NCT00954252

Brief Summary

The purpose of this study is to evaluate the safety and tolerability of single oral doses of CHF 5074 in young healthy male volunteers.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
84

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Oct 2009

Shorter than P25 for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 31, 2009

Completed
7 days until next milestone

First Posted

Study publicly available on registry

August 7, 2009

Completed
2 months until next milestone

Study Start

First participant enrolled

October 1, 2009

Completed
7 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2010

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2010

Completed
Last Updated

February 10, 2015

Status Verified

February 1, 2015

Enrollment Period

7 months

First QC Date

July 31, 2009

Last Update Submit

February 9, 2015

Conditions

Alzheimer's Disease

Outcome Measures

Primary Outcomes (1)

  • Adverse Events

    from Screening through Day +3

Secondary Outcomes (1)

  • Dose linearity of CHF5074 plasma levels (Cmax and AUC0-t)

    Day -1 through Day +3

Study Arms (2)

Test Article

EXPERIMENTAL
Drug: CHF 5074

Placebo

PLACEBO COMPARATOR
Drug: placebo

Interventions

CHF 5074DRUG

1x, oral capsule, single dose

Test Article
placeboDRUG

placebo, oral capsule, single dose

Placebo

Eligibility Criteria

Age18 Years - 45 Years
Sexmale
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • Subject's written informed consent is obtained prior to any study-related procedures.
  • Subject is nonsmoking male between 18 and 45 years of age, inclusive.
  • Subject has a body mass index between 18 and 30 kg/m2, inclusive.
  • Subject is judged, by the investigator, to be in good health on the basis of medical history, complete physical examination including vital signs, 12-lead electrocardiogram (ECG) and standard laboratory tests including complete hematology, blood chemistry (glucose, creatinine, blood urea nitrogen, alanine aminotransferase, aspartate aminotransferase, albumin, alkaline phosphatase, sodium, potassium), thyroid function, urinalysis (glucose, hemoglobin, blood, proteins, pH) and fecal occult blood.
  • Subject understands the procedures and agrees to participate in the study program.

You may not qualify if:

  • Subject is mentally or legally incapacitated.
  • Subject has a history of any illness that, in the opinion of the investigator and according to the protocol, might confound the results of the study or pose additional risk in administering CHF5074 to the subject.
  • Subject has a medical history (within the last 10 years) of major cardiovascular, hepatic or renal disease.
  • Subject has liver function test abnormalities with elevated AST or ALT greater than or equal to 2 times upper limit of normal and/or elevated bilirubin greater than or equal to 2 times upper limit of normal.
  • Subject has renal function test abnormalities, including serum creatinine greater than 1.8 g/dL.
  • Subject has abnormal fasting serum concentrations of TSH, T3 or T4.
  • Subject has a positive result for fecal occult blood testing performed at screening.
  • Subject has clinically significant abnormalities on physical examination, ECG or laboratory tests carried out at screening.
  • Subject has a history of a psychiatric disorder.
  • Subject has significant allergic conditions that require medical treatment or has known hypersensitivity to medications that could be activated by CHF5074 treatment.
  • Subject is positive on testing for hepatitis B surface antigen, hepatitis C antibody or HIV 1 or 2 antibodies.
  • Subject has donated blood within the 1 month prior to screening.
  • Subject has a history of alcohol or drug abuse in the past 12 months.
  • Subject used any psychoactive, recreational or prescription drug within the 4 weeks prior to study drug administration.
  • Subject has used ibuprofen, sulindac sulfide, indomethacin, flurbiprofen within 2 weeks prior to study drug administration.
  • +6 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Iberica Clinical Research Center

Eatontown, NJ 07724, New Jersey, 07724, United States

Location

Related Publications (20)

  • Lesne S, Koh MT, Kotilinek L, Kayed R, Glabe CG, Yang A, Gallagher M, Ashe KH. A specific amyloid-beta protein assembly in the brain impairs memory. Nature. 2006 Mar 16;440(7082):352-7. doi: 10.1038/nature04533.

    PMID: 16541076BACKGROUND

  • Shankar GM, Li S, Mehta TH, Garcia-Munoz A, Shepardson NE, Smith I, Brett FM, Farrell MA, Rowan MJ, Lemere CA, Regan CM, Walsh DM, Sabatini BL, Selkoe DJ. Amyloid-beta protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory. Nat Med. 2008 Aug;14(8):837-42. doi: 10.1038/nm1782. Epub 2008 Jun 22.

    PMID: 18568035BACKGROUND

  • Olson RE, Albright CF. Recent progress in the medicinal chemistry of gamma-secretase inhibitors. Curr Top Med Chem. 2008;8(1):17-33. doi: 10.2174/156802608783334088.

    PMID: 18220929BACKGROUND

  • Lleo A. Activity of gamma-secretase on substrates other than APP. Curr Top Med Chem. 2008;8(1):9-16. doi: 10.2174/156802608783334060.

    PMID: 18220928BACKGROUND

  • Lewis HD, Perez Revuelta BI, Nadin A, Neduvelil JG, Harrison T, Pollack SJ, Shearman MS. Catalytic site-directed gamma-secretase complex inhibitors do not discriminate pharmacologically between Notch S3 and beta-APP cleavages. Biochemistry. 2003 Jun 24;42(24):7580-6. doi: 10.1021/bi034310g.

    PMID: 12809514BACKGROUND

  • Maillard I, Adler SH, Pear WS. Notch and the immune system. Immunity. 2003 Dec;19(6):781-91. doi: 10.1016/s1074-7613(03)00325-x.

    PMID: 14670296BACKGROUND

  • Stanger BZ, Datar R, Murtaugh LC, Melton DA. Direct regulation of intestinal fate by Notch. Proc Natl Acad Sci U S A. 2005 Aug 30;102(35):12443-8. doi: 10.1073/pnas.0505690102. Epub 2005 Aug 17.

    PMID: 16107537BACKGROUND

  • Searfoss GH, Jordan WH, Calligaro DO, Galbreath EJ, Schirtzinger LM, Berridge BR, Gao H, Higgins MA, May PC, Ryan TP. Adipsin, a biomarker of gastrointestinal toxicity mediated by a functional gamma-secretase inhibitor. J Biol Chem. 2003 Nov 14;278(46):46107-16. doi: 10.1074/jbc.M307757200. Epub 2003 Aug 29.

    PMID: 12949072BACKGROUND

  • Wong GT, Manfra D, Poulet FM, Zhang Q, Josien H, Bara T, Engstrom L, Pinzon-Ortiz M, Fine JS, Lee HJ, Zhang L, Higgins GA, Parker EM. Chronic treatment with the gamma-secretase inhibitor LY-411,575 inhibits beta-amyloid peptide production and alters lymphopoiesis and intestinal cell differentiation. J Biol Chem. 2004 Mar 26;279(13):12876-82. doi: 10.1074/jbc.M311652200. Epub 2004 Jan 6.

    PMID: 14709552BACKGROUND

  • Weggen S, Eriksen JL, Das P, Sagi SA, Wang R, Pietrzik CU, Findlay KA, Smith TE, Murphy MP, Bulter T, Kang DE, Marquez-Sterling N, Golde TE, Koo EH. A subset of NSAIDs lower amyloidogenic Abeta42 independently of cyclooxygenase activity. Nature. 2001 Nov 8;414(6860):212-6. doi: 10.1038/35102591.

    PMID: 11700559BACKGROUND

  • Kukar T, Golde TE. Possible mechanisms of action of NSAIDs and related compounds that modulate gamma-secretase cleavage. Curr Top Med Chem. 2008;8(1):47-53. doi: 10.2174/156802608783334042.

    PMID: 18220932BACKGROUND

  • Peretto I, La Porta E. Gamma-secretase modulation and its promise for Alzheimer's disease: a medicinal chemistry perspective. Curr Top Med Chem. 2008;8(1):38-46. doi: 10.2174/156802608783334097.

