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CompletedNCT03381287Updated Aug 11, 2026Results posted

A Multiple Ascending Dose Study of HTD1801 in Adults With Hypercholesterolemia

A Phase 1/2 interventional study of HTD1801 Tablets, 500 mg and HTD1801 Tablets, 1000 mg in Hypercholesterolemia, sponsored by HighTide Therapeutics (Hong Kong) Limited. Completed at 3 sites in Australia. Open to participants aged 18 Years to 70 Years. Per ClinicalTrials.gov, last updated 2026-08-11.

Sponsored by HighTide Therapeutics (Hong Kong) Limited · Phase 1/2, Interventional, and Treatment

Phase
Phase 1/2
Study type
Interventional
Enrollment
50
Allocation
Randomized
Ages
18 Years to 70 Years
Sex
All
01

Study 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.

02

Conditions studied

  • Hypercholesterolemia
03

Who can participate

Ages eligible
18 Years to 70 Years
Sexes eligible
All
Accepts 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

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
04

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Sequential assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
50 participants (actual)

Study arms

  • Experimental
    HTD1801 250 mg BID

    Subjects received 500 mg/day HTD1801

    Drug: HTD1801 Tablets, 500 mg

  • Experimental
    HTD1801 500 mg BID

    Subjects received 1000 mg/day HTD1801

    Drug: HTD1801 Tablets, 1000 mg

  • Experimental
    HTD1801 1000 mg BID

    Subjects received 2000 mg/day HTD1801

    Drug: HTD1801 Tablets, 2000 mg

  • Placebo comparator
    Placebo

    Drug: Placebo to match 500 mg HTD1801 · Drug: Placebo to match 1000 mg HTD1801 · Drug: Placebo to match 2000 mg HTD1801

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)

05

What researchers measure

Primary outcomes

  1. 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

Secondary outcomes

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. Percent Change in Triglycerides From Baseline to Day 28 Within and Between Treatment Groups

    Time frame: Baseline, Day 14, Day 28

  9. Percent Change in Free-fatty Acids (FFA) From Baseline to Day 28 Within and Between Treatment Groups

    Time frame: Baseline, Day 14, Day 28

  10. Percent Change in Lipoprotein-A From Baseline to Day 28 Within and Between Treatment Groups

    Time frame: Baseline, Day 14, Day 28

06

Results

Posted Mar 3, 2023

Participant flow

Participant flow — Overall Study
MilestonePlaceboHTD1801 250 mg BIDHTD1801 500 mg BIDHTD1801 1000 mg BID
Started12121214
Completed12111212
Not completed0102
Withdrew: Withdrawal by subject0100
Withdrew: Adverse event0001
Withdrew: Physician decision0001

Outcome measures

PrimaryNumber 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
Reported as:
Count of participants · Participants
Number of Subjects With Treatment-Emergent Adverse Events (TEAEs)
ParticipantsPlaceboHTD1801 250 mg BIDHTD1801 500 mg BIDHTD1801 1000 mg BID
TEAE810811
Serious TEAE0001
Severe TEAE1000
Drug-related TEAEs4276
TEAEs leading to treatment interrupted or discontinued0001
SecondaryMaximum 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
Reported as:
Mean · ng/mL
Maximum Plasma Concentration (Cmax) of HTD1801 Components After Single-dose Oral Administration
ng/mLHTD1801 250 mgHTD1801 500 mgHTD1801 1000 mg
Berberine (BBR)0.390 ± 0.1630.441 ± 0.2860.865 ± 0.451
Ursodeoxycholic Acid (UDCA)923 ± 4531900 ± 8472900 ± 1520
SecondaryMaximum 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
Reported as:
Mean · ng/mL
Maximum Plasma Concentration (Cmax) of HTD1801 Components After Multiple-dose Oral Administration
ng/mLHTD1801 250 mg BIDHTD1801 500 mg BIDHTD1801 1000 mg BID
Berberine (BBR)0.676 ± 0.2311.510 ± 1.2001.770 ± 1.310
Ursodeoxycholic Acid (UDCA)962 ± 2751900 ± 8253370 ± 966
SecondaryTime 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
Reported as:
Median · hours
Time to Maximum Plasma Concentration (Tmax) of HTD1801 Components After Single-dose Oral Administration
hoursHTD1801 250 mgHTD1801 500 mgHTD1801 1000 mg
Berberine (BBR)3.5 (2.0 to 8.25)4.0 (2.0 to 8.0)4.0 (3.0 to 12.0)
Ursodeoxycholic Acid (UDCA)2.0 (0.50 to 4.0)3.0 (1.0 to 4.07)4.0 (1.0 to 8.0)
SecondaryTime 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
Reported as:
Median · hours
Time to Maximum Plasma Concentration (Tmax) of HTD1801 Components After Multiple-dose Oral Administration
hoursHTD1801 250 mg BIDHTD1801 500 mg BIDHTD1801 1000 mg BID
Berberine (BBR)4.0 (0.0 to 4.0)4.0 (0.25 to 12.0)4.0 (2.0 to 12.0)
Ursodeoxycholic Acid (UDCA)3.0 (2.0 to 12.0)4.0 (2.0 to 8.0)3.0 (0.0 to 4.03)
SecondaryPlasma 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
Reported as:
Mean · hours
Plasma Half-life of HTD1801 Components (T1/2) After Single-dose Oral Administration
hoursHTD1801 250 mgHTD1801 500 mgHTD1801 1000 mg
Berberine (BBR)9.04 ± 1.5010.60 ± 2.517.79 ± 0.60
Ursodeoxycholic Acid (UDCA)2.79 ± 0.928.43 ± 11.305.24 ± 1.64
SecondaryPlasma 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
Reported as:
Mean · hours
Plasma Half-life of HTD1801 Components (T1/2) After Multiple-dose Oral Administration
hoursHTD1801 250 mg BIDHTD1801 500 mg BIDHTD1801 1000 mg BID
Ursodeoxycholic Acid (UDCA)—7.60 ± 2.907.53 ± 2.78
SecondaryPercent 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
Reported as:
Mean · percentage change from baseline
Percent Change in Low-density Lipoprotein-Cholesterol (LDL-C) From Baseline to Day 28 Within and Between Treatment Groups
percentage change from baselinePlaceboHTD1801 250 mg BIDHTD1801 500 mg BIDHTD1801 1000 mg BID
Percent Change from Baseline to Day 143.624 ± 11.9910-3.390 ± 8.3100-1.1550 ± 26.2682-9.296 ± 14.9090
Percent Change from Baseline to Day 28-3.585 ± 21.7628-7.674 ± 13.14070.372 ± 15.3368-9.767 ± 12.6763
SecondaryPercent Change in Triglycerides From Baseline to Day 28 Within and Between Treatment Groups
Time frame:
Baseline, Day 14, Day 28
Reported as:
Mean · percentage change from baseline
Percent Change in Triglycerides From Baseline to Day 28 Within and Between Treatment Groups
percentage change from baselinePlaceboHTD1801 250 mg BIDHTD1801 500 mg BIDHTD1801 1000 mg BID
Percent Change from Baseline to Day 141.724 ± 19.4047-5.788 ± 25.447012.798 ± 34.8867-2.240 ± 28.2301
Percent Change from Baseline to Day 2836.778 ± 30.11137.684 ± 27.805325.882 ± 34.61456.256 ± 18.4114
SecondaryPercent Change in Free-fatty Acids (FFA) From Baseline to Day 28 Within and Between Treatment Groups
Time frame:
Baseline, Day 14, Day 28
Reported as:
Mean · percentage change from baseline
Percent Change in Free-fatty Acids (FFA) From Baseline to Day 28 Within and Between Treatment Groups
percentage change from baselinePlaceboHTD1801 250 mg BIDHTD1801 500 mg BIDHTD1801 1000 mg BID
Percent Change from Baseline to Day 14-41.743 ± 29.7652-38.672 ± 37.1275-41.295 ± 20.1601-32.192 ± 28.0350
Percent Change from Baseline to Day 28-33.153 ± 33.9741-46.458 ± 36.159747.246 ± 18.0392-34.382 ± 24.8417
SecondaryPercent Change in Lipoprotein-A From Baseline to Day 28 Within and Between Treatment Groups
Time frame:
Baseline, Day 14, Day 28
Reported as:
Mean · percentage change from baseline
Percent Change in Lipoprotein-A From Baseline to Day 28 Within and Between Treatment Groups
percentage change from baselinePlaceboHTD1801 250 mg BIDHTD1801 500 mg BIDHTD1801 1000 mg BID
Percent Change from Baseline to Day 14-4.975 ± 27.7800-19.527 ± 22.0535222.4113 ± 214.9631-13.034 ± 27.9322
Percent Change from Baseline to Day 2810.582 ± 20.4217-11.239 ± 33.9248242.570 ± 477.1207-21.916 ± 26.2907

