A Drug-Drug Interaction Study to Evaluate the Effect of Rifampin on the Pharmacokinetics of Apremilast

Study Overview
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Brief Summary
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The purpose of this study is to evaluate how the pharmacokinetics of apremilast may be affected by a single intravenous dose of rifampin and multiple oral doses of rifampin.

Official Title
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A Phase 1, Open-label, Three-period, Fixed-sequence Study to Evaluate the Effects of Rifampin on the Pharmacokinetics of Apremilast (CC-10004) in Healthy Subjects

Conditions
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Healthy Subjects

Intervention / Treatment
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* Drug: Apremilast
* Drug: Rifampin Oral Capsules
* Drug: Rifampin IV Solution


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 55 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, allergic or other major disorders. Use of any prescribed or non-prescribed systemic or topical medication (including vitamins and herbal medicines, e.g. St. John's Wort) within 30 days of the first dose, unless an exception is granted by the sponsor. 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

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: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Apremilast and Rifampin<br>Participants received the following 3 treatment regimens: A single oral dose of 30 mg apremilast on Day 1 (Period 1); A single oral dose of 30 mg apremilast followed 5 minutes later by a 30-minute intravenous infusion of 600 mg rifampin on Day 5 (Period 2); Once daily oral doses of 600 mg rifampin for 15 days (from Day 7 to Day 21) with a single oral dose of 30 mg apremilast co-administered with the rifampin dose on Day 20 (Period 3). | Drug: Apremilast<br>* Tablets for oral administration<br>* Other names: Otezla®;Drug: Rifampin Oral Capsules<br>* Capsules for oral administration<br>* Other names: RIFADIN™;Drug: Rifampin IV Solution<br>* Intravenous (IV) solution<br>* Other names: RIFADIN™;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUCt) of Apremilast | Plasma concentrations of apremilast were determined by means of a validated, sensitive, and specific high performance liquid chromatography/tandem mass spectrometric (LC-MS/MS) assay. | Pre-dose and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 36, and 48 hours following apremilast dosing on Days 1, 5, and 20 | 
| Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC∞) of Apremilast | Plasma concentrations of apremilast were determined by means of a validated, sensitive, and specific high performance liquid chromatography/tandem mass spectrometric (LC-MS/MS) assay. | Pre-dose and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 36, and 48 hours following apremilast dosing on Days 1, 5, and 20 | 
| Maximum Observed Plasma Concentration (Cmax) of Apremilast | Plasma concentrations of apremilast were determined by means of a validated, sensitive, and specific high performance liquid chromatography/tandem mass spectrometric (LC-MS/MS) assay. | Pre-dose and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 36, and 48 hours following apremilast dosing on Days 1, 5, and 20 | 
| Time to Maximum Observed Plasma Concentration (Tmax) of Apremilast | Plasma concentrations of apremilast were determined by means of a validated, sensitive, and specific high performance liquid chromatography/tandem mass spectrometric (LC-MS/MS) assay. | Pre-dose and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 36, and 48 hours following apremilast dosing on Days 1, 5, and 20 | 
| Estimate of the Terminal Elimination Half-life (T1/2) of Apremilast in Plasma | Plasma concentrations of apremilast were determined by means of a validated, sensitive, and specific high performance liquid chromatography/tandem mass spectrometric (LC-MS/MS) assay. | Pre-dose and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 36, and 48 hours following apremilast dosing on Days 1, 5, and 20 | 
| Apparent Total Plasma Clearance (CL/F) of Apremilast | Plasma concentrations of apremilast were determined by means of a validated, sensitive, and specific high performance liquid chromatography/tandem mass spectrometric (LC-MS/MS) assay. | Pre-dose and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 36, and 48 hours following apremilast dosing on Days 1, 5, and 20 | 
| Apparent Volume of Distribution (Vz/F) of Apremilast | Plasma concentrations of apremilast were determined by means of a validated, sensitive, and specific high performance liquid chromatography/tandem mass spectrometric (LC-MS/MS) assay. | Pre-dose and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 36, and 48 hours following apremilast dosing on Days 1, 5, and 20 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Apremilast, drug interaction, pharmacokinetics