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

NCT01561963 | Completed Phase 1 Results

• 1 other identifier: CC-10004-CP-025
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy Subjects

Keywords

Apremilast; drug interaction; pharmacokinetics

Outcome Measures

Primary Outcomes (7)

• 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

Study Arms (1)

Apremilast and Rifampin

EXPERIMENTAL

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; Drug: Rifampin Oral Capsules; Drug: Rifampin IV Solution

Interventions

Apremilast DRUG

Tablets for oral administration

Also known as: CC-10004, Otezla®

Apremilast and Rifampin

Rifampin Oral Capsules DRUG

Capsules for oral administration

Also known as: RIFADIN™

Apremilast and Rifampin

Rifampin IV Solution DRUG

Intravenous (IV) solution

Also known as: RIFADIN™

Apremilast and Rifampin

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male or female subjects of any ethnic origin between ages of 18 and 55 with a body mass index between 18 and 33

You may not qualify if:

• 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

Sponsors & Collaborators

• Amgen: lead

Study Sites (1)

Quintiles

Overland Park, Kansas, 66211, United States

Location

Related Publications (1)

• Liu Y, Zhou S, Wan Y, Wu A, Palmisano M. The impact of co-administration of ketoconazole and rifampicin on the pharmacokinetics of apremilast in healthy volunteers. Br J Clin Pharmacol. 2014 Nov;78(5):1050-7. doi: 10.1111/bcp.12448.

  PMID: 24962564 BACKGROUND

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Interventions

apremilast; Rifampin

Intervention Hierarchy (Ancestors)

Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

medinfo@amgen.com

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 21, 2012
• First Posted: March 23, 2012
• Study Start: February 1, 2012
• Primary Completion: April 1, 2012
• Study Completion: April 1, 2012
• Last Updated: June 9, 2021
• Results First Posted: June 9, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.

Locations

US (1)