Essential TremorPhase 2NCT05387642
A Clinical Trial of PRAX-114 in Participants With Essential Tremor
A Phase 2 study testing 10 mg PRAX-114 or 20 mg PRAX-114 in people with Essential Tremor, run by Praxis Precision Medicines at 3 sites in United States.
Trial summary
This is a 2-part clinical trial to evaluate the safety, tolerability, pharmacokinetics, and efficacy of PRAX-114 in participants with essential tremor (ET). Part A is a randomized, double-blind, placebo-controlled, three-period, three-sequence, crossover design where participants will receive a single dose of 10 mg… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Essential Tremor
- What is being tested?
- 10 mg PRAX-114 or 20 mg PRAX-114
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 3 sitesUnited States
- Study dates
- 5 Apr 2022to 30 Jun 2022
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Has a clinical diagnosis of moderate to severe ET, including, a) tremor syndrome of bilateral upper limb action tremor, b) symptoms for at least 3 years in duration, c) with or without tremor in other locations (eg, head, voice, or lower limbs), d) if the symptoms and signs are judged by the investigator to be due to the diagnosis of ET, it is acceptable for them to also have one or more of the following ET plus signs: i) mild dystonic posturing, ii) mild rest tremor in the setting of advanced ET and in the absence of other features of Parkinsonism, iii) intention tremor, iv) mild increase in tandem gait difficulty.
- Has a TETRAS upper limb score (ie, sum of bilateral upper limb items 4a, 4b, and 4c) of ≥10 as rated by the Investigator at Screening and Baseline. (Exception for Part B only: Tremor severity can fluctuate, and it may be that a participant who met TETRAS upper limb criteria at Screening and Day 1 for Part A no longer meets the tremor severity inclusion criterion above at Screening or on Day 1 of Part B. If all the other eligibility criteria are still met such a participant would still be eligible for inclusion in Part B.)
- If receiving primidone or topiramate for ET, is willing and able to complete discontinuation no later than 14 days prior to Day 1 of Part A. If currently receiving any other medication for ET, is on a stable dose of any of these other medications for ET for 28 days prior to Screening and is willing to maintain stable doses throughout the clinical trial.
- Has a body mass index (BMI) between 18 and 40 kg/m2, inclusive.
Who cannot join
- Has a history or clinical evidence of other medical, neurological, or psychiatric condition that may explain or cause tremor, including but not limited to Parkinson's disease, Huntington's disease, Alzheimer's disease, cerebellar disease (including spinocerebellar ataxias), primary dystonia, Fragile X Tremor/Ataxia syndrome or family history of Fragile X syndrome, traumatic brain injury, psychogenic tremor, alcohol or benzodiazepine abuse or withdrawal, multiple sclerosis, polyneuropathy, and endocrine states such as hyperthyroidism or unstable treatment of hypothyroidism or medication, food, or supplement induced movement disorders (eg, tremor related to beta agonists or caffeine), or other medical, neurological, or psychiatric conditions that may explain or cause tremor.
- Has trauma to the nervous system within 3 months preceding the onset of tremor.
- Has had prior magnetic resonance-guided focused ultrasound or surgical intervention for ET such as deep brain stimulation or thalamotomy.
- Has had botulinum toxin injection for ET in the 6 months prior to Screening.
- Is using the Cala trio health device for ET in the last 14 days prior to Baseline and throughout the study.
- Is unwilling or unable to refrain from episodic use of medication(s)/substance(s) that might interfere with the evaluation of tremor during the trial. Stable use of medication(s)/substance(s) that might impact tremor, including caffeine and beta-agonist bronchodilators, is allowed so long as the tremor is judged by the Investigator to be primarily due to the participant's ET diagnosis.
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- Is unwilling or unable to refrain from use of any sleep aids (eg, eszopiclone, zaleplon and zolpidem) or anxiolytics that are known to be mediated by GABAergic mechanisms (eg, benzodiazepines) within 24 hours prior to any clinic visit. (Exception: Stable use (at least 28 days prior to Screening) of up to 2 ET non-tremor active, non-GABAergic antidepressants and anxiolytics is allowed during the clinical trial after discussion with the medical monitor and/or sponsor designee.) (Note for Part B only: Participants should avoid using sleep aids and anxiolytics that are known to be mediated by GABAergic mechanisms in Part B.)
- Is unwilling or unable to refrain from alcohol 24 hours before and during clinical trial visits, or regular consumption of more than 2 standard alcohol-containing beverages per day for males or more than 1 standard alcohol-containing beverages per day for females and are unwilling to reduce consumption to the appropriate level during the Screening period and maintain this level throughout the Intervention and Follow-up Periods.
- Has a history of substance use disorder consistent with Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria in the opinion of the Investigator.
- Has a lifetime history of seizures, including febrile seizures.
- Is required to take any excluded medication listed in the protocol during the clinical trial. Chronic medication must be stable for at least 4 weeks prior to Screening. Any new non-urgent medications started during the trial and permitted in protocol should be discussed with the Sponsor before initiation, as practicable.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Praxis Research Site
Boca Raton, Florida, 33486
Praxis Research Site
Farmington Hills, Michigan, 48334
Praxis Research Site
Kirkland, Washington, 98034
About this study
Official title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Trial to Explore the Safety, Tolerability, Pharmacokinetics, and Efficacy of PRAX-114 in the Treatment of Adults With Essential Tremor
This is a 2-part clinical trial to evaluate the safety, tolerability, pharmacokinetics, and efficacy of PRAX-114 in participants with essential tremor (ET). Part A is a randomized, double-blind, placebo-controlled, three-period, three-sequence, crossover design where participants will receive a single dose of 10 mg PRAX-114, 20 mg PRAX-114, and matching placebo. Part B is an open-label design where participants from Part A, after washout and confirmation of eligibility may elect to participate in Part B where all participants will receive 10 mg once every morning (QAM) for the first 14 days. Based on investigator judgement of the safety and tolerability, the dose for Days 15 to 28 could be increased to 20 mg QAM.
- Conditions
- Essential Tremor
- Being tested
- 10 mg PRAX-114, 20 mg PRAX-114, and Placebo, 10 mg PRAX-114 or 20 mg PRAX-114
- Keywords
- Essential Tremor, Tremor, GABAA, GABAA receptor, GABAA PAM, Movement Disorders, Central Nervous System Diseases
- Medical subject headings
- Essential Tremor, Tremor, Movement Disorders, Central Nervous System Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
10 mg PRAX-114, 20 mg PRAX-114, and PlaceboDrug
Single dose with a washout period between doses
10 mg PRAX-114 or 20 mg PRAX-114Drug
Once daily oral treatment for 28 days
| Study group | Role | What they receive |
|---|---|---|
| Double-blind Sequence 1 | Experimental | Double-blind treatment sequence of 10 mg, 20 mg, and placebo in the morning Receives: Drug: 10 mg PRAX-114, 20 mg PRAX-114, and Placebo |
| Double-blind Sequence 2 | Experimental | Double-blind treatment sequence of 20 mg, placebo, and 10 mg in the morning Receives: Drug: 10 mg PRAX-114, 20 mg PRAX-114, and Placebo |
| Double-blind Sequence 3 | Experimental | Double-blind treatment sequence of placebo, 10 mg, and 20 mg in the morning Receives: Drug: 10 mg PRAX-114, 20 mg PRAX-114, and Placebo |
| Open-label Period PRAX-114 | Experimental | Open-label extension period - 10 mg or 20 mg PRAX-114 once daily in the morning for 28 days Receives: Drug: 10 mg PRAX-114 or 20 mg PRAX-114 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part A: Incidence and severity of Adverse Events (AE)
The incidence and severity of AEs will be reported by preferred term, including any terms related to clinically significant physical examination findings, as well as vital sign measures (changes in body temperature, pulse rate, respiratory rate, blood pressure [systolic and diastolic]), clinical laboratory measures (chemistry, hematology, urinalysis, and coagulation), electrocardiogram parameters (heart rate, PR, QRS, QT, and corrected QT intervals), Stanford Sleepiness Scale, and Columbia-Suicide Severity Rating Scale (C-SSRS) responses.
Measured: 12 days
Part B: Incidence and severity of AEs
The incidence and severity of AEs will be reported by preferred term, including any terms related to clinically significant physical examination findings, as well as vital sign measures (changes in body temperature, pulse rate, respiratory rate, blood pressure [systolic and diastolic]), clinical laboratory measures (chemistry, hematology, urinalysis, and coagulation), electrocardiogram parameters (heart rate, PR, QRS, QT, and corrected QT intervals), and Columbia-Suicide Severity Rating Scale (C-SSRS) responses.
