A Study to Assess Mass Balance Recovery, Metabolite Profile and Identification of IV and Oral 14C-BC-3781

Healthy Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03131141
• Other study ID #: NAB-BC-3781-1013
• Status: Completed
• Phase: Phase 1
• First received: February 16, 2017
• Last updated: April 1, 2018
• Start date: January 8, 2017
• Est. completion date: March 30, 2018

Study information

• Verified date: April 2018
• Source: Nabriva Therapeutics AG
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: March 30, 2018
• Est. primary completion date: October 9, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 30 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• BC-3781
Lefamulin (BC-3781) is a potent, semi-synthetic antibacterial belonging to a novel class for systemic human use known as the pleuromutilins

Locations

Country	Name	City	State
United Kingdom	Quotient Clinical	Nottingham

Sponsors (2)

Lead Sponsor	Collaborator
Nabriva Therapeutics AG	Quotient Clinical

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Amount of radioactivity eliminated in urine	Amount excreted (Ae) and AE as a percentage of administered dose (%Ae)	Day 1 pre-dose to Day 8 post-dose
Primary	Amount of radioactivity eliminated in feces	Amount excreted (Ae) and AE as a percentage of administered dose (%Ae)	Day 1 pre-dose to Day 8 post-dose
Primary	Amount of radioactivity eliminated in urine and feces	Amount excreted (Ae) and AE as a percentage of administered dose (%Ae)	Day 1 pre-dose to Day 8 post-dose
Primary	Cumulative amount of radioactivity eliminated in urine	Cumulative recovery (CumAe)and CumAe as a percentage of the dose (Cum%Ae)	Day 1 pre-dose to Day 8 post-dose
Primary	Cumulative amount of radioactivity eliminated in feces	Cumulative recovery (CumAe)and CumAe as a percentage of the dose (Cum%Ae)	Day 1 pre-dose to Day 8 post-dose
Primary	Cumulative amount of radioactivity eliminated in urine and feces	Cumulative recovery (CumAe)and CumAe as a percentage of the dose (Cum%Ae)	Day 1 pre-dose to Day 8 post-dose
Secondary	Safety - hematology	Safety as assessed by review of changes in hematology	Day 1 pre-dose to Day 8 post-dose
Secondary	Safety - clinical chemistry	Safety as assessed by review of changes in clinical chemistry	Day 1 pre-dose to Day 8 post-dose
Secondary	Safety - urinalysis	Safety as assessed by review of changes in urinalysis	Day 1 pre-dose to Day 8 post-dose
Secondary	Safety - electrocardiograms	Safety as assessed by review of changes in electrocardiograms	Day 1 pre-dose to Day 8 post-dose
Secondary	Safety - vital signs	Safety as assessed by review of changes in vital signs	Day 1 pre-dose to Day 8 post-dose
Secondary	Safety - adverse events	Safety as assessed by review of adverse events	Day 1 pre-dose to Day 8 post-dose
Secondary	Metabolic profiling and structural identification in plasma	Number of metabolites >10% of circulating radioactivity in plasma	Day 1 pre-dose to Day 8 post-dose
Secondary	Metabolic profiling and structural identification in urine	Number of metabolites >10% of the dose in urine	Day 1 pre-dose to Day 8 post-dose
Secondary	Metabolic profiling and structural identification in feces	Number of metabolites >10% of the dose in feces	Day 1 pre-dose to Day 8 post-dose
Secondary	PK of total radioactivity: lag time (tlag), BC-3781 and major metabolites	Assessment of pharmacokinetics of lefamulin as assessed by radioactivity lag time	Day 1 pre-dose to Day 8 post-dose
Secondary	PK of total radioactivity: Cmax	Peak plasma concentration (Cmax), BC-3781 and major metabolites	Day 1 pre-dose to Day 8 post-dose
Secondary	PK of total radioactivity: AUC	area under the plasma concentration-time curve from time zero to time of last measurable concentration (AUC last) of BC-3781 and major metabolites	Day 1 pre-dose to Day 8 post-dose
Secondary	PK of total radioactivity: AUC (0-infinity)	area under the plasma concentration-time curve from time zero to infinity (AUCinf), BC-3781 and major metabolites	Day 1 pre-dose to Day 8 post-dose
Secondary	PK of total radioactivity: Time to Cmax	Time to reach total maximum observed concentration (tmax), BC-3781 and major metabolites	Day 1 pre-dose to Day 8 post-dose
Secondary	PK of total radioactivity: elimination half-life	elimination half-life (t1/2), BC-3781 and major metabolites	Day 1 pre-dose to Day 8 post-dose