Clinical Trials Highlights: Individual Trials

The Clinical Trials Highlights section in JPD is devoted to raising awareness of the clinical trial landscape in Parkinson’s, promoting discussion and progress in the conduct and outcome of studies. On this page, you can search the individual trials that have been featured. An overview of all articles that have been published in JPD can be found on the main Clinical Trials Highlights page here.

A 52-Week, Open-label, Single-arm Study to Evaluate the Safety and Tolerability of 24-hour Daily Exposure of Continuous Subcutaneous Infusion of ABBV-951 in Subjects With Parkinson’s Disease

Status: 
Recruiting
Sponsor: 
AbbVie
Enrollment: 
130
Study Design: 
This is a phase 3, 52-week, open-label, a single-arm interventional study evaluating the safety and tolerability of continuous s.c. infusion of the active drug ABBV-951. The study is including participants 30 years or older with levodopa responsive idiopathic PD inadequately controlled by their current therapy and having recognizable motor fluctuations, with a minimum of daily 2.5 hrs of OFF time. Standard exclusionary criteria are applied including cognitive impairment that will prevent the participant to safely and effectively adhere to the study requirements. The study is being conducted across multiple international centers. The study includes a screening period, a dose optimization period of 4 weeks followed by 48 weeks of the maintenance period. The study requires a daily 24 hr infusion via a s.c. pump.
Rationale: 
The primary objective of the study overall focuses on the safety profile of the drug. It monitors the following from the day of the infusion through 30 days after the last infusion device is removed. 1. Treatment emergent AE with a focus on AE of special interest defined as any AE of polyneuropathy or weight loss. 2. Effect on blood and urine parameters from baseline to the end of the study. 3. Effect on blood pressure, pulse rate and abnormal electrocardiogram up to 56 weeks. The secondary outcomes focus on the clinical outcome looking at the change from baseline to the end of the study, which is up to 56 weeks. 1. Average normalized daily OFF time and ON time. 2. Parkinson’s symptoms as assessed by the MDS-UPDRS parts I-IV. 3. Quality of life using the PDQ-39 and EQ-5D-5L scores. 4. Sleep symptoms using the Parkinson’s Disease Sleep Scale-2.
Comments: 
Since these are initial studies, their focus is on the safety and tolerability profile. It will be important to demonstrate equal, if not superior, long-term PK profile of the prodrug with similar clinical efficacy as compared to LCIG. The newer drug, if successful, may provide a less invasive alternative to appropriate candidates in comparison to LCIG via PEG-J tube and potentially bypass gastric related complications. The trial is still ongoing and design for the study was presented during the 2019 Movement Disorder Society – International Congress.

Infusion of Apomorphine: Long-term Safety Study (INFUS-ON)

Status: 
Active, No Longer Recruiting
Sponsor: 
US WorldMeds
Enrollment: 
99
Study Design: 
This is a Phase 3, multicentre (18 locations), open-label, safety and tolerability study of continuous apomorphine infusion in subjects with advanced Parkinson’s Disease (PD) whose motor fluctuations remain unsatisfactory with levodopa (or levodopa/carbidopa) and at least one other class of drugs or mode of therapy for PD.
Rationale: 
The primary outcome is the percentage of OFF time during the waking day at week 12 compared to baseline. Secondary outcome measures are all based on efficacy: 1. Percent of daily “on” time without troublesome dyskinesias during waking day, baseline to Week 12; 2. Percent of daily “off” time during the waking day, baseline to weeks 2, 4, 8, 20, 28, 36, 44, and 52, and all treatment extension period visits; 3. Percent of daily “on” time without troublesome dyskinesias during the waking day, baseline to weeks 2, 4, 8, 20, 28, 36, 44, and 52, and all treatment extension period visits; 4. Percent of daily “on” time without dyskinesias, baseline visit to treatment weeks 2, 4, 8, 20, 28, 36, 44, and 52, and all treatment extension period visits; 5. UPDRS - Motor Score, baseline visit to week 12; 6. Clinical Global Impression of Severity (CGI-S) and Change (CGI-C) Scale, baseline visit to treatment weeks 2, 4, 8, 20, 28, 36, 44, and 52; and all treatment extension period visits; 7. Patient Global Impression of Severity (PGI-S) and Change (PGI-C) Scale, baseline visit to treatment weeks 2, 4, 8, 20, 28, 36, 44, and 52, and all treatment extension period visits; 8. Parkinson’s Disease Questionnaire, baseline visit to treatment weeks 2, 4, 8, 20, 28, 36, 44, and 52, and all treatment extension period visits; 9. UPDRS - Activities of Daily Living Score, baseline visit to treatment weeks 2, 4, 8, 20, 28, 36, 44, and 52, and all treatment extension period visits; 10. Proportion of responders, baseline visit to treatment weeks 2, 4, 8, 20, 28, 36, 44, and 52, and all treatment extension period visits; 11. Frequency and total dose of average daily intermittent injection of APOKYN for subjects on APOKYN treatment at study entry, baseline visit to treatment weeks 2, 4, 8, 20, 28, 36, 44, and 52, and all treatment extension period visits.
Comments: 
The INFUS-ON trial is aiming to recruit patients with advanced idiopathic PD, with unsatisfactory motor control despite optimised treatment and OFF periods ≥3 hours per day. Apomorphine is well accepted as efficacious in the treatment of OFF episodes in advanced PD and the rationale for continuous s.c. delivery makes sense. Hopefully, this study will enable drug approval in the US after many years of successful utilization in Europe.

