Trial Outcomes & Findings for Evaluation of Safety and Tolerability of Single Rising Doses of BI 473494 in Healthy Subjects (NCT NCT03195088)

NCT ID: NCT03195088

Last Updated: 2022-07-14

Results Overview

Percentage of participants with drug-related adverse events (AEs) analysed as investigator defined drug-related AEs is presented. Medical judgment was used to determine the relationship between the AEs and the study medication, considering all relevant factors, including pattern of reaction, temporal relationship, de-challenge or re-challenge, confounding factors such as concomitant medication, concomitant diseases and relevant history.

Recruitment status

TERMINATED

Study phase

PHASE1

Target enrollment

16 participants

Primary outcome timeframe

From drug administration until End of trial (EOT), up to 40 days.

Results posted on

2022-07-14

Participant Flow

It was planned to include healthy participants in this single-rising dose trial with a single-blind, partially randomised, placebo controlled and parallel group design. They were recruited from the volunteer's pool of the study site.

All participants were screened for eligibility to participate in the trial by the trial site. The site ensured that the participants met all strictly implemented inclusion/exclusion criteria. Participants were not to be assigned to treatment groups if any one of the specific entry criteria were violated.

Participant milestones

Participant milestones
Measure
Placebo Matching BI 473494
Healthy participants were administered a single dose of placebo matching BI 473494 solution via subcutaneous injection.
BI 473494 35 μg
Healthy participants were administered a single dose of 35 micrograms (μg) BI 473494 solution via subcutaneous injection.
BI 473494 75 μg
Healthy participants were administered a single dose of 75 micrograms (μg) BI 473494 solution via subcutaneous injection.
Overall Study
STARTED
4
6
6
Overall Study
COMPLETED
4
6
6
Overall Study
NOT COMPLETED
0
0
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Evaluation of Safety and Tolerability of Single Rising Doses of BI 473494 in Healthy Subjects

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Placebo Matching BI 473494
n=4 Participants
Healthy participants were administered a single dose of placebo matching BI 473494 solution via subcutaneous injection.
BI 473494 35 μg
n=6 Participants
Healthy participants were administered a single dose of 35 micrograms (μg) BI 473494 solution via subcutaneous injection.
BI 473494 75 μg
n=6 Participants
Healthy participants were administered a single dose of 75 micrograms (μg) BI 473494 solution via subcutaneous injection.
Total
n=16 Participants
Total of all reporting groups
Race (NIH/OMB)
More than one race
0 Participants
n=5 Participants
1 Participants
n=7 Participants
0 Participants
n=5 Participants
1 Participants
n=4 Participants
Age, Continuous
34.3 Years
STANDARD_DEVIATION 5.9 • n=5 Participants
34.0 Years
STANDARD_DEVIATION 7.4 • n=7 Participants
30.2 Years
STANDARD_DEVIATION 6.8 • n=5 Participants
32.6 Years
STANDARD_DEVIATION 6.7 • n=4 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
Sex: Female, Male
Male
4 Participants
n=5 Participants
6 Participants
n=7 Participants
6 Participants
n=5 Participants
16 Participants
n=4 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
Ethnicity (NIH/OMB)
Not Hispanic or Latino
4 Participants
n=5 Participants
6 Participants
n=7 Participants
6 Participants
n=5 Participants
16 Participants
n=4 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
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
Race (NIH/OMB)
Asian
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 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
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
Race (NIH/OMB)
White
4 Participants
n=5 Participants
5 Participants
n=7 Participants
6 Participants
n=5 Participants
15 Participants
n=4 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

PRIMARY outcome

Timeframe: From drug administration until End of trial (EOT), up to 40 days.

Population: Treated set (TS) : The TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of BI 473494.

Percentage of participants with drug-related adverse events (AEs) analysed as investigator defined drug-related AEs is presented. Medical judgment was used to determine the relationship between the AEs and the study medication, considering all relevant factors, including pattern of reaction, temporal relationship, de-challenge or re-challenge, confounding factors such as concomitant medication, concomitant diseases and relevant history.

Outcome measures

Outcome measures
Measure
Placebo Matching BI 473494
n=4 Participants
Healthy participants were administered a single dose of placebo matching BI 473494 solution via subcutaneous injection.
BI 473494 35 μg
n=6 Participants
Healthy participants were administered a single dose of 35 micrograms (μg) BI 473494 solution via subcutaneous injection.
BI 473494 75 μg
n=6 Participants
Healthy participants were administered a single dose of 75 micrograms (μg) BI 473494 solution via subcutaneous injection.
Percentage of Participants With Drug-related Adverse Events (AEs) Analysed as Investigator Defined Drug-related AEs
0.0 Percentage of participants (%)
0.0 Percentage of participants (%)
16.7 Percentage of participants (%)

SECONDARY outcome

Timeframe: Pharmacokinetic samples were taken 1:00 hour:minute (h:m) pre-dose and 3:00, 6:00, 9:00, 12:00, 15:00 , 22:00, 24:00, 28:00, 34:00, 39:00, 48:00, 60:00, 72:00, 96:00, 120:00, 168:00, 240:00, 336:00, 504:00 and 672:00 h:m after drug administration on day 1

Population: Pharmacokinetic (PK) parameter analysis set (PKS): The PKS included all subjects from the TS who received study medication and provided at least one secondary PK parameter that was not excluded due to important protocol deviations with respect to the statistical evaluation of PK endpoints.

AUC0-tz, area under the concentration-time curve of BI 473494 over the time interval from 0 to the last quantifiable time point is presented.

