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CompletedNCT03302091Updated Jun 4, 2021Results posted

A Study in People With Normal Kidney Function and People With Reduced Kidney Function to Test How BI 1467335 is Processed in the Body

A Phase 1 interventional study of BI 1467335 in Renal Insufficiency and Healthy, sponsored by Boehringer Ingelheim. Completed at 1 site in Germany. Open to participants aged 18 Years to 79 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2021-06-04.

Sponsored by Boehringer Ingelheim · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
20
Allocation
Non-randomized
Ages
18 Years to 79 Years
Sex
All
01

Study summary

The primary objective of the current study is to investigate the influence of moderate renal impairment on the pharmacokinetics of multiple doses in comparison to a matched control group with normal renal function.

02

Conditions studied

  • Renal Insufficiency
  • Healthy

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03

Who can participate

Ages eligible
18 Years to 79 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

Inclusion criteria

  • Despite of moderate renal impairment (Group 1) healthy male or female subjects according to the assessment of the investigator, based on a complete medical history including a physical examination, vital signs (Blood pressure (BP), Pulse rate (PR)), 12-lead Electrocardiogram (ECG), and clinical laboratory tests
  • Estimated glomerular filtration rate (eGFR) based on CKD-EPI formula for Group 1 between 30 and 59 mL/min/1.73m2 and for Group 2 ≥ 90 mL/min/1.73m2
  • Age of 18 to 79 years (incl.)
  • BMI of 18.5 to 34 kg/m2 (incl.)
  • Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice (GCP) and local legislation
  • Male subjects, or female subjects who meet any of the following criteria (according to the CTFG Recommendations related to contraception and pregnancy testing in clinical trials, methods with a failure rate of less than 1% per year) starting from at least 30 days before the first administration of trial medication and until 30 days after trial completion, e.g.:

    • Use of adequate contraception, e.g. any of the following methods plus condom: implants, injectables, combined oral or vaginal contraceptives (inhibition of ovulation)
    • Hormonal intrauterine device
    • Sexually abstinent (defined as refraining from heterosexual intercourse during the entire period of risk)
    • A vasectomised sexual partner (provided that vasectomy was performed at least 1 year prior to enrolment and the vasectomised partner has received medical assessment of the surgical success)
    • Surgically sterilised (including bilateral tubal occlusion, hysterectomy)
    • Postmenopausal, defined as at least 1 year of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous levels of FSH above 40 U/L and estradiol below 30 ng/L is confirmatory)

Exclusion criteria

Exclusion Criteria:

Healthy subjects

  • Any finding in the medical examination (including BP, PR or ECG) is deviating from normal and judged as clinically relevant by the investigator
  • Repeated measurement of systolic blood pressure outside the range of 90 to 140 mmHg, diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate outside the range of 50 to 90 bpm
  • Any laboratory value outside the reference range that the investigator considers to be of clinical relevance
  • Any evidence of a concomitant disease judged as clinically relevant by the investigator
  • Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
  • Estimated glomerular filtration rate (eGFR) calculated by CKD-EPI formula \< 90 mL/min/1.73m2

Subjects with moderate renal impairment

  • Subject with significant diseases other than moderate renal impairment. A significant disease is defined as a disease which in the opinion of the investigator:

    • puts the subjects at risk because of participation in the study
    • may influence the results of the study
    • may influence the subject's ability to participate in the study
    • is not in a stable condition Diabetic or hypertensive subjects can be entered in this trial if the disease is not significant according to these criteria.
  • Any finding of the medical examination (including BP, PR and ECG) of clinical relevance
  • Moderate and severe concurrent liver function impairment (e.g. due to hepatorenal syndrome) or biliary obstruction
  • Clinically relevant laboratory abnormalities (except for renal function tests or deviation of clinical laboratory values that are related to renal impairment)
  • eGFR calculated by CKD-EPI formula ≥ 60 mL/min/1.73m2 and \< 30 mL/min/1.73m2

For all subjects

  • Cholecystectomy and/or surgery of the gastrointestinal tract that could interfere with the pharmacokinetics of the trial medication (except appendectomy and simple hernia repair)
  • Diseases of the central nervous system (including but not limited to any kind of seizures or stroke), and other relevant neurological or psychiatric disorders
  • History of relevant orthostatic hypotension, fainting spells, or blackouts
  • Chronic or relevant acute infections
  • History of relevant allergy or hypersensitivity (including allergy to the trial medication or its excipients)
  • Use of drugs within 30 days prior to administration of trial medication if that might reasonably influence the results of the trial (incl. QT/QTc interval prolongation)
  • Participation in another trial where an investigational drug has been administered within 30 days prior to planned administration of trial medication or longer if required by local regulation, or within 5-half-lives of the investigational agent taken (whichever is longer), or current participation in another trial involving administration of investigational drug
  • Smoker (more than 10 cigarettes or 3 cigars or 3 pipes per day)
  • Inability to refrain from smoking on specified trial days
  • Alcohol abuse (consumption of more than 20 g per day for females and 30 g per day for males)
  • Drug abuse or positive drug screening
  • Blood donation of more than 100 mL within 30 days prior to administration of trial medication or intended donation during the trial
  • Intention to perform excessive physical activities within one week prior to administration of trial medication or during the trial
  • Inability to comply with dietary regimen of trial site
  • A marked baseline prolongation of QT/QTc interval (such as QTc intervals that are repeatedly greater than 450 ms in males or repeatedly greater than 470 ms in females) or any other relevant ECG finding at screening
  • A history of additional risk factors for Torsades de Pointes (such as heart failure, hypokalemia, or family history of Long QT Syndrome)
  • Subject is assessed as unsuitable for inclusion by the investigator, for instance, because considered not able to understand and comply with study requirements, or has a condition that would not allow safe participation in the study

Female subjects will not be allowed to participate if any of the following applies:

  • Positive pregnancy test, pregnancy or plans to become pregnant within 30 days after study completion
  • Lactation period

Male subjects will not be allowed to participate if any of the following applies:

  • Male subjects with WOCBP partner who are unwilling to use male contraception (condom or sexual abstinence) from the first administration of trial medication until 30 days after last administration of trial medication
04

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
20 participants (actual)

Study arms

  • Experimental
    BI 1467335 Normal (R)

    Participants with normal renal function.

    Drug: BI 1467335

  • Experimental
    BI 1467335 Moderate (T)

    Participants with moderate renal impairment.

    Drug: BI 1467335

Interventions

  • DrugBI 1467335

    28 day treatment period

05

What researchers measure

Primary outcomes

  1. Area Under the Concentration-time Curve of BI 1467335 in Plasma Over the Time Interval From 0 to 24 Hours After Administration of the First Dose (AUC0-24)

    Area under the concentration-time curve of BI 1467335 in plasma over the time interval from 0 to 24 hours after administration of the first dose AUC 0-24. Standard Error presented is actually geometric Standard Error. PKS-stat including participants data for AUC(0-24). The pharmacokinetic (PK) analysis set (PKS) included all subjects in the TS who provided at least one PK parameter that was defined as primary or secondary endpoint and who were not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability.

    Time frame: Pharmacokinetic (PK) samples were taken 2.00 hours (h) before dosing and 0.25, 0.50, 0.75, 1.00, 1.50, 2.00, 3.00, 4.00, 6.00, 8.00, 10.00, 12.00 and 23.917 h after dosing on day 1.

  2. Maximum Measured Concentration of BI 1467335 in Plasma After Administration of the First Dose (Cmax)

    Maximum measured concentration of BI 1467335 in plasma after administration of the first dose (Cmax). Standard Error presented is actually geometric Standard Error.

    Time frame: Pharmacokinetic (PK) samples were taken 2.00 h before dosing and 0.25, 0.50, 0.75, 1.00, 1.50, 2.00, 3.00, 4.00, 6.00, 8.00, 10.00, 12.00 and 23.917 h after dosing on day 1.

  3. Area Under the Concentration-time Curve of BI 1467335 in Plasma Over the Dosing Interval After Administration of the 28th Dose (AUCτ,28)

    Area under the concentration-time curve of BI 1467335 in plasma over the dosing interval after administration of the 28th dose (AUCτ,28). Standard Error presented is actually geometric Standard Error. As per the protocol, day is counted as "Day 1 = 0:00".

    Time frame: Pharmacokinetic samples were taken 0.0833 h before last dose and 0.25, 0.50, 0.75, 1.00, 1.50, 2.00, 3.00, 4.00, 6.00, 8.00, 10.00, 12.00 and 24.00 h after dosing on day 28.

  4. Maximum Measured Concentration of BI 1467335 in Plasma Following Administration of the 28th Dose (Cmax,28)

    Maximum measured concentration of BI 1467335 in plasma following administration of the 28th dose (Cmax,28). Standard Error presented is actually geometric Standard Error. As per the protocol, day is counted as "Day 1 = 0:00".

    Time frame: Pharmacokinetic samples were taken 0.0833 h before last dose and 0.25, 0.50, 0.75, 1.00, 1.50, 2.00, 3.00, 4.00, 6.00, 8.00, 10.00, 12.00 and 24.00 h after dosing on day 28.

Secondary outcomes

  1. Area Under the Concentration-time Curve of BI 1467335 in Plasma Over the Dosing Interval After Administration of the 14th Dose (AUCτ,14)

    Area under the concentration-time curve of BI 1467335 in plasma over the dosing interval after administration of the 14th dose (AUCτ,14). Standard Error presented is actually geometric Standard Error. As per the protocol, day is counted as "Day 1 = 0:00".

    Time frame: Pharmacokinetic samples were taken 0.0833 h before dosing and 0.25, 0.50, 0.75, 1.00, 1.50, 2.00, 3.00, 4.00, 6.00, 8.00, 10.00, 12.00 and 23.917 h after dosing on day 14.

  2. Maximum Measured Concentration of BI 1467335 in Plasma Following Administration of the 14th Dose (Cmax,14)

    Maximum measured concentration of BI 1467335 in plasma following administration of the 14th dose (Cmax,14). Standard Error presented is actually geometric Standard Error. As per the protocol, day is counted as "Day 1 = 0:00".

    Time frame: Pharmacokinetic samples were taken 0.0833 h before dosing and 0.25, 0.50, 0.75, 1.00, 1.50, 2.00, 3.00, 4.00, 6.00, 8.00, 10.00, 12.00 and 23.917 h after dosing on day 14.

06

Results

Posted Jun 4, 2021

Participant flow

This was open-label, multiple-dose and matched-group design. 20 participants entered (ten in each of the two groups). Participants with moderate renal impairment were assigned to the moderate group and individually matched participants with normal renal function were assigned to the normal group.

Participant flow — Overall Study
MilestoneBI 1467335 Normal (R)BI 1467335 Moderate (T)
Started1010
Completed1010
Not completed00

Outcome measures

PrimaryArea Under the Concentration-time Curve of BI 1467335 in Plasma Over the Time Interval From 0 to 24 Hours After Administration of the First Dose (AUC0-24)

Area under the concentration-time curve of BI 1467335 in plasma over the time interval from 0 to 24 hours after administration of the first dose AUC 0-24. Standard Error presented is actually geometric Standard Error. PKS-stat including participants data for AUC(0-24). The pharmacokinetic (PK) analysis set (PKS) included all subjects in the TS who provided at least one PK parameter that was defined as primary or secondary endpoint and who were not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability.

Time frame:
Pharmacokinetic (PK) samples were taken 2.00 hours (h) before dosing and 0.25, 0.50, 0.75, 1.00, 1.50, 2.00, 3.00, 4.00, 6.00, 8.00, 10.00, 12.00 and 23.917 h after dosing on day 1.
Reported as:
Geometric least squares mean · nanomole*hour/Liter (nmol*h/L)
Area Under the Concentration-time Curve of BI 1467335 in Plasma Over the Time Interval From 0 to 24 Hours After Administration of the First Dose (AUC0-24)
nanomole*hour/Liter (nmol*h/L)BI 1467335 Normal (R)BI 1467335 Moderate (T)
Area Under the Concentration-time Curve of BI 1467335 in Plasma Over the Time Interval From 0 to 24 Hours After Administration of the First Dose (AUC0-24)3.97 ± 1.317.88 ± 1.31
Statistical analysis
  • BI 1467335 Normal (R) vs BI 1467335 Moderate (T) · ANOVA · Adjusted gmean ratio (t/r)%: 198.50 · 90% CI 101.83 to 386.94Standard deviation is actually intra individual geometric coefficient of variation (%).
PrimaryMaximum Measured Concentration of BI 1467335 in Plasma After Administration of the First Dose (Cmax)

Maximum measured concentration of BI 1467335 in plasma after administration of the first dose (Cmax). Standard Error presented is actually geometric Standard Error.