A Study to Evaluate the Safety and Efficacy of IPX203 in Parkinson’s Disease Patients With Motor Fluctuations

Status: 
Recruiting
Sponsor: 
Impax Laboratories LLC (now Amneal)
Enrollment: 
510
Study Design: 
This is a multi-center (89 locations), randomized, double-blind, double-dummy, active-controlled, parallel-group study. It will consist of a 3-week, open-label IR CD-LD dose adjustment period; a 4-week, open-label period for conversion to IPX203; followed by a 13-week double-blind treatment period with subjects randomized in a 1:1 ratio, stratified by center, to receive either IPX203 (with matching IR CD-LD placebo) or IR CD-LD (with matching IPX203 placebo).
Rationale: 
The primary outcome is the change in “good ON” time. Secondary outcome measures are the change in OFF time; patients rated as “much improved” or “very much improved” in Patient Global Impression of Change (PGI-C); change in UPDRS Part III; and change in UPDRS Parts II and III. All the outcome measures will be assessed at the end of the double-blind study period at 13 weeks.
Comments: 
While symptomatic therapies for PD are easier to develop than drugs to modify the course of the disease, easier does not mean easy. This reality is underlined by the recent failure of the previously featured Phase 3 study of Intec Pharma’s Accordion Pill to reach its primary outcome objectives [3]. The Accordion Pill LD/CD containing both immediate and controlled release forms, presented with a unique gastric retentive drug delivery system which allowed for slow release of LD/CD in the stomach. According to the company website, on preliminary review, the study failed to demonstrate a statistically significant difference in OFF times as compared to the IR CD/LD arm. Further analysis and publication of data are pending [4]. The Phase 3 trial of IPX203 is thus a large and comprehensive program with a randomized, double-blind, double-dummy, active-controlled, parallel-group study design. The company’s experience with Rytary (codenamed IPX066 when in development) will be invaluable for the successful implementation of this pivotal Phase 3 study. While not groundbreaking, if successful, a new oral formulation of LD/CD with a longer duration of action will be a welcome addition to the armamentarium of available treatment options for PwPs.

Levodopa Pharmacokinetics in Patients With Parkinson’s Disease and Symptom Fluctuation: A Phase I, Open-label, Randomized, Multicentre, Crossover Study Comparing Intravenous and Subcutaneous Infudopa With Intestinal Duodopa

