Lung Diseases, Interstitial
Conditions
Brief summary
The main objective of the study is to evaluate dose-exposure and safety of nintedanib in children and adolescents with fibrosing Interstitial Lung Disease (ILD).
Interventions
DRUGNintedanib
Capsule
DRUGPlacebo
Capsule
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
6 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Children and adolescents 6 to 17 years old at Visit 2. * Signed and dated written informed consent and assent, where applicable, in accordance with International Conference on Harmonisation-Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial. * Male or female patients. Female of childbearing potential (WOCBP) must confirm that sexual abstinence is standard practice and will be continued until 3 months after last drug intake, or be ready and able to use a highly effective method of birth control per International Conference on Harmonisation (ICH) M3 (R2) that results in a low failure rate of less than 1% per year when used consistently and correctly, in combination with one barrier method, from 28 days prior to initiation of study treatment, during treatment and until 3 months after last drug intake. Sexual abstinence is defined as abstinence from any sexual act that may result in pregnancy. A list of contraception methods meeting these criteria is provided in the parental information. * Patients with evidence of fibrosing Interstitial Lung Disease (ILD) on High-Resolution Computed Tomography (HRCT) within 12 months of Visit 1 as assessed by the investigator and confirmed by central review. * Patients with Forced Vital Capacity (FVC)% predicted ≥25% at Visit 2. \[Note: Predicted normal values will be calculated according to GLI (Global Lung Initiative)\] * Patients with clinically significant disease at Visit 2, as assessed by the investigator based on any of the following: * Fan score ≥3, or * Documented evidence of clinical progression over time based on either * a 5-10% relative decline in FVC% predicted accompanied by worsening symptoms, or * a ≥10% relative decline in FVC % predicted, or * increased fibrosis on HRCT, or * other measures of clinical worsening attributed to progressive lung disease (e.g. increased oxygen requirement, decreased diffusion capacity).
Exclusion criteria
* Aspartate Aminotransferase (AST) and/or Alanine Aminotransferase (ALT)\>1.5 x Upper Level of Normal (ULN) at Visit 1. * Bilirubin \>1.5 x ULN at Visit 1. * Creatinine clearance \<30 mL/min calculated by Schwartz formula at Visit 1. \[Note: Laboratory parameters from Visit 1 have to satisfy the laboratory threshold values as shown above. Visit 2 laboratory results will be available only after randomization. In case at Visit 2 the results do no longer satisfy the entry criteria, the Investigator has to decide whether it is justified that the patient remains on study drug. The justification for decision needs to be documented. Laboratory parameters that are found to be abnormal at Visit 1 are allowed to be re-tested (once) if it is thought to be a measurement error (i.e. there was no abnormal result of this test in the recent history of the patient and there is no related clinical sign) or the result of a temporary and reversible medical condition, once that condition is resolved.\] * Patients with underlying chronic liver disease (Child Pugh A, B or C hepatic impairment) at Visit 1. * Previous treatment with nintedanib. * Other investigational therapy received within 1 month or 5 half-lives (whichever is shorter but ≥1 week) prior to Visit 2. * Significant pulmonary arterial hypertension (PAH) defined by any of the following: * Previous clinical or echocardiographic evidence of significant right heart failure * History of right heart catheterization showing a cardiac index ≤2 l/min/m² * PAH requiring parenteral therapy with epoprostenol/treprostinil * In the opinion of the Investigator, other clinically significant pulmonary abnormalities. * Cardiovascular diseases, any of the following: * Severe hypertension, uncontrolled under treatment, within 6 months of Visit 1. Uncontrolled hypertension is defined as * In children 6 to ≤12 years old: ≥95th percentile + 12 mm Hg or ≥140/90 mm Hg (whichever is lower) (systolic or diastolic blood pressure equal to or greater than the calculated target value) * In adolescents 13 to 17 years old: systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg * Myocardial infarction within 6 months of Visit 1 * Unstable cardiac angina within 6 months of Visit 1 * Bleeding risk, any of the following: * Known genetic predisposition to bleeding * Patients who require * Fibrinolysis, full-dose therapeutic anticoagulation (e.g. vitamin K antagonists, direct thrombin inhibitors, heparin, hirudin) * High dose antiplatelet therapy \[Note: Prophylactic low dose heparin or heparin flush as needed for maintenance of an indwelling intravenous device (e.g. enoxaparin 4000 I.U. s.c. per day), as well as prophylactic use of antiplatelet therapy (e.g. acetyl salicylic acid up to 325 mg/day, or clopidogrel at 75 mg/day, or equivalent doses of other antiplatelet therapy) are not prohibited.\] * History of haemorrhagic central nervous system (CNS) event within 12 months of Visit 1 * Any of the following within 3 months of Visit 1: * Haemoptysis or haematuria * Active gastro-intestinal (GI) bleeding or GI - ulcers * Major injury or surgery (investigator's judgment) * Any of the following coagulation parameters at Visit 1: * International normalized ratio (INR) \>2 * Prolongation of prothrombin time (PT) by \>1.5 x ULN * Prolongation of activated partial thromboplastin time (aPTT) by \>1.5 x ULN * History of thrombotic event (including stroke and transient ischemic attack) within 12 months of Visit 1. * Known hypersensitivity to the trial medication or its components (i.e. soya lecithin). * Patients with documented allergy to peanut or soya. * Other disease that may interfere with testing procedures or in the judgment of the investigator may interfere with trial participation or may put the patient at risk when participating in this trial. * Life expectancy for any concomitant disease other than Interstitial Lung Disease (ILD)\<2.5 years (investigator assessment). * Female patients who are pregnant, nursing, or who plan to become pregnant while in the trial. * Patients not able or willing to adhere to trial procedures, including intake of study medication. * Patients with any diagnosed growth disorder such as growth hormone deficiency or any genetic disorder that is associated with short stature (e.g. Turner Syndrome, Noonan Syndrome, Russell-Silver Syndrome) and/or treatment with growth hormone therapy within 6 months before Visit 2. Patients with short stature considered by the investigator to be due to glucocorticoid therapy may be included. * Patients \<13.5 kg of weight at Visit 1 (same threshold to be used for male and female patients).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Plasma Concentration-time Curve at Steady State (AUCτ,ss) Based on Sampling at Steady State (at Week 2 and Week 26) | At Week 2 and at Week 26: at 5 minutes before and at 0, 1, 2, 3, 4, 6, and 8 hours post administration of the morning dose | Area under the plasma concentration-time curve at steady state (AUCt,ss) based on sampling at steady state (at Week 2 and Week 26) after multiple oral administration of Nintedanib by age group over all treatments. Values of samples taken at Week 2 (for randomised Nintedanib participants) and at Week 26 (for randomised placebo participants) were used. Missing values at Week 2 of randomised Nintedanib participants were replaced with values taken at Week 26. |
| Number of Participants With Treatment-emergent Adverse Events During the Double-blind Period | From first drug administration until the earlier of (i) first intake of open-label nintedanib (exclusive) and (ii) last drug intake, up to 28 weeks | Treatment-emergent was defined as: Adverse events with onset or worsening on or after date of treatment start until end of double-blind period (defined as the day before first intake of open-label nintedanib or last double-blind drug intake + residual effect period, whichever is earlier) were considered as treatment-emergent and were included in the analysis. Adverse events were counted under the treatment as randomized for the double-blind period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With at Least One Treatment-emergent Pathological Findings on Dental Examination or Imaging up to Week 52 | Dental examination: at Week 12, 24, 34, and Week 52; Dental imaging: at Week 24 and at Week 52. | Number of participants with treatment-emergent pathological findings on dental examination (clinical examination) based on dentist assessment or imaging (panoramic x-ray) based on central review were analyzed. Number of participants with treatment-emergent pathological findings on dental imaging were analyzed cumulatively. |
| Number of Participants With Treatment-emergent Adverse Events Over the Whole Trial | From first drug administration until the last drug intake, up to 92 weeks | Treatment-emergent was defined as: Adverse events with onset or worsening on or after date of treatment start until last drug intake + residual effect period was considered as treatment-emergent and was included in the analysis. Adverse events were counted under the treatment as randomized for the double-blind period. |
| Absolute Change From Baseline in Height at Week 24 | MMRM included measurements pre-administration at -4 weeks and at 0, 12, 24, 36, 52, 64, 76, and 88 weeks after first drug administration. MMRM values at Week 24 are reported in the table below | Absolute change from baseline in height at Week 24 was measured with a stadiometer 3 times at each time point. The average of these 3 measurements was taken per time point. Absolute change from baseline in height at Week 24 in the treated set (TS) was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements. |
| Absolute Change From Baseline in Height at Week 52 | MMRM included measurements pre-administration at -4 weeks and at 0, 12, 24, 36, 52, 64, 76, and 88 weeks after first drug administration. MMRM values at Week 52 are reported in the table below | Absolute change from baseline in height at Week 52 was measured with a stadiometer 3 times at each time point. The average of these 3 measurements was taken per time point. Absolute change from baseline in height at Week 52 in the treated set (TS) was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements. |
| Absolute Change From Baseline in Height at Week 76 | Measurements were assessed at Week 0 and at Week 76 | Absolute change from baseline in height at Week 76 was measured with a stadiometer 3 times at each time point. The average of these 3 measurements was taken per time point. MMRM has been calculated but did not provide estimates for this time point due to low sample size. Thus, change in height from baseline to Week 76 was analyzed descriptively only. |
| Absolute Change From Baseline in Sitting Height at Week 24 | MMRM included measurements pre-administration at -4 weeks and at 0, 12, 24, 36, 52, 64, 76, and 88 weeks after first drug administration. MMRM values at Week 24 are reported in the table below. | Absolute change from baseline in sitting height at Week 24 was measured with a stadiometer 3 times at each time point. The average of these 3 measurements was taken per time point. Absolute change from baseline in sitting height at Week 24 in the treated set (TS) was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements. |
| Absolute Change From Baseline in Sitting Height at Week 52 | Measurements were assessed at Week 0 and at Week 52 | Absolute change from baseline in sitting height at Week 52 was measured with a stadiometer 3 times at each time point. The average of these 3 measurements was taken per time point. MMRM has been calculated but did not provide estimates for this time point due to low sample size. Thus, change in sitting height from baseline to Week 52 was analyzed descriptively only. |
| Absolute Change From Baseline in Sitting Height at Week 76 | Measurements were assessed at Week 0 and at Week 76 | Absolute change from baseline in sitting height at Week 76 was measured with a stadiometer 3 times at each time point. The average of these 3 measurements was take per time point. MMRM has been calculated but did not provide estimates for this time point due to low sample size. Thus, change in sitting height from baseline to Week 76 was analyzed descriptively only. |
| Absolute Change From Baseline in Leg Length at Week 24 - Left | MMRM included measurements at 0, 12, 24, 36, 52, 64, and 76 weeks after first drug administration. MMRM values at Week 24 are reported in the table below | Absolute change from baseline in left leg length at Week 24 was assessed by measuring the distance between the anterior iliac spine and the medial malleolus 3 times at each leg and each time point. The average of these 3 measurements was taken per time point. Absolute change from baseline in left leg length at Week 24 in the treated set (TS) was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements. |
| Absolute Change From Baseline in Leg Length at Week 52 - Left | MMRM included measurements at 0, 12, 24, 36, 52, 64, and 76 weeks after first drug administration. MMRM values at Week 52 are reported in the table below | Absolute change from baseline in left leg length at Week 52 was assessed by measuring the distance between the anterior iliac spine and the medial malleolus 3 times at each leg and each time point. The average of these 3 measurements was taken per time point. Absolute change from baseline in left leg length at Week 52 in the treated set (TS) was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements. |
| Absolute Change From Baseline in Leg Length at Week 76 - Left | MMRM included measurements at 0, 12, 24, 36, 52, 64, and 76 weeks after first drug administration. MMRM values at Week 76 are reported in the table below | Absolute change from baseline in left leg length at Week 76 was assessed by measuring the distance between the anterior iliac spine and the medial malleolus 3 times at each leg and each time point. The average of these 3 measurements was taken per time point. Absolute change from baseline in left leg length at Week 76 in the treated set (TS) was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements. |
