A Study to Evaluate the Safety, Tolerability, and Pharmacokinetics (PK, the Measure of How the Human Body Processes a Substance) of ETX0282 When Administered Orally to Healthy Participants

NCT ID: NCT03491748

Last Updated: 2020-01-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 99 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-03-16
• Study Completion Date: 2019-09-11

Brief Summary

This research project is being conducted to investigate the safety, tolerability, and pharmacokinetics (PK) of a single ascending dose (SAD) and multiple ascending doses (MAD) of oral ETX0282 when administered alone and in combination with cefpodoxime proxetil in healthy adult participants.

Detailed Description

This Phase 1, single-center, double-blind, randomized, placebo-controlled study will be conducted to:

• Determine the safety and tolerability of oral ETX0282 when administered as a SAD and MAD to healthy participants;
• Determine the safety and tolerability of oral ETX0282 when administered as a single oral dose in combination with cefpodoxime proxetil to healthy participants;
• Characterize the PK in plasma and in urine of ETX0282 and ETX1317 following administration of single and multiple oral doses of ETX0282 in healthy participants; and
• Determine the PK profile in plasma and in urine of ETX0282 and ETX1317 and of cefpodoxime proxetil and cefpodoxime following administration of single oral doses of ETX0282 and cefpodoxime proxetil alone and when ETX0282 is co-administered with cefpodoxime proxetil at the same time as single oral doses in healthy participants.

Conditions

Healthy Volunteers

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Part A (SAD): Cohort 1, 100 mg ETX0282/Placebo

Part A of the study will explore the safety, tolerability, and pharmacokinetics (PK) of a single ascending dose (SAD) of oral ETX0282. Participants will be treated with a single oral dose of 100 milligrams (mg) ETX0282 or placebo in a fasted state. They will be confined to the Study Unit from Day -1 and discharged following collection of the 72-hour postdose assessments (Day 4).

Group Type: EXPERIMENTAL

ETX0282

Intervention Type: DRUG

Oral Gelatin capsules

Placebo

Intervention Type: DRUG

Oral Gelatin capsules

Part A (SAD): Cohort 2, 200 mg ETX0282/Placebo

Part A of the study will explore the safety, tolerability, and PK of a SAD of oral ETX0282. Participants will be treated with a single oral dose of 200 mg ETX0282 or placebo in a fasted state. They will be confined to the Study Unit from Day -1 and discharged following collection of the 72-hour postdose assessments (Day 4).

Group Type: EXPERIMENTAL

ETX0282

Intervention Type: DRUG

Oral Gelatin capsules

Placebo

Intervention Type: DRUG

Oral Gelatin capsules

Part A (SAD): Cohort 3, 400 mg ETX0282/Placebo

Part A of the study will explore the safety, tolerability, and PK of a SAD of oral ETX0282. Participants will be treated with a single oral dose of 400 mg ETX0282 or placebo in a fasted state. They will be confined to the Study Unit from Day -1 and discharged following collection of the 72-hour postdose assessments (Day 4).

Group Type: EXPERIMENTAL

ETX0282

Intervention Type: DRUG

Oral Gelatin capsules

Placebo

Intervention Type: DRUG

Oral Gelatin capsules

Part A (SAD): Cohort 4, 800 mg ETX0282/Placebo

Part A of the study will explore the safety, tolerability, and PK of a SAD of oral ETX0282. Participants will be treated with a single oral dose of 800 mg ETX0282 or placebo in a fasted state. They will be confined to the Study Unit from Day -1 and discharged following collection of the 72-hour postdose assessments (Day 4).

Group Type: EXPERIMENTAL

ETX0282

Intervention Type: DRUG

Oral Gelatin capsules

Placebo

Intervention Type: DRUG

Oral Gelatin capsules

Part A (SAD): Cohort 5, 600 mg ETX0282/Placebo

Part A of the study will explore the safety, tolerability, and PK of a SAD of oral ETX0282. Participants will be treated with a single oral dose of 600 mg ETX0282 or placebo in a fasted state. They will be confined to the Study Unit from Day -1 and discharged following collection of the 72-hour postdose assessments (Day 4).