Measured: 35 days
Secondary outcomes (2)
Part A: Change from pre-dose to each post-dose timepoint on the Essential Tremor Rating Assessment Scale (TETRAS) combined upper limb (CUL) score
The TETRAS is an essential tremor and activities of daily living rating scale. The full scale has 2 sections, the Performance subscale (PS) and the TETRAS ADL subscale. The TETRAS PS consists of 9 items covering different body regions. TETRAS CUL aggregates the upper limb items from the TETRAS PS including Items 4, 6, 7 and 8. The total score of the 4 items (9 ratings) ranges from 0 to 44 with higher scores indicating greater tremor severity.
Measured: Day 1, Day 5, and Day 9
Part B: Change from baseline to Day 28 on the TETRAS Activities of Daily Living (ADL) subscale scores
The TETRAS ADL subscale consists of 12 items measuring the impact of essential tremor on typical daily activities. These 12 items are rated on a 5-point scale (ranging from 0 to 4). The total score of the 12 items ranges from 0 to 48 with higher scores indicating greater tremor severity.
Measured: Day 1, Day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 May 2022
- Study start5 Apr 2022
- Primary completion30 Jun 2022
- Study completion30 Jun 2022
Why it stopped: Sponsor no longer pursuing indication.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Essential TremorStudies of the same condition, open and under way.
- 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
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Praxis Precision Medicines
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- VP, Clinical Development, Study director, Praxis Precision Medicines
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05387642
- Sponsor's protocol ID
- PRAX-114-231
- Status last verified
- Nov 2022
- First submitted
- 13 May 2022
- Last updated
- 30 Nov 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Randomized, Double-Blind, Placebo-Controlled Trial to Explore the Safety, Tolerability, Pharmacokinetics, and Efficacy of PRAX-114 in the Treatment of Adults With Essential Tremor
- ClinicalTrials.gov ID
- NCT05387642
- Acronym / sponsor ID
- PRAX-114-231
- Conditions
- Essential Tremor
- Keywords
- Essential Tremor, Tremor, GABAA, GABAA receptor, GABAA PAM, Movement Disorders, Central Nervous System Diseases
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Sponsor no longer pursuing indication.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Praxis Precision MedicinesIndustry (pharma, biotech, devices)
- Study start
- 5 Apr 2022 (actual)
- Primary completion
- 30 Jun 2022 (actual)
- Study completion
- 30 Jun 2022 (actual)
- First posted
- 24 May 2022 (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 2-part clinical trial to evaluate the safety, tolerability, pharmacokinetics, and efficacy of PRAX-114 in participants with essential tremor (ET). Part A is a randomized, double-blind, placebo-controlled, three-period, three-sequence, crossover design where participants will receive a single dose of 10 mg PRAX-114, 20 mg PRAX-114, and matching placebo. Part B is an open-label design where participants from Part A, after washout and confirmation of eligibility may elect to participate in Part B where all participants will receive 10 mg once every morning (QAM) for the first 14 days. Based on investigator judgement of the safety and tolerability, the dose for Days 15 to 28 could be increased to 20 mg QAM.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Double-blind Sequence 1 | Experimental | Drug: 10 mg PRAX-114, 20 mg PRAX-114, and PlaceboDouble-blind treatment sequence of 10 mg, 20 mg, and placebo in the morning |
| Double-blind Sequence 2 | Experimental | Drug: 10 mg PRAX-114, 20 mg PRAX-114, and PlaceboDouble-blind treatment sequence of 20 mg, placebo, and 10 mg in the morning |
| Double-blind Sequence 3 | Experimental | Drug: 10 mg PRAX-114, 20 mg PRAX-114, and PlaceboDouble-blind treatment sequence of placebo, 10 mg, and 20 mg in the morning |
| Open-label Period PRAX-114 | Experimental | Drug: 10 mg PRAX-114 or 20 mg PRAX-114Open-label extension period - 10 mg or 20 mg PRAX-114 once daily in the morning for 28 days |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Has a clinical diagnosis of moderate to severe ET, including, a) tremor syndrome of bilateral upper limb action tremor, b) symptoms for at least 3 years in duration, c) with or without tremor in other locations (eg, head, voice, or lower limbs), d) if the symptoms and signs are judged by the investigator to be due to the diagnosis of ET, it is acceptable for them to also have one or more of the following ET plus signs: i) mild dystonic posturing, ii) mild rest tremor in the setting of advanced ET and in the absence of other features of Parkinsonism, iii) intention tremor, iv) mild increase in tandem gait difficulty.
- Has a TETRAS upper limb score (ie, sum of bilateral upper limb items 4a, 4b, and 4c) of ≥10 as rated by the Investigator at Screening and Baseline. (Exception for Part B only: Tremor severity can fluctuate, and it may be that a participant who met TETRAS upper limb criteria at Screening and Day 1 for Part A no longer meets the tremor severity inclusion criterion above at Screening or on Day 1 of Part B. If all the other eligibility criteria are still met such a participant would still be eligible for inclusion in Part B.)
- If receiving primidone or topiramate for ET, is willing and able to complete discontinuation no later than 14 days prior to Day 1 of Part A. If currently receiving any other medication for ET, is on a stable dose of any of these other medications for ET for 28 days prior to Screening and is willing to maintain stable doses throughout the clinical trial.
- Has a body mass index (BMI) between 18 and 40 kg/m2, inclusive.
Key exclusion criteria (11 listed)
- Has a history or clinical evidence of other medical, neurological, or psychiatric condition that may explain or cause tremor, including but not limited to Parkinson's disease, Huntington's disease, Alzheimer's disease, cerebellar disease (including spinocerebellar ataxias), primary dystonia, Fragile X Tremor/Ataxia syndrome or family history of Fragile X syndrome, traumatic brain injury, psychogenic tremor, alcohol or benzodiazepine abuse or withdrawal, multiple sclerosis, polyneuropathy, and endocrine states such as hyperthyroidism or unstable treatment of hypothyroidism or medication, food, or supplement induced movement disorders (eg, tremor related to beta agonists or caffeine), or other medical, neurological, or psychiatric conditions that may explain or cause tremor.
- Has trauma to the nervous system within 3 months preceding the onset of tremor.
- Has had prior magnetic resonance-guided focused ultrasound or surgical intervention for ET such as deep brain stimulation or thalamotomy.
- Has had botulinum toxin injection for ET in the 6 months prior to Screening.
- Is using the Cala trio health device for ET in the last 14 days prior to Baseline and throughout the study.
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 |
|---|---|---|
| 10 mg PRAX-114, 20 mg PRAX-114, and PlaceboSingle dose with a washout period between doses | Drug | Double-blind Sequence 1, Double-blind Sequence 2, Double-blind Sequence 3 |
| 10 mg PRAX-114 or 20 mg PRAX-114Once daily oral treatment for 28 days | Drug | Open-label Period PRAX-114 |
Primary outcome
Part A: Incidence and severity of Adverse Events (AE)
Time frame: 12 days
The incidence and severity of AEs will be reported by preferred term, including any terms related to clinically significant physical examination findings, as well as vital sign measures (changes in body temperature, pulse rate, respiratory rate, blood pressure [systolic and diastolic]), clinical laboratory measures (chemistry, hematology, urinalysis, and coagulation), electrocardiogram parameters (heart rate, PR, QRS, QT, and corrected QT intervals), Stanford Sleepiness Scale, and Columbia-Suicide Severity Rating Scale (C-SSRS) responses.
Part B: Incidence and severity of AEs
Time frame: 35 days
The incidence and severity of AEs will be reported by preferred term, including any terms related to clinically significant physical examination findings, as well as vital sign measures (changes in body temperature, pulse rate, respiratory rate, blood pressure [systolic and diastolic]), clinical laboratory measures (chemistry, hematology, urinalysis, and coagulation), electrocardiogram parameters (heart rate, PR, QRS, QT, and corrected QT intervals), and Columbia-Suicide Severity Rating Scale (C-SSRS) responses.
2 secondary outcomes
Part A: Change from pre-dose to each post-dose timepoint on the Essential Tremor Rating Assessment Scale (TETRAS) combined upper limb (CUL) score
Time frame: Day 1, Day 5, and Day 9
Part B: Change from baseline to Day 28 on the TETRAS Activities of Daily Living (ADL) subscale scores
Time frame: Day 1, Day 28
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 30 Nov 2022.
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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.
VP, Clinical Development study director
Praxis Precision Medicines
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing 10 mg PRAX-114 or 20 mg PRAX-114 in people with Essential Tremor, run by Praxis Precision Medicines at 3 sites in United States.
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 4 inclusion and 11 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 30 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. 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?
Part A: Incidence and severity of Adverse Events (AE) (time frame: 12 days). The study lists 2 primary outcomes in all. 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 30 Nov 2022.