A Study to Assess the Safety, Tolerability, Pharmacokinetics, Food Effect, and Drug-Drug Interaction Potential of ACHN-383 and ACHN-789

A Phase 1 Study to Assess the Safety, Tolerability, Pharmacokinetics, Food Effect, and the Drug-Drug Interaction Potential of Oral ACHN-383 and ACHN-789 in Healthy Subjects

This Phase 1 clinical study is a double-blind, randomized, placebo-controlled, parallel group study to assess the safety, tolerability, pharmacokinetics (PK), food effect, and drug interaction potential of ACHN-383 and ACHN-789 co-administered orally as separate capsules in healthy subjects

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Placebo; Drug: ACHN-383; Drug: ACHN-789

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Perth, Australia
    • Clinical Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• Females of child-bearing potential must not be breast feeding, must have a negative serum pregnancy test, and must use a highly effective method of contraception or be abstinent from sexual activity prior to the first dose of study, during the study and for a specified period following the last dose of study drug
• Males must be willing to use a condom for the duration of the study and for a specified period following the study, unless surgically sterile. In addition, their female partner must use a highly effective method of contraception, for the same period of time, unless surgically sterile
• Body mass index (BMI) of ≥19 kg/m^2 to ≤32 kg/m^2 and weight ≥50 kg to ≤125 kg
• Normal renal function as determined by creatinine clearance (CLcr) rate

Key Exclusion Criteria:

• Pregnant women
• History of any hepatic or biliary disorder or disease
• Any condition that could possibly affect oral drug absorption
• Unstable cardiovascular disease
• Uncontrolled hypertension, asthma, diabetes, thyroid disease, or seizure disorder
• HIV positive
• Active malignancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; Healthy volunteers	Drug: Placebo; Oral dose; Drug: ACHN-383; Oral dose; Drug: ACHN-789; Oral dose
Experimental: Cohort 2; Healthy volunteers	Drug: Placebo; Oral dose; Drug: ACHN-383; Oral dose; Drug: ACHN-789; Oral dose
Experimental: Cohort 3; Healthy volunteers	Drug: Placebo; Oral dose; Drug: ACHN-383; Oral dose; Drug: ACHN-789; Oral dose
Experimental: Cohort 4; Healthy volunteers	Drug: Placebo; Oral dose; Drug: ACHN-383; Oral dose; Drug: ACHN-789; Oral dose
Experimental: Cohort 5; Healthy volunteers	Drug: Placebo; Oral dose; Drug: ACHN-383; Oral dose; Drug: ACHN-789; Oral dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Changes from baseline in clinical laboratory values (CBC, serum chemistry, urine analysis, AST, ALT, ALP, serum bilirubin)	26 days
Changes from baseline in vital signs (temperature, pulse, respiration, blood pressure)	26 days
Incidence and severity of adverse events	26 days
Changes from baseline in the QTcF interval	19 days

