Trial Outcomes & Findings for A Study to Evaluate the Pharmacokinetic Exposure of 2 Formulations of Apremilast in Healthy Adults (NCT NCT02777554)

NCT ID: NCT02777554

Last Updated: 2021-07-22

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

144 participants

Primary outcome timeframe

Apremilast IR: Day 7 predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, and 24 hours after the morning dose. Apremilast XL: Day 7 predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, and 24 hours after the morning dose.

Results posted on

2021-07-22

Participant Flow

This study was conducted at 2 clinical sites in the United States. The study consisted of 2 parts. Part 1 was a multiple-dose two-period, two-sequence, crossover study. Part 2 was a four-period, four-sequence crossover study. Both parts enrolled healthy volunteers.

In Part 1 participants were randomly assigned to 1 of 2 treatment sequences. In Part 2 participants were randomly assigned to 1 of 4 treatment sequences.

Participant milestones

Participant milestones
Measure	Part 1: Apremilast 30 mg IR BID / Apremilast 75 mg XL QD Participants received apremilast 30 mg immediate release (IR) tablet twice a day (BID) for 7 days in treatment period 1 then apremilast 75 mg extended release (XL) formulation once a day (QD) for 7 days in treatment period 2. There was a 5.5 to 9.5-day washout period between each treatment period.	Part 1: Apremilast 75 mg XL QD / Apremilast 30 mg IR BID Participants received apremilast 75 mg XL formulation once a day for 7 days in treatment period 1 then apremilast 30 mg IR tablet twice a day for 7 days in treatment period 2. There was a 6 to 10-day washout period between each treatment period.	Part 2: Sequence 1 Participants received a single dose of apremilast in each of 4 treatment periods according to the following: Treatment period 1: Apremilast 30 mg IR tablet in the morning and evening under fasted conditions; Treatment period 2: Apremilast 75 mg XL formulation after a high-fat meal; Treatment period 3: Apremilast 75 mg XL formulation under fasted conditions; Treatment period 4: Apremilast 75 mg XL formulation after a standard meal. There was a washout period of approximately 6 to 10 days between each treatment period.	Part 2: Sequence 2 Participants received a single dose of apremilast in each of 4 treatment periods according to the following: Treatment period 1: Apremilast 75 mg XL formulation under fasted conditions; Treatment period 2: Apremilast 30 mg IR tablet in the morning and evening under fasted conditions; Treatment period 3: Apremilast 75 mg XL formulation after a standard meal; Treatment period 4: Apremilast 75 mg XL formulation after a high-fat meal. There was a washout period of approximately 6 to 10 days between each treatment period.	Part 2: Sequence 3 Participants received a single dose of apremilast in each of 4 treatment periods according to the following: Treatment period 1: Apremilast 75 mg XL formulation after a standard meal; Treatment period 2: Apremilast 75 mg XL formulation under fasted conditions; Treatment period 3: Apremilast 75 mg XL formulation after a high-fat meal; Treatment period 4: Apremilast 30 mg IR tablet in the morning and evening under fasted conditions. There was a washout period of approximately 6 to 10 days between each treatment period.	Part 2: Sequence 4 Participants received a single dose of apremilast in each of 4 treatment periods according to the following: Treatment period 1: Apremilast 75 mg XL formulation after a high-fat meal; Treatment period 2: Apremilast 75 mg XL formulation after a standard meal; Treatment period 3: Apremilast 30 mg IR tablet in the morning and evening under fasted conditions; Treatment period 4: Apremilast 75 mg XL formulation under fasted conditions. There was a washout period of approximately 6 to 10 days between each treatment period.
Overall Study STARTED	62	62	5	5	5	5
Overall Study COMPLETED	32	37	4	4	5	5
Overall Study NOT COMPLETED	30	25	1	1	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Part 1: Apremilast 30 mg IR BID / Apremilast 75 mg XL QD Participants received apremilast 30 mg immediate release (IR) tablet twice a day (BID) for 7 days in treatment period 1 then apremilast 75 mg extended release (XL) formulation once a day (QD) for 7 days in treatment period 2. There was a 5.5 to 9.5-day washout period between each treatment period.	Part 1: Apremilast 75 mg XL QD / Apremilast 30 mg IR BID Participants received apremilast 75 mg XL formulation once a day for 7 days in treatment period 1 then apremilast 30 mg IR tablet twice a day for 7 days in treatment period 2. There was a 6 to 10-day washout period between each treatment period.	Part 2: Sequence 1 Participants received a single dose of apremilast in each of 4 treatment periods according to the following: Treatment period 1: Apremilast 30 mg IR tablet in the morning and evening under fasted conditions; Treatment period 2: Apremilast 75 mg XL formulation after a high-fat meal; Treatment period 3: Apremilast 75 mg XL formulation under fasted conditions; Treatment period 4: Apremilast 75 mg XL formulation after a standard meal. There was a washout period of approximately 6 to 10 days between each treatment period.	Part 2: Sequence 2 Participants received a single dose of apremilast in each of 4 treatment periods according to the following: Treatment period 1: Apremilast 75 mg XL formulation under fasted conditions; Treatment period 2: Apremilast 30 mg IR tablet in the morning and evening under fasted conditions; Treatment period 3: Apremilast 75 mg XL formulation after a standard meal; Treatment period 4: Apremilast 75 mg XL formulation after a high-fat meal. There was a washout period of approximately 6 to 10 days between each treatment period.
Overall Study Adverse Event	4	4	0	1
Overall Study Withdrawal by Subject	3	1	1	0
Overall Study Discharged early due to hurricane	22	20	0	0
Overall Study Other - Miscellaneous	1	0	0	0

