Study of MB07811 in Subjects With Hypercholesterolemia

Ligand Pharmaceuticals

Status and phase: Withdrawn; Phase 2

Conditions: Hypercholesterolemia

Treatments: Drug: MB07811; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT00879112

MB07811-201

Details and patient eligibility

About

A Phase 2 randomized, placebo controlled study assessing the efficacy, safety, and tolerability of MB07811 given orally to subjects with primary hypercholesterolemia for 12 weeks followed by a 6-week off drug phase.

Full description

This is an outpatient, Phase 2, multicenter, double-blind, placebo-controlled, randomized, parallel-group study assessing the efficacy, safety, and tolerability of MB07811 given orally to subjects with primary hypercholesterolemia for 12 weeks. There will be a 3- to 6-week screening/run-in period, including washout of any lipid-modifying therapies (as needed) prior to randomization. Eligible subjects will be randomized (1:1:1:1) to placebo, or 3 different doses of MB07811 for 12 weeks. After the double-blind treatment phase, all randomized subjects will proceed into a 6-week off-drug phase. Assessments include: laboratory tests, adverse events (AEs), electrocardiograms (ECGs), vitals, and PK samples.

Enrollment: 80 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Body mass index (BMI) 18.50 - 40 kg/m2 inclusive at screening;
• Fasting serum LDL-C ≥145 mg/dL at both Q2 and Q3 visits;
• Fasting mean serum LDL-C <220 mg/dL from Q2 and Q3;

Exclusion criteria

• History of clinically significant cardiovascular disease
• Uncontrolled hypertension
• Significant sinus bradycardia defined as <40 beats per minute (bpm);
• Personal or family history of clinically significant unexplained syncope, near-syncope or unexplained sudden death or QT syndrome;
• Holter monitor report demonstrating any abnormality that is clinically significant, including but not limited to PVC frequency > 1 per minute, any alert criteria or any other condition that requires further evaluation;
• History of clinical significant arrhythmia;
• Resting 12-lead ECG showing QTc >450 msec or <360 msec (males or females), any tachyarrhythmia or morphology change, or any other clinically significant abnormality;
• Any other cardiovascular event requiring hospitalization;
• History or presence of thyroid disorder or other metabolic/endocrine disorder that affects lipids or glucose; Exceptions: polycystic ovarian syndrome (PCOS) and impaired glucose tolerance (IGT) are allowed.
• Liver disease, gallbladder disease, Gilbert's syndrome, biopsy-proven nonalcoholic steatohepatitis (NASH), positive serology for hepatitis B surface antigen (HBsAg) or hepatitis C antibodies; Exceptions: gallbladder disease treated with cholecystectomy
• History of human immunodeficiency virus (HIV);
• Subjects with a prior history of malignancy in past 5 years;Exceptions: Subjects with previous history of basal or squamous cell carcinoma of the skin, or cervical cancer in situ are allowed if successfully treated;
• History of myopathy, including any history of statin-induced myopathy;
• History of intolerance to statins (e.g., myalgias, elevated liver tests);
• History of clinically significant psychiatric disorders, including but not limited to bipolar disorder, major depressive disorder, psychosis;
• Renal dysfunction;
• Alcohol and/or drug abuse within 12 months prior to screening;

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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80 participants in 4 patient groups, including a placebo group

1

Experimental group

Description:

MB07811 Cohort 1

Treatment:

Drug: MB07811

2

Experimental group

Description:

MB07811 Cohort 2

Treatment:

Drug: MB07811

3

Experimental group

Description:

MB07811 Cohort 3

Treatment:

Drug: MB07811

4

Placebo Comparator group

Description:

Cohort 4

Treatment:

Drug: Placebo