Safety and Pharmacokinetics of AVL-292 Following Multiple Doses and the Effect of Food on the Single-dose Pharmacokinetics of AVL-292

Study Overview
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Brief Summary
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This is a 2-part study. The first part is to evaluate the safety, pharmacokinetics (PK) and pharmacodynamics of AVL-292 following multiple oral doses; and the second part is to evaluate the effect of food on the pharmacokinetics of a single oral dose of AVL-292.

Detailed Description
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Part 2 is an open-label, randomized, 2-period, 2-way crossover study to evaluate the effect of a standard high-fat breakfast on the pharmacokinetics of AVL-292. Ten subjects will be enrolled to receive 2 single doses of 200 mg AVL-292, one with food (i.e., fed) and the other without (i.e., fasted), in a randomized sequence.

Official Title
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A Phase 1, Two-part Study to Investigate the Safety and Pharmacokinetics of AVL-292 Following Multiple Oral Doses and to Evaluate the Effect of Food on the Pharmacokinetics of AVL-292 Following a Single Oral Dose in Healthy Adult Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: 50 mg AVL-292
* Drug: 100 mg AVL-292
* Drug: 200 mg AVL-292
* Drug: 350 mg AVL-292
* Drug: Placebo capsules


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male or female subjects of any ethnic origin between ages of 18 and 65 with a body mass index between 18 and 33 Exclusion Criteria: Recent history (i.e., within 3 years) of any clinically significant neurological, gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, endocrine, hematological, dermatological, psychological, ophthalmological, allergic or other major disorders; Use of any prescribed systemic or topical medication within 30 days of the first dose; Use of any non-prescribed systemic or topical medication (including vitamin/mineral supplements and herbal medicines, e.g., St. John's Wort) within 7 days of the first dose administration; Exposure to an investigational drug (new chemical entity) within 30 days prior to the first dose administration

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 50 mg of AVL-292 and Placebo<br>50 mg AVL-292 (2 x 25 mg AVL-292 capsules and 6 placebo capsules) once daily for 7 days administered orally under fasted condition | Drug: 50 mg AVL-292<br> <br> * Other names: AVL-292;Drug: Placebo capsules<br> <br> |
| Experimental: 100 mg of AVL-292 and Placebo<br>100 mg AVL-292 (4 x 25 mg AVL-292 capsules and 4 placebo capsules) once daily for 7 days administered orally under fasted condition | Drug: 100 mg AVL-292<br> <br> * Other names: AVL-292;Drug: Placebo capsules<br> <br> |
| Experimental: 200 mg AVL-292<br>8 x 25 mg AVL-292 capsules orally once daily for 7 days under fasted condition | Drug: 200 mg AVL-292<br> <br> * Other names: AVL-292;|
| Experimental: 350 mg of AVL-292<br>350 mg AVL-292 (14 x 25 mg AVL-292 capsules) once daily for 7 days administered orally under fasted condition | Drug: 350 mg AVL-292<br> <br> * Other names: AVL-292;|
| Placebo Comparator: Placebo - 8 capsules<br>8 placebo capsules once daily for 7 days administered orally under fasted condition | Drug: Placebo capsules<br> <br> |
| Placebo Comparator: Placebo - 14 capsules<br>14 placebo capsules once daily for 7 days administered orally under fasted condition | Drug: Placebo capsules<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events | Number of participants with adverse events | Up to 28 days after last AVL-292 dose | 
| PK-(Cmax) | Maximum observed concentration in plasma | 24 hours after the last AVL-292 dose on days 1 and 7 | 
| PK-(AUC) | Area under the plasma concentration-time curve | 24 hours after the last AVL-292 dose days 1 and 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacodynamic response measured in percentage of target occupancy by AVL-292 in peripheral blood mononuclear cells | Pharmacodynamic response measured in percentage of target occupancy by AVL-292 in peripheral blood mononuclear cells | 24 hours after the last AVL-292 dose days 1 and 7 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AVL-292, Safety, Pharmacokinetics, Pharmacodynamics, Pharmacology, Clinical