A Study in Healthy Volunteers to Evaluate the Safety, Tolerability, Pharmacokinetics, and Drug-Drug Interaction Potential of Single and Multiple Doses of ALG-097558

Study Overview
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Brief Summary
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A multi-part study of ALG-097558 to evaluate safety, tolerability, pharmacokinetics and drug-drug interaction potential after single and multiple doses in healthy volunteers

Official Title
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A First-in-Human Multi-Part Phase 1 Study in Healthy Volunteers to Evaluate the Safety, Tolerability, Pharmacokinetics, and Drug-Drug Interaction Potential of Single and Multiple Doses of ALG-097558

Conditions
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COVID-19

Intervention / Treatment
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* Drug: ALG-097558
* Drug: Placebo
* Drug: Midazolam
* Drug: Itraconazole
* Drug: Carbamazepine
* Drug: ALG-097558 in solution formulation
* Drug: ALG-097558 in tablet formulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria for All Subjects: Male and Female between 18 and 55 years old BMI 18.0 to 32.0 kg/m^2 Female subjects must have a negative serum pregnancy test at screening Subjects must have a 12-lead electrocardiogram (ECG) that meets the protocol criteria Exclusion Criteria for All Subjects: Subjects with any current or previous illness that, in the opinion of the Investigator, might confound the results of the study or pose an additional risk in administering study drug to the subject or that could prevent, limit, or confound the protocol specified assessments or study results' interpretation Subjects with a past history of cardiac arrhythmias, risk factors for Torsade de Pointes syndrome (e.g., hypokalemia, family history of long QT Syndrome) or history or clinical evidence at screening of significant or unstable cardiac disease etc. Subjects with a history of clinically significant drug allergy Excessive use of alcohol defined as regular consumption of ≥14 units/week Unwilling to abstain from alcohol use for 1 week prior to start of the study through end of study follow up Subjects with Hepatitis A, B, C, E or HIV-1/HIV-2 infection or acute infections such as SARS- CoV-2 infection Subjects with renal dysfunction (e.g., estimated creatinine clearance <90 mL/min/1.73 m^2 at screening, calculated by the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formula)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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
Interventional Model Description: Parts 1 and 2 of the study are parallel assignment, with 2 arms. Parts 3, 5, and 6 are fixed sequence, crossover studies. Part 4 is a partially placebo-controlled, fixed sequence, crossover study.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ALG-097558<br>Oral doses of ALG-097558 in Healthy Volunteers, up to 20 doses over 10 days | Drug: ALG-097558<br>* single or multiple doses of ALG-097558<br>|
| Placebo Comparator: Placebo<br>Oral doses of placebo in Healthy Volunteers, up to 20 doses over 10 days | Drug: Placebo<br>* single or multiple doses of placebo<br>|
| Experimental: ALG-097558 and Midazolam<br>Oral doses of ALG-097558, up to 14 doses over 7 days and oral dose of Midazolam, up to 2 doses, over 2 days, in Healthy Volunteers | Drug: ALG-097558<br>* single or multiple doses of ALG-097558<br>Drug: Midazolam<br>* Multiple doses of Midazolam<br>|
| Experimental: ALG-097558, Placebo, and, Itraconazole<br>Oral doses of placebo, up to 2 doses over 2 days, followed by ALG-097558, up to 2 doses over 2 days, and itraconazole up to 10 doses over 10 days, in Healthy Volunteers. | Drug: ALG-097558<br>* single or multiple doses of ALG-097558<br>Drug: Placebo<br>* single or multiple doses of placebo<br>Drug: Itraconazole<br>* Multiple doses of Itraconazole<br>|
| Experimental: ALG-097558 and Carbamazepine<br>Oral doses of ALG-097558, up to 2 doses over 2 days and oral doses of Carbamazepine, up to 30 doses, over 15 days, in Healthy Volunteers | Drug: ALG-097558<br>* single or multiple doses of ALG-097558<br>Drug: Carbamazepine<br>* Multiple doses of Carbamazepine<br>|
| Experimental: ALG-097558 Bioavailability<br>Oral doses of ALG-097558, up to 3 doses over 3 days, both solution and tablet formulations dosed in fasted state, and tablet formulation dosed in fed state, in Healthy Volunteers | Drug: ALG-097558 in solution formulation<br>* ALG-097558 in solution administered in fasted state<br>Drug: ALG-097558 in tablet formulation<br>* ALG-097558 in tablet administered in fasted and fed state<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | The number and severity of treatment emergent adverse events as assessed by DAIDS v2.1 | Up to 11 days for Part 1 | 
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | The number and severity of treatment emergent adverse events as assessed by DAIDS v2.1 | Up to 20 days for Part 2 | 
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | The number and severity of treatment emergent adverse events as assessed by DAIDS v2.1 | Up to 20 days for Part 3 | 
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | The number and severity of treatment emergent adverse events as assessed by DAIDS v2.1 | Up to 23 days for Part 4 | 
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | The number and severity of treatment emergent adverse events as assessed by DAIDS v2.1 | Up to 28 days for Part 5 | 
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | The number and severity of treatment emergent adverse events as assessed by DAIDS v2.1 | Up to 17 days for Part 6 | 
| Area under the concentration time curve [AUC] | Pharmacokinetic parameters of Midazolam and applicable metabolites | Predose (-2 hours) up to 11 days | 
| Time to maximum plasma concentration [Tmax] | Pharmacokinetic parameters of Midazolam and applicable metabolites | Predose (-2 hours) up to 11 days | 
| Maximum plasma concentration [Cmax] | Pharmacokinetic parameters of Midazolam and applicable metabolites | Predose (-2 hours) up to 11 days | 
| Minimum plasma concentration [Cmin] | Pharmacokinetic parameters of Midazolam and applicable metabolites | Predose (-2 hours) up to 11 days | 
| C0 [predose] | Pharmacokinetic parameters of Midazolam and applicable metabolites | Predose (-2 hours) up to 11 days | 
| Half-life [t1/2] | Pharmacokinetic parameters of Midazolam and applicable metabolites | Predose (-2 hours) up to 11 days | 
| Area under the concentration time curve [AUC] | Pharmacokinetic parameters of ALG-07558 and metabolite ALG-097730 following administration of itraconazole or carbamazepine | Predose (-0.75 hours) up to 19 days | 
| Time to maximum plasma concentration [Tmax] | Pharmacokinetic parameters of ALG-07558 and metabolite ALG-097730 following administration of itraconazole or carbamazepine | Predose (-0.75 hours) up to 19 days | 
| Maximum plasma concentration [Cmax] | Pharmacokinetic parameters of ALG-07558 and metabolite ALG-097730 following administration of itraconazole or carbamazepine | Predose (-0.75 hours) up to 19 days | 
| Minimum plasma concentration [Cmin] | Pharmacokinetic parameters of ALG-07558 and metabolite ALG-097730 following administration of itraconazole or carbamazepine | Predose (-0.75 hours) up to 19 days | 
| C0 [predose] | Pharmacokinetic parameters of ALG-07558 and metabolite ALG-097730 following administration of itraconazole or carbamazepine | Predose (-0.75 hours) up to 19 days | 
| Half-life [t1/2] | Pharmacokinetic parameters of ALG-07558 and metabolite ALG-097730 following administration of itraconazole or carbamazepine | Predose (-0.75 hours) up to 19 days | 
| Area under the concentration time curve [AUC] | Pharmacokinetic parameters of ALG-07558 and metabolite ALG-097730 following administration of ALG-097558 in either solution or tablet formulations and following a high fat diet | Predose (-0.75 hours) up to 9 days | 
| Time to maximum plasma concentration [Tmax] | Pharmacokinetic parameters of ALG-07558 and metabolite ALG-097730 following administration of ALG-097558 in either solution or tablet formulations and following a high fat diet | Predose (-0.75 hours) up to 9 days | 
| Maximum plasma concentration [Cmax] | Pharmacokinetic parameters of ALG-07558 and metabolite ALG-097730 following administration of ALG-097558 in either solution or tablet formulations and following a high fat diet | Predose (-0.75 hours) up to 9 days | 
| Minimum plasma concentration [Cmin] | Pharmacokinetic parameters of ALG-07558 and metabolite ALG-097730 following administration of ALG-097558 in either solution or tablet formulations and following a high fat diet | Predose (-0.75 hours) up to 9 days | 
| C0 [predose] | Pharmacokinetic parameters of ALG-07558 and metabolite ALG-097730 following administration of ALG-097558 in either solution or tablet formulations and following a high fat diet | Predose (-0.75 hours) up to 9 days | 
| Half-life [t1/2] | Pharmacokinetic parameters of ALG-07558 and metabolite ALG-097730 following administration of ALG-097558 in either solution or tablet formulations and following a high fat diet | Predose (-0.75 hours) up to 9 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum plasma concentration [Cmax] | Pharmacokinetic parameters of ALG-097558 in plasma | Predose (-0.75 hours) up to 19 days | 
| Area under the concentration time curve [AUC] | Pharmacokinetic parameters of ALG-097558 in plasma | Predose (-0.75 hours) up to 19 days | 
| Time to maximum plasma concentration [Tmax] | Pharmacokinetic parameters of ALG-097558 in plasma | Predose (-0.75 hours) up to 19 days | 
| Minimum plasma concentration [Cmin] | Pharmacokinetic parameters of ALG-097558 in plasma | Predose (-0.75 hours) up to 19 days | 
| Half-life [t1/2] | Pharmacokinetic parameters of ALG-097558 in plasma | Predose (-0.75 hours) up to 19 days | 
| C0 [predose] | Pharmacokinetic parameters of ALG-097558 in plasma | Predose (-0.75 hours) up to 19 days | 
| Dose Proportionality | Pharmacokinetic parameters of ALG-097558 in plasma | Predose (-0.75 hours) up to 19 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Healthy Volunteer