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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01448395
First received: September 30, 2011
Last updated: July 4, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Healthy
Drug: [14C]NXL104
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
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

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Mass balance after a single intravenous (IV) dose of [14C]NXL104 as generated from recovery of total radioactivity excreted in urine [ Time Frame: 168 hours ] [ Designated as safety issue: No ]
  • Routes of [14C]NXL104 metabolism and excretion measured through total radioactivity concentrations in urine [ Time Frame: 168 hours ] [ Designated as safety issue: No ]
  • Whole blood and plasma partitioning of total radioactivity through measurement of total radioactivy levels in blood [ Time Frame: 168 hours ] [ Designated as safety issue: No ]
  • Mass balance after a single intravenous (IV) dose of [14C]NXL104 as generated from recovery of total radioactivity excreted in faeces [ Time Frame: 168 hours ] [ Designated as safety issue: No ]
  • Routes of [14C]NXL104 metabolism and excretion measured through total radioactivity concentrations in faeces [ Time Frame: 168 hours ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 [ Time Frame: 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 ] [ Designated as safety issue: No ]

    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


  • 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 [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • Safety and tolerability of NXL104 as number of patients with adverse events and assessment of Electrocardiogram (ECG) and vital signs results [ Time Frame: 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 ] [ Designated as safety issue: No ]

Enrollment: 6
Study Start Date: October 2011
Study Completion Date: November 2011
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: [14C]NXL104
500mg/100mL intravenous solution

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

Ages Eligible for Study:   30 Years to 65 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01448395

Locations
United Kingdom
Study site
Ruddington, Nottingham, United Kingdom
Sponsors and Collaborators
AstraZeneca
Investigators
Study Director: Paul Newell, MD AstraZeneca
  More Information

Additional Information:
No publications provided

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01448395     History of Changes
Other Study ID Numbers: D4280C00008
Study First Received: September 30, 2011
Last Updated: July 4, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by AstraZeneca:
Mass Balance
Metabolite Identification and Profiling
Metabolite profile and Identification of [14C]NXL104
Mass Balance Recovery

ClinicalTrials.gov processed this record on July 20, 2014