A Study in Healthy Men to Find the Best Formulation for Once Daily Intake of Nintedanib

Study Overview
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Brief Summary
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The main objective of this trial is to assess single dose drug exposure of several newly developed formulation prototypes of Nintedanib compared to Ofev® following oral administration.

Official Title
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A Phase I Study for Formulation Selection and Subsequent Optimization of Two Different Oral Formulations of Nintedanib in Healthy Male Subjects (Open-label, Randomised, Single-dose Study in Three Parts)

Conditions
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Healthy

Intervention / Treatment
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* Drug: Ofev®
* Drug: Nintedanib formulation 1
* Drug: Nintedanib formulation 2


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male subjects (Caucasian and Black only) according to the investigator's assessment, based on a complete medical history including a physical examination, vital signs (blood pressure (BP), pulse rate (PR)), 12-lead electrocardiograms (ECG) and clinical laboratory tests. Age of 18 to 55 years (inclusive). Body mass index (BMI) of 18.5 to 29.9 kg/m2 (inclusive) and absolute body weight of at least 65 kg. Signed and dated written informed consent prior to admission to the study, in accordance with Good Clinical Practice (GCP) and local legislation. Non-smokers for at least 6 months. Subjects who are sexually active must use with their partner, highly effective contraception from the time of administration of trial medication until 30 days after administration of trial medication. Adequate methods are: Condoms plus use of hormonal contraception by the female partner that started at least 2 months prior to administration of trial medication (e.g., implants, injectables, combined oral or vaginal contraceptives, intrauterine device) or; Condoms plus surgical sterilization (vasectomy at least 1 year prior to enrolment) or; Condoms plus surgically sterilised partner (including hysterectomy) or; Condoms plus intrauterine device or; Condoms plus partner of non-childbearing potential (including homosexual men). Subjects are required to use condoms to prevent unintended exposure of the partner (both, male and female) to the study drug via seminal fluid. Male subjects should use a condom throughout the study and for 30 days after last Investigational Medicinal Product (IMP) administration. Alternatively, true abstinence is acceptable when it is in line with the subject's preferred and usual lifestyle. If a subject is usually not sexually active but becomes active with their partner, they must comply with the contraceptive requirements detailed above. Male subjects should not donate sperm for the duration of the study and for at least 30 days after last IMP administration. Male subjects with pregnant or lactating partners are allowed. Exclusion Criteria: Any finding in the medical examination (including BP, PR or ECG) deviating from normal and assessed as clinically relevant by the investigator. Repeated measurement of systolic blood pressure outside the range of 90 to 140 millimetre of mercury (mmHg), diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate outside the range of 45 to 90 beats per minute (bpm). Any laboratory value outside the reference range that the investigator considers to be of clinical relevance. Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) antibody results. Liver enzymes (Aspartate amino transferase (AST) and Alanine amino transferase (ALT)) above upper limit of normal at the screening examination. Any evidence of a concomitant disease assessed as clinically relevant by the investigator. Clinically significant gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological, dermatological or hormonal disorders. Subjects with Gilbert's syndrome are not permitted. Cholecystectomy or other surgery of the gastrointestinal tract that could interfere with the pharmacokinetics of the trial medication (except appendectomy or simple hernia repair). Further exclusion criteria apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part IA - Nintedanib formulation 1, OFEV® (Reference (R))<br> | Drug: Ofev®<br>* Ofev®<br>* Other names: Nintedanib;Drug: Nintedanib formulation 1<br>* Nintedanib formulation 1<br>Drug: Nintedanib formulation 2<br>* Nintedanib formulation 2<br>|
| Experimental: Part IB - Nintedanib formulation 2, R<br> | Drug: Ofev®<br>* Ofev®<br>* Other names: Nintedanib;Drug: Nintedanib formulation 1<br>* Nintedanib formulation 1<br>Drug: Nintedanib formulation 2<br>* Nintedanib formulation 2<br>|
| Experimental: Part II - Nintedanib formulation 1, nintedanib formulation 2, R<br> | Drug: Ofev®<br>* Ofev®<br>* Other names: Nintedanib;Drug: Nintedanib formulation 1<br>* Nintedanib formulation 1<br>Drug: Nintedanib formulation 2<br>* Nintedanib formulation 2<br>|
| Experimental: Part III - Nintedanib formulation 1/nintedanib formulation 2, R<br> | Drug: Ofev®<br>* Ofev®<br>* Other names: Nintedanib;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the concentration-time curve of the analyte in plasma over the time interval from 0 [first dose] extrapolated to infinity which includes also the second Nintedanib dose of the day (AUC0-∞) |  | up to 72 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) |  | up to 72 hours | 
| Maximum measured concentration of the analyte in plasma within the 24h dosing interval (Cmax) |  | up to 24 hours | 
| Concentration of the analyte in plasma 24 h after the (first) dose (C24) |  | up to 24 hours |