Healthy Volunteers
Conditions
Brief summary
The purpose of this study is to assess the bioavailability of Apixaban solution administered through NGT and washed with Dextrose 5% in water (D5W) or infant formula relative to Apixaban solution administered orally in healthy subjects
Interventions
DRUGApixaban
Sponsors
Pfizer
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
\- Healthy subjects as determined by no clinically significant deviation from normal in medical history, physical examination, ECGs, and clinical laboratory determinations
Exclusion criteria
* Any significant acute or chronic medical illness * Any history or evidence of abnormal bleeding or coagulation disorders, intracranial hemorrhage, or abnormal bleeding (including heavy menstrual bleeding that has resulted in anemia within the past 1 year) or coagulation disorders in a first degree relative
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adjusted Geometric Mean Maximum Observed Plasma Concentration (Cmax) of Apixaban | Day 1 (0 h, 0.25h, 0.50h, 1h, 2h, 3h, 4h, 5h, 6h, 9h, 12h, 24h, 36h, 48h, 60h, and 72h post dose) in Periods 1, 2 and 3 | Samples of plasma from participants were obtained at the following times: 0 hour (h) and post dose at 0.25h, 0.50h, 1h, 2h, 3h, 4h, 5h, 6h, 9h, 12h, 24h, 36h, 48h, 60h, and 72h. Apixaban was assayed using a validated Liquid chromatography tandem mass spectrometry (LC-MS/MS) method during the period of known analyte stability. Maximum observed plasma concentration (Cmax) was measured in nanograms per milliliter (ng/mL). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Median Time of Maximum Observed Plasma Concentration (Tmax) of Apixaban | Day 1 (0 h, 0.25h, 0.50h, 1h, 2h, 3h, 4h, 5h, 6h, 9h, 12h, 24h, 36h, 48h, 60h, and 72h post dose) in Periods 1, 2 and 3 | Samples of plasma from participants were obtained at the following times: 0 hour (h), 0.25h, 0.50h, 1h, 2h, 3h, 4h, 5h, 6h, 9h, 12h, 24h, 36h, 48h, 60h, and 72h, relative to the single dose on Day 1 in each cross over period. Apixaban was assayed using a validated LC-MS/MS method during the period of known analyte stability. Maximum observed plasma concentration (Tmax) was measured in hours (h). |
| Adjusted Geometric Mean Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of Last Quantifiable Plasma Concentration, AUC(0-T), of Apixaban | Day 1 (0 h, 0.25h, 0.50h, 1h, 2h, 3h, 4h, 5h, 6h, 9h, 12h, 24h, 36h, 48h, 60h, and 72h post dose) in Periods 1, 2 and 3 | Samples of plasma from participants were obtained at the following times: 0 h, 0.25h, 0.50h, 1h, 2h, 3h, 4h, 5h, 6h, 9h, 12h, 24h, 36h, 48h, 60h, and 72h, relative to the single dose on Day 1 in each cross over period. Apixaban was assayed using a validated LC-MS/MS method during the period of known analyte stability. AUC(0-T) was measured in nanograms\*hours per milliliter (ng\*h/mL). |
| Adjusted Geometric Mean Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time, AUC(INF), of Apixaban | Day 1 (0 h, 0.25h, 0.50h, 1h, 2h, 3h, 4h, 5h, 6h, 9h, 12h, 24h, 36h, 48h, 60h, and 72h post dose) in Periods 1, 2 and 3 | Samples of plasma from participants were obtained at the following times: 0 h, 0.25h, 0.50h, 1h, 2h, 3h, 4h, 5h, 6h, 9h, 12h, 24h, 36h, 48h, 60h, and 72h, relative to the single dose on Day 1 in each cross over period. Apixaban was assayed using a validated LC-MS/MS method during the period of known analyte stability. AUC(0-INF) was measured in ng\*h/mL. |
| Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuation Due to AEs, Death | Day 1 to Day 12 | AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. |
