NCT02641353

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

Completed Phase 1 Results posted Last updated 5 August 2021

What this trial tests

Phase 1 trial testing Apremilast Tablet in Healthy Volunteers in 34 participants. Completed in 27 February 2016.

Timeline

5 January 2016

Primary endpoint
27 February 2016

27 February 2016

Quick facts

Lead sponsor	Amgen
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	crossover
Masking	none
Primary purpose	other
Enrollment	34
Start date	5 January 2016
Primary completion	27 February 2016
Estimated completion	27 February 2016
Sites	1 location across United States

Drugs / interventions tested

• Apremilast Tablet
• Apremilast Oral Suspension

Conditions studied

• Healthy Volunteers — all drugs for Healthy Volunteers →

Sponsor

Amgen — full company profile →

Who can join

Adults 18 to 55, any sex, with Healthy Volunteers. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Maximum Observed Plasma Concentration (Cmax) of Apremilast Primary · 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.

Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.

Group	Value	95% CI
Treatment A: Apremilast 30 mg Tablet - Fasted	323	± 34.5
Treatment B: Apremilast 30 mg Oral Suspension - Fasted	274	± 32.2
Treatment C: Apremilast 30 mg Oral Suspension - Fed	215	± 33.7

Area Under the Concentration-time Curve From Time Zero to the Last Measured Time Point (AUC0-t) for Apremilast Primary · 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.

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.

Group	Value	95% CI
Treatment A: Apremilast 30 mg Tablet - Fasted	3130	± 38.9
Treatment B: Apremilast 30 mg Oral Suspension - Fasted	2740	± 43.1
Treatment C: Apremilast 30 mg Oral Suspension - Fed	3160	± 41.3

Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-∞) for Apremilast Primary · 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.

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.

Group	Value	95% CI
Treatment A: Apremilast 30 mg Tablet - Fasted	3160	± 38.7
Treatment B: Apremilast 30 mg Oral Suspension - Fasted	2760	± 43.2
Treatment C: Apremilast 30 mg Oral Suspension - Fed	3190	± 41.3

Time to Maximum Observed Plasma Concentration (Tmax) of Apremilast Primary · 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.

Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.

Group	Value	95% CI
Treatment A: Apremilast 30 mg Tablet - Fasted	2.00	1.00 – 5.00
Treatment B: Apremilast 30 mg Oral Suspension - Fasted	2.00	1.50 – 5.00
Treatment C: Apremilast 30 mg Oral Suspension - Fed	5.00	1.50 – 12.00

Terminal Elimination Half-life (T1/2) of Apremilast Primary · 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.

Group	Value	95% CI
Treatment A: Apremilast 30 mg Tablet - Fasted	7.89	± 34.5
Treatment B: Apremilast 30 mg Oral Suspension - Fasted	8.51	± 31.8
Treatment C: Apremilast 30 mg Oral Suspension - Fed	7.54	± 30.8

Apparent Clearance of Apremilast From Plasma After Extravascular Administration (CL/F) Primary · 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.

Group	Value	95% CI
Treatment A: Apremilast 30 mg Tablet - Fasted	9.51	± 38.7
Treatment B: Apremilast 30 mg Oral Suspension - Fasted	10.9	± 43.2
Treatment C: Apremilast 30 mg Oral Suspension - Fed	9.42	± 41.3

Apparent Volume of Distribution of Apremilast During the Terminal Phase (Vz/F) Primary · 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.

Group	Value	95% CI
Treatment A: Apremilast 30 mg Tablet - Fasted	108	± 45.2
Treatment B: Apremilast 30 mg Oral Suspension - Fasted	133	± 43.7
Treatment C: Apremilast 30 mg Oral Suspension - Fed	102	± 38.9

Lag Time (Tlag) of Apremilast Primary · 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.

Lag time is the delay between the time of administration and start of absorption.

Group	Value	95% CI
Treatment A: Apremilast 30 mg Tablet - Fasted	0.00	0.00 – 0.00
Treatment B: Apremilast 30 mg Oral Suspension - Fasted	0.00	0.00 – 0.00
Treatment C: Apremilast 30 mg Oral Suspension - Fed	0.00	0.00 – 0.00

Relative Bioavailability (F) of Apremilast Oral Suspension Formulation Primary · 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.

Relative bioavailability of the oral suspension formulation compared to the tablet formulation, calculated as (AUC0-∞/Dose\[oral suspension\]) / (AUC0-∞/Dose\[tablet\]) \* 100%.

Group	Value	95% CI
Treatment B: Apremilast 30 mg Oral Suspension - Fasted	87.6	± 16.1
Treatment C: Apremilast 30 mg Oral Suspension - Fed	101	± 14.3

Number of Participants With Treatment-emergent Adverse Events Secondary · From first dose of study drug in treatment period 1 to 8 days after the last dose; up to 18 days.

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 hospitaliza

Any treatment-emergent adverse event (TEAE)

Group	Value	95% CI
Treatment A: Apremilast 30 mg Tablet - Fasted	8
Treatment B: Apremilast 30 mg Oral Suspension - Fasted	10
Treatment C: Apremilast 30 mg Oral Suspension - Fed	6

TEAEs related to study drug

Group	Value	95% CI
Treatment A: Apremilast 30 mg Tablet - Fasted	4
Treatment B: Apremilast 30 mg Oral Suspension - Fasted	7
Treatment C: Apremilast 30 mg Oral Suspension - Fed	4

Serious adverse events

Group	Value	95% CI
Treatment A: Apremilast 30 mg Tablet - Fasted	0
Treatment B: Apremilast 30 mg Oral Suspension - Fasted	0
Treatment C: Apremilast 30 mg Oral Suspension - Fed	0

TEAEs leading to discontinuation

Group	Value	95% CI
Treatment A: Apremilast 30 mg Tablet - Fasted	0
Treatment B: Apremilast 30 mg Oral Suspension - Fasted	0
Treatment C: Apremilast 30 mg Oral Suspension - Fed	0

TEAEs leading to death

Group	Value	95% CI
Treatment A: Apremilast 30 mg Tablet - Fasted	0
Treatment B: Apremilast 30 mg Oral Suspension - Fasted	0
Treatment C: Apremilast 30 mg Oral Suspension - Fed	0

Adverse events — posted to ClinicalTrials.gov

Time frame: From first dose of study drug in treatment period 1 to 8 days after the last dose; up to 18 days.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Treatment A: Apremilast 30 mg Tablet - Fasted

Serious: 0/34 (0%)

Deaths: —

Treatment B: Apremilast 30 mg Oral Suspension - Fasted

Serious: 0/34 (0%)

Deaths: —

Treatment C: Apremilast 30 mg Oral Suspension - Fed

Serious: 0/34 (0%)

Deaths: —

Total

Serious: 0/34 (0%)

Deaths: —

Other adverse events (8 terms — click to expand)

Reaction	System	Treatment A: Apremilast 30…	Treatment B: Apremilast 30…	Treatment C: Apremilast 30…	Total
Diarrhoea	Gastrointestinal disorders	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—
Headache	Nervous system disorders	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—
Dyspepsia	Gastrointestinal disorders	—	—	—	—
Flatulence	Gastrointestinal disorders	—	—	—	—
Feeling hot	General disorders	—	—	—	—
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	—	—	—	—

Data from ClinicalTrials.gov NCT02641353 adverse events section.

Sponsor's own description

The purpose of this study is to assess how much of apremilast is found in the blood unchanged when administered as an oral suspension compared to when it is administered as a tablet formulation. The effect of food on apremilast oral suspension will also be evaluated. In addition, information on the safety and tolerability of apremilast will be obtained.

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.