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`IX INTERNATIONAL
`SYMPOSIUM ON
`DRUGS AFFECTING
`LIPID METABOLISM
`
`Fiorence (Italy), October 22-25, 1986
`
`Palazzo dei Cong
`Piazza Adua.
`
`'
`
`ABSTRACT BOOK
`
`Mylan Exhibit 1011, Page 1
`
`Mylan Exhibit 1011, Page 1
`
`

`
`EFFECT OF MK-733, Ah INHISXTOR fl? HM5—CoA~REDU£TASE, UN
`S£RUfl LIPIDS {H PAYIERTS WITH FAMILXAL H¥?ERCHOLESTEROLEMZfi
`H. H. Ditschuneit uné H: Ditschuneit
`D1v1s1on 0? fieta5o%1sm, Hutrition and Sastroenterology, Dehartment of
`Internal Medicine, finiversity of Utm, Steinhhveistr. 9, D~79oo Ufm, FRG
`
`Recentiy a new c1ass of funga1 metaboiites that are potent competitive inhibitors
`of HMG~CoA-reductase have been shown to be effective on lowering plasma concentra~
`tions of LDL-cholesterol. The purpose of this study was to est1mato to1ewab111ty
`and efficacy of various doses of 5ynv1no11n (MK-733,
`[1fir[1a:,3c£. 76, 8fi(2§f. 4§f}1
`Botflflj—1,2,3,7,8,8a~Hexahydro-3,?-dimethyi-8-[2-(totrahydro-4-hydroxy-6-oxo~2H-
`pyran~2~y1}athy1]~1~naohtha1ony1 2.2-dimethyihutonoatel
`in hyporcholesteroiemic pa-
`tients.
`16 patients 15 g, 11 35, aged 21 ~ 62 years. with hypercholesteroiemio typo II a
`130 X} and type 11 b (S x) were fireated after giving informed consent. After being
`at toast for 12 weeks.on diet and after a s1ng1e~b11nd piacebn period of 2 weoko pn~
`tients received on a doub1gah11nd basis 1.25, 2.5, 5.o, 10.0, 2o.o and 4o.o mg twice
`dai1y.or placebo. Safety, toierabiiity and efficacy were assessed by clinical and
`1aboratohy measurements week1y. Hosea of 5, 10. 20 and 4o mg h.i.d. for 4 weeks 1n~
`duced a mean reduction of totai cho1estero1 of 33.2 % (26.6 - 16.6 %}
`in 8 patienho.
`Mean reduction of LDL—cho1estero1 amounted to 41.9 (29.5 v d6.6 %)w The decrease of
`cholesterol was evident after one week of treatment and nearly complete after two
`weeks. The effect of the 40.0 mg b.i.d. dose was only s1ight1y greater than the 1o.o
`and 20.0 mg b.i.d. dose. HDL~cho1estero1 and tr1g1ycer1des were not
`inf1uenced o1gn1—
`ficanty. The compound was toierated weii and no serious ciinica1 and iaboratory
`side effects were observed, but the present study is considered as not informative
`as to the safety of the drug. Its safety wou¥d have to be c1ear1y established be~
`fore routine clinicai use of Synvino¥1n is serious contemplated in the treatment of
`hypercho1estero1emia.
`
`HYPGLIPGPRQTEIMEMIC EFFECTS 0? A FQTENT HMG~CGk REDUCTASE
`3R1-52320:
`‘
`INHIBITOR
`R. G. En strom’, B. B1 Woinstein*, F. G. xathawaia’, W. Qoaliena,
`J. B. Esgesen’, M. L. Quaker‘, R. Miaeronflinog
`‘Sandoz Research Instituto, East Hanover, Maw Joraoy, U.S.a.
`‘Department of Bioohemistry, School of Meflioihe, finiversity of New
`Mexico, Albuquerque, New Mexico, fl.S.A.
`
`Since the results of Lipifl Eeaoaruh fllinio*a floxonary Primary Foo-
`vention Trial with.flho1ootyramino,
`there has been heightenad interoot
`in the development of safe on& oifoctive hypolipoprutainemio agents.-
`Efforta at Sandoz.Research.Institute in tho das£gn and 5ynthas£s of
`novel HMG~CoA xeductase inhibitors havo loo to 331-62320:
`[R*,s*—{E)}-
`{1)—sodium~3,5~dihydr0xy~?~{3~{4&flucznpheny1}~1(l~methy1ethy2§~1H-
`indol-2-yl]—hept-6-enoate, whiob shows marked affects in lowering
`several lipid parametera in oats, dogs anfi moakaya; The hygolioopxow
`teinemic properties of SRI~62320,
`in comparison to oompaotin, will be
`the subjeat of this preannhation.
`
`This material may be protected by Copyright law (Title 17 U.S. Code)
`
`Mylan Exhibit 1011, Page 2
`
`Mylan Exhibit 1011, Page 2