Adverse events

Collected over 4 weeks. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Placebo0/12 (0%)0/12 (0%)8/12 (66.7%)
HTD1801 250 mg BID0/12 (0%)0/12 (0%)10/12 (83.3%)
HTD1801 500 mg BID0/12 (0%)0/12 (0%)8/12 (66.7%)
HTD1801 1000 mg BID0/14 (0%)1/14 (7.1%)11/14 (78.6%)
Most frequent serious events
Most frequent serious events
EventPlaceboHTD1801 250 mg BIDHTD1801 500 mg BIDHTD1801 1000 mg BID
CholecystitisHepatobiliary disorders0/120/120/121/14
Hepatitis.Hepatobiliary disorders0/120/120/121/14
Most frequent other events
Showing 10 of 64
Most frequent other events
EventPlaceboHTD1801 250 mg BIDHTD1801 500 mg BIDHTD1801 1000 mg BID
HeadacheNervous system disorders5/125/124/123/14
Decreased appetiteMetabolism and nutrition disorders0/120/123/121/14
DizzinessNervous system disorders0/122/120/120/14
NauseaGastrointestinal disorders1/122/121/120/14
FlatulenceGastrointestinal disorders2/120/120/120/14
DysgeusiaNervous system disorders0/120/121/120/14
MigraineNervous system disorders1/121/120/120/14
TremorNervous system disorders0/121/120/120/14
ConstipationGastrointestinal disorders1/121/121/121/14
DiarrhoeaGastrointestinal disorders0/120/121/121/14

Baseline characteristics

Age, Continuous
Age, Continuous(years)PlaceboHTD1801 250 mg BIDHTD1801 500 mg BIDHTD1801 1000 mg BIDTotal
Mean53.4 (26 to 63)48.4 (27 to 70)54.3 (42 to 63)52.0 (22 to 70)52.0 (22 to 70)
Sex: Female, Male
Sex: Female, Male(Participants)PlaceboHTD1801 250 mg BIDHTD1801 500 mg BIDHTD1801 1000 mg BIDTotal
Female9651030
Male367420
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)PlaceboHTD1801 250 mg BIDHTD1801 500 mg BIDHTD1801 1000 mg BIDTotal
Hispanic or Latino00000
Not Hispanic or Latino1212121450
Unknown or Not Reported00000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)PlaceboHTD1801 250 mg BIDHTD1801 500 mg BIDHTD1801 1000 mg BIDTotal
American Indian or Alaska Native00000
Asian01012
Native Hawaiian or Other Pacific Islander00000
Black or African American00000
White1111121347
More than one race00000
Unknown or Not Reported10001
07

Study locations

3 sites
  • Q-Pharm Pty Ltd.
    Herston, Queensland 4006, Australia
  • CMAX Clinical Research Pty Ltd
    Adelaide, South Australia 5000, Australia
  • Linear Clinical Research
    Nedlands, Western Australia 6009, Australia
08

References and documents

Publications

  • Di Bisceglie AM, Watts GF, Lavin P, Yu M, Bai R, Liu L. Pharmacokinetics and pharmacodynamics of HTD1801 (berberine ursodeoxycholate, BUDCA) in patients with hyperlipidemia. Lipids Health Dis. 2020 Nov 12;19(1):239. doi: 10.1186/s12944-020-01406-4. PubMed 33183320 ↗

Study documents

  • Study protocol · Jan 19, 2018
  • Statistical analysis plan · May 9, 2019

Documents are hosted by the registry — open the source record to download them.

09

Registry details

Key details

Study ID
NCT03381287
Lead sponsor
HighTide Therapeutics (Hong Kong) Limited
Responsible party
Sponsor
First posted
Dec 21, 2017
Start date
Apr 13, 2018
Primary completion
Dec 31, 2018
Completion
Dec 31, 2018
Results posted
Mar 3, 2023
Last update
Aug 11, 2026

Study contacts

Adrian Di Bisceglie, MD,FACP,FAASLD
study director · HighTide Therapeutics USA, LLC

Oversight

FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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