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

Study Overview
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Brief Summary
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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

Official Title
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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

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: ACHN-383
* Drug: ACHN-789
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 |