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| ID | Type | Description | Link |
|---|---|---|---|
| 2015-000732-15 | EudraCT Number |
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The primary objective of this study is to investigate the effect of steady state pirfenidone on the pharmacokinetics of nintedanib and its metabolites following oral administration of 2403 mg/day pirfenidone and to investigate the effect of steady state nintedanib on the pharmacokinetics of pirfenidone at steady state following oral administration of 150 mg bid nintedanib. There will be two cohorts of patients; the first one will consist of patients not treated with pirfenidone or nintedanib, while the second one will consist of patients on pirfenidone treatment.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment naïve | Experimental | Treatment naïve to pirfenidone |
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| Pirfenidone-treated | Experimental | Treatment before with pirfenidone |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| nintedanib | Drug |
| ||
| pirfenidone |
| Measure | Description | Time Frame |
|---|---|---|
| Treatment naïve, Area Under the Concentration-time Curve of the Nintedanib in Plasma Over the Time Interval 0 to the Last Quantifiable Data Point (AUC0-tz). | AUC0-tz , area under the concentration-time curve of nintedanib in plasma over the time interval from 0 to the last quantifiable concentration. Standard error mentioned in the Method of Dispersion is actually a Geometric Standard Error. | Blood samples were collected at pre-dose and at 0:30, 1:00, 2:00, 3:00, 4:00, 6:00, 8:00 and 10:00 hours post dose. |
| Treatment naïve, Maximum Measured Concentration of Nintedanib in Plasma After Single Dose Administration (Cmax). | Cmax, maximum measured concentration of nintedanib in plasma. Standard error mentioned in the Method of Dispersion is actually a Geometric Standard Error. | Blood samples were collected at pre-dose and at 0:30, 1:00, 2:00, 3:00, 4:00, 6:00, 8:00 and 10:00 hours post dose. |
| Pirfenidone-treated, Area Under the Concentration-time Curve of Pirfenidone in Plasma Over a Dosing Interval at Steady State (AUCτ,ss) | AUCτ,ss, area under the concentration-time curve of pirfenidone in plasma over a dosing interval at steady state. Standard error mentioned in the Method of Dispersion is actually a Geometric Standard Error. | Blood samples were collected at pre-dose and at 0:30, 1:00, 2:00, 3:00, 4:00, 6:00, 8:00 and 10:00 hours post dose. |
| Pirfenidone-treated, Maximum Measured Concentration of Pirfenidone in Plasma at Steady State (Cmax,ss) | Cmax,ss, maximum measured concentration of pirfenidone in plasma at steady state. Standard error mentioned in the Method of Dispersion is actually a Geometric Standard Error. | Blood samples were collected at pre-dose and at 0:30, 1:00, 2:00, 3:00, 4:00, 6:00, 8:00 and 10:00 hours post dose. |
| Measure | Description | Time Frame |
|---|---|---|
| Treatment naïve, Area Under the Concentration-time Curve of Nintedanib in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | AUC0-∞, area under the concentration-time curve of nintedanib in plasma over the time interval from 0 extrapolated to infinity. Standard error mentioned in the Method of Dispersion is actually a Geometric Standard Error. | Blood samples were collected at pre-dose and at 0:30, 1:00, 2:00, 3:00, 4:00, 6:00, 8:00 and 10:00 hours post dose. |
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Inclusion criteria:
Any patients diagnosed with IPF and who comply with eligibility requirements may qualify for participation in the trial.
Exclusion criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Boehringer Ingelheim | Boehringer Ingelheim | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Southmead Hospital | Bristol | BS10 5NB | United Kingdom | |||
| Papworth Hospital |
Each patient group was treated according to a fixed sequence design, first with single treatment (R1, R2 respectively) followed by a combined treatment (T1, T2 respectively) which also included an up-titration period. Therefore, generating individual participant flow for each treatment group was not planned in this trial.
This was an open-label, multiple-dose, 2-group trial in patients with idiopathic pulmonary fibrosis (IPF) to investigate the relative bioavailability of nintedanib and pirfenidone when administered alone and after coadministration.
