Trial Outcomes & Findings for Study to Evaluate Bioavailability of Apremilast Oral Suspension Relative to Tablet and to Assess Effect of Food on the Pharmacokinetics (PK) of the Oral Suspension (NCT NCT02641353)
NCT ID: NCT02641353
Last Updated: 2021-08-05
Results Overview
Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
34 participants
Primary outcome timeframe
Predose and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 60 and 72 hours after dosing on day 1 of each treatment period.
Results posted on
2021-08-05
Participant Flow
Participants were enrolled at a single site in the United States. The study consisted of three treatment periods separated by a 5-day washout period.
Participants were randomly assigned to one of six treatment sequences. On day 1 of each treatment sequence participants received one of the following according to their assigned treatment sequence: * Treatment A: Single oral dose of 30 mg apremilast tablet under fasted conditions * Treatment B: Single oral dose of 30 mg apremilast oral suspension formulation under fasted conditions * Treatment C: Single oral dose of 30 mg apremilast oral suspension formulation under fed conditions
Participant milestones
| Measure |
Sequence 1: Treatments ACB
Participants received 30 mg apremilast oral tablet after an overnight fast on day 1 of treatment period 1, 30 mg apremilast oral suspension after a high-fat meal on day 1 of treatment period 2, and 30 mg apremilast oral suspension after an overnight fast on day 1 of treatment period 3.
|
Sequence 2: Treatments CBA
Participants received 30 mg apremilast oral suspension after a high-fat meal on day 1 of treatment period 1, 30 mg apremilast oral suspension after an overnight fast on day 1 of treatment period 2, and 30 mg apremilast oral tablet after an overnight fast on day 1 of treatment period 3.
|
Sequence 3: Treatments BAC
Participants received 30 mg apremilast oral suspension after an overnight fast on day 1 of treatment period 1, 30 mg apremilast oral tablet after an overnight fast on day 1 of treatment period 2, and 30 mg apremilast oral suspension after a high-fat meal on day 1 of treatment period 3.
|
Sequence 4: Treatments ABC
Participants received 30 mg apremilast oral tablet after an overnight fast on day 1 of treatment period 1, 30 mg apremilast oral suspension after an overnight fast on day 1 of treatment period 2, and 30 mg apremilast oral suspension after a high-fat meal on day 1 of treatment period 3.
|
Sequence 5: Treatments CAB
Participants received 30 mg apremilast oral suspension after a high-fat meal on day 1 of treatment period 1, 30 mg apremilast oral tablet after an overnight fast on day 1 of treatment period 2, and 30 mg apremilast oral suspension after an overnight fast on day 1 of treatment period 3.
|
Sequence 6: Treatments BCA
Participants received 30 mg apremilast oral suspension after an overnight fast on day 1 of treatment period 1, 30 mg apremilast oral suspension after a high-fat meal on day 1 of treatment period 2, and 30 mg apremilast oral tablet after an overnight fast on day 1 of treatment period 3.
|
|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
5
|
5
|
6
|
6
|
6
|
6
|
|
Overall Study
COMPLETED
|
5
|
5
|
6
|
6
|
6
|
6
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Study to Evaluate Bioavailability of Apremilast Oral Suspension Relative to Tablet and to Assess Effect of Food on the Pharmacokinetics (PK) of the Oral Suspension
Baseline characteristics by cohort
| Measure |
Total
n=34 Participants
Participants received a single dose of the following three treatments in one of six treatment sequences:
* Treatment A: Single oral dose of 30 mg apremilast tablet under fasted conditions
* Treatment B: Single oral dose of 30 mg apremilast oral suspension formulation under fasted conditions
* Treatment C: Single oral dose of 30 mg apremilast oral suspension formulation under fed conditions
|
|---|---|
|
Age, Continuous
|
33.3 years
n=99 Participants
|
|
Sex: Female, Male
Female
|
9 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
25 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
33 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
|
1 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
Asian
|
1 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
14 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
White
|
17 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
Other
|
1 Participants
n=99 Participants
|
PRIMARY outcome
Timeframe: Predose and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 60 and 72 hours after dosing on day 1 of each treatment period.Population: The pharmacokinetic (PK) population included all participants who received at least one dose of apremilast and had at least one measurable concentration datum.
Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.
Outcome measures
| Measure |
Treatment A: Apremilast 30 mg Tablet - Fasted
n=34 Participants
A single oral dose of 30 mg apremilast tablet after an overnight fast.
|
Treatment B: Apremilast 30 mg Oral Suspension - Fasted
n=34 Participants
A single oral dose of 30 mg apremilast oral suspension formulation (6 mL) after an overnight fast.
|
Treatment C: Apremilast 30 mg Oral Suspension - Fed
n=34 Participants
A single oral dose of 30 mg apremilast oral suspension formulation (6 mL) after a high-fat meal.
|
|---|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) of Apremilast
|
323 ng/mL
Geometric Coefficient of Variation 34.5
|
274 ng/mL
Geometric Coefficient of Variation 32.2
|
215 ng/mL
Geometric Coefficient of Variation 33.7
|
PRIMARY outcome
Timeframe: Predose and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 60 and 72 hours after dosing on day 1 of each treatment period.Population: The pharmacokinetic population
Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay. AUC from time zero to the last measured time point was calculated by the linear trapezoidal method.
Outcome measures
| Measure |
Treatment A: Apremilast 30 mg Tablet - Fasted
n=34 Participants
A single oral dose of 30 mg apremilast tablet after an overnight fast.
|
Treatment B: Apremilast 30 mg Oral Suspension - Fasted
n=34 Participants
A single oral dose of 30 mg apremilast oral suspension formulation (6 mL) after an overnight fast.
|
Treatment C: Apremilast 30 mg Oral Suspension - Fed
n=34 Participants
A single oral dose of 30 mg apremilast oral suspension formulation (6 mL) after a high-fat meal.
|
|---|---|---|---|
|
Area Under the Concentration-time Curve From Time Zero to the Last Measured Time Point (AUC0-t) for Apremilast
|
3130 ng*h/mL
Geometric Coefficient of Variation 38.9
|
2740 ng*h/mL
Geometric Coefficient of Variation 43.1
|
3160 ng*h/mL
Geometric Coefficient of Variation 41.3
|
PRIMARY outcome
Timeframe: Predose and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 60 and 72 hours after dosing on day 1 of each treatment period.Population: The pharmacokinetic population
Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay. AUC from time zero to infinity was calculated as (AUC0-t + Ct/λz), where Ct is the last quantifiable concentration, and λz is the apparent terminal rate constant.
Outcome measures
| Measure |
Treatment A: Apremilast 30 mg Tablet - Fasted
n=34 Participants
A single oral dose of 30 mg apremilast tablet after an overnight fast.
|
Treatment B: Apremilast 30 mg Oral Suspension - Fasted
n=34 Participants
A single oral dose of 30 mg apremilast oral suspension formulation (6 mL) after an overnight fast.
|
Treatment C: Apremilast 30 mg Oral Suspension - Fed
n=34 Participants
A single oral dose of 30 mg apremilast oral suspension formulation (6 mL) after a high-fat meal.
|
|---|---|---|---|
|
Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-∞) for Apremilast
|
3160 ng*h/mL
Geometric Coefficient of Variation 38.7
|
2760 ng*h/mL
Geometric Coefficient of Variation 43.2
|
3190 ng*h/mL
Geometric Coefficient of Variation 41.3
|
PRIMARY outcome
Timeframe: Predose and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 60 and 72 hours after dosing on day 1 of each treatment period.Population: The PK population
Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.
