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
Study Details
Study Description
Brief Summary
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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 1 |
Detailed Description
This is a phase 1, open-label, randomized, three-period, six-sequence crossover study in healthy subjects. The study will consist of a screening phase, baseline (Day -1), three study periods, and a follow-up phone call. Each study period will be four days in duration (Day 1 through Day 4) followed by a five-day washout between doses.
Eligible participants will be admitted into the study center on Day -1 of study Period 1 for baseline measurements. During each study period, participants will receive a single 30 mg oral dose of apremilast on Day 1 according to the assigned treatment sequence. Participants will be confined at the study center from Day 1 of study Period 1 through Day 4 of study Period 3, including the 5 day washout between doses. All participants will be discharged from the study center on Day 4 of study Period 3 following completion of required study procedures. A follow-up phone call will occur approximately four days after the discharge from the study center.
The study will be conducted in compliance with International Conference on Harmonisation (ICH) Good Clinical Practices (GCPs).
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Treatment A: Apremilast 30 mg Tablet - Fasted A single oral dose of 30 mg apremilast tablet after an overnight fast. |
Drug: Apremilast Tablet
30 mg tablet
Other Names:
|
Experimental: Treatment B: Apremilast 30 mg Oral Suspension - Fasted A single oral dose of 30 mg apremilast oral suspension formulation (6 mL) after an overnight fast. |
Drug: Apremilast Oral Suspension
30 mg oral suspension
Other Names:
|
Experimental: 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. |
Drug: Apremilast Oral Suspension
30 mg oral suspension
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Maximum Observed Plasma Concentration (Cmax) of Apremilast [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.
- Area Under the Concentration-time Curve From Time Zero to the Last Measured Time Point (AUC0-t) for Apremilast [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.
- Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-∞) for Apremilast [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.
- Time to Maximum Observed Plasma Concentration (Tmax) of Apremilast [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.
- Terminal Elimination Half-life (T1/2) of Apremilast [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.]
- Apparent Clearance of Apremilast From Plasma After Extravascular Administration (CL/F) [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.]
- Apparent Volume of Distribution of Apremilast During the Terminal Phase (Vz/F) [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 (Tlag) of Apremilast [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.
- Relative Bioavailability (F) of Apremilast Oral Suspension Formulation [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%.
Secondary Outcome Measures
- Number of Participants With Treatment-emergent Adverse Events [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 hospitalization or prolongation of existing hospitalization; Resulted in persistent or significant disability/incapacity; Was a congenital anomaly/birth defect; Constituted an important medical event.
Eligibility Criteria
Criteria
Inclusion Criteria:
Subjects must satisfy ALL of the following criteria to be eligible for enrollment into the study:
-
Must understand and voluntarily sign a written Informed Consent (ICF) prior to any study-related procedures being performed.
-
Must be able to communicate with the investigator, understand and comply with the requirements of the study, and agree to adhere to restrictions and examination schedules.
-
Male and female subjects of any race between 18 to 55 years of age (inclusive), and in good health as determined by the Investigator at the time of signing the informed consent document.
-
Have a Body Mass Index (BMI) between 18 and 33 kg/m^2 (inclusive).
-
No clinically significant laboratory test results as determined by the investigator.
-
At the screening visit, must be afebrile, with supine systolic blood pressure (BP): 90 to 140 mmHg, supine diastolic BP: 50 to 90 mmHg, and pulse rate: 40 to 110 bpm. Eligibility criteria for vital signs performed during check-in and/or predose on Day 1 will be at the discretion of the Investigator.
-
Must have a normal or clinically acceptable 12-lead electrocardiogram (ECG). Subjects must have a QTcF value ≤ 450 msec.
-
Contraception Requirements:
-
Must comply with the following acceptable forms of contraception. All female of childbearing potential (FCBP) must use one of the approved contraceptive options as described below while taking apremilast and for at least 28 days after administration of the last dose of the apremilast.
-
At the time of study entry, and at any time during the study when a FCBP's contraceptive measures or ability to become pregnant changes, the Investigator will educate the subject regarding contraception options and the correct and consistent use of effective contraceptive methods in order to successfully prevent pregnancy
All FCBP must have a negative pregnancy test at Visits 1 and 2. All FCBP subjects who engage in activity in which conception is possible must use one of the approved contraceptive options described below:
Option 1: Any one of the following highly effective methods: hormonal contraception (oral, injection, implant, transdermal patch, vaginal ring); intrauterine device (IUD); tubal ligation; or partner's vasectomy; OR Option 2: Male or female condom (latex condom or non-latex condom NOT made out of natural [animal] membrane [for example, polyurethane]); PLUS one of the following additional barrier methods: (a) diaphragm with spermicide; (b) cervical cap with spermicide; or (c) contraceptive sponge with spermicide.
Male subjects (including those who have had a vasectomy) who engage in activity in which conception is possible must use barrier contraception (latex or non-latex condoms NOT made out of natural [animal] membrane [for example, polyurethane]) while on investigational product (IP) and for at least 28 days after the last dose of IP.
-
Must agree to refrain from donating sperm, blood or plasma (other than for this study) while participating in this study and for at least 28 days after the last dose of investigational product.
-
Subject is willing and able to adhere to the study visit schedule and other protocol requirements
Exclusion Criteria:
The presence of ANY of the following will exclude any healthy subject from enrollment into the study:
-
History of any clinically significant and relevant neurological, psychiatric, gastrointestinal, renal, hepatic, cardiovascular, psychological, pulmonary, metabolic, endocrine, hematological, allergic disease, drug allergies, or other major disorders.
-
Any condition which places the subject at unacceptable risk if he were to participate in the study, or confounds the ability to interpret data from the study.
-
Use of any prescribed systemic or topical medication within 30 days of the first dose administration.
-
Use of any non-prescribed systemic or topical medication (including vitamin/mineral supplements, and herbal medicines) within 14 days of the first dose administration, Any surgical or medical condition possibly affecting drug absorption, distribution, metabolism and excretion, eg, bariatric procedure, colon resection, irritable bowel syndrome, Crohn's disease, etc. Subjects with cholecystectomy and appendectomy may be included.
-
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).
-
Donated blood or plasma within 8 weeks before the first dose administration to a blood bank or blood donation center.
-
History of drug abuse (as defined by the current version of the Diagnostic and Statistical Manual [DSM]) within 2 years before dosing, or a positive drug screen reflecting consumption of illicit drugs.
-
History of alcohol abuse (as defined by the current version of the DSM) within 2 years before dosing, or a positive alcohol screen.
-
Known to have hepatitis, or known to be a carrier of the hepatitis B surface antigen (HBsAg), or hepatitis C antibody (HCV Ab), or have a positive result to the test for HBsAg, HCV Ab, or human immunodeficiency virus (HIV) antibodies at Screening.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Covance Clinical Research Unit Inc | Madison | Wisconsin | United States | 53704 |
Sponsors and Collaborators
- Amgen
Investigators
- Study Director: MD, Amgen
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CC-10004-CP-032
- 20200157
Study Results
Participant Flow
Recruitment Details | 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. |
---|---|
Pre-assignment Detail | 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 |
Arm/Group Title | Sequence 1: Treatments ACB | Sequence 2: Treatments CBA | Sequence 3: Treatments BAC | Sequence 4: Treatments ABC | Sequence 5: Treatments CAB | Sequence 6: Treatments BCA |
---|---|---|---|---|---|---|
Arm/Group Description | 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. | 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. | 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. | 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. | 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. | 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. |
Period Title: Overall Study | ||||||
STARTED | 5 | 5 | 6 | 6 | 6 | 6 |
COMPLETED | 5 | 5 | 6 | 6 | 6 | 6 |
NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline Characteristics
Arm/Group Title | Total |
---|---|
Arm/Group Description | 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 |
Overall Participants | 34 |
Age (years) [Mean (Full Range) ] | |
Mean (Full Range) [years] |
33.3
|
Sex: Female, Male (Count of Participants) | |
Female |
9
26.5%
|
Male |
25
73.5%
|
Ethnicity (NIH/OMB) (Count of Participants) | |
Hispanic or Latino |
1
2.9%
|
Not Hispanic or Latino |
33
97.1%
|
Unknown or Not Reported |
0
0%
|
Race/Ethnicity, Customized (Count of Participants) | |
American Indian or Alaska Native |
1
2.9%
|
Asian |
1
2.9%
|
Black or African American |
14
41.2%
|
White |
17
50%
|
Other |
1
2.9%
|
Outcome Measures
Title | Maximum Observed Plasma Concentration (Cmax) of Apremilast |
---|---|
Description | Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay. |
Time Frame | 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. |
Outcome Measure Data
Analysis Population Description |
---|
The pharmacokinetic (PK) population included all participants who received at least one dose of apremilast and had at least one measurable concentration datum. |
Arm/Group Title | Treatment A: Apremilast 30 mg Tablet - Fasted | Treatment B: Apremilast 30 mg Oral Suspension - Fasted | Treatment C: Apremilast 30 mg Oral Suspension - Fed |
---|---|---|---|
Arm/Group Description | A single oral dose of 30 mg apremilast tablet after an overnight fast. | A single oral dose of 30 mg apremilast oral suspension formulation (6 mL) after an overnight fast. | A single oral dose of 30 mg apremilast oral suspension formulation (6 mL) after a high-fat meal. |
Measure Participants | 34 | 34 | 34 |
Geometric Mean (Geometric Coefficient of Variation) [ng/mL] |
323
(34.5)
|
274
(32.2)
|
215
(33.7)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Treatment A: Apremilast 30 mg Tablet - Fasted, Treatment B: Apremilast 30 mg Oral Suspension - Fasted |
---|---|---|
Comments | To assess the bioavailability between the apremilast oral suspension and tablet formulation an analysis of variance (ANOVA) model, with treatment, sequence, and period as fixed effects and subject nested within sequence as a random effect, was performed on the natural log-transformed Cmax. | |
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 | 84.9 | |
Confidence Interval |
(2-Sided) 90% 77.3 to 93.2 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Ratio of adjusted geometric means (Treatment B / Treatment A) expressed as a percentage. |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Treatment B: Apremilast 30 mg Oral Suspension - Fasted, Treatment C: Apremilast 30 mg Oral Suspension - Fed |
---|---|---|
Comments | To assess the effect of food on the PK of apremilast oral suspension formulation, an ANOVA model, with treatment, sequence, and period as fixed effects and subject nested within sequence as a random effect, was performed on the natural log-transformed Cmax. | |
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 | 78.2 | |
Confidence Interval |
(2-Sided) 90% 71.2 to 86.0 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Ratio of adjusted geometric means (Treatment C / Treatment B) expressed as a percentage. |
Title | Area Under the Concentration-time Curve From Time Zero to the Last Measured Time Point (AUC0-t) for Apremilast |
---|---|
Description | 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. |
Time Frame | 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. |
Outcome Measure Data
Analysis Population Description |
---|
The pharmacokinetic population |
Arm/Group Title | Treatment A: Apremilast 30 mg Tablet - Fasted | Treatment B: Apremilast 30 mg Oral Suspension - Fasted | Treatment C: Apremilast 30 mg Oral Suspension - Fed |
---|---|---|---|
Arm/Group Description | A single oral dose of 30 mg apremilast tablet after an overnight fast. | A single oral dose of 30 mg apremilast oral suspension formulation (6 mL) after an overnight fast. | A single oral dose of 30 mg apremilast oral suspension formulation (6 mL) after a high-fat meal. |
Measure Participants | 34 | 34 | 34 |
Geometric Mean (Geometric Coefficient of Variation) [ng*h/mL] |
3130
(38.9)
|
2740
(43.1)
|
3160
(41.3)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Treatment A: Apremilast 30 mg Tablet - Fasted, Treatment B: Apremilast 30 mg Oral Suspension - Fasted |
---|---|---|
Comments | To assess the bioavailability between the apremilast oral suspension and tablet formulation an ANOVA model, with treatment, sequence, and period as fixed effects and subject nested within sequence as a random effect, was performed on the natural log-transformed AUC0-t. | |
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 | 87.6 | |
Confidence Interval |
(2-Sided) 90% 83.0 to 92.5 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Ratio of adjusted geometric means (Treatment B / Treatment A) expressed as a percentage. |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Treatment B: Apremilast 30 mg Oral Suspension - Fasted, Treatment C: Apremilast 30 mg Oral Suspension - Fed |
---|---|---|
Comments | To assess the effect of food on the PK of apremilast oral suspension formulation, an ANOVA model, with treatment, sequence, and period as fixed effects and subject nested within sequence as a random effect, was performed on the natural log-transformed AUC0-t. | |
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 | 115.3 | |
Confidence Interval |
(2-Sided) 90% 109.2 to 121.7 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Ratio of adjusted geometric means (Treatment C / Treatment B) expressed as a percentage. |
Title | Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-∞) for Apremilast |
---|---|
Description | 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. |
Time Frame | 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. |
Outcome Measure Data
Analysis Population Description |
---|
The pharmacokinetic population |
Arm/Group Title | Treatment A: Apremilast 30 mg Tablet - Fasted | Treatment B: Apremilast 30 mg Oral Suspension - Fasted | Treatment C: Apremilast 30 mg Oral Suspension - Fed |
---|---|---|---|
Arm/Group Description | A single oral dose of 30 mg apremilast tablet after an overnight fast. | A single oral dose of 30 mg apremilast oral suspension formulation (6 mL) after an overnight fast. | A single oral dose of 30 mg apremilast oral suspension formulation (6 mL) after a high-fat meal. |
Measure Participants | 34 | 34 | 34 |
Geometric Mean (Geometric Coefficient of Variation) [ng*h/mL] |
3160
(38.7)
|
2760
(43.2)
|
3190
(41.3)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Treatment A: Apremilast 30 mg Tablet - Fasted, Treatment B: Apremilast 30 mg Oral Suspension - Fasted |
---|---|---|
Comments | To assess the bioavailability between the apremilast oral suspension and tablet formulation an ANOVA model, with treatment, sequence, and period as fixed effects and subject nested within sequence as a random effect, was performed on the natural log-transformed AUC0-∞. | |
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 | 87.8 | |
Confidence Interval |
(2-Sided) 90% 83.2 to 92.6 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Ratio of adjusted geometric means (Treatment B / Treatment A) expressed as a percentage. |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Treatment B: Apremilast 30 mg Oral Suspension - Fasted, Treatment C: Apremilast 30 mg Oral Suspension - Fed |
---|---|---|
Comments | To assess the effect of food on the PK of apremilast oral suspension formulation, an ANOVA model, with treatment, sequence, and period as fixed effects and subject nested within sequence as a random effect, was performed on the natural log-transformed AUC0-∞. | |
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 | 115.0 | |
Confidence Interval |
(2-Sided) 90% 109.0 to 121.7 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Ratio of adjusted geometric means (Treatment C / Treatment B) expressed as a percentage. |
Title | Time to Maximum Observed Plasma Concentration (Tmax) of Apremilast |
---|---|
Description | Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay. |
Time Frame | 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. |
Outcome Measure Data
Analysis Population Description |
---|
The PK population |
Arm/Group Title | Treatment A: Apremilast 30 mg Tablet - Fasted | Treatment B: Apremilast 30 mg Oral Suspension - Fasted | Treatment C: Apremilast 30 mg Oral Suspension - Fed |
---|---|---|---|
Arm/Group Description | A single oral dose of 30 mg apremilast tablet after an overnight fast. | A single oral dose of 30 mg apremilast oral suspension formulation (6 mL) after an overnight fast. | A single oral dose of 30 mg apremilast oral suspension formulation (6 mL) after a high-fat meal. |
Measure Participants | 34 | 34 | 34 |
Median (Full Range) [hours] |
2.00
|
2.00
|
5.00
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Treatment A: Apremilast 30 mg Tablet - Fasted, Treatment B: Apremilast 30 mg Oral Suspension - Fasted |
---|---|---|
Comments | Tmax was analyzed by nonparametric methods. The median difference and 90% confidence interval (CI) of the median difference were calculated from the Hodges-Lehrmann estimate. | |
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.1508 |
Comments | ||
Method | Wilcoxon signed-rank test | |
Comments | ||
Method of Estimation | Estimation Parameter | Median Difference |
Estimated Value | 0.25 | |
Confidence Interval |
(2-Sided) 90% 0.00 to 0.50 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Median difference (Treatment B - Treatment A) calculated from the Hodges-Lehmann estimate |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Treatment B: Apremilast 30 mg Oral Suspension - Fasted, Treatment C: Apremilast 30 mg Oral Suspension - Fed |
---|---|---|
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 | <0.0001 |
Comments | ||
Method | Wilcoxon signed-rank test | |
Comments | ||
Method of Estimation | Estimation Parameter | Median Difference |
Estimated Value | 2.25 | |
Confidence Interval |
(2-Sided) 90% 1.27 to 3.25 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Median difference (Treatment C - Treatment B) calculated from the Hodges-Lehmann estimate |
Title | Terminal Elimination Half-life (T1/2) of Apremilast |
---|---|
Description | |
Time Frame | 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. |
Outcome Measure Data
Analysis Population Description |
---|
PK population |
Arm/Group Title | Treatment A: Apremilast 30 mg Tablet - Fasted | Treatment B: Apremilast 30 mg Oral Suspension - Fasted | Treatment C: Apremilast 30 mg Oral Suspension - Fed |
---|---|---|---|
Arm/Group Description | A single oral dose of 30 mg apremilast tablet after an overnight fast. | A single oral dose of 30 mg apremilast oral suspension formulation (6 mL) after an overnight fast. | A single oral dose of 30 mg apremilast oral suspension formulation (6 mL) after a high-fat meal. |
Measure Participants | 34 | 34 | 34 |
Geometric Mean (Geometric Coefficient of Variation) [hours] |
7.89
(34.5)
|
8.51
(31.8)
|
7.54
(30.8)
|
Title | Apparent Clearance of Apremilast From Plasma After Extravascular Administration (CL/F) |
---|---|
Description | |
Time Frame | 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. |
Outcome Measure Data
Analysis Population Description |
---|
PK population |
Arm/Group Title | Treatment A: Apremilast 30 mg Tablet - Fasted | Treatment B: Apremilast 30 mg Oral Suspension - Fasted | Treatment C: Apremilast 30 mg Oral Suspension - Fed |
---|---|---|---|
Arm/Group Description | A single oral dose of 30 mg apremilast tablet after an overnight fast. | A single oral dose of 30 mg apremilast oral suspension formulation (6 mL) after an overnight fast. | A single oral dose of 30 mg apremilast oral suspension formulation (6 mL) after a high-fat meal. |
Measure Participants | 34 | 34 | 34 |
Geometric Mean (Geometric Coefficient of Variation) [L/h] |
9.51
(38.7)
|
10.9
(43.2)
|
9.42
(41.3)
|
Title | Apparent Volume of Distribution of Apremilast During the Terminal Phase (Vz/F) |
---|---|
Description | |
Time Frame | 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. |
Outcome Measure Data
Analysis Population Description |
---|
PK population |
Arm/Group Title | Treatment A: Apremilast 30 mg Tablet - Fasted | Treatment B: Apremilast 30 mg Oral Suspension - Fasted | Treatment C: Apremilast 30 mg Oral Suspension - Fed |
---|---|---|---|
Arm/Group Description | A single oral dose of 30 mg apremilast tablet after an overnight fast. | A single oral dose of 30 mg apremilast oral suspension formulation (6 mL) after an overnight fast. | A single oral dose of 30 mg apremilast oral suspension formulation (6 mL) after a high-fat meal. |
Measure Participants | 34 | 34 | 34 |
Geometric Mean (Geometric Coefficient of Variation) [L] |
108
(45.2)
|
133
(43.7)
|
102
(38.9)
|
Title | Lag Time (Tlag) of Apremilast |
---|---|
Description | Lag time is the delay between the time of administration and start of absorption. |
Time Frame | 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. |
Outcome Measure Data
Analysis Population Description |
---|
PK population |
Arm/Group Title | Treatment A: Apremilast 30 mg Tablet - Fasted | Treatment B: Apremilast 30 mg Oral Suspension - Fasted | Treatment C: Apremilast 30 mg Oral Suspension - Fed |
---|---|---|---|
Arm/Group Description | A single oral dose of 30 mg apremilast tablet after an overnight fast. | A single oral dose of 30 mg apremilast oral suspension formulation (6 mL) after an overnight fast. | A single oral dose of 30 mg apremilast oral suspension formulation (6 mL) after a high-fat meal. |
Measure Participants | 34 | 34 | 34 |
Median (Full Range) [hours] |
0.00
|
0.00
|
0.00
|
Title | Relative Bioavailability (F) of Apremilast Oral Suspension Formulation |
---|---|
Description | Relative bioavailability of the oral suspension formulation compared to the tablet formulation, calculated as (AUC0-∞/Dose[oral suspension]) / (AUC0-∞/Dose[tablet]) * 100%. |
Time Frame | 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. |
Outcome Measure Data
Analysis Population Description |
---|
PK population. Relative bioavailability calculated for each of the oral suspension treatments as pre-specified in the Protocol. |
Arm/Group Title | Treatment B: Apremilast 30 mg Oral Suspension - Fasted | Treatment C: Apremilast 30 mg Oral Suspension - Fed |
---|---|---|
Arm/Group Description | A single oral dose of 30 mg apremilast oral suspension formulation (6 mL) after an overnight fast. | A single oral dose of 30 mg apremilast oral suspension formulation (6 mL) after a high-fat meal. |
Measure Participants | 34 | 34 |
Geometric Mean (Geometric Coefficient of Variation) [percent availability] |
87.6
(16.1)
|
101
(14.3)
|
Title | Number of Participants With Treatment-emergent Adverse Events |
---|---|
Description | 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. |
Time Frame | From first dose of study drug in treatment period 1 to 8 days after the last dose; up to 18 days. |
Outcome Measure Data
Analysis Population Description |
---|
The safety population included all participants who received at least one dose of apremilast. |
Arm/Group Title | Treatment A: Apremilast 30 mg Tablet - Fasted | Treatment B: Apremilast 30 mg Oral Suspension - Fasted | Treatment C: Apremilast 30 mg Oral Suspension - Fed |
---|---|---|---|
Arm/Group Description | A single oral dose of 30 mg apremilast tablet after an overnight fast. | A single oral dose of 30 mg apremilast oral suspension formulation (6 mL) after an overnight fast. | A single oral dose of 30 mg apremilast oral suspension formulation (6 mL) after a high-fat meal. |
Measure Participants | 34 | 34 | 34 |
Any treatment-emergent adverse event (TEAE) |
8
23.5%
|
10
NaN
|
6
NaN
|
TEAEs related to study drug |
4
11.8%
|
7
NaN
|
4
NaN
|
Serious adverse events |
0
0%
|
0
NaN
|
0
NaN
|
TEAEs leading to discontinuation |
0
0%
|
0
NaN
|
0
NaN
|
TEAEs leading to death |
0
0%
|
0
NaN
|
0
NaN
|
Adverse Events
Time Frame | From first dose of study drug in treatment period 1 to 8 days after the last dose; up to 18 days. | |||||||
---|---|---|---|---|---|---|---|---|
Adverse Event Reporting Description | ||||||||
Arm/Group Title | Treatment A: Apremilast 30 mg Tablet - Fasted | Treatment B: Apremilast 30 mg Oral Suspension - Fasted | Treatment C: Apremilast 30 mg Oral Suspension - Fed | Total | ||||
Arm/Group Description | A single oral dose of 30 mg apremilast tablet after an overnight fast. | A single oral dose of 30 mg apremilast oral suspension formulation (6 mL) after an overnight fast. | A single oral dose of 30 mg apremilast oral suspension formulation (6 mL) after a high-fat meal. | 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 | ||||
All Cause Mortality |
||||||||
Treatment A: Apremilast 30 mg Tablet - Fasted | Treatment B: Apremilast 30 mg Oral Suspension - Fasted | Treatment C: Apremilast 30 mg Oral Suspension - Fed | Total | |||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||
Serious Adverse Events |
||||||||
Treatment A: Apremilast 30 mg Tablet - Fasted | Treatment B: Apremilast 30 mg Oral Suspension - Fasted | Treatment C: Apremilast 30 mg Oral Suspension - Fed | Total | |||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/34 (0%) | 0/34 (0%) | 0/34 (0%) | 0/34 (0%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
Treatment A: Apremilast 30 mg Tablet - Fasted | Treatment B: Apremilast 30 mg Oral Suspension - Fasted | Treatment C: Apremilast 30 mg Oral Suspension - Fed | Total | |||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 5/34 (14.7%) | 10/34 (29.4%) | 3/34 (8.8%) | 15/34 (44.1%) | ||||
Gastrointestinal disorders | ||||||||
Constipation | 0/34 (0%) | 2/34 (5.9%) | 1/34 (2.9%) | 3/34 (8.8%) | ||||
Diarrhoea | 0/34 (0%) | 5/34 (14.7%) | 1/34 (2.9%) | 5/34 (14.7%) | ||||
Dyspepsia | 1/34 (2.9%) | 1/34 (2.9%) | 0/34 (0%) | 2/34 (5.9%) | ||||
Flatulence | 0/34 (0%) | 1/34 (2.9%) | 1/34 (2.9%) | 2/34 (5.9%) | ||||
Nausea | 2/34 (5.9%) | 2/34 (5.9%) | 0/34 (0%) | 4/34 (11.8%) | ||||
General disorders | ||||||||
Feeling hot | 0/34 (0%) | 2/34 (5.9%) | 0/34 (0%) | 2/34 (5.9%) | ||||
Musculoskeletal and connective tissue disorders | ||||||||
Musculoskeletal pain | 1/34 (2.9%) | 1/34 (2.9%) | 0/34 (0%) | 2/34 (5.9%) | ||||
Nervous system disorders | ||||||||
Headache | 2/34 (5.9%) | 2/34 (5.9%) | 2/34 (5.9%) | 4/34 (11.8%) |
Limitations/Caveats
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.
Results Point of Contact
Name/Title | Study Director |
---|---|
Organization | Amgen Inc. |
Phone | 866-572-6436 |
medinfo@amgen.com |
- CC-10004-CP-032
- 20200157