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| ID | Title | Description |
|---|---|---|
| FG000 | Treatment naïve | A single dose of 150 mg nintedanib (R1) was administered alone and, after pirfenidone up-titration, single dose of 150mg in combination with 801 mg tid pirfenidone (T1). Patients administered capsules orally with food. |
| FG001 | Pirfenidone-treated |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| SAP | No | Yes | No | Statistical Analysis Plan | Mar 9, 2017 | Mar 9, 2018 |
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| Drug |
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| Cambridge |
| CB23 3RE |
| United Kingdom |
| Glenfield Hospital | Leicester | LE3 9QP | United Kingdom |
| University College London Hospital | London | NW1 2PG | United Kingdom |
| Guy's Hospital | London | SE1 9RT | United Kingdom |
| Royal Brompton Hospital | London | SW3 6NP | United Kingdom |
| Wythenshawe Hospital | Manchester | M23 9LT | United Kingdom |
| Churchill Hospital | Oxford | OX3 7LE | United Kingdom |
| Southampton General Hospital | Southampton | SO16 6YD | United Kingdom |
Pirfenidone (R2) 801 mg tid was administered alone for 7 days as well as in combination with 150 mg bid nintedanib for another 7 days (T2). Patients administered capsules orally with food. |
| COMPLETED |
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| NOT COMPLETED |
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Treated set (TS): The TS includes all patients who received at least 1 dose of trial medication
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| ID | Title | Description |
|---|---|---|
| BG000 | Treatment naïve | A single dose of 150 mg nintedanib (R1) was administered alone and, after pirfenidone up-titration, single dose of 150mg in combination with 801 mg tid pirfenidone (T1). Patients administered capsules orally with food. |
| BG001 | Pirfenidone-treated | Pirfenidone (R2) 801 mg tid was administered alone for 7 days as well as in combination with 150 mg bid nintedanib for another 7 days (T2). Patients administered capsules orally with food. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| 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 | Treatment naïve, Area Under the Concentration-time Curve of the Nintedanib in Plasma Over the Time Interval 0 to the Last Quantifiable Data Point (AUC0-tz). | AUC0-tz , area under the concentration-time curve of nintedanib in plasma over the time interval from 0 to the last quantifiable concentration. Standard error mentioned in the Method of Dispersion is actually a Geometric Standard Error. | Pharmacokinetic Analysis Set (PKS) - The PKS includes all patients in the treated set with at least one evaluable primary or secondary PK endpoint. (Observed cases) | Posted | Geometric Mean | Standard Error | nanogram*hour/mililitre [ng*h/mL] | Blood samples were collected at pre-dose and at 0:30, 1:00, 2:00, 3:00, 4:00, 6:00, 8:00 and 10:00 hours post dose. |
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| Primary | Treatment naïve, Maximum Measured Concentration of Nintedanib in Plasma After Single Dose Administration (Cmax). | Cmax, maximum measured concentration of nintedanib in plasma. Standard error mentioned in the Method of Dispersion is actually a Geometric Standard Error. | Pharmacokinetic Analysis Set (PKS) - The PKS includes all patients in the treated set with at least one evaluable primary or secondary PK endpoint. (Observed cases) | Posted | Geometric Mean | Standard Error | nanogram/mililitre [ng/mL] | Blood samples were collected at pre-dose and at 0:30, 1:00, 2:00, 3:00, 4:00, 6:00, 8:00 and 10:00 hours post dose. |
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| Primary | Pirfenidone-treated, Area Under the Concentration-time Curve of Pirfenidone in Plasma Over a Dosing Interval at Steady State (AUCτ,ss) | AUCτ,ss, area under the concentration-time curve of pirfenidone in plasma over a dosing interval at steady state. Standard error mentioned in the Method of Dispersion is actually a Geometric Standard Error. | Pharmacokinetic Analysis Set (PKS) - The PKS includes all patients in the treated set with at least one evaluable primary or secondary PK endpoint. (Observed cases) | Posted | Geometric Mean | Standard Error | nanogram*hour/mililitre [ng*h/mL] | Blood samples were collected at pre-dose and at 0:30, 1:00, 2:00, 3:00, 4:00, 6:00, 8:00 and 10:00 hours post dose. |
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| Primary | Pirfenidone-treated, Maximum Measured Concentration of Pirfenidone in Plasma at Steady State (Cmax,ss) | Cmax,ss, maximum measured concentration of pirfenidone in plasma at steady state. Standard error mentioned in the Method of Dispersion is actually a Geometric Standard Error. | Pharmacokinetic Analysis Set (PKS) - The PKS includes all patients in the treated set with at least one evaluable primary or secondary PK endpoint. (Observed cases) | Posted | Geometric Mean | Standard Error | nanogram/mililitre [ng/mL] | Blood samples were collected at pre-dose and at 0:30, 1:00, 2:00, 3:00, 4:00, 6:00, 8:00 and 10:00 hours post dose. |
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| Secondary | Treatment naïve, Area Under the Concentration-time Curve of Nintedanib in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | AUC0-∞, area under the concentration-time curve of nintedanib in plasma over the time interval from 0 extrapolated to infinity. Standard error mentioned in the Method of Dispersion is actually a Geometric Standard Error. | Pharmacokinetic Analysis Set (PKS) - The PKS includes all patients in the treated set with at least one evaluable primary or secondary PK endpoint. (Observed cases) | Posted | Geometric Mean | Standard Error | nanogram*hour/mililitre [ng*h/mL] | Blood samples were collected at pre-dose and at 0:30, 1:00, 2:00, 3:00, 4:00, 6:00, 8:00 and 10:00 hours post dose. |
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From first drug administration until 28 days after last drug administration, up to 6 weeks.
The assessment of safety was a further objective of the trial. Due to the study design, there was a great difference in duration of treatment reference (R) and treatment (T) within each patient group and a long residual effect period of the first treatment that overlapped with the second treatment. Thus the study design did not allow for a reliable comparison of treatment R and T within each patient group regarding safety and the trial team decided to provide the safety assessment only overall.
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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 | Treatment naïve | A single dose of 150 mg nintedanib (R1) was administered alone and, after pirfenidone up-titration, single dose of 150mg in combination with 801 mg tid pirfenidone (T1). Patients administered capsules orally with food. | 0 | 20 | 0 | 20 | 13 | 20 |
| EG001 | Pirfenidone-treated | Pirfenidone (R2) 801 mg tid was administered alone for 7 days as well as in combination with 150 mg bid nintedanib for another 7 days (T2). Patients administered capsules orally with food. | 0 | 17 | 0 | 17 | 15 | 17 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
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| Abdominal wall mass | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
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| Frequent bowel movements | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
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| Gastrointestinal disorder | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
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| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
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| Toothache | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA 20.0 | Systematic Assessment |
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| Influenza | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
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| Lower respiratory tract infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
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| Blood pressure increased | Investigations | MedDRA 20.0 | Systematic Assessment |
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| Decreased appetite | Metabolism and nutrition disorders | MedDRA 20.0 | Systematic Assessment |
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| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
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| Tendon disorder | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
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| Ageusia | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
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| Presyncope | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
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| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
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| Wheezing | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
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| Rash papular | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
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Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Boehringer Ingelheim, Call Center | Boehringer Ingelheim | 1-800-243-0127 | clintriage.rdg@boehringer-ingelheim.com |
| SAP_000.pdf |
| Prot | Yes | No | No | Study Protocol | Jul 29, 2016 | Mar 9, 2018 | Prot_001.pdf |
| ID | Term |
|---|---|
| D054990 | Idiopathic Pulmonary Fibrosis |
| ID | Term |
|---|---|
| D011658 | Pulmonary Fibrosis |
| D017563 | Lung Diseases, Interstitial |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
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| ID | Term |
|---|---|
| C530716 | nintedanib |
| C093844 | pirfenidone |
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| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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