A Study in Healthy Men to Find the Best Formulation for Once Daily Intake of Nintedanib
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)
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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Nottingham, United Kingdom, NG11 6JS
- Quotient Sciences
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
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Experimental: Cohort 1
Each participant received: Nintedanib formulation 1: Monolithic Nintedanib Modified Release Tablet (MR1) as two Prototypes (MR1-1 and MR1-2), compared to the reference (R) treatment: Nintedanib formulation 3: Ofev®.
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Ofev®
Other Names:
Nintedanib formulation 1: Monolithic Nintedanib Modified Release Tablet (MR1) as two Prototypes (MR1-1 and MR1-2).
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Experimental: Cohort 2
Nintedanib formulation 2: Polyox Nintedanib Modified Release Tablet (MR2) as two Prototypes (MR2-1 and MR2-2) compared to the reference (R) treatment: Nintedanib formulation 3: Ofev®.
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Ofev®
Other Names:
Nintedanib formulation 2: Polyox Nintedanib Modified Release Tablet (MR2) as two Prototypes (MR2-1 and MR2-2).
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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Area Under the Concentration-time Curve of 3 Different Formulations of Nintedanib (MR1, MR2 and Ofev®) in Plasma Over the Time Interval From 0 Extrapolated to Infinity Which Includes Also the Second Nintedanib (Ofev®) Dose of the Day (AUC₀-∞)
Time Frame: Within 3 hours (h) prior and 1, 2, 3, 4, 6, 8, 10, 12, 13 (except MR1, MR2), 14, 15, 16, 17 (except R), 18, 20, 22, 24, 34, 48, 58, and 72 h after administration.
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The area under the concentration-time curve over the time interval from 0 [first dose] extrapolated to infinity (AUC₀-∞) was analyzed in 3 different formulations of Nintedanib (MR1, MR2 and Ofev®) and in two cohorts:
The adjusted geometric least squares mean and adjusted geometric standard error were calculated by an analysis of variance (ANOVA) model on the logarithmic scale. |
Within 3 hours (h) prior and 1, 2, 3, 4, 6, 8, 10, 12, 13 (except MR1, MR2), 14, 15, 16, 17 (except R), 18, 20, 22, 24, 34, 48, 58, and 72 h after administration.
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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Area Under the Concentration-time Curve of 3 Different Formulations of Nintedanib (MR1, MR2 and Ofev®) in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC₀-tz)
Time Frame: Within 3 hours (h) prior and 1, 2, 3, 4, 6, 8, 10, 12, 13 (except MR1, MR2), 14, 15, 16, 17 (except R), 18, 20, 22, 24, 34, 48, 58, and 72 h after administration.
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The area under the concentration-time curve over the time interval from 0 to the last quantifiable data point (AUC₀-tz) was analyzed in 3 different formulations of Nintedanib (MR1, MR2 and Ofev®) and in two cohorts:
The adjusted geometric least squares mean and adjusted geometric standard error were calculated by an analysis of variance (ANOVA) model on the logarithmic scale. |
Within 3 hours (h) prior and 1, 2, 3, 4, 6, 8, 10, 12, 13 (except MR1, MR2), 14, 15, 16, 17 (except R), 18, 20, 22, 24, 34, 48, 58, and 72 h after administration.
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Maximum Measured Concentration of 3 Different Formulations of Nintedanib (MR1, MR2 and Ofev®) in Plasma Within the 24h Dosing Interval (Cmax)
Time Frame: Within 3 hours (h) prior and 1.0, 2.0, 3.0, 4.0, 6.0, 8.0, 10.0, 12.0, 13.0 (except MR1, MR2), 14.0, 15.0, 16.0, 17.0 (except R), 18.0, 20.0, 22.0, 24.0, 34.0, 48.0, 58.0, and 72 h after administration
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The maximum measured concentration in plasma was analyzed in 3 different formulations of Nintedanib (MR1, MR2 and Ofev®) and in two cohorts:
The adjusted geometric least squares mean and adjusted geometric standard error were calculated by an analysis of variance (ANOVA) model on the logarithmic scale. |
Within 3 hours (h) prior and 1.0, 2.0, 3.0, 4.0, 6.0, 8.0, 10.0, 12.0, 13.0 (except MR1, MR2), 14.0, 15.0, 16.0, 17.0 (except R), 18.0, 20.0, 22.0, 24.0, 34.0, 48.0, 58.0, and 72 h after administration
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Concentration of 3 Different Formulations of Nintedanib (MR1, MR2 and Ofev®) in Plasma 24 Hours After the First Dose (C₂₄)
Time Frame: Within 3 hours (h) prior and 1, 2, 3, 4, 6, 8, 10, 12, 13 (except MR1, MR2), 14, 15, 16, 17 (except R), 18, 20, 22, 24, 34, 48, 58, and 72 h after administration.
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The measured concentration in plasma 24 hours after first administration was analyzed in 3 different formulations of Nintedanib (MR1, MR2 and Ofev®) and in two cohorts:
The adjusted geometric least squares mean and adjusted geometric standard error were calculated by an analysis of variance (ANOVA) model on the logarithmic scale. |
Within 3 hours (h) prior and 1, 2, 3, 4, 6, 8, 10, 12, 13 (except MR1, MR2), 14, 15, 16, 17 (except R), 18, 20, 22, 24, 34, 48, 58, and 72 h after administration.
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Collaborators and Investigators
Sponsor
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 1199-0452
- 2021-003152-16 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents. Exceptions might apply, e.g. studies in products where Boehringer Ingelheim is not the license holder; studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; studies conducted in a single center or targeting rare diseases (in case of low number of patients and therefore limitations with anonymization).
For more details refer to:
https://www.mystudywindow.com/msw/datatransparency
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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