Trial Outcomes & Findings for A Study in Healthy Men to Find the Best Formulation for Once Daily Intake of Nintedanib (NCT NCT05262751)
NCT ID: NCT05262751
Last Updated: 2024-05-29
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
21 participants
Primary outcome timeframe
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.
Results posted on
2024-05-29
Participant Flow
This trial was a randomised, open-label, crossover, single-dose (once daily \[qd\] for test and twice daily \[bid\] for reference treatment) study in up to 3 parts; trial part 1: 2 parallel groups (Cohort 1, Cohort 2), each a randomised three-period crossover; trial part 2 (optional): one group of randomised three-period crossover; trial part 3 (optional): one group of randomised two-period crossover. Parts 2 and 3 were not performed. The trial was stopped as per protocol during trial part 1.
Only participants 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. Rescue medication was allowed for all participants as required.
Participant milestones
| Measure |
Cohort 1: R | MR1-1 | MR1-2
In this arm participants were treated at 3 treatment visits (= 3 treatment periods). There was a washout period of at least 14 days between each treatment visit, i.e. the morning dose in the preceding treatment period and the morning dose in the following treatment period were separated by at least 14 days.
Treatments:
* First: R, a low oral dose of Ofev® capsule bid with 240 milliliter (ml) of water after a light breakfast and dinner, respectively;
* Second: MR1-1, a single medium oral dose of Nintedanib MR1-1 tablet with 240 ml water in the morning after a light breakfast;
* Third: MR1-2, a single medium oral dose of Nintedanib MR1-2 tablet with 240 ml water in the morning after a light breakfast.
Abbreviations:
R=Reference=Ofev® capsules, MR1-1=Monolithic Nintedanib Modified Release Prototype 1 Tablet, MR1-2=Monolithic Nintedanib Modified Release Prototype 2 Tablet.
|
Cohort 1: MR1-2 | R | MR1-1
In this arm participants were treated at 3 treatment visits (= 3 treatment periods). There was a washout period of at least 14 days between each treatment visit, i.e. the morning dose in the preceding treatment period and the morning dose in the following treatment period were separated by at least 14 days.
Treatments:
* First: MR1-2, a single medium oral dose of Nintedanib MR1-2 tablet with 240 ml water in the morning after a light breakfast;
* Second: R, a low oral dose of Ofev® capsule bid with 240 ml of water after a light breakfast and dinner, respectively;
* Third: MR1-1, a single medium oral dose of Nintedanib MR1-1 tablet with 240 ml water in the morning after a light breakfast.
|
Cohort 1: MR1-1 | MR1-2 | R
In this arm participants were treated at 3 treatment visits (= 3 treatment periods). There was a washout period of at least 14 days between each treatment visit, i.e. the morning dose in the preceding treatment period and the morning dose in the following treatment period were separated by at least 14 days.
Treatments:
* First: MR1-1, a single medium oral dose of Nintedanib MR1-1 tablet with 240 ml water in the morning after a light breakfast;
* Second: MR1-2, a single medium oral dose of Nintedanib MR1-2 tablet with 240 ml water in the morning after a light breakfast;
* Third: R, a low oral dose of Ofev® capsule bid with 240 ml of water after a light breakfast and dinner, respectively.
|
Cohort 2: R | MR2-1 | MR2-2
In this arm participants were treated at 3 treatment visits (= 3 treatment periods). There was a washout period of at least 14 days between each treatment visit, i.e. the morning dose in the preceding treatment period and the morning dose in the following treatment period were separated by at least 14 days.
Treatments:
* First: R, a low oral dose of Ofev® capsule bid with 240 ml of water after a light breakfast and dinner, respectively;
* Second: MR2-1, a single medium oral dose of Nintedanib MR2-1 tablet with 240 ml water in the morning after a light breakfast;
* Third: MR2-2, a single medium oral dose of Nintedanib MR2-2 tablet with 240 ml water in the morning after a light breakfast.
