The primary objective of this study is to assess the pharmacokinetics and the effect of food on the pharmacokinetics of the YTX-7739 tablet formulation following single oral doses of 30 mg in HVs and to compare the relative bioavailability of the…
ID
Source
Brief title
Condition
- Movement disorders (incl parkinsonism)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
* Relative bioavailability of Cmax and AUC0-120h of 30 mg tablet vs capsule
* PK parameters of YTX-7739 as tablet formulation by non-compartmental analysis
of the plasma concentration-time data:
o AUC0-120h, AUClast, AUC extrapolated, CL/F, Cmax, T1/2, Tlag, Tmax, Vz/F
* Change in PK parameters of YTX-7739 as tablet formulation after
administration after a high-fat breakfast by non-compartmental analysis of the
plasma concentration-time data:
o AUC120h, AUClas, AUC extrapolated, CL/F, Cmax, T1/2, Tlag, Tmax, Vz/F
Secondary outcome
* Treatment-emergent (serious) adverse events ((S)AEs) throughout the study at
every study visit
* Concomitant medication throughout the study at every study visit
* Vital signs (Pulse Rate (bpm), Systolic blood pressure (mmHg), Diastolic
blood pressure (mmHg)) as per assessment schedule
* Clinical laboratory tests (Hematology, blood chemistry and urinalysis) as per
assessment schedule
* ECG parameters (Heart Rate (HR) (bpm), PR, QRS, QT, QTcB, QTcF) as per
assessment schedule
* AUC0-inf as tablet and capsule formulation, and change in AUC0-inf after a
high-fat breakfast, by non-compartmental analysis on the plasma
concentration-time data.
Background summary
A phase 1 study to compare the relative bioavailability of a single dose
capsule and tablet formulation of YTX-7739 in healthy volunteers.
YTX-7739 is an oral SCD inhibitor. Through the inhibition of SCD, YTX-7739
decreases monounsaturated fatty acids, thereby reducing aSyn synthesis. This
inhibits the progression of Parkinson's disease.
To date, YTX-7739 has been investigated in an SAD study, where single doses up
to 400 mg were safe and tolerable in healthy volunteers. Currently, YTX-7739 is
being investigated in an MAD study in healthy volunteers and patients with
Parkinson's disease.
The SAD study showed a non-linear relationship between dose and AUC and a food
effect of the capsule.
Therefore a tablet version with improved pharmacokinetic properties has been
developed and will be compared to a capsule.
Also the food effect of the tablet will be investigated.
Study objective
The primary objective of this study is to assess the pharmacokinetics and the
effect of food on the pharmacokinetics of the YTX-7739 tablet formulation
following single oral doses of 30 mg in HVs and to compare the relative
bioavailability of the tablet formulation to the YTX-7739 capsule formulation.
The secondary objective is to determine the tolerability following single oral
doses of 30 mg of the tablet formulation in HVs.
Study design
This study will be an open label study, consisting of 3 treatment periods with
3 weeks of washout in between.
Intervention
Treatment period 1: 30 mg YTX-7739 tablet formulation (2 tablets of 15mg).
Treatment period 2: 30 mg YTX-7739 capsule formulation (2 capsules, 1x25mg, 1x5
mg)
Treatment period 3: 30 mg YTX-7739 tablet formulation (2 tablets of 15mg),
after high-fat breakfast
Study burden and risks
YTX-7739 has been studied up to 400 mg in single dose in a previous SAD study
and was considered safe and well tolerated.
In this study, a dose of 30 mg will be administered, which is 13 times lower.
Subjects will receive the IMP at the CRO for 48 hours of continuous monitoring
after each single dose. In addition, frequent safety assessment will be
conducted during the study.
40 Guest Street, Suite 4410 .
Boston MA 02135
US
40 Guest Street, Suite 4410 .
Boston MA 02135
US
Listed location countries
Age
Inclusion criteria
1. Healthy adult male or female subjects 18-55 years of age, inclusive; defined
as absence of evidence of any active acute or chronic disease or illness
following a detailed medical and surgical history, a complete physical
examination including vital signs, 12-lead ECG, haematology, blood chemistry
and urinalysis;
2. Body mass index (BMI) between 18-30 kg/m2, inclusive, and with a minimum
weight of 50kg and maximum weight of 100kg.
Exclusion criteria
1. Clinically significant findings as determined by medical history taking,
physical examination, ECG, laboratory findings (including lipid or hormone
profiles) and vital signs, as judged by the investigator.
3. Subjects with a QTcF of > 450 ms for males and > 470 ms for females at
screening or a history of long QT syndrome.
8. Being on a diet composed of relevantly altered amounts of fat, protein or
carbohydrates that may affect triglyceride and fatty acid levels (such as
high-fat, gluten-free, carbohydrate-free, protein rich diets).
10. Gastrointestinal disease (such as irritable bowel syndrome, inflammatory
bowel disease, chronic gastritis, peptic ulcer disease, etc.) that could affect
absorption of the study drug.
11 History of gastric surgery, including Roux-en-Y gastric bypass surgery, an
antrectomy with vagotomy, or gastrectomy.
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 | EUCTR2021-004754-28-NL |
| CCMO | NL78956.056.21 |