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

• Sponsor: Amgen (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01634191
• Collaborator: (none)
• Enrollment: 36
• Locations: 2
• Arms: 2
• Actual Duration (Months): 2
• Patients Per Site: 18
• Patients Per Site Per Month: 9.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteer	Drug: Apremilast	Phase 1

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 Design

• Study Type: Interventional
• Actual Enrollment: 36 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• 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
• Actual Study Start Date: Feb 1, 2012
• Actual Primary Completion Date: Mar 1, 2012
• Actual Study Completion Date: Apr 1, 2012

Arms and Interventions

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®

Outcome Measures

Primary Outcome Measures

1. Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUC0-t) 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.]

   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.

2. AUC From Time Zero to Time of Last Quantifiable Concentration (AUC0-t) 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.]

   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.

3. Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-∞) 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.]

   The lower limit of quantitation for apremilast plasma concentrations was 1.0 ng/mL.

4. AUC From Time Zero Extrapolated to Infinity (AUC0-∞) 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.]

   The lower limit of quantitation for apremilast plasma concentrations was 1.0 ng/mL.

5. Maximum Observed Plasma Concentration (Cmax) 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.]

   The lower limit of quantitation for apremilast plasma concentrations was 1.0 ng/mL.

6. Maximum Observed Plasma Concentration 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.]

   The lower limit of quantitation for apremilast plasma concentrations was 1.0 ng/mL.

7. Time to Maximum Observed Plasma Concentration (Tmax) 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.]

   The lower limit of quantitation for apremilast plasma concentrations was 1.0 ng/mL.

8. Time to Maximum Observed Plasma Concentration (Tmax) 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.]

   The lower limit of quantitation for apremilast plasma concentrations was 1.0 ng/mL.

9. 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.]

10. 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.]

11. 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.]

12. 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.]

13. 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.]

14. 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

1. Number of Participants With Adverse Events [From first dose of study drug up to 11 days]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	PRA International	Lenexa	Kansas	United States	66219
2	Clinical Development Services	Dallas	Texas	United States	75247

Sponsors and Collaborators

• Amgen

Investigators

• Study Director: MD, Amgen

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• AmgenTrials clinical trials website

Publications

None provided.

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT01634191
• Other Study ID Numbers: CC-10004-CP-024; 20200149
• First Posted: Jul 6, 2012
• Last Update Posted: Apr 14, 2021
• Last Verified: Mar 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Amgen: Apremilast; pharmacokinetic; safety; Pharmacokinetics and safety in healthy volunteer subjects
• Additional relevant MeSH terms: Apremilast

Study Results

Participant Flow

Recruitment Details	This study was conducted at two clinical research sites in the United States.

Arm/Group Title	Young: Apremilast 30 mg	Elderly: Apremilast 30 mg
Arm/Group Description	Participants aged 18 to 55 years received a single oral dose of 30 mg apremilast on Day 1.	Participants aged 65 to 85 years received a single oral dose of 30 mg apremilast on Day 1.
Period Title: Overall Study
STARTED	18	18
COMPLETED	18	18
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Young Males	Young Females	Elderly Males	Elderly Females	Total
Arm/Group Description	Men aged 18 to 55 years received a single oral dose of 30 mg apremilast on Day 1.	Women aged 18 to 55 years received a single oral dose of 30 mg apremilast on Day 1.	Men aged 65 to 85 years received a single oral dose of 30 mg apremilast on Day 1.	Women aged 65 to 85 years received a single oral dose of 30 mg apremilast on Day 1.	Total of all reporting groups
Overall Participants	8	10	8	10	36
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	33.3 (7.48)	35.2 (7.19)	70.4 (3.62)	70.6 (4.72)	52.4 (19.23)
Sex: Female, Male (Count of Participants)
Female	0 0%	10 100%	0 0%	10 100%	20 55.6%
Male	8 100%	0 0%	8 100%	0 0%	16 44.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	2 20%	0 0%	0 0%	2 5.6%
Not Hispanic or Latino	8 100%	8 80%	8 100%	10 100%	34 94.4%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
White	4 50%	4 40%	8 100%	8 80%	24 66.7%
Black or African American	3 37.5%	6 60%	0 0%	2 20%	11 30.6%
Other	1 12.5%	0 0%	0 0%	0 0%	1 2.8%
Body Mass Index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	26.6 (2.43)	27.5 (2.59)	26.3 (2.69)	27.1 (2.42)	26.9 (2.47)

Outcome Measures

1. Primary Outcome

Title	Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUC0-t) of Apremilast
Description	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.
Time Frame	Day 1 predose and at 0.5, 1, 1.5, 2, 2.5, 3, 5, 8, 12, 24, 36, and 48 hours after dosing.

Outcome Measure Data

Analysis Population Description

The pharmacokinetic (PK) population included all participants who received apremilast and had evaluable PK profiles.

Arm/Group Title	Young: Apremilast	Elderly: Apremilast
Arm/Group Description	Participants aged 18 to 55 years received a single oral dose of 30 mg apremilast on Day 1.	Participants aged 65 to 85 years received a single oral dose of 30 mg apremilast on Day 1.
Measure Participants	18	18
Geometric Mean (Geometric Coefficient of Variation) [h*ng/mL]	2832 (28.1)	3235 (40.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Young: Apremilast, Elderly: Apremilast
	Comments	To assess the effect of age on the PK of apremilast after a single 30 mg dose, a 2-way analysis of variance (ANOVA) model was performed on the log-transformed AUC0-t. The ANOVA model included age group (elderly and young), sex (male and female), and age group by sex as a fixed effect.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Mean Ratio
	Estimated Value	113
	Confidence Interval	(2-Sided) 90%; 94.2 to 135
	Parameter Dispersion	Type: Value:
	Estimation Comments	Geometric mean ratio (Elderly/Young) and 90% confidence interval (CI) of the ratio calculated from a 2-way ANOVA model, and presented as percentages.

2. Secondary Outcome

Title	Number of Participants With Adverse Events
Description	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.
Time Frame	From first dose of study drug up to 11 days

Outcome Measure Data

Analysis Population Description

Participants who received apremilast

Arm/Group Title	Young Males	Young Females	Elderly Males	Elderly Females
Arm/Group Description	Men aged 18 to 55 years received a single oral dose of 30 mg apremilast on Day 1.	Women aged 18 to 55 years received a single oral dose of 30 mg apremilast on Day 1.	Men aged 65 to 85 years received a single oral dose of 30 mg apremilast on Day 1.	Women aged 65 to 85 years received a single oral dose of 30 mg apremilast on Day 1.
Measure Participants	8	10	8	10
Any adverse event	2 25%	1 10%	2 25%	5 50%
Adverse event related to study drug	2 25%	1 10%	0 0%	1 10%
Serious adverse events	0 0%	0 0%	0 0%	0 0%
Serious adverse events related to study drug	0 0%	0 0%	0 0%	0 0%
Discontinued due to adverse event	0 0%	0 0%	0 0%	0 0%
Discontinued due to adverse event related to study drug	0 0%	0 0%	0 0%	0 0%

3. Primary Outcome

Title	AUC From Time Zero to Time of Last Quantifiable Concentration (AUC0-t) of Apremilast by Sex
Description	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.
Time Frame	Day 1 predose and at 0.5, 1, 1.5, 2, 2.5, 3, 5, 8, 12, 24, 36, and 48 hours after dosing.

Outcome Measure Data

Analysis Population Description

The PK population included all participants who received apremilast and had evaluable PK profiles.

Arm/Group Title	Males (Combined)	Females (Combined)
Arm/Group Description	Male participants received a single oral dose of 30 mg apremilast on Day 1.	Female participants received a single oral dose of 30 mg apremilast on Day 1.
Measure Participants	16	20
Geometric Mean (Geometric Coefficient of Variation) [h*ng/mL]	2634 (24.5)	3382 (38.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Young: Apremilast, Elderly: Apremilast
	Comments	To assess the effect of sex on the PK of apremilast after a single 30 mg dose, a 2-way analysis of variance (ANOVA) model was performed on the log-transformed AUC0-t. The ANOVA model included age group (elderly and young), sex (male and female), and age group by sex as a fixed effect.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Mean Ratio
	Estimated Value	128
	Confidence Interval	(2-Sided) 90%; 107 to 154
	Parameter Dispersion	Type: Value:
	Estimation Comments	Geometric mean ratio (Female/Male) and 90% CI of the ratio calculated from a 2-way ANOVA model, and presented as percentages.

4. Primary Outcome

Title	Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-∞) of Apremilast
Description	The lower limit of quantitation for apremilast plasma concentrations was 1.0 ng/mL.
Time Frame	Day 1 predose and at 0.5, 1, 1.5, 2, 2.5, 3, 5, 8, 12, 24, 36, and 48 hours after dosing.

Outcome Measure Data

Analysis Population Description

The PK population included all participants who received apremilast and had evaluable PK profiles.

Arm/Group Title	Young: Apremilast	Elderly: Apremilast
Arm/Group Description	Participants aged 18 to 55 years received a single oral dose of 30 mg apremilast on Day 1.	Participants aged 65 to 85 years received a single oral dose of 30 mg apremilast on Day 1.
Measure Participants	18	18
Geometric Mean (Geometric Coefficient of Variation) [h*ng/mL]	2900 (28.7)	3323 (41.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Young: Apremilast, Elderly: Apremilast
	Comments	To assess the effect of age on the PK of apremilast after a single 30 mg dose, a 2-way analysis of variance (ANOVA) model was performed on the log-transformed AUC0-∞. The ANOVA model included age group (elderly and young), sex (male and female), and age group by sex as a fixed effect.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Mean Ratio
	Estimated Value	113
	Confidence Interval	(2-Sided) 90%; 94.1 to 135
	Parameter Dispersion	Type: Value:
	Estimation Comments	Geometric mean ratio (Elderly/Young) and 90% CI of the ratio calculated from a 2-way ANOVA model, and presented as percentages.

5. Primary Outcome

Title	AUC From Time Zero Extrapolated to Infinity (AUC0-∞) of Apremilast by Sex
Description	The lower limit of quantitation for apremilast plasma concentrations was 1.0 ng/mL.
Time Frame	Day 1 predose and at 0.5, 1, 1.5, 2, 2.5, 3, 5, 8, 12, 24, 36, and 48 hours after dosing.

Outcome Measure Data

Analysis Population Description

The PK population included all participants who received apremilast and had evaluable PK profiles.

Arm/Group Title	Males (Combined)	Females (Combined)
Arm/Group Description	Male participants received a single oral dose of 30 mg apremilast on Day 1.	Female participants received a single oral dose of 30 mg apremilast on Day 1.
Measure Participants	16	20
Geometric Mean (Geometric Coefficient of Variation) [h*ng/mL]	2673 (24.8)	3499 (39.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Young: Apremilast, Elderly: Apremilast
	Comments	To assess the effect of sex on the PK of apremilast after a single 30 mg dose, a 2-way ANOVA model was performed on the log-transformed AUC0-∞. The ANOVA model included age group (elderly and young), sex (male and female), and age group by sex as a fixed effect.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Mean Ratio
	Estimated Value	131
	Confidence Interval	(2-Sided) 90%; 109 to 157
	Parameter Dispersion	Type: Value:
	Estimation Comments	Geometric mean ratio (Female/Male) and 90% CI of the ratio calculated from a 2-way ANOVA model, and presented as percentages.

6. Primary Outcome

Title	Maximum Observed Plasma Concentration (Cmax) of Apremilast
Description	The lower limit of quantitation for apremilast plasma concentrations was 1.0 ng/mL.
Time Frame	Day 1 predose and at 0.5, 1, 1.5, 2, 2.5, 3, 5, 8, 12, 24, 36, and 48 hours after dosing.

Outcome Measure Data

Analysis Population Description

The PK population included all participants who received apremilast and had evaluable PK profiles.

Arm/Group Title	Young: Apremilast	Elderly: Apremilast
Arm/Group Description	Participants aged 18 to 55 years received a single oral dose of 30 mg apremilast on Day 1.	Participants aged 65 to 85 years received a single oral dose of 30 mg apremilast on Day 1.
Measure Participants	18	18
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	302 (26.8)	321 (27.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Young: Apremilast, Elderly: Apremilast
	Comments	To assess the effect of age on the PK of apremilast after a single 30 mg dose, a 2-way analysis of ANOVA model was performed on the log-transformed Cmax. The ANOVA model included age group (elderly and young), sex (male and female), and age group by sex as a fixed effect.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Mean Ratio
	Estimated Value	106
	Confidence Interval	(2-Sided) 90%; 90.5 to 123
	Parameter Dispersion	Type: Value:
	Estimation Comments	Geometric mean ratio (Elderly/Young) and 90% CI of the ratio calculated from a 2-way ANOVA model, and presented as percentages.

7. Primary Outcome

Title	Maximum Observed Plasma Concentration of Apremilast by Sex
Description	The lower limit of quantitation for apremilast plasma concentrations was 1.0 ng/mL.
Time Frame	Day 1 predose and at 0.5, 1, 1.5, 2, 2.5, 3, 5, 8, 12, 24, 36, and 48 hours after dosing.

Outcome Measure Data

Analysis Population Description

The PK population included all participants who received apremilast and had evaluable PK profiles.

Arm/Group Title	Males (Combined)	Females (Combined)
Arm/Group Description	Male participants received a single oral dose of 30 mg apremilast on Day 1.	Female participants received a single oral dose of 30 mg apremilast on Day 1.
Measure Participants	16	20
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	299 (16.6)	322 (33.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Young: Apremilast, Elderly: Apremilast
	Comments	To assess the effect of sex on the PK of apremilast after a single 30 mg dose, a 2-way ANOVA model was performed on the log-transformed Cmax. The ANOVA model included age group (elderly and young), sex (male and female), and age group by sex as a fixed effect.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Mean Ratio
	Estimated Value	108
	Confidence Interval	(2-Sided) 90%; 92.3 to 126
	Parameter Dispersion	Type: Value:
	Estimation Comments	Geometric mean ratio (Female/Male) and 90% CI of the ratio calculated from a 2-way ANOVA model, and presented as percentages.

8. Primary Outcome

Title	Time to Maximum Observed Plasma Concentration (Tmax) of Apremilast
Description	The lower limit of quantitation for apremilast plasma concentrations was 1.0 ng/mL.
Time Frame	Day 1 predose and at 0.5, 1, 1.5, 2, 2.5, 3, 5, 8, 12, 24, 36, and 48 hours after dosing.

Outcome Measure Data

Analysis Population Description

The PK population included all participants who received apremilast and had evaluable PK profiles.

Arm/Group Title	Young: Apremilast	Elderly: Apremilast
Arm/Group Description	Participants aged 18 to 55 years received a single oral dose of 30 mg apremilast on Day 1.	Participants aged 65 to 85 years received a single oral dose of 30 mg apremilast on Day 1.
Measure Participants	18	18
Median (Full Range) [hours]	2.50	2.50

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Young: Apremilast, Elderly: Apremilast
	Comments	Tmax was analyzed by nonparametric methods. The median difference and 90% CI of the median difference were calculated from the Hodges-Lehrmann estimate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.153
	Comments
	Method	Wilcoxon rank-sum test
	Comments
Method of Estimation	Estimation Parameter	Median Difference
	Estimated Value	0.500
	Confidence Interval	(2-Sided) 90%; 0.000 to 2.00
	Parameter Dispersion	Type: Value:
	Estimation Comments	Median difference (Elderly - Young) calculated from the Hodges-Lehmann estimate.

9. Primary Outcome

Title	Time to Maximum Observed Plasma Concentration (Tmax) of Apremilast by Sex
Description	The lower limit of quantitation for apremilast plasma concentrations was 1.0 ng/mL.
Time Frame	Day 1 predose and at 0.5, 1, 1.5, 2, 2.5, 3, 5, 8, 12, 24, 36, and 48 hours after dosing.

Outcome Measure Data

Analysis Population Description

The PK population included all participants who received apremilast and had evaluable PK profiles.

Arm/Group Title	Males (Combined)	Females (Combined)
Arm/Group Description	Male participants received a single oral dose of 30 mg apremilast on Day 1.	Female participants received a single oral dose of 30 mg apremilast on Day 1.
Measure Participants	16	20
Median (Full Range) [hours]	2.5	2.75

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Young: Apremilast, Elderly: Apremilast
	Comments	Tmax was analyzed by nonparametric methods. The median difference and 90% CI of the median difference were calculated from the Hodges-Lehrmann estimate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.169
	Comments
	Method	Wilcoxon rank-sum test
	Comments
Method of Estimation	Estimation Parameter	Median Difference
	Estimated Value	0.500
	Confidence Interval	(2-Sided) 90%; 0.000 to 2.00
	Parameter Dispersion	Type: Value:
	Estimation Comments	Median difference (Female - Male) and 90% CI of the difference calculated from the Hodges-Lehmann estimate.

10. Primary Outcome

Title	Estimate of Terminal Elimination Half-life of Apremilast in Plasma (t1/2)
Time Frame	Day 1 predose and at 0.5, 1, 1.5, 2, 2.5, 3, 5, 8, 12, 24, 36, and 48 hours after dosing.

Outcome Measure Data

Analysis Population Description

The PK population included all participants who received apremilast and had evaluable PK profiles.

Arm/Group Title	Young: Apremilast	Elderly: Apremilast
Arm/Group Description	Participants aged 18 to 55 years received a single oral dose of 30 mg apremilast on Day 1.	Participants aged 65 to 85 years received a single oral dose of 30 mg apremilast on Day 1.
Measure Participants	18	18
Mean (Standard Deviation) [hours]	9.41 (2.65)	9.15 (2.56)

11. Primary Outcome

Title	Estimate of Terminal Elimination Half-life of Apremilast in Plasma by Sex
Time Frame	Day 1 predose and at 0.5, 1, 1.5, 2, 2.5, 3, 5, 8, 12, 24, 36, and 48 hours after dosing.

Outcome Measure Data

Analysis Population Description

The PK population included all participants who received apremilast and had evaluable PK profiles.

Arm/Group Title	Males (Combined)	Females (Combined)
Arm/Group Description	Male participants received a single oral dose of 30 mg apremilast on Day 1.	Female participants received a single oral dose of 30 mg apremilast on Day 1.
Measure Participants	16	20
Mean (Standard Deviation) [hours]	8.06 (1.72)	10.3 (2.76)

12. Primary Outcome

Title	Apparent Total Plasma Clearance When Dosed Orally (CL/F) of Apremilast
Time Frame	Day 1 predose and at 0.5, 1, 1.5, 2, 2.5, 3, 5, 8, 12, 24, 36, and 48 hours after dosing.

Outcome Measure Data

Analysis Population Description

The PK population included all participants who received apremilast and had evaluable PK profiles.

Arm/Group Title	Young: Apremilast	Elderly: Apremilast
Arm/Group Description	Participants aged 18 to 55 years received a single oral dose of 30 mg apremilast on Day 1.	Participants aged 65 to 85 years received a single oral dose of 30 mg apremilast on Day 1.
Measure Participants	18	18
Geometric Mean (Geometric Coefficient of Variation) [L/hr]	10.4 (28.7)	9.03 (41.8)

13. Primary Outcome

Title	Apparent Total Plasma Clearance When Dosed Orally of Apremilast by Sex
Time Frame	Day 1 predose and at 0.5, 1, 1.5, 2, 2.5, 3, 5, 8, 12, 24, 36, and 48 hours after dosing.

Outcome Measure Data

Analysis Population Description

The PK population included all participants who received apremilast and had evaluable PK profiles.

Arm/Group Title	Males (Combined)	Females (Combined)
Arm/Group Description	Male participants received a single oral dose of 30 mg apremilast on Day 1.	Female participants received a single oral dose of 30 mg apremilast on Day 1.
Measure Participants	16	20
Geometric Mean (Geometric Coefficient of Variation) [L/hr]	11.2 (24.8)	8.57 (39.1)

14. Primary Outcome

Title	Apparent Total Volume of Distribution When Dosed Orally (Vz/F) of Apremilast
Time Frame	Day 1 predose and at 0.5, 1, 1.5, 2, 2.5, 3, 5, 8, 12, 24, 36, and 48 hours after dosing.

Outcome Measure Data

Analysis Population Description

The PK population included all participants who received apremilast and had evaluable PK profiles.

Arm/Group Title	Young: Apremilast	Elderly: Apremilast
Arm/Group Description	Participants aged 18 to 55 years received a single oral dose of 30 mg apremilast on Day 1.	Participants aged 65 to 85 years received a single oral dose of 30 mg apremilast on Day 1.
Measure Participants	18	18
Geometric Mean (Geometric Coefficient of Variation) [liters]	136 (38.9)	115 (35.3)

15. Primary Outcome

Title	Apparent Total Volume of Distribution When Dosed Orally (Vz/F) of Apremilast by Sex
Time Frame	Day 1 predose and at 0.5, 1, 1.5, 2, 2.5, 3, 5, 8, 12, 24, 36, and 48 hours after dosing.

Outcome Measure Data

Analysis Population Description

The PK population included all participants who received apremilast and had evaluable PK profiles.

Arm/Group Title	Males (Combined)	Females (Combined)
Arm/Group Description	Male participants received a single oral dose of 30 mg apremilast on Day 1.	Female participants received a single oral dose of 30 mg apremilast on Day 1.
Measure Participants	16	20
Geometric Mean (Geometric Coefficient of Variation) [liters]	128 (30.7)	123 (43.4)

Adverse Events

Time Frame	From first dose of apremilast up to 11 days
Arm/Group Title	Young Males		Young Females		Young (Total)		Elderly Males		Elderly Females		Elderly (Total)		Overall Total
Arm/Group Description	Men aged 18 to 55 years received a single oral dose of 30 mg apremilast on Day 1.		Women aged 18 to 55 years received a single oral dose of 30 mg apremilast on Day 1.		Participants aged 18 to 55 years received a single oral dose of 30 mg apremilast on Day 1.		Men aged 65 to 85 years received a single oral dose of 30 mg apremilast on Day 1.		Women aged 65 to 85 years received a single oral dose of 30 mg apremilast on Day 1.		Participants aged 65 to 85 years received a single oral dose of 30 mg apremilast on Day 1.		All study participants received a single oral dose of 30 mg apremilast on Day 1.
All Cause Mortality
	Young Males		Young Females		Young (Total)		Elderly Males		Elderly Females		Elderly (Total)		Overall Total
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Young Males		Young Females		Young (Total)		Elderly Males		Elderly Females		Elderly (Total)		Overall Total
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/10 (0%)		0/18 (0%)		0/8 (0%)		0/10 (0%)		0/18 (0%)		0/36 (0%)
Other (Not Including Serious) Adverse Events
	Young Males		Young Females		Young (Total)		Elderly Males		Elderly Females		Elderly (Total)		Overall Total
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/8 (25%)		1/10 (10%)		3/18 (16.7%)		2/8 (25%)		5/10 (50%)		7/18 (38.9%)		10/36 (27.8%)
Gastrointestinal disorders
CONSTIPATION	0/8 (0%)		0/10 (0%)		0/18 (0%)		1/8 (12.5%)		0/10 (0%)		1/18 (5.6%)		1/36 (2.8%)
NAUSEA	0/8 (0%)		1/10 (10%)		1/18 (5.6%)		0/8 (0%)		1/10 (10%)		1/18 (5.6%)		2/36 (5.6%)
TOOTHACHE	0/8 (0%)		0/10 (0%)		0/18 (0%)		0/8 (0%)		1/10 (10%)		1/18 (5.6%)		1/36 (2.8%)
VOMITING	0/8 (0%)		1/10 (10%)		1/18 (5.6%)		0/8 (0%)		0/10 (0%)		0/18 (0%)		1/36 (2.8%)
General disorders
PAIN	0/8 (0%)		0/10 (0%)		0/18 (0%)		0/8 (0%)		1/10 (10%)		1/18 (5.6%)		1/36 (2.8%)
Infections and infestations
UPPER RESPIRATORY TRACT INFECTION	0/8 (0%)		0/10 (0%)		0/18 (0%)		0/8 (0%)		2/10 (20%)		2/18 (11.1%)		2/36 (5.6%)
Musculoskeletal and connective tissue disorders
ARTHRALGIA	0/8 (0%)		0/10 (0%)		0/18 (0%)		0/8 (0%)		1/10 (10%)		1/18 (5.6%)		1/36 (2.8%)
BACK PAIN	0/8 (0%)		0/10 (0%)		0/18 (0%)		0/8 (0%)		1/10 (10%)		1/18 (5.6%)		1/36 (2.8%)
Nervous system disorders
HEADACHE	1/8 (12.5%)		0/10 (0%)		1/18 (5.6%)		0/8 (0%)		0/10 (0%)		0/18 (0%)		1/36 (2.8%)
SOMNOLENCE	1/8 (12.5%)		0/10 (0%)		1/18 (5.6%)		0/8 (0%)		0/10 (0%)		0/18 (0%)		1/36 (2.8%)
Respiratory, thoracic and mediastinal disorders
COUGH	0/8 (0%)		0/10 (0%)		0/18 (0%)		0/8 (0%)		1/10 (10%)		1/18 (5.6%)		1/36 (2.8%)
Vascular disorders
PHLEBITIS	0/8 (0%)		0/10 (0%)		0/18 (0%)		1/8 (12.5%)		0/10 (0%)		1/18 (5.6%)		1/36 (2.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.