Status: 
Recruiting
Sponsor: 
Vastra Gotaland Region
Enrollment: 
28
Study Design: 
The current study is a prospective, 3-period-cross-over, open-label multicentre trial comparing i.v. and s.c. administration of the study drug, Infudopa, to Duodopa. The study is including advanced Parkinson’s patients who are already on a stable regimen of LCIG for at least 30 days with a dose between 685mg to 4000mg and be using it for 16- or 24-h. Standard exclusionary criteria apply. The study is being conducted in Sweden and requires three treatment visits. The study has a cross-over design with a minimum of 3 days of Duodopa in between the treatment visits. At each visit, the participant will receive either standard Duodopa infusion, Infudopa intravenously or Infudopa subcutaneously over a 16-h period. The order of the treatment will be non-blinded but randomized. A pre-study optimum dose of Duodopa will be established that will determine the dose of the i.v. and s.c. Infudopa that will yield a corresponding serum levodopa level. The Infudopa i.v. will be dosed at 75% of participant’s individual pre-study Duodopa dose and administered via an indwelling catheter in the arm as a morning rapid constant dose followed by continuous i.v. infusion up to 16-h. Similarly, Infudopa s.c. will be administered over 16-h as a morning rapid constant rate followed by continuous infusion dosed similarly to pre-study Duodopa dose for the participant.
Rationale: 
The primary objective focuses on demonstrating two major pharmacokinetic points. 1. To demonstrate that a steady state plasma concentration of levodopa and carbidopa, equivalent to that of Duodopa, can be achieved after the i.v. and s.c. infusion of Infudopa. 2. To demonstrate that peak-trough fluctuations of levodopa and carbidopa plasma concentrations during the dosage interval of both i.v. and s.c. Infudopa will be comparable to that of Duodopa. Secondary objectives are designed to look at the 1. Safety profile, particularly focusing on local skin reactions, 2. Expanded pharmacokinetic profile of both levodopa and carbidopa after s.c. and i.v. administration compared to Duodopa. The parameters being checked include bioavailability, maximum plasma concentration, time to maximum plasma concentration, area under the curve, and elimination half-life. 3. Effect on clinical parameters focusing on bradykinesia, dyskinesia, and tremors using the clinical rating scale UPDRS and objective assessments via Parkinson’s Kinetigraph.
Comments: 
Infudopa aims to demonstrate an equally efficacious alternative s.c. delivery of carbidopa/levodopa compared to LCIG. If the results are positive, it will be another alternative to LCIG. The Infudopa IntraV, if successful in demonstrating meaningful clinical benefit, will be a potentially interesting addition for use in peri-operative scenarios. Since these are still early phase studies, they rightly aim to demonstrate clinically acceptable PK and safety profile of the active drugs.

Apomorphine Pump in Early Stage of Parkinson’s Disease (EARLY-PUMP)

Status: 
Recruiting
Sponsor: 
Rennes University Hospital
Enrollment: 
192
Study Design: 
This is a phase 3, randomized, parallel arm, interventional study designed to assess whether the use of apomorphine pump in relatively early motor fluctuation stage of PD positively impacts the social and occupational functioning of the PD participants, by improving their quality of life and delaying the appearance of severe disabling motor complications. The study is including adults aged 65 years old or below with idiopathic PD with a disease duration of more than 4 years. They should have the presence of fluctuations and/or dyskinesia but for not more than 3 years. Participants must demonstrate impairment in activities of daily living or impairment of social and occupational functioning due to PD symptoms despite medical management. Standard exclusionary criteria apply. Participants with deep brain stimulation or lesional surgery or with LCIG are excluded. The study is currently recruiting across multiple centers in France. The participants will be recruited over a period of 36 months and randomly assigned to one of the two arms to either receive apomorphine pump with an individually optimized dose or receive the best medical treatment, which could be the best single or combination therapy according to the guidelines of European Federation of Neurological Sciences. Participants will be followed for a year with clinical evaluations at months 6 and 12. The pump will be installed and adjusted at baseline during the first hospitalization and further pump adjustment and readjustment of oral medications are allowed every month. Additionally, there will be another 3-day hospitalization visit at month 3 for pump adjustment. The study will also collect data throughout the study for medico-economic evaluation.
Rationale: 
The study kept the primary outcome as the change in the quality of life using the PDQ39 questionnaire from baseline to 12 months follow up. The secondary outcomes focus on the change in score over the course of 12 months from baseline and include various parameters including patient and neurologist’s global impression of change, MDS-UPDRS I-IV scales, non-motor symptoms scales, change in the best ON, ON with dyskinesia and OFF periods, adverse events. The secondary outcomes also explore changes in sleep, psychosocial functioning, depression, anxiety, and apathy scales.
Results: 
Whether early initiation of infusion therapies can delay or alleviate the negative impact on PwP’s social and economic aspect of life is a critical question that remains unanswered. This study hopes to answer the question. Interestingly apomorphine has been shown to have an anti-dyskinetic effect and as such, will be interesting to find if early infusion delays the onset of the same.

A Clinical Trial Investigating the Efficacy, Safety and Tolerability of Continuous Subcutaneous ND0612 Infusion in Comparison to Oral IR-LD/CD in Subjects With Parkinson’s Disease Experiencing Motor Fluctuations (BouNDless).

