Clinical Trial Results:
A Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study in Parkinson’s Disease Patients With Moderate to Severe Dyskinesia to Assess the Efficacy and Safety/Tolerability of Two Dose Combinations Of JM-010
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Summary
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EudraCT number |
2017-003415-19 |
Trial protocol |
ES IT SK |
Global end of trial date |
21 Mar 2024
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Results information
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Results version number |
v1(current) |
This version publication date |
16 Nov 2024
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First version publication date |
16 Nov 2024
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
JM-010CS03
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
Contera Pharma A/S
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Sponsor organisation address |
DTU Science Park, Venlighedsvej 4, Hørsholm, Denmark, 2970
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Public contact |
Clinical Trials Information, Contera Pharma A/S, +34 900834223, RegistroEspanolDeEstudiosClinicos@druginfo.com
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Scientific contact |
Clinical Trials Information, Contera Pharma A/S, +34 900834223, RegistroEspanolDeEstudiosClinicos@druginfo.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
14 Sep 2024
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
21 Mar 2024
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Global end of trial reached? |
Yes
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Global end of trial date |
21 Mar 2024
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To compare the efficacy of JM-010 (administered as 2 different dose combinations of JM-010) to that of placebo therapy in reducing dyskinesia severity in PD by evaluating the mean change from Baseline to Week 12 on the Unified Dyskinesia Rating Scale (UDysRS).
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Protection of trial subjects |
This study was conducted in accordance with the protocol and consensus ethical principles derived from international guidelines including the Declaration of Helsinki, ICH on GCP Guidelines, applicable International Organization for Standardization ISO 14155 medical device guidelines, and any other applicable national and local legal requirements. The ICF provided to subjects for obtaining subjects’ consent was reviewed and approved by the IRB/IEC prior to its use. The investigator or his/her representative explained the study to the subject or his/her legally authorized representative and answered all questions regarding the study. Subjects and/or their legally authorized representative were informed that their participation was voluntary. Subjects or their legally authorized representative were required to sign a statement of informed consent that met the requirements of 21 Code of Federal Regulations 50, local regulations, ICH guidelines, Health Insurance Portability and Accountability Act requirements, where applicable, and the IRB/IEC or study site.
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Background therapy |
Subjects were continuing with their usual levodopa treatment regimen for the duration of study participation. | ||
Evidence for comparator |
This was placebo-controlled study. | ||
Actual start date of recruitment |
22 Jul 2019
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Slovakia: 7
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Country: Number of subjects enrolled |
Spain: 21
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Country: Number of subjects enrolled |
France: 4
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Country: Number of subjects enrolled |
Germany: 8
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Country: Number of subjects enrolled |
Italy: 14
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Country: Number of subjects enrolled |
Korea, Republic of: 35
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Worldwide total number of subjects |
89
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EEA total number of subjects |
54
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
34
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From 65 to 84 years |
55
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85 years and over |
0
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Recruitment
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Recruitment details |
Subjects were randomized in a 1:1:1 ratio to receive either 1 of the 2 dose combinations of buspirone and zolmitriptan (JM-010) and 1 placebo, or 2 placebos as per the double-dummy study design. | ||||||||||||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
This study comprised of a screening period of 1 to 6 weeks. Subjects with a diagnosis of moderate to severe dyskinesia in Parkinson’s disease (PD) completed a screening visit to assess eligibility to participate in the study. The Screening Set included all subjects who signed the inform consent. | ||||||||||||||||||||||||||||||||||||
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Period 1
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Period 1 title |
Treatment period (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator | ||||||||||||||||||||||||||||||||||||
Blinding implementation details |
This study was double-blinded. This study design included investigator and subject masking.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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JM-010 0.8/8 mg | ||||||||||||||||||||||||||||||||||||
Arm description |
Subjects were treated with buspirone 8 mg/zolmitriptan 0.8 mg. The dose strengths of JM-010 were assessed in dosing regimens from 3 to 6 times per day, in order to match the daily doses of L-DOPA administered by each subject. | ||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
JM-010 (buspirone 8 mg/zolmitriptan 0.8 mg)
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
One JM-010 tablet of 8 mg buspirone / 0.8 mg zolmitriptan (166 mg) + 1 placebo tablet (158 mg) were administrated. The time of administration of JM-010 + placebo was dependent on the subject’s own levodopa dosing regimen. JM-010 was administrated orally in conjunction with each administration of levodopa during a 12-week double-blind treatment period.
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Arm title
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JM-010 0.8/4 mg | ||||||||||||||||||||||||||||||||||||
Arm description |
Subjects were treated with buspirone 4 mg/zolmitriptan 0.8 mg. The dose strengths of JM-010 were assessed in dosing regimens from 3 to 6 times per day, in order to match the daily doses of L-DOPA administered by each subject. | ||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
JM-010 (buspirone 4 mg/zolmitriptan 0.8 mg)
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
One JM-010 tablet of 4 mg buspirone / 0.8 mg zolmitriptan (158 mg) + 1 placebo tablet (166 mg) were administrated. The time of administration of JM-010 + placebo was dependent on the subject’s own levodopa dosing regimen. JM-010 was administrated orally in conjunction with each administration of levodopa during a 12-week double-blind treatment period.
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Arm title
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Placebo | ||||||||||||||||||||||||||||||||||||
Arm description |
Subjects were administrated with 1 placebo tablet (158 mg) + 1 placebo tablet (166 mg). The dose strengths of Placebo were assessed in dosing regimens from 3 to 6 times per day, in order to match the daily doses of L-DOPA administered by each subject. | ||||||||||||||||||||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
One placebo tablet (158 mg) + 1 placebo tablet (166 mg) were administrated. The time of administration of placebo was dependent on the subject’s own levodopa dosing regimen. Placebo was administrated orally in conjunction with each administration of levodopa during a 12-week double-blind treatment period.
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Baseline characteristics reporting groups
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Reporting group title |
JM-010 0.8/8 mg
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Reporting group description |
Subjects were treated with buspirone 8 mg/zolmitriptan 0.8 mg. The dose strengths of JM-010 were assessed in dosing regimens from 3 to 6 times per day, in order to match the daily doses of L-DOPA administered by each subject. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
JM-010 0.8/4 mg
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Reporting group description |
Subjects were treated with buspirone 4 mg/zolmitriptan 0.8 mg. The dose strengths of JM-010 were assessed in dosing regimens from 3 to 6 times per day, in order to match the daily doses of L-DOPA administered by each subject. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Subjects were administrated with 1 placebo tablet (158 mg) + 1 placebo tablet (166 mg). The dose strengths of Placebo were assessed in dosing regimens from 3 to 6 times per day, in order to match the daily doses of L-DOPA administered by each subject. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Full Analysis Set (FAS)
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Subject analysis set type |
Full analysis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
The FAS included all randomly assigned subjects who received at least 1 dose of the study treatment, provide baseline assessment and at least 1 post baseline assessment on the UDysRS. The FAS was the primary population for efficacy.
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End points reporting groups
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Reporting group title |
JM-010 0.8/8 mg
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Reporting group description |
Subjects were treated with buspirone 8 mg/zolmitriptan 0.8 mg. The dose strengths of JM-010 were assessed in dosing regimens from 3 to 6 times per day, in order to match the daily doses of L-DOPA administered by each subject. | ||
Reporting group title |
JM-010 0.8/4 mg
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Reporting group description |
Subjects were treated with buspirone 4 mg/zolmitriptan 0.8 mg. The dose strengths of JM-010 were assessed in dosing regimens from 3 to 6 times per day, in order to match the daily doses of L-DOPA administered by each subject. | ||
Reporting group title |
Placebo
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Reporting group description |
Subjects were administrated with 1 placebo tablet (158 mg) + 1 placebo tablet (166 mg). The dose strengths of Placebo were assessed in dosing regimens from 3 to 6 times per day, in order to match the daily doses of L-DOPA administered by each subject. | ||
Subject analysis set title |
Full Analysis Set (FAS)
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
The FAS included all randomly assigned subjects who received at least 1 dose of the study treatment, provide baseline assessment and at least 1 post baseline assessment on the UDysRS. The FAS was the primary population for efficacy.
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End point title |
UDysRS Total Score from baseline to Week 12 (Full Analysis Set) | ||||||||||||||||||||
End point description |
Mean Change in the UDysRS Total Score was measured from Baseline to Week 12.