Outcome measures

Outcome measures
Measure
Placebo Matching BI 473494
n=6 Participants
Healthy participants were administered a single dose of placebo matching BI 473494 solution via subcutaneous injection.
BI 473494 35 μg
n=6 Participants
Healthy participants were administered a single dose of 35 micrograms (μg) BI 473494 solution via subcutaneous injection.
BI 473494 75 μg
Healthy participants were administered a single dose of 75 micrograms (μg) BI 473494 solution via subcutaneous injection.
Area Under the Concentration-time Curve of BI 473494 Over the Time Interval From 0 to the Last Quantifiable Time Point (AUC0-tz)
162 Nanomole*Hours/Litre (nmol*h/L)
Geometric Coefficient of Variation 24.8
546 Nanomole*Hours/Litre (nmol*h/L)
Geometric Coefficient of Variation 18.5

SECONDARY outcome

Timeframe: Pharmacokinetic samples were taken 1:00 hour:minute (h:m) pre-dose and 3:00, 6:00, 9:00, 12:00, 15:00 , 22:00, 24:00, 28:00, 34:00, 39:00, 48:00, 60:00, 72:00, 96:00, 120:00, 168:00, 240:00, 336:00, 504:00 and 672:00 h:m after drug administration on day 1

Population: Pharmacokinetic (PK) parameter analysis set (PKS): The PKS included all subjects from the TS who received study medication and provided at least one secondary PK parameter that was not excluded due to important protocol deviations with respect to the statistical evaluation of PK endpoints.

Cmax, maximum measured concentration of BI 473494 is presented.

Outcome measures

Outcome measures
Measure
Placebo Matching BI 473494
n=6 Participants
Healthy participants were administered a single dose of placebo matching BI 473494 solution via subcutaneous injection.
BI 473494 35 μg
n=6 Participants
Healthy participants were administered a single dose of 35 micrograms (μg) BI 473494 solution via subcutaneous injection.
BI 473494 75 μg
Healthy participants were administered a single dose of 75 micrograms (μg) BI 473494 solution via subcutaneous injection.
Maximum Measured Concentration of BI 473494 (Cmax)
0.82 Nanomole/Litre (nmol/L)
Geometric Coefficient of Variation 23.1
1.88 Nanomole/Litre (nmol/L)
Geometric Coefficient of Variation 17.5

Adverse Events

Placebo Matching BI 473494

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

BI 473494 35 μg

Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths

BI 473494 75 μg

Serious events: 1 serious events
Other events: 1 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Placebo Matching BI 473494
n=4 participants at risk
Healthy participants were administered a single dose of placebo matching BI 473494 solution via subcutaneous injection.
BI 473494 35 μg
n=6 participants at risk
Healthy participants were administered a single dose of 35 micrograms (μg) BI 473494 solution via subcutaneous injection.
BI 473494 75 μg
n=6 participants at risk
Healthy participants were administered a single dose of 75 micrograms (μg) BI 473494 solution via subcutaneous injection.
Nervous system disorders
Acute polyneuropathy
0.00%
0/4 • From drug administration until End of trial (EOT), up to 40 days.
0.00%
0/6 • From drug administration until End of trial (EOT), up to 40 days.
16.7%
1/6 • From drug administration until End of trial (EOT), up to 40 days.

Other adverse events

Other adverse events
Measure
Placebo Matching BI 473494
n=4 participants at risk
Healthy participants were administered a single dose of placebo matching BI 473494 solution via subcutaneous injection.
BI 473494 35 μg
n=6 participants at risk
Healthy participants were administered a single dose of 35 micrograms (μg) BI 473494 solution via subcutaneous injection.
BI 473494 75 μg
n=6 participants at risk
Healthy participants were administered a single dose of 75 micrograms (μg) BI 473494 solution via subcutaneous injection.
Musculoskeletal and connective tissue disorders
Back pain
0.00%
0/4 • From drug administration until End of trial (EOT), up to 40 days.
33.3%
2/6 • From drug administration until End of trial (EOT), up to 40 days.
0.00%
0/6 • From drug administration until End of trial (EOT), up to 40 days.
Nervous system disorders
Head discomfort
0.00%
0/4 • From drug administration until End of trial (EOT), up to 40 days.
0.00%
0/6 • From drug administration until End of trial (EOT), up to 40 days.
16.7%
1/6 • From drug administration until End of trial (EOT), up to 40 days.
Nervous system disorders
Hypoaesthesia
0.00%
0/4 • From drug administration until End of trial (EOT), up to 40 days.
0.00%
0/6 • From drug administration until End of trial (EOT), up to 40 days.
16.7%
1/6 • From drug administration until End of trial (EOT), up to 40 days.
Nervous system disorders
Paraesthesia
0.00%
0/4 • From drug administration until End of trial (EOT), up to 40 days.
0.00%
0/6 • From drug administration until End of trial (EOT), up to 40 days.
16.7%
1/6 • From drug administration until End of trial (EOT), up to 40 days.
Psychiatric disorders
Sleep disorder
0.00%
0/4 • From drug administration until End of trial (EOT), up to 40 days.
0.00%
0/6 • From drug administration until End of trial (EOT), up to 40 days.
16.7%
1/6 • From drug administration until End of trial (EOT), up to 40 days.
Vascular disorders
Peripheral coldness
0.00%
0/4 • From drug administration until End of trial (EOT), up to 40 days.
0.00%
0/6 • From drug administration until End of trial (EOT), up to 40 days.
16.7%
1/6 • From drug administration until End of trial (EOT), up to 40 days.

Additional Information

Boehringer Ingelheim, Call Center

Boehringer Ingelheim

Phone: 1-800-243-0127

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