Nonalcoholic Steatohepatitis (NASH), Overweight or Obesity
Conditions
Brief summary
This Phase 1/2 study will evaluate safety, efficacy, PK, and PD of FT-4101 as a single agent in overweight/obese subjects with NASH. The study may be conducted in up to 2 dosing cohorts.
Interventions
DRUGFT-4101
FT-4101 will be supplied as active capsules and will be administered per the protocol defined frequency and dose level.
DRUGFT-4101 placebo
FT-4101 placebo will be supplied as placebo capsule matching in size and color to all the active capsules and will be administered per the protocol defined frequency and dose level.
OTHERDeuterated Water
Deuterated water will be provided as individual ready-to-use, single dose bottles each containing 50 mL of deuterated water (70%).
Sponsors
ProSciento, Inc.
Forma Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Meets all of the following criteria: 1. CAP ≥ 300 dB/m by FibroScan® OR Liver biopsy within 24 months, consistent with NASH with stage 2-3 fibrosis 2. Screening MRI-PDFF with ≥ 10% steatosis. * Body mass index (BMI) \> 25.0 to \< 45.0 kg/m2 * Stable body weight * Subjects with T2DM may also be included, if: 1. Subject with T2DM is on stable doses of metformin monotherapy (subjects on combination therapy of metformin and sulfonylurea (SU) need to undergo washout period prior to dosing) with no changes in medication within the previous 6 months 2. HbA1c \< 9% (one retest is permitted with the result of the last test being conclusive) 3. Fasting plasma glucose (FPG) \< 240 mg/dL (\<13.3 mmol/L) * Waist circumference ≤ 57 inches * Female subjects must be non-pregnant and non-lactating Key
Exclusion criteria
* Type 1 diabetes and type 2 diabetic subjects on insulin therapy * Diabetic complications, such as acute proliferative retinopathy * Recurrent severe hypoglycemia or hypoglycemic unawareness or recent severe ketoacidosis * History of, or active, chronic liver disease due to alcohol, auto-immune, primary biliary cholangitis, HIV, HBV or active HCV-infection, Wilson's, α-1-antitrypsin deficiency, hemochromatosis, etc., and not due to NASH disease * History of clinically significant or decompensated chronic liver disease including esophageal varices, ascites, encephalopathy or any hospitalization for treatment of chronic liver disease; or MELD score ≥ 10. * History of significant cirrhosis of the liver * Alcohol consumption greater than 14 drinks per week for men or greater than 7 drinks per week for women and/or positive alcohol breath test * Introduction of an anti-obesity drug in the past 6 months prior to screening * History of gastrointestinal malabsorptive bariatric surgery, any other gastrointestinal surgery that may induce malabsorption, history of bowel resection \> 20 cm, any malabsorption disorder, severe gastroparesis, any GI procedure for weight loss, as well as clinically significant gastrointestinal disorders within less than 5 years * Ingestion of drugs known to produce hepatic steatosis including corticosteroids, high- dose estrogens, methotrexate, tetracycline or amiodarone in the previous 6 months * History of, or current cardiac dysrhythmias and/or a history of cardiovascular disease events, including congestive heart failure, unstable coronary artery disease, myocardial infarction * Significant systemic or major illnesses other than liver disease, including cerebrovascular disease, pulmonary disease, renal failure, organ transplantation, serious psychiatric disease, malignancy that, in the opinion of the investigator, would preclude treatment with FT-4101 and/or adequate follow up * History of chronic skin conditions such as psoriasis, eczema or any recurring rash/dermatitis requiring oral or topical corticosteroids or other topical applications within 12 months * Hair loss or unexplained alopecia within 12 months * History of chronic eye conditions, Sjögren syndrome or any history of dry eyes or allergic conjunctivitis requiring artificial tears or medicated eye drops or previous refractive surgery within 12 months (Subjects with dry eyes due to wearing contact lenses