Effect of Food on the Pharmacokinetics of Single Oral Dose Administration of a Fixed-Dose Combination of SYR-322 and Metformin Hydrochloride in Healthy Adult Male Subjects

Study Overview
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Brief Summary
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This is a randomized, open-label, crossover study to determine the effect of food when a combination tablet of SYR-322 and metformin hydrochloride ( hereinafter referred to as SYR-322-MET tablet) is orally administered under fasting conditions in the morning or after breakfast in Japanese healthy adult male subjects.

Detailed Description
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The primary objective of this clinical trial is to determine the effect of food on the pharmacokinetics of single oral dose administration of SYR-322-MET tablets in Japanese healthy adult male subjects

Official Title
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A Randomized, Open-label, Crossover Study to Determine the Effect of Food on the Pharmacokinetics of Single Oral Dose Administration of a Fixed-Dose Combination of SYR-322 and Metformin Hydrochloride in Healthy Adult Male Subjects

Conditions
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Clinical Pharmacology

Intervention / Treatment
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* Drug: SYR-322-MET


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: In the opinion of the investigator or subinvestigator, the subject is capable of understanding and complying with protocol requirements. The subject signs and dates a written, informed consent form prior to the initiation of any study procedures. The subject is a Japanese healthy adult male. The subject is aged 20 to 35 years, inclusive, at the time of informed consent. The subject has a body weight of 50 kg or more with a BMI of ≥18.5 kg/m2 and <25.0 kg/m2 at screening. Exclusion Criteria: The subject has received any investigational compound within 16 weeks (112 days) prior to the start of study drug administration in Period 1. The subject has received SYR-322 or metformin hydrochloride in a previous clinical study or as a therapeutic agent. The subject is an immediate family member, study site employee, or is in a dependant relationship with a study site employee who is involved in the conduct of this study (eg, spouse, parent, child, sibling) or may consent under duress. The subject has uncontrolled, clinically significant neurologic, cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, urologic, or endocrine disease or other abnormality, which may impact the ability of the subject to participate or potentially confound the study results. The subject has a known hypersensitivity to drugs. The subject has a positive urine drug result for drugs of abuse (defined as any illicit drug use) at screening. The subject has a history of drug abuse or history of alcohol abuse within 2 years prior to the screening visit or unwilling to agree to abstain from alcohol and drugs throughout the study. Subject has taken any excluded medication, supplements, or food products during the time periods listed in the Excluded Medications and Dietary Products table. Subject has evidence of current cardiovascular, central nervous system, hepatic, hematopoietic disease, renal dysfunction, metabolic or endocrine dysfunction, serious allergy, asthma, hypoxemia, hypertension, seizures, or allergic skin rash. There is any finding in the subject's medical history, physical examination, or safety laboratory tests giving reasonable suspicion of a disease that would contraindicate taking DPP-4 inhibitors or biguanides, or a similar drug in the same class, or that might interfere with the conduct of the study. This includes, but is not limited to, peptic ulcer disease, seizure disorders, and cardiac arrhythmias. The subject has current or recent [within 24 weeks (168 days) prior to the initiation of study treatment in Period 1] gastrointestinal disease that would be expected to influence the absorption of drugs (i.e., a history of malabsorption, esophageal reflux, peptic ulcer disease, erosive esophagitis, frequent [more than once per week] occurrence of heartburn, or any surgical intervention [e.g., cholecystectomy]). The subject has a history of cancer. The subject has a positive test result for hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV), human immunodeficiency virus (HIV) antibody/antigen, or serological reactions for syphilis at screening. The subject has poor peripheral venous access. The subject has undergone whole blood collection of at least 200 mL within 4 weeks (28 days) or at least 400 mL within 12 weeks (84 days) prior to the start of study medication administration Period 1. The subject has undergone whole blood collection of at least 800 mL in total within 52 weeks (364 days) prior to the start of study medication administration in Period 1. The subject has undergone blood component collection within 2 weeks (14 days) prior to the start of study medication administration in Period 1. The subject has a screening or prior to the start of study medication administration on Day 1 in Period 1 hemoglobin level <12.5 g/dL. The subject has a screening or prior to the start of study medication administration on Day 1 in Period 1 abnormal (clinically significant) 12-lead ECG. Subject has abnormal screening or prior to the start of study medication administration on Day 1 in Period 1 laboratory values that suggest a clinically significant underlying disease or subject with the following lab abnormalities: ALT and/or AST >1.5 the upper limits of normal. Subject who, in the opinion of the investigator, is unlikely to comply with the protocol or is unsuitable for any other reason.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fasted dosing followed by fed dosing<br>Oral administration | Drug: SYR-322-MET<br>* Oral administration of SYR-322-MET<br>|
| Experimental: Fed dosing followed by fasted dosing<br>Oral administration | Drug: SYR-322-MET<br>* Oral administration of SYR-322-MET<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC (0-72): Area Under the Plasma Concentration-time Curve From Time 0 to 72 Hours Postdose for Unchanged SYR-322 (SYR-322Z) | AUC (0-72) is measure of area under the curve from time 0 to 72 hours post dose. | 3 hours prior to administration (predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose | 
| AUC (0-tlqc): Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for SYR-322Z | AUC (0-tlqc) is a measure of total plasma exposure to the drug from Time 0 to Time of the Last Quantifiable Concentration (AUC [0-tlqc]). | 3 hours prior to administration (predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose | 
| Cmax: Maximum Observed Plasma Concentration for SYR-322Z | Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve. | 3 hours prior to administration (predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose | 
| Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for SYR-322Z | Tmax: Time to reach the maximum plasma concentration (Cmax), equal to time (hours) to Cmax. | 3 hours prior to administration (predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose | 
| AUC (0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for SYR-322Z | AUC (0-inf) is a measure of total plasma exposure to the drug from time zero extrapolated to infinity. | 3 hours prior to administration (predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose | 
| Apparent Terminal Elimination Rate Constant (λz) for SYR-322Z | Terminal elimination rate constant, calculated as the negative of the slope of the log-linear regression of the natural logarithm concentration-time curve during the terminal phase. | 3 hours prior to administration (predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose | 
| Terminal Phase Elimination Half-life (T1/2) for SYR-322Z | Terminal phase elimination half-life (T1/2) is the time required for half of the drug to be eliminated from the plasma. | 3 hours prior to administration (predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose | 
| Apparent Clearance After Extra Vascular Administration (CL/F) for SYR-322Z | CL/F is apparent clearance of the drug from the plasma, calculated as the drug dose divided AUC (0-inf), expressed in liter/hour (L/hr). | 3 hours prior to administration, and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 hours after administration | 
| Mean Residence Time (MRT) for SYR-322Z | Mean residence time (MRT) calculated as area under the first moment plasma concentration-time curve (AUMC [0-inf]) divided by AUC (0-inf). (AUMC [0-inf]) is the area under the first moment plasma concentration-time curve from time 0 to infinity. | 3 hours prior to administration (predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose | 
| MRT (0-tlqc): Mean Residence Time From Time 0 to Time of the Last Quantifiable Concentration (Tlqc) for SYR-322Z | MRT (0-tlqc) is a measure of the mean residence time from time 0 to time of the last quantifiable concentration (tlqc) calculated as MRT (0-tlqc) =AUMC (0-tlqc)/AUC (0-tlqc). AUMC (0-tlqc) is the area under the first moment plasma concentration-time curve from time 0 to time of the last quantifiable concentration (tlqc), calculated using the linear trapezoidal rule. | 3 hours prior to administration (predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose | 
| AUC (0-72): Area Under the Plasma Concentration-time Curve From Time 0 to 72 Hours Post Dose for SYR-322 Metabolites M-I and M-II | AUC (0-72) is measure of area under the curve from time 0 to 72 hours post dose. | 3 hours prior to administration (predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose | 
| AUC (0-tlqc): Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for SYR-322 Metabolites M-I and M-II | AUC (0-tlqc) is a measure of total plasma exposure to the drug from Time 0 to Time of the Last Quantifiable Concentration (AUC [0-tlqc]). | 3 hours prior to administration (predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose | 
| MRT (0-tlqc): Mean Residence Time From Time 0 to Time of the Last Quantifiable Concentration (Tlqc) for SYR-322 Metabolites M-I and M-II | MRT (0-tlqc) is a measure of the mean residence time from time 0 to time of the last quantifiable concentration (tlqc) calculated as MRT (0-tlqc) =AUMC (0-tlqc)/AUC (0-tlqc). AUMC (0-tlqc) is the area under the first moment plasma concentration-time curve from time 0 to time of the last quantifiable concentration (tlqc), calculated using the linear trapezoidal rule. | 3 hours prior to administration (predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose | 
| Cmax: Maximum Observed Plasma Concentration for SYR-322 Metabolites M-I and M-II | Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve. | 3 hours prior to administration (predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose | 
| Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for SYR-322 Metabolites M-I and M-II | Tmax: Time to reach the maximum plasma concentration (Cmax), equal to time (hours) to Cmax. | 3 hours prior to administration (predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose | 
| AUC (0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for SYR-322 Metabolites M-I and M-II | AUC (0-inf) is a measure of total plasma exposure to the drug from time zero extrapolated to infinity. | 3 hours prior to administration (predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose | 
| Apparent Terminal Elimination Rate Constant (λz) for SYR-322 Metabolites M-I and M-II | Terminal elimination rate constant, calculated as the negative of the slope of the log-linear regression of the natural logarithm concentration-time curve during the terminal phase. | 3 hours prior to administration (predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose | 
| Terminal Phase Elimination Half-life (T1/2) for SYR-322 Metabolites M-I and M-II | Terminal phase elimination half-life (T1/2) is the time required for half of the drug to be eliminated from the plasma. | 3 hours prior to administration (predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose | 
| Mean Residence Time (MRT) for SYR-322 Metabolites M-I and M-II | Mean residence time (MRT) calculated as area under the first moment plasma concentration-time curve (AUMC [0-inf]) divided by AUC (0-inf). AUMC (0-inf) is the area under the first moment plasma concentration-time curve from time 0 to infinity. | 3 hours prior to administration (predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose | 
| AUC (0-48): Area Under the Plasma Concentration-time Curve From Time 0 to 48 Hours Postdose for Metformin | AUC (0-48) is measure of area under the curve from time 0 to 48 hours post dose. | 3 hours prior to administration (predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose | 
| AUC (0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Metformin | AUC (0-tlqc) is a measure of total plasma exposure to the drug from Time 0 to Time of the Last Quantifiable Concentration (AUC [0-tlqc]). | 3 hours prior to administration (predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose | 
| MRT (0-tlqc): Mean Residence Time From Time 0 to Time of the Last Quantifiable Concentration (Tlqc) for Metformin | MRT (0-tlqc) is a measure of the mean residence time from time 0 to time of the last quantifiable concentration (tlqc) calculated as MRT (0-tlqc) =AUMC (0-tlqc)/AUC (0-tlqc). AUMC (0-tlqc) is the area under the first moment plasma concentration-time curve from time 0 to time of the last quantifiable concentration (tlqc), calculated using the linear trapezoidal rule. | 3 hours prior to administration (predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose | 
| Cmax: Maximum Observed Plasma Concentration for Metformin | Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve. | 3 hours prior to administration (predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose | 
| Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Metformin | Tmax: Time to reach the maximum plasma concentration (Cmax), equal to time (hours) to Cmax. | 3 hours prior to administration (predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose | 
| AUC (0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Metformin | AUC (0-inf) is a measure of total plasma exposure to the drug from time zero extrapolated to infinity. | 3 hours prior to administration (predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose | 
| Apparent Terminal Elimination Rate Constant (λz) for Metformin | Terminal elimination rate constant, calculated as the negative of the slope of the log-linear regression of the natural logarithm concentration-time curve during the terminal phase. | 3 hours prior to administration (predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose | 
| Terminal Phase Elimination Half-life (T1/2) for Metformin | Terminal phase elimination half-life (T1/2) is the time required for half of the drug to be eliminated from the plasma. | 3 hours prior to administration (predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose | 
| Apparent Clearance After Extra Vascular Administration (CL/F) for Metformin | CL/F is apparent clearance of the drug from the plasma, calculated as the drug dose divided AUC (0-inf), expressed in L/hr. | 3 hours prior to administration (predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose | 
| Mean Residence Time (MRT) for Metformin | Mean residence time (MRT) calculated as area under the first moment plasma concentration-time curve (AUMC [0-inf]) divided by AUC (0-inf). AUMC (0-inf) is the area under the first moment plasma concentration-time curve from time 0 to infinity. | 3 hours prior to administration (predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose | 
| Urinary Excretion Ratio of SYR-322Z From 0 to 12 Hours Postdose | Cumulative urinary excretion ratio of unchanged SYR-322 was calculated as the percentage of SYR-322 dose. | 0 to 12 hours postdose | 
| Urinary Excretion Ratio of SYR-322Z From 0 to 24 Hours Postdose | Cumulative urinary excretion ratio of unchanged SYR-322 was calculated as the percentage of SYR-322 dose. | 0 to 24 hours postdose | 
| Urinary Excretion Ratio of SYR-322Z From 0 to 48 Hours Postdose | Cumulative urinary excretion ratio of unchanged SYR-322 was calculated as the percentage of SYR-322 dose. | 0 to 48 hours postdose | 
| Urinary Excretion Ratio of SYR-322Z From 0 to 72 Hours Postdose | Cumulative urinary excretion ratio of unchanged SYR-322 was calculated as the percentage of SYR-322 dose. | 0 to 72 hours postdose | 
| Urinary Excretion Ratio of SYR-322 Metabolites M-I and M-II From 0 to 12 Hours Postdose | Cumulative urinary excretion ratio of SYR-322 metabolites M-I and M-II was calculated as the percentage of SYR-322 dose. | 0 to 12 hours postdose | 
| Urinary Excretion Ratio of SYR-322 Metabolites M-I and M-II From 0 to 24 Hours Postdose | Cumulative urinary excretion ratio of SYR-322 metabolites M-I and M-II was calculated as the percentage of SYR-322 dose. | 0 to 24 hours post dose | 
| Urinary Excretion Ratio of SYR-322 Metabolites M-I and M-II From 0 to 48 Hours Postdose | Cumulative urinary excretion ratio of SYR-322 metabolites M-I and M-II was calculated as the percentage of SYR-322 dose. | 0 to 48 hours postdose | 
| Urinary Excretion Ratio of SYR-322 Metabolites M-I and M-II From 0 to 72 Hours Postdose | Cumulative urinary excretion ratio of SYR-322 metabolites M-I and M-II was calculated as the percentage of SYR-322 dose. | 0 to 72 hours postdose | 
| Urinary Excretion Ratio of Metformin From Time 0 to 12 Hours Postdose | Cumulative urinary excretion ratio of metformin was calculated as the percentage of metformin dose. | 0 to 12 hours postdose | 
| Urinary Excretion Ratio of Metformin From 0 to 24 Hours Postdose | Cumulative urinary excretion ratio of metformin was calculated as the percentage of metformin dose. | 0 to 24 hours postdose | 
| Urinary Excretion Ratio of Metformin From 0 to 48 Hours Postdose | Cumulative urinary excretion ratio of metformin was calculated as the percentage of metformin dose. | 0 to 48 hours postdose | 
| CLr: Renal Clearance of SYR-322Z | CLr is a measure of apparent clearance of the drug from the urine. The clearance is the rate at which waste substances are cleared from the blood. | 3 hours prior to administration (predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose | 
| CLr: Renal Clearance of Metformin | CLr is a measure of apparent clearance of the drug from the urine. | 3 hours prior to administration (predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Inhibition Rate of Dipeptidyl-peptidase-4 (DPP-4) Activity | DPP-4 activity and inhibition rate of DPP-4 activity was assessed from the plasma samples collected from the participants. Inhibition of DPP-4 enzyme was used to determine the antihyperglycemic activity of the investigational product. | 3 hours prior to administration (predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 24 hours postdose | 
| DPP-4 Activity | DPP-4 activity was assessed from the plasma samples collected from the participants. | 3 hours prior to administration (predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 24 hours postdose | 
| AUC (0-24): Area Under the Inhibition Rate of Plasma DPP-4 Activity-time Curve From Time 0 to 24 Hours | Area under the inhibition rate of plasma DPP-4 activity-time curve from time 0 to 24 hours was determined from the inhibition-time curve. | 3 hours prior to administration (predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 24 hours postdose | 
| Emax: Maximum Inhibition Rate of Plasma DPP-4 Activity | Maximum inhibition rate of plasma DPP-4 activity was determined from the inhibition-time curve. | 3 hours prior to administration (predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 24 hours postdose | 
| Tmax: Time to Reach Emax | Time to reach Emax for the first time was determined from the inhibition-time curve. | 3 hours prior to administration (predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 24 hours postdose | 
| Number of Participants Reporting 1 or More Treatment-emergent Adverse Events | An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. | Baseline up to the day of discharge (Day 4) in the second intervention period | 
| Number of Participants With Clinically Significant Change From Baseline in Vital Signs | Vital signs included body temperature (infra-axillary), supine blood pressure resting more than 5 minutes (systolic and diastolic [Millimeters of mercury]), respiratory rate and pulse (beats per minute). Clinically significant change in vital signs observed at any time point are reported. | 3 hours prior to administration (predose) and 2, 24 and 72 hours postdose | 
| Number of Participants With Clinically Significant Change From Baseline in Body Weight | Clinically significant change participant's body weight observed at any time point are reported. | 3 hours prior to administration (predose), 24 and 72 hours postdose | 
| Number of Participants With Significant Change From Baseline in Electrocardiograms | Clinically significant change in electrocardiograms observed at any time point are reported. | 3 hours prior to administration (predose) and 2, 24 and 72 hours postdose | 
| Number of Participants With Laboratory-related Treatment Emergent Adverse Events (TEAEs) | Laboratory assessments included hematology, serum chemistry and urinalysis. Any laboratory-related TEAE reported at any time point were reported in this measure. | 3 hours prior to administration (predose), 24 and 72 hours postdose |