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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 50 mg of AVL-292 and Placebo | Experimental | 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 |
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| 100 mg of AVL-292 and Placebo | Experimental | 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 |
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| 200 mg AVL-292 | Experimental | 8 x 25 mg AVL-292 capsules orally once daily for 7 days under fasted condition |
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| 350 mg of AVL-292 | Experimental | 350 mg AVL-292 (14 x 25 mg AVL-292 capsules) once daily for 7 days administered orally under fasted condition |
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| Placebo - 8 capsules | Placebo Comparator | 8 placebo capsules once daily for 7 days administered orally under fasted condition |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 50 mg AVL-292 | Drug |
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| 100 mg AVL-292 |
| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Maria Palmisano, MD | Celgene Corporation | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Covance Clinical Research Unit | Dallas | Texas | 75247 | United States |
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| Placebo - 14 capsules |
| Placebo Comparator |
14 placebo capsules once daily for 7 days administered orally under fasted condition |
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| Drug |
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| 200 mg AVL-292 | Drug |
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| 350 mg AVL-292 | Drug |
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| Placebo capsules | Drug |
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