Back to resultsA Multiple Ascending Dose Study of HTD1801 in Adults With Hypercholesterolemia
Primary Purpose
Hypercholesterolemia
Status
Completed
Phase
Phase 1
Locations
Australia
Study Type
Interventional
Intervention
HTD1801 Tablets, 500 mg
HTD1801 Tablets, 1000 mg
HTD1801 Tablets, 2000 mg
Placebo to match 500 mg HTD1801
Placebo to match 1000 mg HTD1801
Placebo to match 2000 mg HTD1801
Sponsored by
About this trial
This is an interventional treatment trial for Hypercholesterolemia
Eligibility Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
Sites / Locations
- Q-Pharm Pty Ltd.
- CMAX Clinical Research Pty Ltd
- Linear Clinical Research
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Placebo Comparator
Arm Label
HTD1801 250 mg BID
HTD1801 500 mg BID
HTD1801 1000 mg BID
Placebo
Arm Description
Subjects received 500 mg/day HTD1801
Subjects received 1000 mg/day HTD1801
Subjects received 2000 mg/day HTD1801
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Maximum Plasma Concentration (Cmax) of HTD1801 Components After Single-dose Oral Administration
Maximum Plasma Concentration (Cmax) of HTD1801 Components After Multiple-dose Oral Administration
Time to Maximum Plasma Concentration (Tmax) of HTD1801 Components After Single-dose Oral Administration
Time to Maximum Plasma Concentration (Tmax) of HTD1801 Components After Multiple-dose Oral Administration
Plasma Half-life of HTD1801 Components (T1/2) After Single-dose Oral Administration
Plasma Half-life of HTD1801 Components (T1/2) After Multiple-dose Oral Administration
Percent Change in Low-density Lipoprotein-Cholesterol (LDL-C) From Baseline to Day 28 Within and Between Treatment Groups
Percent Change in Triglycerides From Baseline to Day 28 Within and Between Treatment Groups
Percent Change in Free-fatty Acids (FFA) From Baseline to Day 28 Within and Between Treatment Groups
Percent Change in Lipoprotein-A From Baseline to Day 28 Within and Between Treatment Groups
Full Information
NCT ID
NCT03381287
First Posted
December 18, 2017
Last Updated
August 2, 2022
Sponsor
HighTide Biopharma Pty Ltd
1. Study Identification
Unique Protocol Identification Number
NCT03381287
Brief Title
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
2. Study Status
Record Verification Date
August 2022
Overall Recruitment Status
Completed
Study Start Date
April 13, 2018 (Actual)
Primary Completion Date
December 31, 2018 (Actual)
Study Completion Date
December 31, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
HighTide Biopharma Pty Ltd
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypercholesterolemia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
50 (Actual)
8. Arms, Groups, and Interventions
Arm Title
HTD1801 250 mg BID
Arm Type
Experimental
Arm Description
Subjects received 500 mg/day HTD1801
Arm Title
HTD1801 500 mg BID
Arm Type
Experimental
Arm Description
Subjects received 1000 mg/day HTD1801
Arm Title
HTD1801 1000 mg BID
Arm Type
Experimental
Arm Description
Subjects received 2000 mg/day HTD1801
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
HTD1801 Tablets, 500 mg
Intervention Description
500 mg/day (250 mg BID)
Intervention Type
Drug
Intervention Name(s)
HTD1801 Tablets, 1000 mg
Intervention Description
1000 mg/day (500 mg BID)
Intervention Type
Drug
Intervention Name(s)
HTD1801 Tablets, 2000 mg
Intervention Description
2000 mg/day (1000 mg BID)
Intervention Type
Drug
Intervention Name(s)
Placebo to match 500 mg HTD1801
Intervention Description
2 tablets/day (1 tablet BID)
Intervention Type
Drug
Intervention Name(s)
Placebo to match 1000 mg HTD1801
Intervention Description
4 tablets/day (2 tablet BID)
Intervention Type
Drug
Intervention Name(s)
Placebo to match 2000 mg HTD1801
Intervention Description
8 tablets/day (4 tablet BID)
Primary Outcome Measure Information:
Title
Number of Subjects With Treatment-Emergent Adverse Events (TEAEs)
Description
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 Outcome Measure Information:
Title
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
Title
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
Title
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
Title
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
Title
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
Title
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
Title
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
Title
Percent Change in Triglycerides From Baseline to Day 28 Within and Between Treatment Groups
Time Frame
Baseline, Day 14, Day 28
Title
Percent Change in Free-fatty Acids (FFA) From Baseline to Day 28 Within and Between Treatment Groups
Time Frame
Baseline, Day 14, Day 28
Title
Percent Change in Lipoprotein-A From Baseline to Day 28 Within and Between Treatment Groups
Time Frame
Baseline, Day 14, Day 28
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
Exclusion Criteria:
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Adrian Di Bisceglie, MD,FACP,FAASLD
Organizational Affiliation
HighTide Therapeutics USA, LLC
Official's Role
Study Director
Facility Information:
Facility Name
Q-Pharm Pty Ltd.
City
Herston
State/Province
Queensland
ZIP/Postal Code
4006
Country
Australia
Facility Name
CMAX Clinical Research Pty Ltd
City
Adelaide
State/Province
South Australia
ZIP/Postal Code
5000
Country
Australia
Facility Name
Linear Clinical Research
City
Nedlands
State/Province
Western Australia
ZIP/Postal Code
6009
Country
Australia
12. IPD Sharing Statement
Citations:
PubMed Identifier
33183320
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.
Results Reference
derived
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A Multiple Ascending Dose Study of HTD1801 in Adults With Hypercholesterolemia
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