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Eligible male and female subjects with renal impairment (aged 18-78 years) and healthy control subjects (aged 35 to 78 years) will be enrolled in the study. Subjects with renal impairment will be enrolled and entered into three groups based on their renal function: Mild Impairment, Moderate Impairment, and Severe Impairment(not requiring dialysis). Control subjects will have normal renal function.
The screening visits will occur within 14 days prior to plerixafor administration on study day one. Subjects will be monitored for 10 hours following administration of the study drug. In addition, subjects will return to the clinic at 24 and 48 hours after plerixafor administration for blood samples and safety assessments.
This is a phase I, open label, multi-center study in which up to eighteen subjects with renal impairment and six healthy control subjects with normal renal function will receive a single dose of plerixafor (240 µg/kg) administered by subcutaneous (SC) injection.
Eligible male and female subjects with renal impairment (aged 18-78 years) and healthy control subjects (aged in the upper age range of the renal impairment subjects) will be enrolled in the study. Subjects with renal impairment will be enrolled and stratified into three cohorts using their Screening 24 hour urine collection to measured creatinine clearance (CLcr) values (an estimate of Glomerular Filtration Rate): Mild Impairment (CLcr = 51-80 ml/min), Moderate Impairment (CLcr = 31-50 ml/min), and Severe Impairment (CLcr <31 ml/min, not requiring dialysis). Control subjects will have normal renal function (CLcr >90 ml/min), as determined by a Screening 24 hour urine collection.
The screening visits will occur within 14 days prior to plerixafor administration on study day one. Subjects will be monitored for 10 hours following administration of the study drug. In addition, subjects will return to the clinic at 24 and 48 hours after plerixafor administration for blood samples and safety assessments.
This study was previously posted by AnorMED, Inc. In November 2006, AnorMED, Inc. was acquired by Genzyme Corporation. Genzyme Corporation is the sponsor of the trial.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Normal renal function | Active Comparator | Participants with normal renal function (creatinine clearance (CLcr) > 90 ml/min) who serve as the study control. Participants treated with one dose of plerixafor (240 µg/kg) administered by subcutaneous (SC) injection. |
|
| Mild renal impairment | Experimental | Participants have mild renal impairment (creatinine clearance (CLcr) = 51 to 80 mL/min). Participants treated with one dose of plerixafor (240 µg/kg) administered by subcutaneous (SC) injection. |
|
| Moderate renal impairment | Experimental | Participants have moderate renal impairment (creatinine clearance (CLcr) = 31 to 50 mL/min). Participants treated with one dose of plerixafor (240 µg/kg) administered by subcutaneous (SC) injection. |
|
| Severe renal impairment | Experimental | Participants have severe renal impairment (creatinine clearance (CLcr) < 31 mL/min, not requiring dialysis). Participants treated with one dose of plerixafor (240 µg/kg) administered by subcutaneous (SC) injection. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| plerixafor | Drug | Single dose of plerixafor (240 µg/kg) administered by subcutaneous (SC) injection |
|
| Measure | Description | Time Frame |
|---|---|---|
| Dose-Normalized Maximum Concentration of Plerixafor (Cmax) | Evaluation of Cmax following a single dose of 240 µg/kg plerixafor administered on Day 1. Cmax was normalized by dose. | Pre-dose of plerixafor to 24 hours post-plerixafor |
| Dose-Normalized Area Under the Plerixafor Concentration Time Curve From Time 0 to 24 Hours Post-dose (AUC0-24h) | Evaluation of AUC0-24 hour following a single dose of 240 µg/kg plerixafor administered on Day 1. AUC0-24 was normalized by dose. | Pre-dose of plerixafor to 24 hours post-plerixafor |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Absolute CD34+ Cell Counts at Day 2 | Change in circulating CD34+ cells from baseline to Day 2 (24 hours post-plerixafor) following a single dose of plerixafor. Change from baseline = CD34+ cell count at 24 hours post dose - CD34+ cell count at Baseline. | Baseline, Day 2 |
| Change From Baseline in Absolute White Blood Cell (WBC) Counts at Day 2 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Monitor | Genzyme, a Sanofi Company | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Apex Research of Riverside | Santa Ana | California | 92705 | United States | ||
| Prism Research, 1000 Westgate Dr. suite 149 |
Cohort enrollment into the study was staged based on baseline creatinine clearance levels, with moderate renal impairment and control participants enrolled first. Severe renal impairment were enrolled following completion of the moderate renal impairment. Participants with mild renal impairment were enrolled last.
