Hypercholesterolemia
Conditions
Brief summary
This is a randomized, double-blind, placebo-controlled, multicenter, multiple ascending dose (MAD) study to evaluate the safety and tolerability, pharmacokinetic (PK), and pharmacodynamic (PD) profiles of HTD1801 in overweight to obese adults with hypercholesterolemia. There were 3 cohorts of dose levels as 500, 1000 and 2000 mg/day, with 16 subjects planned for each cohort randomized 3:1 to receive either HTD1801 or Placebo.
Interventions
DRUGHTD1801 Tablets, 500 mg
500 mg/day (250 mg BID)
DRUGHTD1801 Tablets, 1000 mg
1000 mg/day (500 mg BID)
DRUGHTD1801 Tablets, 2000 mg
2000 mg/day (1000 mg BID)
DRUGPlacebo to match 500 mg HTD1801
2 tablets/day (1 tablet BID)
DRUGPlacebo to match 1000 mg HTD1801
4 tablets/day (2 tablet BID)
DRUGPlacebo to match 2000 mg HTD1801
8 tablets/day (4 tablet BID)
Sponsors
HighTide Therapeutics (Hong Kong) Limited
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Have given written informed consent 2. Males or females aged 18 to 70 years old at the time of first dosing 3. Have a body mass index (BMI) of \>25.0 and ≤ 45.0 kg/m2 at Screening 4. Have a documented history of hypercholesterolemia, defined as LDL-C ≥ 2.59 mmol/L
Exclusion criteria
1. The use of any anti-dyslipidemia agent within 28 days prior to dosing 2. History of a total cholesterol ≥ 10.35 mmol/L or triglyceride ≥ 11.3 mmol/L 3. History of a clinically significant cardiac arrhythmia or clinically significant abnormal ECG results at Screening 4. Significant peripheral or coronary vascular disease 5. Clinically significant abnormal blood pressure at Screening or Baseline, defined as supine blood pressure ≥160/100 mmHg, or ≤ 90/60 mmHg 6. Primary hypothyroidism (thyroid stimulating hormone \[TSH\] \> upper limit or normal \[ULN\] and free T4 \< lower limit of normal \[LLN\]), primary subclinical hypothyroidism (screening TSH \> ULN and free T4 within normal limits \[WNL\]), or secondary hypothyroidism (screening TSH \< LLN and free T4\< LLN) at Screening 7. Glucose-6-phosphate dehydrogenase (G6PD) deficiency
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) | 4 weeks | TEAEs are defined as any AEs that commenced on or after exposure to study drug or any pre-existing AE that worsened in either intensity or frequency after exposure to study drug. |
Secondary
| Measure | Time frame |
|---|---|
| Maximum Plasma Concentration (Cmax) of HTD1801 Components After Single-dose Oral Administration | 0. 0.25, 0.5, 1, 2, 3, 4, 8, 12 and 24 hours on Day 1 |
| Maximum Plasma Concentration (Cmax) of HTD1801 Components After Multiple-dose Oral Administration | 0. 0.25, 0.5, 1, 2, 3, 4, 8, 12 and 24 hours on Day 28 |
| Time to Maximum Plasma Concentration (Tmax) of HTD1801 Components After Single-dose Oral Administration | 0. 0.25, 0.5, 1, 2, 3, 4, 8, 12 and 24 hours on Day 1 |
| Time to Maximum Plasma Concentration (Tmax) of HTD1801 Components After Multiple-dose Oral Administration | 0. 0.25, 0.5, 1, 2, 3, 4, 8, 12 and 24 hours on Day 28 |
| Plasma Half-life of HTD1801 Components (T1/2) After Single-dose Oral Administration | 0.25, 0.5, 1, 2, 3, 4, 8, 12 and 24 hours on Day 1 |
| Plasma Half-life of HTD1801 Components (T1/2) After Multiple-dose Oral Administration | 0. 0.25, 0.5, 1, 2, 3, 4, 8, 12 and 24 hours on Day 28 |
| Percent Change in Low-density Lipoprotein-Cholesterol (LDL-C) From Baseline to Day 28 Within and Between Treatment Groups | Baseline, Day 14, Day 28 |
| Percent Change in Triglycerides From Baseline to Day 28 Within and Between Treatment Groups | Baseline, Day 14, Day 28 |
| Percent Change in Free-fatty Acids (FFA) From Baseline to Day 28 Within and Between Treatment Groups | Baseline, Day 14, Day 28 |
| Percent Change in Lipoprotein-A From Baseline to Day 28 Within and Between Treatment Groups | Baseline, Day 14, Day 28 |
Countries
Australia
Contacts
STUDY_DIRECTORAdrian Di Bisceglie, MD,FACP,FAASLD
HighTide Therapeutics USA, LLC
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo to match 500 mg HTD1801: 2 tablets/day (1 tablet BID)
