-administered the strength of treatment determined during the Dose Titration Phase in up to 5 'OFF' episodes per day for 12 weeks in the at-home portion of the study. Patients returned to the clinic in 4-week intervals for safety and efficacy assessments. Patients completed a dosing diary at home for 2 days prior to the scheduled visit. |
|
|
| OG001 | APL-130277 (Maintenance) | Patients who completed the Dose Titration Phase and were randomized in a blinded manner (1:1 ratio) to receive APL-130277 in the 12-week double-blind Maintenance Treatment Phase. Patients self-administered the strength of treatment determined during the Dose Titration Phase in up to 5 'OFF' episodes per day for 12 weeks in the at-home portion of the study. Patients returned to the clinic in 4-week intervals for safety and efficacy assessments. Patients completed a dosing diary at home for 2 days prior to the scheduled visit. |
|
|
|
| OG001 | APL-130277 (Maintenance) | Patients who completed the Dose Titration Phase and were randomized in a blinded manner (1:1 ratio) to receive APL-130277 in the 12-week double-blind Maintenance Treatment Phase. Patients self-administered the strength of treatment determined during the Dose Titration Phase in up to 5 'OFF' episodes per day for 12 weeks in the at-home portion of the study. Patients returned to the clinic in 4-week intervals for safety and efficacy assessments. Patients completed a dosing diary at home for 2 days prior to the scheduled visit. |
|
|
|
| OG001 | APL-130277 (Maintenance) | Patients who completed the Dose Titration Phase and were randomized in a blinded manner (1:1 ratio) to receive APL-130277 in the 12-week double-blind Maintenance Treatment Phase. Patients self-administered the strength of treatment determined during the Dose Titration Phase in up to 5 'OFF' episodes per day for 12 weeks in the at-home portion of the study. Patients returned to the clinic in 4-week intervals for safety and efficacy assessments. Patients completed a dosing diary at home for 2 days prior to the scheduled visit. |
|
|
|
| OG001 | APL-130277 (Maintenance) | Patients who completed the Dose Titration Phase and were randomized in a blinded manner (1:1 ratio) to receive APL-130277 in the 12-week double-blind Maintenance Treatment Phase. Patients self-administered the strength of treatment determined during the Dose Titration Phase in up to 5 'OFF' episodes per day for 12 weeks in the at-home portion of the study. Patients returned to the clinic in 4-week intervals for safety and efficacy assessments. Patients completed a dosing diary at home for 2 days prior to the scheduled visit. |
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