Parkinson's DiseasePhase 2NCT03436953
A Phase 2 Study of CX-8998 in Adults With Tremor Associated With Parkinson's Disease
A Phase 2 study testing CX-8998 in people with Parkinson's Disease and Tremor, run by Jazz Pharmaceuticals.
Trial 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… Read more about this study
- Who is it for?
- Ages 40 to 80 years
- Conditions the study is for
- Parkinson's Disease, Tremor
- What is being tested?
- CX-8998
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Dec 2019to Dec 2020
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
- Any other condition and/or situation that causes the Investigator or Study Safety Representative to deem a subject unsuitable for the study (e.g., due to expected study medication non-compliance, inability to medically tolerate the study procedures, or a subject's unwillingness to comply with study-related procedures).
- Treatment with an investigational agent within 30 days prior to the first dose of CX-8998 or planning to receive an investigational agent during the study.
About this study
Official title: A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study of CX-8998 for Tremor Associated With Parkinson's Disease
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.
Read the detailed description
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.
Subjects will be randomized 1:1 to one of two treatment groups. Group A will receive titrating doses of CX-8998 up to 10 mg BID and Group B will receive placebo.
Subjects will participate for a total of up to 12 weeks, including screening, the 4-week treatment period and follow-up.
- Conditions
- Parkinson's Disease, Tremor
- Being tested
- CX-8998, Placebo
- Medical subject headings
- Parkinson Disease, Tremor
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CX-8998Drug
T-type calcium channel blocker
PlaceboDrug
Placebo comparator
| Study group | Role | What they receive |
|---|---|---|
| CX-8998 T-type calcium channel blocker | Experimental | Not described Receives: Drug: CX-8998 |
| Comparator | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
The ADL section of TETRAS has 12 items, each rated 0, 1, 2, 3 or 4. The maximum total score is 48. Item 1 addresses speech; item 10 addresses occupational impairment; and item 12 assesses social impact. The other 9 items assess activities that are affected primarily by upper limb tremor
Measured: Baseline through completion of study treatment period, an average of 28 days
Change from Baseline to Day 28 in accelerometry score
Accelerometry will be used to obtain quantitative measurements of tremor. The Kinesia ONE device will be placed on the index finger and worn in the clinic immediately after execution of the MDS-UPDRS and/or TETRAS performance subscale. A total of 4 tasks will be performed on the left side and then again on the right side to assess resting, postural, kinetic, and lateral wing beating tremor. Each task will be performed for 15 seconds.
Measured: 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
Treatment-emergent adverse events are all adverse events occurring during the treatment period or a pretreatment event that worsens in intensity during the treatment period.
Measured: Through study completion, an average of 12 weeks
Changes from baseline in QTcF
Fridericia's Correction Formula (QTCF) is a formula which takes into account the physiologic shortening of the QT interval which occurs as the heart rate increases, permitting comparison of the QT interval across a range of rates.
Measured: 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
Treatment-emergent adverse events are all adverse events occurring during the treatment period or a pretreatment event that worsens in intensity during the treatment period.
Measured: Duration of study, an average of 12 weeks
Percentage of subjects with Serious Adverse Events as assessed by CTCAE v4.0
Any adverse event that results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect observed in any offspring of the subject conceived during treatment with the study drug or is an important medical event.
Measured: Duration of study, an average of 12 weeks
Percentage of subjects with Adverse Events of Special Interest as assessed by CTCAE v4.0
An adverse event of special interest is a serious adverse event as defined in Outcome 8.
Measured: Duration of study, an average of 12 weeks
Columbia-Suicide Severity Rating Scale (C-SSRS)
The Columbia-Suicide Severity Rating Scale (C-SSRS) is a questionnaire used for suicide assessment. A numerical score is derived from the C-SSRS categories. The score is created at each assessment for each patient and is used for determining treatment emergence. Suicidal Ideation Score: The maximum suicidal ideation category (1-5 on the C-SSRS) present at the assessment.
Measured: Screening through study completion, an average of 8 weeks
Epworth Sleepiness Scale
The Epworth Sleepiness Scale (ESS) is a scale intended to measure daytime sleepiness that is measured by use of a very short questionnaire. The questionnaire asks the subject to rate his or her probability of falling asleep on a scale of increasing probability from 0 to 3 for 8 different situations. The scores are added together to obtain a single number.
Measured: Baseline through completion of study treatment period, an average of 28 days
Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS)
The QUIP-RS was developed to assess the severity of impulse control disorders and related behavior symptoms and to monitor changes in symptoms over time. The QUIP-RS has 4 primary questions (pertaining to commonly reported thoughts, urges/desires, and behaviors associated with impulsive control disorders), each of which is applied to 4 impulsive behaviors (compulsive gambling, buying, eating, and sexual behavior) and 3 related disorders (medication use, punding, and hobbyism). It uses a 5-point scale to gauge the frequency of behaviors. Scores for each behavior and related disorder range from 0 to 16, with a higher score indicating greater severity (ie, frequency) of symptoms. The total QUIP-RS score for all impulsive control disorders and related disorders combined ranges from 0 to 112.
