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Trial registered on ANZCTR


Registration number
ACTRN12617001512314
Ethics application status
Approved
Date submitted
24/10/2017
Date registered
27/10/2017
Date last updated
24/08/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase 1, Double-Blind, Randomized, Placebo-Controlled, First in Human Study of PRAX-330 to Assess the Safety, Tolerability and Pharmacokinetics of Single Ascending Oral Doses in Healthy Subjects
Scientific title
A Phase 1, Double-Blind, Randomized, Placebo-Controlled, First in Human Study of PRAX-330 to Assess the Safety, Tolerability and Pharmacokinetics of Single Ascending Oral Doses in Healthy Subjects
Secondary ID [1] 293175 0
Nil Known
Universal Trial Number (UTN)
U1111-1204-0125
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Epilepsy 305162 0
Condition category
Condition code
Neurological 304484 304484 0 0
Epilepsy

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study will be performed in healthy male subjects with administration of a single oral dose of PRAX-330 or vehicle (placebo) in solution in a sequential ascending manner. In Cohorts 1 through 7 subjects will be fasted overnight (no food or drink except water) for 10 hours prior to dosing. Cohort 8 will be a food effect cohort with dose level to be determined based upon the safety, tolerability, and pharmacokinetic (PK) evaluation of earlier cohorts. For the food effect cohort, study drug will be administered after an overnight fast (no food or drink, except water, for at least 10 hours prior to dosing). Subjects in Cohort 8 will receive a single dose of study drug in a fed state (30 minutes following the start of a high-fat meal).

Up to 56 healthy male subjects will be enrolled. Within each cohort, the subjects will be randomized in a 3:1 ratio with 6 subjects in the active group and 2 subjects in the placebo group.

Eligible subjects will receive study treatment with a starting dose of 0.1 mg dose escalated up to 15 mg. The last cohort will be to evaluate the food effect at a maximally tolerated dose (8 subjects from a previously evaluated cohort).
Intervention code [1] 299422 0
Treatment: Drugs
Comparator / control treatment
Placebo (vehicle) oral solution, same as PRAX-330 solution but without active ingredient.
Control group
Placebo

Outcomes
Primary outcome [1] 303718 0
Safety and tolerability, including the assessment of physical examinations, ECGs, vital signs, clinical laboratory results, and adverse events.
Timepoint [1] 303718 0
A complete physical examination (PE) will be performed at Screening, Day -1 and Day 8. In addition PEs will be performed at the same time points as vital signs are measured (see below).

Standard 12-lead ECGs will be performed at the following time points: 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5 3, 4, 6, 8, 12, 24, 48, 72, and 168 hours post-dose.

Vital signs measurement (blood pressure, heart rate, respiration rate, and body temperature) will be collected at the following time points: 0 (pre-dose), 0.25, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, and 168 hours post-dose

Blood sample collection for clinical laboratory analyses will be collected pre-dose (day-1), and on day 2 at 24 hrs post-dose, day 4 at 72 hrs post-dose and day 8 at 168 hrs post-dose.

Adverse events (AE) and concomitant medications will be recorded throughout the study period.
Primary outcome [2] 303719 0
Pharmacokinetics.
The following PK parameters will be assessed from plasma concentration-time data:
• Cmax, maximum observed concentration
• Tmax, time to Cmax
• AUC0-t, area under the plasma concentration-time curve from time 0 to last measurable concentration
• AUC0-8, area under the concentration-time curve from time 0 extrapolated to infinity
• T1/2, apparent terminal elimination half-life
• CL/F, oral clearance
• Vz/F, apparent volume of distribution following extravascular administration
• Tlag, time elapsed from time 0 to the last time of sample below quantitative limit

For Cohort 5, lumbar punctures will be performed on all subjects for the determination of the cerebrospinal fluid (CSF) PK profile to be collected 24 hours post-dose.
Timepoint [2] 303719 0
Serial blood samples (for PK) will be collected at the following time points: 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5 3, 3.5, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, 72 and 168 hours post-dose
Secondary outcome [1] 339957 0
The effect of food on the pharmacokinetic profile of oral PRAX-330 in healthy male subjects. The following PK parameters will be assessed from plasma concentration-time data:
• Cmax maximum observed concentration
• Tmax time to Cmax
• AUC0-t area under the plasma concentration-time curve from time 0 to last measurable concentration
• AUC0-8 area under the concentration-time curve from time 0 extrapolated to infinity
• T1/2 apparent terminal elimination half-life
• CL/F oral clearance
• Vz/F apparent volume of distribution following extravascular administration
• Tlag time elapsed from time 0 to the last time of sample below quantitative limit
Timepoint [1] 339957 0
Serial blood samples (for PK) will be collected at the following time points: 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5 3, 3.5, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, 72 and 168 hours post-dose

Eligibility
Key inclusion criteria
1. Male subjects between ages 18-50 years (inclusive) at time of Screening
2. Weight of at least 50 kg with body mass index (BMI) between 18 and 30 kg/m2 (inclusive)
3. Resting supine vital signs at Screening within the following ranges:
- Systolic blood pressure (SBP) 90 to 140 mmHg
- Diastolic blood pressure (DBP) 40 to 90 mmHg
- Heart rate (HR) 40 to 100 beats per minute
4. Male subjects with female partners of childbearing potential must be using 2 acceptable methods of contraception, including at least one barrier method, from the day of first dose of study drug to at least 90 days after the last dose of study drug. Periodic abstinence and withdrawal are not acceptable methods of contraception
5. Willing and able to comply with the requirements of the protocol and directions from the clinic staff
6. Willing to avoid consumption of grapefruit, grapefruit juice and Seville oranges within 2 weeks prior to first dose of study drug until discharge from the clinic
7. Willing to avoid consumption of nicotine (including nicotine gum) and alcoholic beverages within 2 weeks prior to first dose of study drug until discharge from the clinic
8. Understand and willing to sign informed consent
Minimum age
18 Years
Maximum age
50 Years
Gender
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Ongoing or history of any medical or surgical condition that, in the judgment of the Investigator, might jeopardize the subject’s safety or interfere with the absorption, distribution, metabolism or excretion of the study drug
2. Any abnormal electrocardiographic (ECG) findings at Screening judged to be clinically significant by the Investigator
3. Any abnormal laboratory value or physical examination findings at Screening that is judged by the Investigator as clinically significant
4. Hemoglobin <12 g/dL
5. Serology test positive for HIV, or hepatitis B or C at Screening.
6. Positive drug test for ethanol, barbiturates, cocaine, methamphetamines, Methadone, benzodiazepines, phencyclidine, tetrahydrocannabinols, methylenedioxymethamphetamine, opiates, or amphetamines at Screening and clinic Check-in
7. Positive urine cotinine test at Screening and Check-in
8. Use of systemic prescription medications or over-the-counter (OTC) medication, including multivitamins, and dietary and herbal supplement within 2 weeks or 5 times the terminal half-lives of the medication prior to first dose of study drug, whichever is longer and for the duration of the study.
9. Use of any experimental or investigational drug or device within 30 days prior to first dose of study drug or 5 half-lives of the drug, whichever is longer
10. Donation or loss of =400 mL blood within 8 weeks and/or donation of plasma within 7 days prior to initial dosing of study drug
11. History of drug or alcohol abuse within 12 months prior to initial dosing of study drug
12. Psychosocial or addictive disorders that would interfere with subject’s ability to give informed consent or could compromise compliance with the protocol

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Random treatment assignments are held by a third party who would be contacted in the event of a request for unblinding.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomization using a randomization table generated by computer software
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint(s)
Safety
Statistical methods / analysis
Approximately 56 healthy subjects will be enrolled into the study to ensure 8 evaluable subjects per cohort with up to 7 cohorts. As the primary objectives of this study are to describe, for the first time in humans, the safety and tolerability of single ascending doses of oral PRAX-330 in healthy subjects, no statistical significance tests are planned. Consequently, the sample size for this study was not selected on the basis of statistical power calculations.
Descriptive statistics will include mean, SD, Minimum, maximum, percent coefficient of variation (%CV), and geometric mean will be presented by dose group for the clinical outcomes and the plasma concentration of PRAX-330 at each scheduled sample time point.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 9242 0
Nucleus Network - Melbourne
Recruitment postcode(s) [1] 17899 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 297803 0
Commercial sector/Industry
Name [1] 297803 0
Praxis Precision Medicines Australia Pty Ltd
Address [1] 297803 0
Tower Two Collins Square, Level 36
727 Collins Street
Docklands Vic 3008
Country [1] 297803 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Praxis Precision Medicines Australia Pty Ltd
Address
Tower Two Collins Square, Level 36
727 Collins Street
Docklands Vic 3008
Country
Australia
Secondary sponsor category [1] 296844 0
None
Name [1] 296844 0
Address [1] 296844 0
Country [1] 296844 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298862 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 298862 0
89 Commercial Road, Melbourne
VIC 3004

Ethics committee country [1] 298862 0
Australia
Date submitted for ethics approval [1] 298862 0
23/10/2017
Approval date [1] 298862 0
28/11/2017
Ethics approval number [1] 298862 0

Summary
Brief summary
The study is a Phase 1, double-blind, randomized, placebo-controlled, first in human study of PRAX-330 to assess the safety, tolerability and pharmacokinetics of single ascending oral doses in healthy subjects. The food effect on the pharmacokinetics of PRAX-330 will also be evaluated.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 78470 0
Dr Jason Lickliter
Address 78470 0
Nucleus Network Limited
Level 5 Burnet Institute. AMREP Precinct
89 Commercial Road, Melbourne
VIC 3004
Country 78470 0
Australia
Phone 78470 0
+613 8593 9860
Fax 78470 0
Email 78470 0
j.lickliter@nucleusnetwork.com.au
Contact person for public queries
Name 78471 0
Dr Bernard Ravina
Address 78471 0
Praxis Precision Medicines Inc.
101 Main Street, Suite 1210
Cambridge, MA 02142
Country 78471 0
United States of America
Phone 78471 0
+1 617 300 8507
Fax 78471 0
Email 78471 0
clinicaltrials@praxismedicines.com
Contact person for scientific queries
Name 78472 0
Dr Kiran Reddy
Address 78472 0
Praxis Precision Medicines Inc.
101 Main Street, Suite 1210
Cambridge, MA 02142
Country 78472 0
United States of America
Phone 78472 0
+1 617 949 2220
Fax 78472 0
Email 78472 0
kiran@praxismedicines.com

No data has been provided for results reporting
Summary results
Not applicable