Outcome measures
| Measure |
Treatment A: Apremilast 30 mg Tablet - Fasted
n=34 Participants
A single oral dose of 30 mg apremilast tablet after an overnight fast.
|
Treatment B: Apremilast 30 mg Oral Suspension - Fasted
n=34 Participants
A single oral dose of 30 mg apremilast oral suspension formulation (6 mL) after an overnight fast.
|
Treatment C: Apremilast 30 mg Oral Suspension - Fed
n=34 Participants
A single oral dose of 30 mg apremilast oral suspension formulation (6 mL) after a high-fat meal.
|
|---|---|---|---|
|
Time to Maximum Observed Plasma Concentration (Tmax) of Apremilast
|
2.00 hours
Interval 1.0 to 5.0
|
2.00 hours
Interval 1.5 to 5.0
|
5.00 hours
Interval 1.5 to 12.0
|
PRIMARY outcome
Timeframe: Predose and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 60 and 72 hours after dosing on day 1 of each treatment period.Population: PK population
Outcome measures
| Measure |
Treatment A: Apremilast 30 mg Tablet - Fasted
n=34 Participants
A single oral dose of 30 mg apremilast tablet after an overnight fast.
|
Treatment B: Apremilast 30 mg Oral Suspension - Fasted
n=34 Participants
A single oral dose of 30 mg apremilast oral suspension formulation (6 mL) after an overnight fast.
|
Treatment C: Apremilast 30 mg Oral Suspension - Fed
n=34 Participants
A single oral dose of 30 mg apremilast oral suspension formulation (6 mL) after a high-fat meal.
|
|---|---|---|---|
|
Terminal Elimination Half-life (T1/2) of Apremilast
|
7.89 hours
Geometric Coefficient of Variation 34.5
|
8.51 hours
Geometric Coefficient of Variation 31.8
|
7.54 hours
Geometric Coefficient of Variation 30.8
|
PRIMARY outcome
Timeframe: Predose and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 60 and 72 hours after dosing on day 1 of each treatment period.Population: PK population
Outcome measures
| Measure |
Treatment A: Apremilast 30 mg Tablet - Fasted
n=34 Participants
A single oral dose of 30 mg apremilast tablet after an overnight fast.
|
Treatment B: Apremilast 30 mg Oral Suspension - Fasted
n=34 Participants
A single oral dose of 30 mg apremilast oral suspension formulation (6 mL) after an overnight fast.
|
Treatment C: Apremilast 30 mg Oral Suspension - Fed
n=34 Participants
A single oral dose of 30 mg apremilast oral suspension formulation (6 mL) after a high-fat meal.
|
|---|---|---|---|
|
Apparent Clearance of Apremilast From Plasma After Extravascular Administration (CL/F)
|
9.51 L/h
Geometric Coefficient of Variation 38.7
|
10.9 L/h
Geometric Coefficient of Variation 43.2
|
9.42 L/h
Geometric Coefficient of Variation 41.3
|
PRIMARY outcome
Timeframe: Predose and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 60 and 72 hours after dosing on day 1 of each treatment period.Population: PK population
Outcome measures
| Measure |
Treatment A: Apremilast 30 mg Tablet - Fasted
n=34 Participants
A single oral dose of 30 mg apremilast tablet after an overnight fast.
|
Treatment B: Apremilast 30 mg Oral Suspension - Fasted
n=34 Participants
A single oral dose of 30 mg apremilast oral suspension formulation (6 mL) after an overnight fast.
|
Treatment C: Apremilast 30 mg Oral Suspension - Fed
n=34 Participants
A single oral dose of 30 mg apremilast oral suspension formulation (6 mL) after a high-fat meal.
|
|---|---|---|---|
|
Apparent Volume of Distribution of Apremilast During the Terminal Phase (Vz/F)
|
108 L
Geometric Coefficient of Variation 45.2
|
133 L
Geometric Coefficient of Variation 43.7
|
102 L
Geometric Coefficient of Variation 38.9
|
PRIMARY outcome
Timeframe: Predose and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 60 and 72 hours after dosing on day 1 of each treatment period.Population: PK population
Lag time is the delay between the time of administration and start of absorption.
Outcome measures
| Measure |
Treatment A: Apremilast 30 mg Tablet - Fasted
n=34 Participants
A single oral dose of 30 mg apremilast tablet after an overnight fast.
|
Treatment B: Apremilast 30 mg Oral Suspension - Fasted
n=34 Participants
A single oral dose of 30 mg apremilast oral suspension formulation (6 mL) after an overnight fast.
|
Treatment C: Apremilast 30 mg Oral Suspension - Fed
n=34 Participants
A single oral dose of 30 mg apremilast oral suspension formulation (6 mL) after a high-fat meal.
|
|---|---|---|---|
|
Lag Time (Tlag) of Apremilast
|
0.00 hours
Interval 0.0 to 0.0
|
0.00 hours
Interval 0.0 to 0.0
|
0.00 hours
Interval 0.0 to 0.0
|
PRIMARY outcome
Timeframe: Predose and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 60 and 72 hours after dosing on day 1 of each treatment period.Population: PK population. Relative bioavailability calculated for each of the oral suspension treatments as pre-specified in the Protocol.
Relative bioavailability of the oral suspension formulation compared to the tablet formulation, calculated as (AUC0-∞/Dose\[oral suspension\]) / (AUC0-∞/Dose\[tablet\]) \* 100%.
Outcome measures
| Measure |
Treatment A: Apremilast 30 mg Tablet - Fasted
n=34 Participants
A single oral dose of 30 mg apremilast tablet after an overnight fast.
|
Treatment B: Apremilast 30 mg Oral Suspension - Fasted
n=34 Participants
A single oral dose of 30 mg apremilast oral suspension formulation (6 mL) after an overnight fast.
|
Treatment C: Apremilast 30 mg Oral Suspension - Fed
A single oral dose of 30 mg apremilast oral suspension formulation (6 mL) after a high-fat meal.
|
|---|---|---|---|
|
Relative Bioavailability (F) of Apremilast Oral Suspension Formulation
|
87.6 percent availability
Geometric Coefficient of Variation 16.1
|
101 percent availability
Geometric Coefficient of Variation 14.3
|
—
|
SECONDARY outcome
Timeframe: From first dose of study drug in treatment period 1 to 8 days after the last dose; up to 18 days.Population: The safety population included 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 participant's health, including laboratory test values, regardless of etiology. A treatment-emergent AE (TEAE) was defined as any AE that occurred after dosing of the study drug. A serious adverse event (SAE) 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.
Outcome measures
| Measure |
Treatment A: Apremilast 30 mg Tablet - Fasted
n=34 Participants
A single oral dose of 30 mg apremilast tablet after an overnight fast.
|
Treatment B: Apremilast 30 mg Oral Suspension - Fasted
n=34 Participants
A single oral dose of 30 mg apremilast oral suspension formulation (6 mL) after an overnight fast.
|
Treatment C: Apremilast 30 mg Oral Suspension - Fed
n=34 Participants
A single oral dose of 30 mg apremilast oral suspension formulation (6 mL) after a high-fat meal.
|
|---|---|---|---|
|
Number of Participants With Treatment-emergent Adverse Events
Any treatment-emergent adverse event (TEAE)
|
8 Participants
|
10 Participants
|
6 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events
TEAEs related to study drug
|
4 Participants
|
7 Participants
|
4 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events
Serious adverse events
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events
TEAEs leading to discontinuation
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events
TEAEs leading to death
|
0 Participants
|
0 Participants
|
0 Participants
|
Adverse Events
Treatment A: Apremilast 30 mg Tablet - Fasted
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Treatment B: Apremilast 30 mg Oral Suspension - Fasted
Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths
Treatment C: Apremilast 30 mg Oral Suspension - Fed
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Total
Serious events: 0 serious events
Other events: 15 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Treatment A: Apremilast 30 mg Tablet - Fasted
n=34 participants at risk
A single oral dose of 30 mg apremilast tablet after an overnight fast.
|
Treatment B: Apremilast 30 mg Oral Suspension - Fasted
n=34 participants at risk
A single oral dose of 30 mg apremilast oral suspension formulation (6 mL) after an overnight fast.
|
Treatment C: Apremilast 30 mg Oral Suspension - Fed
n=34 participants at risk
A single oral dose of 30 mg apremilast oral suspension formulation (6 mL) after a high-fat meal.
|
Total
n=34 participants at risk
Participants received a single dose of the following three treatments in one of six treatment sequences:
* Treatment A: Single oral dose of 30 mg apremilast tablet under fasted conditions
* Treatment B: Single oral dose of 30 mg apremilast oral suspension formulation under fasted conditions
* Treatment C: Single oral dose of 30 mg apremilast oral suspension formulation under fed conditions
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/34 • From first dose of study drug in treatment period 1 to 8 days after the last dose; up to 18 days.
|
5.9%
2/34 • From first dose of study drug in treatment period 1 to 8 days after the last dose; up to 18 days.
|
2.9%
1/34 • From first dose of study drug in treatment period 1 to 8 days after the last dose; up to 18 days.
|
8.8%
3/34 • From first dose of study drug in treatment period 1 to 8 days after the last dose; up to 18 days.
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/34 • From first dose of study drug in treatment period 1 to 8 days after the last dose; up to 18 days.
|
14.7%
5/34 • From first dose of study drug in treatment period 1 to 8 days after the last dose; up to 18 days.
|
2.9%
1/34 • From first dose of study drug in treatment period 1 to 8 days after the last dose; up to 18 days.
|
14.7%
5/34 • From first dose of study drug in treatment period 1 to 8 days after the last dose; up to 18 days.
|
|
Gastrointestinal disorders
Dyspepsia
|
2.9%
1/34 • From first dose of study drug in treatment period 1 to 8 days after the last dose; up to 18 days.
|
2.9%
1/34 • From first dose of study drug in treatment period 1 to 8 days after the last dose; up to 18 days.
|
0.00%
0/34 • From first dose of study drug in treatment period 1 to 8 days after the last dose; up to 18 days.
|
5.9%
2/34 • From first dose of study drug in treatment period 1 to 8 days after the last dose; up to 18 days.
|
|
Gastrointestinal disorders
Flatulence
|
0.00%
0/34 • From first dose of study drug in treatment period 1 to 8 days after the last dose; up to 18 days.
|
2.9%
1/34 • From first dose of study drug in treatment period 1 to 8 days after the last dose; up to 18 days.
|
2.9%
1/34 • From first dose of study drug in treatment period 1 to 8 days after the last dose; up to 18 days.
|
5.9%
2/34 • From first dose of study drug in treatment period 1 to 8 days after the last dose; up to 18 days.
|
|
Gastrointestinal disorders
Nausea
|
5.9%
2/34 • From first dose of study drug in treatment period 1 to 8 days after the last dose; up to 18 days.
|
5.9%
2/34 • From first dose of study drug in treatment period 1 to 8 days after the last dose; up to 18 days.
|
0.00%
0/34 • From first dose of study drug in treatment period 1 to 8 days after the last dose; up to 18 days.
|
11.8%
4/34 • From first dose of study drug in treatment period 1 to 8 days after the last dose; up to 18 days.
|
|
General disorders
Feeling hot
|
0.00%
0/34 • From first dose of study drug in treatment period 1 to 8 days after the last dose; up to 18 days.
|
5.9%
2/34 • From first dose of study drug in treatment period 1 to 8 days after the last dose; up to 18 days.
|
0.00%
0/34 • From first dose of study drug in treatment period 1 to 8 days after the last dose; up to 18 days.
|
5.9%
2/34 • From first dose of study drug in treatment period 1 to 8 days after the last dose; up to 18 days.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
2.9%
1/34 • From first dose of study drug in treatment period 1 to 8 days after the last dose; up to 18 days.
|
2.9%
1/34 • From first dose of study drug in treatment period 1 to 8 days after the last dose; up to 18 days.
|
0.00%
0/34 • From first dose of study drug in treatment period 1 to 8 days after the last dose; up to 18 days.
|
5.9%
2/34 • From first dose of study drug in treatment period 1 to 8 days after the last dose; up to 18 days.
|
|
Nervous system disorders
Headache
|
5.9%
2/34 • From first dose of study drug in treatment period 1 to 8 days after the last dose; up to 18 days.
|
5.9%
2/34 • From first dose of study drug in treatment period 1 to 8 days after the last dose; up to 18 days.
|
5.9%
2/34 • From first dose of study drug in treatment period 1 to 8 days after the last dose; up to 18 days.
|
11.8%
4/34 • From first dose of study drug in treatment period 1 to 8 days after the last dose; up to 18 days.
|
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