Study to Evaluate Bioavailability of Apremilast Oral Suspension Relative to Tablet and to Assess Effect of Food on the Pharmacokinetics (PK) of the Oral Suspension

NCT02641353 | Completed Phase 1 Results

• 2 other identifiers: CC-10004-CP-03220200157
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess how much of apremilast is found in the blood unchanged when administered as an oral suspension compared to when it is administered as a tablet formulation. The effect of food on apremilast oral suspension will also be evaluated. In addition, information on the safety and tolerability of apremilast will be obtained.

Conditions

Healthy Volunteers

Keywords

Apremilast; Healthy volunteers; Bioavailability; Food effect; Pharmacokinetic

Outcome Measures

Primary Outcomes (9)

• Maximum Observed Plasma Concentration (Cmax) of Apremilast

  Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.

  Predose and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 60 and 72 hours after dosing on day 1 of each treatment period.

• Area Under the Concentration-time Curve From Time Zero to the Last Measured Time Point (AUC0-t) for Apremilast

  Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay. AUC from time zero to the last measured time point was calculated by the linear trapezoidal method.

  Predose and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 60 and 72 hours after dosing on day 1 of each treatment period.

• Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-∞) for Apremilast

  Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay. AUC from time zero to infinity was calculated as (AUC0-t + Ct/λz), where Ct is the last quantifiable concentration, and λz is the apparent terminal rate constant.

  Predose and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 60 and 72 hours after dosing on day 1 of each treatment period.

• Time to Maximum Observed Plasma Concentration (Tmax) of Apremilast

  Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.

  Predose and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 60 and 72 hours after dosing on day 1 of each treatment period.

• Terminal Elimination Half-life (T1/2) of Apremilast

  Predose and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 60 and 72 hours after dosing on day 1 of each treatment period.

• Apparent Clearance of Apremilast From Plasma After Extravascular Administration (CL/F)

  Predose and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 60 and 72 hours after dosing on day 1 of each treatment period.

• Apparent Volume of Distribution of Apremilast During the Terminal Phase (Vz/F)

  Predose and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 60 and 72 hours after dosing on day 1 of each treatment period.

• Lag Time (Tlag) of Apremilast

  Lag time is the delay between the time of administration and start of absorption.

  Predose and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 60 and 72 hours after dosing on day 1 of each treatment period.

• Relative Bioavailability (F) of Apremilast Oral Suspension Formulation

  Relative bioavailability of the oral suspension formulation compared to the tablet formulation, calculated as (AUC0-∞/Dose\[oral suspension\]) / (AUC0-∞/Dose\[tablet\]) \* 100%.

  Predose and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 60 and 72 hours after dosing on day 1 of each treatment period.

Secondary Outcomes (1)

• Number of Participants With Treatment-emergent Adverse Events

  From first dose of study drug in treatment period 1 to 8 days after the last dose; up to 18 days.

Study Arms (3)

Treatment A: Apremilast 30 mg Tablet - Fasted

EXPERIMENTAL

A single oral dose of 30 mg apremilast tablet after an overnight fast.

Drug: Apremilast Tablet

Treatment B: Apremilast 30 mg Oral Suspension - Fasted

EXPERIMENTAL

A single oral dose of 30 mg apremilast oral suspension formulation (6 mL) after an overnight fast.

Drug: Apremilast Oral Suspension

Treatment C - Apremilast 30 mg Oral Suspension - Fed

EXPERIMENTAL

A single oral dose of 30 mg apremilast oral suspension formulation (6 mL) after a high-fat meal.

Drug: Apremilast Oral Suspension

Interventions

Apremilast Tablet DRUG

30 mg tablet

Also known as: Otzela, CC-10004

Treatment A: Apremilast 30 mg Tablet - Fasted

Apremilast Oral Suspension DRUG

30 mg oral suspension

Also known as: Otzela, CC-10004

Treatment B: Apremilast 30 mg Oral Suspension - Fasted; Treatment C - Apremilast 30 mg Oral Suspension - Fed

Eligibility Criteria

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

You may qualify if:

• Subjects must satisfy ALL of the following criteria to be eligible for enrollment into the study:
• Must understand and voluntarily sign a written Informed Consent (ICF) prior to any study-related procedures being performed.
• Must be able to communicate with the investigator, understand and comply with the requirements of the study, and agree to adhere to restrictions and examination schedules.
• Male and female subjects of any race between 18 to 55 years of age (inclusive), and in good health as determined by the Investigator at the time of signing the informed consent document.
• Have a Body Mass Index (BMI) between 18 and 33 kg/m\^2 (inclusive).
• No clinically significant laboratory test results as determined by the investigator.
• At the screening visit, must be afebrile, with supine systolic blood pressure (BP): 90 to 140 mmHg, supine diastolic BP: 50 to 90 mmHg, and pulse rate: 40 to 110 bpm. Eligibility criteria for vital signs performed during check-in and/or predose on Day 1 will be at the discretion of the Investigator.
• Must have a normal or clinically acceptable 12-lead electrocardiogram (ECG). Subjects must have a QTcF value ≤ 450 msec.
• Contraception Requirements:
• Must comply with the following acceptable forms of contraception. All female of childbearing potential (FCBP) must use one of the approved contraceptive options as described below while taking apremilast and for at least 28 days after administration of the last dose of the apremilast.
• At the time of study entry, and at any time during the study when a FCBP's contraceptive measures or ability to become pregnant changes, the Investigator will educate the subject regarding contraception options and the correct and consistent use of effective contraceptive methods in order to successfully prevent pregnancy
• All FCBP must have a negative pregnancy test at Visits 1 and 2. All FCBP subjects who engage in activity in which conception is possible must use one of the approved contraceptive options described below:
• Option 1: Any one of the following highly effective methods: hormonal contraception (oral, injection, implant, transdermal patch, vaginal ring); intrauterine device (IUD); tubal ligation; or partner's vasectomy; OR Option 2: Male or female condom (latex condom or non-latex condom NOT made out of natural \[animal\] membrane \[for example, polyurethane\]); PLUS one of the following additional barrier methods: (a) diaphragm with spermicide; (b) cervical cap with spermicide; or (c) contraceptive sponge with spermicide.
• Male subjects (including those who have had a vasectomy) who engage in activity in which conception is possible must use barrier contraception (latex or non-latex condoms NOT made out of natural \[animal\] membrane \[for example, polyurethane\]) while on investigational product (IP) and for at least 28 days after the last dose of IP.
• Must agree to refrain from donating sperm, blood or plasma (other than for this study) while participating in this study and for at least 28 days after the last dose of investigational product.

You may not qualify if:

• The presence of ANY of the following will exclude any healthy subject from enrollment into the study:
• History of any clinically significant and relevant neurological, psychiatric, gastrointestinal, renal, hepatic, cardiovascular, psychological, pulmonary, metabolic, endocrine, hematological, allergic disease, drug allergies, or other major disorders.
• Any condition which places the subject at unacceptable risk if he were to participate in the study, or confounds the ability to interpret data from the study.
• Use of any prescribed systemic or topical medication within 30 days of the first dose administration.
• Use of any non-prescribed systemic or topical medication (including vitamin/mineral supplements, and herbal medicines) within 14 days of the first dose administration, Any surgical or medical condition possibly affecting drug absorption, distribution, metabolism and excretion, eg, bariatric procedure, colon resection, irritable bowel syndrome, Crohn's disease, etc. Subjects with cholecystectomy and appendectomy may be included.
• 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).
• Donated blood or plasma within 8 weeks before the first dose administration to a blood bank or blood donation center.
• History of drug abuse (as defined by the current version of the Diagnostic and Statistical Manual \[DSM\]) within 2 years before dosing, or a positive drug screen reflecting consumption of illicit drugs.
• History of alcohol abuse (as defined by the current version of the DSM) within 2 years before dosing, or a positive alcohol screen.
• Known to have hepatitis, or known to be a carrier of the hepatitis B surface antigen (HBsAg), or hepatitis C antibody (HCV Ab), or have a positive result to the test for HBsAg, HCV Ab, or human immunodeficiency virus (HIV) antibodies at Screening.

Sponsors & Collaborators

• Amgen: lead

Study Sites (1)

Covance Clinical Research Unit Inc

Madison, Wisconsin, 53704, United States

Location

MeSH Terms

Interventions

apremilast

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: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: December 23, 2015
• First Posted: December 29, 2015
• Study Start: January 5, 2016
• Primary Completion: February 27, 2016
• Study Completion: February 27, 2016
• Last Updated: August 5, 2021
• Results First Posted: August 5, 2021

Record last verified: 2021-07

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)