We updated the design of this site on September 25th. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 6 of 7 for:    CHF 5074

Safety, Pharmacokinetics and Pharmacodynamics Study of Treatment With CHF 5074 in Healthy Young Male Subjects (CT01)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00954252
First Posted: August 7, 2009
Last Update Posted: February 10, 2015
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
CERESPIR
  Purpose
The purpose of this study is to evaluate the safety and tolerability of single oral doses of CHF 5074 in young healthy male volunteers.

Condition Intervention Phase
Alzheimer's Disease Drug: CHF 5074 Drug: placebo Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Official Title: Placebo-Controlled, Ascending Single-Dose Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of CHF 5074 in Healthy Young Male Subjects

Resource links provided by NLM:


Further study details as provided by CERESPIR:

Primary Outcome Measures:
  • Adverse Events [ Time Frame: from Screening through Day +3 ]

Secondary Outcome Measures:
  • Dose linearity of CHF5074 plasma levels (Cmax and AUC0-t) [ Time Frame: Day -1 through Day +3 ]

Enrollment: 84
Study Start Date: October 2009
Study Completion Date: May 2010
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Test Article Drug: CHF 5074
1x, oral capsule, single dose
Drug: CHF 5074
2x, oral capsule, single dose
Drug: CHF 5074
4x, oral capsule, single dose
Drug: CHF 5074
8x, oral capsule, single dose
Drug: CHF 5074
16x, oral capsule, single dose
Drug: CHF 5074
24x, oral capsule, single dose
Placebo Comparator: Placebo Drug: placebo
placebo, oral capsule, single dose

Detailed Description:

The primary endpoint of the study is to determine the maximum tolerated dose (MTD) of CHF5074 after single oral administration to young healthy male volunteers.

The secondary objective of this study is to evaluate the pharmacokinetics of CHF5074 after single oral administration to young healthy male volunteers. The secondary endpoint of this study is to verify if CHF5074 plasma levels (Cmax and AUC0-t) increase proportionally with the dose (dose-linearity).

The exploratory objective of this study is to evaluate the pharmacodynamics of CHF5074 after single oral administration to young healthy male volunteers. The respective exploratory endpoint is to assess the relationship between individual maximum CHF5074 plasma concentrations and corresponding A-beta42 plasma concentrations corrected for baseline A-beta42 levels.

  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  • Subject has used any other over-the-counter drug within 1 week prior to study drug administration Occasional treatment with acetaminophen or aspirin is permitted but must be reported to the investigator. Vitamins are permitted.
  • Subject is positive on urine drug screening for drugs of abuse (cannabinoids, cocaine, opiates, amphetamines, barbiturates, benzodiazepines).
  • Subject has evidence of alcohol on screening blood work and breathalyzer test.
  • Subject does not agree to use a medically acceptable contraceptive (abstain from sexual intercourse, or use a condom with spermicide) for 7 days after study drug administration, or has not had a vasectomy at least 6 months prior to study participation.
  • Subject is unlikely to comply with the study protocol or unable to understand the nature and scope of the study or the possible benefits or unwanted effects of the study treatments.
  • Subject has participated in another investigational study within 30 days prior to screening.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00954252


Locations
United States, New Jersey
Iberica Clinical Research Center
Eatontown, NJ 07724, New Jersey, United States, 07724
Sponsors and Collaborators
CERESPIR
Investigators
Principal Investigator: Joel S Ross, MD, FACP Iberica Clinical Research Center
  More Information

Publications:
Lesné 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.
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.
Olson RE, Albright CF. Recent progress in the medicinal chemistry of gamma-secretase inhibitors. Curr Top Med Chem. 2008;8(1):17-33. Review.
Lleó A. Activity of gamma-secretase on substrates other than APP. Curr Top Med Chem. 2008;8(1):9-16. Review.
Lewis HD, Pérez 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.
Maillard I, Adler SH, Pear WS. Notch and the immune system. Immunity. 2003 Dec;19(6):781-91. Review.
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. Epub 2005 Aug 17.
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. Epub 2003 Aug 29.
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. Epub 2004 Jan 6.
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.
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.
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. Review.
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.
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. Epub 2007 Sep 25.
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. Epub 2007 Jan 16.
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.
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.
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.
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.
Ciliutti P, Oberto G. CHF 5074. Micronucleous test in rats. RTC Study No. 70260. November 28, 2008.

Responsible Party: CERESPIR
ClinicalTrials.gov Identifier: NCT00954252     History of Changes
Other Study ID Numbers: CCD-0814-PR-0008
First Submitted: July 31, 2009
First Posted: August 7, 2009
Last Update Posted: February 10, 2015
Last Verified: February 2015

Additional relevant MeSH terms:
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders


To Top