Trial Outcomes & Findings for Effect of Food on the Pharmacokinetics of Apremilast (CC-10004) in Healthy Adults (NCT NCT01634178)
NCT ID: NCT01634178
Last Updated: 2021-04-21
Results Overview
Plasma concentrations of apremilast were determined by using a validated liquid chromatography-tandem mass spectrometry assay.
COMPLETED
PHASE1
46 participants
Day 1 of each treatment period at pre-dose, and at 0.5, 1, 1.5, 2, 2.5, 3, 5, 8, 12, 24, 36, and 48 hours after dosing.
2021-04-21
Participant Flow
This study was conducted at one clinical research site in the United States.
The study consisted of 2 periods. Participants were randomly assigned to one of two treatment sequences; Fasted then Fed or Fed then Fasted. Each participant was to receive 1 dose of apremilast under fasted conditions and 1 dose of apremilast under fed conditions in each period, respectively, depending on their sequence assignment. There was a 5 to 10 day washout period between each dose.
Participant milestones
| Measure |
Sequence 1: Apremilast Fasted / Fed
Participants were randomized to receive a single 30 mg apremilast tablet administered under fasted conditions in Period 1 and a single 30 mg apremilast tablet administered after a high fat meal in Period 2.
|
Sequence 2: Apremilast Fed / Fasted
Participants were randomized to receive a single 30 mg apremilast tablet administered after a high fat meal in Period 1 and a single 30 mg apremilast tablet administered under fasted conditions in Period 2.
|
|---|---|---|
|
Treatment Period 1
STARTED
|
23
|
23
|
|
Treatment Period 1
COMPLETED
|
23
|
22
|
|
Treatment Period 1
NOT COMPLETED
|
0
|
1
|
|
Treatment Period 2
STARTED
|
23
|
22
|
|
Treatment Period 2
COMPLETED
|
22
|
22
|
|
Treatment Period 2
NOT COMPLETED
|
1
|
0
|
Reasons for withdrawal
| Measure |
Sequence 1: Apremilast Fasted / Fed
Participants were randomized to receive a single 30 mg apremilast tablet administered under fasted conditions in Period 1 and a single 30 mg apremilast tablet administered after a high fat meal in Period 2.
|
Sequence 2: Apremilast Fed / Fasted
Participants were randomized to receive a single 30 mg apremilast tablet administered after a high fat meal in Period 1 and a single 30 mg apremilast tablet administered under fasted conditions in Period 2.
|
|---|---|---|
|
Treatment Period 1
Adverse Event
|
0
|
1
|
|
Treatment Period 2
Adverse Event
|
1
|
0
|
Baseline Characteristics
Effect of Food on the Pharmacokinetics of Apremilast (CC-10004) in Healthy Adults
Baseline characteristics by cohort
| Measure |
Apremilast
n=46 Participants
Participants received one dose of 30 mg apremilast administered under fasted conditions and one dose of 30 mg apremilast after a full fat meal.
|
|---|---|
|
Age, Continuous
|
38.5 years
STANDARD_DEVIATION 13.45 • n=99 Participants
|
|
Sex: Female, Male
Female
|
25 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
21 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
17 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
29 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
White
|
31 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
13 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
Asian
|
1 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
|
1 Participants
n=99 Participants
|
PRIMARY outcome
Timeframe: Day 1 of each treatment period at pre-dose, and at 0.5, 1, 1.5, 2, 2.5, 3, 5, 8, 12, 24, 36, and 48 hours after dosing.Population: The pharmacokinetic (PK) population included all participants who received at least 1 dose of apremilast and had evaluable PK profiles.
Plasma concentrations of apremilast were determined by using a validated liquid chromatography-tandem mass spectrometry assay.
Outcome measures
| Measure |
Apremilast - Fasted
n=45 Participants
Participants received a single 30 mg apremilast tablet administered under fasted conditions.
|
Apremilast - Fed
n=44 Participants
Participants received a single 30 mg apremilast tablet administered after a high fat meal.
|
|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) of Apremilast
|
339.86 ng/mL
Geometric Coefficient of Variation 26.5
|
333.85 ng/mL
Geometric Coefficient of Variation 30.0
|
PRIMARY outcome
Timeframe: Day 1 of each treatment period at pre-dose, and at 0.5, 1, 1.5, 2, 2.5, 3, 5, 8, 12, 24, 36, and 48 hours after dosing.Population: The PK population included all participants who received at least 1 dose of apremilast and had evaluable PK profiles.
