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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Placebo capsules; Drug: 50 mg AVL-292; Drug: 100 mg AVL-292; Drug: 200 mg AVL-292; Drug: 350 mg AVL-292

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 54
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75247
      • Covance Clinical Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 50 mg of AVL-292 and Placebo; 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: Placebo capsules; Drug: 50 mg AVL-292; Other Names: AVL-292
Experimental: 100 mg of AVL-292 and Placebo; 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: Placebo capsules; Drug: 100 mg AVL-292; Other Names: AVL-292
Experimental: 200 mg AVL-292; 8 x 25 mg AVL-292 capsules orally once daily for 7 days under fasted condition	Drug: 200 mg AVL-292; Other Names: AVL-292
Experimental: 350 mg of AVL-292; 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; Other Names: AVL-292
Placebo Comparator: Placebo - 8 capsules; 8 placebo capsules once daily for 7 days administered orally under fasted condition	Drug: Placebo capsules
Placebo Comparator: Placebo - 14 capsules; 14 placebo capsules once daily for 7 days administered orally under fasted condition	Drug: Placebo capsules

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Celgene

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2012
• Primary Completion (Actual): October 8, 2012
• Study Completion (Actual): October 8, 2012

Study Registration Dates

• First Submitted: September 21, 2012
• First Submitted That Met QC Criteria: September 24, 2012
• First Posted (Estimate): September 25, 2012

Study Record Updates

• Last Update Posted (Actual): November 4, 2019
• Last Update Submitted That Met QC Criteria: October 31, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: Safety; Pharmacokinetics; Pharmacodynamics; Pharmacology, Clinical; AVL-292
• Other Study ID Numbers: AVL-292-004