A Phase 2 Study of CX-8998 in Adults With Tremor Associated With Parkinson's Disease

NCT03436953 | Withdrawn Phase 2 FDA Drug

• 1 other identifier: CX-8998-CLN2-003
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a Phase 2, multicenter, double-blind, placebo-controlled, parallel-group study consisting of a screening period of up to 4 weeks, a 4 week randomized double-blind, dose-titration treatment period, followed by a 1 week safety follow-up period after the last dose of study medication, and a scheduled follow-up safety telephone call one week later.

Conditions

Parkinson's Disease; Tremor

Outcome Measures

Primary Outcomes (1)

• Change from Baseline to Day 28 on the MDS-UPDRS Tremor Score as scored by the central rater

  The MDS-UPDRS is a multi-dimensional scale that assesses the motor and non-motor impact of PD across four parts. Part I: Non-Motor Experiences of Daily Living; Part II: Motor Experiences of Daily Living; Part III: Motor Examination; and Part IV: Motor Complications.

  Baseline through completion of study treatment period, an average of 28 days

Secondary Outcomes (12)

• Change from Baseline to Day 28 on the TETRAS Activity of Daily Living subscale

  Baseline through completion of study treatment period, an average of 28 days

• Change from Baseline to Day 28 in accelerometry score

  Baseline through completion of study treatment period, an average of 28 days

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] as assessed by CTCAE v4.0

  Through study completion, an average of 12 weeks

• Changes from baseline in QTcF

  Baseline through study completion, an average of 5 weeks

• Percentage of subjects who did not complete the study due to Treatment Emergent Adverse Events as assessed by CTCAE v4.0

  Duration of study, an average of 12 weeks

Study Arms (2)

CX-8998 T-type calcium channel blocker

EXPERIMENTAL

Drug: CX-8998

Comparator

PLACEBO COMPARATOR

Drug: Placebo

Interventions

CX-8998 DRUG

T-type calcium channel blocker

CX-8998 T-type calcium channel blocker

Placebo DRUG

Placebo comparator

Comparator

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men or non-pregnant, non-breastfeeding women 40 to 80 years-of-age who are able to read and understand English.
• Mini Mental State Exam (MMSE) score ≥ 24.
• Clinical diagnosis of idiopathic Parkinson's disease and presence of at least 2 out of 3 cardinal characteristics (tremor, rigidity, and/or bradykinesia).
• Hoehn \& Yahr Stage I III (inclusive) if not experiencing motor fluctuations. If experiencing motor fluctuations, must be Hoehn \& Yahr Stage I IV (inclusive) when OFF or I-III (inclusive) when ON.
• An MDS-UPDRS tremor score (sum of items 2.10, 3.15, 3.16, 3.17, 3.18) of a least 10 (during ON for subjects experiencing fluctuations) (centrally rated) (Forjaz et al., 2015). A limited number of subjects with an MDS-UPDRS of 8 or 9 may be included with Sponsor approval.
• Treated with a stable regimen of anti-parkinsonian and/or anti-tremor medication (with the exception of primidone) for at least 2 weeks prior to screening. Changes to anti-parkinsonian or anti-tremor medications after screening is not permitted.

You may not qualify if:

• Current diagnosis of: a. essential tremor / b. cerebellar disease
• Presence or known history of: a. significant visual hallucinations (in the opinion of the Investigator and/or Study Safety Representative) / b. significant impulse control disorder (ICD) (in the opinion of the Investigator and/or Study Safety Representative).
• History or clinical features consistent with an atypical parkinsonian syndrome.
• Dyskinesia or dystonia that would, in the opinion of the investigator, central rater, or Sponsor, interfere with the assessment of tremor.
• Exposure to tremorigenic drugs or drug withdrawal states within the 30 days prior to the first planned dose of study drug.
• Direct or indirect trauma to the nervous system within 3 months preceding the onset of tremor.
• History or clinical evidence of psychogenic tremor origin. Known history of other medical or neurological conditions that may cause or explain subject's tremor.
• Prior MR-guided Focused Ultrasound or surgical intervention (e.g., deep brain stimulation, ablative thalamotomy or gamma knife thalamotomy) for treatment of tremor or Parkinson's disease.
• Use of medication(s) in the past month that might produce tremor or interfere with the evaluation of tremor.
• Inability to refrain from use of medication/substance(s) that might produce tremor or interfere with the evaluation of tremor on study visit days.
• Positive urine drug screen for drugs of abuse, except if this is explained by use of an allowed prescription medicine.
• Regular use of more than two units of alcohol per day.
• Use of prescription or non-prescription drugs or other products (i.e. grapefruit juice) known to be strong inhibitors or inducers of CYP3A4 which cannot be discontinued 2 weeks prior to Day 1 of dosing and withheld throughout the study.
• Concurrent illnesses that would be a contraindication to trial participation.
• Psychological, social, familial, or geographical reasons that would hinder or prevent compliance with the requirements of the protocol or compromise the informed consent process.

Sponsors & Collaborators

• Jazz Pharmaceuticals: lead

MeSH Terms

Conditions

Parkinson Disease; Tremor

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Dyskinesias; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Stacey Boyer, PhD

  Jazz Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 7, 2018
• First Posted: February 19, 2018
• Study Start: December 1, 2019
• Primary Completion: September 1, 2020
• Study Completion: December 1, 2020
• Last Updated: May 28, 2021

Record last verified: 2021-05