Abbreviations:
R=Reference=Ofev® capsules, MR2-1=Polyox Nintedanib Modified Release Prototype 1 Tablet, MR2-2=Polyox Nintedanib Modified Release Prototype 2 Tablet.
|
Cohort 2: MR2-2 | R | MR2-1
In this arm participants were treated at 3 treatment visits (= 3 treatment periods). There was a washout period of at least 14 days between each treatment visit, i.e. the morning dose in the preceding treatment period and the morning dose in the following treatment period were separated by at least 14 days.
Treatments:
* First: MR2-2, a single medium oral dose of Nintedanib MR2-2 tablet with 240 ml water in the morning after a light breakfast;
* Second: R, a low oral dose of Ofev® capsule bid with 240 ml of water after a light breakfast and dinner, respectively;
* Third: MR2-1, a single medium oral dose of Nintedanib MR2-1 tablet with 240 ml water in the morning after a light breakfast.
|
Cohort 2: MR2-1 | MR2-2 | R
In this arm participants were treated at 3 treatment visits (= 3 treatment periods). There was a washout period of at least 14 days between each treatment visit, i.e. the morning dose in the preceding treatment period and the morning dose in the following treatment period were separated by at least 14 days.
Treatments:
* First: MR2-1, a single medium oral dose of Nintedanib MR2-1 tablet with 240 ml water in the morning after a light breakfast;
* Second: MR2-2, a single medium oral dose of Nintedanib MR2-2 tablet with 240 ml water in the morning after a light breakfast;
* Third: R, a low oral dose of Ofev® capsule bid with 240 ml of water after a light breakfast and dinner, respectively.
|
|---|---|---|---|---|---|---|
|
Treatment Period 1
STARTED
|
3
|
2
|
2
|
5
|
5
|
4
|
|
Treatment Period 1
COMPLETED
|
3
|
2
|
2
|
5
|
5
|
4
|
|
Treatment Period 1
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Washout Period 1
STARTED
|
3
|
2
|
2
|
5
|
5
|
4
|
|
Washout Period 1
COMPLETED
|
3
|
2
|
2
|
5
|
5
|
4
|
|
Washout Period 1
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Treatment Period 2
STARTED
|
3
|
2
|
2
|
5
|
5
|
4
|
|
Treatment Period 2
COMPLETED
|
3
|
2
|
2
|
5
|
5
|
4
|
|
Treatment Period 2
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Washout Period 2
STARTED
|
3
|
2
|
2
|
5
|
5
|
4
|
|
Washout Period 2
COMPLETED
|
2
|
2
|
2
|
5
|
5
|
4
|
|
Washout Period 2
NOT COMPLETED
|
1
|
0
|
0
|
0
|
0
|
0
|
|
Treatment Period 3
STARTED
|
2
|
2
|
2
|
5
|
5
|
4
|
|
Treatment Period 3
Treated
|
2
|
1
|
2
|
5
|
5
|
4
|
|
Treatment Period 3
COMPLETED
|
2
|
1
|
2
|
5
|
5
|
4
|
|
Treatment Period 3
NOT COMPLETED
|
0
|
1
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Cohort 1: R | MR1-1 | MR1-2
In this arm participants were treated at 3 treatment visits (= 3 treatment periods). There was a washout period of at least 14 days between each treatment visit, i.e. the morning dose in the preceding treatment period and the morning dose in the following treatment period were separated by at least 14 days.
Treatments:
* First: R, a low oral dose of Ofev® capsule bid with 240 milliliter (ml) of water after a light breakfast and dinner, respectively;
* Second: MR1-1, a single medium oral dose of Nintedanib MR1-1 tablet with 240 ml water in the morning after a light breakfast;
* Third: MR1-2, a single medium oral dose of Nintedanib MR1-2 tablet with 240 ml water in the morning after a light breakfast.
Abbreviations:
R=Reference=Ofev® capsules, MR1-1=Monolithic Nintedanib Modified Release Prototype 1 Tablet, MR1-2=Monolithic Nintedanib Modified Release Prototype 2 Tablet.
|
Cohort 1: MR1-2 | R | MR1-1
In this arm participants were treated at 3 treatment visits (= 3 treatment periods). There was a washout period of at least 14 days between each treatment visit, i.e. the morning dose in the preceding treatment period and the morning dose in the following treatment period were separated by at least 14 days.
