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

NCT05262751 | Completed Phase 1 Results

• 2 other identifiers: 1199-04522021-003152-16
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy

Outcome Measures

Primary Outcomes (1)

• 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-∞)

  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: * Cohort 1: Nintedanib formulation 1: Monolithic Nintedanib Modified Release Tablet (MR1) as two Prototypes (MR1-1 and MR1-2), * Cohort 2: Nintedanib formulation 2: Polyox Nintedanib Modified Release Tablet (MR2) as two Prototypes (MR2-1 and MR2-2), and each compared to the reference (R) treatment: Nintedanib formulation 3: Ofev® capsules. 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.

Secondary Outcomes (3)

• 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)

  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.

• Maximum Measured Concentration of 3 Different Formulations of Nintedanib (MR1, MR2 and Ofev®) in Plasma Within the 24h Dosing Interval (Cmax)

  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

• Concentration of 3 Different Formulations of Nintedanib (MR1, MR2 and Ofev®) in Plasma 24 Hours After the First Dose (C₂₄)

  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.

Study Arms (2)

Cohort 1

EXPERIMENTAL

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®.

Drug: Ofev®; Drug: Nintedanib formulation 1

Cohort 2

EXPERIMENTAL

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®.

Drug: Ofev®; Drug: Nintedanib formulation 2

Interventions

Ofev® DRUG

Ofev®

Also known as: Nintedanib

Cohort 1; Cohort 2

Nintedanib formulation 1 DRUG

Nintedanib formulation 1: Monolithic Nintedanib Modified Release Tablet (MR1) as two Prototypes (MR1-1 and MR1-2).

Cohort 1

Nintedanib formulation 2 DRUG

Nintedanib formulation 2: Polyox Nintedanib Modified Release Tablet (MR2) as two Prototypes (MR2-1 and MR2-2).

Cohort 2

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (1)

Quotient Sciences

Nottingham, NG11 6JS, United Kingdom

Location

Related Links

• Related Info

MeSH Terms

Interventions

nintedanib

Limitations and Caveats

As per protocol Parts 2 and 3 were not performed. The trial was stopped as per protocol during trial Part 1.

Results Point of Contact

• Title: Boehringer Ingelheim, Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 1, 2022
• First Posted: March 2, 2022
• Study Start: March 28, 2022
• Primary Completion: November 30, 2022
• Study Completion: November 30, 2022
• Last Updated: May 29, 2024
• Results First Posted: May 29, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)