Placebo to match 1000 mg HTD1801: 4 tablets/day (2 tablet BID)
Placebo to match 2000 mg HTD1801: 8 tablets/day (4 tablet BID) | 12 |
| HTD1801 250 mg BID Subjects received 500 mg/day HTD1801
HTD1801 Tablets, 500 mg: 500 mg/day (250 mg BID) | 12 |
| HTD1801 500 mg BID Subjects received 1000 mg/day HTD1801
HTD1801 Tablets, 1000mg: 1000 mg/day (500 mg BID) | 12 |
| HTD1801 1000 mg BID Subjects received 2000 mg/day HTD1801
HTD1801 Tablets, 2000 mg: 2000 mg/day (1000 mg BID) | 14 |
| Total | 50 |
Baseline characteristics
| Characteristic | Placebo | HTD1801 250 mg BID | HTD1801 500 mg BID | HTD1801 1000 mg BID | Total |
|---|---|---|---|---|---|
| Age, Continuous | 53.4 years | 48.4 years | 54.3 years | 52.0 years | 52.0 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants | 12 Participants | 12 Participants | 14 Participants | 50 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 11 Participants | 11 Participants | 12 Participants | 13 Participants | 47 Participants |
| Sex: Female, Male Female | 9 Participants | 6 Participants | 5 Participants | 10 Participants | 30 Participants |
| Sex: Female, Male Male | 3 Participants | 6 Participants | 7 Participants | 4 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 14 |
| other Total, other adverse events | 8 / 12 | 10 / 12 | 8 / 12 | 11 / 14 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 | 0 / 12 | 1 / 14 |
Outcome results
Primary
Number of Subjects With Treatment-Emergent Adverse Events (TEAEs)
TEAEs are defined as any AEs that commenced on or after exposure to study drug or any pre-existing AE that worsened in either intensity or frequency after exposure to study drug.
Time frame: 4 weeks
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) | Severe TEAE | 1 Participants |
| Placebo | Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) | Serious TEAE | 0 Participants |
| Placebo | Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) | Drug-related TEAEs | 4 Participants |
| Placebo | Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) | TEAEs leading to treatment interrupted or discontinued | 0 Participants |
| Placebo | Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) | TEAE | 8 Participants |
| HTD1801 250 mg BID | Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) | TEAEs leading to treatment interrupted or discontinued | 0 Participants |
| HTD1801 250 mg BID | Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) | Serious TEAE | 0 Participants |
| HTD1801 250 mg BID | Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) | TEAE | 10 Participants |
| HTD1801 250 mg BID | Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) | Drug-related TEAEs | 2 Participants |
| HTD1801 250 mg BID | Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) | Severe TEAE | 0 Participants |
| HTD1801 500 mg BID | Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) | TEAEs leading to treatment interrupted or discontinued | 0 Participants |
| HTD1801 500 mg BID | Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) | Serious TEAE | 0 Participants |
| HTD1801 500 mg BID | Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) | Drug-related TEAEs | 7 Participants |
| HTD1801 500 mg BID | Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) | TEAE | 8 Participants |
| HTD1801 500 mg BID | Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) | Severe TEAE | 0 Participants |
| HTD1801 1000 mg BID | Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) | TEAEs leading to treatment interrupted or discontinued | 1 Participants |
| HTD1801 1000 mg BID | Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) | TEAE | 11 Participants |
| HTD1801 1000 mg BID | Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) | Severe TEAE | 0 Participants |
| HTD1801 1000 mg BID | Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) | Drug-related TEAEs | 6 Participants |
| HTD1801 1000 mg BID | Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) | Serious TEAE | 1 Participants |
Secondary
Maximum Plasma Concentration (Cmax) of HTD1801 Components After Multiple-dose Oral Administration
Time frame: 0. 0.25, 0.5, 1, 2, 3, 4, 8, 12 and 24 hours on Day 28
Population: Specific PK samples were excluded from the PK analysis dataset as they were identified to have outside the established stability range for frozen sample storage.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Maximum Plasma Concentration (Cmax) of HTD1801 Components After Multiple-dose Oral Administration | Berberine (BBR) | 0.676 ng/mL | Standard Deviation 0.231 |
| Placebo | Maximum Plasma Concentration (Cmax) of HTD1801 Components After Multiple-dose Oral Administration | Ursodeoxycholic Acid (UDCA) | 962 ng/mL | Standard Deviation 275 |
| HTD1801 250 mg BID | Maximum Plasma Concentration (Cmax) of HTD1801 Components After Multiple-dose Oral Administration | Berberine (BBR) | 1.510 ng/mL | Standard Deviation 1.2 |
| HTD1801 250 mg BID | Maximum Plasma Concentration (Cmax) of HTD1801 Components After Multiple-dose Oral Administration | Ursodeoxycholic Acid (UDCA) | 1900 ng/mL | Standard Deviation 825 |
| HTD1801 500 mg BID | Maximum Plasma Concentration (Cmax) of HTD1801 Components After Multiple-dose Oral Administration | Berberine (BBR) | 1.770 ng/mL | Standard Deviation 1.31 |
| HTD1801 500 mg BID | Maximum Plasma Concentration (Cmax) of HTD1801 Components After Multiple-dose Oral Administration | Ursodeoxycholic Acid (UDCA) | 3370 ng/mL | Standard Deviation 966 |
Secondary
Maximum Plasma Concentration (Cmax) of HTD1801 Components After Single-dose Oral Administration
Time frame: 0. 0.25, 0.5, 1, 2, 3, 4, 8, 12 and 24 hours on Day 1
Population: Specific PK samples were excluded from the PK analysis dataset as they were identified to have outside the established stability range for frozen sample storage.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Maximum Plasma Concentration (Cmax) of HTD1801 Components After Single-dose Oral Administration | Berberine (BBR) | 0.390 ng/mL | Standard Deviation 0.163 |
| Placebo | Maximum Plasma Concentration (Cmax) of HTD1801 Components After Single-dose Oral Administration | Ursodeoxycholic Acid (UDCA) | 923 ng/mL | Standard Deviation 453 |
| HTD1801 250 mg BID | Maximum Plasma Concentration (Cmax) of HTD1801 Components After Single-dose Oral Administration | Berberine (BBR) | 0.441 ng/mL | Standard Deviation 0.286 |
| HTD1801 250 mg BID | Maximum Plasma Concentration (Cmax) of HTD1801 Components After Single-dose Oral Administration | Ursodeoxycholic Acid (UDCA) | 1900 ng/mL | Standard Deviation 847 |
| HTD1801 500 mg BID | Maximum Plasma Concentration (Cmax) of HTD1801 Components After Single-dose Oral Administration | Berberine (BBR) | 0.865 ng/mL | Standard Deviation 0.451 |
| HTD1801 500 mg BID | Maximum Plasma Concentration (Cmax) of HTD1801 Components After Single-dose Oral Administration | Ursodeoxycholic Acid (UDCA) | 2900 ng/mL | Standard Deviation 1520 |
Secondary
Percent Change in Free-fatty Acids (FFA) From Baseline to Day 28 Within and Between Treatment Groups
Time frame: Baseline, Day 14, Day 28
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percent Change in Free-fatty Acids (FFA) From Baseline to Day 28 Within and Between Treatment Groups | Percent Change from Baseline to Day 14 | -41.743 percentage change from baseline | Standard Deviation 29.7652 |
| Placebo | Percent Change in Free-fatty Acids (FFA) From Baseline to Day 28 Within and Between Treatment Groups | Percent Change from Baseline to Day 28 | -33.153 percentage change from baseline | Standard Deviation 33.9741 |
| HTD1801 250 mg BID | Percent Change in Free-fatty Acids (FFA) From Baseline to Day 28 Within and Between Treatment Groups | Percent Change from Baseline to Day 28 | -46.458 percentage change from baseline | Standard Deviation 36.1597 |
| HTD1801 250 mg BID | Percent Change in Free-fatty Acids (FFA) From Baseline to Day 28 Within and Between Treatment Groups | Percent Change from Baseline to Day 14 | -38.672 percentage change from baseline | Standard Deviation 37.1275 |
| HTD1801 500 mg BID | Percent Change in Free-fatty Acids (FFA) From Baseline to Day 28 Within and Between Treatment Groups | Percent Change from Baseline to Day 14 | -41.295 percentage change from baseline | Standard Deviation 20.1601 |
| HTD1801 500 mg BID | Percent Change in Free-fatty Acids (FFA) From Baseline to Day 28 Within and Between Treatment Groups | Percent Change from Baseline to Day 28 | 47.246 percentage change from baseline | Standard Deviation 18.0392 |
| HTD1801 1000 mg BID | Percent Change in Free-fatty Acids (FFA) From Baseline to Day 28 Within and Between Treatment Groups | Percent Change from Baseline to Day 14 | -32.192 percentage change from baseline | Standard Deviation 28.035 |
| HTD1801 1000 mg BID | Percent Change in Free-fatty Acids (FFA) From Baseline to Day 28 Within and Between Treatment Groups | Percent Change from Baseline to Day 28 | -34.382 percentage change from baseline | Standard Deviation 24.8417 |
Secondary
Percent Change in Lipoprotein-A From Baseline to Day 28 Within and Between Treatment Groups
Time frame: Baseline, Day 14, Day 28
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percent Change in Lipoprotein-A From Baseline to Day 28 Within and Between Treatment Groups | Percent Change from Baseline to Day 14 | -4.975 percentage change from baseline | Standard Deviation 27.78 |
| Placebo | Percent Change in Lipoprotein-A From Baseline to Day 28 Within and Between Treatment Groups | Percent Change from Baseline to Day 28 | 10.582 percentage change from baseline | Standard Deviation 20.4217 |
| HTD1801 250 mg BID | Percent Change in Lipoprotein-A From Baseline to Day 28 Within and Between Treatment Groups | Percent Change from Baseline to Day 28 | -11.239 percentage change from baseline | Standard Deviation 33.9248 |
| HTD1801 250 mg BID | Percent Change in Lipoprotein-A From Baseline to Day 28 Within and Between Treatment Groups | Percent Change from Baseline to Day 14 | -19.527 percentage change from baseline | Standard Deviation 22.0535 |
| HTD1801 500 mg BID | Percent Change in Lipoprotein-A From Baseline to Day 28 Within and Between Treatment Groups | Percent Change from Baseline to Day 14 | 222.4113 percentage change from baseline | Standard Deviation 214.9631 |
| HTD1801 500 mg BID | Percent Change in Lipoprotein-A From Baseline to Day 28 Within and Between Treatment Groups | Percent Change from Baseline to Day 28 | 242.570 percentage change from baseline | Standard Deviation 477.1207 |
| HTD1801 1000 mg BID | Percent Change in Lipoprotein-A From Baseline to Day 28 Within and Between Treatment Groups | Percent Change from Baseline to Day 14 | -13.034 percentage change from baseline | Standard Deviation 27.9322 |
| HTD1801 1000 mg BID | Percent Change in Lipoprotein-A From Baseline to Day 28 Within and Between Treatment Groups | Percent Change from Baseline to Day 28 | -21.916 percentage change from baseline | Standard Deviation 26.2907 |
Secondary
Percent Change in Low-density Lipoprotein-Cholesterol (LDL-C) From Baseline to Day 28 Within and Between Treatment Groups
Time frame: Baseline, Day 14, Day 28
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percent Change in Low-density Lipoprotein-Cholesterol (LDL-C) From Baseline to Day 28 Within and Between Treatment Groups | Percent Change from Baseline to Day 14 | 3.624 percentage change from baseline | Standard Deviation 11.991 |
| Placebo | Percent Change in Low-density Lipoprotein-Cholesterol (LDL-C) From Baseline to Day 28 Within and Between Treatment Groups | Percent Change from Baseline to Day 28 | -3.585 percentage change from baseline | Standard Deviation 21.7628 |
| HTD1801 250 mg BID | Percent Change in Low-density Lipoprotein-Cholesterol (LDL-C) From Baseline to Day 28 Within and Between Treatment Groups | Percent Change from Baseline to Day 28 | -7.674 percentage change from baseline | Standard Deviation 13.1407 |
| HTD1801 250 mg BID | Percent Change in Low-density Lipoprotein-Cholesterol (LDL-C) From Baseline to Day 28 Within and Between Treatment Groups | Percent Change from Baseline to Day 14 | -3.390 percentage change from baseline | Standard Deviation 8.31 |
| HTD1801 500 mg BID | Percent Change in Low-density Lipoprotein-Cholesterol (LDL-C) From Baseline to Day 28 Within and Between Treatment Groups | Percent Change from Baseline to Day 14 | -1.1550 percentage change from baseline | Standard Deviation 26.2682 |
| HTD1801 500 mg BID | Percent Change in Low-density Lipoprotein-Cholesterol (LDL-C) From Baseline to Day 28 Within and Between Treatment Groups | Percent Change from Baseline to Day 28 | 0.372 percentage change from baseline | Standard Deviation 15.3368 |
| HTD1801 1000 mg BID | Percent Change in Low-density Lipoprotein-Cholesterol (LDL-C) From Baseline to Day 28 Within and Between Treatment Groups | Percent Change from Baseline to Day 14 | -9.296 percentage change from baseline | Standard Deviation 14.909 |
| HTD1801 1000 mg BID | Percent Change in Low-density Lipoprotein-Cholesterol (LDL-C) From Baseline to Day 28 Within and Between Treatment Groups | Percent Change from Baseline to Day 28 | -9.767 percentage change from baseline | Standard Deviation 12.6763 |
Secondary
Percent Change in Triglycerides From Baseline to Day 28 Within and Between Treatment Groups
Time frame: Baseline, Day 14, Day 28
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percent Change in Triglycerides From Baseline to Day 28 Within and Between Treatment Groups | Percent Change from Baseline to Day 14 | 1.724 percentage change from baseline | Standard Deviation 19.4047 |
| Placebo | Percent Change in Triglycerides From Baseline to Day 28 Within and Between Treatment Groups | Percent Change from Baseline to Day 28 | 36.778 percentage change from baseline | Standard Deviation 30.1113 |
| HTD1801 250 mg BID | Percent Change in Triglycerides From Baseline to Day 28 Within and Between Treatment Groups | Percent Change from Baseline to Day 28 | 7.684 percentage change from baseline | Standard Deviation 27.8053 |
| HTD1801 250 mg BID | Percent Change in Triglycerides From Baseline to Day 28 Within and Between Treatment Groups | Percent Change from Baseline to Day 14 | -5.788 percentage change from baseline | Standard Deviation 25.447 |
| HTD1801 500 mg BID | Percent Change in Triglycerides From Baseline to Day 28 Within and Between Treatment Groups | Percent Change from Baseline to Day 14 | 12.798 percentage change from baseline | Standard Deviation 34.8867 |
| HTD1801 500 mg BID | Percent Change in Triglycerides From Baseline to Day 28 Within and Between Treatment Groups | Percent Change from Baseline to Day 28 | 25.882 percentage change from baseline | Standard Deviation 34.6145 |
| HTD1801 1000 mg BID | Percent Change in Triglycerides From Baseline to Day 28 Within and Between Treatment Groups | Percent Change from Baseline to Day 14 | -2.240 percentage change from baseline | Standard Deviation 28.2301 |
| HTD1801 1000 mg BID | Percent Change in Triglycerides From Baseline to Day 28 Within and Between Treatment Groups | Percent Change from Baseline to Day 28 | 6.256 percentage change from baseline | Standard Deviation 18.4114 |
Secondary
Plasma Half-life of HTD1801 Components (T1/2) After Multiple-dose Oral Administration
Time frame: 0. 0.25, 0.5, 1, 2, 3, 4, 8, 12 and 24 hours on Day 28
Population: Specific PK samples were excluded from the PK analysis dataset as they were identified to have outside the established stability range for frozen sample storage.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HTD1801 250 mg BID | Plasma Half-life of HTD1801 Components (T1/2) After Multiple-dose Oral Administration | Ursodeoxycholic Acid (UDCA) | 7.60 hours | Standard Deviation 2.9 |
| HTD1801 500 mg BID | Plasma Half-life of HTD1801 Components (T1/2) After Multiple-dose Oral Administration | Ursodeoxycholic Acid (UDCA) | 7.53 hours | Standard Deviation 2.78 |
| Unknown | Plasma Half-life of HTD1801 Components (T1/2) After Multiple-dose Oral Administration | Berberine (BBR) | — hours | — |
Secondary
Plasma Half-life of HTD1801 Components (T1/2) After Single-dose Oral Administration
