Bioavailability and Pharmacokinetics of Lefamulin When Administered to Fed and Fasted Healthy Subjects

A Study to Assess the Bioavailability and Pharmacokinetics of an Immediate Release Tablet Formulation of Lefamulin When Administered to Fed and Fasted Healthy Subjects in Comparison to an Intravenous Formulation and a Capsule Formulation

A Phase 1 study to assess the bioavailability and pharmacokinetics of a 600 mg immediate release tablet formulation of lefamulin when administered to fed and fasted healthy subjects in comparison to an intravenous formulation and a capsule formulation.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Lefamulin

Detailed Description

This is a single center, single cohort, open label, randomized, four- period cross-over study with healthy subjects receiving a single dose of lefamulin at four study sessions at least 4 days apart. Lefamulin will be taken: 1) as 600 mg IR tablet orally in the fasted state; 2) as 600 mg API in capsule (3 x 200 mg capsules) orally in the fasted state; 3) as 150 mg i.v. infusion in 250 mL citrate buffered saline over 1 h; 4) as 600 mg IR tablet orally one hour after breakfast.

The order will be randomized. A total of 20 healthy subjects will be enrolled in the study. The same subjects will take part in all study sessions.

After each study session, the Safety Monitoring Team will review the safety and tolerance data before the commencement of the subsequent session.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Nottingham, United Kingdom, NG11 9JS
    • Quotient Clinical

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy subjects 18-55 years of age
• Good state of health (mentally and physically) as determined by the investigator
• Body mass index within the range 19 to 32 kg/m2 inclusive
• A signed and dated written informed consent form
• The subject is able to understand and willing to comply with protocol requirements and timetables, instructions and protocol-stated restrictions

Exclusion Criteria:

• Any acute or chronic illness or clinically relevant abnormality identified on the screening medical assessment, laboratory tests or ECG (12-lead or Holter), unless in the opinion of the investigator, in consultation with the Nabriva medical monitor, it will not interfere with the study procedures, affect the outcome of the study or compromise the safety of the subject
• A known history of chronic liver or biliary disease, history of Gilbert's syndrome or an elevated bilirubin level
• History of gastritis, gastrointestinal tract disorders or other clinical condition or previous surgery that might affect the absorption, distribution, biotransformation, or excretion of lefamulin
• Use of prescription or non-prescription drugs within 7 days or 10 times the elimination half-life (whichever is longer) prior to first dose of study medication
• Any intake of prescription or non-prescription drugs known to induce or inhibit drug-metabolizing enzymes or transport system enzymes within a period of less than 10 times the respective elimination half-life, or intake of grapefruit juice or grapefruit containing products within 7 days prior to first dose of study drug.

Study Plan

How is the study designed?

Design Details

• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Treatment A; Lefamulin as a 600 mg IR tablet in the fasted state	Drug: Lefamulin; Lefamulin administered iv or orally in the fasted state and orally in the fed state; Other Names: BC-3781
EXPERIMENTAL: Treatment B; Lefamulin as 600 mg API in capsule (three 200 mg capsules) in the fasted state	Drug: Lefamulin; Lefamulin administered iv or orally in the fasted state and orally in the fed state; Other Names: BC-3781
EXPERIMENTAL: Treatment C; Lefamulin as 150 mg i.v. in 250 mL citrate buffered saline infused over 1 h	Drug: Lefamulin; Lefamulin administered iv or orally in the fasted state and orally in the fed state; Other Names: BC-3781
EXPERIMENTAL: Treatment D; Lefamulin as a 600 mg IR tablet one hour after breakfast	Drug: Lefamulin; Lefamulin administered iv or orally in the fasted state and orally in the fed state; Other Names: BC-3781

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The area under the concentration time curve (AUC) of an intravenous and oral formulation of lefamulin in the fasting state	36 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The area under the concentration time curve (AUC) of a tablet and capsule formulation of lefamulin in the fasting state		36 hours
The area under the concentration time curve (AUC) of a 600 mg IR tablet of lefamulin in the fed state		36 hours
Assessment of the safety and tolerability of lefamulin when administered, as single doses orally and i.v. to healthy subjects aged 18 to 55 years (adverse events, laboratory assessments, vital signs and electrocardiograms)	Assessment of safety and tolerability by recording adverse events, laboratory assessments, vital signs and electrocardiograms	36 hours

Collaborators and Investigators

• Sponsor: Nabriva Therapeutics AG
• Investigators: Study Chair: William T Prince, MB, BChir, Nabriva Therapeutics AG

Study record dates

Study Major Dates

• Study Start: June 1, 2015
• Primary Completion (ACTUAL): June 1, 2015
• Study Completion (ACTUAL): June 1, 2015

Study Registration Dates

• First Submitted: July 27, 2015
• First Submitted That Met QC Criteria: September 22, 2015
• First Posted (ESTIMATE): September 23, 2015

Study Record Updates

• Last Update Posted (ESTIMATE): September 23, 2015
• Last Update Submitted That Met QC Criteria: September 22, 2015
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Absolute bioavailability
• Additional Relevant MeSH Terms: Anti-Infective Agents; Anti-Bacterial Agents; Lefamulin
• Other Study ID Numbers: NAB-BC-3781-1107