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End point type |
Primary
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End point timeframe |
From Baseline till Week 12
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Statistical analysis title |
Statistical analysis - JM-010 0.8/8 mg vs Placebo | ||||||||||||||||||||
Statistical analysis description |
Estimates of the mean change and difference in mean change from baseline in the JM-010 treatment arm was compared to the placebo group using a MMRM analysis. The model was: mean change in the UDysRS total score = treatment arm + visit + baseline + treatment visit. An unstructured covariance matrix was used. If the model failed to converge by using unstructured covariance matrix, compound symmetry matrix was used. Degrees of freedom was calculated using the Kenward-Roger procedure.
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Comparison groups |
JM-010 0.8/8 mg v Placebo
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Number of subjects included in analysis |
56
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||||||
P-value |
= 0.193 | ||||||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||||||
Parameter type |
Least-squared Mean | ||||||||||||||||||||
Point estimate |
-4.2
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Confidence interval |
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level |
90% | ||||||||||||||||||||
sides |
2-sided
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lower limit |
-9.4 | ||||||||||||||||||||
upper limit |
1.1 | ||||||||||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
3.16
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Statistical analysis title |
Statistical analysis - JM-010 0.8/4 mg vs Placebo | ||||||||||||||||||||
Statistical analysis description |
Estimates of the mean change and difference in mean change from baseline in the JM-010 treatment arm was compared to the placebo group using a MMRM analysis. The model was: mean change in the UDysRS total score = treatment arm + visit + baseline + treatment visit. An unstructured covariance matrix was used. If the model failed to converge by using unstructured covariance matrix, compound symmetry matrix was used. Degrees of freedom was calculated using the Kenward-Roger procedure.
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Comparison groups |
Placebo v JM-010 0.8/4 mg
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Number of subjects included in analysis |
57
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||||||
P-value |
= 0.932 | ||||||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||||||
Parameter type |
Least-squared Mean | ||||||||||||||||||||
Point estimate |
-0.3
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Confidence interval |
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level |
90% | ||||||||||||||||||||
sides |
2-sided
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lower limit |
-5.5 | ||||||||||||||||||||
upper limit |
5 | ||||||||||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
3.13
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Adverse events information
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Timeframe for reporting adverse events |
During treatment period
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Adverse event reporting additional description |
The incidence of all treatment-emergent adverse events (TEAEs) reported during the study was similar between JM-010 0.8/8 mg and placebo groups and higher in the JM-010 0.8/4 mg group. There were no SAEs and deaths reported in Safety Set.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
27.0
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Reporting groups
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Reporting group title |
JM-010 0.8/8 mg
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Reporting group description |
Subjects were treated with buspirone 8 mg/zolmitriptan 0.8 mg. The dose strengths of JM-010 were assessed in dosing regimens from 3 to 6 times per day, in order to match the daily doses of L-DOPA administered by each subject. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
JM-010 0.8/4 mg
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Reporting group description |
Subjects were treated with buspirone 4 mg/zolmitriptan 0.8 mg. The dose strengths of JM-010 were assessed in dosing regimens from 3 to 6 times per day, in order to match the daily doses of L-DOPA administered by each subject. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Subjects were administrated with 1 placebo tablet (158 mg) + 1 placebo tablet (166 mg). The dose strengths of Placebo were assessed in dosing regimens from 3 to 6 times per day, in order to match the daily doses of L-DOPA administered by each subject. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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30 Nov 2018 |
Removed text “patients with moderate to severe dyskinesia” and added “to week 12” in primary objective, added “double-blind, double-dummy” to the study design, updated exclusion criteria, the “pharmacodynamic” assessment was removed from throughout protocol, and added pharmacokinetic endpoints and assessment section. |
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19 Sep 2019 |
Removed text “patients with moderate to severe dyskinesia” from the primary objective in the synopsis; Primary objective updated to include the text “to week 12”, added “double-blind, double-dummy” to the study design, updated exclusion criteria. |
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24 Mar 2021 |
Updated number of participating study sites and the total duration of study, Corrected the definition of an overdose and reporting overdose with and without AE/SAE. |
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15 Oct 2021 |
Updated events not meeting the definition of an AE for clarification and activities in Schedule of Events. |
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25 Jul 2022 |
Updated number of study sites and the total duration of study. |
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06 Oct 2022 |
Changed the address of Contera Pharma A/S office to new address. |
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05 Apr 2023 |
Updated eligibility age to 85 years, updated other inclusion and exclusion criteria, updated prior and concomitant therapy, vital signs and schedule of events sections to allow use of selective MAO-B inhibitors, updated method of assigning participants to treatment groups by region of enrollment (Europe and Korea). |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
