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Trial registered on ANZCTR


Registration number
ACTRN12618000961246
Ethics application status
Approved
Date submitted
28/05/2018
Date registered
7/06/2018
Date last updated
30/01/2020
Date data sharing statement initially provided
26/02/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Study of PRAX-944 to Assess the Safety, Tolerability, PK, and Efficacy of Escalating Doses in Adults with Absence Seizures
Scientific title
A Phase 2, Open-label Study of PRAX-944 to Assess the Safety, Tolerability, Pharmacokinetics, and Efficacy of Escalating Multiple Oral Doses in Adults with Generalized Epileptic Syndromes with Absence Seizures
Secondary ID [1] 294980 0
PRAX-944-201
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Absence Seizures 307985 0
Condition category
Condition code
Neurological 307021 307021 0 0
Epilepsy

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
PRAX-944 will be taken, in conjunction with the patient’s current antiepileptic medications, at the following doses:
- Dose Level 1: 20 mg once daily for 7 days
- Dose Level 2: 20 mg twice daily for 7 days
- Taper: 20 mg once daily for 2 days and then 20 mg twice daily for 5 days

Patients will only receive enough study drug to complete the dose level or taper at home, e.g. a 5 or 6 day supply. They will complete a home study drug diary, which will indicate the number and time each dose was taken. They will then return to the study site for initiation of the next dose level or taper.
Intervention code [1] 301307 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 306006 0
Safety and tolerability of escalating multiple doses of PRAX-944 will be assessed through clinical laboratory evaluations, physical examination, vital signs, electrocardiography (ECG), electroencephalography (EEG), the Columbia-Suicide Severity Rating Scale (C-SSRS), and collection of patient-reported adverse events.
Timepoint [1] 306006 0
Baseline to Day 27
Secondary outcome [1] 347284 0
Pharmacokinetics of escalating multiple doses of PRAX-944 will be performed by LC/MS quantification of drug levels in plasma. Parameters include maximum observed concentration (Cmax) and at steady-state (Cmax,ss), Time of Cmax (Tmax) and Cmax,SS (Tmax,ss), area under the concentration-time curve (AUCtau or AUCss), total clearance at steady-state (CLss), and volume of distribution at steady-state (Vss).
Timepoint [1] 347284 0
Baseline, Day 1, Day 8, Day 14, Day 22 and Day 27
Secondary outcome [2] 347285 0
The efficacy of PRAX-944 as an adjunctive antiepileptic treatment of absence seizures assessed by:
- Number of absence seizures via self-reported patient diary
Timepoint [2] 347285 0
Baseline, Day 1, Day 8, Day 14, Day 22 and Day 27
Secondary outcome [3] 347651 0
The efficacy of PRAX-944 as an adjunctive antiepileptic treatment of absence seizures assessed by:
- Number of bilateral synchronous symmetrical spike waves discharges via EEG
Timepoint [3] 347651 0
Baseline, Day 1, Day 8, Day 14, Day 22 and Day 27
Secondary outcome [4] 347652 0
The efficacy of PRAX-944 as an adjunctive antiepileptic treatment of absence seizures assessed by:
- Total time with spike wave discharges via EEG
Timepoint [4] 347652 0
Baseline, Day 1, Day 8, Day 14, Day 22 and Day 27
Secondary outcome [5] 347653 0
The efficacy of PRAX-944 as an adjunctive antiepileptic treatment of absence seizures assessed by:
- Number of generalized tonic-clonic seizures via self-reported patient diary
Timepoint [5] 347653 0
Baseline, Day 1, Day 8, Day 14, Day 22 and Day 27
Secondary outcome [6] 347654 0
The efficacy of PRAX-944 as an adjunctive antiepileptic treatment of absence seizures assessed by:
- Number of myoclonic clusters via self-reported patient diary
Timepoint [6] 347654 0
Baseline, Day 1, Day 8, Day 14, Day 22 and Day 27
Secondary outcome [7] 347655 0
The efficacy of PRAX-944 as an adjunctive antiepileptic treatment of absence seizures assessed by:
- Clinical Global Impression (CGI), a clinician rated scale
Timepoint [7] 347655 0
Baseline, Day 1, Day 8, Day 14, Day 22 and Day 27

Eligibility
Key inclusion criteria
- Male or female between the ages of 18 and 60 years of age (inclusive)
- Clinical diagnosis of an epileptic syndrome
- Absence seizures persisting despite documented trials with at least two standard anti-epileptic treatments.
- Stable dose of all medications or interventions for epilepsy
Minimum age
18 Years
Maximum age
60 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Clinically significant unstable medical condition other than epilepsy
- History of alcohol or substance abuse
- History of focal epilepsy or epileptiform patterns consistent with focal epilepsy
- Inadequately treated psychotic or mood disorder
- Presence of severe intellectual disability, severe autism spectrum disorder or severe developmental disorder
- Significant hepatic or renal disease
- History of any suicide attempt or other suicidal behavior within the past year

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Data analysis is complete
Reason for early stopping/withdrawal
Other reasons/comments
Other reasons
Sponsor decision
Date of first participant enrolment
Anticipated
17/09/2018
Actual
17/01/2019
Date of last participant enrolment
Anticipated
Actual
9/05/2019
Date of last data collection
Anticipated
5/06/2019
Actual
5/06/2019
Sample size
Target
12
Accrual to date
Final
3
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 299569 0
Commercial sector/Industry
Name [1] 299569 0
Praxis Precision Medicines, Pty, Ltd.
Country [1] 299569 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Praxis Precision Medicines, Pty, Ltd.
Address
Tower Two Collins Square, Level 36,
727 Collins Street Docklands Vic 3008
Australia
Country
Australia
Secondary sponsor category [1] 298876 0
None
Name [1] 298876 0
Address [1] 298876 0
Country [1] 298876 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300467 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 300467 0
55 Commercial Rd,
Melbourne VIC 3004
Ethics committee country [1] 300467 0
Australia
Date submitted for ethics approval [1] 300467 0
28/05/2018
Approval date [1] 300467 0
27/11/2018
Ethics approval number [1] 300467 0

Summary
Brief summary
The study is an open-label study of PRAX-944 to assess the safety, pharmacokinetics, and efficacy of escalating multiple oral doses in up to 12 adults with generalized epileptic syndromes with absence seizures. Each patient will complete 3 study periods: Screening, Treatment Period (up to 2 dose levels followed by a taper) and Safety Follow-up.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 83754 0
Prof Terence O'Brien
Address 83754 0
Epilepsy Research Unit – 4 Centre Block, Level 4
The Alfred Hospital
55 Commercial Rd, Melbourne
Country 83754 0
Australia
Phone 83754 0
+61 3 9076 2029
Fax 83754 0
Email 83754 0
[email protected]
Contact person for public queries
Name 83755 0
Bernard Ravina
Address 83755 0
Praxis Precision Medicines
One Broadway
Cambridge, MA 02142
Country 83755 0
United States of America
Phone 83755 0
+1 617 300 8500
Fax 83755 0
Email 83755 0
[email protected]
Contact person for scientific queries
Name 83756 0
Kiran Reddy
Address 83756 0
Praxis Precision Medicines
One Broadway
Cambridge, MA 02142
Country 83756 0
United States of America
Phone 83756 0
+1 617 949 2220
Fax 83756 0
Email 83756 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
No individual participant data will be shared


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.