Primary ObjectivesPart 1 * Single Ascending DoseThe primary objective of the single ascending dose (SAD) part of the study is to characterize the safety and tolerability of a single dose of PTC857 in healthy subjects.Part 2 * Multiple Ascending…
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- Central nervous system infections and inflammations
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Outcome measures
Primary outcome
Primary Endpoints:
Part 1 * Single Ascending Dose
The primary endpoint of the SAD part of the study is the overall safety profile
characterized by type, frequency, severity, timing, and relationship to study
treatment of any adverse events (AEs), vital signs, laboratory abnormalities,
physical examination abnormalities, C-SSRS scores, or electrocardiogram (ECG)
abnormalities.
Part 2 * Multiple Ascending Dose
The primary endpoint of the MAD part of the study is the overall safety profile
characterized by type, frequency, severity, timing, and relationship to study
treatment of any AEs, vital signs, laboratory abnormalities, physical
examination abnormalities,
C-SSRS scores, or ECG abnormalities.
Part 3 * Food Effect
The primary endpoint of the FE part of the study is the food effect on PK
parameters including area under the curve (AUC) from time zero to the last
quantifiable concentration (AUC0-t), maximum observed concentration (Cmax), and
time corresponding to occurrence of Cmax (Tmax) after administration of a
single dose of PTC857 in healthy subjects.
Secondary outcome
Secondary Endpoints:
Part 1 * Single Ascending Dose
The secondary endpoints of the SAD part of the study are:
PK parameters including AUC0-t, Cmax, Tmax, and dose normalized AUC
(AUC0-t/D and AUC0-inf/D) and dose normalized Cmax (Cmax/D).
The PTC857 dose range for Part 2 (MAD) of the study.
Part 2 * Multiple Ascending Dose
The secondary endpoints of the MAD part of the study are:
PK parameters including AUC0-tau, Cmax, Tmax, tEHL, dose normalized AUC0-tau
(AUC0-tau/D), Cmax/D, and the accumulation ratio based on AUC (Racc).
The PTC857 dose range and regimen for subsequent Phase 2 studies.
Part 3 * Food Effect
The secondary endpoint of the FE part of the study is any food effect on the
safety and tolerability of a single dose of PTC857 in healthy subjects
characterized by type, frequency, severity, timing, and relationship to study
treatment of any AEs, vital signs, laboratory abnormalities, physical
examination abnormalities, C-SSRS scores or ECG abnormalities.
Background summary
PTC857 is an orally bioavailable small molecule being developed by PTC
Therapeutics, Inc. (PTC) for the treatment of neurological diseases
characterized by high levels of oxidative stress and mitochondrial pathology,
including Parkinson*s disease. PTC857 functions as an inhibitor of the
oxidoreductase 15-lipoxygenase (15-LO) to reduce oxidative stress and spare
reduced glutathione. Reduced glutathione is an essential intermediary
metabolite that serves as the primary native cellular antioxidant and the
cell*s primary defense against reactive oxygen species (ROS). In diseases
characterized by high levels of oxidative stress, ROS production outstrips the
available supply of glutathione resulting in depletion of glutathione and
ROS-mediated cell injury and cell death. PTC857 inhibits 15-LO, the
upregulation of which leads to a cascade of biological processes leading to a
specific form of cell death termed ferroptosis. By inhibiting 15-LO, PTC857 is
predicted to slow or prevent neurodegeneration in Parkinson's disease through
the mechanism of action of inhibiting ferroptosis.
Study objective
Primary Objectives
Part 1 * Single Ascending Dose
The primary objective of the single ascending dose (SAD) part of the study is
to characterize the safety and tolerability of a single dose of PTC857 in
healthy subjects.
Part 2 * Multiple Ascending Dose
The primary objective of the multiple ascending dose (MAD) part of the study is
to characterize the safety and tolerability of multiple doses of PTC857 in
healthy subjects.
Part 3 * Food Effect
The primary objective of the food effect (FE) part of the study is to
characterize the effect of food on the PK after administration of PTC857 in
healthy subjects.
Secondary Objectives
Part 1 * Single Ascending Dose
The secondary objectives of the SAD part of the study are:
To characterize the single dose plasma PK profile of PTC857 in healthy subjects.
To determine a dose range for PTC857 that is appropriate for use in Part 2
(MAD) of the study.
Part 2 * Multiple Ascending Dose
The secondary objectives of the MAD part of the study are:
To characterize the multiple dose plasma PK profile of PTC857 in healthy
subjects.
To determine a dose range and regimen for PTC857 that is anticipated to be
safe, well tolerated and to cause an effect in subsequent Phase 2 studies.
Part 3 * Food Effect
The secondary objective of the FE part of the study is to characterize the
safety and tolerability of a single dose of PTC857 administered in healthy
subjects in fed and fasted states.
Study design
This is a 3 part, single-center, randomized, double-blind, placebo-controlled,
SAD, MAD, and FE study.
The study will be monitored by a Safety Review Committee (SRC). The intent of
the SRC is to ensure that treatment does not pose undue risk to subjects.
Safety and tolerability be assessed by the SRC between each cohort prior to
ascending from one dose level to the next-higher dose level in Part 1 (SAD) and
Part 2 (MAD) and prior to initiating Part 2 (MAD) and Part 3 (FE).
See CSP for details for each part.
Intervention
PTC857 is available for clinical trial use in the form of capsules (compounded)
at 50 mg strength. Placebo is available as matching PTC857 for administration.
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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Age
Inclusion criteria
Healthy male or female subjects aged from 18 to 55 years old, inclusive, at
Screening.
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.
BMI of * 19.0 kg/m2 and * 35.0 kg/m2 with a body weight * 50.0 kg for male
subjects and a body weight * 45.0 kg for female subjects at Screening.
Healthy as determined by the Investigator, based upon a medical evaluation
including medical history, physical examination, laboratory tests, triplicate
ECG recording (average QTcF * 450 msec) and vital signs. Out of range values
can be repeated once.
Exclusion criteria
History of coagulopathy.
History of fat malabsorption.
Dietary restrictions that preclude participation.
Females who are pregnant or nursing.
Subjects with a prior medical history of clinically significant
gastrointestinal, renal, hepatic, neurologic, hematologic, endocrine,
oncologic, pulmonary, immunologic,psychiatric, or cardiovascular disease or any
other condition which, in the opinion of the Investigator, would jeopardize the
safety of the subject or impact the validity of the study results.
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 | EUCTR2020-001328-32-NL |
| CCMO | NL73801.056.20 |