Clinical trial NCT01448395: Mass Balance Recovery, Metabolite Profile and Metabolite Identification of [14C]NXL104
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Mass Balance
Metabolite Identification and Profiling
Metabolite profile and Identification of [14C]NXL104
Mass Balance Recovery
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2011-10-07
Enrollment: 6
Sex: MALE
Minimum age (years): 30
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Mass balance after a single intravenous (IV) dose of [14C]NXL104 as generated from recovery of total radioactivity excreted in urine
timeFrame: 168 hours
measure: Routes of [14C]NXL104 metabolism and excretion measured through total radioactivity concentrations in urine
timeFrame: 168 hours
measure: Whole blood and plasma partitioning of total radioactivity through measurement of total radioactivy levels in blood
timeFrame: 168 hours
measure: Mass balance after a single intravenous (IV) dose of [14C]NXL104 as generated from recovery of total radioactivity excreted in faeces
timeFrame: 168 hours
measure: Routes of [14C]NXL104 metabolism and excretion measured through total radioactivity concentrations in faeces
timeFrame: 168 hours
Secondary outcomes:
measure: 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
timeFrame: 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
measure: 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
timeFrame: 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
measure: Safety and tolerability of NXL104 as number of patients with adverse events and assessment of Electrocardiogram (ECG) and vital signs results
timeFrame: 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
Other outcomes:
Locations:
city: Ruddington
country: United Kingdom
facility: Study site
state: Nottingham
Study officials:
affiliation: AstraZeneca
name: Paul Newell, MD
role: STUDY_DIRECTOR
References: