Clinical Trial 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.

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.

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.

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.

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 in Parkinson’s Disease in paTients with mOderate to seveRe dyskInesiA (ASTORIA)

Status: 
Not Yet Recruiting
Sponsor: 
Contera Pharma
Enrollment: 
81
Study Design: 
Randomized, double-blind, double dummy, placebo-controlled, parallel group study. This Phase 2 study is comparing two dose levels of JM-010 with placebo - 4mg buspirone/0.8mg zolmitriptan and 8mg buspirone/0.8mg zolmitriptan. The time period will be 12 weeks with a further 2 weeks follow up for safety purposes. There will also be a pharmacokinetic (PK) sub-study. There are three sub-groups in the study with participants randomised in a 1:1:1 ratio. Group 1 will receive the first active dose plus a placebo; group 2 the second active dose plus a placebo; and group 3 two placebos. The study is seeking PwP between the ages of 18 and 80 on a stable regimen of levodopa. Inclusion criteria also include stable peak effect dyskinesia and at least one hour of ON state dyskinesia during waking hours, with no more than six administrations of levodopa per day. Exclusively diphasic, OFF state, myoclonic, dystonic, or akathetic dyskinesia without peak-dose dyskinesia are all excluded.
Rationale: 
Primary - the efficacy of JM-010 compared to placebo using the UDysRS over 12 weeks. Secondary outcomes are also focused on efficacy: 1. UDysRS total score changes from baseline to weeks 2, 4 and 8; 2. MDS-UPDRS Parts I to IV from baseline to week 2, 4, 8, 12; 3. Clinician’s Global Impression of Change (CGIC) score at week 12; 4. Change in ON time with troublesome dyskinesia, ON time with non-troublesome dyskinesia, ON time without dyskinesia, and OFF time as measured by Hauser patient diaries at weeks 2, 4, 8 and 12.
Results: 
The first trial specifically explores the anti-dyskinetic benefit of buspirone and is monitoring its effect on parkinsonism as well. The 2nd study explores if buspirone potentiates the anti-dyskinetic effect of amantadine and the last study tests the synergistic effect of buspirone with zolmitriptan. All studies are studying a lower dose of buspirone, unlikely to worsen parkinsonism. Whether buspirone will deliver on the results as an anti-dyskinetic is yet to be seen.

Buspirone, in Combination With Amantadine, for the Treatment of Levodopa-induced Dyskinesia

Status: 
Recruiting
Sponsor: 
Oregon Health and Science University
Enrollment: 
15
Study Design: 
This is a phase 1, single-center, double-blinded, randomized, placebo-controlled, two-period cross-over study designed to assess the safety, tolerability, and efficacy of combination therapy of buspirone and amantadine on dyskinesia. They are enrolling PD participants between 18 to 99 years of age on a stable medication regimen. Participants should have mild to severe dyskinesia and should be on amantadine (200-500mg/day) with insufficient control. Standard exclusionary criteria are applied. This study will not include participants with DBS. Included participants will be randomized to one of the two study arms. Arm 1: Buspirone titrated up over the course of 2 weeks to reach 30mg/day for a week. Arm 2: Placebo titrated up to match arm 1. Participants will be crossed over the treatment sequence. Monitoring is done every 2 weeks for safety, tolerance, compliance and dyskinesia assessment.
Rationale: 
The primary outcome measure will assess the: 1. Area under the curve – measurements for dyskinesia for a 6-hr levodopa dose cycle; 2. Change in UdysRS up to 6 weeks; 3. Safety and tolerability assessment by monitoring adverse events for up to 6 weeks. No secondary outcomes have been specified.
Comments: 
None.

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.

ADX48621 for the Treatment of Levodopa Induced Dyskinesia in Patients With Parkinson’s Disease

Status: 
Completed
Sponsor: 
Addex Pharma
Enrollment: 
83
Study Design: 
Phase 2, Randomized, Double-blind, Placebo-controlled, Parallel Group, Multicenter Study to Evaluate the Safety, Tolerability and Efficacy of ADX48621 (dipraglurant). The trial design contained a dose escalation from 50mg once daily up to 100mg three times a day.
Rationale: 
The primary outcome measure was the number of participants with abnormal safety and tolerability assessment parameters after 4 weeks. Secondary outcome measures were the severity of dyskinesia as measured by the modified Abnormal Involuntary Movement Scale (mAIMS) after 4 weeks; change in PD severity as measured by participant diary at weeks 1, 2, 3 and 4, UPDRS part III at weeks 2 and 4, UPDRS total score at week 4; and participant and clinician-rated global impression of change in dyskinesia and PD at 4 weeks.
Comments: 
The dipraglurant treatment group of 52 participants had a higher incidence of adverse events (AEs) – 88.5% – than the placebo group of 24 (75%). While most participants completed the dose escalation, 2 participants in the active group discontinued due to AEs. No treatment effects were seen in safety monitoring variables. Dipraglurant had a statistically significant effect against placebo as measured by mAIMS on day 1 (19.9% vs 4.1%). By day 28 a strong placebo response (21.5%) compared to the dipraglurant measure (31.4%) meant that statistical significance was not achieved at the end of the study. The clinician-rated global impression of change showed a statistically significant improvement with dipraglurant (71.2%) versus placebo (49.9%). According to participant diaries, daily on time with dyskinesia reduced and on time without dyskinesia increased. Two pivotal Phase 3 studies are scheduled to start by the end of 2019. Both studies plan the same enrolment (200 participants) split equally between dipraglurant and placebo, with the same primary and secondary outcomes. The first study (#301) will start an open label extension (OLE) after 3 months; the second study (#302) starts the OLE after 6 months. The Phase 3 studies are expected to report results in the third quarter of 2021. As with other experimental therapies for dyskinesia, dipraglurant has been granted orphan drug status by the US FDA, allowing seven years of market exclusivity.

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