A Multiple Ascending Dose Study of HTD1801 in Adults With Hypercholesterolemia

NCT03381287 | Completed Phase 1 Results

• 1 other identifier: HTD1801.PCT004
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 3

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.

Conditions

Hypercholesterolemia

Outcome Measures

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.

  4 weeks

Secondary Outcomes (10)

• 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

Study Arms (4)

HTD1801 250 mg BID

EXPERIMENTAL

Subjects received 500 mg/day HTD1801

Drug: HTD1801 Tablets, 500 mg

HTD1801 500 mg BID

EXPERIMENTAL

Subjects received 1000 mg/day HTD1801

Drug: HTD1801 Tablets, 1000 mg

HTD1801 1000 mg BID

EXPERIMENTAL

Subjects received 2000 mg/day HTD1801

Drug: HTD1801 Tablets, 2000 mg

Placebo

PLACEBO COMPARATOR

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

Interventions

HTD1801 Tablets, 500 mg DRUG

500 mg/day (250 mg BID)

HTD1801 250 mg BID

HTD1801 Tablets, 1000 mg DRUG

1000 mg/day (500 mg BID)

HTD1801 500 mg BID

HTD1801 Tablets, 2000 mg DRUG

2000 mg/day (1000 mg BID)

HTD1801 1000 mg BID

Placebo to match 500 mg HTD1801 DRUG

2 tablets/day (1 tablet BID)

Placebo

Placebo to match 1000 mg HTD1801 DRUG

4 tablets/day (2 tablet BID)

Placebo

Placebo to match 2000 mg HTD1801 DRUG

8 tablets/day (4 tablet BID)

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have given written informed consent
• Males or females aged 18 to 70 years old at the time of first dosing
• Have a body mass index (BMI) of \>25.0 and ≤ 45.0 kg/m2 at Screening
• Have a documented history of hypercholesterolemia, defined as LDL-C ≥ 2.59 mmol/L

You may not qualify if:

• The use of any anti-dyslipidemia agent within 28 days prior to dosing
• History of a total cholesterol ≥ 10.35 mmol/L or triglyceride ≥ 11.3 mmol/L
• History of a clinically significant cardiac arrhythmia or clinically significant abnormal ECG results at Screening
• Significant peripheral or coronary vascular disease
• Clinically significant abnormal blood pressure at Screening or Baseline, defined as supine blood pressure ≥160/100 mmHg, or ≤ 90/60 mmHg
• 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
• Glucose-6-phosphate dehydrogenase (G6PD) deficiency

Sponsors & Collaborators

• HighTide Biopharma Pty Ltd: lead

Study Sites (3)

Q-Pharm Pty Ltd.

Herston, Queensland, 4006, Australia

Location

CMAX Clinical Research Pty Ltd

Adelaide, South Australia, 5000, Australia

Location

Linear Clinical Research

Nedlands, Western Australia, 6009, Australia

Location

Related Publications (1)

• 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.

  PMID: 33183320 DERIVED

MeSH Terms

Conditions

Hypercholesterolemia

Condition Hierarchy (Ancestors)

Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Dr. Adrian Di Bisceglie, CMO
• Organization: HighTide Therapeutics

adibisceglie@hightidetx.com

314-791-0593

Study Officials

• Adrian Di Bisceglie, MD,FACP,FAASLD

  HighTide Therapeutics USA, LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 18, 2017
• First Posted: December 21, 2017
• Study Start: April 13, 2018
• Primary Completion: December 31, 2018
• Study Completion: December 31, 2018
• Last Updated: March 3, 2023
• Results First Posted: March 3, 2023

Record last verified: 2022-08

Locations

AU (3)