| Absolute Change From Baseline in Leg Length at Week 24 - Right | MMRM included measurements at 0, 12, 24, 36, 52, 64, and 76 weeks after first drug administration. MMRM values at Week 24 are reported in the table below | Absolute change from baseline in right leg length at Week 24 was assessed by measuring the distance between the anterior iliac spine and the medial malleolus 3 times at each leg and each time point. The average of these 3 measurements was taken per time point. Absolute change from baseline in right leg length at Week 24 in the treated set (TS) was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements. |
| Absolute Change From Baseline in Leg Length at Week 52 - Right | MMRM included measurements at 0, 12, 24, 36, 52, 64, and 76 weeks after first drug administration. MMRM values at Week 52 are reported in the table below | Absolute change from baseline in right leg length at Week 52 was assessed by measuring the distance between the anterior iliac spine and the medial malleolus 3 times at each leg and each time point. The average of these 3 measurements was taken per time point. Absolute change from baseline in right leg length at Week 52 in the treated set (TS) was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements. |
| Absolute Change From Baseline in Leg Length at Week 76 - Right | MMRM included measurements at 0, 12, 24, 36, 52, 64, and 76 weeks after first drug administration. MMRM values at Week 76 are reported in the table below | Absolute change from baseline in right leg length at Week 76 was assessed by measuring the distance between the anterior iliac spine and the medial malleolus 3 times at each leg and each time point. The average of these 3 measurements was taken per time point. Absolute change from baseline in right leg length at Week 76 in the treated set (TS) was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements. |
| Absolute Change From Baseline in Forced Vital Capacity (FVC) % Predicted at Week 24 | MMRM included measurements pre-administration at -4 weeks and at 0, 2, 6, 12, 24, 26, 36, and 52 weeks after first drug administration. MMRM values at Week 24 are reported in the table below | Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible. The predicted values were calculated according to the Global Lungs Initiative (GLI) 2012 equations. Absolute change from baseline in Forced Vital Capacity (FVC) % predicted at Week 24 in the treated set(TS) was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements. |
| Number of Participants With at Least One Treatment-emergent Pathological Finding of Epiphyseal Growth Plate on Imaging up to Week 24, and Week 52 | Up to Week 24 (included values at Week 12 and Week 24); Up to Week 52 (included values at Week 12, 24, 36 and 52) | Number of participants with at least one treatment-emergent pathological finding of the epiphyseal growth plate imaging (Magnetic Resonance Imaging (MRI)s/x-rays) were analyzed cumulatively and based on central review. |
| Absolute Change From Baseline in Pediatric Quality of Life Questionnaire™(PedsQL™) at Week 24 - Parent Report | MMRM included measurements at 0, 24, and 52 weeks after first drug administration. MMRM values at Week 24 are reported in the table below | The PedsQL™ questionnaires consists of 23 items (i) and 4 dimensions: physical (8i), emotional (5i), social (5i) and school (5i) functioning. A 5-point Likert response scale (0 = never (worst outcome) to 4=almost always (best outcome)) was used except for the Young Child Report, where a 3-point scale (0=not at all (worst outcome) to 4=a lot (best outcome)) was used. Items were reverse-scored and linearly transformed to a 0-100 scale (0 = 100 to 4 = 0). Higher scores indicated better health-related quality of life. To create total scores, the mean was computed. Absolute change from baseline in PedsQL™ reported by parents was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements. |
| Absolute Change From Baseline in Pediatric Quality of Life Questionnaire™(PedsQL™) at Week 52 - Parent Report | MMRM included measurements at 0, 24, and 52 weeks after first drug administration. MMRM values at Week 52 are reported in the table below | The PedsQL™ questionnaires consists of 23 items (i) and 4 dimensions: physical (8i), emotional (5i), social (5i) and school (5i) functioning. A 5-point Likert response scale (0 = never (worst outcome) to 4=almost always (best outcome)) was used except for the Young Child Report, where a 3-point scale (0=not at all (worst outcome) to 4=a lot (best outcome)) was used. Items were reverse-scored and linearly transformed to a 0-100 scale (0 = 100 to 4 = 0). Higher scores indicated better health-related quality of life. To create total scores, the mean was computed. Absolute change from baseline in PedsQL™ reported by parents was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements. |
| Absolute Change From Baseline in Pediatric Quality of Life Questionnaire™(PedsQL™) at Week 24 - Participant Report | MMRM included measurements at 0, 24, and 52 weeks after first drug administration. MMRM values at Week 24 are reported in the table below | The PedsQL™ questionnaires consists of 23 items (i) and 4 dimensions: physical (8i), emotional (5i), social (5i) and school (5i) functioning. A 5-point Likert response scale (0 = never (worst outcome) to 4=almost always (best outcome)) was used except for the Young Child Report, where a 3-point scale (0=not at all (worst outcome) to 4=a lot (best outcome)) was used. Items were reverse-scored and linearly transformed to a 0-100 scale (0 = 100 to 4 = 0). Higher scores indicated better health-related quality of life. To create total scores, the mean was computed. Absolute change from baseline in PedsQL™ was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements. |
| Absolute Change From Baseline in Pediatric Quality of Life Questionnaire™(PedsQL™) at Week 52 - Participant Report | MMRM included measurements at 0, 24, and 52 weeks after first drug administration. MMRM values at Week 52 are reported in the table below | The PedsQL™ questionnaires consists of 23 items (i) and 4 dimensions: physical (8i), emotional (5i), social (5i) and school (5i) functioning. A 5-point Likert response scale (0 = never (worst outcome) to 4=almost always (best outcome)) was used except for the Young Child Report, where a 3-point scale (0=not at all (worst outcome) to 4=a lot (best outcome)) was used. Items were reverse-scored and linearly transformed to a 0-100 scale (0 = 100 to 4 = 0). Higher scores indicated better health-related quality of life. To create total scores, the mean was computed. Absolute change from baseline in PedsQL™ was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements. |
| Absolute Change From Baseline in Oxygen Saturation (SpO₂) on Room Air at Rest at Week 24 | MMRM included measurements pre-administration at -4 weeks and at 0, 2, 6, 12, 24, 26, 36, and 52 weeks after first drug administration. MMRM values at Week 24 are reported in the table below | Oxygen saturation (SpO₂) was measured after minimum 5 minutes on room air by standard pulse oximetry at rest. Absolute change from baseline in SpO₂ at Week 24 in the treated set(TS) was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements. |
| Absolute Change From Baseline in Oxygen Saturation (SpO₂) on Room Air at Rest at Week 52 | MMRM included measurements pre-administration at -4 weeks and at 0, 2, 6, 12, 24, 26, 36, and 52 weeks after first drug administration. MMRM values at Week 52 are reported in the table below | Oxygen saturation (SpO₂) was measured after minimum 5 minutes on room air by standard pulse oximetry at rest. Absolute change from baseline in SpO₂ at Week 52 in the treated set(TS) was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements. |
| Absolute Change From Baseline in 6 Minutes (Min) Walk Distance at Week 24 | MMRM included measurements at 0, 24, and 52 weeks after first drug administration. MMRM values at Week 24 are reported in the table below | Absolute change from baseline in 6 minutes (min) walk distance at Week 24 in the treated set (TS) was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements. |
| Absolute Change From Baseline in 6 Minutes (Min) Walk Distance at Week 52 | MMRM included measurements at 0, 24, and 52 weeks after first drug administration. MMRM values at Week 52 are reported in the table below | Absolute change from baseline in 6 minutes (min) walk distance at Week 52 in the treated set(TS) was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements. |
| Participants Acceptability Based on the Size of Capsules at Week 24 - Patient Question | Acceptability was assessed at Week 24 | Acceptability is defined as the overall ability and willingness of the participant to use the medicinal product as intended. Acceptability based on the capsule size was assessed by a acceptability questionnaire (1 item with 3 categories as shown below) for participants. In case the participant was considered not old enough as per investigator judgment the caregiver could assist with the completion. In addition to the commercially available 100 milligram (mg) soft capsules (oblong shape, 6 millimeter (mm) diameter and 16 mm length) and 150 mg soft capsules (oblong shape, 7 mm diameter and 18 mm length), 25 mg Nintedanib soft capsules of smaller size (oval shape, 5 mm diameter and 8 mm length) were provided in this trial for participants who were assigned to a dose smaller than 100 mg or were unable to swallow the larger 100 mg or 150 mg capsules. |
| Participants Acceptability Based on the Size of Capsules at Week 24 - Investigator Question | Acceptability was assessed at Week 24 | Acceptability is defined as the overall ability and willingness of the participant to use the medicinal product as intended. Acceptability based on the capsule size was assessed by a acceptability questionnaire (1 item with 3 categories as shown below) for investigators. In addition to the commercially available 100 milligram (mg) soft capsules (oblong shape, 6 millimeter (mm) diameter and 16 mm length) and 150 mg soft capsules (oblong shape, 7 mm diameter and 18 mm length), 25 mg Nintedanib soft capsules of smaller size (oval shape, 5 mm diameter and 8 mm length) were provided in this trial for participants who were assigned to a dose smaller than 100 mg or were unable to swallow the larger 100 mg or 150 mg capsules. |
| Participants Acceptability Based on the Number of Capsules at Week 24 - Patient Question | Acceptability was assessed at Week 24 | Acceptability is defined as the overall ability and willingness of the participant to use the medicinal product as intended. Acceptability based on the number of capsule was assessed by a acceptability questionnaire (1 item with 3 categories as shown below) for participants. In case the participant was considered not old enough as per investigator judgment the caregiver could assist with the completion. In addition to the commercially available 100 milligram (mg) soft capsules (oblong shape, 6 millimeter (mm) diameter and 16 mm length) and 150 mg soft capsules (oblong shape, 7 mm diameter and 18 mm length), 25 mg Nintedanib soft capsules of smaller size (oval shape, 5 mm diameter and 8 mm length) were provided in this trial for participants who were assigned to a dose smaller than 100 mg or were unable to swallow the larger 100 mg or 150 mg capsules. Medication dosage was based on the participant's body weight and number of capsules per administration ranged from 2 to \>6 capsules. |
| Number of Participants With Occurrence of First Respiratory-related Hospitalization Over the Whole Trial | From first drug administration until the last drug intake + 28 days residual effect period (REP), up to 92.6 weeks | Number of participants with occurrence of first respiratory-related hospitalization over the whole trial. The number of participants with first respiratory-related hospitalization is reported instead of a metric summarizing the time-to-event data with unit of time, as the numbers resulting from the Kaplan-Meier-analysis were even below the first quartile. |
| Number of Participants With Occurrence of First Acute Interstitial Lung Disease (ILD) Exacerbation or Death Over the Whole Trial | From first drug administration until the last drug intake + 28 days REP, up to 92.6 weeks | Number of participants with occurrence of first acute Interstitial Lung Disease (ILD) exacerbation or death over the whole trial. The number of participants with first acute ILD exacerbation is reported instead of a metric summarizing the time-to-event data with unit of time, as the numbers resulting from the Kaplan-Meier-analysis were even below the first quartile. |
| Number of Participants With Occurrence of Death Over the Whole Trial | From first drug administration until the last drug intake + 28 days REP, up to 92.6 weeks | Number of participants with occurrence of death over the whole trial over the whole trial was computed. The number of participants with occurrence of death is reported instead of a metric summarizing the time-to-event data with unit of time, as the numbers resulting from the Kaplan-Meier-analysis were even below the first quartile. |
| Absolute Change From Baseline in Forced Vital Capacity (FVC) % Predicted at Week 52 | MMRM included measurements pre-administration at -4 weeks and at 0, 2, 6, 12, 24, 26, 36, and 52 weeks after first drug administration. MMRM values at Week 52 are reported in the table below | Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible. The predicted values were calculated according to the Global Lungs Initiative (GLI) 2012 equations. Absolute change from baseline in Forced Vital Capacity (FVC) % predicted at Week 52 in the treated set(TS) was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements. |
| Number of Participants With Treatment-emergent Pathological Findings on Dental Examination or Imaging up to Week 24 | Dental examination: at Week 12 and Week 24; Dental imaging: at Week 24 | Number of participants with treatment-emergent pathological findings on dental examination (clinical examination) based on dentist assessment or imaging (panoramic x-ray) based on central review were analyzed. Number of participants with treatment-emergent pathological findings on dental imaging were analyzed cumulatively. |
Countries
Argentina, Australia, Belgium, Brazil, Canada, Czechia, Denmark, Finland, France, Greece, Hungary, Italy, Mexico, Norway, Poland, Portugal, Russia, Spain, Ukraine, United Kingdom, United States
Participant flow
Recruitment details
This was a multicenter, multinational, prospective clinical trial to evaluate the dose-exposure and safety of Nintedanib on top of standard of care (SOC) in children and adolescents (6 to 17 years old) with clinically significant fibrosing Interstitial Lung Disease (ILD) in two parts. A randomised, placebo-controlled, double-blind treatment period of 24 weeks (double-blind period (DBP)) was followed by an open-label Nintedanib period (OLNP)) of variable duration.
Pre-assignment details
Only subjects that met all the study inclusion and none of the exclusion criteria were to be entered in the study. All participants were free to withdraw from the clinical trial at any time for any reason given. Close monitoring of all participants was adhered to throughout the trial conduct. Treatment interruption and dose reduction were allowed as medically indicated.
Participants by arm
| Arm | Count |
|---|---|
| DBP+OLNP: Randomised to Placebo This arm shows placebo randomised participants treated orally with a Nintedanib matching placebo soft capsule twice daily with a dose interval of approximately 12 hours from one dose to the next dose in the double-blind period (DBP).
Participants who continued with the open-label Nintedanib period (OLNP) after the DBP switched to active Nintedanib treatment in the OLNP and were treated orally with Nintedanib twice daily with a dose interval of approximately 12 hours from one dose to the next dose.
Medication dosage was per administration 50 milligram (mg) \[2 capsules with strength 25 mg\],75 mg \[3 capsules with strength 25 mg\], 100 mg \[1 capsule with strength 100 mg or 4 capsules with strength 25 mg\] or 150 mg \[1 capsule with strength 150 mg or 6 capsules with strength 25 mg\] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed.
In this arm participants received placebo first (DBP) and then Nintedanib (OLNP).
DBP: Planned was from first randomised trial drug intake to last blinded drug intake.
OLNP: Planned was from first open-label Nintedanib intake to last open-label Nintedanib intake. | 13 |
| DBP+OLNP: Randomised to Nintedanib This arm shows Nintedanib randomised participants treated orally with Nintedanib in the DBP and OLNP twice daily with a dose interval of approximately 12 hours from one dose to the next dose.
Medication dosage was per administration 50 milligram (mg) \[2 capsules with strength 25 mg\],75 mg \[3 capsules with strength 25 mg\], 100 mg \[1 capsule with strength 100 mg or 4 capsules with strength 25 mg\] or 150 mg \[1 capsule with strength 150 mg or 6 capsules with strength 25 mg\] based on the participant's weight at baseline (= 0 weeks). The dosage was adjusted at subsequent visits if the participant's weight had changed.
In this arm participants received Nintedanib in both periods (DBP + OLNP). Participants in this arm do not entail participants from the 'randomised to placebo' arm.
DBP: Planned was from first randomised trial drug intake to last blinded drug intake.
OLNP: Planned was from first open-label Nintedanib intake to last open-label Nintedanib intake. | 26 |
| Total | 39 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Double-blind Period | Completed prematurely due to administrative end of trial and did not continue with OLNP | 2 | 2 |
| Double-blind Period | Discontinued treatment due to adverse event | 0 | 2 |
| Double-blind Period | Discontinued treatment due to other reason | 0 | 1 |
| Open-label Nintedanib Period (OLNP) | Discontinuation of trial medication due to other reason | 0 | 1 |
Baseline characteristics
| Characteristic | DBP+OLNP: Randomised to Nintedanib | Total | DBP+OLNP: Randomised to Placebo |
|---|---|---|---|
| Age, Continuous | 12.5 Years STANDARD_DEVIATION 3.6 | 12.6 Years STANDARD_DEVIATION 3.3 | 12.9 Years STANDARD_DEVIATION 2.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants | 12 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 18 Participants | 26 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 3 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 19 Participants | 31 Participants | 12 Participants |
| Sex: Female, Male Female | 10 Participants | 15 Participants | 5 Participants |
| Sex: Female, Male Male | 16 Participants | 24 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 11 | 0 / 26 |
| other Total, other adverse events | 11 / 13 | 11 / 11 | 26 / 26 |
| serious Total, serious adverse events | 1 / 13 | 2 / 11 | 5 / 26 |
Outcome results
Primary
Area Under the Plasma Concentration-time Curve at Steady State (AUCτ,ss) Based on Sampling at Steady State (at Week 2 and Week 26)
Area under the plasma concentration-time curve at steady state (AUCt,ss) based on sampling at steady state (at Week 2 and Week 26) after multiple oral administration of Nintedanib by age group over all treatments. Values of samples taken at Week 2 (for randomised Nintedanib participants) and at Week 26 (for randomised placebo participants) were used. Missing values at Week 2 of randomised Nintedanib participants were replaced with values taken at Week 26.
Time frame: At Week 2 and at Week 26: at 5 minutes before and at 0, 1, 2, 3, 4, 6, and 8 hours post administration of the morning dose
Population: Pharmacokinetic parameter analysis set (PKS):~This set includes all patients in the treated set (TS) who provide at least one pharmacokinetic (PK) endpoint that was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| DBP+OLNP: 6 to < 12 Years - Exposed to Nintedanib | Area Under the Plasma Concentration-time Curve at Steady State (AUCτ,ss) Based on Sampling at Steady State (at Week 2 and Week 26) | 175 Hours times nanogram per mililiter | Geometric Coefficient of Variation 85.1 |
| DBP+OLNP: 12 to <18 Years - Exposed to Nintedanib | Area Under the Plasma Concentration-time Curve at Steady State (AUCτ,ss) Based on Sampling at Steady State (at Week 2 and Week 26) | 167 Hours times nanogram per mililiter | Geometric Coefficient of Variation 83.6 |
Primary
Number of Participants With Treatment-emergent Adverse Events During the Double-blind Period
Treatment-emergent was defined as: Adverse events with onset or worsening on or after date of treatment start until end of double-blind period (defined as the day before first intake of open-label nintedanib or last double-blind drug intake + residual effect period, whichever is earlier) were considered as treatment-emergent and were included in the analysis. Adverse events were counted under the treatment as randomized for the double-blind period.
Time frame: From first drug administration until the earlier of (i) first intake of open-label nintedanib (exclusive) and (ii) last drug intake, up to 28 weeks
Population: Treated set (TS): The TS consisted of participants who were randomised to a treatment group and received at least one dose of study medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| DBP+OLNP: 6 to < 12 Years - Exposed to Nintedanib | Number of Participants With Treatment-emergent Adverse Events During the Double-blind Period | 11 Participants |
| DBP+OLNP: 12 to <18 Years - Exposed to Nintedanib | Number of Participants With Treatment-emergent Adverse Events During the Double-blind Period | 22 Participants |
Secondary
Absolute Change From Baseline in 6 Minutes (Min) Walk Distance at Week 24
Absolute change from baseline in 6 minutes (min) walk distance at Week 24 in the treated set (TS) was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements.
Time frame: MMRM included measurements at 0, 24, and 52 weeks after first drug administration. MMRM values at Week 24 are reported in the table below
Population: Treated set (TS): The TS consisted of participants who were randomised to a treatment group and received at least one dose of study medication. Only participants with correctly measured baseline and at least one post-baseline measurement were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| DBP+OLNP: 6 to < 12 Years - Exposed to Nintedanib | Absolute Change From Baseline in 6 Minutes (Min) Walk Distance at Week 24 | 10.5 Meter |
| DBP+OLNP: 12 to <18 Years - Exposed to Nintedanib | Absolute Change From Baseline in 6 Minutes (Min) Walk Distance at Week 24 | 17.6 Meter |
p-value: 0.801295% CI: [-50.7, 65]Mixed Model Repeated Measures (MMRM)
Secondary
Absolute Change From Baseline in 6 Minutes (Min) Walk Distance at Week 52
Absolute change from baseline in 6 minutes (min) walk distance at Week 52 in the treated set(TS) was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements.
Time frame: MMRM included measurements at 0, 24, and 52 weeks after first drug administration. MMRM values at Week 52 are reported in the table below
Population: Treated set (TS): The TS consisted of participants who were randomised to a treatment group and received at least one dose of study medication. Only participants with correctly measured baseline and at least one post-baseline measurement were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| DBP+OLNP: 6 to < 12 Years - Exposed to Nintedanib | Absolute Change From Baseline in 6 Minutes (Min) Walk Distance at Week 52 | 28.1 Meter (m) |
| DBP+OLNP: 12 to <18 Years - Exposed to Nintedanib | Absolute Change From Baseline in 6 Minutes (Min) Walk Distance at Week 52 | -4.9 Meter (m) |
p-value: 0.340195% CI: [-103.1, 37.2]Mixed Model Repeated Measures (MMRM)
Secondary
Absolute Change From Baseline in Forced Vital Capacity (FVC) % Predicted at Week 24
Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible. The predicted values were calculated according to the Global Lungs Initiative (GLI) 2012 equations. Absolute change from baseline in Forced Vital Capacity (FVC) % predicted at Week 24 in the treated set(TS) was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements.
Time frame: MMRM included measurements pre-administration at -4 weeks and at 0, 2, 6, 12, 24, 26, 36, and 52 weeks after first drug administration. MMRM values at Week 24 are reported in the table below
Population: Treated set (TS): The TS consisted of participants who were randomised to a treatment group and received at least one dose of study medication. Only participants with correctly measured baseline and at least one post-baseline measurement were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| DBP+OLNP: 6 to < 12 Years - Exposed to Nintedanib | Absolute Change From Baseline in Forced Vital Capacity (FVC) % Predicted at Week 24 | -0.8939 Percentage of predicted FVC |
| DBP+OLNP: 12 to <18 Years - Exposed to Nintedanib | Absolute Change From Baseline in Forced Vital Capacity (FVC) % Predicted at Week 24 | 0.3112 Percentage of predicted FVC |
p-value: 0.596295% CI: [-3.3966, 5.807]Mixed Model Repeated Measures (MMRM)
Secondary
Absolute Change From Baseline in Forced Vital Capacity (FVC) % Predicted at Week 52
Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible. The predicted values were calculated according to the Global Lungs Initiative (GLI) 2012 equations. Absolute change from baseline in Forced Vital Capacity (FVC) % predicted at Week 52 in the treated set(TS) was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements.
Time frame: MMRM included measurements pre-administration at -4 weeks and at 0, 2, 6, 12, 24, 26, 36, and 52 weeks after first drug administration. MMRM values at Week 52 are reported in the table below
Population: Treated set (TS): The TS consisted of participants who were randomised to a treatment group and received at least one dose of study medication. Only participants with correctly measured baseline and at least one post-baseline measurement were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| DBP+OLNP: 6 to < 12 Years - Exposed to Nintedanib | Absolute Change From Baseline in Forced Vital Capacity (FVC) % Predicted at Week 52 | -0.9827 Percentage of predicted FVC |
| DBP+OLNP: 12 to <18 Years - Exposed to Nintedanib | Absolute Change From Baseline in Forced Vital Capacity (FVC) % Predicted at Week 52 | 0.7906 Percentage of predicted FVC |
p-value: 0.577695% CI: [-4.7015, 8.2481]Mixed Model Repeated Measures (MMRM)
Secondary
Absolute Change From Baseline in Height at Week 24
Absolute change from baseline in height at Week 24 was measured with a stadiometer 3 times at each time point. The average of these 3 measurements was taken per time point. Absolute change from baseline in height at Week 24 in the treated set (TS) was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements.
Time frame: MMRM included measurements pre-administration at -4 weeks and at 0, 12, 24, 36, 52, 64, 76, and 88 weeks after first drug administration. MMRM values at Week 24 are reported in the table below
Population: Treated set (TS): The TS consisted of participants who were randomised to a treatment group and received at least one dose of study medication. Only participants with correctly measured baseline and at least one post-baseline measurement were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| DBP+OLNP: 6 to < 12 Years - Exposed to Nintedanib | Absolute Change From Baseline in Height at Week 24 | 1.3 Centimeter |
| DBP+OLNP: 12 to <18 Years - Exposed to Nintedanib | Absolute Change From Baseline in Height at Week 24 | 1.3 Centimeter |
Comparison: No formal hypotheses were testedp-value: 0.985895% CI: [-0.8, 0.8]Mixed Model Repeated Measures (MMRM)
Secondary
Absolute Change From Baseline in Height at Week 52
Absolute change from baseline in height at Week 52 was measured with a stadiometer 3 times at each time point. The average of these 3 measurements was taken per time point. Absolute change from baseline in height at Week 52 in the treated set (TS) was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements.
Time frame: MMRM included measurements pre-administration at -4 weeks and at 0, 12, 24, 36, 52, 64, 76, and 88 weeks after first drug administration. MMRM values at Week 52 are reported in the table below
Population: Treated set (TS): The TS consisted of participants who were randomised to a treatment group and received at least one dose of study medication. Only participants with correctly measured baseline and at least one post-baseline measurement were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| DBP+OLNP: 6 to < 12 Years - Exposed to Nintedanib | Absolute Change From Baseline in Height at Week 52 | 2.8 Centimeter |
| DBP+OLNP: 12 to <18 Years - Exposed to Nintedanib | Absolute Change From Baseline in Height at Week 52 | 2.8 Centimeter |
Comparison: No formal hypotheses were testedp-value: 0.976995% CI: [-1.7, 1.6]Mixed Model Repeated Measures (MMRM)
Secondary
Absolute Change From Baseline in Height at Week 76
Absolute change from baseline in height at Week 76 was measured with a stadiometer 3 times at each time point. The average of these 3 measurements was taken per time point. MMRM has been calculated but did not provide estimates for this time point due to low sample size. Thus, change in height from baseline to Week 76 was analyzed descriptively only.
Time frame: Measurements were assessed at Week 0 and at Week 76
Population: Treated set (TS): The TS consisted of participants who were randomised to a treatment group and received at least one dose of study medication. Only participants with correctly measured baseline and at least one post-baseline measurement were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DBP+OLNP: 6 to < 12 Years - Exposed to Nintedanib | Absolute Change From Baseline in Height at Week 76 | At Baseline | 143.7 Centimeter | Standard Deviation 11.2 |
| DBP+OLNP: 6 to < 12 Years - Exposed to Nintedanib | Absolute Change From Baseline in Height at Week 76 | At Week 76 | 150.0 Centimeter | Standard Deviation 15.7 |
| DBP+OLNP: 12 to <18 Years - Exposed to Nintedanib | Absolute Change From Baseline in Height at Week 76 | At Baseline | 162.5 Centimeter | Standard Deviation 15.8 |
| DBP+OLNP: 12 to <18 Years - Exposed to Nintedanib | Absolute Change From Baseline in Height at Week 76 | At Week 76 | 165.5 Centimeter | Standard Deviation 13 |
Secondary
Absolute Change From Baseline in Leg Length at Week 24 - Left
Absolute change from baseline in left leg length at Week 24 was assessed by measuring the distance between the anterior iliac spine and the medial malleolus 3 times at each leg and each time point. The average of these 3 measurements was taken per time point. Absolute change from baseline in left leg length at Week 24 in the treated set (TS) was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements.
Time frame: MMRM included measurements at 0, 12, 24, 36, 52, 64, and 76 weeks after first drug administration. MMRM values at Week 24 are reported in the table below
Population: Treated set (TS): The TS consisted of participants who were randomised to a treatment group and received at least one dose of study medication. Only participants with correctly measured baseline and at least one post-baseline measurement were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| DBP+OLNP: 6 to < 12 Years - Exposed to Nintedanib | Absolute Change From Baseline in Leg Length at Week 24 - Left | 1.6 Centimeters |
| DBP+OLNP: 12 to <18 Years - Exposed to Nintedanib | Absolute Change From Baseline in Leg Length at Week 24 - Left | 1.7 Centimeters |
p-value: 0.88295% CI: [-1.5, 1.8]Mixed Model Repeated Measures (MMRM)
Secondary
Absolute Change From Baseline in Leg Length at Week 24 - Right
Absolute change from baseline in right leg length at Week 24 was assessed by measuring the distance between the anterior iliac spine and the medial malleolus 3 times at each leg and each time point. The average of these 3 measurements was taken per time point. Absolute change from baseline in right leg length at Week 24 in the treated set (TS) was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements.
Time frame: MMRM included measurements at 0, 12, 24, 36, 52, 64, and 76 weeks after first drug administration. MMRM values at Week 24 are reported in the table below
Population: Treated set (TS): The TS consisted of participants who were randomised to a treatment group and received at least one dose of study medication. Only participants with correctly measured baseline and at least one post-baseline measurement were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| DBP+OLNP: 6 to < 12 Years - Exposed to Nintedanib | Absolute Change From Baseline in Leg Length at Week 24 - Right | 1.6 Centimeters |
| DBP+OLNP: 12 to <18 Years - Exposed to Nintedanib | Absolute Change From Baseline in Leg Length at Week 24 - Right | 1.6 Centimeters |
p-value: 0.992895% CI: [-1.6, 1.6]Mixed Model Repeated Measures (MMRM)
Secondary
Absolute Change From Baseline in Leg Length at Week 52 - Left
Absolute change from baseline in left leg length at Week 52 was assessed by measuring the distance between the anterior iliac spine and the medial malleolus 3 times at each leg and each time point. The average of these 3 measurements was taken per time point. Absolute change from baseline in left leg length at Week 52 in the treated set (TS) was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements.
Time frame: MMRM included measurements at 0, 12, 24, 36, 52, 64, and 76 weeks after first drug administration. MMRM values at Week 52 are reported in the table below
Population: Treated set (TS): The TS consisted of participants who were randomised to a treatment group and received at least one dose of study medication. Only participants with correctly measured baseline and at least one post-baseline measurement were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| DBP+OLNP: 6 to < 12 Years - Exposed to Nintedanib | Absolute Change From Baseline in Leg Length at Week 52 - Left | 2.8 Centimeter |
| DBP+OLNP: 12 to <18 Years - Exposed to Nintedanib | Absolute Change From Baseline in Leg Length at Week 52 - Left | 2.9 Centimeter |
Comparison: No formal hypotheses were testedp-value: 0.965295% CI: [-3.2, 3.3]Mixed Model Repeated Measures (MMRM)
Secondary
Absolute Change From Baseline in Leg Length at Week 52 - Right
Absolute change from baseline in right leg length at Week 52 was assessed by measuring the distance between the anterior iliac spine and the medial malleolus 3 times at each leg and each time point. The average of these 3 measurements was taken per time point. Absolute change from baseline in right leg length at Week 52 in the treated set (TS) was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements.
Time frame: MMRM included measurements at 0, 12, 24, 36, 52, 64, and 76 weeks after first drug administration. MMRM values at Week 52 are reported in the table below
Population: Treated set (TS): The TS consisted of participants who were randomised to a treatment group and received at least one dose of study medication. Only participants with correctly measured baseline and at least one post-baseline measurement were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| DBP+OLNP: 6 to < 12 Years - Exposed to Nintedanib | Absolute Change From Baseline in Leg Length at Week 52 - Right | 2.8 Centimeter |
| DBP+OLNP: 12 to <18 Years - Exposed to Nintedanib | Absolute Change From Baseline in Leg Length at Week 52 - Right | 3.4 Centimeter |
Comparison: No formal hypotheses were testedp-value: 0.636695% CI: [-2.3, 3.6]Mixed Model Repeated Measures (MMRM)
Secondary
Absolute Change From Baseline in Leg Length at Week 76 - Left
Absolute change from baseline in left leg length at Week 76 was assessed by measuring the distance between the anterior iliac spine and the medial malleolus 3 times at each leg and each time point. The average of these 3 measurements was taken per time point. Absolute change from baseline in left leg length at Week 76 in the treated set (TS) was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements.
Time frame: MMRM included measurements at 0, 12, 24, 36, 52, 64, and 76 weeks after first drug administration. MMRM values at Week 76 are reported in the table below
Population: Treated set (TS): The TS consisted of participants who were randomised to a treatment group and received at least one dose of study medication. Only participants with correctly measured baseline and at least one post-baseline measurement were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| DBP+OLNP: 6 to < 12 Years - Exposed to Nintedanib | Absolute Change From Baseline in Leg Length at Week 76 - Left | 5.2 Centimeter |
| DBP+OLNP: 12 to <18 Years - Exposed to Nintedanib | Absolute Change From Baseline in Leg Length at Week 76 - Left | 2.6 Centimeter |
Comparison: No formal hypotheses were testedp-value: 0.408495% CI: [-9.3, 4]Mixed Model Repeated Measures (MMRM)
Secondary
Absolute Change From Baseline in Leg Length at Week 76 - Right
Absolute change from baseline in right leg length at Week 76 was assessed by measuring the distance between the anterior iliac spine and the medial malleolus 3 times at each leg and each time point. The average of these 3 measurements was taken per time point. Absolute change from baseline in right leg length at Week 76 in the treated set (TS) was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements.
Time frame: MMRM included measurements at 0, 12, 24, 36, 52, 64, and 76 weeks after first drug administration. MMRM values at Week 76 are reported in the table below
Population: Treated set (TS): The TS consisted of participants who were randomised to a treatment group and received at least one dose of study medication. Only participants with correctly measured baseline and at least one post-baseline measurement were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| DBP+OLNP: 6 to < 12 Years - Exposed to Nintedanib | Absolute Change From Baseline in Leg Length at Week 76 - Right | 3.9 Centimeter |
| DBP+OLNP: 12 to <18 Years - Exposed to Nintedanib | Absolute Change From Baseline in Leg Length at Week 76 - Right | 4.3 Centimeter |
Comparison: No formal hypotheses were testedp-value: 0.882395% CI: [-5.2, 5.9]Mixed Model Repeated Measures (MMRM)
Secondary
Absolute Change From Baseline in Oxygen Saturation (SpO₂) on Room Air at Rest at Week 24
Oxygen saturation (SpO₂) was measured after minimum 5 minutes on room air by standard pulse oximetry at rest. Absolute change from baseline in SpO₂ at Week 24 in the treated set(TS) was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements.
Time frame: MMRM included measurements pre-administration at -4 weeks and at 0, 2, 6, 12, 24, 26, 36, and 52 weeks after first drug administration. MMRM values at Week 24 are reported in the table below
Population: Treated set (TS): The TS consisted of participants who were randomised to a treatment group and received at least one dose of study medication. Only participants with correctly measured baseline and at least one post-baseline measurement were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| DBP+OLNP: 6 to < 12 Years - Exposed to Nintedanib | Absolute Change From Baseline in Oxygen Saturation (SpO₂) on Room Air at Rest at Week 24 | -2.25 Percentage of SpO₂ |
| DBP+OLNP: 12 to <18 Years - Exposed to Nintedanib | Absolute Change From Baseline in Oxygen Saturation (SpO₂) on Room Air at Rest at Week 24 | 0.07 Percentage of SpO₂ |
p-value: 0.090895% CI: [-0.39, 5.02]Mixed Model Repeated Measures (MMRM)
Secondary
Absolute Change From Baseline in Oxygen Saturation (SpO₂) on Room Air at Rest at Week 52
Oxygen saturation (SpO₂) was measured after minimum 5 minutes on room air by standard pulse oximetry at rest. Absolute change from baseline in SpO₂ at Week 52 in the treated set(TS) was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements.
Time frame: MMRM included measurements pre-administration at -4 weeks and at 0, 2, 6, 12, 24, 26, 36, and 52 weeks after first drug administration. MMRM values at Week 52 are reported in the table below
Population: Treated set (TS): The TS consisted of participants who were randomised to a treatment group and received at least one dose of study medication. Only participants with correctly measured baseline and at least one post-baseline measurement were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| DBP+OLNP: 6 to < 12 Years - Exposed to Nintedanib | Absolute Change From Baseline in Oxygen Saturation (SpO₂) on Room Air at Rest at Week 52 | -2.60 Percentage of SpO₂ |
| DBP+OLNP: 12 to <18 Years - Exposed to Nintedanib | Absolute Change From Baseline in Oxygen Saturation (SpO₂) on Room Air at Rest at Week 52 | -0.32 Percentage of SpO₂ |
p-value: 0.122295% CI: [-0.69, 5.25]Mixed Model Repeated Measures (MMRM)
Secondary
Absolute Change From Baseline in Pediatric Quality of Life Questionnaire™(PedsQL™) at Week 24 - Parent Report
The PedsQL™ questionnaires consists of 23 items (i) and 4 dimensions: physical (8i), emotional (5i), social (5i) and school (5i) functioning. A 5-point Likert response scale (0 = never (worst outcome) to 4=almost always (best outcome)) was used except for the Young Child Report, where a 3-point scale (0=not at all (worst outcome) to 4=a lot (best outcome)) was used. Items were reverse-scored and linearly transformed to a 0-100 scale (0 = 100 to 4 = 0). Higher scores indicated better health-related quality of life. To create total scores, the mean was computed. Absolute change from baseline in PedsQL™ reported by parents was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements.
Time frame: MMRM included measurements at 0, 24, and 52 weeks after first drug administration. MMRM values at Week 24 are reported in the table below
Population: Treated set (TS): The TS consisted of participants who were randomised to a treatment group and received at least one dose of study medication. Only participants with correctly measured baseline and at least one post-baseline measurement were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| DBP+OLNP: 6 to < 12 Years - Exposed to Nintedanib | Absolute Change From Baseline in Pediatric Quality of Life Questionnaire™(PedsQL™) at Week 24 - Parent Report | 5.615 Unit on scale |
| DBP+OLNP: 12 to <18 Years - Exposed to Nintedanib | Absolute Change From Baseline in Pediatric Quality of Life Questionnaire™(PedsQL™) at Week 24 - Parent Report | 5.481 Unit on scale |
p-value: 0.975595% CI: [-8.975, 8.707]Mixed Model Repeated Measures (MMRM)
Secondary
Absolute Change From Baseline in Pediatric Quality of Life Questionnaire™(PedsQL™) at Week 24 - Participant Report
The PedsQL™ questionnaires consists of 23 items (i) and 4 dimensions: physical (8i), emotional (5i), social (5i) and school (5i) functioning. A 5-point Likert response scale (0 = never (worst outcome) to 4=almost always (best outcome)) was used except for the Young Child Report, where a 3-point scale (0=not at all (worst outcome) to 4=a lot (best outcome)) was used. Items were reverse-scored and linearly transformed to a 0-100 scale (0 = 100 to 4 = 0). Higher scores indicated better health-related quality of life. To create total scores, the mean was computed. Absolute change from baseline in PedsQL™ was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements.
Time frame: MMRM included measurements at 0, 24, and 52 weeks after first drug administration. MMRM values at Week 24 are reported in the table below
Population: Treated set (TS): The TS consisted of participants who were randomised to a treatment group and received at least one dose of study medication. Only participants with correctly measured baseline and at least one post-baseline measurement were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| DBP+OLNP: 6 to < 12 Years - Exposed to Nintedanib | Absolute Change From Baseline in Pediatric Quality of Life Questionnaire™(PedsQL™) at Week 24 - Participant Report | 5.484 Unit on scale |
| DBP+OLNP: 12 to <18 Years - Exposed to Nintedanib | Absolute Change From Baseline in Pediatric Quality of Life Questionnaire™(PedsQL™) at Week 24 - Participant Report | 6.514 Unit on scale |
p-value: 0.761395% CI: [-5.848, 7.908]Mixed Model Repeated Measures (MMRM)
Secondary
Absolute Change From Baseline in Pediatric Quality of Life Questionnaire™(PedsQL™) at Week 52 - Parent Report
The PedsQL™ questionnaires consists of 23 items (i) and 4 dimensions: physical (8i), emotional (5i), social (5i) and school (5i) functioning. A 5-point Likert response scale (0 = never (worst outcome) to 4=almost always (best outcome)) was used except for the Young Child Report, where a 3-point scale (0=not at all (worst outcome) to 4=a lot (best outcome)) was used. Items were reverse-scored and linearly transformed to a 0-100 scale (0 = 100 to 4 = 0). Higher scores indicated better health-related quality of life. To create total scores, the mean was computed. Absolute change from baseline in PedsQL™ reported by parents was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements.
Time frame: MMRM included measurements at 0, 24, and 52 weeks after first drug administration. MMRM values at Week 52 are reported in the table below
Population: Treated set (TS): The TS consisted of participants who were randomised to a treatment group and received at least one dose of study medication. Only participants with correctly measured baseline and at least one post-baseline measurement were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| DBP+OLNP: 6 to < 12 Years - Exposed to Nintedanib | Absolute Change From Baseline in Pediatric Quality of Life Questionnaire™(PedsQL™) at Week 52 - Parent Report | 4.377 Unit on scale |
| DBP+OLNP: 12 to <18 Years - Exposed to Nintedanib | Absolute Change From Baseline in Pediatric Quality of Life Questionnaire™(PedsQL™) at Week 52 - Parent Report | 7.830 Unit on scale |
p-value: 0.51495% CI: [-7.25, 14.157]Mixed Model Repeated Measures (MMRM)
Secondary
Absolute Change From Baseline in Pediatric Quality of Life Questionnaire™(PedsQL™) at Week 52 - Participant Report
The PedsQL™ questionnaires consists of 23 items (i) and 4 dimensions: physical (8i), emotional (5i), social (5i) and school (5i) functioning. A 5-point Likert response scale (0 = never (worst outcome) to 4=almost always (best outcome)) was used except for the Young Child Report, where a 3-point scale (0=not at all (worst outcome) to 4=a lot (best outcome)) was used. Items were reverse-scored and linearly transformed to a 0-100 scale (0 = 100 to 4 = 0). Higher scores indicated better health-related quality of life. To create total scores, the mean was computed. Absolute change from baseline in PedsQL™ was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements.
Time frame: MMRM included measurements at 0, 24, and 52 weeks after first drug administration. MMRM values at Week 52 are reported in the table below
Population: Treated set (TS): The TS consisted of participants who were randomised to a treatment group and received at least one dose of study medication. Only participants with correctly measured baseline and at least one post-baseline measurement were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| DBP+OLNP: 6 to < 12 Years - Exposed to Nintedanib | Absolute Change From Baseline in Pediatric Quality of Life Questionnaire™(PedsQL™) at Week 52 - Participant Report | 0.902 Unit on scale |
| DBP+OLNP: 12 to <18 Years - Exposed to Nintedanib | Absolute Change From Baseline in Pediatric Quality of Life Questionnaire™(PedsQL™) at Week 52 - Participant Report | 1.243 Unit on scale |
p-value: 0.946895% CI: [-10.026, 10.707]Mixed Model Repeated Measures (MMRM)
Secondary
Absolute Change From Baseline in Sitting Height at Week 24
Absolute change from baseline in sitting height at Week 24 was measured with a stadiometer 3 times at each time point. The average of these 3 measurements was taken per time point. Absolute change from baseline in sitting height at Week 24 in the treated set (TS) was based on a Mixed Model Repeated Measures (MMRM), with fixed categorical effects of (randomised) treatment at each visit, age-group and the fixed continuous effects of baseline at each visit, and random effect for participant. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-participant measurements.
Time frame: MMRM included measurements pre-administration at -4 weeks and at 0, 12, 24, 36, 52, 64, 76, and 88 weeks after first drug administration. MMRM values at Week 24 are reported in the table below.
Population: Treated set (TS): The TS consisted of participants who were randomised to a treatment group and received at least one dose of study medication. Only participants with correctly measured baseline and at least one post-baseline measurement were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| DBP+OLNP: 6 to < 12 Years - Exposed to Nintedanib | Absolute Change From Baseline in Sitting Height at Week 24 | 1.0 Centimeters |
| DBP+OLNP: 12 to <18 Years - Exposed to Nintedanib | Absolute Change From Baseline in Sitting Height at Week 24 | 2.1 Centimeters |
p-value: 0.444295% CI: [-1.8, 4]Mixed Model Repeated Measures (MMRM)
Secondary
Absolute Change From Baseline in Sitting Height at Week 52
Absolute change from baseline in sitting height at Week 52 was measured with a stadiometer 3 times at each time point. The average of these 3 measurements was taken per time point. MMRM has been calculated but did not provide estimates for this time point due to low sample size. Thus, change in sitting height from baseline to Week 52 was analyzed descriptively only.
Time frame: Measurements were assessed at Week 0 and at Week 52
Population: Treated set (TS): The TS consisted of participants who were randomised to a treatment group and received at least one dose of study medication. Only participants with non-missing results were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DBP+OLNP: 6 to < 12 Years - Exposed to Nintedanib | Absolute Change From Baseline in Sitting Height at Week 52 | At Baseline | 78.7 Centimeters | Standard Deviation 11.8 |
| DBP+OLNP: 6 to < 12 Years - Exposed to Nintedanib | Absolute Change From Baseline in Sitting Height at Week 52 | At Week 52 | 79.0 Centimeters | Standard Deviation 12.2 |
| DBP+OLNP: 12 to <18 Years - Exposed to Nintedanib | Absolute Change From Baseline in Sitting Height at Week 52 | At Week 52 | 79.3 Centimeters | Standard Deviation 8.6 |
| DBP+OLNP: 12 to <18 Years - Exposed to Nintedanib | Absolute Change From Baseline in Sitting Height at Week 52 | At Baseline | 77.6 Centimeters | Standard Deviation 9.4 |
Secondary
Absolute Change From Baseline in Sitting Height at Week 76
Absolute change from baseline in sitting height at Week 76 was measured with a stadiometer 3 times at each time point. The average of these 3 measurements was take per time point. MMRM has been calculated but did not provide estimates for this time point due to low sample size. Thus, change in sitting height from baseline to Week 76 was analyzed descriptively only.
Time frame: Measurements were assessed at Week 0 and at Week 76
Population: Treated set (TS): The TS consisted of participants who were randomised to a treatment group and received at least one dose of study medication. Only participants with non-missing results were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DBP+OLNP: 6 to < 12 Years - Exposed to Nintedanib | Absolute Change From Baseline in Sitting Height at Week 76 | At Baseline | 65.0 Centimeters | — |
| DBP+OLNP: 6 to < 12 Years - Exposed to Nintedanib | Absolute Change From Baseline in Sitting Height at Week 76 | At Week 76 | 65.0 Centimeters | — |
| DBP+OLNP: 12 to <18 Years - Exposed to Nintedanib | Absolute Change From Baseline in Sitting Height at Week 76 | At Baseline | 83.0 Centimeters | Standard Deviation 4.2 |
| DBP+OLNP: 12 to <18 Years - Exposed to Nintedanib | Absolute Change From Baseline in Sitting Height at Week 76 | At Week 76 | 84.5 Centimeters | Standard Deviation 3.5 |
Secondary
Number of Participants With at Least One Treatment-emergent Pathological Finding of Epiphyseal Growth Plate on Imaging up to Week 24, and Week 52
Number of participants with at least one treatment-emergent pathological finding of the epiphyseal growth plate imaging (Magnetic Resonance Imaging (MRI)s/x-rays) were analyzed cumulatively and based on central review.
Time frame: Up to Week 24 (included values at Week 12 and Week 24); Up to Week 52 (included values at Week 12, 24, 36 and 52)
Population: Treated set (TS): The TS consisted of participants who were randomised to a treatment group and received at least one dose of study medication.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| DBP+OLNP: 6 to < 12 Years - Exposed to Nintedanib | Number of Participants With at Least One Treatment-emergent Pathological Finding of Epiphyseal Growth Plate on Imaging up to Week 24, and Week 52 | At Week 24 | 1 Participants |
| DBP+OLNP: 6 to < 12 Years - Exposed to Nintedanib | Number of Participants With at Least One Treatment-emergent Pathological Finding of Epiphyseal Growth Plate on Imaging up to Week 24, and Week 52 | At Week 52 | 2 Participants |
| DBP+OLNP: 12 to <18 Years - Exposed to Nintedanib | Number of Participants With at Least One Treatment-emergent Pathological Finding of Epiphyseal Growth Plate on Imaging up to Week 24, and Week 52 | At Week 24 | 2 Participants |
| DBP+OLNP: 12 to <18 Years - Exposed to Nintedanib | Number of Participants With at Least One Treatment-emergent Pathological Finding of Epiphyseal Growth Plate on Imaging up to Week 24, and Week 52 | At Week 52 | 3 Participants |
Secondary
Number of Participants With at Least One Treatment-emergent Pathological Findings on Dental Examination or Imaging up to Week 52
Number of participants with treatment-emergent pathological findings on dental examination (clinical examination) based on dentist assessment or imaging (panoramic x-ray) based on central review were analyzed. Number of participants with treatment-emergent pathological findings on dental imaging were analyzed cumulatively.
Time frame: Dental examination: at Week 12, 24, 34, and Week 52; Dental imaging: at Week 24 and at Week 52.
Population: Treated set (TS): The TS consisted of participants who were randomised to a treatment group and received at least one dose of study medication.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| DBP+OLNP: 6 to < 12 Years - Exposed to Nintedanib | Number of Participants With at Least One Treatment-emergent Pathological Findings on Dental Examination or Imaging up to Week 52 | Dental imaging: Other findings | 3 Participants |
| DBP+OLNP: 6 to < 12 Years - Exposed to Nintedanib | Number of Participants With at Least One Treatment-emergent Pathological Findings on Dental Examination or Imaging up to Week 52 | Dental examination: Pathological findings up to week 52 | 3 Participants |
| DBP+OLNP: 6 to < 12 Years - Exposed to Nintedanib | Number of Participants With at Least One Treatment-emergent Pathological Findings on Dental Examination or Imaging up to Week 52 | Dental imaging: Stunted growth of dental root | 0 Participants |
| DBP+OLNP: 6 to < 12 Years - Exposed to Nintedanib | Number of Participants With at Least One Treatment-emergent Pathological Findings on Dental Examination or Imaging up to Week 52 | Dental imaging: Accelerated growth of dental root | 0 Participants |
| DBP+OLNP: 6 to < 12 Years - Exposed to Nintedanib | Number of Participants With at Least One Treatment-emergent Pathological Findings on Dental Examination or Imaging up to Week 52 | Dental imaging: extra / supernumerary teeth | 0 Participants |
| DBP+OLNP: 6 to < 12 Years - Exposed to Nintedanib | Number of Participants With at Least One Treatment-emergent Pathological Findings on Dental Examination or Imaging up to Week 52 | Dental imaging: Impacted permanent teeth | 2 Participants |
| DBP+OLNP: 6 to < 12 Years - Exposed to Nintedanib | Number of Participants With at Least One Treatment-emergent Pathological Findings on Dental Examination or Imaging up to Week 52 | Dental imaging: Additional findings | 1 Participants |
| DBP+OLNP: 12 to <18 Years - Exposed to Nintedanib | Number of Participants With at Least One Treatment-emergent Pathological Findings on Dental Examination or Imaging up to Week 52 | Dental imaging: Other findings | 2 Participants |
| DBP+OLNP: 12 to <18 Years - Exposed to Nintedanib | Number of Participants With at Least One Treatment-emergent Pathological Findings on Dental Examination or Imaging up to Week 52 | Dental imaging: extra / supernumerary teeth | 0 Participants |
| DBP+OLNP: 12 to <18 Years - Exposed to Nintedanib | Number of Participants With at Least One Treatment-emergent Pathological Findings on Dental Examination or Imaging up to Week 52 | Dental examination: Pathological findings up to week 52 | 7 Participants |
| DBP+OLNP: 12 to <18 Years - Exposed to Nintedanib | Number of Participants With at Least One Treatment-emergent Pathological Findings on Dental Examination or Imaging up to Week 52 | Dental imaging: Additional findings | 6 Participants |
| DBP+OLNP: 12 to <18 Years - Exposed to Nintedanib | Number of Participants With at Least One Treatment-emergent Pathological Findings on Dental Examination or Imaging up to Week 52 | Dental imaging: Stunted growth of dental root | 6 Participants |
| DBP+OLNP: 12 to <18 Years - Exposed to Nintedanib | Number of Participants With at Least One Treatment-emergent Pathological Findings on Dental Examination or Imaging up to Week 52 | Dental imaging: Impacted permanent teeth | 5 Participants |
| DBP+OLNP: 12 to <18 Years - Exposed to Nintedanib | Number of Participants With at Least One Treatment-emergent Pathological Findings on Dental Examination or Imaging up to Week 52 | Dental imaging: Accelerated growth of dental root | 0 Participants |
Secondary
Number of Participants With Occurrence of Death Over the Whole Trial
Number of participants with occurrence of death over the whole trial over the whole trial was computed. The number of participants with occurrence of death is reported instead of a metric summarizing the time-to-event data with unit of time, as the numbers resulting from the Kaplan-Meier-analysis were even below the first quartile.
Time frame: From first drug administration until the last drug intake + 28 days REP, up to 92.6 weeks
Population: Treated set (TS): The TS consisted of participants who were randomised to a treatment group and received at least one dose of study medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| DBP+OLNP: 6 to < 12 Years - Exposed to Nintedanib | Number of Participants With Occurrence of Death Over the Whole Trial | 0 Participants |
| DBP+OLNP: 12 to <18 Years - Exposed to Nintedanib | Number of Participants With Occurrence of Death Over the Whole Trial | 0 Participants |
Secondary
Number of Participants With Occurrence of First Acute Interstitial Lung Disease (ILD) Exacerbation or Death Over the Whole Trial
Number of participants with occurrence of first acute Interstitial Lung Disease (ILD) exacerbation or death over the whole trial. The number of participants with first acute ILD exacerbation is reported instead of a metric summarizing the time-to-event data with unit of time, as the numbers resulting from the Kaplan-Meier-analysis were even below the first quartile.
Time frame: From first drug administration until the last drug intake + 28 days REP, up to 92.6 weeks
Population: Treated set (TS): The TS consisted of participants who were randomised to a treatment group and received at least one dose of study medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| DBP+OLNP: 6 to < 12 Years - Exposed to Nintedanib | Number of Participants With Occurrence of First Acute Interstitial Lung Disease (ILD) Exacerbation or Death Over the Whole Trial | 0 Participants |
| DBP+OLNP: 12 to <18 Years - Exposed to Nintedanib | Number of Participants With Occurrence of First Acute Interstitial Lung Disease (ILD) Exacerbation or Death Over the Whole Trial | 2 Participants |
Secondary
Number of Participants With Occurrence of First Respiratory-related Hospitalization Over the Whole Trial
Number of participants with occurrence of first respiratory-related hospitalization over the whole trial. The number of participants with first respiratory-related hospitalization is reported instead of a metric summarizing the time-to-event data with unit of time, as the numbers resulting from the Kaplan-Meier-analysis were even below the first quartile.
Time frame: From first drug administration until the last drug intake + 28 days residual effect period (REP), up to 92.6 weeks
Population: Treated set (TS): The TS consisted of participants who were randomised to a treatment group and received at least one dose of study medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| DBP+OLNP: 6 to < 12 Years - Exposed to Nintedanib | Number of Participants With Occurrence of First Respiratory-related Hospitalization Over the Whole Trial | 0 Participants |
| DBP+OLNP: 12 to <18 Years - Exposed to Nintedanib | Number of Participants With Occurrence of First Respiratory-related Hospitalization Over the Whole Trial | 3 Participants |
Secondary
Number of Participants With Treatment-emergent Adverse Events Over the Whole Trial
Treatment-emergent was defined as: Adverse events with onset or worsening on or after date of treatment start until last drug intake + residual effect period was considered as treatment-emergent and was included in the analysis. Adverse events were counted under the treatment as randomized for the double-blind period.
Time frame: From first drug administration until the last drug intake, up to 92 weeks
Population: Treated set (TS): The TS consisted of participants who were randomised to a treatment group and received at least one dose of study medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| DBP+OLNP: 6 to < 12 Years - Exposed to Nintedanib | Number of Participants With Treatment-emergent Adverse Events Over the Whole Trial | 11 Participants |
| DBP+OLNP: 12 to <18 Years - Exposed to Nintedanib | Number of Participants With Treatment-emergent Adverse Events Over the Whole Trial | 11 Participants |
| DBP+OLNP: Randomised to Nintedanib | Number of Participants With Treatment-emergent Adverse Events Over the Whole Trial | 26 Participants |
Secondary
Number of Participants With Treatment-emergent Pathological Findings on Dental Examination or Imaging up to Week 24
Number of participants with treatment-emergent pathological findings on dental examination (clinical examination) based on dentist assessment or imaging (panoramic x-ray) based on central review were analyzed. Number of participants with treatment-emergent pathological findings on dental imaging were analyzed cumulatively.
Time frame: Dental examination: at Week 12 and Week 24; Dental imaging: at Week 24
Population: Treated set (TS): The TS consisted of participants who were randomised to a treatment group and received at least one dose of study medication.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| DBP+OLNP: 6 to < 12 Years - Exposed to Nintedanib | Number of Participants With Treatment-emergent Pathological Findings on Dental Examination or Imaging up to Week 24 | Dental imaging: Accelerated growth of dental root | 0 Participants |
| DBP+OLNP: 6 to < 12 Years - Exposed to Nintedanib | Number of Participants With Treatment-emergent Pathological Findings on Dental Examination or Imaging up to Week 24 | Dental imaging: Impacted permanent teeth | 2 Participants |
| DBP+OLNP: 6 to < 12 Years - Exposed to Nintedanib | Number of Participants With Treatment-emergent Pathological Findings on Dental Examination or Imaging up to Week 24 | Dental imaging: Stunted growth of dental root | 0 Participants |
| DBP+OLNP: 6 to < 12 Years - Exposed to Nintedanib | Number of Participants With Treatment-emergent Pathological Findings on Dental Examination or Imaging up to Week 24 | Dental imaging: Additional findings | 1 Participants |
| DBP+OLNP: 6 to < 12 Years - Exposed to Nintedanib | Number of Participants With Treatment-emergent Pathological Findings on Dental Examination or Imaging up to Week 24 | Dental imaging: extra / supernumerary teeth | 0 Participants |
| DBP+OLNP: 6 to < 12 Years - Exposed to Nintedanib | Number of Participants With Treatment-emergent Pathological Findings on Dental Examination or Imaging up to Week 24 | Dental imaging: Other findings | 2 Participants |
| DBP+OLNP: 6 to < 12 Years - Exposed to Nintedanib | Number of Participants With Treatment-emergent Pathological Findings on Dental Examination or Imaging up to Week 24 | Dental examination: Pathological findings up to week 24 | 1 Participants |
| DBP+OLNP: 12 to <18 Years - Exposed to Nintedanib | Number of Participants With Treatment-emergent Pathological Findings on Dental Examination or Imaging up to Week 24 | Dental imaging: Other findings | 1 Participants |
| DBP+OLNP: 12 to <18 Years - Exposed to Nintedanib | Number of Participants With Treatment-emergent Pathological Findings on Dental Examination or Imaging up to Week 24 | Dental examination: Pathological findings up to week 24 | 5 Participants |
| DBP+OLNP: 12 to <18 Years - Exposed to Nintedanib | Number of Participants With Treatment-emergent Pathological Findings on Dental Examination or Imaging up to Week 24 | Dental imaging: Stunted growth of dental root | 6 Participants |
| DBP+OLNP: 12 to <18 Years - Exposed to Nintedanib | Number of Participants With Treatment-emergent Pathological Findings on Dental Examination or Imaging up to Week 24 | Dental imaging: Accelerated growth of dental root | 0 Participants |
| DBP+OLNP: 12 to <18 Years - Exposed to Nintedanib | Number of Participants With Treatment-emergent Pathological Findings on Dental Examination or Imaging up to Week 24 | Dental imaging: extra / supernumerary teeth | 0 Participants |
| DBP+OLNP: 12 to <18 Years - Exposed to Nintedanib | Number of Participants With Treatment-emergent Pathological Findings on Dental Examination or Imaging up to Week 24 | Dental imaging: Impacted permanent teeth | 4 Participants |
| DBP+OLNP: 12 to <18 Years - Exposed to Nintedanib | Number of Participants With Treatment-emergent Pathological Findings on Dental Examination or Imaging up to Week 24 | Dental imaging: Additional findings | 5 Participants |
Secondary
Participants Acceptability Based on the Number of Capsules at Week 24 - Patient Question
Acceptability is defined as the overall ability and willingness of the participant to use the medicinal product as intended. Acceptability based on the number of capsule was assessed by a acceptability questionnaire (1 item with 3 categories as shown below) for participants. In case the participant was considered not old enough as per investigator judgment the caregiver could assist with the completion. In addition to the commercially available 100 milligram (mg) soft capsules (oblong shape, 6 millimeter (mm) diameter and 16 mm length) and 150 mg soft capsules (oblong shape, 7 mm diameter and 18 mm length), 25 mg Nintedanib soft capsules of smaller size (oval shape, 5 mm diameter and 8 mm length) were provided in this trial for participants who were assigned to a dose smaller than 100 mg or were unable to swallow the larger 100 mg or 150 mg capsules. Medication dosage was based on the participant's body weight and number of capsules per administration ranged from 2 to \>6 capsules.
Time frame: Acceptability was assessed at Week 24
Population: Treated set (TS): The TS consisted of participants who were randomised to a treatment group and received at least one dose of study medication. Only participants with non-missing results were included in the analysis.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| DBP+OLNP: 6 to < 12 Years - Exposed to Nintedanib | Participants Acceptability Based on the Number of Capsules at Week 24 - Patient Question | I had no problem swallowing them | 7 Participants |
| DBP+OLNP: 6 to < 12 Years - Exposed to Nintedanib | Participants Acceptability Based on the Number of Capsules at Week 24 - Patient Question | I could not swallow them sometimes | 0 Participants |
| DBP+OLNP: 6 to < 12 Years - Exposed to Nintedanib | Participants Acceptability Based on the Number of Capsules at Week 24 - Patient Question | I swallowed them but it was difficult | 0 Participants |
| DBP+OLNP: 12 to <18 Years - Exposed to Nintedanib | Participants Acceptability Based on the Number of Capsules at Week 24 - Patient Question | I could not swallow them sometimes | 0 Participants |
| DBP+OLNP: 12 to <18 Years - Exposed to Nintedanib | Participants Acceptability Based on the Number of Capsules at Week 24 - Patient Question | I swallowed them but it was difficult | 0 Participants |
| DBP+OLNP: 12 to <18 Years - Exposed to Nintedanib | Participants Acceptability Based on the Number of Capsules at Week 24 - Patient Question | I had no problem swallowing them | 16 Participants |
| DBP+OLNP: Randomised to Nintedanib | Participants Acceptability Based on the Number of Capsules at Week 24 - Patient Question | I could not swallow them sometimes | 0 Participants |
| DBP+OLNP: Randomised to Nintedanib | Participants Acceptability Based on the Number of Capsules at Week 24 - Patient Question | I had no problem swallowing them | 2 Participants |
| DBP+OLNP: Randomised to Nintedanib | Participants Acceptability Based on the Number of Capsules at Week 24 - Patient Question | I swallowed them but it was difficult | 0 Participants |
| DBP: Randomised to Nintedanib - Capsule Size of 100 mg Capsule | Participants Acceptability Based on the Number of Capsules at Week 24 - Patient Question | I had no problem swallowing them | 3 Participants |
| DBP: Randomised to Nintedanib - Capsule Size of 100 mg Capsule | Participants Acceptability Based on the Number of Capsules at Week 24 - Patient Question | I swallowed them but it was difficult | 0 Participants |
| DBP: Randomised to Nintedanib - Capsule Size of 100 mg Capsule | Participants Acceptability Based on the Number of Capsules at Week 24 - Patient Question | I could not swallow them sometimes | 0 Participants |
| DBP: Randomised to Placebo - Capsule Size of 150 mg Capsule | Participants Acceptability Based on the Number of Capsules at Week 24 - Patient Question | I swallowed them but it was difficult | 0 Participants |
| DBP: Randomised to Placebo - Capsule Size of 150 mg Capsule | Participants Acceptability Based on the Number of Capsules at Week 24 - Patient Question | I had no problem swallowing them | 1 Participants |
| DBP: Randomised to Placebo - Capsule Size of 150 mg Capsule | Participants Acceptability Based on the Number of Capsules at Week 24 - Patient Question | I could not swallow them sometimes | 0 Participants |
| DBP: Randomised to Nintedanib - Capsule Size of 150 mg Capsule | Participants Acceptability Based on the Number of Capsules at Week 24 - Patient Question | I swallowed them but it was difficult | 0 Participants |
| DBP: Randomised to Nintedanib - Capsule Size of 150 mg Capsule | Participants Acceptability Based on the Number of Capsules at Week 24 - Patient Question | I had no problem swallowing them | 3 Participants |
| DBP: Randomised to Nintedanib - Capsule Size of 150 mg Capsule | Participants Acceptability Based on the Number of Capsules at Week 24 - Patient Question | I could not swallow them sometimes | 0 Participants |
| DBP: Randomised to Placebo - >6 Capsules | Participants Acceptability Based on the Number of Capsules at Week 24 - Patient Question | I swallowed them but it was difficult | 0 Participants |
| DBP: Randomised to Placebo - >6 Capsules | Participants Acceptability Based on the Number of Capsules at Week 24 - Patient Question | I had no problem swallowing them | 1 Participants |
| DBP: Randomised to Placebo - >6 Capsules | Participants Acceptability Based on the Number of Capsules at Week 24 - Patient Question | I could not swallow them sometimes | 0 Participants |
| DBP: Randomised to Nintedanib - >6 Capsules | Participants Acceptability Based on the Number of Capsules at Week 24 - Patient Question | I had no problem swallowing them | 0 Participants |
| DBP: Randomised to Nintedanib - >6 Capsules | Participants Acceptability Based on the Number of Capsules at Week 24 - Patient Question | I swallowed them but it was difficult | 0 Participants |
| DBP: Randomised to Nintedanib - >6 Capsules | Participants Acceptability Based on the Number of Capsules at Week 24 - Patient Question | I could not swallow them sometimes | 0 Participants |
Secondary
Participants Acceptability Based on the Size of Capsules at Week 24 - Investigator Question
Acceptability is defined as the overall ability and willingness of the participant to use the medicinal product as intended. Acceptability based on the capsule size was assessed by a acceptability questionnaire (1 item with 3 categories as shown below) for investigators. In addition to the commercially available 100 milligram (mg) soft capsules (oblong shape, 6 millimeter (mm) diameter and 16 mm length) and 150 mg soft capsules (oblong shape, 7 mm diameter and 18 mm length), 25 mg Nintedanib soft capsules of smaller size (oval shape, 5 mm diameter and 8 mm length) were provided in this trial for participants who were assigned to a dose smaller than 100 mg or were unable to swallow the larger 100 mg or 150 mg capsules.
Time frame: Acceptability was assessed at Week 24
Population: Treated set (TS): The TS consisted of participants who were randomised to a treatment group and received at least one dose of study medication.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| DBP+OLNP: 6 to < 12 Years - Exposed to Nintedanib | Participants Acceptability Based on the Size of Capsules at Week 24 - Investigator Question | Yes | 0 Participants |
| DBP+OLNP: 6 to < 12 Years - Exposed to Nintedanib | Participants Acceptability Based on the Size of Capsules at Week 24 - Investigator Question | Missing | 3 Participants |
| DBP+OLNP: 6 to < 12 Years - Exposed to Nintedanib | Participants Acceptability Based on the Size of Capsules at Week 24 - Investigator Question | No | 1 Participants |
| DBP+OLNP: 12 to <18 Years - Exposed to Nintedanib | Participants Acceptability Based on the Size of Capsules at Week 24 - Investigator Question | Yes | 0 Participants |
| DBP+OLNP: 12 to <18 Years - Exposed to Nintedanib | Participants Acceptability Based on the Size of Capsules at Week 24 - Investigator Question | Missing | 4 Participants |
| DBP+OLNP: 12 to <18 Years - Exposed to Nintedanib | Participants Acceptability Based on the Size of Capsules at Week 24 - Investigator Question | No | 2 Participants |
| DBP+OLNP: Randomised to Nintedanib | Participants Acceptability Based on the Size of Capsules at Week 24 - Investigator Question | Missing | 3 Participants |
| DBP+OLNP: Randomised to Nintedanib | Participants Acceptability Based on the Size of Capsules at Week 24 - Investigator Question | No | 1 Participants |
| DBP+OLNP: Randomised to Nintedanib | Participants Acceptability Based on the Size of Capsules at Week 24 - Investigator Question | Yes | 0 Participants |
| DBP: Randomised to Nintedanib - Capsule Size of 100 mg Capsule | Participants Acceptability Based on the Size of Capsules at Week 24 - Investigator Question | Yes | 0 Participants |
| DBP: Randomised to Nintedanib - Capsule Size of 100 mg Capsule | Participants Acceptability Based on the Size of Capsules at Week 24 - Investigator Question | No | 2 Participants |
| DBP: Randomised to Nintedanib - Capsule Size of 100 mg Capsule | Participants Acceptability Based on the Size of Capsules at Week 24 - Investigator Question | Missing | 12 Participants |
| DBP: Randomised to Placebo - Capsule Size of 150 mg Capsule | Participants Acceptability Based on the Size of Capsules at Week 24 - Investigator Question | Missing | 3 Participants |
| DBP: Randomised to Placebo - Capsule Size of 150 mg Capsule | Participants Acceptability Based on the Size of Capsules at Week 24 - Investigator Question | No | 0 Participants |
| DBP: Randomised to Placebo - Capsule Size of 150 mg Capsule | Participants Acceptability Based on the Size of Capsules at Week 24 - Investigator Question | Yes | 0 Participants |
| DBP: Randomised to Nintedanib - Capsule Size of 150 mg Capsule | Participants Acceptability Based on the Size of Capsules at Week 24 - Investigator Question | Yes | 0 Participants |
| DBP: Randomised to Nintedanib - Capsule Size of 150 mg Capsule | Participants Acceptability Based on the Size of Capsules at Week 24 - Investigator Question | No | 1 Participants |
| DBP: Randomised to Nintedanib - Capsule Size of 150 mg Capsule | Participants Acceptability Based on the Size of Capsules at Week 24 - Investigator Question | Missing | 1 Participants |
Secondary
Participants Acceptability Based on the Size of Capsules at Week 24 - Patient Question
Acceptability is defined as the overall ability and willingness of the participant to use the medicinal product as intended. Acceptability based on the capsule size was assessed by a acceptability questionnaire (1 item with 3 categories as shown below) for participants. In case the participant was considered not old enough as per investigator judgment the caregiver could assist with the completion. In addition to the commercially available 100 milligram (mg) soft capsules (oblong shape, 6 millimeter (mm) diameter and 16 mm length) and 150 mg soft capsules (oblong shape, 7 mm diameter and 18 mm length), 25 mg Nintedanib soft capsules of smaller size (oval shape, 5 mm diameter and 8 mm length) were provided in this trial for participants who were assigned to a dose smaller than 100 mg or were unable to swallow the larger 100 mg or 150 mg capsules.
Time frame: Acceptability was assessed at Week 24
Population: Treated set (TS): The TS consisted of participants who were randomised to a treatment group and received at least one dose of study medication. Only participants with non-missing results were included in the analysis.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| DBP+OLNP: 6 to < 12 Years - Exposed to Nintedanib | Participants Acceptability Based on the Size of Capsules at Week 24 - Patient Question | Large | 0 Participants |
| DBP+OLNP: 6 to < 12 Years - Exposed to Nintedanib | Participants Acceptability Based on the Size of Capsules at Week 24 - Patient Question | OK | 4 Participants |
| DBP+OLNP: 6 to < 12 Years - Exposed to Nintedanib | Participants Acceptability Based on the Size of Capsules at Week 24 - Patient Question | Very Large | 0 Participants |
| DBP+OLNP: 12 to <18 Years - Exposed to Nintedanib | Participants Acceptability Based on the Size of Capsules at Week 24 - Patient Question | Large | 0 Participants |
| DBP+OLNP: 12 to <18 Years - Exposed to Nintedanib | Participants Acceptability Based on the Size of Capsules at Week 24 - Patient Question | OK | 6 Participants |
| DBP+OLNP: 12 to <18 Years - Exposed to Nintedanib | Participants Acceptability Based on the Size of Capsules at Week 24 - Patient Question | Very Large | 0 Participants |
| DBP+OLNP: Randomised to Nintedanib | Participants Acceptability Based on the Size of Capsules at Week 24 - Patient Question | Large | 0 Participants |
| DBP+OLNP: Randomised to Nintedanib | Participants Acceptability Based on the Size of Capsules at Week 24 - Patient Question | OK | 4 Participants |
| DBP+OLNP: Randomised to Nintedanib | Participants Acceptability Based on the Size of Capsules at Week 24 - Patient Question | Very Large | 0 Participants |
| DBP: Randomised to Nintedanib - Capsule Size of 100 mg Capsule | Participants Acceptability Based on the Size of Capsules at Week 24 - Patient Question | Large | 0 Participants |
| DBP: Randomised to Nintedanib - Capsule Size of 100 mg Capsule | Participants Acceptability Based on the Size of Capsules at Week 24 - Patient Question | OK | 14 Participants |
| DBP: Randomised to Nintedanib - Capsule Size of 100 mg Capsule | Participants Acceptability Based on the Size of Capsules at Week 24 - Patient Question | Very Large | 0 Participants |
| DBP: Randomised to Placebo - Capsule Size of 150 mg Capsule | Participants Acceptability Based on the Size of Capsules at Week 24 - Patient Question | Large | 0 Participants |
| DBP: Randomised to Placebo - Capsule Size of 150 mg Capsule | Participants Acceptability Based on the Size of Capsules at Week 24 - Patient Question | OK | 3 Participants |
| DBP: Randomised to Placebo - Capsule Size of 150 mg Capsule | Participants Acceptability Based on the Size of Capsules at Week 24 - Patient Question | Very Large | 0 Participants |
| DBP: Randomised to Nintedanib - Capsule Size of 150 mg Capsule | Participants Acceptability Based on the Size of Capsules at Week 24 - Patient Question | OK | 2 Participants |
| DBP: Randomised to Nintedanib - Capsule Size of 150 mg Capsule | Participants Acceptability Based on the Size of Capsules at Week 24 - Patient Question | Very Large | 0 Participants |
| DBP: Randomised to Nintedanib - Capsule Size of 150 mg Capsule | Participants Acceptability Based on the Size of Capsules at Week 24 - Patient Question | Large | 0 Participants |