Time frame: 0.25, 0.5, 1, 2, 3, 4, 8, 12 and 24 hours on Day 1
Population: Specific PK samples were excluded from the PK analysis dataset as they were identified to have outside the established stability range for frozen sample storage.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Plasma Half-life of HTD1801 Components (T1/2) After Single-dose Oral Administration | Berberine (BBR) | 9.04 hours | Standard Deviation 1.5 |
| Placebo | Plasma Half-life of HTD1801 Components (T1/2) After Single-dose Oral Administration | Ursodeoxycholic Acid (UDCA) | 2.79 hours | Standard Deviation 0.92 |
| HTD1801 250 mg BID | Plasma Half-life of HTD1801 Components (T1/2) After Single-dose Oral Administration | Berberine (BBR) | 10.60 hours | Standard Deviation 2.51 |
| HTD1801 250 mg BID | Plasma Half-life of HTD1801 Components (T1/2) After Single-dose Oral Administration | Ursodeoxycholic Acid (UDCA) | 8.43 hours | Standard Deviation 11.3 |
| HTD1801 500 mg BID | Plasma Half-life of HTD1801 Components (T1/2) After Single-dose Oral Administration | Berberine (BBR) | 7.79 hours | Standard Deviation 0.6 |
| HTD1801 500 mg BID | Plasma Half-life of HTD1801 Components (T1/2) After Single-dose Oral Administration | Ursodeoxycholic Acid (UDCA) | 5.24 hours | Standard Deviation 1.64 |
Secondary
Time to Maximum Plasma Concentration (Tmax) of HTD1801 Components After Multiple-dose Oral Administration
Time frame: 0. 0.25, 0.5, 1, 2, 3, 4, 8, 12 and 24 hours on Day 28
Population: Specific PK samples were excluded from the PK analysis dataset as they were identified to have outside the established stability range for frozen sample storage.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Time to Maximum Plasma Concentration (Tmax) of HTD1801 Components After Multiple-dose Oral Administration | Berberine (BBR) | 4.0 hours |
| Placebo | Time to Maximum Plasma Concentration (Tmax) of HTD1801 Components After Multiple-dose Oral Administration | Ursodeoxycholic Acid (UDCA) | 3.0 hours |
| HTD1801 250 mg BID | Time to Maximum Plasma Concentration (Tmax) of HTD1801 Components After Multiple-dose Oral Administration | Berberine (BBR) | 4.0 hours |
| HTD1801 250 mg BID | Time to Maximum Plasma Concentration (Tmax) of HTD1801 Components After Multiple-dose Oral Administration | Ursodeoxycholic Acid (UDCA) | 4.0 hours |
| HTD1801 500 mg BID | Time to Maximum Plasma Concentration (Tmax) of HTD1801 Components After Multiple-dose Oral Administration | Berberine (BBR) | 4.0 hours |
| HTD1801 500 mg BID | Time to Maximum Plasma Concentration (Tmax) of HTD1801 Components After Multiple-dose Oral Administration | Ursodeoxycholic Acid (UDCA) | 3.0 hours |
Secondary
Time to Maximum Plasma Concentration (Tmax) of HTD1801 Components After Single-dose Oral Administration
Time frame: 0. 0.25, 0.5, 1, 2, 3, 4, 8, 12 and 24 hours on Day 1
Population: Specific PK samples were excluded from the PK analysis dataset as they were identified to have outside the established stability range for frozen sample storage.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Time to Maximum Plasma Concentration (Tmax) of HTD1801 Components After Single-dose Oral Administration | Berberine (BBR) | 3.5 hours |
| Placebo | Time to Maximum Plasma Concentration (Tmax) of HTD1801 Components After Single-dose Oral Administration | Ursodeoxycholic Acid (UDCA) | 2.0 hours |
| HTD1801 250 mg BID | Time to Maximum Plasma Concentration (Tmax) of HTD1801 Components After Single-dose Oral Administration | Berberine (BBR) | 4.0 hours |
| HTD1801 250 mg BID | Time to Maximum Plasma Concentration (Tmax) of HTD1801 Components After Single-dose Oral Administration | Ursodeoxycholic Acid (UDCA) | 3.0 hours |
| HTD1801 500 mg BID | Time to Maximum Plasma Concentration (Tmax) of HTD1801 Components After Single-dose Oral Administration | Berberine (BBR) | 4.0 hours |
| HTD1801 500 mg BID | Time to Maximum Plasma Concentration (Tmax) of HTD1801 Components After Single-dose Oral Administration | Ursodeoxycholic Acid (UDCA) | 4.0 hours |