Clinical trial NCT03381287: A Multiple Ascending Dose Study of HTD1801 in Adults With Hypercholesterolemia
Official title: A Randomized, Double Blind, Placebo Controlled, Multicenter, Multiple Ascending Dose Study to Evaluate the Safety and Tolerability of HTD1801 in Adults With Hypercholesterolemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Hypercholesterolemia
Lead sponsor: HighTide Biopharma Pty Ltd
Sponsor class: INDUSTRY
First posted: 2017-12-21
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of Subjects With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: 4 weeks
Secondary outcomes:
measure: Maximum Plasma Concentration (Cmax) of HTD1801 Components After Single-dose Oral Administration
timeFrame: 0. 0.25, 0.5, 1, 2, 3, 4, 8, 12 and 24 hours on Day 1
measure: Maximum Plasma Concentration (Cmax) of HTD1801 Components After Multiple-dose Oral Administration
timeFrame: 0. 0.25, 0.5, 1, 2, 3, 4, 8, 12 and 24 hours on Day 28
measure: Time to Maximum Plasma Concentration (Tmax) of HTD1801 Components After Single-dose Oral Administration
timeFrame: 0. 0.25, 0.5, 1, 2, 3, 4, 8, 12 and 24 hours on Day 1
measure: Time to Maximum Plasma Concentration (Tmax) of HTD1801 Components After Multiple-dose Oral Administration
timeFrame: 0. 0.25, 0.5, 1, 2, 3, 4, 8, 12 and 24 hours on Day 28
measure: Plasma Half-life of HTD1801 Components (T1/2) After Single-dose Oral Administration
timeFrame: 0.25, 0.5, 1, 2, 3, 4, 8, 12 and 24 hours on Day 1
measure: Plasma Half-life of HTD1801 Components (T1/2) After Multiple-dose Oral Administration
timeFrame: 0. 0.25, 0.5, 1, 2, 3, 4, 8, 12 and 24 hours on Day 28
measure: Percent Change in Low-density Lipoprotein-Cholesterol (LDL-C) From Baseline to Day 28 Within and Between Treatment Groups
timeFrame: Baseline, Day 14, Day 28
measure: Percent Change in Triglycerides From Baseline to Day 28 Within and Between Treatment Groups
timeFrame: Baseline, Day 14, Day 28
measure: Percent Change in Free-fatty Acids (FFA) From Baseline to Day 28 Within and Between Treatment Groups
timeFrame: Baseline, Day 14, Day 28
measure: Percent Change in Lipoprotein-A From Baseline to Day 28 Within and Between Treatment Groups
timeFrame: Baseline, Day 14, Day 28
Other outcomes:
Locations:
city: Herston
country: Australia
facility: Q-Pharm Pty Ltd.
state: Queensland
city: Adelaide
country: Australia
facility: CMAX Clinical Research Pty Ltd
state: South Australia
city: Nedlands
country: Australia
facility: Linear Clinical Research
state: Western Australia
Study officials:
affiliation: HighTide Therapeutics USA, LLC
name: Adrian Di Bisceglie, MD,FACP,FAASLD
role: STUDY_DIRECTOR
References:
citation: 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.