A Multiple Ascending Dose Study of HTD1801 in Adults With Hypercholesterolemia

HighTide Therapeutics

Status and phase: Completed; Phase 2; Phase 1

Conditions: Hypercholesterolemia

Treatments: Drug: Placebo to match 500 mg HTD1801; Drug: Placebo to match 2000 mg HTD1801; Drug: HTD1801 Tablets, 1000 mg; Drug: HTD1801 Tablets, 500 mg; Drug: Placebo to match 1000 mg HTD1801; Drug: HTD1801 Tablets, 2000 mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT03381287

HTD1801.PCT004

Details and patient eligibility

About

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.

Enrollment: 50 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Quadruple Blind

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50 participants in 4 patient groups, including a placebo group

HTD1801 250 mg BID

Experimental group

Description:

Subjects received 500 mg/day HTD1801

Treatment:

Drug: HTD1801 Tablets, 500 mg

HTD1801 500 mg BID

Experimental group

Description:

Subjects received 1000 mg/day HTD1801

Treatment:

Drug: HTD1801 Tablets, 1000 mg

HTD1801 1000 mg BID

Experimental group

Description:

Subjects received 2000 mg/day HTD1801

Treatment:

Drug: HTD1801 Tablets, 2000 mg

Placebo

Placebo Comparator group

Treatment:

Drug: Placebo to match 500 mg HTD1801

Drug: Placebo to match 2000 mg HTD1801

Drug: Placebo to match 1000 mg HTD1801