are eligible) * History of major depression, anxiety, suicidal behavior or attempts, or other unstable psychiatric disorders (within 2 years of screening), requiring medical treatment * Uncontrolled hypertension * Any device or other contraindication with the MRI examination * Ingestion of deuterated water within the previous 6 months * Positive test for hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV Ab), or human immunodeficiency virus type 1 (HIV-1) or type 2 (HIV-2) antibody * Participation in any other clinical interventional study receiving active treatment within the previous 30 days or 5 half-lives, whichever is longer * Unable to abstain from smoking during confinement periods * History of illicit drug abuse * Clinically under the effect of marijuana at screening * Unwillingness to abstain from grapefruit (grapefruit containing food and beverages), star fruit (carambola), pomegranate, Seville orange and other food components that may interact with CYP3A4 from check-in throughout the entire course of the study * Donation or loss of \> 500 mL of blood or blood product within 56 days of dosing
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Liver Fat on Magnetic Resonance Imaging- Proton Density Fat Fraction (MRI-PDFF) | At week 12 | Change from baseline in percentage of liver fat on MRI-PDFF is reported. |
| Change From Baseline in Vital Signs: Blood Pressure (BP) | Baseline, Day 92 | Change from baseline in blood pressure (systolic and diastolic) are reported. |
| Change From Baseline in Vital Signs: Heart Rate (HR) | Baseline, Day 92 | Change from baseline in heart rate is reported. |
| Change From Baseline in Vital Signs: Respiratory Rate | Baseline, Day 92 | Change from baseline in respiratory rate is reported. |
| Change From Baseline in Vital Signs: Temperature | Baseline, Day 92 | Change from baseline in temperature is reported. |
| Change From Baseline in 12-lead Electrocardiogram (ECG) Parameters: ECG Mean Heart Rate | Baseline, Day 92 | Change from baseline in ECG mean heart rate is reported. |
| Change From Baseline in 12-lead ECG Parameters: QT Interval | Baseline, Day 92 | Change from baseline in QT interval is reported. |
| Change From Baseline in 12-lead ECG Parameters: PR Interval | Baseline, Day 92 | Change from baseline in PR interval is reported. |
| Change From Baseline in 12-lead ECG Parameters: QRS Interval | Baseline, Day 92 | Change from baseline in QRS interval is reported. |
| Change From Baseline in 12-lead ECG Parameters: RR Interval | Baseline, Day 92 | Change from baseline in RR interval is reported. |
| Change From Baseline in 12-lead ECG Parameters: QTc (Corrected) Using the Fridericia Correction (QTcF) Interval | Baseline, Day 92 | Change from baseline in QTcF interval is reported. |
| Percent Change From Baseline in Liver Fat on Magnetic Resonance Imaging- Proton Density Fat Fraction (MRI-PDFF) | At week 12 | Percent change from baseline in liver fat on MRI-PDFF is reported. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | From start of study drug administration up to 20 weeks | TEAEs were defined as an adverse events (AEs) with an onset that occurred after receiving the first dose of the study drug (AE start date greater than or equal to \[\>=\] first dose date) and within 30 days after receiving the last dose of the study drug (AE start date - last dose date less than or equal to \[\<=\] 30). Number of participants with TEAEs are reported. |
| Number of Participants With Clinically Significant Changes in Laboratory Values | Up to 20 weeks | Number of participants with clinically significant changes in laboratory values (hematology, serum chemistry, and urinalysis) are reported. |
| Number of Participants With Clinically Significant Changes in Physical Examination | Up to 20 weeks | Number of participants with clinically significant changes in physical examination are reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Liver Fat on MRI-PDFF | At week 6 | Change from baseline in percentage of liver fat on MRI-PDFF is reported. |
| Percent Change From Baseline in Liver Fat on MRI-PDFF | At week 6 | Percent change from baseline in liver fat on MRI-PDFF is reported. |
| Change From Baseline in Alanine Aminotransferase (ALT) | Baseline, Day 92 | Change from baseline in ALT is reported. |
| Percentage of Participants Experiencing a Relative Reduction of 30% or Greater of Liver Fat as Assessed by MRI-PDFF | At week 12 | Percentage of participants experiencing a relative reduction of 30% or greater of liver fat as assessed by MRI-PDFF at week 12 are reported. |
| Change From Baseline in Aspartate Aminotransferase (AST) | Baseline, Day 92 | Change from baseline in AST is reported. |
| Change From Baseline in Alkaline Phosphatase | Baseline, Day 92 | Change from baseline in alkaline phosphatase is reported. |
| Change From Baseline in Total Bilirubin | Baseline, Day 92 | Change from baseline in total bilirubin is reported. |
| Maximum Plasma Concentration (Cmax) of FT-4101 | Cycle 1 (Day 1), Cycle 4 (Day 14); each Cycle length = 21 days | Maximum plasma concentration (Cmax) of FT-4101 is reported |
| Area Under the Concentration-time Curve for a Dosing Interval (AUCtau) of FT-4101 | Cycle 1 (Day 1), Cycle 4 (Day 14); each Cycle length = 21 days | — |
| Data for This Endpoint Was Not Collected and Analysed. | Cycle 1 (Day 1), Cycle 4 (Day 14); each Cycle length = 21 days | — |
| Change From Baseline in Gamma-glutamyl Transferase (γGT) | Baseline, Day 92 | Change from baseline in γGT is reported. |
Countries
United States
Participant flow
Pre-assignment details
Participants were randomized at a ratio of 2:1 in FT-4101 treatment group and placebo.
Participants by arm
| Arm | Count |
|---|---|
| FT-4101 3.0 mg Participants received 3.0 mg of FT-4101 capsule orally once daily for 2 weeks, followed by 1 week of no treatment. This cycle continued until the end of week 12, for up to 4 dosing cycle (each cycle 21 days). | 9 |
| Placebo Participants received FT-4101 matching placebo capsule orally once daily for 2 weeks, followed by 1 week of no treatment. This cycle continued until the end of week 12, for up to 4 dosing cycle (each cycle 21 days). | 5 |
| Total | 14 |
Baseline characteristics
| Characteristic | Placebo | Total | FT-4101 3.0 mg |
|---|---|---|---|
| Age, Continuous | 47.0 Years STANDARD_DEVIATION 15.76 | 44.9 Years STANDARD_DEVIATION 12.13 | 43.8 Years STANDARD_DEVIATION 10.52 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 13 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 14 Participants | 9 Participants |
| Sex: Female, Male Female | 2 Participants | 9 Participants | 7 Participants |
| Sex: Female, Male Male | 3 Participants | 5 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 5 |
| other Total, other adverse events | 3 / 9 | 3 / 5 |
| serious Total, serious adverse events | 0 / 9 | 0 / 5 |
Outcome results
Primary
Change From Baseline in 12-lead ECG Parameters: PR Interval
Change from baseline in PR interval is reported.
Time frame: Baseline, Day 92
Population: The Safety analysis set included all randomized participants who received IP (FT-4101 or placebo) or deuterated water.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FT-4101 3.0 mg | Change From Baseline in 12-lead ECG Parameters: PR Interval | -7.0 msec | Standard Deviation 13.63 |
| Placebo | Change From Baseline in 12-lead ECG Parameters: PR Interval | 2.2 msec | Standard Deviation 10.64 |
Primary
Change From Baseline in 12-lead ECG Parameters: QRS Interval
Change from baseline in QRS interval is reported.
Time frame: Baseline, Day 92
Population: The Safety analysis set included all randomized participants who received IP (FT-4101 or placebo) or deuterated water.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FT-4101 3.0 mg | Change From Baseline in 12-lead ECG Parameters: QRS Interval | 1.9 msec | Standard Deviation 8.62 |
| Placebo | Change From Baseline in 12-lead ECG Parameters: QRS Interval | 0.8 msec | Standard Deviation 8.38 |
Primary
Change From Baseline in 12-lead ECG Parameters: QTc (Corrected) Using the Fridericia Correction (QTcF) Interval
Change from baseline in QTcF interval is reported.
Time frame: Baseline, Day 92
Population: The Safety analysis set included all randomized participants who received IP (FT-4101 or placebo) or deuterated water.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FT-4101 3.0 mg | Change From Baseline in 12-lead ECG Parameters: QTc (Corrected) Using the Fridericia Correction (QTcF) Interval | 0.6 msec | Standard Deviation 10.92 |
| Placebo | Change From Baseline in 12-lead ECG Parameters: QTc (Corrected) Using the Fridericia Correction (QTcF) Interval | 1.0 msec | Standard Deviation 14 |
Primary
Change From Baseline in 12-lead ECG Parameters: QT Interval
Change from baseline in QT interval is reported.
Time frame: Baseline, Day 92
Population: The Safety analysis set included all randomized participants who received IP (FT-4101 or placebo) or deuterated water.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FT-4101 3.0 mg | Change From Baseline in 12-lead ECG Parameters: QT Interval | 0.2 milliseconds (msec) | Standard Deviation 14.28 |
| Placebo | Change From Baseline in 12-lead ECG Parameters: QT Interval | -4.2 milliseconds (msec) | Standard Deviation 22.8 |
Primary
Change From Baseline in 12-lead ECG Parameters: RR Interval
Change from baseline in RR interval is reported.
Time frame: Baseline, Day 92
Population: The Safety analysis set included all randomized participants who received IP (FT-4101 or placebo) or deuterated water.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FT-4101 3.0 mg | Change From Baseline in 12-lead ECG Parameters: RR Interval | 1.7 msec | Standard Deviation 138.73 |
| Placebo | Change From Baseline in 12-lead ECG Parameters: RR Interval | -40.8 msec | Standard Deviation 93.04 |
Primary
Change From Baseline in 12-lead Electrocardiogram (ECG) Parameters: ECG Mean Heart Rate
Change from baseline in ECG mean heart rate is reported.
Time frame: Baseline, Day 92
Population: The Safety analysis set included all randomized participants who received IP (FT-4101 or placebo) or deuterated water.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FT-4101 3.0 mg | Change From Baseline in 12-lead Electrocardiogram (ECG) Parameters: ECG Mean Heart Rate | 0.3 beats/min | Standard Deviation 11.46 |
| Placebo | Change From Baseline in 12-lead Electrocardiogram (ECG) Parameters: ECG Mean Heart Rate | 2.6 beats/min | Standard Deviation 6.23 |
Primary
Change From Baseline in Liver Fat on Magnetic Resonance Imaging- Proton Density Fat Fraction (MRI-PDFF)
Change from baseline in percentage of liver fat on MRI-PDFF is reported.
Time frame: At week 12
Population: The preliminary efficacy analysis set included all participants who received FT-4101 or placebo with at least one quantifiable baseline and one post-baseline MRI-PDFF without major protocol deviations or violations that would have an impact on PD (Specifically MRI-PDFF).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FT-4101 3.0 mg | Change From Baseline in Liver Fat on Magnetic Resonance Imaging- Proton Density Fat Fraction (MRI-PDFF) | -3.65 Percentage of liver fat | Standard Deviation 4.389 |
| Placebo | Change From Baseline in Liver Fat on Magnetic Resonance Imaging- Proton Density Fat Fraction (MRI-PDFF) | 4.16 Percentage of liver fat | Standard Deviation 2.236 |
Primary
Change From Baseline in Vital Signs: Blood Pressure (BP)
Change from baseline in blood pressure (systolic and diastolic) are reported.
Time frame: Baseline, Day 92
Population: The Safety analysis set included all randomized participants who received IP (FT-4101 or placebo) or deuterated water.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FT-4101 3.0 mg | Change From Baseline in Vital Signs: Blood Pressure (BP) | Systolic BP | -0.2 millimeters of mercury (mmHg) | Standard Deviation 16.45 |
| FT-4101 3.0 mg | Change From Baseline in Vital Signs: Blood Pressure (BP) | Diastolic BP | 0.4 millimeters of mercury (mmHg) | Standard Deviation 14.93 |
| Placebo | Change From Baseline in Vital Signs: Blood Pressure (BP) | Systolic BP | -5.2 millimeters of mercury (mmHg) | Standard Deviation 8.44 |
| Placebo | Change From Baseline in Vital Signs: Blood Pressure (BP) | Diastolic BP | -2.4 millimeters of mercury (mmHg) | Standard Deviation 6.11 |
Primary
Change From Baseline in Vital Signs: Heart Rate (HR)
Change from baseline in heart rate is reported.
