Study of MB07811 in Subjects With Hypercholesterolemia

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Assess the Efficacy, Safety, and Tolerability of MB07811 for 12 Weeks Followed by a 6-Week Off Drug Phase in Subjects With Primary Hypercholesterolemia

Conditions
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Hypercholesterolemia

Intervention / Treatment
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* Drug: MB07811
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>MB07811 Cohort 1 | Drug: MB07811<br>* Oral<br>|
| Experimental: 2<br>MB07811 Cohort 2 | Drug: MB07811<br>* Oral<br>|
| Experimental: 3<br>MB07811 Cohort 3 | Drug: MB07811<br>* Oral<br>|
| Placebo Comparator: 4<br>Cohort 4 | Drug: Placebo<br>* Oral<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the effects of MB07811 compared to placebo on LDL-C |  | 12-weeks of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the effects of MB07811 on other lipid markers compared to placebo |  | 12 weeks | 
| Assess the safety and tolerability of MB07811 |  | after 12 weeks of treatment and during off-drug phase | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hyperlipidemia