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

Sponsor
Nabriva Therapeutics AG (Industry)
Overall Status
Completed
CT.gov ID
NCT03131141
Collaborator
Quotient Clinical (Other)
10
Enrollment
1
Location
2
Arms
14.7
Actual Duration (Months)
0.7
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 1

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

Study Design

Study Type:
Interventional
Actual Enrollment :
10 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Masking Description:
open label
Primary Purpose:
Basic Science
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
Actual Study Start Date :
Jan 8, 2017
Actual Primary Completion Date :
Oct 9, 2017
Actual Study Completion Date :
Mar 30, 2018

Arms and Interventions

Arm Intervention/Treatment
Experimental: Cohort A

Cohort A will receive a single IV administration of 14C-BC-3781 containing 150 mg BC-3781 and NMT 4.3 MBq (117 µCi) 14C, administered as an infusion over 60 min after a light breakfast

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
Other Names:
  • Lefamulin

    		•
    Experimental: Cohort B

    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

    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
    Other Names:
  • Lefamulin

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Amount of radioactivity eliminated in urine [Day 1 pre-dose to Day 8 post-dose]

      Amount excreted (Ae) and AE as a percentage of administered dose (%Ae)

    2. Amount of radioactivity eliminated in feces [Day 1 pre-dose to Day 8 post-dose]

      Amount excreted (Ae) and AE as a percentage of administered dose (%Ae)

    3. Amount of radioactivity eliminated in urine and feces [Day 1 pre-dose to Day 8 post-dose]

      Amount excreted (Ae) and AE as a percentage of administered dose (%Ae)

    4. Cumulative amount of radioactivity eliminated in urine [Day 1 pre-dose to Day 8 post-dose]

      Cumulative recovery (CumAe)and CumAe as a percentage of the dose (Cum%Ae)

    5. Cumulative amount of radioactivity eliminated in feces [Day 1 pre-dose to Day 8 post-dose]

      Cumulative recovery (CumAe)and CumAe as a percentage of the dose (Cum%Ae)

    6. Cumulative amount of radioactivity eliminated in urine and feces [Day 1 pre-dose to Day 8 post-dose]

      Cumulative recovery (CumAe)and CumAe as a percentage of the dose (Cum%Ae)

    Secondary Outcome Measures

    1. Safety - hematology [Day 1 pre-dose to Day 8 post-dose]

      Safety as assessed by review of changes in hematology

    2. Safety - clinical chemistry [Day 1 pre-dose to Day 8 post-dose]

      Safety as assessed by review of changes in clinical chemistry

    3. Safety - urinalysis [Day 1 pre-dose to Day 8 post-dose]

      Safety as assessed by review of changes in urinalysis

    4. Safety - electrocardiograms [Day 1 pre-dose to Day 8 post-dose]

      Safety as assessed by review of changes in electrocardiograms

    5. Safety - vital signs [Day 1 pre-dose to Day 8 post-dose]

      Safety as assessed by review of changes in vital signs

    6. Safety - adverse events [Day 1 pre-dose to Day 8 post-dose]

      Safety as assessed by review of adverse events

    7. Metabolic profiling and structural identification in plasma [Day 1 pre-dose to Day 8 post-dose]

      Number of metabolites >10% of circulating radioactivity in plasma

    8. Metabolic profiling and structural identification in urine [Day 1 pre-dose to Day 8 post-dose]

      Number of metabolites >10% of the dose in urine

    9. Metabolic profiling and structural identification in feces [Day 1 pre-dose to Day 8 post-dose]

      Number of metabolites >10% of the dose in feces

    10. PK of total radioactivity: lag time (tlag), BC-3781 and major metabolites [Day 1 pre-dose to Day 8 post-dose]

      Assessment of pharmacokinetics of lefamulin as assessed by radioactivity lag time

    11. PK of total radioactivity: Cmax [Day 1 pre-dose to Day 8 post-dose]

      Peak plasma concentration (Cmax), BC-3781 and major metabolites

    12. PK of total radioactivity: AUC [Day 1 pre-dose to Day 8 post-dose]

      area under the plasma concentration-time curve from time zero to time of last measurable concentration (AUC last) of BC-3781 and major metabolites

    13. PK of total radioactivity: AUC (0-infinity) [Day 1 pre-dose to Day 8 post-dose]

      area under the plasma concentration-time curve from time zero to infinity (AUCinf), BC-3781 and major metabolites

    14. PK of total radioactivity: Time to Cmax [Day 1 pre-dose to Day 8 post-dose]

      Time to reach total maximum observed concentration (tmax), BC-3781 and major metabolites

    15. PK of total radioactivity: elimination half-life [Day 1 pre-dose to Day 8 post-dose]

      elimination half-life (t1/2), BC-3781 and major metabolites

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    30 Years to 65 Years
    Sexes Eligible for Study:
    Male
    Accepts Healthy Volunteers:
    Yes
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Quotient Clinical Nottingham United Kingdom NG11 6JS

    Sponsors and Collaborators

    • Nabriva Therapeutics AG
    • Quotient Clinical

    Investigators

    • Study Director: Elyse Seltzer, MD, Nabriva Therapeutics AG

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Nabriva Therapeutics AG
    ClinicalTrials.gov Identifier:
    NCT03131141
    Other Study ID Numbers:
    • NAB-BC-3781-1013
    First Posted:
    Apr 27, 2017
    Last Update Posted:
    Apr 3, 2018
    Last Verified:
    Apr 1, 2018
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Lefamulin

    Study Results

    No Results Posted as of Apr 3, 2018