A Multiple Ascending Dose Study of HTD1801 in Adults With Hypercholesterolemia

Study Overview
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Brief Summary
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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.

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

Conditions
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Hypercholesterolemia

Intervention / Treatment
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* 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


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 | Measure Description | 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 |