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| ID | Title | Description |
|---|---|---|
| FG000 | Normal Renal Function | Participants with normal renal function (creatinine clearance (CLcr) > 90 ml/min) used as a control. Participants treated with one dose of plerixafor (240 µg/kg) administered by subcutaneous (SC) injection. |
| FG001 | Mild Renal Impairment | Participants with mild renal impairment (CLcr = 51 to 80 mL/min). Participants treated with one dose of plerixafor (240 µg/kg) administered by subcutaneous (SC) injection. |
| FG002 | Moderate Renal Impairment | Participants with moderate renal impairment (CLcr = 31 to 50 mL/min). Participants treated with one dose of plerixafor (240 µg/kg) administered by subcutaneous (SC) injection. |
| FG003 | Severe Renal Impairment | Participants with severe renal impairment (CLcr < 31 mL/min, not requiring dialysis). Participants treated with one dose of plerixafor (240 µg/kg) administered by subcutaneous (SC) injection. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Normal Renal Function | Participants with normal renal function (creatinine clearance (CLcr) > 90 ml/min) used as a control. Participants treated with one dose of plerixafor (240 µg/kg) administered by subcutaneous (SC) injection. |
| BG001 | Mild Renal Impairment |
| 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 | Dose-Normalized Maximum Concentration of Plerixafor (Cmax) | Evaluation of Cmax following a single dose of 240 µg/kg plerixafor administered on Day 1. Cmax was normalized by dose. | Intent-to-treat population | Posted | Mean | Standard Deviation | ng/mL/ug | Pre-dose of plerixafor to 24 hours post-plerixafor |
|
From the time of the first dose of plerixafor to study Day 3 (study completion).
In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables.
Each AE table includes events, regardless of reported relationship to study treatment or grade.
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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 | Normal Renal Function | Participants with normal renal function (creatinine clearance (CLcr) > 90 ml/min) used as a control. Participants treated with one dose of plerixafor (240 µg/kg) administered by subcutaneous (SC) injection. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Leukocytosis | Blood and lymphatic system disorders | MedDRA 10.0 | Systematic Assessment | This event of leukocytosis reflects a white blood cell (WBC) count of 26.44*10^9/L. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Genzyme Medical Information | Genzyme Corporation | 1-800-745-4447 |
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| ID | Term |
|---|---|
| D051437 | Renal Insufficiency |
| ID | Term |
|---|---|
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
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| ID | Term |
|---|---|
| C088327 | plerixafor |
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|
Change in absolute white blood cells from baseline to Day 2 (24 hours post-plerixafor) following a single dose of plerixafor. Change from baseline = absolute white blood cells at 24 hours post dose - absolute white blood cells at Baseline. |
| Baseline and Day 2 |
| Number of Participants in Overall Safety Summary of Adverse Events (TEAE) | Number of participants with adverse events (AEs) collected from Day 1 (post plerixafor administration) to Day 3. AEs were graded by the investigator using the World Health Organization (WHO) Adverse Event Grading Scale and were assessed for severity (mild, moderate, severe, life-threatening) and relatedness to study treatment (5 point scale from 'not related' to 'definitely related'). | up to Day 3 |
| Saint Paul |
| Minnesota |
| 55114 |
| United States |
| Creighton University Medical Center | Omaha | Nebraska | 68131 | United States |
Participants with mild renal impairment (CLcr = 51 to 80 mL/min). Participants treated with one dose of plerixafor (240 µg/kg) administered by subcutaneous (SC) injection. |
| BG002 | Moderate Renal Impairment | Participants with moderate renal impairment (CLcr = 31 to 50 mL/min). Participants treated with one dose of plerixafor (240 µg/kg) administered by subcutaneous (SC) injection. |
| BG003 | Severe Renal Impairment | Participants with severe renal impairment (CLcr < 31 mL/min, not requiring dialysis). Participants treated with one dose of plerixafor (240 µg/kg) administered by subcutaneous (SC) injection. |
| BG004 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Number | participants |
|
| OG002 | Moderate Renal Impairment | Participants with moderate renal impairment (CLcr = 31 to 50 mL/min). Participants treated with one dose of plerixafor (240 µg/kg) administered by subcutaneous (SC) injection. |
| OG003 | Severe Renal Impairment | Participants with severe renal impairment (CLcr < 31 mL/min, not requiring dialysis). Participants treated with one dose of plerixafor (240 µg/kg) administered by subcutaneous (SC) injection. |
|
|
|
| Secondary | Change From Baseline in Absolute CD34+ Cell Counts at Day 2 | Change in circulating CD34+ cells from baseline to Day 2 (24 hours post-plerixafor) following a single dose of plerixafor. Change from baseline = CD34+ cell count at 24 hours post dose - CD34+ cell count at Baseline. | An intent-to-treat approach was used to calculate the outcome measure in each arm/group. | Posted | Mean | Standard Deviation | cells/mm^3 | Baseline, Day 2 |
|
|
|
| Secondary | Change From Baseline in Absolute White Blood Cell (WBC) Counts at Day 2 | Change in absolute white blood cells from baseline to Day 2 (24 hours post-plerixafor) following a single dose of plerixafor. Change from baseline = absolute white blood cells at 24 hours post dose - absolute white blood cells at Baseline. | An intent-to-treat approach was used to calculate the outcome measure in each arm/group. | Posted | Mean | Standard Deviation | cells/mm^3 | Baseline and Day 2 |
|
|
|
| Primary | Dose-Normalized Area Under the Plerixafor Concentration Time Curve From Time 0 to 24 Hours Post-dose (AUC0-24h) | Evaluation of AUC0-24 hour following a single dose of 240 µg/kg plerixafor administered on Day 1. AUC0-24 was normalized by dose. | Intent-to-treat population | Posted | Mean | Standard Deviation | hr*ng/mL/ug | Pre-dose of plerixafor to 24 hours post-plerixafor |
|
|
|
|
| Secondary | Number of Participants in Overall Safety Summary of Adverse Events (TEAE) | Number of participants with adverse events (AEs) collected from Day 1 (post plerixafor administration) to Day 3. AEs were graded by the investigator using the World Health Organization (WHO) Adverse Event Grading Scale and were assessed for severity (mild, moderate, severe, life-threatening) and relatedness to study treatment (5 point scale from 'not related' to 'definitely related'). | The safety analyses were performed on the Safety Population which consisted of all subjects who received plerixafor. | Posted | Number | participants | up to Day 3 |
|
|
|
| 0 |
| 6 |
| 4 |
| 6 |
| EG001 | Mild Renal Impairment | Participants with mild renal impairment (CLcr = 51 to 80 mL/min). Participants treated with one dose of plerixafor (240 µg/kg) administered by subcutaneous (SC) injection. | 0 | 6 | 4 | 6 |
| EG002 | Moderate Renal Impairment | Participants with moderate renal impairment (CLcr = 31 to 50 mL/min). Participants treated with one dose of plerixafor (240 µg/kg) administered by subcutaneous (SC) injection. | 0 | 5 | 2 | 5 |
| EG003 | Severe Renal Impairment | Participants with severe renal impairment (CLcr < 31 mL/min, not requiring dialysis). Participants treated with one dose of plerixafor (240 µg/kg) administered by subcutaneous (SC) injection. | 0 | 6 | 5 | 6 |
|
| Abdominal distension | Gastrointestinal disorders | MedDRA 10.0 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 10.0 | Systematic Assessment |
|
| Hypoaesthesia oral | Gastrointestinal disorders | MedDRA 10.0 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 10.0 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 10.0 | Systematic Assessment |
|
| Feeling hot | General disorders | MedDRA 10.0 | Systematic Assessment |
|
| Injection site bruising | General disorders | MedDRA 10.0 | Systematic Assessment |
|
| Injection site erythema | General disorders | MedDRA 10.0 | Systematic Assessment |
|
| Injection site rash | General disorders | MedDRA 10.0 | Systematic Assessment |
|
| Injection site reaction | General disorders | MedDRA 10.0 | Systematic Assessment |
|
| Red blood cells urine positive | Investigations | MedDRA 10.0 | Systematic Assessment |
|
| Urinary sediment present | Investigations | MedDRA 10.0 | Systematic Assessment |
|
| Urine analysis abnormal | Investigations | MedDRA 10.0 | Systematic Assessment |
|
| White blood cell count increased | Investigations | MedDRA 10.0 | Systematic Assessment |
|
| White blood cells urine positive | Investigations | MedDRA 10.0 | Systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 10.0 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 10.0 | Systematic Assessment |
|
| Dysgeusia | Nervous system disorders | MedDRA 10.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 10.0 | Systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MedDRA 10.0 | Systematic Assessment |
|
| Sinus headache | Nervous system disorders | MedDRA 10.0 | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA 10.0 | Systematic Assessment |
|
| Hyperventilation | Respiratory, thoracic and mediastinal disorders | MedDRA 10.0 | Systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MedDRA 10.0 | Systematic Assessment |
|
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA 10.0 | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 10.0 | Systematic Assessment |
|
| Flushing | Vascular disorders | MedDRA 10.0 | Systematic Assessment |
|
| Phlebitis | Vascular disorders | MedDRA 10.0 | Systematic Assessment |
|
In multi-site studies, PI can publish after Genzyme publishes or 12 months after study completion. PI gives Genzyme a draft 30 days before publication. Genzyme can ask that confidential information be removed, and can defer publication another 90 days upon notifying PI that it will file a patent application on inventions contained in the draft.
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| Ratio of least squares means (%) |
| 151.44 |
| 90 |
| 115.78 |
| 198.09 |
| No |
| Superiority or Other |
| Ratio of least squares means (%) | 169.51 | 90 | 129.59 | 221.72 | No | Superiority or Other |
| AE Severity (Moderate) |
|
| AE Severity (Severe) |
|
| AE Severity (Life Threatening) |
|
| AE Relationship to Drug (Definitely related) |
|
| AE Relationship to Drug (Probably related) |
|
| AE Relationship to Drug (Possibly related) |
|
| AE Relationship to Drug (Probably not related) |
|
| AE Relationship to Drug (Definitely not related) |
|