Secondary Outcome Measures

Outcome Measure	Time Frame
PK parameter: Maximum peak observed concentration (Cmax) after single-dose administration of ACHN-789	1 day
PK parameter: Maximum peak observed concentration (Cmax) after single-dose administration of ACHN-383	3 days
PK parameter: Time to maximum concentration (Tmax) after single-dose administration of ACHN-789	1 day
PK parameter: Time to maximum concentration (Tmax) after single-dose administration of ACHN-383	3 days
PK parameter: Area under the concentration-time curve (AUC) after single-dose administration of ACHN-789	1 day
PK parameter: Area under the concentration-time curve (AUC) after single-dose administration of ACHN-383	3 days
PK parameter: Half-life (t1/2) after single-dose administration of ACHN-789	1 day
PK parameter: Half-life (t1/2) after single-dose administration of ACHN-383	3 days
PK parameter: Apparent systemic clearance (CL/F) after single-dose administration of ACHN-789	1 day
PK parameter: Apparent systemic clearance (CL/F) after single-dose administration of ACHN-383	3 days
PK parameter: Apparent volume of distribution (Vz/F) after single-dose administration of ACHN-789	1 day
PK parameter: Apparent volume of distribution (Vz/F) after single-dose administration of ACHN-383	3 days
PK parameter: Amount excreted in urine (Ae) after single-dose administration of ACHN-789	1 day
PK parameter: Amount excreted in urine (Ae) after single-dose administration of ACHN-383	3 days
PK parameter: Renal clearance (CLr) after single-dose administration of ACHN-789	1 day
PK parameter: Renal clearance (CLr) after single-dose administration of ACHN-383	3 days
PK parameter: Cmax after single-dose administration of ACHN-383 and ACHN-789 given concurrently	1 day
PK parameter: Cmax after single-dose administration of ACHN-383 and ACHN-789 given concurrently	5 days
PK parameter: Tmax after single-dose administration of ACHN-383 and ACHN-789 given concurrently	1 day
PK parameter: Tmax after single-dose administration of ACHN-383 and ACHN-789 given concurrently	5 days
PK parameter: AUC after single-dose administration of ACHN-383 and ACHN-789 given concurrently	1 day
PK parameter: AUC after single-dose administration of ACHN-383 and ACHN-789 given concurrently	5 days
PK parameter: t1/2 after single-dose administration of ACHN-383 and ACHN-789 given concurrently	1 day
PK parameter: t1/2 after single-dose administration of ACHN-383 and ACHN-789 given concurrently	5 days
PK parameter: CL/F after single-dose administration of ACHN-383 and ACHN-789 given concurrently	1 day
PK parameter: CL/F after single-dose administration of ACHN-383 and ACHN-789 given concurrently	5 days
PK parameter: Vz/F after single-dose administration of ACHN-383 and ACHN-789 given concurrently	1 day
PK parameter: Vz/F after single-dose administration of ACHN-383 and ACHN-789 given concurrently	5 days
PK parameter: Ae after single-dose administration of ACHN-383 and ACHN-789 given concurrently	1 day
PK parameter: Ae after single-dose administration of ACHN-383 and ACHN-789 given concurrently	5 days
PK parameter: CLr after single-dose administration of ACHN-383 and ACHN-789 given concurrently	1 day
PK parameter: CLr after single-dose administration of ACHN-383 and ACHN-789 given concurrently	5 days
PK parameter: Cmax after single-dose administration of ACHN-383 and ACHN-789 given concurrently 30 minutes after a high-fat, high-calorie meal	6 days
PK parameter: Tmax after single-dose administration of ACHN-383 and ACHN-789 given concurrently 30 minutes after a high-fat, high-calorie meal	6 days
PK parameter: AUC after single-dose administration of ACHN-383 and ACHN-789 given concurrently 30 minutes after a high-fat, high-calorie meal	6 days
PK parameter: t1/2 after single-dose administration of ACHN-383 and ACHN-789 given concurrently 30 minutes after a high-fat, high-calorie meal	6 days
PK parameter: CL/F after single-dose administration of ACHN-383 and ACHN-789 given concurrently 30 minutes after a high-fat, high-calorie meal	6 days
PK parameter: Vz/F after single-dose administration of ACHN-383 and ACHN-789 given concurrently 30 minutes after a high-fat, high-calorie meal	6 days
PK parameter: Ae after single-dose administration of ACHN-383 and ACHN-789 given concurrently 30 minutes after a high-fat, high-calorie meal	6 days
PK parameter: CLr after single-dose administration of ACHN-383 and ACHN-789 given concurrently 30 minutes after a high-fat, high-calorie meal	6 days
PK parameter: Cmax after multiple-dose administration of ACHN-383 and ACHN-789 given concurrently	19 days
PK parameter: Cmin after multiple-dose administration of ACHN-383 and ACHN-789 given concurrently	19 days
PK parameter: Tmax after multiple-dose administration of ACHN-383 and ACHN-789 given concurrently	19 days
PK parameter: AUC after multiple-dose administration of ACHN-383 and ACHN-789 given concurrently	19 days
PK parameter: t1/2 after multiple-dose administration of ACHN-383 and ACHN-789 given concurrently	19 days
PK parameter: CL/F after multiple-dose administration of ACHN-383 and ACHN-789 given concurrently	19 days
PK parameter: Vz/F after multiple-dose administration of ACHN-383 and ACHN-789 given concurrently	19 days
PK parameter: Ae after multiple-dose administration of ACHN-383 and ACHN-789 given concurrently	19 days
PK parameter: CLr after multiple-dose administration of ACHN-383 and ACHN-789 given concurrently	19 days
Urine concentrations of ACHN-789 after single dose administration	1 day
Urine concentrations of ACHN-383 after single-dose administration	3 days
Urine concentrations of ACHN-383 and ACHN-789 after single-dose administration given concurrently	1 day
Urine concentrations of ACHN-383 and ACHN-789 after single-dose administration given concurrently	5 days
Urine concentrations of ACHN-383 and ACHN-789 after multiple-dose administration given concurrently	19 days

Collaborators and Investigators

• Sponsor: Achaogen, Inc.
• Investigators: Study Director: Daniel J Cloutier, PharmD, Achaogen, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): May 17, 2017
• Primary Completion (Actual): October 15, 2017
• Study Completion (Actual): October 15, 2017

Study Registration Dates

• First Submitted: May 15, 2017
• First Submitted That Met QC Criteria: May 20, 2017
• First Posted (Actual): May 23, 2017

Study Record Updates

• Last Update Posted (Actual): December 2, 2017
• Last Update Submitted That Met QC Criteria: November 29, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Other Study ID Numbers: ACHN-172-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No