    PMID: 18220931BACKGROUND

  • Peretto I, Radaelli S, Parini C, Zandi M, Raveglia LF, Dondio G, Fontanella L, Misiano P, Bigogno C, Rizzi A, Riccardi B, Biscaioli M, Marchetti S, Puccini P, Catinella S, Rondelli I, Cenacchi V, Bolzoni PT, Caruso P, Villetti G, Facchinetti F, Del Giudice E, Moretto N, Imbimbo BP. Synthesis and biological activity of flurbiprofen analogues as selective inhibitors of beta-amyloid(1)(-)(42) secretion. J Med Chem. 2005 Sep 8;48(18):5705-20. doi: 10.1021/jm0502541.

    PMID: 16134939BACKGROUND

  • Imbimbo BP, Del Giudice E, Colavito D, D'Arrigo A, Dalle Carbonare M, Villetti G, Facchinetti F, Volta R, Pietrini V, Baroc MF, Serneels L, De Strooper B, Leon A. 1-(3',4'-Dichloro-2-fluoro[1,1'-biphenyl]-4-yl)-cyclopropanecarboxylic acid (CHF5074), a novel gamma-secretase modulator, reduces brain beta-amyloid pathology in a transgenic mouse model of Alzheimer's disease without causing peripheral toxicity. J Pharmacol Exp Ther. 2007 Dec;323(3):822-30. doi: 10.1124/jpet.107.129007. Epub 2007 Sep 25.

    PMID: 17895400BACKGROUND

  • Imbimbo BP, Del Giudice E, Cenacchi V, Volta R, Villetti G, Facchinetti F, Riccardi B, Puccini P, Moretto N, Grassi F, Ottonello S, Leon A. In vitro and in vivo profiling of CHF5022 and CHF5074 Two beta-amyloid1-42 lowering agents. Pharmacol Res. 2007 Apr;55(4):318-28. doi: 10.1016/j.phrs.2006.12.010. Epub 2007 Jan 16.

    PMID: 17292621BACKGROUND

  • Imbimbo BP, Hutter-Paier B, Villetti G, Facchinetti F, Cenacchi V, Volta R, Lanzillotta A, Pizzi M, Windisch M. CHF5074, a novel gamma-secretase modulator, attenuates brain beta-amyloid pathology and learning deficit in a mouse model of Alzheimer's disease. Br J Pharmacol. 2009 Mar;156(6):982-93. doi: 10.1111/j.1476-5381.2008.00097.x.

    PMID: 19239474BACKGROUND

  • Sisti R, Nyska A. CHF 5074: 4-week oral toxicity study in rats followed by a 4-week recovery period. RTC Study No. 71470. February 9, 2009.

    BACKGROUND

  • Grassetti A, Nyska A. CHF 5074. 4 week oral toxicity study in dogs followed by a 4 week recovery period. RTC Study No. 71470. February 4, 2009.

    BACKGROUND

  • Cinelli S, Oberto G. CHF 5074. Unscheduled DNA Synthesis (UDS) in primary rat hepatocytes after in vivo treatment (autoradiographic methods). RTC Study No. 70270. December 4, 2008.

    BACKGROUND

  • Ciliutti P, Oberto G. CHF 5074. Micronucleous test in rats. RTC Study No. 70260. November 28, 2008.

    BACKGROUND

MeSH Terms

Conditions

Alzheimer Disease

Interventions

1-(3',4'-dichloro-2-fluoro(1,1'-biphenyl)-4-yl)cyclopropanecarboxylic acid

Condition Hierarchy (Ancestors)

DementiaBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesTauopathiesNeurodegenerative DiseasesNeurocognitive DisordersMental Disorders

Study Officials

  • Joel S Ross, MD, FACP

    Iberica Clinical Research Center

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 31, 2009

First Posted

August 7, 2009

Study Start

October 1, 2009

Primary Completion

May 1, 2010

Study Completion

May 1, 2010

Last Updated

February 10, 2015

Record last verified: 2015-02

Locations

US(1)