A Multiple Ascending Dose Study of HTD1801 in Adults With Hypercholesterolemia

Phase 1

Completed

Interventions: 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

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.

Recruitment & Eligibility

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

Arm && Interventions

Primary Outcome Measures

Name	Time	Method
Number of Subjects With Treatment-Emergent Adverse Events (TEAEs)	4 weeks	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

Name	Time	Method
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
Percent Change in Lipoprotein-A From Baseline to Day 28 Within and Between Treatment Groups	Baseline, Day 14, Day 28
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
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 Free-fatty Acids (FFA) 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

Locations (3): Q-Pharm Pty Ltd.
🇦🇺
Herston, Queensland, Australia
CMAX Clinical Research Pty Ltd
🇦🇺
Adelaide, South Australia, Australia
Linear Clinical Research
🇦🇺
Nedlands, Western Australia, Australia