FHL-101
A phase 1, randomized, double-blind, single-dose escalation study
followed by a multiple-dose escalating study of Glyceryl Tribenzoate (GTB)
capsules in healthy subjects
Design
- A two-part (single ascending dose and multiple ascending dose)
placebo-controlled, double-blind study - Number of volunteers in the single ascending dose phase: 24
- Number of volunteers in multiple ascending dose phase: 20
Patient Population
Inclusion criteria
- Healthy participants 18 to 50 years of age inclusive with body mass index (BMI) ≥ 18 kg/m² and ≤ 30 kg/m²
- Participants must not be pregnant or lactating at screening, and take adequate method of contraception from Screening until 30 days
after last dose of study medication - Negative for SARS-CoV-2 virus at admission Day -1 and Day 1 (during the SAD, Fed portion of the study, and MAD)
- Participant does not have dysphagia and discomfort with swallowing tablets/capsules
Exclusion criteria
- Use of any investigational product or device within 30 days prior to enrollment or during the study
- Use of prescription or over-the-counter medications within 2 weeks of enrollment (excluding hormonal contraceptives and acetaminophen)
unless deemed acceptable by the Investigator in consultation with the Sponsor - A positive drug and/or alcohol test at Screening and on Day – 1 or has a history of drug or alcohol abuse within 2 years before Screening
- Unable to abstain from ingesting alcohol or smoking for 72 hours prior to dosing and throughout the study
- Concurrent use of probenecid, penicillin or other ß-lactams, or other drugs which undergo active tubular secretion in the kidneys
- A clinically significant history of endocrinologic, hematologic, hepatic, immunologic, metabolic, cardiovascular, urologic, pulmonary, neurologic,
dermatologic, psychiatric, renal, and/or other major diseases or malignancy - Allergy to sodium benzoate
- Has an active suicidal plan/intent or thoughts in the past 6 months or a suicide attempt in the past 3 years
For both part A (single ascending dose)
and part B (multiple ascending dose)
Primary endpoints
- Incidence of Treatment-Emergent Adverse Events (TEAEs) until 30 days after the last administration of the study medication
- Incidence of TEAEs leading to withdrawal of study drug or study discontinuation
- Change from baseline in clinical laboratory results
- Change from baseline in physical examination results
- Change from baseline in vital signs
- Change from baseline in 12-lead electrocardiogram
- Change from baseline at each scheduled visit in the Columbia-suicide severity rating scale (C-SSRS). (Part B only)
Secondary endpoints
- PK parameters derived from plasma concentrations of GTB and Benzoic Acid
- PD markers in Plasma and Urine will be described in the PK/PD SAP including but not limited to the amount and percent excreted of hippuric acid
in relative to dose
Single Ascending Dose Phase
-
01
SCREENING
28 days
n=24 -
02
TREATMENT
Part A
1 day fasting + 3 days in confinementWashout period for patients
participating in part BPart B
1 day fed (high-fat meal)
+ 3 days in confinement -
03
FOLLOW-UP
14 days and
30 days post-dose
Multiple Ascending Dose Phase
-
01
SCREENING
28 days
n=16 -
02
TREATMENT
7 days treatment exposure
+ 3 days in confinement -
03
FOLLOW-UP
14 days and
30 days post-dose
FHL-301
A phase 2, double-blind, multi-center, placebo-controlled clinical study of Gemfibrozil
For more information, please go to clinicaltrials.gov
Design
- Conducted in the USA and Asia
- No. of patients: 32 (planned)
- Randomization of FHL-301:Placebo = 1:1
Patient Population
Inclusion criteria
- Patients with confirmed diagnosis of Parkinson’s disease, age 40-75 years old
- Patients must not be pregnant of lactating at screening, and take adequate contraception methods throughout the study
- Patients who are treatment naive or have history of prior incidental treatment with dopaminergic agents for no more than 30 days
- Patients with Hoehn and Yahr Stage of 1.0 and 2.0 at screening
Exclusion criteria
- Patients with unclear diagnosis or with presence of secondary Parkinsonism or other neurodegenerative diseases
- Patients with significant unstable conditions or any health condition that may be deemed inappropriate to take part in the trial
- Patients who are taking medications that are contraindicated for use with FHL-301
For both part A (single ascending dose)
and part B (multiple ascending dose)
Primary endpoints
- Change from Baseline in the MDS UPDRS Part III at maintenance Week 48
Secondary endpoints
- Occurrence of Treatment Emergent Adverse Events
- Changes from baseline to maintenance (Week 48) in physical exam, vital signs, Columbia Suicide Severity Rating Scale (C-SSRS) and laboratory assessments
- Change from baseline at each scheduled assessment during the titration and maintenance period in 12-lead electrocardiogram (ECG)
Total Study Duration : 51 weeks
-
01
SCREENING
Before Treatment Period
n=32
Hoehn and Yahr
Stage of 1.0 to 2.0 -
02
TITRATION
3 weeks
FHL-301 dose escalation
Escalated on weekly basis
until maximum tolerated dose -
03
MAINTENANCE
48 weeks
Use maximum tolerated dose
from titration periodPerform efficacy evaluation regularly
Perform safety evaluation
throughout the study
