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Trial registered on ANZCTR


Registration number
ACTRN12618000350224p
Ethics application status
Submitted, not yet approved
Date submitted
21/02/2018
Date registered
8/03/2018
Date last updated
8/03/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
A study to evaluate the Safety and Pharmacokinetics (Pharmacokintecus, the measure of how the human body processes a substance) of ETX0282 when administered orally to healthy participants.
Scientific title
A Phase 1, Double Blind, Randomized, Placebo-Controlled Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of oral ETX0282 Administered in Healthy Subjects
Secondary ID [1] 293760 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Enterobacteriaceae Infections 306143 0
Condition category
Condition code
Infection 305258 305258 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Part A - Single Ascending Dose (SAD)
Cohort 1 : single dose 100mg oral ETX0282 or placebo
Cohort 2: single dose 200mg oral ETX0282 or placebo
Cohort 3: single dose 400mg oral ETX0282 or placebo
Cohort 4: single dose 800mg oral ETX0282 or placebo
Cohort 5: single dose 1600mg oral ETX0282 or placebo
Cohort 6: single dose 800mg oral ETX0282 or placebo in elderly subjects (aged 65 years or older).
Participants will be confined to the Study Unit from Day -1 and discharged following collection of the 72 hour post dose assessments (Day4).
Part B - single dose ETX0282
Cohort 7: single dose 800mg oral ETX0282 or placebo (Day 1 ) while fasted and 800mg single oral dose of ETX0282 or placebo on (Day 4) with high-fat meal.
Participants will be confined to the Study Unit from Day -1 and discharged following collection of the 72 hour post fed state dose assessments (Day 7 ).
Part C - Multiple Ascending Dose (MAD)
Cohort 8: single dose 100mg oral ETX0282 or placebo on morning (Day 1), Twice Daily dosing (Day 2 through Day 7) and single dose on morning of (Day 8).
Cohort 9: single dose 200mg oral ETX0282 or placebo on morning (Day 1), Twice Daily dosing (Day2 through Day 7) and single dose on morning of (Day 8).
Cohort 10: single dose 400mg oral ETX0282 or placebo on morning (Day 1), BID dosing (Day2 through Day 7) and single dose on morning of (Day 8).
Cohort 11: single dose 800mg oral ETX0282 or placebo on morning (Day 1), Twice Daily dosing (Day2 through Day 7) and single dose on morning of (Day 8).
Participants will be confined to the Study Unit from Day -1 and discharged following collection of the 72 hour post fed state dose assessments (Day 11).
Part D - Single Dose ETX0282 in combination with Cefpodoxime Proxetil
Cohort 12: Day 1 - single oral dose 800mg ETX0282 or placebo given in a fasted state
Cohort 12: Day 4 - single oral dose 400mg Cefpodoxime Proxetil given in a fasted state
Cohort 12: Day 7 - single oral dose 800mg ETX0282 or placebo plus 400mg oral dose Cefpodoxime Proxetil at the same time in a fasted state.
Participants will be confined to the Study Unit from Day -1 and discharged following collection of the 72 hour post fed state dose assessments (Day 10).
Part E - Multiple dose combination of ETX0282 and Cefpodoxime Proxetil
Cohort 13: 800mg oral dose ETX0282 or placebo plus 400mg oral dose Cefpodoxime Proxetil given twice daily through (Day 10) and once on (Day 11) in a fasted state.
Participants will be confined to the Study Unit from Day -1 and discharged following collection of the 72 hour post Day 11 dose assessments (Day 14).
Drug will be prepared and administered by a qualified site pharmacist. Drug accountability will be performed by the pharmacists and monitored by the Unblinded CRA during the monitoring visits.
Intervention code [1] 300054 0
Treatment: Drugs
Comparator / control treatment
Gelatin Capsules
Control group
Placebo

Outcomes
Primary outcome [1] 304412 0
To determine the safety and tolerability of oral ETX0282 when administered as a single ascending dose (SAD) and multiple ascending dose (MAD) to healthy subjects. This will be assessed by looking at the incidence, severity, causality and seriousness of adverse events; changes in clinical laboratory evaluations; changes in vital signs parameters, physical examinations; and ECGs (electrocardiograms).
Timepoint [1] 304412 0
Adverse event information will be recorded from the time of admission to the study unit until 14 days after the last dose of study drug.

Primary outcome [2] 304413 0
To determine the safety and tolerability of oral ETX0282 when administered as a single oral dose in combination with cefpodoxime proxetil to healthy subjects. This will be assessed by looking at the incidence, severity, causality and seriousness of adverse events; changes in clinical laboratory evaluations; changes in vital signs parameters, physical examinations; and ECGs (electrocardiograms).
Timepoint [2] 304413 0
Adverse event information will be recorded from the time of admission to the study unit until 14 days after the last dose of study drug.
Primary outcome [3] 304414 0
To characterize the pharmacokinetics (PK) in plasma and in urine of ETX0282 and ETX1317 following administration of single and multiple oral doses of ETX0282 in healthy subjects. This will be assessed by looking at the pharmacokinetic profile of ETX0282 and ETX1317 following administration of ETX0282 as single and multiple oral doses and in combination with cefpodoxime proxetil.
ETX1317 is the active component of the pro-drug ETX0282. ETX1317 pharmacokinetic levels will be measured in plasma.
Timepoint [3] 304414 0
Pharmacokinetic samples will be collected during the treatment period at :
predose (0), 0.5, 1, 1.5, 2, 2.5, 3, 4 ,6, 8, 10, 12, 16, 24, 48 and 72 hours postdose (Part A)
predose (0), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 8, 12, 16, 24, 48 and 72 hours postdose (Part B)
predose (0), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, and 24 hours post first dose; at troughs of Day 3, Day 5, and Day 8 and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12 hours post dose (Part C)
predose (0), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 48 and 72 hours postdose (Part D)
predose; at trough on Day 2, Day 4, Day 7, Day 9 and Day 11; and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12 hours after last dose (Part E)

Secondary outcome [1] 343065 0
To determine the PK profile in plasma and urine of a single oral dose of ETX0282 and ETX1317 in healthy elderly subjects. This will be assessed by looking at the PK profile of oral ETX0282 and ETX1317 following administration of ETX0282 as single dose in healthy elderly subjects. ETX1317 is the active component of the pro-drug ETX0282. ETX1317 pharmacokinetic levels will be measured in plasma.
Timepoint [1] 343065 0
Pharmacokinetic samples will be collected during the treatment period at predose (0), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 48 and 72 hours postdose (Part A)
Secondary outcome [2] 343071 0
To determine the safety and tolerability of oral ETX0282 and co-administered cefpodoxime
proxetil when ETX0282 is co-administered with cefpodoxime proxetil in multiple doses to
healthy subjects. This will be assessed by looking at the Incidence, severity, causality, and seriousness of AE's, changes in clinical laboratory evaluations (hematology, clinical chemistry, urinalysis) Changes in vital signs parameters (blood pressure, heart rate, respiratory rate, and temperature), ECG in elderly subjects.
Timepoint [2] 343071 0
Adverse event information will be recorded from the time of admission to the study unit until 14 days after last dose of study drug.
Secondary outcome [3] 343072 0
To determine the PK profile in plasma and in urine of ETX0282 and ETX1317 and of cefpodoxime proxetil and cefpodoxime following administration of multiple doses of oral ETX0282 and co-administered cefpodoxime proxetil when ETX0282 is co-administered at the same time with cefpodoxime proxetil in multiple doses to healthy subjects. This will be assessed by looking at the pharmacokinetic profile of oral ETX0282 and ETX1317 and of cefpodoxime proxetil and cefpodoxime following administration of ETX0282 multiple doses in combination with cefpodoxime proxetil. ETX1317 is the active component of the pro-drug ETX0282. ETX1317 pharmacokinetic levels will be measured in plasma.
Timepoint [3] 343072 0
Pharmacokinetic samples will be collected during the treatment period.at predose; at trough on Day 2, Day 4, Day 7, Day 9, and Day 11; and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12 hours after the last dose (Part E)

