A Multiple Ascending Dose Study of HTD1801 in Adults With Hypercholesterolemia

A Randomized, Double Blind, Placebo Controlled, Multicenter, Multiple Ascending Dose Study to Evaluate the Safety and Tolerability of HTD1801 in Adults With Hypercholesterolemia

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.

Study Overview

• Status: Completed
• Conditions: Hypercholesterolemia
• Intervention / Treatment: Drug: HTD1801 Tablets, 500 mg; Drug: HTD1801 Tablets, 1000 mg; Drug: HTD1801 Tablets, 2000 mg; Drug: Placebo to match 500 mg HTD1801; Drug: Placebo to match 1000 mg HTD1801; Drug: Placebo to match 2000 mg HTD1801

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo to match 500 mg HTD1801; 2 tablets/day (1 tablet BID); Drug: Placebo to match 1000 mg HTD1801; 4 tablets/day (2 tablet BID); Drug: Placebo to match 2000 mg HTD1801; 8 tablets/day (4 tablet BID)
Experimental: HTD1801 250 mg BID; Subjects received 500 mg/day HTD1801	Drug: HTD1801 Tablets, 500 mg; 500 mg/day (250 mg BID)
Experimental: HTD1801 500 mg BID; Subjects received 1000 mg/day HTD1801	Drug: HTD1801 Tablets, 1000 mg; 1000 mg/day (500 mg BID)
Experimental: HTD1801 1000 mg BID; Subjects received 2000 mg/day HTD1801	Drug: HTD1801 Tablets, 2000 mg; 2000 mg/day (1000 mg BID)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	4 weeks

Secondary Outcome Measures

Outcome 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

Collaborators and Investigators

• Sponsor: HighTide Biopharma Pty Ltd

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start (Actual): April 13, 2018
• Primary Completion (Actual): December 31, 2018
• Study Completion (Actual): December 31, 2018

Study Registration Dates

• First Submitted: December 18, 2017
• First Submitted That Met QC Criteria: December 18, 2017
• First Posted (Actual): December 21, 2017

Study Record Updates

• Last Update Posted (Estimate): March 3, 2023
• Last Update Submitted That Met QC Criteria: August 2, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Hypercholesterolemia
• Other Study ID Numbers: HTD1801.PCT004

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No