Baseline Characteristics

A Study to Evaluate the Pharmacokinetic Exposure of 2 Formulations of Apremilast in Healthy Adults

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part 1 n=124 Participants Participants in Part 1 received apremilast 30 mg IR tablet BID for 7 days and apremilast 75 mg XL formulation QD for 7 days in each treatment period depending on sequence assignment.	Part 2 n=20 Participants Participants in Part 2 received a single dose of the following treatments in 4 treatment periods according to sequence assignment: * Apremilast 30 mg IR tablet in the morning and evening under fasted conditions; * Apremilast 75 mg XL formulation after a high-fat meal; * Apremilast 75 mg XL formulation under fasted conditions; * Apremilast 75 mg XL formulation after a standard meal.	Total n=144 Participants Total of all reporting groups
Age, Continuous	37.8 years n=5 Participants	34.7 years n=7 Participants	37.4 years n=5 Participants
Sex: Female, Male Female	46 Participants n=5 Participants	7 Participants n=7 Participants	53 Participants n=5 Participants
Sex: Female, Male Male	78 Participants n=5 Participants	13 Participants n=7 Participants	91 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	52 Participants n=5 Participants	8 Participants n=7 Participants	60 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	72 Participants n=5 Participants	12 Participants n=7 Participants	84 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	47 Participants n=5 Participants	10 Participants n=7 Participants	57 Participants n=5 Participants
Race/Ethnicity, Customized White	70 Participants n=5 Participants	10 Participants n=7 Participants	80 Participants n=5 Participants
Race/Ethnicity, Customized Asian	4 Participants n=5 Participants	0 Participants n=7 Participants	4 Participants n=5 Participants
Race/Ethnicity, Customized Other	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: Apremilast IR: Day 7 predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, and 24 hours after the morning dose. Apremilast XL: Day 7 predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, and 24 hours after the morning dose.

Population: The pharmacokinetic (PK) population (all participants who received at least one dose of apremilast and had at least one measurable concentration datum) with available data.

Outcome measures

Outcome measures
Measure	Part 1: Apremilast 30 mg IR BID n=91 Participants Participants received apremilast 30 mg IR tablet BID for 7 days.	Part 1: Apremilast 75 mg XL QD n=89 Participants Participants received apremilast 75 mg XL formulation QD for 7 days.	Part 2: Apremilast 75 mg XL (Standard Meal) Participants received a single dose of apremilast 75 mg XL formulation after a standard meal.	Part 2: Apremilast 75 mg XL (High Fat Meal) Participants received a single dose of apremilast 75 mg XL formulation after a high-fat meal.	Part 2: Apremilast 75 mg XL (Standard Meal) Participants received a single dose of apremilast 75 mg XL formulation after a standard meal.	Part 2: Apremilast 75 mg XL (High Fat Meal) Participants received a single dose of apremilast 75 mg XL formulation after a high-fat meal.
Part 1: Peak Maximum Plasma Concentration (Cmax) of Apremilast	451 ng/mL Geometric Coefficient of Variation 49.0	459 ng/mL Geometric Coefficient of Variation 35.0	—	—	—	—

PRIMARY outcome

Population: The PK population with available data

Outcome measures

Outcome measures
Measure	Part 1: Apremilast 30 mg IR BID n=91 Participants Participants received apremilast 30 mg IR tablet BID for 7 days.	Part 1: Apremilast 75 mg XL QD n=89 Participants Participants received apremilast 75 mg XL formulation QD for 7 days.	Part 2: Apremilast 75 mg XL (Standard Meal) Participants received a single dose of apremilast 75 mg XL formulation after a standard meal.	Part 2: Apremilast 75 mg XL (High Fat Meal) Participants received a single dose of apremilast 75 mg XL formulation after a high-fat meal.	Part 2: Apremilast 75 mg XL (Standard Meal) Participants received a single dose of apremilast 75 mg XL formulation after a standard meal.	Part 2: Apremilast 75 mg XL (High Fat Meal) Participants received a single dose of apremilast 75 mg XL formulation after a high-fat meal.
Part 1: Area Under the Concentration-time Curve From Time Zero to 24 Hours Postdose (AUC0-24) of Apremilast	6370 ng*hr/mL Geometric Coefficient of Variation 51.2	6090 ng*hr/mL Geometric Coefficient of Variation 46.1	—	—	—	—

PRIMARY outcome

Timeframe: Apremilast IR: Predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the morning dose. Apremilast XL: Predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, 60, and 72 hours postdose.