Eligibility
Key inclusion criteria
1. Aged 18 to 55 years (inclusive) In addition, for Cohort 6 in Part A, 8 subjects greater than or equal to 65 years of age will be enrolled.
2. Be in general good health without clinically significant medical history.
3. Provide voluntary written informed consent prior to any study procedures and are willing and able to comply with the prescribed treatment protocol and evaluations.
4. Body Mass Index (BMI) less than or equal to 32.0 kg/m2.
5. Clinical laboratory values within the normal limits as defined by the clinical laboratory, unless the Principal Investigator decided that out-of-range values are not clinically significant.
6.Negative screen for drugs of abuse, alcohol, hepatitis B surface antigen (HBSAg), hepatitis C virus antibody (HCV Ab), and human immunodeficiency virus (HIV) at screening; and drugs of abuse, alcohol predose on Day -1.
7. Female subjects must be of non-childbearing potential (postmenopausal or with evidence of tubal ligation) or using a medically acceptable (highly effective method) contraceptive regimen and must have a negative pregnancy test at screening (serum) and on Day -1 (urine) prior to study drug dosing. Male subjects must be surgically sterile or using a medically acceptable contraceptive regimen. Men should not donate sperm during the study or for 90 days after the final dose of study medication.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. History of any moderate or severe hypersensitivity or allergic reaction to any beta-lactam antimicrobial (e.g; penicillin or cephalosporin).
2. History of hypersensitivity or severe allergic reaction of any type to medications, bee stings, food, or environmental factors. A severe allergic reaction is defined as any of the following : anaphylaxis, urticarial, or angioedema.
3. Use of prescription or over-the-counter medications within 7 days of IP administration, with the exception of contraceptive medications, paracetamol, oral non-steroid anti-inflammatory agents, topical over-the-counter preparations, and routine vitamins (if they do not exceed an intake of 20 to 600 times the recommended daily dose), unless agreed as non-clinically relevant by the Principle Investigator and Sponsor.
4. Participation in an investigational drug or device study within 30 days before study drug dosing. i.e., there was at least 30 days between the last dose in a prior study and dose administration in this study.
5. Current smoker or difficulty abstaining from smoking for the duration of study confinement.
6. History of major organ dysfunction.
7. Infection or any serious underlying medical condition that would impair the subject from receiving study drug.
8. History of excessive alcohol intake (more than 4 standard drinks daily, on average) or use of recreational drugs within the last 3 months.
9 Standard donation of blood within 30 days of the study.
10. Concomitant disease or condition, including laboratory abnormality, which could interfere with the conduct of the study or which would, in the opinion of the Investigator, pose an unacceptable risk to the subject in this study.
11. Anticipated need for surgery or hospitalization during the study.
12. Surgery within 30 days before study enrollment..
13. Unwillingness or inability to comply with the study protocol for any other reason.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation involves contacting the holder of the allocation schedule who is the off-site pharmacist with no contact to participants
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomization using a randomization table created by computer software (ie computerized sequence (ie : computerized sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
Intervention assignment
Other
Other design features
Participants will be assigned to different dosages and treatments depending on which study part and cohort they are enrolled into.
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis
Statistical Analysis will be performed using SAS v9.3 (SAS Institute, Cary, USA).

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
2/04/2018
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
116
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 9730 0
Nucleus Network - Melbourne
Recruitment postcode(s) [1] 18508 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 298374 0
Commercial sector/Industry
Name [1] 298374 0
Entasis Therapeutics, Inc.
Country [1] 298374 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
INC Research/ Inventiv Health
Address
159 Port Road,
Hindmarsh SA 5007
Country
Australia
Secondary sponsor category [1] 297499 0
None
Name [1] 297499 0
Address [1] 297499 0
Country [1] 297499 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 299367 0
The Alfred Hospital
Ethics committee address [1] 299367 0
Ethics committee country [1] 299367 0
Australia
Date submitted for ethics approval [1] 299367 0
31/01/2018
Approval date [1] 299367 0
Ethics approval number [1] 299367 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 80198 0
Dr Jason Lickliter
Address 80198 0
Nucleus Network
Level 5, Burnet Tower, AMREP Precinct,
Commercial Road,
Melbourne VIC 3004
Country 80198 0
Australia
Phone 80198 0
+61 390768609
Fax 80198 0
Email 80198 0
j.lickliter@nucleusnetwork.com
Contact person for public queries
Name 80199 0
Elaine Wong
Address 80199 0
Nucleus Network,
Level 5, Burnet Tower, AMREP Precinct,
89 Commercial Road,
Melbourne VIC 3004.
Country 80199 0
Australia
Phone 80199 0
+61 (3) 8593 9859
Fax 80199 0
+61 (3) 9076 8911
Email 80199 0
e.wong@nucleusnetwork.com.au
Contact person for scientific queries
Name 80200 0
David Fuller
Address 80200 0
INC Research/Inventiv Health
Suite 1, Level 2, 924 Pacific Highway
Gordon NSW 2072, Australia
Country 80200 0
Australia
Phone 80200 0
+61 2 8437 9238
Fax 80200 0
Email 80200 0
david.fuller@incresearch.com

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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