IDIS:9300011[lJ-V1.0.C-V1.0
`
`BMS-201038
`
`Indication:
`
`Hyperlipidemia
`
`Protocol No.:
`
`CVl45-009
`
`Phase:
`
`I
`
`Study Initiation Date:
`
`19-Feb-1999
`
`Study Completion Date:
`
`22-Dec-1999
`
`Report Date:
`
`07-Jan-2002
`
`THE EFFECTS OF CHRONIC DOSING OF BMS-201038 ON HEPATIC FAT
`
`ACCUMULATION AND REVERSIBILITY AS ASSESSED BY NUCLEAR
`
`MAGNETIC RESONANCE SPECTROSCOPY (NMRS)
`
`AN ABBREVIATED CLINICAL STUDY REPORT
`
`
`
`
`
`
`This document is a confidential communication of Bristol-Myers Squibb Company. Acceptance of this
`document constitutes an agreement by the recipient that no unpublished information contained herein will
`be published or disclosed without Bristol-Myers Squibb Company's prior written approval. except that this
`
`document may be disclosed to appropriate Institutional Review Committees so long as they are requested to
`
`kee it confidential. This study was conducted in accordance with Good Clinical Practice.
`
`
`
`Name and Affiliation of Principal Investigators:
`'
`William Insull, MD. (Houston), Carlos Dujovne, M.D.(Kansas), Howard Knapp, M.D.,
`Ph.D.(University of Iowa), Daniel Radcr, M.D.(University of Pennsylvania), Evan Stein,
`M.D., Ph.D. (Cincinnati)
`
`Company Signatory
`Richard A. Reeves, M.D.
`Bristol-Myers Squibb
`Princeton, NJ 08543-4000
`Tel: 609-252-3452
`
`Fax: 609-252-6313
`
`Department of Clinical Discovery
`Drug Discovery and Exploratory Development
`Bristol-Myers Squibb Pharmaceutical Research Institute
`Bristol-Myers Squibb Company
`Bristol-Myers Squibb
`Princeton, NJ 08543-4000
`
`1 of 5
`
`PENN EX. 2057
`CFAD V. UPENN
`IPR2015—01836
`
`RAN
`
`

`
`CV1-1 5-00°
`
`BMS-20 l 038
`Abbreviated Clinical Study Report
`
`FINAL REPORT SYNOPSIS
`
`INTRODUCTION: BMS-201038 is an inhibitor of microsomal u-iglyceride transfer protein (MTP). In
`studies conducted in human volunteers BMS-201038 was shown to be a potent agent for lowering LDL~C
`and uiglycerides. As an inhibitor of MTP it has the potential to increase hepatic fat content. To assess the
`possible accumulation of hepatic fat, a nuclear magnetic resonance spectroscopy (NMRS) technique was
`developed. This technique was originally described as a method to assess fat content in bone marrow, and
`subsequently developed as part of the MT? program to determine percent fat
`in the liver. In Protocol
`CVl45-002. this technique demonstrated that at all doses of BMS-201038 from l0 mg QD to 100 mg QD.
`there appeared to be an increase in hepatic fat content. To further define the safety of this compound. a
`Reversibility Protocol. CV145-009. was developed to assess the extent of any hepatic fat accumulation and
`the degree of reversibility at 6 weeks post dosing of any accumulated hepatic faL Based on the results of
`this trial, fi.tI1h8l' clinical development on BMS-201038 was discontinued due to safety concerns. Therefore
`an Abbreviated Study Report is being issued.
`
`TITLE OF STUDY:
`
`The Effects of Chronic Dosing of BMS-201038 on Hepatic Fat Accumulation
`and Reversibility as Assessed by Nuclear Magnetic Resonance Spectroscopy
`{NMR5)
`
`INVESTIGATORS:
`
`Study conducted at 5 study centers in the USA. The Principal investigators
`(site number) were William lnsull, M.D. (001), Carlos Dujovne. M.D. (002),
`Howard Knapp, M.D.. Ph.D. (003), Daniel Rader, M.D. (007), Evan Stein,
`MD, Ph.D. (O08)
`
`STUDY CENIER5;
`
`00]: Lipid Research Clinic. Baylor College of Medicine, Houston. TX
`
`002: Mid-Continent Clinical Trials, Overland, KS
`
`003: Lipid Research Clinic, Iowa City, IA
`
`PUBLICATIONS:
`
`004: Hospital of the University of Pennsylvania, Philadelphia, PA
`
`008: Metabolic and Atherosclerosis Research Center, Cincinnati. OH
`None
`
`STUDY PERIOD:
`
`Date first subject enrolled:
`
`I9-Feb-I999
`
`Date last subject completed: 22~Dec-1999
`
`
`
`
`
`IDIS:930U0110J—v1.0.C—V1.0
`
`CLINICAL PHASE:
`
`I 2
`
`of 5
`
`PENN EX. 2057
`CFAD V. UPENN
`IPR2015—01836
`Aunt‘!
`
`

`
`BMS-201038
`
`C\W4S-00°
`Abbrcvialcd Climcal Studv R: on
`
`
`
`J-V1.0,C--v1.0
`
`;.
`1-4
`r-1
`
`DOO(
`
`'1
`G\
`
`PENN EX. 2057
`CFAD V. UPENN
`IPR2015—01836
`
`f'\J"\3
`
`U1
`
`HDH
`
`

`
`BMS-201038
`
`C\'l-‘.5-O09
`Abbrcxiaxcd Clmical Sludv R on
`
`J-V1.0,C-V1.0
`
`\-
`-1
`-I
`
`oooma
`
`s
`
`PENN EX. 2057
`CFAD V. UPENN
`IPR2015—01836
`
`U)
`:H
`
`HC
`
`

`
`EMS-201038
`
`
`
`3-V1.0,C-V1.0
`
`uv
`
`-I
`-4
`
`ooona
`
`s
`
`PENN EX. 2057
`CFAD V. UPENN
`IPR2015—01836
`
`O05
`
`In
`
`HDH
`
`

`
`
`
`
`
`IDIS:93000110J—v1.0,C-V1.0
`
`BMS-201038
`
`Abbreviated Clinical Study Report
`
`CV I-45-00°
`
`6 of 6
`
`PENN EX. 2057
`CFAD V. ITPENN
`IPR2015—01836
`nnf