Renal Insufficiency
Conditions
Brief summary
This study is open to people with and without kidney problems. People can join the study if they are 18 years or older and have a body mass index (BMI) between 18.5 and 35 kg/m2. Iclepertin is a medicine that is being developed to treat diseases of the brain. The purpose of this study is to find out whether having kidney problems influences how iclepertin is taken up in the body. All participants take iclepertin once as a tablet. Participants are in the study for 2 to 3 weeks. During this time, they visit the study site 6 times. For one of the visits, participants stay 4 nights at the study site. The site staff measures the amount of iclepertin in the blood. The doctors also regularly check participants' health and take note of any unwanted effects.
Interventions
DRUGBI 425809
Iclepertin orally as film-coated tablet.
Sponsors
Boehringer Ingelheim
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Non-randomised, single dose, open-label, individual-matched design.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
applicable to all participants * Male or female participants * Age of at least 18 years (inclusive) * BMI of 18.5 to 35 kilogram per square metre (kg/m2) (inclusive) * Signed and dated written informed consent in accordance with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) - Good Clinical Practice (GCP) and local legislation prior to admission to the trial * Male participants are not required to use contraception * Woman of childbearing potential (WOCP) are allowed to participate provided they use a highly effective contraception from at least 30 days before the administration of trial medication until 30 days after trial completion. The following methods of contraception are considered adequate for female participants of childbearing potential: * Use of combined (oestrogen and progestogen containing) hormonal contraception that prevents ovulation (oral, intravaginal or transdermal), plus condom * Use of progestogen-only hormonal contraception that inhibits ovulation (only injectables or implants), plus condom * Use of intrauterine device (IUD) or intrauterine hormone-releasing system (IUS) * Sexually abstinent * A vasectomised sexual partner who received medical assessment of the surgical success (documented absence of sperm) and provided that partner is the sole sexual partner of the trial participant. Female participants are not considered to be of childbearing potential if they are either surgically sterilised (including hysterectomy) or postmenopausal, defined as no menses for 1 year without an alternative medical cause (in questionable cases a blood sample with levels of Follicle-stimulating hormone (FSH) above 40 Units per Litre (U/L) and oestradiol below 30 nanogram per Litre (ng/L) is confirmatory) Inclusion criteria applying only to participants with impaired renal function * Renal impairment based on assessment of estimated Glomerular Filtration Rate (eGFR) at screening (severe renal impairment: 15-29 millilitre per minute per 1.73 square metre (mL/min/1.73 m2), moderate renal impairment: 30-59 mL/min/1.73 m2, mild renal impairment: 60-89 mL/min/1.73 m2) * Chronic renal impairment \> 12 months (documented renal impairment indicated by reduced eGFR for more than 12 months until screening) * Absence of clinically significant abnormalities, as based on a complete medical history including a full physical examination, vital signs (Blood Pressure (BP), Pulse Rate (PR)), 12-lead electrocardiogram (ECG), and clinical laboratory tests at both screening and check-in, with the exception of findings that in the opinion of the investigator are consistent with the participant's renal impairment * Medication and/or treatment regimens must have been stable (i.e., no dose adjustments) for at least 4 weeks prior to the screening period and should be kept stable until study completion. Fluctuating treatment regimens may be considered for inclusion on a case-by-case basis if the underlying disease is under control in the opinion of the investigator and must be agreed to by both the investigator and the sponsor's medical monitor Inclusion criteria applying only to participants with normal renal function * Individually matched to participants with renal impairment according to sex, age, and weight, and race * eGFR ≥ 90 mL/min/1.73 m2 * Absence of clinically significant abnormalities identified by a detailed medical history, full physical examination, vital signs and 12-lead ECG at both screening and check-in visits * Absence of clinically significant abnormalities identified by a laboratory test at screening visit
Exclusion criteria
applying to all participants * Any evidence of a concomitant disease assessed as clinically relevant by the investigator * Cholecystectomy or other surgery of the gastrointestinal tract that could interfere with the pharmacokinetics (PK) of the trial medication (except appendectomy or simple hernia repair) * Diseases of the Central Nervous System (CNS) (including but not limited to any kind of seizures or stroke), and other relevant neurological or psychiatric disorders (including but not limited to major depressive disorder) * History of relevant orthostatic hypotension, fainting spells, or blackouts * Relevant chronic or acute infections * Any documented active or suspected malignancy or history of malignancy within 5 years prior to screening, except appropriately treated basal cell carcinoma of the skin * History of relevant allergy or hypersensitivity (including allergy to the trial medication or its excipients) * Use of drugs within 30 days (or 5 of its half-lives, whichever is longer) of planned administration of trial medication that might reasonably influence the results of the trial (including drugs that cause ECG interval from the start of the QRS complex to the end of the T wave (QT interval) / QT interval corrected for heart rate, e.g. using the method of Fridericia (QTcF) or Bazett (QTcB) (QTc interval) prolongation ) Further
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve of Iclepertin in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | Within 2 hours (h) prior to drug administration and 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 24, 36, 48, 72, 96, 120 and 144 h after drug administration. | Area under the concentration-time curve of Iclepertin in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) is reported. Geometric Least Squares Mean and adjusted geometric standard error were calculated using an analysis of variance (ANOVA) model on the logarithmic scale. The pharmacokinetic (PK) endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model, which included effects accounting for the following sources of variation: 'degree of renal impairment' as fixed effect, 'matched pair' as random effect. These quantities were then back-transformed to the original scale. Geometric Mean=Geometric Least Squares Mean and Standard Error= adjusted geometric standard error. |
| Maximum Measured Concentration of Iclepertin in Plasma (Cmax) | Within 2 hours (h) prior to drug administration and 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 24, 36, 48, 72, 96, 120 and 144 h after drug administration. | Maximum measured concentration of Iclepertin in plasma (Cmax) is reported. Geometric Least Squares Mean and adjusted geometric standard error were calculated using an analysis of variance (ANOVA) model on the logarithmic scale. The pharmacokinetic (PK) endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model, which included effects accounting for the following sources of variation: 'degree of renal impairment' as fixed effect, 'matched pair' as random effect. These quantities were then back-transformed to the original scale. Geometric Mean=Geometric Least Squares Mean and Standard Error= adjusted geometric standard error. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve of Iclepertin in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | Within 2 hours (h) prior to drug administration and 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 24, 36, 48, 72, 96, 120 and 144 h after drug administration. | Area under the concentration-time curve of Iclepertin in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) is reported. Geometric Least Squares Mean and adjusted geometric standard error were calculated using an analysis of variance (ANOVA) model on the logarithmic scale. The pharmacokinetic (PK) endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model, which included effects accounting for the following sources of variation: 'degree of renal impairment' as fixed effect, 'matched pair' as random effect. These quantities were then back-transformed to the original scale. Geometric Mean=Geometric Least Squares Mean and Standard Error= adjusted geometric standard error. |
Countries
Germany
Participant flow
Recruitment details
This was a non-randomised, single-dose, open-label, parallel, individual-matched design trial. This trial included participants with either impaired or normal renal function who were treated with BI 425809 (Iclepertin).
Pre-assignment details
All participants were screened for eligibility prior to participation in the trial. Participants attended a specialist site which ensured that the participants strictly met all inclusion and none of the exclusion criteria. Participants were not to be entered in the trial if any of the entry criteria were violated.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 71.5 Years STANDARD_DEVIATION 11.1 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 36 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 7 | 0 / 8 | 0 / 7 |
| other Total, other adverse events | 4 / 8 | 0 / 8 | 1 / 8 | 1 / 7 | 0 / 8 | 0 / 7 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 7 | 0 / 8 | 0 / 7 |
Outcome results
None listed