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Darusentan Effect on PET Uptake Heterogeneity (Darusentan)

25. juli 2014 opdateret af: K.Lance Gould

A Phase 2, Investigator-Initiated, Feasibility Study to Evaluate the Mechanisms of Coronary Endothelial Dysfunction Imaged As Resting Myocardial Perfusion Heterogeneity After Endothelin Receptor Blockade With Darusentan

The primary objective of this study is to test the hypothesis that myocardial perfusion heterogeneity, quantified by Markovian Homogeneity analysis of cardiac PET perfusion images, will improve in a quantitative manner after treatment with selective ETA receptor antagonist darusentan 100 mg per day for 2 weeks compared to baseline and post-treatment PET scans in clinically stable subjects with coronary atherosclerosis and/or risk factors.

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

This 6-week, Phase 2, randomized, double-blind, crossover, investigator-initiated, single-center study will determine the feasibility of detecting the effect of darusentan 100 mg once daily on the extent of myocardial perfusion heterogeneity in subjects with documented CAD, as measured by cardiac PET imaging. Prior to the initiation of any study procedures, an Informed Consent Form and HIPAA Authorization will be reviewed and signed by each subject. Screening assessments and evaluations may be conducted over a period of not more than 4 weeks.

Following a baseline PET scan (PET 1) subjects will be randomized to one of two treatment groups (Group 1 or Group 2), and receive blinded treatment for a total of 4 weeks. The 4-week treatment period will have two phases, Phase 1 and Phase 2. Group 1 will receive darusentan 100 mg for 2 weeks during Phase 1, then placebo for 2 weeks during Phase 2. Group 2 will receive placebo for 2 weeks during Phase 1, then darusentan 100 mg for 2 weeks during Phase 2. Following 4 weeks of treatment with blinded study drug, subjects in both treatment groups will be withdrawn from study drug for an additional 2 weeks. Maximum darusentan exposure in this study will be 2 weeks, and maximum placebo exposure in this study will be 2 weeks. Adjustments to the number or dosage of concomitant medications required for study entry will not be permitted at any time during the study.

A physical exam will be done at baseline and week 6 as well as blood chemistry and hematology samples taken. Vital signs and any adverse events will be monitored at each visit.

Efficacy will be assessed through cardiac PET imaging. In total, four PET scans will be administered: the first at the Randomization Visit (PET 1, Week 0); the second at the conclusion of Phase 1 (PET 2, Week 2); the third at the conclusion of Phase 2 (PET 3, Week 4) and the fourth at the conclusion of the Withdrawal period (PET 4, Week 6).

Subjects will be instructed to take their study drug with or without food once daily at approximately the same time in the morning throughout the course of the study. Subjects will also be instructed to take all concomitant medications consistently and at the same time each day throughout the study.

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

40

Fase

  • Fase 2

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

  • Forenede Stater
    • Texas
      • Houston, Texas, Forenede Stater, 77030
        • Weatherhead PET Center for Preventing and Reversing Atherosclerosis, UT Medical School, Memorial Hermann Hospital

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år og ældre (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

Inclusion Criteria:

  1. Subjects must be competent to provide written informed consent. Subjects must sign an IRB approved ICF and HIPAA Authorization prior to the initiation of any study procedures. All men must be informed of the potential risks of testicular tubular atrophy and infertility associated with taking study drug, and queried regarding their understanding of the potential risks as described in the ICF.
  2. Subjects must be greater than 18 years of age.
  3. Female subjects must be surgically sterile or documented as post-menopausal for at least 2 years.
  4. Subjects must have documented coronary artery disease as evidenced by previous myocardial infarction, interventional procedure, significant stenosis by cardiac catheterization, or an abnormal perfusion study.
  5. Subjects must have an abnormal PET scan.

Exclusion Criteria:

  1. Subjects with acute heart failure
  2. Subjects with sustained or symptomatic hypotension (SBP 90 mmHg)
  3. Subjects with uncontrolled hypertension (SBP of 170 mmHg or DBP of 100 mmHg) at Screening
  4. Subjects with unstable angina pectoris
  5. Subjects with acute myocardial infarction, stroke, transient ischemic attack, or coronary angioplasty within the last 6 months
  6. Subjects with primary valvular disease
  7. Subjects with significant vascular aneurysm
  8. Subjects with a documented history of renal failure
  9. Subjects with liver disease (total bilirubin 3 mg/dL or serum ALT or AST >2X ULN)
  10. Subjects with active malignancy
  11. Subjects with a fatal non-cardiovascular disease that they are expected to succumb to within 1 year
  12. Female subjects that are pregnant or lactating
  13. Female subjects with the potential for child-bearing
  14. Female subjects being treated with hormone therapies
  15. Subjects with uncontrolled diabetes mellitus
  16. Subjects with diabetes with gastro paresis or severe neuropathy
  17. Subjects with a history of substance abuse within the last 2 years
  18. Subjects who have participated in a clinical study involving another investigational drug or device within 1 month of the Screening Visit
  19. Subjects with known hypersensitivity or allergy to L-arginine, aminophylline, adenosine, or dipyridamole
  20. Subjects who have a planned surgical procedure during the course of the study
  21. Subjects taking herbal food supplements (L-carnitine, L-arginine or Ginko biloba)
  22. Subjects with known active or dormant type 2 herpes simplex virus infections
  23. Subjects with a contraindication to treatment with an ERA. Contraindications may include, but are not limited to, evidence of elevated liver function tests (e.g., aminotransferases >2X ULN) or an event defined as a serious adverse event attributed to previous treatment with an ERA
  24. Subjects who are judged by the investigator to be ineligible for this study for any other reason

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: Randomiseret
  • Interventionel model: Crossover opgave
  • Maskning: Dobbelt

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Aktiv komparator: Group 1
Group 1 will receive oral darusentan 100mg for 2 weeks during Phase 1 then placebo for 2 weeks during Phase 2.
Medicin: darusentan 100 mg
All subjects will receive oral darusentan 100 mg for a total of 2 weeks and placebo for 2 weeks.
Andre navne:
  • darusentan
  • CID 177236
  • LU-135252
  • HMR-4005
  • 171714-84-4
Aktiv komparator: Group 2
Group 2 will receive placebo for 2 weeks during Phase 1 then oral darusentan 100 mg for two weeks during Phase 2
Medicin: darusentan 100 mg
All subjects will receive oral darusentan 100 mg for a total of 2 weeks and placebo for 2 weeks.
Andre navne:
  • darusentan
  • CID 177236
  • LU-135252
  • HMR-4005
  • 171714-84-4

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Change During Darusentan Treatment in the Markovian Homogeneity Number, a Value That Quantitates Myocardial Perfusion Heterogeneity
Tidsramme: 0, 2, 4, and 6 weeks
Markovian homogeneity analysis characterizes an image produced by a PET scan by examining the probability that a pixel with a given intensity will have a neighbor with a different intensity. The homogeneity index ranges from >0 to 1, where a value near 0 represents an image with a high probability that neighboring pixels have intensity values that differ greatly, and a value near 1 represents an image with a high probability that neighboring pixels have similar intensity values.
0, 2, 4, and 6 weeks

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Change During Darusentan Treatment in Absolute Flow at Rest and Hyperemia
Tidsramme: 0, 2, 4, and 6 weeks
0, 2, 4, and 6 weeks
Change During Darusentan Treatment in the Coronary Flow Reserve (CFR)
Tidsramme: 0, 2, 4, and 6 weeks
CFR is calculated as the unitless ratio between hyperemic to resting flow
0, 2, 4, and 6 weeks

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

K.Lance Gould

Samarbejdspartnere

Gilead Sciences

Efterforskere

  • Ledende efterforsker: K Lance Gould, MD, University of Texas Medical School at Houston
  • Ledende efterforsker: Nils Johnson, MD, University of Texas Medical School at Houston

Publikationer og nyttige links

Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.

Generelle publikationer

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart

1. juni 2009

Primær færdiggørelse (Faktiske)

1. august 2011

Studieafslutning (Faktiske)

1. august 2011

Datoer for studieregistrering

Først indsendt

19. august 2008

Først indsendt, der opfyldte QC-kriterier

19. august 2008

Først opslået (Skøn)

20. august 2008

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Skøn)

15. august 2014

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

25. juli 2014

Sidst verificeret

1. juli 2014

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • HSC-MS-08-0380

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

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