Clinical trial NCT01634191: Effects of Age and Sex on the Pharmacokinetics of Apremilast in Healthy Adults
Official title: An Open-Label, Single-Dose Study to Evaluate the Effects of Age and Sex on the Pharmacokinetics of Apremilast (CC-10004) in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteer
Keywords: Apremilast
pharmacokinetic
safety
Pharmacokinetics and safety in healthy volunteer subjects
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2012-07-06
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUC0-t) of Apremilast
timeFrame: Day 1 predose and at 0.5, 1, 1.5, 2, 2.5, 3, 5, 8, 12, 24, 36, and 48 hours after dosing.
measure: AUC From Time Zero to Time of Last Quantifiable Concentration (AUC0-t) of Apremilast by Sex
timeFrame: Day 1 predose and at 0.5, 1, 1.5, 2, 2.5, 3, 5, 8, 12, 24, 36, and 48 hours after dosing.
measure: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-∞) of Apremilast
timeFrame: Day 1 predose and at 0.5, 1, 1.5, 2, 2.5, 3, 5, 8, 12, 24, 36, and 48 hours after dosing.
measure: AUC From Time Zero Extrapolated to Infinity (AUC0-∞) of Apremilast by Sex
timeFrame: Day 1 predose and at 0.5, 1, 1.5, 2, 2.5, 3, 5, 8, 12, 24, 36, and 48 hours after dosing.
measure: Maximum Observed Plasma Concentration (Cmax) of Apremilast
timeFrame: Day 1 predose and at 0.5, 1, 1.5, 2, 2.5, 3, 5, 8, 12, 24, 36, and 48 hours after dosing.
measure: Maximum Observed Plasma Concentration of Apremilast by Sex
timeFrame: Day 1 predose and at 0.5, 1, 1.5, 2, 2.5, 3, 5, 8, 12, 24, 36, and 48 hours after dosing.
measure: Time to Maximum Observed Plasma Concentration (Tmax) of Apremilast
timeFrame: Day 1 predose and at 0.5, 1, 1.5, 2, 2.5, 3, 5, 8, 12, 24, 36, and 48 hours after dosing.
measure: Time to Maximum Observed Plasma Concentration (Tmax) of Apremilast by Sex
timeFrame: Day 1 predose and at 0.5, 1, 1.5, 2, 2.5, 3, 5, 8, 12, 24, 36, and 48 hours after dosing.
measure: Estimate of Terminal Elimination Half-life of Apremilast in Plasma (t1/2)
timeFrame: Day 1 predose and at 0.5, 1, 1.5, 2, 2.5, 3, 5, 8, 12, 24, 36, and 48 hours after dosing.
measure: Estimate of Terminal Elimination Half-life of Apremilast in Plasma by Sex
timeFrame: Day 1 predose and at 0.5, 1, 1.5, 2, 2.5, 3, 5, 8, 12, 24, 36, and 48 hours after dosing.
measure: Apparent Total Plasma Clearance When Dosed Orally (CL/F) of Apremilast
timeFrame: Day 1 predose and at 0.5, 1, 1.5, 2, 2.5, 3, 5, 8, 12, 24, 36, and 48 hours after dosing.
measure: Apparent Total Plasma Clearance When Dosed Orally of Apremilast by Sex
timeFrame: Day 1 predose and at 0.5, 1, 1.5, 2, 2.5, 3, 5, 8, 12, 24, 36, and 48 hours after dosing.
measure: Apparent Total Volume of Distribution When Dosed Orally (Vz/F) of Apremilast
timeFrame: Day 1 predose and at 0.5, 1, 1.5, 2, 2.5, 3, 5, 8, 12, 24, 36, and 48 hours after dosing.
measure: Apparent Total Volume of Distribution When Dosed Orally (Vz/F) of Apremilast by Sex
timeFrame: 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 outcomes:
measure: Number of Participants With Adverse Events
timeFrame: From first dose of study drug up to 11 days
Other outcomes:
Locations:
city: Lenexa
country: United States
facility: PRA International
state: Kansas
city: Dallas
country: United States
facility: Clinical Development Services
state: Texas
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: