Study of Dutogliptin in Combination With Filgrastim in Post-Myocardial Infarction
Study Details
Study Description
Brief Summary
A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Safety and Efficacy Study of Dutogliptin in Combination with Filgrastim in Early Recovery Post-Myocardial Infarction
Condition or Disease | Intervention/Treatment | Phase |
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Phase 2 |
Detailed Description
Dutogliptin 60 mg administered by twice daily subcutaneous (SC) injection for 14 days in combination with a fixed standard dose of filgrastim (10 µg/kg) administered SC daily for 5 days. This study will be conducted in adults with ST-elevation myocardial infarction (STEMI) with successful revascularization following percutaneous coronary intervention (PCI) and stent implantation.
Primary Objective
• To evaluate the safety and tolerability of dutogliptin in combination with filgrastim in subjects with STEMI compared with placebo
Secondary Objectives
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To assess preliminary efficacy of dutogliptin in combination with filgrastim in subjects with STEMI compared with placebo as determined by cardiac magnetic resonance imaging (cMRI)
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To determine the pharmacokinetics (PK) of dutogliptin in a subset of the study population
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To establish the pharmacodynamics (PD) of dutogliptin (plasma DPP4 activity) in a subset of the study population
Exploratory Objectives
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To examine the effects of dutogliptin in combination with filgrastim on:
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Change from baseline in plasma stromal cell-derived factor (SDF)-1a levels
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Change from baseline in plasma biomarkers, including N-terminal pro-b-type natriuretic peptide (NT-proBNP) and high sensitivity troponin
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Active Comparator: Dutogliptin/filgrastim combination Twice daily SC injections of 60 mg dutogliptin tartrate for 14 days in combination with 10 µg/kg filgrastim injectable product for 5 days |
Drug: Dutogliptin Tartrate
Active treatment
Other Names:
Drug: Filgrastim Injectable Product
Active treatment
Other Names:
|
Placebo Comparator: Placebo control Twice daily dutogliptin SC placebos for 14 days in combination with matching filgrastim SC placebos for 5 days |
Drug: Placebos
placebo control
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Safety assessment of the number of Grade 3 and 4 treatment emergent AEs or serious AEs (SAEs) as assessed by CTCAE v4.0.AEs (SAEs) as assessed by CTCAE v4.0. [90 days]
Assess the tolerability of a combination of dutogliptin and filgrastim
Secondary Outcome Measures
- Cardiovascular efficacy LVEF [90 days]
Left ventricular ejection fraction (%) by MRI
- Cardiovascular efficacy LVESV [90 days]
Left ventricular end systolic volume (mL) by MRI
- Cardiovascular efficacy LVEDV [90 days]
Left ventricular end diastolic volume (mL) by MRI
- Cardiovascular tissue damage reduction [90 days]
Infarct size (mm2)
- Cardiovascular LFM [90 days]
Left ventricular mass (mm2)
- Cardiovascular motion [90 days]
Regional wall motion (mm)
- Pharmacokinetics (PK) [14 days]
Assess the systemic exposure (dutogliptin AUC) of s.c. administered dutogliptin
- Pharmacodynamics (PD) [14 days]
Assess the PD effects (plasma DPP4 activity) of s.c. administered dutogliptin
Eligibility Criteria
Criteria
Inclusion Criteria:
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- Male or female born between 1933 and 2000.
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Body weight <96 kg (212 lb).
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Able to provide written informed consent, including signing and dating the informed consent form (ICF).
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Diagnosis of STEMI (defined as new ST-segment elevation at the J point of at least 2 continuous leads of >2 mm [0.2 mV] in men or >1.5 mm [0.1 mV] in women in leads V2 and V3 OR >1 mm in any other contiguous precordial leads or the limb leads [for both men and women]) with PCI (bare metal or drug-eluting stent) and Thrombolysis in Myocardial Infarction flow grade 2 or 3 occurring >2 hours and <24 hours after symptom onset.
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LVEF ≤45% obtained by cECHO performed within 36 hours post-stent placement.
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Receiving standard medical therapy for post-MI treatment, according to local procedures and Principal Investigator discretion
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Female subjects of childbearing potential must have a negative serum pregnancy test at Screening and an additional negative urine pregnancy test prior to the first dose of IMP unless regulated differently by national legislation.
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Sexually active female subjects of childbearing potential (i.e., women who are not postmenopausal or who have not had a bilateral oophorectomy, hysterectomy, or tubal ligation) and all male subjects (who have not been surgically sterilized by vasectomy) must agree to use effective contraception during the study.
Exclusion criteria
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Previous MI prior to Screening.
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Complex peri/post-MI clinical course, including arrhythmias, cardiogenic shock, pulmonary edema requiring mechanical ventilation, or requirement for vasopressor medications.
