Effect of Food on the Pharmacokinetics of Apremilast (CC-10004) in Healthy Adults

Study Overview
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Brief Summary
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The purpose of the study is to evaluate the effects of a high fat meal on the pharmacokinetics of a single dose of 30 mg apremilast in healthy adults.

Detailed Description
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Participants will be randomized to receive a single dose of 30 mg apremilast during each of the 2 periods; once under fasting conditions and once after a high fat meal. Participants will be randomly assigned to receive apremilast either fasted first, then fed, or fed first then fasted. Participants will check into the study center on Day -1 of each period, will be dosed on Day 1, and discharged from the study center on Day 3 after all scheduled pharmacokinetic blood draws and safety evaluations. After a washout of 5 to 10 days, participants will return for period 2 during which they will receive apremilast according to their assigned sequence.

Official Title
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A Phase 1, Open-Label, Randomized, Two-Period, Two-Sequence Crossover Study to Assess the Effect of Food on the Pharmacokinetics of a Single 30 mg Tablet of Apremilast (CC-10004) in Healthy Subjects

Conditions
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Healthy Volunteer

Intervention / Treatment
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* Drug: Apremilast


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 inclusive with a body mass index (BMI) between 18 and 33. Females who are able to become pregnant have a negative pregnancy test at screening and baseline, and must agree to use one of the following: a highly effective form of contraception (ex. Non-oral hormonal, intrauterine device) OR oral hormonal contraceptive plus one additional form of barrier contraception OR Two forms of barrier contraception These must be effective by the time of screening. All other females must have been surgically sterilized at least 6 months prior to screening or be postmenopausal (to be confirmed by lab tests). Males must agree to use latex or polyurethane condoms when engaging in sex during the study and for at least 28 days after dosing. Exclusion Criteria: Any condition, including the presence of laboratory abnormalities, or psychiatric illness, that would prevent the subject from signing the Informed Consent form, places the subject at unacceptable risk if he were to participate in the study, or confounds the ability to interpret data from the study. Presence of any surgical or medical conditions possibly affecting drug absorption, distribution, metabolism, and excretion, or plans to have elective or medical procedures during the conduct of the trial. Exposure to an investigational drug (new chemical entity) within 30 days prior to the first dose administration or 5 half-lives of that investigational drug, if known (whichever is longer). Subjects with known serum hepatitis, is a known carrier of hepatitis B surface antigen, hepatitis C antibody, or human immunodeficiency virus antibody. Subjects who have used prescription systemic or topical medications within 30 days of dosing, unless it is being used to treat a stable, chronic medical condition. This includes medication that is an inhibitor or inducer of P-glycoprotein transporter and CYP-3A4/5 used within 14 days of dosing.

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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sequence 1: Apremilast Fasted / Fed<br>In Period 1 participants will receive a single 30 mg apremilast tablet administered under fasted conditions and in Period 2 participants will receive a single 30 mg apremilast tablet administered after a high fat meal. | Drug: Apremilast<br>* Tablet for oral administration<br>* Other names: Otezla®;|
| Experimental: Sequence 2: Apremilast Fed / Fasted<br>In Period 1 participants will receive a single 30 mg apremilast tablet administered after a high fat meal and in Period 2 participants will receive a single 30 mg apremilast tablet administered under fasted conditions. | Drug: Apremilast<br>* Tablet for oral administration<br>* Other names: Otezla®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Plasma Concentration (Cmax) of Apremilast | Plasma concentrations of apremilast were determined by using a validated liquid chromatography-tandem mass spectrometry assay. | Day 1 of each treatment period at pre-dose, and at 0.5, 1, 1.5, 2, 2.5, 3, 5, 8, 12, 24, 36, and 48 hours after dosing. | 
| Time to Maximum Observed Plasma Concentration (Tmax) of Apremilast | Plasma concentrations of apremilast were determined by using a validated liquid chromatography-tandem mass spectrometry assay. | Day 1 of each treatment period at pre-dose, and at 0.5, 1, 1.5, 2, 2.5, 3, 5, 8, 12, 24, 36, and 48 hours after dosing. | 
| Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUC0-t) of Apremilast | Plasma concentrations of apremilast were determined by using a validated liquid chromatography-tandem mass spectrometry assay. AUC0-t was calculated using the linear trapezoidal method (linear up log down) when concentrations were increasing and the logarithmic trapezoidal method when concentrations were decreasing. | Day 1 of each treatment period at pre-dose, and at 0.5, 1, 1.5, 2, 2.5, 3, 5, 8, 12, 24, 36, and 48 hours after dosing. | 
| Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-∞) of Apremilast | Plasma concentrations of apremilast were determined by using a validated liquid chromatography-tandem mass spectrometry assay. | Day 1 of each treatment period at pre-dose, and at 0.5, 1, 1.5, 2, 2.5, 3, 5, 8, 12, 24, 36, and 48 hours after dosing. | 
| Estimate of Terminal Elimination Half-life of Apremilast in Plasma (t1/2) | Plasma concentrations of apremilast were determined by using a validated liquid chromatography-tandem mass spectrometry assay. | Day 1 of each treatment period at pre-dose, and at 0.5, 1, 1.5, 2, 2.5, 3, 5, 8, 12, 24, 36, and 48 hours after dosing. | 
| Apparent Total Plasma Clearance When Dosed Orally (CL/F) of Apremilast | Plasma concentrations of apremilast were determined by using a validated liquid chromatography-tandem mass spectrometry assay. | Day 1 of each treatment period at pre-dose, and at 0.5, 1, 1.5, 2, 2.5, 3, 5, 8, 12, 24, 36, and 48 hours after dosing. | 
| Apparent Total Volume of Distribution When Dosed Orally (Vz/F) of Apremilast | Plasma concentrations of apremilast were determined by using a validated liquid chromatography-tandem mass spectrometry assay. | Day 1 of each treatment period at pre-dose, and at 0.5, 1, 1.5, 2, 2.5, 3, 5, 8, 12, 24, 36, and 48 hours after dosing. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events | An adverse event (AE) was any noxious, unintended, or untoward medical occurrence that appeared or worsened in a participant during the course of this study. It could have been a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values, regardless of etiology. Any worsening (i.e., any clinically significant adverse change in the frequency or intensity of a preexisting condition) was considered an AE. | From first dose of study drug in Period 1 up to 5 to 10 days after dosing in Period 2, approximately 20 days. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Apremilast,, pharmacokinetic, safety, Safety and pharmacokinetics in healthy volunteer subjects