Group Type: EXPERIMENTAL

ETX0282

Intervention Type: DRUG

Oral Gelatin capsules

Placebo

Intervention Type: DRUG

Oral Gelatin capsules

Part A (SAD): Cohort 6 (Elderly), 300 mg ETX0282/Placebo

Part A of the study will explore the safety, tolerability, and PK of a SAD of oral ETX0282. Elderly participants (aged 65 years or older) will be treated with a single oral dose of 300 mg ETX0282 or placebo in a fasted state. They will be confined to the Study Unit from Day -1 and discharged following collection of the 72-hour postdose assessments (Day 4).

Group Type: EXPERIMENTAL

ETX0282

Intervention Type: DRUG

Oral Gelatin capsules

Placebo

Intervention Type: DRUG

Oral Gelatin capsules

Part B (Food Effect): Cohort 7, 100 mg ETX0282/Placebo

Part B of the study will explore the effect of food on oral ETX0282. Participants will be treated with a single oral dose of 100 mg ETX0282 or placebo (Day 1) while fasted and with a single oral dose of 100 mg ETX0282 or placebo (Day 4) with a high-fat meal. They 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).

Group Type: EXPERIMENTAL

ETX0282

Intervention Type: DRUG

Oral Gelatin capsules

Placebo

Intervention Type: DRUG

Oral Gelatin capsules

Part C (MAD): Cohort 9, 200 mg ETX0282/Placebo

Part C of the study will explore the safety, tolerability, and PK of MAD of oral ETX0282. Part C will be administered in a fed state. Participants will be treated with a single oral dose of 200 mg ETX0282 or placebo on the morning of Day 1, and will then be dosed three times a day (TID) beginning on the morning of Day 2 (i.e., 24 hours after the Day 1 dose) through Day 7. Participants will be treated with a single oral dose of 200 mg ETX0282 or placebo on the morning of Day 8. They will be confined to the Study Unit from Day -1 and discharged following collection of the 72-hour post Day 8 dose assessments (Day 11).

Group Type: EXPERIMENTAL

ETX0282

Intervention Type: DRUG

Oral Gelatin capsules

Placebo

Intervention Type: DRUG

Oral Gelatin capsules

Part C (MAD): Cohort 10, 200 mg ETX0282/Placebo

Part C of the study will explore the safety, tolerability, and PK of MAD of oral ETX0282. Part C will be administered in a fed state. Participants will be treated with a single oral dose of 200 mg ETX0282 or placebo on the morning of Day 1, and will then be dosed TID beginning on the morning of Day 2 (i.e., 24 hours after the Day 1 dose) through Day 7. Participants will be treated with a single oral dose of 200 mg ETX0282 or placebo on the morning of Day 8. They will be confined to the Study Unit from Day -1 and discharged following collection of the 72-hour post Day 8 dose assessments (Day 11).

Group Type: EXPERIMENTAL

ETX0282

Intervention Type: DRUG

Oral Gelatin capsules

Placebo

Intervention Type: DRUG

Oral Gelatin capsules

Part D: Cohort 12, ETX0282/Placebo plus Cefpodoxime Proxetil

Part D of the study will explore the safety, tolerability, and PK of oral ETX0282 when administered as a single oral dose in combination with cefpodoxime proxetil tablets to healthy participants in a fed state. Participants will be treated with a single oral dose of 600 mg ETX0282 or placebo in a fed state on Day 1, with a single oral dose of 400 mg cefpodoxime proxetil in a fed state on Day 4, and with a single oral dose of 600 mg ETX0282 or placebo plus a single oral dose of 400 mg cefpodoxime proxetil dosed at the same time in a fed state on Day 7. They will be confined to the Study Unit from Day -1 and discharged following collection of the 72-hour post Day 7 dose assessments (Day 10).

Group Type: EXPERIMENTAL

ETX0282

Intervention Type: DRUG

Oral Gelatin capsules

Cefpodoxime proxetil

Intervention Type: DRUG

Oral tablets

Placebo

Intervention Type: DRUG

Oral Gelatin capsules

Part B (Food Effect): Cohort 14, 300 mg ETX0282/Placebo

Part B of the study will explore the effect of food on oral ETX0282. Participants will be treated with a single oral dose of 300 mg ETX0282 or placebo (Day 1) while fasted and with a single oral dose of 300 mg ETX0282 or placebo (Day 4) with a high-fat meal. They 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).

Group Type: EXPERIMENTAL

ETX0282

Intervention Type: DRUG

Oral Gelatin capsules

Placebo

Intervention Type: DRUG

Oral Gelatin capsules

Part G: Cohort 17, 300 mg ETX0282/Placebo

Part G of the study will explore the tolerability and PK profile of oral ETX0282 when administered either as a single dose (i.e., 300 mg as a single dose) or in 4 equal, divided doses over a 6 hour period (i.e., 75 mg every 2 hours for 4 doses \[a 300 mg total dose\]) when administered in a fasted state. Participants will receive the 2 treatments in a cross-over design according to one of 2 randomized sequences: AB or BA. Treatment A: 0 hours, 4 × 75 mg ETX0282/placebo; 2, 4, and 6 hours, 1 × 75 mg placebo. Treatment B: 0 hours, 1 × 75 mg ETX0282/placebo and 3 × 75 mg placebo; 2, 4, and 6 hours, 1 × 75 mg ETX0282/placebo. Participants will be confined to the Study Unit from Day -1 and discharged following collection of the 24 hours post Day 4 dose assessments (Day 5).

Group Type: EXPERIMENTAL

ETX0282

Intervention Type: DRUG

Oral Gelatin capsules

Placebo

Intervention Type: DRUG

Oral Gelatin capsules

Interventions

ETX0282

Oral Gelatin capsules

Intervention Type: DRUG

Cefpodoxime proxetil

Oral tablets

Intervention Type: DRUG

Placebo

Oral Gelatin capsules

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Aged 18 to 55 years (inclusive) for all participants except for those in Cohort 6 (in Part A); for Cohort 6, only participants aged ≥ 65 years will be enrolled.
• Be in general good health without clinically significant medical history
• Provide voluntary written informed consent prior to any study procedures and are willing and able to comply with the prescribed treatment protocol and evaluations
• Body mass index (BMI) ≥18.0 kilograms per meters squared (kg/m^2) and ≤32.0 kg/m^2
• Clinical laboratory values within the normal limits as defined by the clinical laboratory, unless the Principal Investigator decides that out-of-range values are not clinically significant
• Negative screen for drugs of abuse, alcohol, hepatitis B surface antigen, hepatitis C virus antibody, and human immunodeficiency virus at Screening; and drugs of abuse, alcohol predose on Day -1
• Female participants 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 participants 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.

Exclusion Criteria

• History of any moderate or severe hypersensitivity or allergic reaction to any β-lactam antimicrobial (e.g., penicillin or cephalosporin)
• 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, urticaria, or angioedema.
• Use of prescription or over-the-counter medications within 7 days of investigational product administration, with the exception of contraceptive medications, paracetamol, oral non-steroidal 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 Principal Investigator and Sponsor
• Participation in an investigational drug or device study within 30 days before study drug dosing, i.e., there were at least 30 days between the last dose in a prior study and dose administration in this study
• Current smoker or difficulty abstaining from smoking for the duration of study confinement
• History of major organ dysfunction
• Infection or any serious underlying medical condition that would impair the participant from receiving study drug
• History of excessive alcohol intake (more than 4 standard drinks daily, on average) or use of recreational drugs within the last 3 months
• Standard donation of blood within 30 days of the study
• 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 participant in this study
• Anticipated need for surgery or hospitalization during the study
• Surgery within 30 days before study enrolment
• Unwillingness or inability to comply with the study protocol for any other reason

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Entasis Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Nucleus Network

Melbourne, Victoria, Australia

Countries

Australia

Other Identifiers

1010452

Identifier Type: OTHER

Identifier Source: secondary_id

CS0282-2017-0001

Identifier Type: -

Identifier Source: org_study_id