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Significant pre-existing cardiomyopathy with known LVEF ≤45% or moderate to severe mitral or aortic valvular disease.
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Amyloidosis, hypertrophic obstructive cardiomyopathy, restrictive cardiomyopathy, or constrictive pericarditis.
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Existing heart transplant.
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Ventricular tachycardia or fibrillation not associated with an acute ischemic episode.
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Uncontrolled hypertension (systolic >180 mmHg or diastolic >120 mmHg).
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Treatment with any DPP4 inhibitors (e.g., alogliptin, linagliptin, vildagliptin, saxagliptin, sitagliptin) or G-CSF medication (e.g., filgrastim, lenograstim, pegfilgrastim, lipegfilgrastim) within 4 months prior to Randomization.
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Contraindication to treatment with filgrastim, including known allergy to filgrastim or other G-CSF medication.
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Anemia defined as hemoglobin <9 g/dL prior to Randomization.
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Thrombocytosis (platelets >500 k/µL).
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Known positive serology for hepatitis B, hepatitis C, or human immunodeficiency virus (HIV).
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Alanine aminotransferase (ALT) concentrations >3 times the upper limit of normal (ULN) or bilirubin >2 x ULN prior to Randomization, according to local laboratory assessments.
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History of cirrhosis and Child-Pugh score B or C.
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Current fever greater than 101.4 °F (38.6 °C) or recent systemic infection within 2 weeks prior to Randomization.
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Contraindication to cMRI procedure, including prior implantable cardioverter defibrillator placement, known reaction to gadolinium, claustrophobia, non-MRI-compatible, cochlear implant, morbid obesity, or presence of ferromagnetic material including shunts, shrapnel, penile prostheses, or blood vessel coil.
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Pregnant, planning to become pregnant, or nursing female subjects.
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Autoimmune disease requiring immunosuppressive therapy or chronic steroid treatment >5 mg/day prednisolone or equivalent.
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Significant renal impairment defined as estimated glomerular filtration rate <45 mL/min/1.73 m2, using the Chronic Kidney Disease Epidemiology Collaboration equation.
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Active neoplasm requiring surgery, chemotherapy, or radiation within the prior 12 months (subjects with a history of malignancy who have undergone curative resection or otherwise not requiring treatment for at least 12 months prior to Screening with no detectable recurrence are allowed).
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Malignant hematological disease, i.e., chronic myeloid leukemia or myelodysplastic syndrome.
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History of cerebrovascular accident or transient ischemic attack in the past 6 months.
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History of pneumonia in the last 4 weeks.
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History of any significant medical or psychiatric disorder that in the opinion of the investigator would make the subject unsuitable for participation in the study.
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Treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) or treatment with an investigational biologic drug within 6 weeks prior to randomization.
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Participation in another concurrent clinical trial involving a therapeutic intervention (participation in observational studies and/or registry studies is permitted).
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Unable or unwilling to comply with the requirements of the study.
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Subject and/or an immediate family member is an employee of the investigational site directly affiliated with this study, the sponsor or the contract research organization.
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Considered by the investigator to be unsuitable to participate in the study for any other reason.
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Persons who are in an institution as a result of an administrative or judicial order, or soldiers.
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History of alcohol or drug abuse.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Clinical department of Cardiology | Graz | Austria | ||
2 | Klinikum Klagenfurt am Wörthersee | Klagenfurt | Austria | 9020 | |
3 | Algemeen Stedelijk Ziekenhuis Aalst | Aalst | Belgium | ||
4 | Military Hospital | Budapest | Hungary | ||
5 | Semmelweis Egyetem Városmajori Szív- és Érgyógyászati Klinika | Budapest | Hungary | ||
6 | Debreceni Egyetem Kardiológiai és Szívsebészeti Klinika | Debrecen | Hungary | ||
7 | Borsod-Abaúj-Zemplén Megyei Központi Kórház és Egyetemi Oktatókórház | Miskolc | Hungary | ||
8 | Maasstad Ziekenhuis | Rotterdam | Netherlands | ||
9 | Nicolaus Copernicus University | Bydgoszcz | Poland | ||
10 | SPS Szpital Zachodni | Grodzisk Mazowiecki | Poland | 05-825 | |
11 | Samodzielny Publiczny Szpital Wojewódzki im. Papieża Jana Pawła II | Zamość | Poland | ||
12 | Centralny Szpital Kliniczny Uniwersytetu Medycznego w Lodzi ul. Pomorska 251 | Łódź | Poland | 92-213 |
Sponsors and Collaborators
- Recardio, Inc.
Investigators
- Study Chair: Roman Schenk, MD, Recardio, Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- REC-DUT-002