Primary ObjectivesPart 1:To characterize the safety and tolerability of single ascending doses of PTC518 in healthy subjects.Part 2:To characterize the safety and tolerability of PTC518 administered for 14 or up to 21 days in healthy subjects.Part 3…
ID
Source
Brief title
Condition
- Congenital and hereditary disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Part 1 - Single Ascending Dose:
Type, frequency, severity, timing, and relationship to study treatment of any
adverse events (AEs), laboratory abnormalities, vital signs abnormalities,
physical examination abnormalities or ECG abnormalities when PTC518 is
administered as a single dose.
Part 2 - Multiple Ascending Dose:
Type, frequency, severity, timing, and relationship to study treatment of any
AEs, laboratory abnormalities, vital signs abnormalities, physical examination
abnormalities, ECG abnormalities, and C-SSRS scores when PTC518 is administered
as multiple doses.
Part 3 - CSF
PTC518 concentrations in blood and CSF when PTC518 is administered for 7 days.
Part 4 - Food Effect:
PK parameters, eg, Tmax, Cmax, AUC, elimination half-life (t1/2), apparent
total body clearance (CL/F), and apparent volume of distribution (Vd/F) when
PTC518 is administered in fed (Part 4) and fasted (Part 1) states.
Part 5 (MD28D):
Type, frequency, severity, timing, and relationship to study treatment of any
AEs, laboratory abnormalities, vital signs abnormalities, physical examination
abnormalities, ECG abnormalities, and C-SSRS scores when PTC518 is administered
as multiple doses.
Secondary outcome
Part 1 - Single Ascending Dose:
PK parameters, eg, Tmax, Cmax, AUC, elimination half-life (t1/2), apparent
total body clearance (CL/F), and apparent volume of distribution (Vz/F) when
PTC518 is administered as a single dose.
Part 2 - Multiple Ascending Dose:
PK parameters, eg, Tmax, Cmax, AUC, elimination half-life (t1/2), apparent
total body clearance (CL/F), and apparent volume of distribution (Vz/F) when
PTC518 is administered as multiple doses.
QT, and the corrected QT interval by Fridericia*s formula (QTcF) extracted from
Holter monitoring and PTC518 plasma concentration-QTc effects.
Part 3 - CSF
Type, frequency, severity, timing, and relationship to study treatment of any
AEs, laboratory abnormalities, vital signs abnormalities, physical examination
abnormalities, ECG abnormalities and C-SSRS scores when PTC518 is administered
for 7 days.
Part 4 - Food Effect:
Type, frequency, severity, timing, and relationship to study treatment of any
AEs, laboratory abnormalities, vital signs abnormalities, physical examination
abnormalities or ECG abnormalities when PTC518 is administered in fed state and
compare with those in part 1 (fasted).
Part 5 (MD28D):
PK parameters, eg, Tmax, Cmax, AUC, T1/2, CL/F, and V z/F when PTC518 is
administered as multiple doses.
QT, and the corrected QT interval by Fridericia*s formula (QTcF) extracted from
Holter monitoring and PTC518 plasma concentration-QTc effects.
Background summary
PTC518 is an orally bioavailable, selective Huntingtin (HTT) pre-mRNA splicing
modifier designed to distribute uniformly and decrease the levels of HTT
protein in the central nervous system (CNS) and periphery. This small molecule
modulates splicing of the HTT pre-mRNA, resulting in the inclusion of a novel
pseudoexon (located within an intron) carrying a premature translation
termination codon. This leads to the degradation of HTT mRNA, and a reduction
in HTT protein levels.For further details see the IB.
Study objective
Primary Objectives
Part 1:
To characterize the safety and tolerability of single ascending doses of PTC518
in healthy subjects.
Part 2:
To characterize the safety and tolerability of PTC518 administered for 14 or up
to 21 days in healthy subjects.
Part 3:
To characterize the pharmacokinetics in plasma and cerebrospinal fluid (CSF)
after administration of PTC518 for 7 days in healthy subjects.
Part 4:
To characterize the food effect on the PK in plasma of PTC518 after
administration of a single dose of PTC518 in healthy subjects.
Part 5:
To characterize the safety and tolerability of PTC518 administered for up to 28
days in healthy subjects.
Secondary Objectives
Part 1:
To characterize the pharmacokinetics of single doses of PTC518 in healthy
subjects.
Part 2:
• To characterize the pharmacokinetics of PTC518 administered for 14 or up to
21 days in healthy subjects.
• To assess the QTc and drug concentration effect of PTC518 after repeated
ascending doses.
Part 3:
To assess safety and tolerability of PTC518 after administration for 7 days in
healthy subjects.
Part 4:
To characterize the safety and tolerability of single doses of PTC518
administered in the fed state in healthy subjects.
Part 5:
To characterize the pharmacokinetics of PTC518 administered for up to 28 days
in healthy subjects
Study design
This is a 5 part, single-center, randomized SAD, MAD, and FE study.
Intervention
PTC518 as 5 mg and 50 mg tablets.
Study burden and risks
Since the study is being executed in healthy volunteers, there are no
anticipated benefits of the IMP. Please see the IB for further
information.
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South Plainfield NJ 07080
US
100 Corporate Court 100 Corporate Court
South Plainfield NJ 07080
US
Listed location countries
Age
Inclusion criteria
1. For Part 1, Part 2, Part 4, and Part 5: Healthy male or female subjects aged
from 18 to 65 years old, inclusive, at Screening. For Part 3: healthy male of
female subjects aged 50 to 65 years old, inclusive, at Screening.
2. Subjects must understand the nature of the study and must provide signed and
dated written informed consent before the conduct of any study-related
procedures.
3. Body Mass Index (BMI) of >=18.5 kg/m2 and <=30.0 kg/m2 with a body weight
>=50.0 kg for male subjects and a body weight >=45.0 kg for female subjects at
Screening.
4. Healthy as determined by the Investigator, based upon a medical evaluation
including medical history, physical examination, laboratory test results, ECG
recording (e.g. QTcF <= 450 msec for males and QTcF <= 470 ms for females) and
vital signs. Out of range values can be repeated once.
5. Male subjects and female subjects of childbearing potential must be willing
to use 2 methods of birth control for the duration of the study and for 30 days
after the last dosing.
Exclusion criteria
1. Subjects that participated in any drug or device clinical investigation
within 60 days prior to Screening or who anticipate participating in any drug
or device clinical investigation within the duration of this study.
2. Prior or ongoing medical condition (e.g., concomitant illness, psychiatric
condition), medical history, physical findings that, in the Investigator*s
opinion, could adversely affect the safety of the subject or could impair the
assessment of study results.
3. An abnormal general neurological examination.
4. Presence of any clinically significant abnormality during Screening.
5. Any psychological, emotional problems, any disorders or resultant therapy
that is likely to invalidate informed consent or limit the ability of the
subject to comply with the protocol requirements.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2020-003439-33-NL |
| CCMO | NL74780.000.20 |