Plasma concentrations of apremilast were determined by using a validated liquid chromatography-tandem mass spectrometry assay.
Outcome measures
| Measure |
Apremilast - Fasted
n=45 Participants
Participants received a single 30 mg apremilast tablet administered under fasted conditions.
|
Apremilast - Fed
n=44 Participants
Participants received a single 30 mg apremilast tablet administered after a high fat meal.
|
|---|---|---|
|
Time to Maximum Observed Plasma Concentration (Tmax) of Apremilast
|
2.50 hours
Interval 0.62 to 5.02
|
3.00 hours
Interval 1.0 to 8.0
|
PRIMARY outcome
Timeframe: Day 1 of each treatment period at pre-dose, and at 0.5, 1, 1.5, 2, 2.5, 3, 5, 8, 12, 24, 36, and 48 hours after dosing.Population: The PK population included all participants who received at least 1 dose of apremilast and had evaluable PK profiles.
Plasma concentrations of apremilast were determined by using a validated liquid chromatography-tandem mass spectrometry assay. AUC0-t was calculated using the linear trapezoidal method (linear up log down) when concentrations were increasing and the logarithmic trapezoidal method when concentrations were decreasing.
Outcome measures
| Measure |
Apremilast - Fasted
n=45 Participants
Participants received a single 30 mg apremilast tablet administered under fasted conditions.
|
Apremilast - Fed
n=44 Participants
Participants received a single 30 mg apremilast tablet administered after a high fat meal.
|
|---|---|---|
|
Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUC0-t) of Apremilast
|
3083.05 ng*hr/mL
Geometric Coefficient of Variation 34.0
|
3436.39 ng*hr/mL
Geometric Coefficient of Variation 33.0
|
PRIMARY outcome
Timeframe: Day 1 of each treatment period at pre-dose, and at 0.5, 1, 1.5, 2, 2.5, 3, 5, 8, 12, 24, 36, and 48 hours after dosing.Population: The PK population included all participants who received at least 1 dose of apremilast and had evaluable PK profiles.
Plasma concentrations of apremilast were determined by using a validated liquid chromatography-tandem mass spectrometry assay.
Outcome measures
| Measure |
Apremilast - Fasted
n=45 Participants
Participants received a single 30 mg apremilast tablet administered under fasted conditions.
|
Apremilast - Fed
n=44 Participants
Participants received a single 30 mg apremilast tablet administered after a high fat meal.
|
|---|---|---|
|
Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-∞) of Apremilast
|
3157.96 ng*hr/mL
Geometric Coefficient of Variation 34.6
|
3506.19 ng*hr/mL
Geometric Coefficient of Variation 33.9
|
PRIMARY outcome
Timeframe: Day 1 of each treatment period at pre-dose, and at 0.5, 1, 1.5, 2, 2.5, 3, 5, 8, 12, 24, 36, and 48 hours after dosing.Population: The PK population included all participants who received at least 1 dose of apremilast and had evaluable PK profiles.
Plasma concentrations of apremilast were determined by using a validated liquid chromatography-tandem mass spectrometry assay.
Outcome measures
| Measure |
Apremilast - Fasted
n=45 Participants
Participants received a single 30 mg apremilast tablet administered under fasted conditions.
|
Apremilast - Fed
n=44 Participants
Participants received a single 30 mg apremilast tablet administered after a high fat meal.
|
|---|---|---|
|
Estimate of Terminal Elimination Half-life of Apremilast in Plasma (t1/2)
|
8.88 hours
Geometric Coefficient of Variation 21.2
|
7.99 hours
Geometric Coefficient of Variation 18.9
|
PRIMARY outcome
Timeframe: Day 1 of each treatment period at pre-dose, and at 0.5, 1, 1.5, 2, 2.5, 3, 5, 8, 12, 24, 36, and 48 hours after dosing.Population: The PK population included all participants who received at least 1 dose of apremilast and had evaluable PK profiles.
Plasma concentrations of apremilast were determined by using a validated liquid chromatography-tandem mass spectrometry assay.
Outcome measures
| Measure |
Apremilast - Fasted
n=45 Participants
Participants received a single 30 mg apremilast tablet administered under fasted conditions.
|
Apremilast - Fed
n=44 Participants
Participants received a single 30 mg apremilast tablet administered after a high fat meal.
|
|---|---|---|
|
Apparent Total Plasma Clearance When Dosed Orally (CL/F) of Apremilast
|
9499.80 mL/hr
Geometric Coefficient of Variation 34.6
|
8556.28 mL/hr
Geometric Coefficient of Variation 33.9
|
PRIMARY outcome
Timeframe: Day 1 of each treatment period at pre-dose, and at 0.5, 1, 1.5, 2, 2.5, 3, 5, 8, 12, 24, 36, and 48 hours after dosing.Population: The PK population included all participants who received at least 1 dose of apremilast and had evaluable PK profiles.
Plasma concentrations of apremilast were determined by using a validated liquid chromatography-tandem mass spectrometry assay.
Outcome measures
| Measure |
Apremilast - Fasted
n=45 Participants
Participants received a single 30 mg apremilast tablet administered under fasted conditions.
|
Apremilast - Fed
n=44 Participants
Participants received a single 30 mg apremilast tablet administered after a high fat meal.
|
|---|---|---|
|
Apparent Total Volume of Distribution When Dosed Orally (Vz/F) of Apremilast
|
121735.96 mL
Geometric Coefficient of Variation 38.2
|
98582.15 mL
Geometric Coefficient of Variation 28.0
|
SECONDARY outcome
Timeframe: From first dose of study drug in Period 1 up to 5 to 10 days after dosing in Period 2, approximately 20 days.Population: The safety population included all participants who received at least 1 dose of apremilast.
An adverse event (AE) was any noxious, unintended, or untoward medical occurrence that appeared or worsened in a participant during the course of this 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 preexisting condition) was considered an AE.
Outcome measures
| Measure |
Apremilast - Fasted
n=45 Participants
Participants received a single 30 mg apremilast tablet administered under fasted conditions.
|
Apremilast - Fed
n=46 Participants
Participants received a single 30 mg apremilast tablet administered after a high fat meal.
|
|---|---|---|
|
Number of Participants With Adverse Events
Any adverse event
|
9 Participants
|
5 Participants
|
|
Number of Participants With Adverse Events
Adverse events related to study drug
|
4 Participants
|
3 Participants
|
|
Number of Participants With Adverse Events
Serious adverse events
|
0 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
Discontinued due to adverse event
|
0 Participants
|
2 Participants
|
|
Number of Participants With Adverse Events
Discontinued due to adverse event related to study drug
|
0 Participants
|
1 Participants
|
Adverse Events
Apremilast - Fasted
Apremilast - Fed
Total
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Apremilast - Fasted
n=45 participants at risk
Participants received a single 30 mg apremilast tablet administered under fasted conditions.
|
Apremilast - Fed
n=46 participants at risk
Participants received a single 30 mg apremilast tablet administered after a high fat meal.
|
Total
n=46 participants at risk
Participants received one dose of 30 mg apremilast administered under fasted conditions and one dose of 30 mg apremilast after a full fat meal.
|
|---|---|---|---|
|
Gastrointestinal disorders
Nausea
|
6.7%
3/45 • From first dose of study drug in Period 1 up to 5 to 10 days after dosing in Period 2, approximately 20 days.
Adverse events are reported for all participants who received at least 1 dose of study drug.
|
4.3%
2/46 • From first dose of study drug in Period 1 up to 5 to 10 days after dosing in Period 2, approximately 20 days.
Adverse events are reported for all participants who received at least 1 dose of study drug.
|
10.9%
5/46 • From first dose of study drug in Period 1 up to 5 to 10 days after dosing in Period 2, approximately 20 days.
Adverse events are reported for all participants who received at least 1 dose of study drug.
|
|
Nervous system disorders
Headache
|
6.7%
3/45 • From first dose of study drug in Period 1 up to 5 to 10 days after dosing in Period 2, approximately 20 days.
Adverse events are reported for all participants who received at least 1 dose of study drug.
|
2.2%
1/46 • From first dose of study drug in Period 1 up to 5 to 10 days after dosing in Period 2, approximately 20 days.
Adverse events are reported for all participants who received at least 1 dose of study drug.
|
6.5%
3/46 • From first dose of study drug in Period 1 up to 5 to 10 days after dosing in Period 2, approximately 20 days.
Adverse events are reported for all participants who received at least 1 dose of study drug.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER