Safety, Tolerability and Efficacy of Microsomal Triglyceride Protein (MTP) Inhibitor - F...
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`A service of the U.S. National Institutes of Health
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`Trial record 1 of 1 for: NCT01556906
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`Safety, Tolerability and Efficacy of Microsomal Triglyceride Protein (MTP) Inhibitor
`
`This study has been completed.
`
`Sponsor:
`Aegerion Pharmaceuticals, Inc.
`
`Collaborators:
`University of Pennsylvania
`Doris Duke Charitable Foundation
`
`Information provided by (Responsible Party):
`Aegerion Pharmaceuticals, Inc.
`
`ClinicalTrials.gov Identifier:
`NCT01556906
`First received: March 7, 2012
`Last updated: April 4, 2013
`Last verified: April 2013
`History of Changes
`
`Full Text View
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`Study Results
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`Disclaimer
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`How to Read a Study Record
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` Purpose
`
`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)].
`
`Condition
`
`Intervention
`
`Phase
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`Homozygous Familial Hypercholesterolemia
`
`Drug: Lomitapide
`
`Phase 2
`
`Interventional
`Study Type:
`Study Design: Endpoint Classification: Safety/Efficacy Study
`Intervention Model: Single Group Assignment
`Masking: Open Label
`Primary Purpose: Treatment
`
`Official Title:
`
`A Phase II Open Label, Dose-Escalation Study to Determine the Safety, Tolerability and Efficacy of Microsomal Triglyceride
`Transfer Protein (MTP) Inhibitor BMS-201038 in Patients With Homozygous Familial Hypercholeterolemia
`
`Resource links provided by NLM:
`
`Genetics Home Reference related topics: Chanarin-Dorfman syndrome cholesteryl ester storage disease hypercholesterolemia
`
`MedlinePlus related topics: Cholesterol
`
`Drug Information available for: Lomitapide
`
`Genetic and Rare Diseases Information Center resources: Hyperlipoproteinemia Type 2 Sphingolipidosis
`
`U.S. FDA Resources
`
`Further study details as provided by Aegerion Pharmaceuticals, Inc.:
`
`Primary Outcome Measures:
`• LDL-C [ Time Frame: Up to 16 weeks of treatment comapred to Baseline ] [ Designated as safety issue: No ]
`
`https://clinicaltrials.gov/ct2/show/NCT01556906?term=NCT01556906&rank=1
`
`12/7/2015
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`Page 1 of 4
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`PENN EX. 2003
`CFAD V. UPENN
`IPR2015-01835
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`

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`Safety, Tolerability and Efficacy of Microsomal Triglyceride Protein (MTP) Inhibitor - F...
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`Percent change in LDL-C compared to Baseline.
`
`Secondary Outcome Measures:
`• Absolute Change From Baseline in Alanine Aminotransferase (ALT) [ Time Frame: Baseline and 16 weeks of treatment ]
`[ Designated as safety issue: Yes ]
`Absolute change from Baseline in ALT
`
`• Absolute Change From Baseline in Aspartate Aminotransferase (AST) [ Time Frame: Baseline and 16 weeks of treatment ]
`[ Designated as safety issue: Yes ]
`Absolute change from Baseline in AST
`
`• Absolute Change From Baseline in Total Bilirubin [ Time Frame: Baseline and 16 weeks of treatment ] [ Designated as safety issue: Yes ]
`Absolute change from Baseline in total bilirubin
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`• Absolute Change From Baseline in Hepatic Fat Percent [ Time Frame: Baseline and 16 weeks of treatment ] [ Designated as safety issue: Yes ]
`Absolute change from Baseline in hepatic fat percent
`
`• Absolute Change From Baseline in Forced Expiratory Volume During 1 Second (FEV1) [ Time Frame: Baseline and 16 weeks of treatment ]
`[ Designated as safety issue: Yes ]
`Absolute change from Baseline in FEV1
`
`• Absolute Change From Baseline in Carbon Monoxide Lung Diffusing Capacity (DLCO)(a Pulmonary Function Test) [ Time Frame: Baseline and
`16 weeks of treatment ] [ Designated as safety issue: Yes ]
`Absolute change from Baseline in DLCO
`
`• Absolute Change From Baseline in Vitamin A [ Time Frame: Baseline and 16 weeks of treatment ] [ Designated as safety issue: Yes ]
`Absolute change from Baseline in vitamin A
`
`• Absolute Change From Baseline in Vitamin E [ Time Frame: Baseline and 16 weeks of treatment ] [ Designated as safety issue: Yes ]
`Absolute change from Baseline in vitamin E
`
`• Absolute Change From Baseline in Vitamin D [ Time Frame: Baseline and 16 weeks of treatment ] [ Designated as safety issue: Yes ]
`Absolute Change From Baseline in Vitamin D
`
`• Absolute Change From Baseline in Ratio of Vitamin E to Total Lipids [ Time Frame: Baseline and 16 weeks of treatment ]
`[ Designated as safety issue: Yes ]
`Absolute Change From Baseline in ratio of vitamin E to total lipids
`
`• Absolute Change From Baseline in Alpha Linoleic Acid (ALA) [ Time Frame: Baseline and 16 weeks of treatment ]
`[ Designated as safety issue: Yes ]
`Absolute Change From Baseline in ALA
`
`• Absolute Change From Baseline in Eicosapentaenoic Acid (EPA) [ Time Frame: Baseline and 16 weeks of treatment ]
`[ Designated as safety issue: Yes ]
`Absolute Change From Baseline in EPA
`
`• Absolute Change From Baseline in Docosahexaenoic Acid (DHA) [ Time Frame: Baseline and 16 weeks of treatment ]
`[ Designated as safety issue: Yes ]
`Absolute Change From Baseline in DHA
`
`• Absolute Change From Baseline in Linoleic Acid (LA) [ Time Frame: Baseline and 16 weeks of treatment ] [ Designated as safety issue: Yes ]
`Absolute Change From Baseline in LA
`
`Enrollment:
`Study Start Date:
`
`6
`June 2003
`
`https://clinicaltrials.gov/ct2/show/NCT01556906?term=NCT01556906&rank=1
`
`12/7/2015
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`Page 2 of 4
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`PENN EX. 2003
`CFAD V. UPENN
`IPR2015-01835
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`

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`Safety, Tolerability and Efficacy of Microsomal Triglyceride Protein (MTP) Inhibitor - F...
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`February 2004
`Study Completion Date:
`Primary Completion Date: February 2004 (Final data collection date for primary outcome measure)
`
`Arms
`
`Experimental: Lomitapide
`This is an open label trial where all patients receive lomitapide (AEGR733/BMS-
`201038)at escalating doses
`
`Assigned Interventions
`
`Drug: Lomitapide
`Oral administration with escalating doses
`administered once daily
`Other Names:
`• AEGR-733
`• BMS-201038
`
`Detailed Description:
`This is a single center, open-label, Phase 2 clinical trial designed to evaluate the safety, tolerability, and pharmacodynamics of lomitapide in the
`treatment of patients with homozygous familial hypercholesterolemia (HoFH).
`Patients are required to stop all lipid-lowering therapies, including apheresis, within 4 weeks prior to the Baseline visit and throughout the study.
`Patients are placed on a rigorous low-fat diet (<10% of energy from total dietary fat) at the Screening assessment; dietary counseling by a
`registered dietitian will be initiated at Screening and will continue at each subsequent study visit.
`Patients initially receive 0.03 mg/kg of lomitapide orally every day for 4 weeks. Intra-patient dose escalation to 0.1 mg/kg, 0.3 mg/kg/day and 1.0
`mg/kg/day occur every 4 weeks if specific protocol-defined stopping rules related to Grade 3 or 4 toxicities or serious adverse events (SAEs) do not
`apply.
`The study includes 15 study visits over 22 weeks: a Screening visit (Visit 1) conducted within 2 weeks prior to dosing, a Baseline visit (Visit 2)
`conducted on Day 1 prior to the first dose, 12 visits conducted during the treatment period (Visits 3 through 14), and a Follow-up visit (Visit 15)
`conducted approximately 4 weeks after the last dose of lomitapide.
`Screening and Baseline procedures include medical and medication history, physical examination, vital signs, 12-lead electrocardiogram (ECG),
`pulmonary function tests (PFTs), safety laboratory tests, fat soluble vitamin levels and a fatty acid profile. Nuclear magnetic resonance
`spectroscopy (NMRS) of the liver will be conducted at Baseline, at the end of each dosing period, and at the follow up visit to assess hepatic fat
`content. Baseline efficacy assessment includes a fasting lipid profile (TC, LDL-C [directly measured], VLDL-C, high density lipoprotein-cholesterol
`[HDL-C], triglycerides, and apolipoproteins [apo B, apo AI, apo AII, apo CIII, apo E] and Lp(a)).
`Safety and lipid profile assessments are repeated during the treatment period and at the Follow-up visit conducted 28 days after the last dose of
`lomitapide.
`
` Eligibility
`
`13 Years and older
`Ages Eligible for Study:
`Both
`Genders Eligible for Study:
`Accepts Healthy Volunteers: No
`
`Criteria
`Inclusion Criteria:
`1. Males and females ≥13 years of age
`2. 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
`3. Body weight ≥40 kg
`4. Negative screening pregnancy test if female of child-bearing potential
`5. Subjects must be willing and able to comply with all study-related procedures
`6. 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.
`Exclusion Criteria:
`1. Uncontrolled hypertension defined as: systolic blood pressure >180 mmHg, diastolic blood pressure >95 mmHg
`2. History of chronic renal insufficiency (serum creatinine >2.5 mg/dL)
`3. History of liver disease or abnormal LFTs at screening (>3x upper limit of normal [ULN])
`4. Any major surgical procedure occurring < 3 months prior to the screening visit
`5. Cardiac insufficiency defined by the New York Heart Association classification as functional Class III or Class IV
`6. History of a non-skin malignancy within the previous 5 years
`7. History of alcohol or drug abuse
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`https://clinicaltrials.gov/ct2/show/NCT01556906?term=NCT01556906&rank=1
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`12/7/2015
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`Page 3 of 4
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`PENN EX. 2003
`CFAD V. UPENN
`IPR2015-01835
`
`

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`Safety, Tolerability and Efficacy of Microsomal Triglyceride Protein (MTP) Inhibitor - F...
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`Page 4 of 4
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`8. Participation in an investigational drug study within 6 weeks prior to the screening visit
`9. 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.
`
` Contacts and Locations
`
`Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a
`study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general
`information, see Learn About Clinical Studies.
`
`Please refer to this study by its ClinicalTrials.gov identifier: NCT01556906
`
`Locations
`
`United States, Pennsylvania
`University of Pennsylvania
`Philadelphia, Pennsylvania, United States, 19104
`
`Sponsors and Collaborators
`Aegerion Pharmaceuticals, Inc.
`University of Pennsylvania
`Doris Duke Charitable Foundation
`
`Investigators
`Principal Investigator: Dan J Rader, MD University of Pennsylvania
`
` More Information
`
`Publications:
`
`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.
`
`Aegerion Pharmaceuticals, Inc.
`Responsible Party:
`ClinicalTrials.gov Identifier: NCT01556906 History of Changes
`Other Study ID Numbers:
`UP1001
`Study First Received:
`March 7, 2012
`Results First Received:
`January 18, 2013
`Last Updated:
`April 4, 2013
`Health Authority:
`United States: Food and Drug Administration
`
`Additional relevant MeSH terms:
`Hypercholesterolemia
`Hyperlipoproteinemia Type II
`Dyslipidemias
`Genetic Diseases, Inborn
`Hyperlipidemias
`
`ClinicalTrials.gov processed this record on December 04, 2015
`
`Hyperlipoproteinemias
`Lipid Metabolism Disorders
`Lipid Metabolism, Inborn Errors
`Metabolic Diseases
`Metabolism, Inborn Errors
`
`https://clinicaltrials.gov/ct2/show/NCT01556906?term=NCT01556906&rank=1
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`12/7/2015
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`Page 4 of 4
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`PENN EX. 2003
`CFAD V. UPENN
`IPR2015-01835