Time frame:
Pharmacokinetic (PK) samples were taken 2.00 h before dosing and 0.25, 0.50, 0.75, 1.00, 1.50, 2.00, 3.00, 4.00, 6.00, 8.00, 10.00, 12.00 and 23.917 h after dosing on day 1.
Reported as:
Geometric least squares mean · nanomole/Liter (nmol/L)
Maximum Measured Concentration of BI 1467335 in Plasma After Administration of the First Dose (Cmax)
nanomole/Liter (nmol/L)BI 1467335 Normal (R)BI 1467335 Moderate (T)
Maximum Measured Concentration of BI 1467335 in Plasma After Administration of the First Dose (Cmax)3.03 ± 1.246.01 ± 1.24
Statistical analysis
  • BI 1467335 Normal (R) vs BI 1467335 Moderate (T) · ANOVA · Adjusted gmean ratio (t/r)%: 198.42 · 90% CI 116.56 to 337.78Standard deviation is actually intra individual geometric coefficient of variation (%).
PrimaryArea Under the Concentration-time Curve of BI 1467335 in Plasma Over the Dosing Interval After Administration of the 28th Dose (AUCτ,28)

Area under the concentration-time curve of BI 1467335 in plasma over the dosing interval after administration of the 28th dose (AUCτ,28). Standard Error presented is actually geometric Standard Error. As per the protocol, day is counted as "Day 1 = 0:00".

Time frame:
Pharmacokinetic samples were taken 0.0833 h before last dose and 0.25, 0.50, 0.75, 1.00, 1.50, 2.00, 3.00, 4.00, 6.00, 8.00, 10.00, 12.00 and 24.00 h after dosing on day 28.
Reported as:
Geometric least squares mean · nanomole*hours/Liter (nmol*h/L)
Area Under the Concentration-time Curve of BI 1467335 in Plasma Over the Dosing Interval After Administration of the 28th Dose (AUCτ,28)
nanomole*hours/Liter (nmol*h/L)BI 1467335 Normal (R)BI 1467335 Moderate (T)
Area Under the Concentration-time Curve of BI 1467335 in Plasma Over the Dosing Interval After Administration of the 28th Dose (AUCτ,28)692.42 ± 1.231566.88 ± 1.23
Statistical analysis
  • BI 1467335 Normal (R) vs BI 1467335 Moderate (T) · ANOVA · Adjusted gmean ratio (t/r)%: 226.29 · 90% CI 156.35 to 327.53Standard deviation is actually intra individual geometric coefficient of variation (%).
PrimaryMaximum Measured Concentration of BI 1467335 in Plasma Following Administration of the 28th Dose (Cmax,28)

Maximum measured concentration of BI 1467335 in plasma following administration of the 28th dose (Cmax,28). Standard Error presented is actually geometric Standard Error. As per the protocol, day is counted as "Day 1 = 0:00".

Time frame:
Pharmacokinetic samples were taken 0.0833 h before last dose and 0.25, 0.50, 0.75, 1.00, 1.50, 2.00, 3.00, 4.00, 6.00, 8.00, 10.00, 12.00 and 24.00 h after dosing on day 28.
Reported as:
Geometric least squares mean · nanomole/Liter (nmol/L)
Maximum Measured Concentration of BI 1467335 in Plasma Following Administration of the 28th Dose (Cmax,28)
nanomole/Liter (nmol/L)BI 1467335 Normal (R)BI 1467335 Moderate (T)
Maximum Measured Concentration of BI 1467335 in Plasma Following Administration of the 28th Dose (Cmax,28)100.57 ± 1.13141.20 ± 1.13
Statistical analysis
  • BI 1467335 Normal (R) vs BI 1467335 Moderate (T) · ANOVA · Adjusted gmean ratio (t/r)%: 140.40 · 90% CI 108.06 to 182.43Standard deviation is actually intra individual geometric coefficient of variation (%).
SecondaryArea Under the Concentration-time Curve of BI 1467335 in Plasma Over the Dosing Interval After Administration of the 14th Dose (AUCτ,14)

Area under the concentration-time curve of BI 1467335 in plasma over the dosing interval after administration of the 14th dose (AUCτ,14). Standard Error presented is actually geometric Standard Error. As per the protocol, day is counted as "Day 1 = 0:00".

Time frame:
Pharmacokinetic samples were taken 0.0833 h before dosing and 0.25, 0.50, 0.75, 1.00, 1.50, 2.00, 3.00, 4.00, 6.00, 8.00, 10.00, 12.00 and 23.917 h after dosing on day 14.
Reported as:
Geometric least squares mean · nanomole*hour/Liter (nmol*h/L)
Area Under the Concentration-time Curve of BI 1467335 in Plasma Over the Dosing Interval After Administration of the 14th Dose (AUCτ,14)
nanomole*hour/Liter (nmol*h/L)BI 1467335 Normal (R)BI 1467335 Moderate (T)
Area Under the Concentration-time Curve of BI 1467335 in Plasma Over the Dosing Interval After Administration of the 14th Dose (AUCτ,14)321.23 ± 1.34532.06 ± 1.34
Statistical analysis
  • BI 1467335 Normal (R) vs BI 1467335 Moderate (T) · ANOVA · Adjusted gmean ratio (t/r)%: 165.63 · 90% CI 107.51 to 255.17Standard deviation is actually intra individual geometric coefficient of variation (%).
SecondaryMaximum Measured Concentration of BI 1467335 in Plasma Following Administration of the 14th Dose (Cmax,14)

Maximum measured concentration of BI 1467335 in plasma following administration of the 14th dose (Cmax,14). Standard Error presented is actually geometric Standard Error. As per the protocol, day is counted as "Day 1 = 0:00".

Time frame:
Pharmacokinetic samples were taken 0.0833 h before dosing and 0.25, 0.50, 0.75, 1.00, 1.50, 2.00, 3.00, 4.00, 6.00, 8.00, 10.00, 12.00 and 23.917 h after dosing on day 14.
Reported as:
Geometric least squares mean · nanomole/Liter (nmol/L)
Maximum Measured Concentration of BI 1467335 in Plasma Following Administration of the 14th Dose (Cmax,14)
nanomole/Liter (nmol/L)BI 1467335 Normal (R)BI 1467335 Moderate (T)
Maximum Measured Concentration of BI 1467335 in Plasma Following Administration of the 14th Dose (Cmax,14)73.41 ± 1.1694.28 ± 1.16
Statistical analysis
  • BI 1467335 Normal (R) vs BI 1467335 Moderate (T) · ANOVA · Adjusted gmean ratio (t/r)%: 128.44 · 90% CI 99.64 to 165.57Standard deviation is actually intra individual geometric coefficient of variation (%).

Adverse events

Collected over From first day of study drug administration until End of trial (EOT), up to 41 days.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
BI 1467335 Normal (R)0/10 (0%)0/10 (0%)2/10 (20%)
BI 1467335 Moderate (T)0/10 (0%)0/10 (0%)2/10 (20%)
Most frequent other events
Most frequent other events
EventBI 1467335 Normal (R)BI 1467335 Moderate (T)
HeadacheNervous system disorders1/102/10
VomitingGastrointestinal disorders0/101/10
Rash pruriticSkin and subcutaneous tissue disorders1/100/10

Baseline characteristics

Treated Set (TS): The TS included all subjects who were documented to have taken at least one dose of trial medication. This is the full analysis set population in the sense of International council for harmonisation - efficacy guideline 9: statistical principles for clinical trials (ICH-E9).

Age, Continuous
Age, Continuous(Years)BI 1467335 Normal (R)BI 1467335 Moderate (T)Total
Mean67.5 ± 9.568.7 ± 10.968.1 ± 10.0
Sex: Female, Male
Sex: Female, Male(Participants)BI 1467335 Normal (R)BI 1467335 Moderate (T)Total
Female448
Male6612
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)BI 1467335 Normal (R)BI 1467335 Moderate (T)Total
Hispanic or Latino000
Not Hispanic or Latino101020
Unknown or Not Reported000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)BI 1467335 Normal (R)BI 1467335 Moderate (T)Total
American Indian or Alaska Native000
Asian000
Native Hawaiian or Other Pacific Islander000
Black or African American000
White101020
More than one race000
Unknown or Not Reported000
07

Study locations

1 site
  • CRS Clinical Research Services Kiel GmbH
    Kiel, 24105, Germany
08

References and documents

Related links

Study documents

  • Study protocol · Mar 15, 2018
  • Statistical analysis plan · Oct 10, 2018

Documents are hosted by the registry — open the source record to download them.

09

Registry details

Key details

Study ID
NCT03302091
Lead sponsor
Boehringer Ingelheim
Responsible party
Sponsor
First posted
Oct 4, 2017
Start date
Oct 17, 2017
Primary completion
Aug 16, 2018
Completion
Aug 16, 2018
Results posted
Jun 4, 2021
Last update
Jun 4, 2021

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
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