A Study of Suvecaltamide in Adults with Moderate to Severe Residual Tremor in Parkinson's Disease

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Cavion Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

21 Jun 2023 → 11 Nov 2024

Decision date (initial)

2024-10-15

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Cavion Inc., a subsidiary of Jazz Pharmaceuticals, Inc.

External identifiers

EU CT number

2024-515177-94-00

EudraCT number

2022-001063-27

ClinicalTrials.gov

NCT05642442

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Pharmacodynamic, Pharmacogenomic, Dose response, Others, Efficacy

To evaluate the efficacy of suvecaltamide administered once daily for 17 weeks to improve functional and performance-based impairment due to tremor.

Secondary objectives 1

1. To evaluate the safety and tolerability of suvecaltamide administered once daily for 17 weeks.

Conditions and MedDRA coding

Parkinson's Disease

Study design 3 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

IPD plan description

In accordance with ICMJE requirements, Jazz Pharmaceuticals may provide qualified external researchers access to individual participant data (IPD) and clinical trial data that underlie the results of this trial upon request.  Qualified researchers can submit a request on https://www.jazzpharma.com/science/clinical-trial-data-sharing/ as outlined. Jazz Pharmaceuticals reserves the right not to consider a request. For inquiries about Jazz’s data sharing policy contact [email protected]

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. 1. Male and female participants ages 40 to 85 years inclusive, at time of signing the ICF
2. 2. Body mass index from 17 to 45 kg/m2 (inclusive) at Screening
3. 3. Diagnosis of clinically probable or clinically established PD meeting the MDS 2015 criteria within the past 5 years.
4. 4. 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.
5. 5. 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.
6. 6. 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.
7. 7. Participants have moderate to severe impairment associated with tremor at both the Screening and Baseline Visits.
8. 8. Contraception: a. Male participants: Male participants are eligible to participate if they agree to the following during with study contraception during the study intervention period and for at least 30 days after the last dose of study intervention. b. Female participants: A female participant is eligible to participate if she is not pregnant or breastfeeding, and comply with 1 of the contraceptive conditions.
9. 9. Capable of giving signed informed consent as described in Section 10.1.3 of the protocol which includes compliance with the requirements and restrictions listed in the ICF and in the protocol.
10. 10. Willing and able to comply with the study design schedule and other requirements.

Exclusion criteria 31

1. 1. Female participants who are pregnant, nursing, or lactating or plan to become pregnant during the study or within 90 days of study completion.
2. 10. History or presence of gastrointestinal disease which is likely to significantly interfere with the absorption, metabolism, or elimination of suvecaltamide.
3. 11. History or presence of hepatic or renal disease, or any other condition that may interfere with absorption, distribution, metabolism, or excretion of drugs.
4. 12. Presence of significant cardiovascular disease at Screening.
5. 13. History or presence of bipolar and related mood disorders, schizophrenia, schizophrenia spectrum disorders, or other psychotic disorders.
6. 14. 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.
7. 15. 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.
8. 16. 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.
9. 17.Prior or planned surgical intervention to treat PD.
10. 18.PRN use of PD medications or other anti-tremor medications or continuous infusion of PD medication.
11. 19.Inability to refrain from using a mechanical device for the management of tremor during the study.
12. 2. 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, including, but not limited to: psychogenic tremor; myoclonus or ataxia; cerebellar disease; traumatic brain injury; alcohol abuse or withdrawal; mercury poisoning; hyperthyroidism; pheochromocytoma; multiple sclerosis; clinically significant polyneuropathy in the opinion of the investigator; or family history or diagnosis of Fragile X syndrome. Note: Participants with a history of essential tremor are eligible.
13. 20.Botulinum toxin injection in the 6 months before Screening or planned use at any time during the study.
14. 21.Currently taking dopamine antagonists or depleting medications.
15. 22.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.
16. 23.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.
17. 24.Use of proton pump inhibitors, which cannot be discontinued at least 2 weeks before Baseline, or planned use at any time during the study.
18. 25.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.
19. 26.Laboratory value(s) at Screening outside the laboratory reference range that is/are considered markedly abnormal.
20. 27.Urine drug screen positive at Screening for drugs of abuse unless explained by use of an allowed prescription medication.
21. 28.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.
22. 29.Regular consumption of > 600 mg caffeine per day or > 6 cups of coffee per day.
23. 3. Hoehn & Yahr stage 5 (confinement to bed or wheelchair unless aided).
24. 30.Allergy or sensitivity to any ingredients in the study intervention formulation or placebo.
25. 31.Any other condition and/or situation that causes the investigator or Medical Monitor to deem a participant unsuitable for the study
26. 4. Participants who only experience tremor during their “OFF” periods.
27. 5. 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.
28. 6. Clinically significant symptomatic orthostatic hypotension in the opinion of the investigator.
29. 7. Has evidence at Screening of cognitive impairment as defined by a MoCA score < 22 or has cognitive impairment that in the opinion of the investigator would prevent completion of study procedures or the ability to provide informed consent.
30. 8. Received any study intervention in a previous suvecaltamide (JZP385, formerly CX8998 and MK-8998) clinical study.
31. 9.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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Evaluate the efficacy of suvecaltamide administered once daily for 17 weeks to improve functional and performance-based impairment due to tremor

Secondary endpoints 1

1. 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

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Cavion Inc.

Sponsor organisation

Cavion Inc.

Address

3170 Porter Drive

City

Palo Alto

Postcode

94304-1212

Country

United States

Scientific contact point

Organisation

Cavion Inc.

Contact name

Clinical Trial Disclosure and Transparency

Public contact point

Organisation

Cavion Inc.

Contact name

Clinical Trial Disclosure and Transparency

Third parties 11

Locations

3 EU/EEA countries · 17 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 19 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications