Mass Balance Recovery, Metabolite Profile and Metabolite Identification of [14C]NXL104

Study Overview
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Brief Summary
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A study to look at how radiolabelled NXL104 is taken up, broken down and removed by the body when given as an injection into the blood stream.

Detailed Description
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An Open Label Single-Dose Study in Healthy Male Subjects Designed to Assess the Mass Balance Recovery, Metabolite profile and Metabolite Identification of [14C]NXL104.

Official Title
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An Open Label Single-Dose Study in Healthy Male Subjects Designed to Assess the Mass Balance Recovery, Metabolite Profile and Metabolite Identification of [14C]NXL104

Conditions
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Healthy

Intervention / Treatment
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* Drug: [14C]NXL104


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of informed consent prior to any study specific procedures. Healthy male subjects aged 30-65 years inclusive. Male subjects should be willing to use an adequate method of contraception (as defined in Section 5.1) from the day of dosing until 3 months after dosing with the investigational product. Have a body mass index (BMI) between 18 and 32 kg/m2 inclusive and weigh at least 50 kg and no more than 100 kg. Clinically normal physical examination and laboratory findings as judged by the investigator, including negative test results for drug abuse, alcohol, CO breath test and negative test results for Hepatitis B surface antigen, antibodies to Hepatitis C. Exclusion Criteria: Any clinically significant disease or disorder (e.g. cardiovascular, pulmonary, gastrointestinal, liver, renal, neurological, musculoskeletal, endocrine, metabolic, malignant, psychiatric, major physical impairment). Any clinically relevant abnormal findings in physical examination, vital signs, clinical chemistry, haematology, urinalysis, which, in the opinion of the investigator, may put the subject at risk because of his participation in the study. QTc > 450 ms or QT > 500 ms or other ECG abnormality making interpretation more difficult, as judged by the investigator, or a history of additional risk factors for Torsades de Points (eg heart failure, hypokalemia, family history of long QT syndrome). Radiation exposure from clinical studies, including that from the present study, excluding background radiation but including diagnostic X-rays and other medical exposures, exceeding 5 mSv in the last twelve months or 10 mSv in the last five years. Participation in another clinical study with an investigational product during the last 3 months.

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 65 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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: [14C]NXL104<br>* 500mg/100mL intravenous solution<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mass balance after a single intravenous (IV) dose of [14C]NXL104 as generated from recovery of total radioactivity excreted in urine |  | 168 hours | 
| Routes of [14C]NXL104 metabolism and excretion measured through total radioactivity concentrations in urine |  | 168 hours | 
| Whole blood and plasma partitioning of total radioactivity through measurement of total radioactivy levels in blood |  | 168 hours | 
| Mass balance after a single intravenous (IV) dose of [14C]NXL104 as generated from recovery of total radioactivity excreted in faeces |  | 168 hours | 
| Routes of [14C]NXL104 metabolism and excretion measured through total radioactivity concentrations in faeces |  | 168 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| IV pharmacokinetics (PK) of [14C]NXL104 through calculation of Cmax, Tmax, AUC0-infinity, T1/2, MRT, terminal elimination rate constant, amount of NXL104 (Ae), % excreted, will be calculated from NXL104 concentrations in urine and faeces | Explanations for abbreviations: Cmax = Maximum concentration Tmax = Time taken to reach maximum concentration AUC 0-Infinity = Area under the plasma concentration-time curve 0-Infinity T1/2 = Terminal half-life MRT = Mean Residence Time | Predose, 0.25, 0.5, 1,1.25,1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120, 144, 168 hours | 
| Metabolites of [14C]NXL104 in plasma, whole blood, urine and faeces calculated from plasma,urine and faces concentration levels.Identification of major metabolites in plasma,urine and faeces where possible |  | Whole blood:Predose, 0.25, 0.5, 1,1.25,1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120, 144, 168 hoursUrine and Faeces samples Predose-144 hours | 
| Safety and tolerability of NXL104 as number of patients with adverse events and assessment of Electrocardiogram (ECG) and vital signs results |  | Electrocardiogram (ECG) recordings at Screening Pre-dose, 1 ,24 and 168 hoursContinuous ECG monitoring 0-1 hourVital signs measurements screening pre-dose, 0.5, 1, 2, 24 and 168 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mass Balance, Metabolite Identification and Profiling, Metabolite profile and Identification of [14C]NXL104, Mass Balance Recovery