| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated | |
| E.1.1.1 | Medical condition in easily understood language | |
| E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 | | E.1.2 | Level | PT | | E.1.2 | Classification code | 10061536 | | E.1.2 | Term | Parkinson's disease | | E.1.2 | System Organ Class | 10029205 - Nervous system disorders | |
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial | To evaluate the efficacy of suvecaltamide administered once daily for 17 weeks to improve functional and performance-based impairment due to tremor.
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| E.2.2 | Secondary objectives of the trial | | To evaluate the efficacy of suvecaltamide administered once daily for 17 weeks to improve functional impairment due to tremor. | |
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria | Male and female participants ages 40 to 85 years inclusive, at time of signing the ICF.
Body mass index from 17 to 45 kg/m2 (inclusive) at Screening.
Diagnosis of clinically probable or clinically established idiopathic PD meeting the MDS 2015 criteria within the past 5 years.
Participants must be individually optimized on PD medications for the treatment of other cardinal signs of PD (bradykinesia, rigidity) per the judgement of the investigator. Optimized treatment is defined as the maximum therapeutic effect obtained with PD medications when no further improvement is expected regardless of any additional adjustments to these medications or when the PD medications or adjustments to these medications are anticipated to result in intolerable side effects. This will be based on the investigator’s clinical judgement
Participants must be on a stable dosing regimen of their permitted PD and/or other tremor medications for the treatment of motor symptoms for at least 6 weeks prior to Screening and do not anticipate the need to make any changes for the duration of the study. A lack of use of medications used to treat motor symptoms also must be stable for 6 weeks prior to Screening and remain stable for the duration of the study
For participants who experience motor fluctuations, tremor must also be present during “ON” periods and participants should be able to have tremor symptoms evaluated during “ON” periods, as determined by the investigator, in relation to the participant’s PD medications. If necessary, participants may take their PD medications in the clinic during visits where tremor symptoms are evaluated
Participants have moderate to severe impairment associated with tremor at both the Screening and Baseline Visits
Contraception:
Male participants:
Male participants are eligible to participate if they agree with study contraception during the study intervention period and for at least 30 days after the last dose of study intervention
Female participants:
A female participant is eligible to participate if she is not pregnant or breastfeeding, and following 1 of the contraception conditions
Capable of giving signed informed consent as described in Section 10.1.3 which includes compliance with the requirements and restrictions listed in the ICF and in this protocol
Willing and able to comply with the study design schedule and other requirements
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| E.4 | Principal exclusion criteria | Female participants who are pregnant, nursing, or lactating or plan to become pregnant during the study or within 90 days of study completion
Known history or current evidence of other medical or neurological conditions that may cause or explain the participant’s tremor in the opinion of the investigator
Hoehn & Yahr stage 5
Participants who only experience tremor during their “OFF” periods
Severity of motor fluctuations or medication-induced dyskinesia that would interfere with the assessment of tremor and/or “ON”/“OFF” periods that are unpredictable per the opinion of the investigator
Clinically significant symptomatic orthostatic hypotension
Has evidence at Screening of cognitive impairment that would prevent completion of study procedures or the ability to provide informed consent
Received any study intervention in a previous suvecaltamide clinical study
History or presence of a clinically significant acute or unstable medical condition, chronic infection, malignancy other than basal cell carcinoma or resected noninvasive cutaneous squamous cell carcinoma, or surgical history that could affect the safety of the participant or interfere with study efficacy, safety, or PK assessments; or the ability of the participant to complete the study
History or presence of gastrointestinal disease which is likely to significantly interfere with the absorption, metabolism, or elimination of suvecaltamide.
History or presence of hepatic or renal disease, or any other condition that may interfere with absorption, distribution, metabolism, or excretion of drugs
Presence of significant cardiovascular disease at Screening
History or presence of bipolar and related mood disorders, schizophrenia, schizophrenia spectrum disorders, or other psychotic disorders
Current suicidal risk as determined from history, by presence of active suicidal ideation, or any history of suicide attempt; current or past major depressive episode. Participants with stable treated depression are allowed; the participant’s antidepressant treatment must be stable for at least 6 months prior to Screening and expected to remain stable for the duration of the study
History or presence of substance use disorder, known drug dependence, or seeking treatment for alcohol or substance abuse related disorder. Nicotine use disorder would not be exclusionary if it does not impact tremor
Treatment-naïve patients are excluded from participating in the study
PRN use of medication/substance(s) that might interfere with the evaluation of tremor on study visit days, such as, but not limited to, stimulant decongestants, beta-agonist bronchodilators, benzodiazepine, sedative/hypnotics, and alcohol. Participants who consume caffeine or use tobacco should take their regular amount of caffeine or tobacco on the clinic days
Prior or planned surgical intervention to treat PD
PRN use of PD medications or other anti-tremor medications or continuous infusion of PD medication
Inability to refrain from using a mechanical device for the management of tremor during the study
Botulinum toxin injection in the 6 months before Screening or planned use at any time during the study
Currently taking dopamine antagonists or depleting medications
Use of prescription or nonprescription drugs or other products known to be inducers of CYP3A4, which cannot be discontinued at least 4 weeks before Baseline, or planned use at any time during the study
Use of prescription or nonprescription drugs or other products known to be strong or moderate inhibitors of CYP3A4, which cannot be discontinued 2 weeks or 5 half-lives, whichever is longer, before Baseline, or planned use at any time during the study
Use of proton pump inhibitors, which cannot be discontinued at least 2 weeks before Baseline, or planned use at any time during the study
Received an investigational drug in the past 30 days or 5 half-lives prior to the Baseline Visit or plans to use an investigational drug during the study
Laboratory value(s) at Screening outside the laboratory reference range that is/are considered markedly abnormal
Urine drug screen positive at Screening for drugs of abuse unless explained by use of an allowed prescription medication.
Daily or near-daily use of more than 2 units of alcohol per day. A unit of alcohol is defined as a 12-fluid ounce glass of beer, a 5-fluid ounce glass of wine, or a 1.5-fluid ounce glass of spirit
Regular consumption of > 600 mg caffeine per day or > 6 cups of coffee per day
Allergy or sensitivity to any ingredients in the study intervention formulation or placebo
Any other condition and/or situation that causes the investigator or Medical Monitor to deem a participant unsuitable for the study
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| E.5 End points |
| E.5.1 | Primary end point(s) | | Evaluate the efficacy of suvecaltamide administered once daily for 17 weeks to improve functional and performance-based impairment due to tremor | |
| E.5.1.1 | Timepoint(s) of evaluation of this end point | | Change from Baseline to Week 17 on the TETRAS composite outcome score | |
| E.5.2 | Secondary end point(s) | Efficacy:
Evaluate the efficacy of suvecaltamide administered once daily for 17 weeks to improve functional impairment due to tremor
safety:
Incidence and severity of AEs as well as evaluation of safety laboratory assessments, vital signs, ECG results, C-SSRS and QUIP-RS. | |
| E.5.2.1 | Timepoint(s) of evaluation of this end point | Time point is throughout the study. AE evaluation specifically begins after first dose.
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| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description | |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 | The trial involves single site in the Member State concerned | No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 8 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 17 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned | |
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 | Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial | | LPLV - English | | LPLV - German | |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 3 |
| E.8.9.1 | In the Member State concerned days | 19 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
| E.8.9.2 | In all countries concerned by the trial days | 19 |
