Effects of Age and Sex on the Pharmacokinetics of Apremilast in Healthy Adults

An Open-Label, Single-Dose Study to Evaluate the Effects of Age and Sex on the Pharmacokinetics of Apremilast (CC-10004) in Healthy Subjects

The purpose of the study is to evaluate the effects of age and sex on the pharmacokinetics and safety of a single oral dose of 30 mg apremilast in healthy adults.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteer
• Intervention / Treatment: Drug: Apremilast

Detailed Description

This is an open-label, parallel group study where eligible elderly adults (aged 65-85 years inclusive) and younger adults (aged 18-55 years inclusive) and who are matched to the elderly participants by sex and body mass index (BMI) (± 10%) will receive a single dose of 30 mg apremilast under fasting conditions.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Lenexa, Kansas, United States, 66219
      • PRA International
  • Texas
    • Dallas, Texas, United States, 75247
      • Clinical Development Services

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Inclusion Criteria for elderly group

1. Healthy male or female subjects of any ethnic origin between ages of 65 and 85 inclusive with a body mass index (BMI) between 18 and 35.
2. Females must have been surgically sterilized at least 6 months prior to screening or be postmenopausal (to be confirmed by lab tests).
3. Males must agree to use latex or polyurethane condoms when engaging in sex during the study and for at least 28 days after dosing.
4. Elderly subjects with stable, chronic medical condition may be eligible if the condition is well-controlled and medications do not interfere with study procedures or pharmacokinetic interpretation

Inclusion Criteria for younger group:

1. Healthy male or female of any ethnic origin between the ages of 18 and 55 inclusive with a BMI between 18 and 35.
2. Males must agree to use latex or polyurethane condoms when engaging in sex during the study and for at least 28 days after dosing.

3. 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. For younger females who are not able to become pregnant, the conditions for the elderly females will apply.

Exclusion Criteria:

1. 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.
2. 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.
3. 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).
4. Subjects with known serum hepatitis, is a known carrier of hepatitis B surface antigen, hepatitis C antibody, or human immunodeficiency virus antibody.
5. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Elderly: Apremilast 30 mg; Participants aged 65 to 85 years received a single oral dose of 30 mg apremilast on Day 1.	Drug: Apremilast; One oral 30 mg dose of apremilast; Other Names: CC-10004; Otezla®
Experimental: Younger: Apremilast 30 mg; Participants aged 18 to 55 years received a single oral dose of 30 mg apremilast on Day 1.	Drug: Apremilast; One oral 30 mg dose of apremilast; Other Names: CC-10004; Otezla®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUC0-t) of Apremilast	The lower limit of quantitation for apremilast plasma concentrations was 1.0 ng/mL. AUC0-t was calculated using the linear trapezoidal method when concentrations were increasing and the logarithmic trapezoidal method when concentrations were decreasing.	Day 1 predose and at 0.5, 1, 1.5, 2, 2.5, 3, 5, 8, 12, 24, 36, and 48 hours after dosing.
AUC From Time Zero to Time of Last Quantifiable Concentration (AUC0-t) of Apremilast by Sex	The lower limit of quantitation for apremilast plasma concentrations was 1.0 ng/mL. AUC0-t was calculated using the linear trapezoidal method when concentrations were increasing and the logarithmic trapezoidal method when concentrations were decreasing.	Day 1 predose 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	The lower limit of quantitation for apremilast plasma concentrations was 1.0 ng/mL.	Day 1 predose and at 0.5, 1, 1.5, 2, 2.5, 3, 5, 8, 12, 24, 36, and 48 hours after dosing.
AUC From Time Zero Extrapolated to Infinity (AUC0-∞) of Apremilast by Sex	The lower limit of quantitation for apremilast plasma concentrations was 1.0 ng/mL.	Day 1 predose and at 0.5, 1, 1.5, 2, 2.5, 3, 5, 8, 12, 24, 36, and 48 hours after dosing.
Maximum Observed Plasma Concentration (Cmax) of Apremilast	The lower limit of quantitation for apremilast plasma concentrations was 1.0 ng/mL.	Day 1 predose and at 0.5, 1, 1.5, 2, 2.5, 3, 5, 8, 12, 24, 36, and 48 hours after dosing.
Maximum Observed Plasma Concentration of Apremilast by Sex	The lower limit of quantitation for apremilast plasma concentrations was 1.0 ng/mL.	Day 1 predose 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	The lower limit of quantitation for apremilast plasma concentrations was 1.0 ng/mL.	Day 1 predose 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 by Sex	The lower limit of quantitation for apremilast plasma concentrations was 1.0 ng/mL.	Day 1 predose 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)		Day 1 predose 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 by Sex		Day 1 predose 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		Day 1 predose 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 of Apremilast by Sex		Day 1 predose 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		Day 1 predose 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 by Sex		Day 1 predose 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 the 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 pre-existing condition) was considered an AE.	From first dose of study drug up to 11 days

Collaborators and Investigators

• Sponsor: Amgen

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2012
• Primary Completion (Actual): March 1, 2012
• Study Completion (Actual): April 1, 2012

Study Registration Dates

• First Submitted: July 3, 2012
• First Submitted That Met QC Criteria: July 5, 2012
• First Posted (Estimate): July 6, 2012

Study Record Updates

• Last Update Posted (Actual): April 14, 2021
• Last Update Submitted That Met QC Criteria: March 22, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: safety; pharmacokinetic; Apremilast; Pharmacokinetics and safety in healthy volunteer subjects
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Phosphodiesterase Inhibitors; Phosphodiesterase 4 Inhibitors; Apremilast
• Other Study ID Numbers: CC-10004-CP-024; 20200149 (Other Identifier: Amgen Study ID)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
• IPD Sharing 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.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No