Study of MB07811 in Subjects With Hypercholesterolemia

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Hypercholesterolemia
• Intervention / Treatment: Drug: Placebo; Drug: MB07811

Detailed 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.

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States, 92128
      • Scripps Clinic, Clinical Research
  • Florida
    • Jacksonville, Florida, United States, 32216
      • Jacksonville Center for Clinical Research
    • Pembroke Pines, Florida, United States, 33024
      • University Clinical Research
  • Illinois
    • Chicago, Illinois, United States, 60654
      • Radiant Research
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Midwest Institute for Clinical Research
  • Kentucky
    • Madisonville, Kentucky, United States, 42431
      • Commonwealth BioMedical Research
  • Michigan
    • Troy, Michigan, United States, 48098
      • Troy Internal Medicine
  • South Carolina
    • Goose Creek, South Carolina, United States, 29445
      • Coastal Carolina Research Center, Inc.
  • Texas
    • Dallas, Texas, United States, 75234
      • Research Across America
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • National Clinical Research - Norfolk
    • Richmond, Virginia, United States, 23294
      • National Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; MB07811 Cohort 1	Drug: MB07811; Oral
Experimental: 2; MB07811 Cohort 2	Drug: MB07811; Oral
Experimental: 3; MB07811 Cohort 3	Drug: MB07811; Oral
Placebo Comparator: 4; Cohort 4	Drug: Placebo; Oral

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Ligand Pharmaceuticals
• Investigators: Study Director: Trish Novak, Ph.D., Metabasis Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start: April 1, 2009
• Primary Completion (Anticipated): December 1, 2009
• Study Completion (Anticipated): December 1, 2009

Study Registration Dates

• First Submitted: April 8, 2009
• First Submitted That Met QC Criteria: April 8, 2009
• First Posted (Estimate): April 9, 2009

Study Record Updates

• Last Update Posted (Estimate): August 12, 2011
• Last Update Submitted That Met QC Criteria: August 10, 2011
• Last Verified: August 1, 2011

More Information

Terms related to this study

• Keywords: Hyperlipidemia
• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Hypercholesterolemia
• Other Study ID Numbers: MB07811-201