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The purpose of this study was to investigate the use of systemic intracoronary administration of albumin-bound paclitaxel, ABI-007, for the prevention and reduction of restenosis following de novo stenting or following angioplasty for in-stent restenosis.
This study consisted of a Phase I non-randomized dose escalation phase to determine the maximum tolerated dose and a randomized Phase II component to assess preliminary efficacy. Nanoparticle paclitaxel was administered by intracoronary catheter following either successful and uncomplicated stenting of de novo lesions in native coronary arteries or following successful and uncomplicated balloon angioplasty of instent restenosis (ISR) lesions.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 10 mg/m^2 nanoparticle paclitaxel | Experimental | Participants received a single dose of 10 mg/m^2 nanoparticle paclitaxel administered via intracoronary catheter immediately following percutaneous transluminal coronary angioplasty/stenting (de novo lesion) or balloon angioplasty (in-stent restenosis lesions). |
|
| 22 mg/m^2 nanoparticle paclitaxel | Experimental | Participants received a single dose of 22 mg/m^2 nanoparticle paclitaxel administered via intracoronary catheter immediately following percutaneous transluminal coronary angioplasty/stenting (de novo lesions) or balloon angioplasty (in-stent restenosis lesions). |
|
| 35 mg/m^2 nanoparticle paclitaxel | Experimental | Participants received a single dose of 35 mg/m^2 nanoparticle paclitaxel administered via intracoronary catheter immediately following percutaneous transluminal coronary angioplasty/stenting (de novo lesions) or balloon angioplasty (in-stent restenosis lesions). |
|
| 45 mg/m^2 nanoparticle paclitaxel | Experimental | Participants received a single dose of 45 mg/m^2 nanoparticle paclitaxel administered via intracoronary catheter immediately following percutaneous transluminal coronary angioplasty/stenting (de novo lesions) or balloon angioplasty (in-stent restenosis lesions). |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Nanoparticle Paclitaxel | Drug | Nanoparticle albumin-bound paclitaxel, administered via intracoronary catheter. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Phase I: Number of Participants With Dose-limiting Toxicities | Toxicities were evaluated based on the U.S. National Cancer Institute (NCI) Common Terminology Criteria (CTC) for Adverse Events version 3.0. Any drug-related toxicities considered CTC Grade 3 or 4 were considered dose limiting. The maximum tolerated dose was defined as the lesser of 45 mg/m^2 or the dose at which any drug related toxicities were observed. | Up to 1 week following percutaneous coronary intervention. |
| Number of Participants With Procedural Complications | Procedural complications include the following:
| From Day 0 - Day 1 (from study drug administration until 24 hours post-procedure). |
| Number of Participants With Treatment Emergent Adverse Events (AEs) | An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product. An SAE is any event that:
| Up to 6 months. |
| Number of Participants With Major Adverse Cardiac Events (MACE) at 1 Month | Major Adverse Cardiac Events (MACE) includes cardiac death, Coronary Artery Bypass Surgery, Myocardial Infarction, Target Vessel Revascularization (TVR) or Target Lesion Revascularization (TLR) and stent/vessel thrombotic occlusion. |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Binary Restenosis | Binary restenosis was assessed by quantitative coronary angiography and defined as >50% diameter stenosis within the stented region (In-stent) or the stented region plus 5 mm on either side of the stent (In-segment) at follow-up. Angiograms were centrally assessed by the Angiographic Core Laboratory. | 6 months |
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Inclusion Criteria:
Exclusion Criteria:
Target de novo lesion was treated with a drug-eluting stent
Target ISR lesion requires any treatment other than balloon angioplasty
Patient has both a de novo lesion and an ISR lesion.
If more than 2 lesions are treated with percutaneous coronary intervention (PCI), or it is anticipated that additional lesions will require treatment within 2 months.
Previous PCI within preceding two months.
Intended surgical intervention within 6 months of enrollment in the study.
Unprotected left main disease with >50% stenosis
Malapposition, dissection, or unmasking of a significant narrowing in the inflow or outflow area of the implanted stent.
Women who are pregnant and women of child bearing potential who do not use adequate contraception
Previous participation in another study with any investigational drug or device within the past 30 days or current enrollment in any other clinical protocol or investigational drug or device trial.
Patient has a life expectancy of less than 12 months or there are factors making clinical and/or angiographic follow-up difficult
Any significant medical condition which, in the investigator's opinion, may interfere with the patient's optimal participation in the study
Heart transplant candidate or recipient
Patient is immunosuppressed or is HIV positive.
Patient has experienced a Q wave or a non Q wave myocardial infarction (MI) with documented total creatine kinase (CK) ≥2 times normal within the preceding 24 hours and the CK and creatine kinase-MB fraction (CK-MB) enzymes remain above normal at the time of the procedure.
Cardiogenic shock: sustained systolic blood pressure (SBP) less than 80 mmHg, with no response to fluids or SBP less than 100 mmHg with vasopressors (in absence of bradycardia)
Any individual who may refuse a blood transfusion
Documented major gastro-intestinal bleeding within 3 months
The following lab values at baseline are exclusionary:
Known allergy/hypersensitivity/contraindication to the study drug; to any taxanes; or to any required study treatment: aspirin, clopidogrel bisulfate, stent materials
Pre-existing peripheral neuropathy of National Cancer Institute (NCI) Toxicity Grade > 1.
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| Name | Affiliation | Role |
|---|---|---|
| Jose' Iglesias, MD | Celgene Corporation | Study Director |
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122 patients were randomized into the study and 112 received study medication.
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| ID | Title | Description |
|---|---|---|
| FG000 | 10 mg/m^2 Nanoparticle Paclitaxel | Participants received a single dose of 10 mg/m^2 nanoparticle paclitaxel administered via intracoronary catheter immediately following percutaneous transluminal coronary angioplasty/stenting (de novo lesion) or balloon angioplasty (in-stent restenosis lesions). |
| FG001 | 22 mg/m^2 Nanoparticle Paclitaxel | Participants received a single dose of 22 mg/m^2 nanoparticle paclitaxel administered via intracoronary catheter immediately following percutaneous transluminal coronary angioplasty/stenting (de novo lesions) or balloon angioplasty (in-stent restenosis lesions). |
| FG002 | 35 mg/m^2 Nanoparticle Paclitaxel | Participants received a single dose of 35 mg/m^2 nanoparticle paclitaxel administered via intracoronary catheter immediately following percutaneous transluminal coronary angioplasty/stenting (de novo lesions) or balloon angioplasty (in-stent restenosis lesions). |
| FG003 | 45 mg/m^2 Nanoparticle Paclitaxel | Participants received a single dose of 45 mg/m^2 nanoparticle paclitaxel administered via intracoronary catheter immediately following percutaneous transluminal coronary angioplasty/stenting (de novo lesions) or balloon angioplasty (in-stent restenosis lesions). |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Phase I |
| |||||||||||||
| Phase II |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 10 mg/m^2 Nanoparticle Paclitaxel | Participants received a single dose of 10 mg/m^2 nanoparticle paclitaxel administered via intracoronary catheter immediately following percutaneous transluminal coronary angioplasty/stenting (de novo lesion) or balloon angioplasty (in-stent restenosis lesions). |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Phase I: Number of Participants With Dose-limiting Toxicities | Toxicities were evaluated based on the U.S. National Cancer Institute (NCI) Common Terminology Criteria (CTC) for Adverse Events version 3.0. Any drug-related toxicities considered CTC Grade 3 or 4 were considered dose limiting. The maximum tolerated dose was defined as the lesser of 45 mg/m^2 or the dose at which any drug related toxicities were observed. | Phase I treated population. | Posted | Number | participants | Up to 1 week following percutaneous coronary intervention. |
|
Up to 6 months.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 10 mg/m^2 Nanoparticle Paclitaxel | Participants received a single dose of 10 mg/m^2 nanoparticle paclitaxel administered via intracoronary catheter immediately following percutaneous transluminal coronary angioplasty/stenting (de novo lesion) or balloon angioplasty (in-stent restenosis lesions). |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| In-stent coronary artery restenosis | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Aspartate aminotransferase increased | Investigations | MedDRA | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Associate Director, Clinical Trials Disclosure | Celgene Corporation | 1-888-260-1599 | clinicaltrialdisclosure@celgene.com |
| ID | Term |
|---|---|
| D023903 | Coronary Restenosis |
| ID | Term |
|---|---|
| D023921 | Coronary Stenosis |
| D003327 | Coronary Disease |
| D017202 | Myocardial Ischemia |
| D006331 | Heart Diseases |
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| ID | Term |
|---|---|
| D013660 | Taxes |
| D000068196 | Albumin-Bound Paclitaxel |
| ID | Term |
|---|---|
| D004467 | Economics |
| D004472 | Health Care Economics and Organizations |
| D017239 | Paclitaxel |
| D043823 | Taxoids |
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|
| From the day of Percutaneous Coronary Intervention to 1 Month. |
| Number of Participants With Major Adverse Cardiac Events (MACE) at 6 Months | Major Adverse Cardiac Events (MACE) includes cardiac death, Coronary Artery Bypass Surgery, Myocardial Infarction, Target Vessel Revascularization (TVR) or Target Lesion Revascularization (TLR) and stent/vessel thrombotic occlusion. | From the day of Percutaneous Coronary Intervention to Month 6. |
| Late Lumen Loss | Late lumen loss represents the extent of neointimal hyperplasia within the stented region (In-stent) or the stented region plus 5 mm on either side of the stent (In-segment) and was measured by quantitative coronary angiography. Late Loss = Minimum Lumen Diameter (MLD) Post Procedure minus the MLD at Follow-up. | Day 0 (post-procedure baseline) and 6 months. |
| Percentage of In-Stent Volume Obstruction at 6 Months | In-stent volume obstruction at 6 months was measured by intra-vascular ultrasound (IVUS) and centrally assessed by the IVUS Core Laboratory. Percent in-stent volume obstruction was calculated as neointimal volume / stent volume * 100. | 6 months |
| COMPLETED |
|
| NOT COMPLETED |
|
|
| 22 mg/m^2 Nanoparticle Paclitaxel |
Participants received a single dose of 22 mg/m^2 nanoparticle paclitaxel administered via intracoronary catheter immediately following percutaneous transluminal coronary angioplasty/stenting (de novo lesions) or balloon angioplasty (in-stent restenosis lesions). |
| BG002 | 35 mg/m^2 Nanoparticle Paclitaxel | Participants received a single dose of 35 mg/m^2 nanoparticle paclitaxel administered via intracoronary catheter immediately following percutaneous transluminal coronary angioplasty/stenting (de novo lesions) or balloon angioplasty (in-stent restenosis lesions). |
| BG003 | 45 mg/m^2 Nanoparticle Paclitaxel | Participants received a single dose of 45 mg/m^2 nanoparticle paclitaxel administered via intracoronary catheter immediately following percutaneous transluminal coronary angioplasty/stenting (de novo lesions) or balloon angioplasty (in-stent restenosis lesions). |
| BG004 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Number | participants |
|
| Weight | Mean | Standard Deviation | kg |
|
| Lesion type | Number | participants |
|
| Diabetes mellitis | Number | participants |
|
| Minimum Lumen Diameter | Participant population = 3, 47, 3, 50 (103 total). Measures were obtained from the angiographic evaluation. | Mean | Standard Deviation | mm |
|
| Reference Diameter | Participant population = 3, 50, 3, 54 (110 total). Measures were obtained from the angiographic evaluation. | Mean | Standard Deviation | mm |
|
| Lesion Length | Participant population = 3, 50, 3, 54 (110 total). Measures were obtained from the angiographic evaluation. | Mean | Standard Deviation | mm |
|
| Diameter Stenosis | Participant population = 3, 51, 3, 54 (111 total). Measures were obtained from the angiographic evaluation. | Mean | Standard Deviation | % diameter stenosis |
|
| OG001 | 22 mg/m^2 Nanoparticle Paclitaxel | Participants received a single dose of 22 mg/m^2 nanoparticle paclitaxel administered via intracoronary catheter immediately following percutaneous transluminal coronary angioplasty/stenting (de novo lesions) or balloon angioplasty (in-stent restenosis lesions). |
| OG002 | 35 mg/m^2 Nanoparticle Paclitaxel | Participants received a single dose of 35 mg/m^2 nanoparticle paclitaxel administered via intracoronary catheter immediately following percutaneous transluminal coronary angioplasty/stenting (de novo lesions) or balloon angioplasty (in-stent restenosis lesions). |
| OG003 | 45 mg/m^2 Nanoparticle Paclitaxel | Participants received a single dose of 45 mg/m^2 nanoparticle paclitaxel administered via intracoronary catheter immediately following percutaneous transluminal coronary angioplasty/stenting (de novo lesions) or balloon angioplasty (in-stent restenosis lesions). |
|
|
| Primary | Number of Participants With Procedural Complications | Procedural complications include the following:
| Treated population. | Posted | Number | participants | From Day 0 - Day 1 (from study drug administration until 24 hours post-procedure). |
|
|
|
|
| Primary | Number of Participants With Treatment Emergent Adverse Events (AEs) | An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product. An SAE is any event that:
| Treated population. | Posted | Number | participants | Up to 6 months. |
|
|
|
|
| Secondary | Percentage of Participants With Binary Restenosis | Binary restenosis was assessed by quantitative coronary angiography and defined as >50% diameter stenosis within the stented region (In-stent) or the stented region plus 5 mm on either side of the stent (In-segment) at follow-up. Angiograms were centrally assessed by the Angiographic Core Laboratory. | Treated Population. | Posted | Number | percentage of participants | 6 months |
|
|
|
|
| Primary | Number of Participants With Major Adverse Cardiac Events (MACE) at 1 Month | Major Adverse Cardiac Events (MACE) includes cardiac death, Coronary Artery Bypass Surgery, Myocardial Infarction, Target Vessel Revascularization (TVR) or Target Lesion Revascularization (TLR) and stent/vessel thrombotic occlusion. | Treated population. | Posted | Number | participants | From the day of Percutaneous Coronary Intervention to 1 Month. |
|
|
|
|
| Primary | Number of Participants With Major Adverse Cardiac Events (MACE) at 6 Months | Major Adverse Cardiac Events (MACE) includes cardiac death, Coronary Artery Bypass Surgery, Myocardial Infarction, Target Vessel Revascularization (TVR) or Target Lesion Revascularization (TLR) and stent/vessel thrombotic occlusion. | Treated population. | Posted | Number | participants | From the day of Percutaneous Coronary Intervention to Month 6. |
|
|
|
|
| Secondary | Late Lumen Loss | Late lumen loss represents the extent of neointimal hyperplasia within the stented region (In-stent) or the stented region plus 5 mm on either side of the stent (In-segment) and was measured by quantitative coronary angiography. Late Loss = Minimum Lumen Diameter (MLD) Post Procedure minus the MLD at Follow-up. | Treated population for whom data was available (indicated by "n"). | Posted | Mean | Standard Deviation | mm | Day 0 (post-procedure baseline) and 6 months. |
|
|
|
|
| Secondary | Percentage of In-Stent Volume Obstruction at 6 Months | In-stent volume obstruction at 6 months was measured by intra-vascular ultrasound (IVUS) and centrally assessed by the IVUS Core Laboratory. Percent in-stent volume obstruction was calculated as neointimal volume / stent volume * 100. | Treated population for whom data was available. | Posted | Mean | Standard Deviation | Percentage of obstruction | 6 months |
|
|
|
|
| 0 |
| 3 |
| 3 |
| 3 |
| EG001 | 22 mg/m^2 Nanoparticle Paclitaxel | Participants received a single dose of 22 mg/m^2 nanoparticle paclitaxel administered via intracoronary catheter immediately following percutaneous transluminal coronary angioplasty/stenting (de novo lesions) or balloon angioplasty (in-stent restenosis lesions). | 14 | 51 | 34 | 51 |
| EG002 | 35 mg/m^2 Nanoparticle Paclitaxel | Participants received a single dose of 35 mg/m^2 nanoparticle paclitaxel administered via intracoronary catheter immediately following percutaneous transluminal coronary angioplasty/stenting (de novo lesions) or balloon angioplasty (in-stent restenosis lesions). | 0 | 3 | 3 | 3 |
| EG003 | 45 mg/m^2 Nanoparticle Paclitaxel | Participants received a single dose of 45 mg/m^2 nanoparticle paclitaxel administered via intracoronary catheter immediately following percutaneous transluminal coronary angioplasty/stenting (de novo lesions) or balloon angioplasty (in-stent restenosis lesions). | 18 | 55 | 31 | 55 |
| Coronary artery restenosis | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
|
| Thoracic vertebral fracture | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
|
| Myocardial infarction | Cardiac disorders | MedDRA | Systematic Assessment |
|
| Angina pectoris | Cardiac disorders | MedDRA | Systematic Assessment |
|
| Bradycardia | Cardiac disorders | MedDRA | Systematic Assessment |
|
| Chest pain | General disorders | MedDRA | Systematic Assessment |
|
| Chest discomfort | General disorders | MedDRA | Systematic Assessment |
|
| Arterial disorder | Vascular disorders | MedDRA | Systematic Assessment |
|
| Arterial restenosis | Vascular disorders | MedDRA | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Coronary angioplasty | Surgical and medical procedures | MedDRA | Systematic Assessment |
|
| Blood creatine phosphokinase MB increased | Investigations | MedDRA | Systematic Assessment |
|
| Troponin T increased | Investigations | MedDRA | Systematic Assessment |
|
| Blood creatine phosphokinase increased | Investigations | MedDRA | Systematic Assessment |
|
| Electrocardiogram ST-T change | Investigations | MedDRA | Systematic Assessment |
|
| White blood cell count decreased | Investigations | MedDRA | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA | Systematic Assessment |
|
| Troponin increased | Investigations | MedDRA | Systematic Assessment |
|
| Chest discomfort | General disorders | MedDRA | Systematic Assessment |
|
| Chest pain | General disorders | MedDRA | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA | Systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Presyncope | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Vision blurred | Eye disorders | MedDRA | Systematic Assessment |
|
| Abdominal discomfort | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
|
| Haematoma | Vascular disorders | MedDRA | Systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA | Systematic Assessment |
|
| Angina pectoris | Cardiac disorders | MedDRA | Systematic Assessment |
|
| Contusion | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
|
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA | Systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
|
| D002318 |
| Cardiovascular Diseases |
| D014652 | Vascular Diseases |
| D043822 |
| Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D004224 | Diterpenes |
| D013729 | Terpenes |
| D000418 | Albumins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| Patients with at Least 1 Serious AE |
|
| In-segment |
|
| Fisher Exact |
| 0.400 |
| 95 |
| No |
| Superiority or Other |
| In-segment [n=3, 47, 3, 50] |
|
| Fisher Exact |
| 0.495 |
| 95 |
| No |
| Superiority or Other |