A Drug-Drug Interaction Study to Evaluate the Effect of Rifampin on the Pharmacokinetics of Apremilast

Sponsor
Amgen (Industry)
Overall Status
Completed
CT.gov ID
NCT01561963
Collaborator
(none)
21
1
1
2
10.7

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

Study Type:
Interventional
Actual Enrollment :
21 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Other
Official Title:
A Phase 1, Open-label, Three-period, Fixed-sequence Study to Evaluate the Effects of Rifampin on the Pharmacokinetics of Apremilast (CC-10004) in Healthy Subjects
Actual Study Start Date :
Feb 1, 2012
Actual Primary Completion Date :
Apr 1, 2012
Actual Study Completion Date :
Apr 1, 2012

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:
  • CC-10004
  • Otezla®
  • Drug: Rifampin Oral Capsules
    Capsules for oral administration
    Other Names:
  • RIFADIN™
  • Drug: Rifampin IV Solution
    Intravenous (IV) solution
    Other Names:
  • RIFADIN™
  • Outcome Measures

    Primary Outcome Measures

    1. 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.

    2. 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.

    3. 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.

    4. 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.

    5. 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.

    6. 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.

    7. 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

    Ages Eligible for Study:
    18 Years to 55 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    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

    Responsible Party:
    Amgen
    ClinicalTrials.gov Identifier:
    NCT01561963
    Other Study ID Numbers:
    • CC-10004-CP-025
    First Posted:
    Mar 23, 2012
    Last Update Posted:
    Jun 9, 2021
    Last Verified:
    May 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Keywords provided by Amgen
    Additional relevant MeSH terms:

    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

    1. Primary Outcome
    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
    2. Primary Outcome
    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
    3. Primary Outcome
    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
    4. Primary Outcome
    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
    5. Primary Outcome
    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)
    6. Primary Outcome
    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)
    7. Primary Outcome
    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

    [Not Specified]

    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
    Email medinfo@amgen.com
    Responsible Party:
    Amgen
    ClinicalTrials.gov Identifier:
    NCT01561963
    Other Study ID Numbers:
    • CC-10004-CP-025
    First Posted:
    Mar 23, 2012
    Last Update Posted:
    Jun 9, 2021
    Last Verified:
    May 1, 2021