Treatments:
* First: MR1-2, a single medium oral dose of Nintedanib MR1-2 tablet with 240 ml water in the morning after a light breakfast;
* Second: R, a low oral dose of Ofev® capsule bid with 240 ml of water after a light breakfast and dinner, respectively;
* Third: MR1-1, a single medium oral dose of Nintedanib MR1-1 tablet with 240 ml water in the morning after a light breakfast.
|
Cohort 1: MR1-1 | MR1-2 | R
In this arm participants were treated at 3 treatment visits (= 3 treatment periods). There was a washout period of at least 14 days between each treatment visit, i.e. the morning dose in the preceding treatment period and the morning dose in the following treatment period were separated by at least 14 days.
Treatments:
* First: MR1-1, a single medium oral dose of Nintedanib MR1-1 tablet with 240 ml water in the morning after a light breakfast;
* Second: MR1-2, a single medium oral dose of Nintedanib MR1-2 tablet with 240 ml water in the morning after a light breakfast;
* Third: R, a low oral dose of Ofev® capsule bid with 240 ml of water after a light breakfast and dinner, respectively.
|
Cohort 2: R | MR2-1 | MR2-2
In this arm participants were treated at 3 treatment visits (= 3 treatment periods). There was a washout period of at least 14 days between each treatment visit, i.e. the morning dose in the preceding treatment period and the morning dose in the following treatment period were separated by at least 14 days.
Treatments:
* First: R, a low oral dose of Ofev® capsule bid with 240 ml of water after a light breakfast and dinner, respectively;
* Second: MR2-1, a single medium oral dose of Nintedanib MR2-1 tablet with 240 ml water in the morning after a light breakfast;
* Third: MR2-2, a single medium oral dose of Nintedanib MR2-2 tablet with 240 ml water in the morning after a light breakfast.
Abbreviations:
R=Reference=Ofev® capsules, MR2-1=Polyox Nintedanib Modified Release Prototype 1 Tablet, MR2-2=Polyox Nintedanib Modified Release Prototype 2 Tablet.
|
Cohort 2: MR2-2 | R | MR2-1
In this arm participants were treated at 3 treatment visits (= 3 treatment periods). There was a washout period of at least 14 days between each treatment visit, i.e. the morning dose in the preceding treatment period and the morning dose in the following treatment period were separated by at least 14 days.
Treatments:
* First: MR2-2, a single medium oral dose of Nintedanib MR2-2 tablet with 240 ml water in the morning after a light breakfast;
* Second: R, a low oral dose of Ofev® capsule bid with 240 ml of water after a light breakfast and dinner, respectively;
* Third: MR2-1, a single medium oral dose of Nintedanib MR2-1 tablet with 240 ml water in the morning after a light breakfast.
|
Cohort 2: MR2-1 | MR2-2 | R
In this arm participants were treated at 3 treatment visits (= 3 treatment periods). There was a washout period of at least 14 days between each treatment visit, i.e. the morning dose in the preceding treatment period and the morning dose in the following treatment period were separated by at least 14 days.
Treatments:
* First: MR2-1, a single medium oral dose of Nintedanib MR2-1 tablet with 240 ml water in the morning after a light breakfast;
* Second: MR2-2, a single medium oral dose of Nintedanib MR2-2 tablet with 240 ml water in the morning after a light breakfast;
* Third: R, a low oral dose of Ofev® capsule bid with 240 ml of water after a light breakfast and dinner, respectively.
|
|---|---|---|---|---|---|---|
|
Washout Period 2
Adverse Event
|
1
|
0
|
0
|
0
|
0
|
0
|
|
Treatment Period 3
Not treated because of an adverse event
|
0
|
1
|
0
|
0
|
0
|
0
|
Baseline Characteristics
A Study in Healthy Men to Find the Best Formulation for Once Daily Intake of Nintedanib
Baseline characteristics by cohort
| Measure |
Cohort 1: R | MR1-1 | MR1-2
n=3 Participants
In this arm participants were treated at 3 treatment visits (= 3 treatment periods). There was a washout period of at least 14 days between each treatment visit, i.e. the morning dose in the preceding treatment period and the morning dose in the following treatment period were separated by at least 14 days.
Treatments:
* First: R, a low oral dose of Ofev® capsule bid with 240 milliliter (ml) of water after a light breakfast and dinner, respectively;
* Second: MR1-1, a single medium oral dose of Nintedanib MR1-1 tablet with 240 ml water in the morning after a light breakfast;
* Third: MR1-2, a single medium oral dose of Nintedanib MR1-2 tablet with 240 ml water in the morning after a light breakfast.
Abbreviations:
R=Reference=Ofev® capsules, MR1-1=Monolithic Nintedanib Modified Release Prototype 1 Tablet, MR1-2=Monolithic Nintedanib Modified Release Prototype 2 Tablet.
|
Cohort 1: MR1-2 | R | MR1-1
n=2 Participants
In this arm participants were treated at 3 treatment visits (= 3 treatment periods). There was a washout period of at least 14 days between each treatment visit, i.e. the morning dose in the preceding treatment period and the morning dose in the following treatment period were separated by at least 14 days.
Treatments:
* First: MR1-2, a single medium oral dose of Nintedanib MR1-2 tablet with 240 ml water in the morning after a light breakfast;
* Second: R, a low oral dose of Ofev® capsule bid with 240 ml of water after a light breakfast and dinner, respectively;
* Third: MR1-1, a single medium oral dose of Nintedanib MR1-1 tablet with 240 ml water in the morning after a light breakfast.
|
Cohort 1: MR1-1 | MR1-2 | R
n=2 Participants
In this arm participants were treated at 3 treatment visits (= 3 treatment periods). There was a washout period of at least 14 days between each treatment visit, i.e. the morning dose in the preceding treatment period and the morning dose in the following treatment period were separated by at least 14 days.
Treatments:
* First: MR1-1, a single medium oral dose of Nintedanib MR1-1 tablet with 240 ml water in the morning after a light breakfast;
* Second: MR1-2, a single medium oral dose of Nintedanib MR1-2 tablet with 240 ml water in the morning after a light breakfast;
* Third: R, a low oral dose of Ofev® capsule bid with 240 ml of water after a light breakfast and dinner, respectively.
|
Cohort 2: R | MR2-1 | MR2-2
n=5 Participants
In this arm participants were treated at 3 treatment visits (= 3 treatment periods). There was a washout period of at least 14 days between each treatment visit, i.e. the morning dose in the preceding treatment period and the morning dose in the following treatment period were separated by at least 14 days.
Treatments:
* First: R, a low oral dose of Ofev® capsule bid with 240 ml of water after a light breakfast and dinner, respectively;
* Second: MR2-1, a single medium oral dose of Nintedanib MR2-1 tablet with 240 ml water in the morning after a light breakfast;
* Third: MR2-2, a single medium oral dose of Nintedanib MR2-2 tablet with 240 ml water in the morning after a light breakfast.
Abbreviations:
R=Reference=Ofev® capsules, MR2-1=Polyox Nintedanib Modified Release Prototype 1 Tablet, MR2-2=Polyox Nintedanib Modified Release Prototype 2 Tablet.
|
Cohort 2: MR2-2 | R | MR2-1
n=5 Participants
In this arm participants were treated at 3 treatment visits (= 3 treatment periods). There was a washout period of at least 14 days between each treatment visit, i.e. the morning dose in the preceding treatment period and the morning dose in the following treatment period were separated by at least 14 days.
Treatments:
* First: MR2-2, a single medium oral dose of Nintedanib MR2-2 tablet with 240 ml water in the morning after a light breakfast;
* Second: R, a low oral dose of Ofev® capsule bid with 240 ml of water after a light breakfast and dinner, respectively;
* Third: MR2-1, a single medium oral dose of Nintedanib MR2-1 tablet with 240 ml water in the morning after a light breakfast.
|
Cohort 2: MR2-1 | MR2-2 | R
n=4 Participants
In this arm participants were treated at 3 treatment visits (= 3 treatment periods). There was a washout period of at least 14 days between each treatment visit, i.e. the morning dose in the preceding treatment period and the morning dose in the following treatment period were separated by at least 14 days.
Treatments:
* First: MR2-1, a single medium oral dose of Nintedanib MR2-1 tablet with 240 ml water in the morning after a light breakfast;
* Second: MR2-2, a single medium oral dose of Nintedanib MR2-2 tablet with 240 ml water in the morning after a light breakfast;
* Third: R, a low oral dose of Ofev® capsule bid with 240 ml of water after a light breakfast and dinner, respectively.
|
Total
n=21 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|
|
Age, Continuous
|
42.7 Years
STANDARD_DEVIATION 16.2 • n=5 Participants
|
36.5 Years
STANDARD_DEVIATION 20.5 • n=7 Participants
|
44.5 Years
STANDARD_DEVIATION 7.8 • n=5 Participants
|
35.8 Years
STANDARD_DEVIATION 8.6 • n=4 Participants
|
32.2 Years
STANDARD_DEVIATION 9.2 • n=21 Participants
|
34.5 Years
STANDARD_DEVIATION 11.6 • n=8 Participants
|
36.6 Years
STANDARD_DEVIATION 10.9 • n=8 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
5 Participants
n=21 Participants
|
4 Participants
n=8 Participants
|
21 Participants
n=8 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
5 Participants
n=21 Participants
|
4 Participants
n=8 Participants
|
21 Participants
n=8 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
1 Participants
n=8 Participants
|
|
Race (NIH/OMB)
White
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
4 Participants
n=21 Participants
|
4 Participants
n=8 Participants
|
19 Participants
n=8 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
1 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
PRIMARY outcome
Timeframe: 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.Population: Pharmacokinetic (PK) parameter analysis set (PKS): This set includes all subjects in the treated set (TS) who provide at least one PK endpoint that was defined as primary or secondary and was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. Only subjects with available PK data were included in this analysis.
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.
Outcome measures
| Measure |
Cohort 1: Reference (R)
n=7 Participants
A low oral dose of Ofev® (Reference (R)) capsule bid was administered with 240 millilitre (ml) of water after a light breakfast and dinner, respectively on one day.
|
Cohort 1: Test Treatment 1 (MR1-1)
n=3 Participants
A single medium oral dose of Monolithic Nintedanib Modified Release Prototype 1 Tablet (MR1-1) was administered with 240 ml water in the morning after a light breakfast on one day.
|
Cohort 1: Test Treatment 2 (MR1-2)
n=4 Participants
A single medium oral dose of Monolithic Nintedanib Modified Release Prototype 2 Tablet (MR1-2) was administered with 240 ml water in the morning after a light breakfast on one day.
|
Cohort 2: Reference (R)
n=13 Participants
A low oral dose of Ofev® capsule (R) bid was administered with 240 ml of water after a light breakfast and dinner, respectively on one day.
|
Cohort 2: Test Treatment 1 (MR2-1)
n=12 Participants
A single medium oral dose of Polyox Nintedanib Modified Release Prototype 1 Tablet (MR2-1) was administered with 240 ml water in the morning after a light breakfast on one day.
|
Cohort 2: Test Treatment 2 (MR2-2)
n=11 Participants
A single medium oral dose of Nintedanib Polyox Nintedanib Modified Release Prototype 2 Tablet (MR2-2) was administered with 240 ml water in the morning after a light breakfast on one day.
|
|---|---|---|---|---|---|---|
|
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-∞)
|
359.80 Hours times nanogram per milliliter
Standard Error NA
Adjusted geometric standard error = 1.18
|
60.04 Hours times nanogram per milliliter
Standard Error NA
Adjusted geometric standard error = 1.46
|
48.72 Hours times nanogram per milliliter
Standard Error NA
Adjusted geometric standard error = 1.26
|
241.32 Hours times nanogram per milliliter
Standard Error NA
Adjusted geometric standard error = 1.15
|
100.88 Hours times nanogram per milliliter
Standard Error NA
Adjusted geometric standard error = 1.16
|
103.55 Hours times nanogram per milliliter
Standard Error NA
Adjusted geometric standard error = 1.16
|
SECONDARY outcome
Timeframe: 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.Population: Pharmacokinetic (PK) parameter analysis set (PKS): This set includes all subjects in the treated set (TS) who provide at least one PK endpoint that was defined as primary or secondary and was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. Only subjects with available PK data were included in this analysis.
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: * 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.
Outcome measures
| Measure |
Cohort 1: Reference (R)
n=7 Participants
A low oral dose of Ofev® (Reference (R)) capsule bid was administered with 240 millilitre (ml) of water after a light breakfast and dinner, respectively on one day.
|
Cohort 1: Test Treatment 1 (MR1-1)
n=6 Participants
A single medium oral dose of Monolithic Nintedanib Modified Release Prototype 1 Tablet (MR1-1) was administered with 240 ml water in the morning after a light breakfast on one day.
|
Cohort 1: Test Treatment 2 (MR1-2)
n=6 Participants
A single medium oral dose of Monolithic Nintedanib Modified Release Prototype 2 Tablet (MR1-2) was administered with 240 ml water in the morning after a light breakfast on one day.
|
Cohort 2: Reference (R)
n=13 Participants
A low oral dose of Ofev® capsule (R) bid was administered with 240 ml of water after a light breakfast and dinner, respectively on one day.
|
Cohort 2: Test Treatment 1 (MR2-1)
n=14 Participants
A single medium oral dose of Polyox Nintedanib Modified Release Prototype 1 Tablet (MR2-1) was administered with 240 ml water in the morning after a light breakfast on one day.
|
Cohort 2: Test Treatment 2 (MR2-2)
n=14 Participants
A single medium oral dose of Nintedanib Polyox Nintedanib Modified Release Prototype 2 Tablet (MR2-2) was administered with 240 ml water in the morning after a light breakfast on one day.
|
|---|---|---|---|---|---|---|
|
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)
|
326.48 Hours times nanogram per milliliter
Standard Error NA
Adjusted geometric standard error = 1.21
|
30.54 Hours times nanogram per milliliter
Standard Error NA
Adjusted geometric standard error = 1.24
|
40.51 Hours times nanogram per milliliter
Standard Error NA
Adjusted geometric standard error = 1.23
|
226.69 Hours times nanogram per milliliter
Standard Error NA
Adjusted geometric standard error = 1.19
|
85.91 Hours times nanogram per milliliter
Standard Error NA
Adjusted geometric standard error = 1.19
|
81.35 Hours times nanogram per milliliter
Standard Error NA
Adjusted geometric standard error = 1.19
|
SECONDARY outcome
Timeframe: 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 administrationPopulation: Pharmacokinetic (PK) parameter analysis set (PKS): This set includes all subjects in the treated set (TS) who provide at least one PK endpoint that was defined as primary or secondary and was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. Only subjects with available PK data were included in this analysis.
The maximum measured concentration in plasma 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.
Outcome measures
| Measure |
Cohort 1: Reference (R)
n=7 Participants
A low oral dose of Ofev® (Reference (R)) capsule bid was administered with 240 millilitre (ml) of water after a light breakfast and dinner, respectively on one day.
|
Cohort 1: Test Treatment 1 (MR1-1)
n=6 Participants
A single medium oral dose of Monolithic Nintedanib Modified Release Prototype 1 Tablet (MR1-1) was administered with 240 ml water in the morning after a light breakfast on one day.
|
Cohort 1: Test Treatment 2 (MR1-2)
n=6 Participants
A single medium oral dose of Monolithic Nintedanib Modified Release Prototype 2 Tablet (MR1-2) was administered with 240 ml water in the morning after a light breakfast on one day.
|
Cohort 2: Reference (R)
n=13 Participants
A low oral dose of Ofev® capsule (R) bid was administered with 240 ml of water after a light breakfast and dinner, respectively on one day.
|
Cohort 2: Test Treatment 1 (MR2-1)
n=14 Participants
A single medium oral dose of Polyox Nintedanib Modified Release Prototype 1 Tablet (MR2-1) was administered with 240 ml water in the morning after a light breakfast on one day.
|
Cohort 2: Test Treatment 2 (MR2-2)
n=14 Participants
A single medium oral dose of Nintedanib Polyox Nintedanib Modified Release Prototype 2 Tablet (MR2-2) was administered with 240 ml water in the morning after a light breakfast on one day.
|
|---|---|---|---|---|---|---|
|
Maximum Measured Concentration of 3 Different Formulations of Nintedanib (MR1, MR2 and Ofev®) in Plasma Within the 24h Dosing Interval (Cmax)
|
32.02 Nanogram per milliliter
Standard Error NA
Adjusted geometric standard error = 1.32
|
3.87 Nanogram per milliliter
Standard Error NA
Adjusted geometric standard error = 1.35
|
7.66 Nanogram per milliliter
Standard Error NA
Adjusted geometric standard error = 1.34
|
17.55 Nanogram per milliliter
Standard Error NA
Adjusted geometric standard error = 1.19
|
12.03 Nanogram per milliliter
Standard Error NA
Adjusted geometric standard error = 1.18
|
11.73 Nanogram per milliliter
Standard Error NA
Adjusted geometric standard error = 1.18
|
SECONDARY outcome
Timeframe: 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.Population: Pharmacokinetic (PK) parameter analysis set (PKS): This set includes all subjects in the treated set (TS) who provide at least one PK endpoint that was defined as primary or secondary and was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. Only subjects with available PK data were included in this analysis.
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: * 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.
Outcome measures
| Measure |
Cohort 1: Reference (R)
n=7 Participants
A low oral dose of Ofev® (Reference (R)) capsule bid was administered with 240 millilitre (ml) of water after a light breakfast and dinner, respectively on one day.
|
Cohort 1: Test Treatment 1 (MR1-1)
n=5 Participants
A single medium oral dose of Monolithic Nintedanib Modified Release Prototype 1 Tablet (MR1-1) was administered with 240 ml water in the morning after a light breakfast on one day.
|
Cohort 1: Test Treatment 2 (MR1-2)
n=5 Participants
A single medium oral dose of Monolithic Nintedanib Modified Release Prototype 2 Tablet (MR1-2) was administered with 240 ml water in the morning after a light breakfast on one day.
|
Cohort 2: Reference (R)
n=13 Participants
A low oral dose of Ofev® capsule (R) bid was administered with 240 ml of water after a light breakfast and dinner, respectively on one day.
|
Cohort 2: Test Treatment 1 (MR2-1)
n=13 Participants
A single medium oral dose of Polyox Nintedanib Modified Release Prototype 1 Tablet (MR2-1) was administered with 240 ml water in the morning after a light breakfast on one day.
|
Cohort 2: Test Treatment 2 (MR2-2)
n=12 Participants
A single medium oral dose of Nintedanib Polyox Nintedanib Modified Release Prototype 2 Tablet (MR2-2) was administered with 240 ml water in the morning after a light breakfast on one day.
|
|---|---|---|---|---|---|---|
|
Concentration of 3 Different Formulations of Nintedanib (MR1, MR2 and Ofev®) in Plasma 24 Hours After the First Dose (C₂₄)
|
5.48 Nanogram per milliliter
Standard Error NA
Adjusted geometric standard error = 1.15
|
0.66 Nanogram per milliliter
Standard Error NA
Adjusted geometric standard error = 1.18
|
0.77 Nanogram per milliliter
Standard Error NA
Adjusted geometric standard error = 1.17
|
4.10 Nanogram per milliliter
Standard Error NA
Adjusted geometric standard error = 1.14
|
1.32 Nanogram per milliliter
Standard Error NA
Adjusted geometric standard error = 1.14
|
1.29 Nanogram per milliliter
Standard Error NA
Adjusted geometric standard error = 1.14
|
Adverse Events
Cohort 1: Reference (R)
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Cohort 1: Test Treatment 1 (MR1-1)
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Cohort 1: Test Treatment 2 (MR1-2)
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Cohort 2: Reference (R)
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Cohort 2: Test Treatment 1 (MR2-1)
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Cohort 2: Test Treatment 2 (MR2-2)
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Cohort 1: Reference (R)
n=7 participants at risk
A low oral dose of Ofev® (Reference (R)) capsule bid was administered with 240 millilitre (ml) of water after a light breakfast and dinner, respectively on one day.
|
Cohort 1: Test Treatment 1 (MR1-1)
n=6 participants at risk
A single medium oral dose of Monolithic Nintedanib Modified Release Prototype 1 Tablet (MR1-1) was administered with 240 ml water in the morning after a light breakfast on one day.
|
Cohort 1: Test Treatment 2 (MR1-2)
n=6 participants at risk
A single medium oral dose of Monolithic Nintedanib Modified Release Prototype 2 Tablet (MR1-2) was administered with 240 ml water in the morning after a light breakfast on one day.
|
Cohort 2: Reference (R)
n=14 participants at risk
A low oral dose of Ofev® capsule (R) bid was administered with 240 ml of water after a light breakfast and dinner, respectively on one day.
|
Cohort 2: Test Treatment 1 (MR2-1)
n=14 participants at risk
A single medium oral dose of Polyox Nintedanib Modified Release Prototype 1 Tablet (MR2-1) was administered with 240 ml water in the morning after a light breakfast on one day.
|
Cohort 2: Test Treatment 2 (MR2-2)
n=14 participants at risk
A single medium oral dose of Nintedanib Polyox Nintedanib Modified Release Prototype 2 Tablet (MR2-2) was administered with 240 ml water in the morning after a light breakfast on one day.
|
|---|---|---|---|---|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/7 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
0.00%
0/6 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
0.00%
0/6 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
7.1%
1/14 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
0.00%
0/14 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
0.00%
0/14 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/7 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
0.00%
0/6 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
0.00%
0/6 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
7.1%
1/14 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
7.1%
1/14 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
0.00%
0/14 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
|
General disorders
Chills
|
0.00%
0/7 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
0.00%
0/6 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
0.00%
0/6 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
0.00%
0/14 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
7.1%
1/14 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
0.00%
0/14 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
|
General disorders
Fatigue
|
0.00%
0/7 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
0.00%
0/6 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
0.00%
0/6 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
7.1%
1/14 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
0.00%
0/14 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
0.00%
0/14 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
|
Infections and infestations
COVID-19
|
14.3%
1/7 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
16.7%
1/6 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
0.00%
0/6 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
0.00%
0/14 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
0.00%
0/14 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
0.00%
0/14 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
|
Infections and infestations
Impetigo
|
14.3%
1/7 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
0.00%
0/6 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
0.00%
0/6 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
0.00%
0/14 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
0.00%
0/14 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
0.00%
0/14 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/7 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
0.00%
0/6 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
0.00%
0/6 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
7.1%
1/14 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
0.00%
0/14 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
7.1%
1/14 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/7 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
0.00%
0/6 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
0.00%
0/6 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
0.00%
0/14 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
7.1%
1/14 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
7.1%
1/14 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
|
Injury, poisoning and procedural complications
Arthropod bite
|
0.00%
0/7 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
0.00%
0/6 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
0.00%
0/6 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
7.1%
1/14 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
0.00%
0/14 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
0.00%
0/14 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
14.3%
1/7 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
0.00%
0/6 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
0.00%
0/6 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
0.00%
0/14 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
0.00%
0/14 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
0.00%
0/14 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.00%
0/7 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
0.00%
0/6 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
0.00%
0/6 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
0.00%
0/14 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
0.00%
0/14 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
7.1%
1/14 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
|
Nervous system disorders
Headache
|
14.3%
1/7 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
0.00%
0/6 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
0.00%
0/6 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
7.1%
1/14 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
14.3%
2/14 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
0.00%
0/14 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
|
Nervous system disorders
Migraine
|
0.00%
0/7 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
0.00%
0/6 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
0.00%
0/6 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
0.00%
0/14 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
7.1%
1/14 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
0.00%
0/14 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.00%
0/7 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
0.00%
0/6 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
0.00%
0/6 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
7.1%
1/14 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
0.00%
0/14 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
0.00%
0/14 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
|
Skin and subcutaneous tissue disorders
Skin mass
|
0.00%
0/7 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
0.00%
0/6 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
0.00%
0/6 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
0.00%
0/14 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
0.00%
0/14 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
7.1%
1/14 • From first drug administration in this period to at least 14 days thereafter OR until next drug administration of the following period, whatever occurred first, up to 22 days after last drug administration.
Treated set (TS): The treated set included all participants who were randomized and treated with at least one dose of study drug.
|
Additional Information
Boehringer Ingelheim, Call Center
Boehringer Ingelheim
Phone: 1-800-243-0127
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER