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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Apremilast and Rifampin | Experimental | Participants received the following 3 treatment regimens:
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Apremilast | Drug | Tablets for oral administration |
|
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUCt) of Apremilast | 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. | 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 |
| Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC∞) of Apremilast | 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. | 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 |
| Maximum Observed Plasma Concentration (Cmax) of Apremilast | 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. | 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 |
| Time to Maximum Observed Plasma Concentration (Tmax) of Apremilast | 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. | 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 |
| Estimate of the Terminal Elimination Half-life (T1/2) of Apremilast in Plasma | 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| MD | Amgen | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Quintiles | Overland Park | Kansas | 66211 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24962564 | Background | Liu Y, Zhou S, Wan Y, Wu A, Palmisano M. The impact of co-administration of ketoconazole and rifampicin on the pharmacokinetics of apremilast in healthy volunteers. Br J Clin Pharmacol. 2014 Nov;78(5):1050-7. doi: 10.1111/bcp.12448. |
| Label | URL |
|---|---|
| AmgenTrials clinical trials website | View source |
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De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
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This study was conducted at one clinical site in Overland Park, Kansas, USA.
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| ID | Title | Description |
|---|---|---|
| FG000 | Apremilast and Rifampin | 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. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Apremilast and Rifampin | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUCt) of Apremilast | 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. | The pharmacokinetic population included all participants who received at least one dose of apremilast and had evaluable PK profiles. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | 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 |
|
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
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Apremilast Alone | Participants received a single oral dose of 30 mg apremilast on Day 1 (Period 1). |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| CONJUNCTIVAL HYPERAEMIA | Eye disorders | MedDRA 15.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Amgen Inc. | 866-572-6436 | medinfo@amgen.com |
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| ID | Term |
|---|---|
| C505730 | apremilast |
| D012293 | Rifampin |
| ID | Term |
|---|---|
| D012294 | Rifamycins |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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| Rifampin Oral Capsules | Drug | Capsules for oral administration |
|
|
| Rifampin IV Solution | Drug | Intravenous (IV) solution |
|
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| 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 |
| Apparent Total Plasma Clearance (CL/F) of Apremilast | 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. | 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 |
| Apparent Volume of Distribution (Vz/F) of Apremilast | 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. | 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 |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Body Mass Index (BMI) | Mean | Standard Deviation | kg/m² |
|
| Apremilast + IV Rifampin |
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). |
| OG002 | Apremilast + Multiple Dose Oral Rifampin | 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). |
|
|
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| Primary | Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC∞) of Apremilast | 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. | The pharmacokinetic population included all participants who received at least one dose of apremilast and had evaluable PK profiles. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | 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 |
|
|
|
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| Primary | Maximum Observed Plasma Concentration (Cmax) of Apremilast | 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. | The pharmacokinetic population included all participants who received at least one dose of apremilast and had evaluable PK profiles. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 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 |
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|
|
|
| Primary | Time to Maximum Observed Plasma Concentration (Tmax) of Apremilast | 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. | The pharmacokinetic population included all participants who received at least one dose of apremilast and had evaluable PK profiles. | Posted | Median | Full Range | hours | 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 |
|
|
|
|
