Clinical trial NCT03131141: A Study to Assess Mass Balance Recovery, Metabolite Profile and Identification of IV and Oral 14C-BC-3781
Official title: An Open Label, Single-dose, Single-period Study Designed to Assess the Mass Balance Recovery, Metabolite Profile and Metabolite Identification of 14C-BC-3781 Administered Via the Intravenous or Oral Routes to Healthy Male Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Nabriva Therapeutics AG
Sponsor class: INDUSTRY
Collaborators: name: Quotient Clinical
First posted: 2017-04-27
Enrollment: 10
Sex: MALE
Minimum age (years): 30
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: This is a single-centre, open-label, non-randomized, single dose study in healthy male subjects designed to assess mass balance recovery, metabolite profile and metabolite identification of radio-labeled BC-3781 administered via the intravenous or oral routes.

Detailed description: This is a single-centre, open-label, non-randomised, single dose study to assess the pharmacokinetics, mass balance recovery, and metabolite profiling and identification following administration of iv or oral 14C-BC-3781 to healthy male subjects It is planned to enrol 2 cohorts of 5 subjects or 10 subjects in total. The active substance being investigated in this study is radiolabeled lefamulin (\[14C\] BC 3781), present in the investigational medicinal products (IMPs) as the acetate salt (\[14C\]-BC-3781.Ac).

Subjects assigned to Cohort A will receive a single IV administration of 14C-BC-3781 containing 150 mg BC-3781 and not more than (NMT) 4.3 MBq (117 µCi) 14C, administered as an infusion over 60 min after a light breakfast.

Subjects assigned to Cohort B will receive a single oral administration of 14C-BC-3781 containing 600 mg BC-3781 and NMT 4.1 MBq (112 µCi) 14C, in the fasted state

Eligibility criteria: Inclusion Criteria:

* Healthy males
* Aged 30 to 65 years
* Body mass index of 18.0 to 35.0 kg/m2, inclusive
* Must have regular bowel movements
* Must provide written informed consent
* Must agree to use an adequate method of contraception

Exclusion Criteria:

* Subjects who have received any IMP in a clinical research study within the previous 3 months
* History of any drug or alcohol abuse in the past 2 years
* Regular alcohol consumption in males \>21 units per week and females \>14 units per week
* Radiation exposure, including that from the present study, excluding background radiation but including diagnostic x-rays and other medical exposures, exceeding 5 mSv in the last 12 months or 10 mSv in the last 5 years. No occupationally exposed worker, as defined in the Ionising Radiation Regulations 1999, shall participate in the study
* Subjects who do not have suitable veins for multiple venepunctures/cannulation as assessed by the investigator at screening
* Subjects who have been dosed in an ADME study in the last 12 months
* Clinically significant abnormal biochemistry, haematology or urinalysis as judged by the investigator
* Positive drugs of abuse test result at screening and admission
* Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) results
* Evidence of renal impairment at screening, as indicated by an estimated creatinine clearance (CLcr) of \<90 mL/min using the Cockcroft-Gault equation
* Significant history of cardiovascular, renal, hepatic, chronic respiratory or gastrointestinal disease, or psychiatric disorders as judged by the investigator
* A familial history or presence of Long QT syndrome
* Subjects with QT interval corrected according to Fridericia's formula (QTcF) \>480 ms
* A serum potassium level of less than 3.5 mmol/L at screening
* Serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients
* Presence or history of clinically significant allergy requiring treatment, as judged by the investigator.
* Donation or loss of greater than 400 mL of blood within the previous 3 months
* Have taken medications known to be strong P-gp inhibitors, or strong CYP3A4 inducers or inhibitors, within 28 days before IMP administration
* Subjects who are taking, or have taken, any prescribed or over-the-counter drug (other than 4 g per day paracetamol or herbal remedies) in the 14 days before IMP administration

Primary outcomes:
measure: Amount of radioactivity eliminated in urine
timeFrame: Day 1 pre-dose to Day 8 post-dose
measure: Amount of radioactivity eliminated in feces
timeFrame: Day 1 pre-dose to Day 8 post-dose
measure: Amount of radioactivity eliminated in urine and feces
timeFrame: Day 1 pre-dose to Day 8 post-dose
measure: Cumulative amount of radioactivity eliminated in urine
timeFrame: Day 1 pre-dose to Day 8 post-dose
measure: Cumulative amount of radioactivity eliminated in feces
timeFrame: Day 1 pre-dose to Day 8 post-dose
measure: Cumulative amount of radioactivity eliminated in urine and feces
timeFrame: Day 1 pre-dose to Day 8 post-dose
Secondary outcomes:
measure: Safety - hematology
timeFrame: Day 1 pre-dose to Day 8 post-dose
measure: Safety - clinical chemistry
timeFrame: Day 1 pre-dose to Day 8 post-dose
measure: Safety - urinalysis
timeFrame: Day 1 pre-dose to Day 8 post-dose
measure: Safety - electrocardiograms
timeFrame: Day 1 pre-dose to Day 8 post-dose
measure: Safety - vital signs
timeFrame: Day 1 pre-dose to Day 8 post-dose
measure: Safety - adverse events
timeFrame: Day 1 pre-dose to Day 8 post-dose
measure: Metabolic profiling and structural identification in plasma
timeFrame: Day 1 pre-dose to Day 8 post-dose
measure: Metabolic profiling and structural identification in urine
timeFrame: Day 1 pre-dose to Day 8 post-dose
measure: Metabolic profiling and structural identification in feces
timeFrame: Day 1 pre-dose to Day 8 post-dose
measure: PK of total radioactivity: lag time (tlag), BC-3781 and major metabolites
timeFrame: Day 1 pre-dose to Day 8 post-dose
measure: PK of total radioactivity: Cmax
timeFrame: Day 1 pre-dose to Day 8 post-dose
measure: PK of total radioactivity: AUC
timeFrame: Day 1 pre-dose to Day 8 post-dose
measure: PK of total radioactivity: AUC (0-infinity)
timeFrame: Day 1 pre-dose to Day 8 post-dose
measure: PK of total radioactivity: Time to Cmax
timeFrame: Day 1 pre-dose to Day 8 post-dose
measure: PK of total radioactivity: elimination half-life
timeFrame: Day 1 pre-dose to Day 8 post-dose
Other outcomes:
Locations:
city: Nottingham
country: United Kingdom
facility: Quotient Clinical
Study officials:
affiliation: Nabriva Therapeutics AG
name: Elyse Seltzer, MD
role: STUDY_DIRECTOR
References: