Safety, Tolerability and Efficacy of Microsomal Triglyceride Protein (MTP) Inhibitor

NCT01556906 | Completed Phase 2 Results DMC

• 1 other identifier: UP1001
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this study is to evaluate the safety and tolerability of 4 doses of lomitapide (AEGR-733; BMS-201038) given as an initial low dose and then escalated through an additional 3 dose levels over a 16-week period. The secondary objectives of this study included the evaluation of the pharmacodynamics of lomitapide based on:

• Percent change in low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglycerides, and very low density lipoprotein cholesterol (VLDL-C) concentrations at the end of each 4-week dosing period compared to the Baseline value of each parameter at the end of the previous dose phase(s).
• Changes in other plasma lipoproteins: apolipoproteins (apo B, apo AI, apo AII, apo CIII, apo E) and lipoprotein a \[Lp(a)\].

Conditions

Homozygous Familial Hypercholesterolemia

Outcome Measures

Primary Outcomes (1)

• LDL-C

  Percent change in LDL-C compared to Baseline.

  Up to 16 weeks of treatment comapred to Baseline

Secondary Outcomes (14)

• Absolute Change From Baseline in Alanine Aminotransferase (ALT)

  Baseline and 16 weeks of treatment

• Absolute Change From Baseline in Aspartate Aminotransferase (AST)

  Baseline and 16 weeks of treatment

• Absolute Change From Baseline in Total Bilirubin

  Baseline and 16 weeks of treatment

• Absolute Change From Baseline in Hepatic Fat Percent

  Baseline and 16 weeks of treatment

• Absolute Change From Baseline in Forced Expiratory Volume During 1 Second (FEV1)

  Baseline and 16 weeks of treatment

Study Arms (1)

Lomitapide

EXPERIMENTAL

This is an open label trial where all patients receive lomitapide (AEGR733/BMS-201038)at escalating doses

Drug: Lomitapide

Interventions

Lomitapide DRUG

Oral administration with escalating doses administered once daily

Also known as: AEGR-733, BMS-201038

Lomitapide

Eligibility Criteria

• Age: 13 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and females ≥13 years of age
• Clinical diagnosis of HoFH AND one of the following (a, b, or c):
• Documented functional mutation in both LDL receptor alleles, OR
• Skin fibroblast LDL receptor activity \<20% of normal, OR
• TC \>500 mg/dL AND triglycerides \< 300 mg/dL AND both parents with documented TC \>250 mg/dL
• Body weight ≥40 kg
• Negative screening pregnancy test if female of child-bearing potential
• Subjects must be willing and able to comply with all study-related procedures
• Subjects must be willing and able to go off all lipid-lowering medications, dietary supplements (psyllium preparations) and LDL apheresis within 4 weeks prior to the Baseline visit until the end of the study.

You may not qualify if:

• Uncontrolled hypertension defined as: systolic blood pressure \>180 mmHg, diastolic blood pressure \>95 mmHg
• History of chronic renal insufficiency (serum creatinine \>2.5 mg/dL)
• History of liver disease or abnormal LFTs at screening (\>3x upper limit of normal \[ULN\])
• Any major surgical procedure occurring \< 3 months prior to the screening visit
• Cardiac insufficiency defined by the New York Heart Association classification as functional Class III or Class IV
• History of a non-skin malignancy within the previous 5 years
• History of alcohol or drug abuse
• Participation in an investigational drug study within 6 weeks prior to the screening visit
• Serious or unstable medical or psychological conditions that, in the opinion of the Investigator, would compromise the patient's safety or successful participation in the study.

Sponsors & Collaborators

• Aegerion Pharmaceuticals, Inc.: lead
• University of Pennsylvania: collaborator
• Doris Duke Charitable Foundation: collaborator

Study Sites (1)

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (1)

• Cuchel M, Bloedon LT, Szapary PO, Kolansky DM, Wolfe ML, Sarkis A, Millar JS, Ikewaki K, Siegelman ES, Gregg RE, Rader DJ. Inhibition of microsomal triglyceride transfer protein in familial hypercholesterolemia. N Engl J Med. 2007 Jan 11;356(2):148-56. doi: 10.1056/NEJMoa061189.

  PMID: 17215532 RESULT

MeSH Terms

Conditions

Homozygous Familial Hypercholesterolemia

Interventions

BMS201038

Condition Hierarchy (Ancestors)

Hyperlipoproteinemia Type II; Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hyperlipoproteinemias; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Aegerion Pharmaceutical

617-500-7867

Study Officials

• Dan J Rader, MD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 7, 2012
• First Posted: March 19, 2012
• Study Start: June 1, 2003
• Primary Completion: February 1, 2004
• Study Completion: February 1, 2004
• Last Updated: April 10, 2013
• Results First Posted: February 22, 2013

Record last verified: 2013-04

Locations

US (1)