| Primary | Estimate of the Terminal Elimination Half-life (T1/2) of Apremilast in Plasma | 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. | The pharmacokinetic population included all participants who received at least one dose of apremilast and had evaluable PK profiles. | Posted | Geometric Mean | Geometric Coefficient of Variation | hours | 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 |
|
|
|
| Primary | Apparent Total Plasma Clearance (CL/F) of Apremilast | 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. | The pharmacokinetic population included all participants who received at least one dose of apremilast and had evaluable PK profiles. | Posted | Geometric Mean | Geometric Coefficient of Variation | L/h | 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 |
|
|
|
| Primary | Apparent Volume of Distribution (Vz/F) of Apremilast | 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. | The pharmacokinetic population included all participants who received at least one dose of apremilast and had evaluable PK profiles. | Posted | Geometric Mean | Geometric Coefficient of Variation | liters | 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 |
|
|
|
| 0 |
| 21 |
| 2 |
| 21 |
| EG001 | Apremilast + IV Rifampin | 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). | 0 | 20 | 4 | 20 |
| EG002 | Apremilast + Multiple Dose Oral Rifampin | 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). | 0 | 20 | 9 | 20 |
| EG003 | Overall Study - All Treatment Regimens | 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. | 0 | 21 | 12 | 21 |
| ABDOMINAL PAIN LOWER | Gastrointestinal disorders | MedDRA 15.0 | Systematic Assessment |
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| ABDOMINAL PAIN UPPER | Gastrointestinal disorders | MedDRA 15.0 | Systematic Assessment |
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| DIARRHOEA | Gastrointestinal disorders | MedDRA 15.0 | Systematic Assessment |
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| DYSPHAGIA | Gastrointestinal disorders | MedDRA 15.0 | Systematic Assessment |
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| ASTHENIA | General disorders | MedDRA 15.0 | Systematic Assessment |
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| CHILLS | General disorders | MedDRA 15.0 | Systematic Assessment |
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| FEELING HOT | General disorders | MedDRA 15.0 | Systematic Assessment |
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| INFUSION SITE ERYTHEMA | General disorders | MedDRA 15.0 | Systematic Assessment |
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| RHINITIS | Infections and infestations | MedDRA 15.0 | Systematic Assessment |
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| BLOOD CREATINE PHOSPHOKINASE INCREASED | Investigations | MedDRA 15.0 | Systematic Assessment |
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| HEPATIC ENZYME INCREASED | Investigations | MedDRA 15.0 | Systematic Assessment |
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| BACK PAIN | Musculoskeletal and connective tissue disorders | MedDRA 15.0 | Systematic Assessment |
|
| GROIN PAIN | Musculoskeletal and connective tissue disorders | MedDRA 15.0 | Systematic Assessment |
|
| MUSCLE TWITCHING | Musculoskeletal and connective tissue disorders | MedDRA 15.0 | Systematic Assessment |
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| MUSCULOSKELETAL CHEST PAIN | Musculoskeletal and connective tissue disorders | MedDRA 15.0 | Systematic Assessment |
|
| MUSCULOSKELETAL PAIN | Musculoskeletal and connective tissue disorders | MedDRA 15.0 | Systematic Assessment |
|
| MYALGIA | Musculoskeletal and connective tissue disorders | MedDRA 15.0 | Systematic Assessment |
|
| PAIN IN EXTREMITY | Musculoskeletal and connective tissue disorders | MedDRA 15.0 | Systematic Assessment |
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| HEADACHE | Nervous system disorders | MedDRA 15.0 | Systematic Assessment |
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| MUSCLE CONTRACTIONS INVOLUNTARY | Nervous system disorders | MedDRA 15.0 | Systematic Assessment |
|
| DYSURIA | Renal and urinary disorders | MedDRA 15.0 | Systematic Assessment |
|
| TESTICULAR PAIN | Reproductive system and breast disorders | MedDRA 15.0 | Systematic Assessment |
|
| EPISTAXIS | Respiratory, thoracic and mediastinal disorders | MedDRA 15.0 | Systematic Assessment |
|
| NASAL CONGESTION | Respiratory, thoracic and mediastinal disorders | MedDRA 15.0 | Systematic Assessment |
|
| RHINORRHOEA | Respiratory, thoracic and mediastinal disorders | MedDRA 15.0 | Systematic Assessment |
|
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.
| D047029 | Lactams, Macrocyclic |
| D047028 | Macrocyclic Compounds |
| D011083 | Polycyclic Compounds |
| 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. | Ratio of Geometric Least Squares Means | 27.96 | 2-Sided | 90 | 25.70 | 30.41 | Apremilast + Multiple Dose Oral Rifampin / Apremilast Alone | Equivalence | 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%. |
| 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. | Ratio of Geometric Least Squares Means | 56.80 | 2-Sided | 90 | 51.84 | 62.25 | Apremilast + Multiple Dose Oral Rifampin / Apremilast Alone | Equivalence | 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%. |
Tmax was analyzed using nonparametric methods. The median difference and 90% CI of the median difference were calculated from the Hodges-Lehrmann estimate. |
| Wilcoxon signed rank test |
| 0.1141 |
| Median Difference |
| -0.50 |
| 2-Sided |
| 90 |
| -1.00 |
| 0.00 |
Apremilast + Multiple Dose Oral Rifampin - Apremilast Alone |
| Other |