Clinical trial NCT00879112: Study of MB07811 in Subjects With Hypercholesterolemia
Official title: 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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Hypercholesterolemia
Keywords: Hyperlipidemia
Lead sponsor: Ligand Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2009-04-09
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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;

Primary outcomes:
measure: Evaluate the effects of MB07811 compared to placebo on LDL-C
timeFrame: 12-weeks of treatment
Secondary outcomes:
measure: Evaluate the effects of MB07811 on other lipid markers compared to placebo
timeFrame: 12 weeks
measure: Assess the safety and tolerability of MB07811
timeFrame: after 12 weeks of treatment and during off-drug phase
Other outcomes:
Locations:
city: San Diego
country: United States
facility: Scripps Clinic, Clinical Research
state: California
city: Jacksonville
country: United States
facility: Jacksonville Center for Clinical Research
state: Florida
city: Pembroke Pines
country: United States
facility: University Clinical Research
state: Florida
city: Chicago
country: United States
facility: Radiant Research
state: Illinois
city: Indianapolis
country: United States
facility: Midwest Institute for Clinical Research
state: Indiana
city: Madisonville
country: United States
facility: Commonwealth Biomedical Research
state: Kentucky
city: Troy
country: United States
facility: Troy Internal Medicine
state: Michigan
city: Goose Creek
country: United States
facility: Coastal Carolina Research Center, Inc.
state: South Carolina
city: Dallas
country: United States
facility: Research Across America
state: Texas
city: Norfolk
country: United States
facility: National Clinical Research - Norfolk
state: Virginia
city: Richmond
country: United States
facility: National Clinical Research
state: Virginia
Study officials:
affiliation: Metabasis Therapeutics, Inc.
name: Trish Novak, Ph.D.
role: STUDY_DIRECTOR
References: