A Drug-Drug Interaction Study to Evaluate the Effect of Rifampin on the Pharmacokinetics of Apremilast
Study Details
Study Description
Brief Summary
The purpose of this study is to evaluate how the pharmacokinetics of apremilast may be affected by a single intravenous dose of rifampin and multiple oral doses of rifampin.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Apremilast and Rifampin Participants received the following 3 treatment regimens: A single oral dose of 30 mg apremilast on Day 1 (Period 1); A single oral dose of 30 mg apremilast followed 5 minutes later by a 30-minute intravenous infusion of 600 mg rifampin on Day 5 (Period 2); Once daily oral doses of 600 mg rifampin for 15 days (from Day 7 to Day 21) with a single oral dose of 30 mg apremilast co-administered with the rifampin dose on Day 20 (Period 3). |
Drug: Apremilast
Tablets for oral administration
Other Names:
Drug: Rifampin Oral Capsules
Capsules for oral administration
Other Names:
Drug: Rifampin IV Solution
Intravenous (IV) solution
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUCt) of Apremilast [Pre-dose and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 36, and 48 hours following apremilast dosing on Days 1, 5, and 20]
Plasma concentrations of apremilast were determined by means of a validated, sensitive, and specific high performance liquid chromatography/tandem mass spectrometric (LC-MS/MS) assay.
- Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC∞) of Apremilast [Pre-dose and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 36, and 48 hours following apremilast dosing on Days 1, 5, and 20]
Plasma concentrations of apremilast were determined by means of a validated, sensitive, and specific high performance liquid chromatography/tandem mass spectrometric (LC-MS/MS) assay.
- Maximum Observed Plasma Concentration (Cmax) of Apremilast [Pre-dose and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 36, and 48 hours following apremilast dosing on Days 1, 5, and 20]
Plasma concentrations of apremilast were determined by means of a validated, sensitive, and specific high performance liquid chromatography/tandem mass spectrometric (LC-MS/MS) assay.
- Time to Maximum Observed Plasma Concentration (Tmax) of Apremilast [Pre-dose and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 36, and 48 hours following apremilast dosing on Days 1, 5, and 20]
Plasma concentrations of apremilast were determined by means of a validated, sensitive, and specific high performance liquid chromatography/tandem mass spectrometric (LC-MS/MS) assay.
- Estimate of the Terminal Elimination Half-life (T1/2) of Apremilast in Plasma [Pre-dose and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 36, and 48 hours following apremilast dosing on Days 1, 5, and 20]
Plasma concentrations of apremilast were determined by means of a validated, sensitive, and specific high performance liquid chromatography/tandem mass spectrometric (LC-MS/MS) assay.
- Apparent Total Plasma Clearance (CL/F) of Apremilast [Pre-dose and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 36, and 48 hours following apremilast dosing on Days 1, 5, and 20]
Plasma concentrations of apremilast were determined by means of a validated, sensitive, and specific high performance liquid chromatography/tandem mass spectrometric (LC-MS/MS) assay.
- Apparent Volume of Distribution (Vz/F) of Apremilast [Pre-dose and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 36, and 48 hours following apremilast dosing on Days 1, 5, and 20]
Plasma concentrations of apremilast were determined by means of a validated, sensitive, and specific high performance liquid chromatography/tandem mass spectrometric (LC-MS/MS) assay.
Eligibility Criteria
Criteria
Inclusion Criteria:
- Healthy male or female subjects of any ethnic origin between ages of 18 and 55 with a body mass index between 18 and 33
Exclusion Criteria:
-
Recent history (i.e., within 3 years) of any clinically significant neurological, gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, endocrine, hematological, dermatological, psychological, allergic or other major disorders.
-
Use of any prescribed or non-prescribed systemic or topical medication (including vitamins and herbal medicines, e.g. St. John's Wort) within 30 days of the first dose, unless an exception is granted by the sponsor.
-
Presence of any surgical or medical conditions possibly affecting drug absorption, distribution, metabolism, and excretion, or plans to have elective or medical procedures during the conduct of the trial.
-
Exposure to an investigational drug (new chemical entity) within 30 days prior to the first dose administration
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Quintiles | Overland Park | Kansas | United States | 66211 |
Sponsors and Collaborators
- Amgen
Investigators
- Study Director: MD, Amgen
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
- CC-10004-CP-025
Study Results
Participant Flow
Recruitment Details | This study was conducted at one clinical site in Overland Park, Kansas, USA. |
---|---|
Pre-assignment Detail |
Arm/Group Title | Apremilast and Rifampin |
---|---|
Arm/Group Description | Participants received the following 3 treatment regimens: Period 1: A single oral dose of 30 mg apremilast on Day 1; Period 2: A single oral dose of 30 mg apremilast followed 5 minutes later by a 30-minute intravenous (IV) infusion of 600 mg rifampin on Day 5; Period 3: Once daily oral doses of 600 mg rifampin for 15 days (from Day 7 to Day 21) with a single oral dose of 30 mg apremilast co-administered with the rifampin dose on Day 20. |
Period Title: Overall Study | |
STARTED | 21 |
Received Period 1 Treatment | 21 |
Received Period 2 Treatment | 20 |
Received Period 3 Treatment | 20 |
COMPLETED | 20 |
NOT COMPLETED | 1 |
Baseline Characteristics
Arm/Group Title | Apremilast and Rifampin |
---|---|
Arm/Group Description | Participants received the following 3 treatment regimens: Period 1: A single oral dose of 30 mg apremilast on Day 1; Period 2: A single oral dose of 30 mg apremilast followed 5 minutes later by a 30-minute intravenous infusion of 600 mg rifampin on Day 5; Period 3: Once daily oral doses of 600 mg rifampin for 15 days (from Day 7 to Day 21) with a single oral dose of 30 mg apremilast co-administered with the rifampin dose on Day 20. |
Overall Participants | 21 |
Age (years) [Mean (Standard Deviation) ] | |
Mean (Standard Deviation) [years] |
34
(9.6)
|
Sex: Female, Male (Count of Participants) | |
Female |
1
4.8%
|
Male |
20
95.2%
|
Ethnicity (NIH/OMB) (Count of Participants) | |
Hispanic or Latino |
1
4.8%
|
Not Hispanic or Latino |
20
95.2%
|
Unknown or Not Reported |
0
0%
|
Race/Ethnicity, Customized (Count of Participants) | |
White |
12
57.1%
|
Black or African American |
9
42.9%
|
Body Mass Index (BMI) (kg/m²) [Mean (Standard Deviation) ] | |
Mean (Standard Deviation) [kg/m²] |
29.14
(2.974)
|
Outcome Measures
Title | Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUCt) of Apremilast |
---|---|
Description | Plasma concentrations of apremilast were determined by means of a validated, sensitive, and specific high performance liquid chromatography/tandem mass spectrometric (LC-MS/MS) assay. |
Time Frame | Pre-dose and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 36, and 48 hours following apremilast dosing on Days 1, 5, and 20 |
Outcome Measure Data
Analysis Population Description |
---|
The pharmacokinetic population included all participants who received at least one dose of apremilast and had evaluable PK profiles. |
Arm/Group Title | Apremilast Alone | Apremilast + IV Rifampin | Apremilast + Multiple Dose Oral Rifampin |
---|---|---|---|
Arm/Group Description | Participants received a single oral dose of 30 mg apremilast on Day 1 (Period 1). | Participants received a single oral dose of 30 mg apremilast followed 5 minutes later by a 30-minute intravenous infusion of 600 mg rifampin on Day 5 (Period 2). | Participants received once daily oral doses of 600 mg rifampin for 15 days (from Day 7 to Day 21) with a single oral dose of 30 mg apremilast co-administered with the rifampin dose on Day 20 (Period 3). |
Measure Participants | 21 | 19 | 19 |
Geometric Mean (Geometric Coefficient of Variation) [ng*h/mL] |
3070
(31.3)
|
2940
(31.3)
|
850
(33.7)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Apremilast Alone, Apremilast + IV Rifampin |
---|---|---|
Comments | The effect of rifampicin on the PK of apremilast was evaluated using a linear mixed effect analysis of variance on the log-transformed values of AUCt of apremilast, to estimate the mean ratio of apremilast administered with and without rifampicin treatment. The model included treatment as fixed effect, and subject as a random effect. | |
Type of Statistical Test | Equivalence | |
Comments | No statistically significant interaction between apremilast and rifampicin was confirmed if both the upper and lower 90% confidence interval (CI) limits for the geometric least squares mean ratios of apremilast administered with rifampicin to apremilast alone fell within the no effect boundary of 80% to 125%. | |
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Ratio of Geometric Least Squares Means |
Estimated Value | 96.35 | |
Confidence Interval |
(2-Sided) 90% 88.56 to 104.82 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Apremilast + IV Rifampin / Apremilast Alone |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Apremilast Alone, Apremilast + Multiple Dose Oral Rifampin |
---|---|---|
Comments | The effect of rifampicin on the PK of apremilast was evaluated using a linear mixed effect analysis of variance on the log-transformed values of AUCt of apremilast, to estimate the mean ratio of apremilast administered with and without rifampicin treatment. The model included treatment as fixed effect, and subject as a random effect. | |
Type of Statistical Test | Equivalence | |
Comments | No statistically significant interaction between apremilast and rifampicin was confirmed if both the upper and lower 90% CI limits for the geometric least squares mean ratios of apremilast administered with rifampicin to apremilast alone fell within the no effect boundary of 80% to 125%. | |
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Ratio of Geometric Least Squares Means |
Estimated Value | 27.88 | |
Confidence Interval |
(2-Sided) 90% 25.63 to 30.34 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Apremilast + Multiple Dose Oral Rifampin / Apremilast Alone |
Title | Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC∞) of Apremilast |
---|---|
Description | Plasma concentrations of apremilast were determined by means of a validated, sensitive, and specific high performance liquid chromatography/tandem mass spectrometric (LC-MS/MS) assay. |
Time Frame | Pre-dose and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 36, and 48 hours following apremilast dosing on Days 1, 5, and 20 |
Outcome Measure Data
Analysis Population Description |
---|
The pharmacokinetic population included all participants who received at least one dose of apremilast and had evaluable PK profiles. |
Arm/Group Title | Apremilast Alone | Apremilast + IV Rifampin | Apremilast + Multiple Dose Oral Rifampin |
---|---|---|---|
Arm/Group Description | Participants received a single oral dose of 30 mg apremilast on Day 1 (Period 1). | Participants received a single oral dose of 30 mg apremilast followed 5 minutes later by a 30-minute intravenous infusion of 600 mg rifampin on Day 5 (Period 2). | Participants received once daily oral doses of 600 mg rifampin for 15 days (from Day 7 to Day 21) with a single oral dose of 30 mg apremilast co-administered with the rifampin dose on Day 20 (Period 3). |
Measure Participants | 21 | 19 | 19 |
Geometric Mean (Geometric Coefficient of Variation) [ng*h/mL] |
3120
(31.5)
|
2980
(31.2)
|
869
(32.9)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Apremilast Alone, Apremilast + IV Rifampin |
---|---|---|
Comments | The effect of rifampicin on the PK of apremilast was evaluated using a linear mixed effect analysis of variance on the log-transformed values of AUC∞ of apremilast, to estimate the mean ratio of apremilast administered with and without rifampicin treatment. The model included treatment as fixed effect, and subject as a random effect. | |
Type of Statistical Test | Equivalence | |
Comments | No statistically significant interaction between apremilast and rifampicin was confirmed if both the upper and lower 90% CI limits for the geometric least squares mean ratios of apremilast administered with rifampicin to apremilast alone fell within the no effect boundary of 80% to 125%. | |
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Ratio of Geometric Least Squares Means |
Estimated Value | 95.71 | |
Confidence Interval |
(2-Sided) 90% 87.99 to 104.12 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Apremilast + IV Rifampin / Apremilast Alone |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Apremilast Alone, Apremilast + Multiple Dose Oral Rifampin |
---|---|---|
Comments | The effect of rifampicin on the PK of apremilast was evaluated using a linear mixed effect analysis of variance on the log-transformed values of AUC∞ of apremilast, to estimate the mean ratio of apremilast administered with and without rifampicin treatment. The model included treatment as fixed effect, and subject as a random effect. | |
Type of Statistical Test | Equivalence | |
Comments | No statistically significant interaction between apremilast and rifampicin was confirmed if both the upper and lower 90% CI limits for the geometric least squares mean ratios of apremilast administered with rifampicin to apremilast alone fell within the no effect boundary of 80% to 125%. | |
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Ratio of Geometric Least Squares Means |
Estimated Value | 27.96 | |
Confidence Interval |
(2-Sided) 90% 25.70 to 30.41 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Apremilast + Multiple Dose Oral Rifampin / Apremilast Alone |
Title | Maximum Observed Plasma Concentration (Cmax) of Apremilast |
---|---|
Description | Plasma concentrations of apremilast were determined by means of a validated, sensitive, and specific high performance liquid chromatography/tandem mass spectrometric (LC-MS/MS) assay. |
Time Frame | Pre-dose and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 36, and 48 hours following apremilast dosing on Days 1, 5, and 20 |
Outcome Measure Data
Analysis Population Description |
---|
The pharmacokinetic population included all participants who received at least one dose of apremilast and had evaluable PK profiles. |
Arm/Group Title | Apremilast Alone | Apremilast + IV Rifampin | Apremilast + Multiple Dose Oral Rifampin |
---|---|---|---|
Arm/Group Description | Participants received a single oral dose of 30 mg apremilast on Day 1 (Period 1). | Participants received a single oral dose of 30 mg apremilast followed 5 minutes later by a 30-minute intravenous infusion of 600 mg rifampin on Day 5 (Period 2). | Participants received once daily oral doses of 600 mg rifampin for 15 days (from Day 7 to Day 21) with a single oral dose of 30 mg apremilast co-administered with the rifampin dose on Day 20 (Period 3). |
Measure Participants | 21 | 19 | 19 |
Geometric Mean (Geometric Coefficient of Variation) [ng/mL] |
290
(24.5)
|
331
(25.1)
|
166
(23.2)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Apremilast Alone, Apremilast + IV Rifampin |
---|---|---|
Comments | The effect of rifampicin on the PK of apremilast was evaluated using a linear mixed effect analysis of variance on the log-transformed values of Cmax of apremilast, to estimate the mean ratio of apremilast administered with and without rifampicin treatment. The model included treatment as fixed effect, and subject as a random effect. | |
Type of Statistical Test | Equivalence | |
Comments | No statistically significant interaction between apremilast and rifampicin was confirmed if both the upper and lower 90% CI limits for the geometric least squares mean ratios of apremilast administered with rifampicin to apremilast alone fell within the no effect boundary of 80% to 125%. | |
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Ratio of Geometric Least Squares Means |
Estimated Value | 113.07 | |
Confidence Interval |
(2-Sided) 90% 103.18 to 123.91 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Apremilast + IV Rifampin / Apremilast Alone |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Apremilast Alone, Apremilast + Multiple Dose Oral Rifampin |
---|---|---|
Comments | The effect of rifampicin on the PK of apremilast was evaluated using a linear mixed effect analysis of variance on the log-transformed values of Cmax of apremilast, to estimate the mean ratio of apremilast administered with and without rifampicin treatment. The model included treatment as fixed effect, and subject as a random effect. | |
Type of Statistical Test | Equivalence | |
Comments | No statistically significant interaction between apremilast and rifampicin was confirmed if both the upper and lower 90% CI limits for the geometric least squares mean ratios of apremilast administered with rifampicin to apremilast alone fell within the no effect boundary of 80% to 125%. | |
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Ratio of Geometric Least Squares Means |
Estimated Value | 56.80 | |
Confidence Interval |
(2-Sided) 90% 51.84 to 62.25 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Apremilast + Multiple Dose Oral Rifampin / Apremilast Alone |
Title | Time to Maximum Observed Plasma Concentration (Tmax) of Apremilast |
---|---|
Description | Plasma concentrations of apremilast were determined by means of a validated, sensitive, and specific high performance liquid chromatography/tandem mass spectrometric (LC-MS/MS) assay. |
Time Frame | Pre-dose and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 36, and 48 hours following apremilast dosing on Days 1, 5, and 20 |
Outcome Measure Data
Analysis Population Description |
---|
The pharmacokinetic population included all participants who received at least one dose of apremilast and had evaluable PK profiles. |
Arm/Group Title | Apremilast Alone | Apremilast + IV Rifampin | Apremilast + Multiple Dose Oral Rifampin |
---|---|---|---|
Arm/Group Description | Participants received a single oral dose of 30 mg apremilast on Day 1 (Period 1). | Participants received a single oral dose of 30 mg apremilast followed 5 minutes later by a 30-minute intravenous infusion of 600 mg rifampin on Day 5 (Period 2). | Participants received once daily oral doses of 600 mg rifampin for 15 days (from Day 7 to Day 21) with a single oral dose of 30 mg apremilast co-administered with the rifampin dose on Day 20 (Period 3). |
Measure Participants | 21 | 19 | 19 |
Median (Full Range) [hours] |
2.00
|
1.50
|
1.00
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Apremilast Alone, Apremilast + IV Rifampin |
---|---|---|
Comments | Tmax was analyzed using 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 | 0.2656 |
Comments | ||
Method | Wilcoxon signed rank test | |
Comments | ||
Method of Estimation | Estimation Parameter | Median Difference |
Estimated Value | -0.25 | |
Confidence Interval |
(2-Sided) 90% -0.75 to 0.00 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Apremilast + IV Rifampin - Apremilast Alone |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Apremilast Alone, Apremilast + Multiple Dose Oral Rifampin |
---|---|---|
Comments | Tmax was analyzed using 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 | 0.1141 |
Comments | ||
Method | Wilcoxon signed rank test | |
Comments | ||
Method of Estimation | Estimation Parameter | Median Difference |
Estimated Value | -0.50 | |
Confidence Interval |
(2-Sided) 90% -1.00 to 0.00 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Apremilast + Multiple Dose Oral Rifampin - Apremilast Alone |
Title | Estimate of the Terminal Elimination Half-life (T1/2) of Apremilast in Plasma |
---|---|
Description | Plasma concentrations of apremilast were determined by means of a validated, sensitive, and specific high performance liquid chromatography/tandem mass spectrometric (LC-MS/MS) assay. |
Time Frame | Pre-dose and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 36, and 48 hours following apremilast dosing on Days 1, 5, and 20 |
Outcome Measure Data
Analysis Population Description |
---|
The pharmacokinetic population included all participants who received at least one dose of apremilast and had evaluable PK profiles. |
Arm/Group Title | Apremilast Alone | Apremilast + IV Rifampin | Apremilast + Multiple Dose Oral Rifampin |
---|---|---|---|
Arm/Group Description | Participants received a single oral dose of 30 mg apremilast on Day 1 (Period 1). | Participants received a single oral dose of 30 mg apremilast followed 5 minutes later by a 30-minute intravenous infusion of 600 mg rifampin on Day 5 (Period 2). | Participants received once daily oral doses of 600 mg rifampin for 15 days (from Day 7 to Day 21) with a single oral dose of 30 mg apremilast co-administered with the rifampin dose on Day 20 (Period 3). |
Measure Participants | 21 | 19 | 19 |
Geometric Mean (Geometric Coefficient of Variation) [hours] |
8.12
(14.1)
|
7.35
(18.5)
|
6.13
(24.8)
|
Title | Apparent Total Plasma Clearance (CL/F) of Apremilast |
---|---|
Description | Plasma concentrations of apremilast were determined by means of a validated, sensitive, and specific high performance liquid chromatography/tandem mass spectrometric (LC-MS/MS) assay. |
Time Frame | Pre-dose and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 36, and 48 hours following apremilast dosing on Days 1, 5, and 20 |
Outcome Measure Data
Analysis Population Description |
---|
The pharmacokinetic population included all participants who received at least one dose of apremilast and had evaluable PK profiles. |
Arm/Group Title | Apremilast Alone | Apremilast + IV Rifampin | Apremilast + Multiple Dose Oral Rifampin |
---|---|---|---|
Arm/Group Description | Participants received a single oral dose of 30 mg apremilast on Day 1 (Period 1). | Participants received a single oral dose of 30 mg apremilast followed 5 minutes later by a 30-minute intravenous infusion of 600 mg rifampin on Day 5 (Period 2). | Participants received once daily oral doses of 600 mg rifampin for 15 days (from Day 7 to Day 21) with a single oral dose of 30 mg apremilast co-administered with the rifampin dose on Day 20 (Period 3). |
Measure Participants | 21 | 19 | 19 |
Geometric Mean (Geometric Coefficient of Variation) [L/h] |
9.60
(31.5)
|
10.1
(31.2)
|
34.5
(32.9)
|
Title | Apparent Volume of Distribution (Vz/F) of Apremilast |
---|---|
Description | Plasma concentrations of apremilast were determined by means of a validated, sensitive, and specific high performance liquid chromatography/tandem mass spectrometric (LC-MS/MS) assay. |
Time Frame | Pre-dose and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 36, and 48 hours following apremilast dosing on Days 1, 5, and 20 |
Outcome Measure Data
Analysis Population Description |
---|
The pharmacokinetic population included all participants who received at least one dose of apremilast and had evaluable PK profiles. |
Arm/Group Title | Apremilast Alone | Apremilast + IV Rifampin | Apremilast + Multiple Dose Oral Rifampin |
---|---|---|---|
Arm/Group Description | Participants received a single oral dose of 30 mg apremilast on Day 1 (Period 1). | Participants received a single oral dose of 30 mg apremilast followed 5 minutes later by a 30-minute intravenous infusion of 600 mg rifampin on Day 5 (Period 2). | Participants received once daily oral doses of 600 mg rifampin for 15 days (from Day 7 to Day 21) with a single oral dose of 30 mg apremilast co-administered with the rifampin dose on Day 20 (Period 3). |
Measure Participants | 21 | 19 | 19 |
Geometric Mean (Geometric Coefficient of Variation) [liters] |
112
(35.8)
|
107
(43.4)
|
305
(51.6)
|
Adverse Events
Time Frame | Period 1 (Apremilast Alone): Day 1 to day 4; Period 2 (Apremilast + IV Rifampin): Day 5 to day 6; Period 3 (Apremilast + Multiple Dose Oral Rifampin): Day 7 up to day 32; Overall Study (All Treatment Regimens): Up to 32 days | |||||||
---|---|---|---|---|---|---|---|---|
Adverse Event Reporting Description | ||||||||
Arm/Group Title | Apremilast Alone | Apremilast + IV Rifampin | Apremilast + Multiple Dose Oral Rifampin | Overall Study - All Treatment Regimens | ||||
Arm/Group Description | Participants received a single oral dose of 30 mg apremilast on Day 1 (Period 1). | Participants received a single oral dose of 30 mg apremilast followed 5 minutes later by a 30-minute intravenous infusion of 600 mg rifampin on Day 5 (Period 2). | Participants received once daily oral doses of 600 mg rifampin for 15 days (from Day 7 to Day 21) with a single oral dose of 30 mg apremilast co-administered with the rifampin dose on Day 20 (Period 3). | Participants received the following 3 treatment regimens: Period 1: A single oral dose of 30 mg apremilast on Day 1; Period 2: A single oral dose of 30 mg apremilast followed 5 minutes later by a 30-minute intravenous infusion of 600 mg rifampin on Day 5; Period 3: Once daily oral doses of 600 mg rifampin for 15 days (from Day 7 to Day 21) with a single oral dose of 30 mg apremilast co-administered with the rifampin dose on Day 20. | ||||
All Cause Mortality |
||||||||
Apremilast Alone | Apremilast + IV Rifampin | Apremilast + Multiple Dose Oral Rifampin | Overall Study - All Treatment Regimens | |||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||
Serious Adverse Events |
||||||||
Apremilast Alone | Apremilast + IV Rifampin | Apremilast + Multiple Dose Oral Rifampin | Overall Study - All Treatment Regimens | |||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 0/21 (0%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
Apremilast Alone | Apremilast + IV Rifampin | Apremilast + Multiple Dose Oral Rifampin | Overall Study - All Treatment Regimens | |||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 2/21 (9.5%) | 4/20 (20%) | 9/20 (45%) | 12/21 (57.1%) | ||||
Eye disorders | ||||||||
CONJUNCTIVAL HYPERAEMIA | 0/21 (0%) | 1/20 (5%) | 0/20 (0%) | 1/21 (4.8%) | ||||
Gastrointestinal disorders | ||||||||
ABDOMINAL PAIN LOWER | 0/21 (0%) | 0/20 (0%) | 1/20 (5%) | 1/21 (4.8%) | ||||
ABDOMINAL PAIN UPPER | 0/21 (0%) | 1/20 (5%) | 0/20 (0%) | 1/21 (4.8%) | ||||
DIARRHOEA | 0/21 (0%) | 1/20 (5%) | 1/20 (5%) | 1/21 (4.8%) | ||||
DYSPHAGIA | 0/21 (0%) | 0/20 (0%) | 1/20 (5%) | 1/21 (4.8%) | ||||
General disorders | ||||||||
ASTHENIA | 0/21 (0%) | 0/20 (0%) | 1/20 (5%) | 1/21 (4.8%) | ||||
CHILLS | 0/21 (0%) | 0/20 (0%) | 1/20 (5%) | 1/21 (4.8%) | ||||
FEELING HOT | 0/21 (0%) | 0/20 (0%) | 1/20 (5%) | 1/21 (4.8%) | ||||
INFUSION SITE ERYTHEMA | 0/21 (0%) | 1/20 (5%) | 0/20 (0%) | 1/21 (4.8%) | ||||
Infections and infestations | ||||||||
RHINITIS | 0/21 (0%) | 0/20 (0%) | 2/20 (10%) | 2/21 (9.5%) | ||||
Investigations | ||||||||
BLOOD CREATINE PHOSPHOKINASE INCREASED | 0/21 (0%) | 0/20 (0%) | 1/20 (5%) | 1/21 (4.8%) | ||||
HEPATIC ENZYME INCREASED | 0/21 (0%) | 0/20 (0%) | 1/20 (5%) | 1/21 (4.8%) | ||||
Musculoskeletal and connective tissue disorders | ||||||||
BACK PAIN | 0/21 (0%) | 0/20 (0%) | 1/20 (5%) | 1/21 (4.8%) | ||||
GROIN PAIN | 0/21 (0%) | 1/20 (5%) | 1/20 (5%) | 1/21 (4.8%) | ||||
MUSCLE TWITCHING | 0/21 (0%) | 1/20 (5%) | 0/20 (0%) | 1/21 (4.8%) | ||||
MUSCULOSKELETAL CHEST PAIN | 0/21 (0%) | 1/20 (5%) | 0/20 (0%) | 1/21 (4.8%) | ||||
MUSCULOSKELETAL PAIN | 0/21 (0%) | 0/20 (0%) | 1/20 (5%) | 1/21 (4.8%) | ||||
MYALGIA | 0/21 (0%) | 1/20 (5%) | 0/20 (0%) | 1/21 (4.8%) | ||||
PAIN IN EXTREMITY | 0/21 (0%) | 1/20 (5%) | 0/20 (0%) | 1/21 (4.8%) | ||||
Nervous system disorders | ||||||||
HEADACHE | 2/21 (9.5%) | 1/20 (5%) | 1/20 (5%) | 4/21 (19%) | ||||
MUSCLE CONTRACTIONS INVOLUNTARY | 0/21 (0%) | 0/20 (0%) | 1/20 (5%) | 1/21 (4.8%) | ||||
Renal and urinary disorders | ||||||||
DYSURIA | 0/21 (0%) | 0/20 (0%) | 1/20 (5%) | 1/21 (4.8%) | ||||
Reproductive system and breast disorders | ||||||||
TESTICULAR PAIN | 0/21 (0%) | 1/20 (5%) | 0/20 (0%) | 1/21 (4.8%) | ||||
Respiratory, thoracic and mediastinal disorders | ||||||||
EPISTAXIS | 0/21 (0%) | 0/20 (0%) | 1/20 (5%) | 1/21 (4.8%) | ||||
NASAL CONGESTION | 0/21 (0%) | 0/20 (0%) | 1/20 (5%) | 1/21 (4.8%) | ||||
RHINORRHOEA | 0/21 (0%) | 0/20 (0%) | 1/20 (5%) | 1/21 (4.8%) |
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-025