Time frame: Baseline, Day 92
Population: The Safety analysis set included all randomized participants who received IP (FT-4101 or placebo) or deuterated water.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FT-4101 3.0 mg | Change From Baseline in Vital Signs: Heart Rate (HR) | 4.4 Beats per minutes (beats/min) | Standard Deviation 8.32 |
| Placebo | Change From Baseline in Vital Signs: Heart Rate (HR) | 0.2 Beats per minutes (beats/min) | Standard Deviation 2.59 |
Primary
Change From Baseline in Vital Signs: Respiratory Rate
Change from baseline in respiratory rate is reported.
Time frame: Baseline, Day 92
Population: The Safety analysis set included all randomized participants who received IP (FT-4101 or placebo) or deuterated water.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FT-4101 3.0 mg | Change From Baseline in Vital Signs: Respiratory Rate | -1.6 Breaths per minute (breaths/min) | Standard Deviation 1.42 |
| Placebo | Change From Baseline in Vital Signs: Respiratory Rate | -0.6 Breaths per minute (breaths/min) | Standard Deviation 1.34 |
Primary
Change From Baseline in Vital Signs: Temperature
Change from baseline in temperature is reported.
Time frame: Baseline, Day 92
Population: The Safety analysis set included all randomized participants who received IP (FT-4101 or placebo) or deuterated water.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FT-4101 3.0 mg | Change From Baseline in Vital Signs: Temperature | 0.22 Degree Celsius (C) | Standard Deviation 0.239 |
| Placebo | Change From Baseline in Vital Signs: Temperature | -0.08 Degree Celsius (C) | Standard Deviation 0.409 |
Primary
Number of Participants With Clinically Significant Changes in Laboratory Values
Number of participants with clinically significant changes in laboratory values (hematology, serum chemistry, and urinalysis) are reported.
Time frame: Up to 20 weeks
Population: The Safety analysis set included all randomized participants who received IP (FT-4101 or placebo) or deuterated water.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| FT-4101 3.0 mg | Number of Participants With Clinically Significant Changes in Laboratory Values | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Changes in Laboratory Values | 0 Participants |
Primary
Number of Participants With Clinically Significant Changes in Physical Examination
Number of participants with clinically significant changes in physical examination are reported.
Time frame: Up to 20 weeks
Population: The Safety analysis set included all randomized participants who received IP (FT-4101 or placebo) or deuterated water.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| FT-4101 3.0 mg | Number of Participants With Clinically Significant Changes in Physical Examination | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Changes in Physical Examination | 0 Participants |
Primary
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
TEAEs were defined as an adverse events (AEs) with an onset that occurred after receiving the first dose of the study drug (AE start date greater than or equal to \[\>=\] first dose date) and within 30 days after receiving the last dose of the study drug (AE start date - last dose date less than or equal to \[\<=\] 30). Number of participants with TEAEs are reported.
Time frame: From start of study drug administration up to 20 weeks
Population: The Safety analysis set included all randomized participants who received investigational product (IP) (FT-4101 or placebo) or deuterated water.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| FT-4101 3.0 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 3 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 3 Participants |
Primary
Percent Change From Baseline in Liver Fat on Magnetic Resonance Imaging- Proton Density Fat Fraction (MRI-PDFF)
Percent change from baseline in liver fat on MRI-PDFF is reported.
Time frame: At week 12
Population: The preliminary efficacy analysis set included all participants who received FT-4101 or placebo with at least one quantifiable baseline and one post-baseline MRI-PDFF without major protocol deviations or violations that would have an impact on pharmacodynamics (PD) (Specifically MRI-PDFF).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FT-4101 3.0 mg | Percent Change From Baseline in Liver Fat on Magnetic Resonance Imaging- Proton Density Fat Fraction (MRI-PDFF) | -18.02 Percent change of liver fat | Standard Deviation 20.066 |
| Placebo | Percent Change From Baseline in Liver Fat on Magnetic Resonance Imaging- Proton Density Fat Fraction (MRI-PDFF) | 25.98 Percent change of liver fat | Standard Deviation 15.67 |
Secondary
Area Under the Concentration-time Curve for a Dosing Interval (AUCtau) of FT-4101
Time frame: Cycle 1 (Day 1), Cycle 4 (Day 14); each Cycle length = 21 days
Population: Data for this endpoint was not collected and analysed as there were no participants.
| Arm | Measure | Group | Value |
|---|---|---|---|
| Unknown | Area Under the Concentration-time Curve for a Dosing Interval (AUCtau) of FT-4101 | Cycle 1 (Day 1) | — |
| Unknown | Area Under the Concentration-time Curve for a Dosing Interval (AUCtau) of FT-4101 | Cycle 4 (Day 14) | — |
Secondary
Change From Baseline in Alanine Aminotransferase (ALT)
Change from baseline in ALT is reported.
Time frame: Baseline, Day 92
Population: The pharmacodynamic (PD) analysis set was to include all participants who received FT-4101 or placebo without major protocol deviations or violations that would have had an impact on PD.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| FT-4101 3.0 mg | Change From Baseline in Alanine Aminotransferase (ALT) | -3.0 units per liter (U/L) | Standard Error 6.29 |
| Placebo | Change From Baseline in Alanine Aminotransferase (ALT) | 40.8 units per liter (U/L) | Standard Error 8.02 |
Secondary
Change From Baseline in Alkaline Phosphatase
Change from baseline in alkaline phosphatase is reported.
Time frame: Baseline, Day 92
Population: The pharmacodynamic (PD) analysis set was to include all participants who received FT-4101 or placebo without major protocol deviations or violations that would have had an impact on PD.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| FT-4101 3.0 mg | Change From Baseline in Alkaline Phosphatase | 1.023 U/L | Standard Error 2.2841 |
| Placebo | Change From Baseline in Alkaline Phosphatase | 13.764 U/L | Standard Error 2.8903 |
Secondary
Change From Baseline in Aspartate Aminotransferase (AST)
Change from baseline in AST is reported.
Time frame: Baseline, Day 92
Population: The pharmacodynamic (PD) analysis set was to include all participants who received FT-4101 or placebo without major protocol deviations or violations that would have had an impact on PD.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| FT-4101 3.0 mg | Change From Baseline in Aspartate Aminotransferase (AST) | -1.161 U/L | Standard Error 4.2789 |
| Placebo | Change From Baseline in Aspartate Aminotransferase (AST) | 12.457 U/L | Standard Error 5.432 |
Secondary
Change From Baseline in Gamma-glutamyl Transferase (γGT)
Change from baseline in γGT is reported.
Time frame: Baseline, Day 92
Population: The pharmacodynamic (PD) analysis set was to include all participants who received FT-4101 or placebo without major protocol deviations or violations that would have had an impact on PD.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| FT-4101 3.0 mg | Change From Baseline in Gamma-glutamyl Transferase (γGT) | -2.058 U/L | Standard Error 9.1733 |
| Placebo | Change From Baseline in Gamma-glutamyl Transferase (γGT) | 46.293 U/L | Standard Error 11.658 |
Secondary
Change From Baseline in Liver Fat on MRI-PDFF
Change from baseline in percentage of liver fat on MRI-PDFF is reported.
Time frame: At week 6
Population: The preliminary efficacy analysis set included all participants who received FT-4101 or placebo with at least one quantifiable baseline and one post-baseline MRI-PDFF without major protocol deviations or violations that would have an impact on PD (Specifically MRI-PDFF).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FT-4101 3.0 mg | Change From Baseline in Liver Fat on MRI-PDFF | -0.10 Percentage of liver fat | Standard Deviation 3.395 |
| Placebo | Change From Baseline in Liver Fat on MRI-PDFF | 3.58 Percentage of liver fat | Standard Deviation 4.06 |
Secondary
Change From Baseline in Total Bilirubin
Change from baseline in total bilirubin is reported.
Time frame: Baseline, Day 92
Population: The pharmacodynamic (PD) analysis set was to include all participants who received FT-4101 or placebo without major protocol deviations or violations that would have had an impact on PD.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| FT-4101 3.0 mg | Change From Baseline in Total Bilirubin | -0.59 micromoles per liter (umol/L) | Standard Error 0.735 |
| Placebo | Change From Baseline in Total Bilirubin | -1.09 micromoles per liter (umol/L) | Standard Error 0.932 |
Secondary
Data for This Endpoint Was Not Collected and Analysed.
Time frame: Cycle 1 (Day 1), Cycle 4 (Day 14); each Cycle length = 21 days
Population: Data for this endpoint was not collected and analysed as there were no participants.
| Arm | Measure | Group | Value |
|---|---|---|---|
| Unknown | Data for This Endpoint Was Not Collected and Analysed. | Cycle 1 (Day 1) | — |
| Unknown | Data for This Endpoint Was Not Collected and Analysed. | Cycle 4 (Day 14) | — |
Secondary
Maximum Plasma Concentration (Cmax) of FT-4101
Maximum plasma concentration (Cmax) of FT-4101 is reported
Time frame: Cycle 1 (Day 1), Cycle 4 (Day 14); each Cycle length = 21 days
Population: The pharmacokinetic (PK) analysis set included all participants who received FT-4101 with sufficient evaluable PK concentration data appropriate for the evaluation of interest without major protocol deviations or violations that would have an impact on the absorption, distribution, metabolism, or excretion.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FT-4101 3.0 mg | Maximum Plasma Concentration (Cmax) of FT-4101 | Cycle 1 (Day 1) | 62.3 nanograms per milliliter (ng/mL) | Standard Deviation 22.2 |
| FT-4101 3.0 mg | Maximum Plasma Concentration (Cmax) of FT-4101 | Cycle 4 (Day 14) | 118 nanograms per milliliter (ng/mL) | Standard Deviation 38.6 |
Secondary
Percentage of Participants Experiencing a Relative Reduction of 30% or Greater of Liver Fat as Assessed by MRI-PDFF
Percentage of participants experiencing a relative reduction of 30% or greater of liver fat as assessed by MRI-PDFF at week 12 are reported.
Time frame: At week 12
Population: The preliminary efficacy analysis set included all participants who received FT-4101 or placebo with at least one quantifiable baseline and one post-baseline MRI-PDFF without major protocol deviations or violations that would have an impact on PD (Specifically MRI-PDFF).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FT-4101 3.0 mg | Percentage of Participants Experiencing a Relative Reduction of 30% or Greater of Liver Fat as Assessed by MRI-PDFF | 25.0 Percentage of participants |
| Placebo | Percentage of Participants Experiencing a Relative Reduction of 30% or Greater of Liver Fat as Assessed by MRI-PDFF | 0 Percentage of participants |
Secondary
Percent Change From Baseline in Liver Fat on MRI-PDFF
Percent change from baseline in liver fat on MRI-PDFF is reported.
Time frame: At week 6
Population: The preliminary efficacy analysis set included all participants who received FT-4101 or placebo with at least one quantifiable baseline and one post-baseline MRI-PDFF without major protocol deviations or violations that would have an impact on PD (Specifically MRI-PDFF).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FT-4101 3.0 mg | Percent Change From Baseline in Liver Fat on MRI-PDFF | -0.73 Percent change of liver fat | Standard Deviation 16.272 |
| Placebo | Percent Change From Baseline in Liver Fat on MRI-PDFF | 22.07 Percent change of liver fat | Standard Deviation 27.154 |