Investigation of Safety, Pharmacokinetics and Pharmacodynamics of Different Doses of BIWH 3 in Patients With Chronic Critical Limb Ischaemia

Peripheral Arterial Disease Clinical Trial

— COINART-1  

Official title:

A Randomised, Double-blind, Placebo-controlled, Dose Escalation Study to Investigate Safety, Pharmacokinetics and Pharmacodynamics of Different Doses (0.2, 0.6, 2.0, 6.0, and 20.0 μg/hr) of BIWH 3 Administered for 6 Hours in Patients With Chronic Critical Limb Ischaemia (CLI, Fontaine Class III or IV). COINART-1 Trial (First COllateral INto ARTery Trial)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02215824
• Other study ID #: 1181.1
• Status: Terminated
• Phase: Phase 1
• First received: August 12, 2014
• Last updated: August 21, 2014
• Start date: October 2002

Study information

• Verified date: August 2014
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationNetherlands: Medicines Evaluation Board (MEB)Denmark: Danish Health and Medicines AuthoritySwitzerland: Swissmedic
• Study type: Interventional

Clinical Trial Summary

The primary aim of this trial was to investigate the safety of a 6 hour intraarterial infusion of BIWH 3 (pyro-Glu-rhMCP-1) in patients with severe peripheral arterial occlusive disease (PAOD) and chronic Critical Limb Ischaemia (Fontaine class III or IV).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 7
• Est. primary completion date: October 2003
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion:

• Patient must have severe PAOD with Chronic Critical Limb Ischaemia, Fontaine class III (ischaemic pain at rest) or IV (tissue ulceration or gangrene) due to atherosclerotic disease

• Patient must be >= 18 years of age

• Patient must give written informed consent

• Patient must have a life expectancy of at least six months

Exclusion:

• Transient ischaemic attack (TIA), cerebral vascular accident (CVA), myocardial infarction (MI) or episode of unstable angina within the past two months

• Ophthalmologic conditions: moderate to severe nonproliferative retinopathy, proliferative retinopathy, age related maculopathy with choroidal neovascularisation, macular edema, intraocular surgery within the previous 6 months, retinal vein occlusion

• Presence of a clinically significant disease which in the opinion of the investigator may either put the patient at risk because of participation in the study or a disease which may influence the result of the study or the patient's ability to participate in the study

• ECG results outside of the reference range of clinical relevance including, but not limited to QTcB > 480 msec, PR interval > 240 msec, QRS interval > 140 msec

• History of malignant disease, or a positive result on any of the required cancer screening tests, unless a definitive subsequent evaluation for cancer is determined to be negative

• Patients at increased risk of colorectal cancer, including any of the following (1) colorectal cancer pr polyps in a first-degree relative younger than 60 or in two first-degree relatives of any age, (2) family history of familial adenomatous polyposis or hereditary non-polyposis colon cancer, (3) history of adenomatous polyps, or (4) history of chronic inflammatory bowel disease (chronic ulcerative colitis or Crohn's disease)

• Abnormalities greater than two times the upper limit of normal in any of the following laboratory values at Visit 1: alanine-aminotransferase (ALT), aspartate-aminotransferase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase or lactic dehydrogenase (LDH); abnormalities greater than 1.5 times the upper limit of normal of total bilirubin or white blood cell count

• Any concurrent infectious disease requiring treatment

• Severe renal insufficiency (estimated creatinine clearance < 30 mL/min)

• Duffy antigen negative blood type with co-existing moderate to severe renal insufficiency (estimated creatinine clearance < 80 mL/min), to avoid potential risk of significant increase of monocyte chemoattractant protein-1 (MCP-1) levels

• Known glomerulonephritis, even if creatinine clearance is apparently normal

• Thrombocytopenia, i.e. platelet count <100,000 cells/µl at Visit 1

• History of drug or alcohol abuse within the past 2 two years or active drug or alcohol abuse, present alcohol intake more than three drinks per day

• Inability to comply with the protocol

• Treatment with an investigational drug within 30 days or 5 half-lives, whichever is greater before Visit 2

• Use of cilostazol if cilostazol therapy was started within 2 months prior to trial enrollment, or planned initiation of cilostazol therapy during the trial period. Patients who have been on cilostazol for > 2 months prior to enrollment may be enrolled

• Inability to discontinue the intake of coumadin until after completion of the treatment period. Patients who were on coumadin must have an international normalised ratio (INR) < 1.8 at Visit 2

• Previous enrollment in this trial

• Hypersensitivity or allergy to heparin, conventional angiographic contrast dye, or magnetic resonance angiography (MRA) contrast

• Inability to undergo MRA (e.g. heart pacemaker, artificial heart valve, implanted neurostimulator, intrauterine device (IUD), metallic ear implant, implanted port for delivering insulin, or other foreign or implanted or metallic objects such as bullet fragments, metal plates, pins, screws or staples, joint replacement, or penile implant)

• Know HIV-infection

• Unwillingness to take blood products

• Pregnancy (to be excluded by serum and urine beta-human chorionic gonadotropin-test in women of childbearing potential) or breast feeding

• Female of childbearing potential (not 12 months post-menopausal or surgically sterilized) not using one of the following methods of birth control: hormonal contraceptives, oral or injectable/implantable

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Peripheral Arterial Disease
• Peripheral Vascular Diseases

Intervention

Drug:
• BIWH 3

• Placebo

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of patients with adverse events		up to 180 days after drug administration	No
Primary	Number of patients with clinically relevant changes in vital signs (heart rate, blood pressure, body temperature)		baseline, up to 180 days after drug administration	No
Primary	Number of patients with clinically relevant changes in laboratory evaluations		baseline, up to 180 days after drug administration	No
Primary	Number of patients with clinically relevant changes in 12- lead electrocardiogram (ECG)		baseline, up to 180 days after drug administration	No
Primary	Number of patients with clinically relevant changes in markers of inflammation	measured by C-reactive Protein (CRP) and erythrocyte sedimentation rate (ESR)	baseline, up to 180 days after drug administration	No
Primary	Number of patients with clinically relevant changes in ophthalmic examinations		baseline, up to 180 days after drug administration	No
Primary	Number of patients with changes from baseline in progression of atherosclerosis	measured by carotid duplex imaging	day 180	No
Primary	Number of patients with changes in local disease defined by degree of stenosis	assessed by magnetic resonance angiography	up to 6 months post treatment	No
Primary	Number of patients with changes from baseline in result of cancer screening		day 180	No
Primary	Number of patients developing an antibody response to BIWH 3		baseline, up to 180 days	No
Secondary	Changes in transcutaneous oxygen pressure (tcPO2)		baseline, up to 180 days after drug administration	No
Secondary	Changes in lower extremity magnetic resonance angiography (MRA)		baseline, up to 180 days after drug administration	No
Secondary	Changes in ankle brachial or toe brachial index		baseline, up to 180 days after drug administration	No
Secondary	Occurence of amputations		up to 180 days after drug administration	No
Secondary	Progression of ulcer healing		up to 180 days after drug administration	No
Secondary	Changes from baseline on visual analogue scale assessment of pain at rest		up to 180 days after drug administration	No
Secondary	BIWH 3 plasma concentration		up to 180 days after drug administration	No
Secondary	Occurrence of Mac-1 positive staining monocytes		up to 180 days after drug administration	No

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