Measured: Screening through study completion, an average of 8 weeks
University of Miami Parkinson's disease Hallucinations Questionnaire (UM-PDHQ)
The UM-PDHQ is a 20-item clinician-administered questionnaire that is completed during a structured interview. Questions are divided into 2 groups: a quantitative group that consists of 6 questions (modality, frequency, duration, insight, emotional burden) and a qualitative group that consists of 14 questions. Scores range from 0-14.
Measured: Screening, Baseline and Day 28, an average of 28 days
Hospital Anxiety and Depression Scale (HADS)
The Hospital Anxiety and Depression Scale (HADS), a self-assessment scale, was developed to detect states of depression, anxiety and emotional distress. The HADS is a 14-item scale that generates ordinal data. Seven of the items relate to anxiety, and 7 of the items relate to depression. Each item on the questionnaire is scored from 0 to 3, with individual scores ranging between 0 and 21 for either anxiety or depression.
Measured: Screening and Day 28, an average of 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2018
- Study startDec 2019 (estimated)
- Primary completionSep 2020 (estimated)
- Study completionDec 2020 (estimated)
Why it stopped: The program was not initiated nor were any patients ever enrolled. The investigations detailed in the submitted protocol were incorporated into another program.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Parkinson's DiseaseStudies of the same condition, open and under way.
- More trials run by Jazz PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jazz Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Stacey Boyer, PhD, Study director, Jazz Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03436953
- Sponsor's protocol ID
- CX-8998-CLN2-003
- Status last verified
- May 2021
- First submitted
- 7 Feb 2018
- Last updated
- 28 May 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 28 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study of CX-8998 for Tremor Associated With Parkinson's Disease
- ClinicalTrials.gov ID
- NCT03436953
- Acronym / sponsor ID
- CX-8998-CLN2-003
- Conditions
- Parkinson's Disease, Tremor
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: The program was not initiated nor were any patients ever enrolled. The investigations detailed in the submitted protocol were incorporated into another program.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Jazz PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Dec 2019 (estimated)
- Primary completion
- Sep 2020 (estimated)
- Study completion
- Dec 2020 (estimated)
- First posted
- 19 Feb 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Subjects will be randomized 1:1 to one of two treatment groups. Group A will receive titrating doses of CX-8998 up to 10 mg BID and Group B will receive placebo.
Subjects will participate for a total of up to 12 weeks, including screening, the 4-week treatment period and follow-up.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CX-8998 T-type calcium channel blocker | Experimental | Drug: CX-8998 |
| Comparator | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 40 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (17 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CX-8998T-type calcium channel blocker | Drug | CX-8998 T-type calcium channel blocker |
| PlaceboPlacebo comparator | Drug | Comparator |
Primary outcome
Change from Baseline to Day 28 on the MDS-UPDRS Tremor Score as scored by the central rater
Time frame: Baseline through completion of study treatment period, an average of 28 days
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.
12 secondary outcomes
Change from Baseline to Day 28 on the TETRAS Activity of Daily Living subscale
Time frame: Baseline through completion of study treatment period, an average of 28 days
Change from Baseline to Day 28 in accelerometry score
Time frame: 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
Time frame: Through study completion, an average of 12 weeks
Changes from baseline in QTcF
Time frame: 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
Time frame: Duration of study, an average of 12 weeks
Percentage of subjects with Serious Adverse Events as assessed by CTCAE v4.0
Time frame: Duration of study, an average of 12 weeks
Percentage of subjects with Adverse Events of Special Interest as assessed by CTCAE v4.0
Time frame: Duration of study, an average of 12 weeks
Columbia-Suicide Severity Rating Scale (C-SSRS)
Time frame: Screening through study completion, an average of 8 weeks
Epworth Sleepiness Scale
Time frame: Baseline through completion of study treatment period, an average of 28 days
Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS)
Time frame: Screening through study completion, an average of 8 weeks
University of Miami Parkinson's disease Hallucinations Questionnaire (UM-PDHQ)
Time frame: Screening, Baseline and Day 28, an average of 28 days
Hospital Anxiety and Depression Scale (HADS)
Time frame: Screening and Day 28, an average of 28 days
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 May 2021.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stacey Boyer, PhD study director
Jazz Pharmaceuticals
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing CX-8998 in people with Parkinson's Disease and Tremor, run by Jazz Pharmaceuticals.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 28 May 2021. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from Baseline to Day 28 on the MDS-UPDRS Tremor Score as scored by the central rater (time frame: Baseline through completion of study treatment period, an average of 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 May 2021.