Status: 
Recruiting
Sponsor: 
Neuroderm Ltd
Enrollment: 
300
Study Design: 
The BouNDless study is a multi-center (4 locations), randomized, active-controlled, double-blind, double-dummy, parallel-group design. After screening, subjects will start on an open label immediate release (IR) LD/CD adjustment period, followed by a ND0612 open-label adjustment period. Once optimised, patients will be randomised to receive either ND0612 or matching placebo, both accompanied by IR LD/CD. There is an option to move to an open-label extension study (NCT02726386) lasting for a further year. Neuroderm plans to recruit patients with moderate to advanced PD, between the ages of 30 and 80. They must have a good response to levodopa, with a modified Hoehn & Yahr score of ≤3 when ON. There must be at least 2 hours of OFF time per day. The patient must be taking ≥4 levodopa doses/day (≥3 doses/day of Rytary) at a total daily dose of ≥400mg.
Rationale: 
The primary outcome measure is the change in daily ON time without troublesome dyskinesia (sum of ON time without dyskinesia and ON time with non-troublesome dyskinesia) using a patient diary over 12 weeks. The secondary outcome measure is the change in OFF time using a patient diary, also over 12 weeks.
Results: 
Together with Abbvie’s ABBV-951, ND0612 will offer an alternative to intra-jejunal gels, potentially with more control of dosage to obtain optimal symptom relief. This mode of delivery of LD/CD is likely to be much more acceptable to patients, hopefully at a lower overall cost. The disadvantage of ND0612 is a limit of levodopa dose that can be delivered via the pump over 24 hours which will require use of add on oral medications by most patients.

Efficacy and Tolerability of IRL790 in Parkinson’s Disease Dyskinesia

Status: 
Recruiting
Sponsor: 
Integrative Research Laboratories
Enrollment: 
74
Study Design: 
Randomized, double blind, placebo controlled, multi-centre (20 locations) assessing a 2.5mg capsule of IRL-790. Inclusion criteria require PwP between the ages of 18 and 79 on a stable regimen of anti-parkinsonian medication. They must display waking day dyskinesia of >25% determined as a score of >2 on question 4.1 of the UPDRS part IV. One intriguing inclusion criterion is that participants must be willing and able to avoid direct exposure to sunlight from day 1 to day 28.
Rationale: 
Primary outcome: the UDysRS score at 4 weeks. Secondary outcomes are also focused on efficacy, all measured at 4 weeks: 1. UDysRS parts III and IV; 2. Participant diaries assessing change in daily off time, measured every half hour during 24 hours at visit 1; 3. UPDRS part III; 4. UPDRS part IV questions 4.1 and 4.2 related to dyskinesia.
Comments: 
This study is a Phase 2a study to further assess efficacy of IRL-790 in the reduction of dyskinesia. The trial is still in the early stages but it will be interesting to see if D3 antagonism can deliver anti dyskinetic benefits without compromising motor control.

A 14-week, Double-blind, Randomized, Three-arm, Parallel-Group Study to Assess the Efficacy and Safety of Two Doses of Pridopidine Versus Placebo for the Treatment of Levodopa-induced Dyskinesia in Patients With Parkinson’s Disease (gLIDe)

Status: 
Recruiting
Sponsor: 
Prilenia Therapeutics
Enrollment: 
135
Study Design: 
This is a multicentre, double-blind, randomized, three-arm, parallel-group Phase 2 study evaluating the efficacy and safety of two doses of pridopidine vs placebo for dyskinesia in PD participants. The study will include participants with a clinical diagnosis of PD between the ages of 30 and 85 years. Mild to moderate dyskinesia is a prerequisite. Participants are required to be on a stable medication regimen (PD and non-PD) for at least 28 days prior to the study start date and be able to maintain that through the study duration. Standard exclusionary criteria apply. Participants with surgical intervention such as DBS are excluded. The participants will be randomized to one of 3 parallel arms: Arm 1- dose 1 in the form of oral capsules for 12 weeks following a 2 week titration period; Arm 2- dose 2 in the form of oral capsules for 12 weeks following a 2-week titration period; Arm 3- placebo in the form of oral capsules for 14 weeks. The study is currently recruiting participants at two sites in the USA.
Rationale: 
The primary outcome measure explores the change in dyskinesia from baseline to week 14. The score is calculated as a sum of parts 1, 3, and 4 of the UdysRS. No secondary outcomes have been posted.
Comments: 
The pharmacology of the molecule and data from animal studies are promising. Given an established safety profile, it is one step ahead in the development for dyskinesia. Physiologically its effect is similar to GDNF growth factors in terms of neuronal dopamine protection and sprouting in the nigrostriatal axons. Though it failed to show efficacy for the HD population, its effect on dyskinesia is yet to be determined.

Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled, 4-way Crossover, Dose-finding Study of Eltoprazine Safety, Tolerability, and Efficacy in the Treatment of Levodopa-induced Dyskinesia in Patients With Parkinson’s Disease

Status: 
Active
Sponsor: 
Amarantus BioScience Holdings, Inc.
Enrollment: 
60
Study Design: 
This is a double blind, placebo-controlled, crossover, dose range finding interventional study designed to assess the safety, tolerability, and efficacy of Eltoprazine on dyskinesia in PD participants. They are exploring 3 treatment doses and will assess their efficacy as compared to the placebo on the severity of dyskinesia, parkinsonian symptoms and participant function along with safety and tolerability. The study uses standard scales as noted below along with motion sensors and electronic diaries. The inclusion criteria require individuals between 30 to 85 years of age with a diagnosis of PD of at least 3 years duration and should be on stable dose of levodopa for 4 weeks prior to screening visit. The dyskinesia is required to be: 1. moderate to severely disabling; 2. present during 25% of the waking day on an average; and 3. present for at least 3 months prior to study entry. Standard exclusionary criteria are applied. Participants with surgical treatment for PD namely DBS are not blindly excluded but will be, if the procedure was done within the last 6 months of study inclusion or is planned during the study. There are 4 study arms as noted here, all with dosing for 3 weeks: 1. Eltoprazine HCl 2.5mg BID (5mg/day); 2. Eltoprazine HCl 5mg BID (10mg/day); 3. Eltoprazine 7.5mg BID (15mg/day); 4. Placebo capsules BID. Participants will be randomly assigned to each of the 4 arms. They will complete the 3-week treatment cycle before crossing over to the next study arm. The study is being conducted in USA at the Parkinson’s Disease and Movement Disorders Center at Boca Raton, FL.
Rationale: 
The primary outcome measure is the change in the total UDysRS score. This will be assessed at the end of each treatment period on days 21, 42, 63 and 84. Secondary outcome measures will include: 1. Effect on PD motor symptoms as assessed by MDS-UPDRS, participant diaries and physiological meas-urement using the motion sensor system after 84 days; 2. Change in dyskinesia severity using the physiological motion sensor system after 84 days; 3. Participant function using the questionnaires in MDS-UPDRS and UDyRS to quantify dyskinesia and par-kinsonian motor symptoms. This will also be assessed after 84 days; 4. Lastly, safety and tolerability as assessed by adverse events, physical and neurological exams, safe labor-atory values, vital signs and ECG. This will be assessed after 94 days.
Comments: 
The molecule carries potential for meaningful benefit in dyskinesia. The design of the Phase 1/2a study limits any effective assessment of efficacy. In 2016, the US FDA granted the molecule orphan drug designation status for PD. Since 2017, Eltoprazine’s development has been handled by Elto Pharma, Inc., a joint venture between Amanrantus and PsychoGenics. Elto Pharma recently entered into agreement with Coeptis Pharmaceuticals, Inc. regarding further development. Though the results from the phase 2b study were expected by now, given the delay, we will have to wait to find out whether the molecule is truly efficacious for dyskinesia without compromising the levodopa benefits.

Buspirone Treatment of Iatrogenic Dyskinesias in Advanced Parkinson’s Disease. Multicenter, International, Placebo-controlled, Randomised, Double-Blind Trial

Status: 
Recruiting
Sponsor: 
Assistance Publique – Hopitaux de Paris
Enrollment: 
100
Study Design: 
The study is a phase 3 multicenter, randomized, placebo-controlled, double-blind trial looking at the efficacy of buspirone in reducing dyskinesia in PD participants. They aim to enrol 100 clinically diagnosed PD participants between 35 to 80 years of age. The dyskinesia is required to be moderately disabling and to be present more than 25% of the waking time. The participant should be able to identify dyskinesia, ON and OFF periods. They should be on stable antiparkinsonian medications and be considered optimally treated at the time of inclusion. Standard exclusionary criteria are applied. Participants with DBS can be included if the procedure was done 12 months before inclusion and they are on stable stimulation parameters for at least 4 weeks prior to the first visit. The study will randomly assign participants to two study arms. Arm 1 will receive buspirone orally in escalating doses. For the first two weeks, they will be on 10mg daily morning dose followed by 10mg twice a day for the next two weeks to finally build up to 10mg three times a day from week 5 to 12. Arm 2 will receive capsules of placebo and administered in escalating doses to match the arm 1. Assessments will be done every 2 weeks and at the end of the study.
Rationale: 
The primary outcome evaluates change in the UdysRS between the placebo and treatment arm from baseline to week 12. Secondary outcomes include: 1. Comparison of efficacy between the two arms as measured by MDS-UPDRS parts 3 and 4 at different time points within the period of 13 weeks treatment duration; 2. Comparison of quality of life between the two arms as measured by MDS-UPDRS parts 1 and 2 at different time points within the 13 weeks treatment duration; 3. Comparison between the two arms as measured by side effects profile at different time points within the 13 weeks treatment duration; 4. The maximum dose tolerated by the participants at different time points within the 13 weeks treatment duration.
Comments: 
None.

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