Population: PK population; two participants were excluded from PK analyses due to predose concentrations \> 5% than their Cmax values.

Outcome measures

Outcome measures
Measure	Part 1: Apremilast 30 mg IR BID n=18 Participants Participants received apremilast 30 mg IR tablet BID for 7 days.	Part 1: Apremilast 75 mg XL QD n=17 Participants Participants received apremilast 75 mg XL formulation QD for 7 days.	Part 2: Apremilast 75 mg XL (Standard Meal) n=16 Participants Participants received a single dose of apremilast 75 mg XL formulation after a standard meal.	Part 2: Apremilast 75 mg XL (High Fat Meal) n=17 Participants Participants received a single dose of apremilast 75 mg XL formulation after a high-fat meal.	Part 2: Apremilast 75 mg XL (Standard Meal) Participants received a single dose of apremilast 75 mg XL formulation after a standard meal.	Part 2: Apremilast 75 mg XL (High Fat Meal) Participants received a single dose of apremilast 75 mg XL formulation after a high-fat meal.
Part 2: Peak Maximum Plasma Concentration (Cmax) of Apremilast	379 ng/mL Geometric Coefficient of Variation 29.9	402 ng/mL Geometric Coefficient of Variation 32.5	436 ng/mL Geometric Coefficient of Variation 33.2	496 ng/mL Geometric Coefficient of Variation 25.2	—	—

PRIMARY outcome

Population: PK population; two participants were excluded from PK analyses due to predose concentrations \> 5% than their Cmax values.

Outcome measures

Outcome measures
Measure	Part 1: Apremilast 30 mg IR BID n=18 Participants Participants received apremilast 30 mg IR tablet BID for 7 days.	Part 1: Apremilast 75 mg XL QD n=17 Participants Participants received apremilast 75 mg XL formulation QD for 7 days.	Part 2: Apremilast 75 mg XL (Standard Meal) n=16 Participants Participants received a single dose of apremilast 75 mg XL formulation after a standard meal.	Part 2: Apremilast 75 mg XL (High Fat Meal) n=17 Participants Participants received a single dose of apremilast 75 mg XL formulation after a high-fat meal.	Part 2: Apremilast 75 mg XL (Standard Meal) Participants received a single dose of apremilast 75 mg XL formulation after a standard meal.	Part 2: Apremilast 75 mg XL (High Fat Meal) Participants received a single dose of apremilast 75 mg XL formulation after a high-fat meal.
Part 2: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Observable Concentration (AUC0-t) of Apremilast	7030 ng*h/mL Geometric Coefficient of Variation 31.5	6650 ng*h/mL Geometric Coefficient of Variation 42.5	7580 ng*h/mL Geometric Coefficient of Variation 31.1	7400 ng*h/mL Geometric Coefficient of Variation 31.1	—	—

PRIMARY outcome

Population: PK population; two participants were excluded from PK analyses due to predose concentrations \> 5% than their Cmax values.

Outcome measures

Outcome measures
Measure	Part 1: Apremilast 30 mg IR BID n=18 Participants Participants received apremilast 30 mg IR tablet BID for 7 days.	Part 1: Apremilast 75 mg XL QD n=17 Participants Participants received apremilast 75 mg XL formulation QD for 7 days.	Part 2: Apremilast 75 mg XL (Standard Meal) n=16 Participants Participants received a single dose of apremilast 75 mg XL formulation after a standard meal.	Part 2: Apremilast 75 mg XL (High Fat Meal) n=17 Participants Participants received a single dose of apremilast 75 mg XL formulation after a high-fat meal.	Part 2: Apremilast 75 mg XL (Standard Meal) Participants received a single dose of apremilast 75 mg XL formulation after a standard meal.	Part 2: Apremilast 75 mg XL (High Fat Meal) Participants received a single dose of apremilast 75 mg XL formulation after a high-fat meal.
Part 2: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-∞) of Apremilast	7100 ng*h/mL Geometric Coefficient of Variation 31.4	6680 ng*h/mL Geometric Coefficient of Variation 42.4	7600 ng*h/mL Geometric Coefficient of Variation 31.1	7450 ng*h/mL Geometric Coefficient of Variation 31.1	—	—

SECONDARY outcome

Timeframe: Part 1: Up to 7 days after last dose in each treatment period (14 days); Part 2: Up to 7 days after each dose.

Population: All participants who received at least one dose of apremilast

An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the subject's health, including laboratory test values, regardless of etiology. A serious AE is any AE occurring at any dose that: * Resulted in death; * Was life-threatening; * Required inpatient hospitalization or prolongation of existing hospitalization; * Resulted in persistent or significant disability/incapacity; * Was a congenital anomaly/birth defect; * Constituted an important medical event. The Investigator determined the relationship between the administration of study drug and the occurrence of each AE as Not Suspected or Suspected as defined in the Protocol.