| Number of Participants With Clinically Significant Electrocardiogram, Vital Sign, or Physical Examination Findings | Screening, Day 1 of Periods, 1, 2, and 3, and Day 4 of Period 3 | 12-lead electrocardiograms (ECGs) and Vital Signs were performed at Screening, and Day 1 of Periods 1, 2 and 3 (pre-dose and prior to NGT placement, if done). Vital signs and ECGs were also performed on Day 4 of Period 3, prior to discharge from the study. Vital signs included body temperature, respiratory rate, seated blood pressure and heart rate. Blood pressure and heart rate were measured after the participant had been seated quietly for at least 5 minutes. Participants had physical examinations on Period 1, Day 1 (pre-dose) and Day 4 of Period 3, prior to study discharge. |
| Number of Participants With Marked Abnormality in Hematology, Chemistry and Urinalysis Laboratory Tests | Screening, Day -1, Day 4 of Periods, 1, 2, and 3 | Participants were required to fast for at least 10 hours prior to the collection of specimens for clinical laboratory tests. Tests were performed at Screening, Day -1, and Day 4 of each period 1 - 3. Leukocyte criteria: Lower limits of normal (LLN), upper limits of normal (ULN), pre-treatment (preRX). Low Leukocytes: if value \< 0.9\*LLN, or if preRX \< LLN then use \< 0.85\* preRX. High lymphocytes: if value \> 7.500 10\^3 cells/ µL. Low neutrophils plus bands: if value \<= 1.500 10\^3 cells/µL. High creatine kinase: if value \> 1.5\* ULN. Blood in urine: if value \>= 2 plus, or if preRX \>= 1 plus then use \>= 2\*preRX. |
| Mean Plasma Elimination Half-Life (T-HALF) of Apixaban | Day 1 (0 h, 0.25h, 0.50h, 1h, 2h, 3h, 4h, 5h, 6h, 9h, 12h, 24h, 36h, 48h, 60h, and 72h post dose) in Periods 1, 2 and 3 | Samples of plasma from participants were obtained at the following times: 0 h, 0.25h, 0.50h, 1h, 2h, 3h, 4h, 5h, 6h, 9h, 12h, 24h, 36h, 48h, 60h, and 72h, relative to the single dose on Day 1 in each cross over period. Apixaban was assayed using a validated LC-MS/MS method during the period of known analyte stability. T-HALF was measured in hours (h). |
Countries
United States
Participant flow
Recruitment details
Participants were admitted to the clinical facility on the evening prior to dosing (Day -1) and remained confined to the clinic for the duration of study.
Pre-assignment details
75 enrolled; 21 randomized; 21 treated. Of the 54 not treated: 47 no longer met study criteria, 1 not needed due to adequate number of participants, 3 withdrew consent, 1 died due to substance abuse, 1 no show, 1 discharged as alternate. Study was 3-treatment crossover administered over 3 periods. ≥4 days washout after doses in Periods 1 and 2.
Participants by arm
| Arm | Count |
|---|---|
| 5mg Apixaban After a 10 hour fast, participants were randomized to one of six treatment sequences (ABC, ACB, BAC, BCA, CAB or CBA) administered over 3 periods. Fasted participants received a single dose of apixaban 5 mg on Day 1 of Periods 1, 2, and 3. Treatment A was administered via oral syringe, Treatment B was administered via an NGT followed by 60 mL of D5W via an NGT, and Treatment C was administered via an NGT, followed by 60 mL of infant formula via an NGT. There was at least a 4 day washout before receiving the next scheduled treatment in the next period. | 21 |
| Total | 21 |
Baseline characteristics
| Characteristic | 5mg Apixaban |
|---|---|
| Age, Continuous | 33 years STANDARD_DEVIATION 6.7 |
| Region of Enrollment United States | 21 participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 21 | 4 / 21 | 3 / 21 |
| serious Total, serious adverse events | 0 / 21 | 0 / 21 | 0 / 21 |
Outcome results
Primary
Adjusted Geometric Mean Maximum Observed Plasma Concentration (Cmax) of Apixaban
Samples of plasma from participants were obtained at the following times: 0 hour (h) and post dose at 0.25h, 0.50h, 1h, 2h, 3h, 4h, 5h, 6h, 9h, 12h, 24h, 36h, 48h, 60h, and 72h. Apixaban was assayed using a validated Liquid chromatography tandem mass spectrometry (LC-MS/MS) method during the period of known analyte stability. Maximum observed plasma concentration (Cmax) was measured in nanograms per milliliter (ng/mL).
Time frame: Day 1 (0 h, 0.25h, 0.50h, 1h, 2h, 3h, 4h, 5h, 6h, 9h, 12h, 24h, 36h, 48h, 60h, and 72h post dose) in Periods 1, 2 and 3
Population: All participants who received study drug and had adequate PK profiles were included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| 5mg Apixaban Via Oral Syringe (A) | Adjusted Geometric Mean Maximum Observed Plasma Concentration (Cmax) of Apixaban | 190.873 ng/mL |
| 5mg Apixaban Via NGT Followed by D5W (B) | Adjusted Geometric Mean Maximum Observed Plasma Concentration (Cmax) of Apixaban | 181.862 ng/mL |
| 5 mg Apixaban Via NGT Followed by Infant Formula (C) | Adjusted Geometric Mean Maximum Observed Plasma Concentration (Cmax) of Apixaban | 153.693 ng/mL |
Comparison: B versus A90% CI: [0.873, 1.04]
Comparison: C versus A90% CI: [0.749, 0.865]
Secondary
Adjusted Geometric Mean Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time, AUC(INF), of Apixaban
Samples of plasma from participants were obtained at the following times: 0 h, 0.25h, 0.50h, 1h, 2h, 3h, 4h, 5h, 6h, 9h, 12h, 24h, 36h, 48h, 60h, and 72h, relative to the single dose on Day 1 in each cross over period. Apixaban was assayed using a validated LC-MS/MS method during the period of known analyte stability. AUC(0-INF) was measured in ng\*h/mL.
Time frame: Day 1 (0 h, 0.25h, 0.50h, 1h, 2h, 3h, 4h, 5h, 6h, 9h, 12h, 24h, 36h, 48h, 60h, and 72h post dose) in Periods 1, 2 and 3
Population: All participants who received study drug and had adequate PK profiles were included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| 5mg Apixaban Via Oral Syringe (A) | Adjusted Geometric Mean Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time, AUC(INF), of Apixaban | 1292.775 ng*h/mL |
| 5mg Apixaban Via NGT Followed by D5W (B) | Adjusted Geometric Mean Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time, AUC(INF), of Apixaban | 1250.913 ng*h/mL |
| 5 mg Apixaban Via NGT Followed by Infant Formula (C) | Adjusted Geometric Mean Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time, AUC(INF), of Apixaban | 1192.387 ng*h/mL |
Comparison: B versus A90% CI: [0.926, 1.011]
Comparison: C versus A90% CI: [0.899, 0.947]
Secondary
Adjusted Geometric Mean Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of Last Quantifiable Plasma Concentration, AUC(0-T), of Apixaban
Samples of plasma from participants were obtained at the following times: 0 h, 0.25h, 0.50h, 1h, 2h, 3h, 4h, 5h, 6h, 9h, 12h, 24h, 36h, 48h, 60h, and 72h, relative to the single dose on Day 1 in each cross over period. Apixaban was assayed using a validated LC-MS/MS method during the period of known analyte stability. AUC(0-T) was measured in nanograms\*hours per milliliter (ng\*h/mL).
Time frame: Day 1 (0 h, 0.25h, 0.50h, 1h, 2h, 3h, 4h, 5h, 6h, 9h, 12h, 24h, 36h, 48h, 60h, and 72h post dose) in Periods 1, 2 and 3
Population: All participants who received study drug and had adequate PK profiles were included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| 5mg Apixaban Via Oral Syringe (A) | Adjusted Geometric Mean Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of Last Quantifiable Plasma Concentration, AUC(0-T), of Apixaban | 1269.784 ng*h/mL |
| 5mg Apixaban Via NGT Followed by D5W (B) | Adjusted Geometric Mean Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of Last Quantifiable Plasma Concentration, AUC(0-T), of Apixaban | 1226.339 ng*h/mL |
| 5 mg Apixaban Via NGT Followed by Infant Formula (C) | Adjusted Geometric Mean Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of Last Quantifiable Plasma Concentration, AUC(0-T), of Apixaban | 1166.572 ng*h/mL |
Comparison: B versus A90% CI: [0.924, 1.01]
Comparison: C versus A90% CI: [0.896, 0.942]
Secondary
Mean Plasma Elimination Half-Life (T-HALF) of Apixaban
Samples of plasma from participants were obtained at the following times: 0 h, 0.25h, 0.50h, 1h, 2h, 3h, 4h, 5h, 6h, 9h, 12h, 24h, 36h, 48h, 60h, and 72h, relative to the single dose on Day 1 in each cross over period. Apixaban was assayed using a validated LC-MS/MS method during the period of known analyte stability. T-HALF was measured in hours (h).
Time frame: Day 1 (0 h, 0.25h, 0.50h, 1h, 2h, 3h, 4h, 5h, 6h, 9h, 12h, 24h, 36h, 48h, 60h, and 72h post dose) in Periods 1, 2 and 3
Population: All participants who received study drug and had adequate PK profiles were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 5mg Apixaban Via Oral Syringe (A) | Mean Plasma Elimination Half-Life (T-HALF) of Apixaban | 10.5 h | Standard Deviation 4.2 |
| 5mg Apixaban Via NGT Followed by D5W (B) | Mean Plasma Elimination Half-Life (T-HALF) of Apixaban | 10.4 h | Standard Deviation 4.5 |
| 5 mg Apixaban Via NGT Followed by Infant Formula (C) | Mean Plasma Elimination Half-Life (T-HALF) of Apixaban | 10.6 h | Standard Deviation 3.8 |
Secondary
Median Time of Maximum Observed Plasma Concentration (Tmax) of Apixaban
Samples of plasma from participants were obtained at the following times: 0 hour (h), 0.25h, 0.50h, 1h, 2h, 3h, 4h, 5h, 6h, 9h, 12h, 24h, 36h, 48h, 60h, and 72h, relative to the single dose on Day 1 in each cross over period. Apixaban was assayed using a validated LC-MS/MS method during the period of known analyte stability. Maximum observed plasma concentration (Tmax) was measured in hours (h).
Time frame: Day 1 (0 h, 0.25h, 0.50h, 1h, 2h, 3h, 4h, 5h, 6h, 9h, 12h, 24h, 36h, 48h, 60h, and 72h post dose) in Periods 1, 2 and 3
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 5mg Apixaban Via Oral Syringe (A) | Median Time of Maximum Observed Plasma Concentration (Tmax) of Apixaban | 0.517 h |
| 5mg Apixaban Via NGT Followed by D5W (B) | Median Time of Maximum Observed Plasma Concentration (Tmax) of Apixaban | 1.000 h |
| 5 mg Apixaban Via NGT Followed by Infant Formula (C) | Median Time of Maximum Observed Plasma Concentration (Tmax) of Apixaban | 1.00 h |
Secondary
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuation Due to AEs, Death
AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization.
Time frame: Day 1 to Day 12
Population: All participants who received study drug were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 5mg Apixaban Via Oral Syringe (A) | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuation Due to AEs, Death | Death | 0 participants |
| 5mg Apixaban Via Oral Syringe (A) | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuation Due to AEs, Death | Discontinuation Due to AE | 0 participants |
| 5mg Apixaban Via Oral Syringe (A) | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuation Due to AEs, Death | SAE | 0 participants |
| 5mg Apixaban Via Oral Syringe (A) | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuation Due to AEs, Death | Adverse Events | 2 participants |
| 5mg Apixaban Via NGT Followed by D5W (B) | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuation Due to AEs, Death | Discontinuation Due to AE | 0 participants |
| 5mg Apixaban Via NGT Followed by D5W (B) | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuation Due to AEs, Death | Death | 0 participants |
| 5mg Apixaban Via NGT Followed by D5W (B) | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuation Due to AEs, Death | SAE | 0 participants |
| 5mg Apixaban Via NGT Followed by D5W (B) | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuation Due to AEs, Death | Adverse Events | 4 participants |
| 5 mg Apixaban Via NGT Followed by Infant Formula (C) | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuation Due to AEs, Death | SAE | 0 participants |
| 5 mg Apixaban Via NGT Followed by Infant Formula (C) | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuation Due to AEs, Death | Discontinuation Due to AE | 0 participants |
| 5 mg Apixaban Via NGT Followed by Infant Formula (C) | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuation Due to AEs, Death | Adverse Events | 3 participants |
| 5 mg Apixaban Via NGT Followed by Infant Formula (C) | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuation Due to AEs, Death | Death | 0 participants |
Secondary
Number of Participants With Clinically Significant Electrocardiogram, Vital Sign, or Physical Examination Findings
12-lead electrocardiograms (ECGs) and Vital Signs were performed at Screening, and Day 1 of Periods 1, 2 and 3 (pre-dose and prior to NGT placement, if done). Vital signs and ECGs were also performed on Day 4 of Period 3, prior to discharge from the study. Vital signs included body temperature, respiratory rate, seated blood pressure and heart rate. Blood pressure and heart rate were measured after the participant had been seated quietly for at least 5 minutes. Participants had physical examinations on Period 1, Day 1 (pre-dose) and Day 4 of Period 3, prior to study discharge.
Time frame: Screening, Day 1 of Periods, 1, 2, and 3, and Day 4 of Period 3
Population: All participants who received study drug were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 5mg Apixaban Via Oral Syringe (A) | Number of Participants With Clinically Significant Electrocardiogram, Vital Sign, or Physical Examination Findings | Physical Examination | 0 participants |
| 5mg Apixaban Via Oral Syringe (A) | Number of Participants With Clinically Significant Electrocardiogram, Vital Sign, or Physical Examination Findings | Vital Signs | 0 participants |
| 5mg Apixaban Via Oral Syringe (A) | Number of Participants With Clinically Significant Electrocardiogram, Vital Sign, or Physical Examination Findings | ECG | 0 participants |
| 5mg Apixaban Via NGT Followed by D5W (B) | Number of Participants With Clinically Significant Electrocardiogram, Vital Sign, or Physical Examination Findings | Physical Examination | 0 participants |
| 5mg Apixaban Via NGT Followed by D5W (B) | Number of Participants With Clinically Significant Electrocardiogram, Vital Sign, or Physical Examination Findings | ECG | 0 participants |
| 5mg Apixaban Via NGT Followed by D5W (B) | Number of Participants With Clinically Significant Electrocardiogram, Vital Sign, or Physical Examination Findings | Vital Signs | 0 participants |
| 5 mg Apixaban Via NGT Followed by Infant Formula (C) | Number of Participants With Clinically Significant Electrocardiogram, Vital Sign, or Physical Examination Findings | Vital Signs | 0 participants |
| 5 mg Apixaban Via NGT Followed by Infant Formula (C) | Number of Participants With Clinically Significant Electrocardiogram, Vital Sign, or Physical Examination Findings | ECG | 0 participants |
| 5 mg Apixaban Via NGT Followed by Infant Formula (C) | Number of Participants With Clinically Significant Electrocardiogram, Vital Sign, or Physical Examination Findings | Physical Examination | 0 participants |
Secondary
Number of Participants With Marked Abnormality in Hematology, Chemistry and Urinalysis Laboratory Tests
Participants were required to fast for at least 10 hours prior to the collection of specimens for clinical laboratory tests. Tests were performed at Screening, Day -1, and Day 4 of each period 1 - 3. Leukocyte criteria: Lower limits of normal (LLN), upper limits of normal (ULN), pre-treatment (preRX). Low Leukocytes: if value \< 0.9\*LLN, or if preRX \< LLN then use \< 0.85\* preRX. High lymphocytes: if value \> 7.500 10\^3 cells/ µL. Low neutrophils plus bands: if value \<= 1.500 10\^3 cells/µL. High creatine kinase: if value \> 1.5\* ULN. Blood in urine: if value \>= 2 plus, or if preRX \>= 1 plus then use \>= 2\*preRX.
Time frame: Screening, Day -1, Day 4 of Periods, 1, 2, and 3
Population: Participants who received study drug were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 5mg Apixaban Via Oral Syringe (A) | Number of Participants With Marked Abnormality in Hematology, Chemistry and Urinalysis Laboratory Tests | Low Leukocytes | 1 participants |
| 5mg Apixaban Via Oral Syringe (A) | Number of Participants With Marked Abnormality in Hematology, Chemistry and Urinalysis Laboratory Tests | High Lymphocytes | 1 participants |
| 5mg Apixaban Via Oral Syringe (A) | Number of Participants With Marked Abnormality in Hematology, Chemistry and Urinalysis Laboratory Tests | Low Neutrophils plus bands | 5 participants |
| 5mg Apixaban Via Oral Syringe (A) | Number of Participants With Marked Abnormality in Hematology, Chemistry and Urinalysis Laboratory Tests | High Creatine Kinase | 1 participants |
| 5mg Apixaban Via Oral Syringe (A) | Number of Participants With Marked Abnormality in Hematology, Chemistry and Urinalysis Laboratory Tests | Blood in Urine | 1 participants |