Clinical trial NCT05071729: A Study to Learn How Elinzanetant Moves Into, Through, and Out of the Body, How Safe it is, and How it Affects the Body in Participants With Kidneys That do Not Work as Well as They Should Compared to Participants Whose Kidneys Work Normally
Official title: Open-label Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Elinzanetant in Participants With Impaired Renal Function in Comparison to Matched Controls With Normal Renal Function
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Vasomotor Symptoms as a Sex Hormone-dependent Disorder in Women and Men
Keywords: Hot flushes
Elinzanetant
Investigation of pharmacokinetics and safety in renal impaired participants
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2021-10-08
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Researchers are looking for a better way to treat people who have vasomotor symptoms (VMS).

The symptoms of VMS are hot flashes. These symptoms can be caused by changes in sex hormone levels. An example of a change in sex hormone levels is when a woman reaches the time in their life where they no longer have their period. Hormones are substances in the blood that help body organs to work in specific ways. Women who no longer have their period may have a protein called neurokinin sending more signals than usual to other parts of the body. Researchers think that this may play a role in causing VMS.

In this study, the researchers want to learn more about a new substance called elinzanetant. Researchers think elinzanetant may help people with VMS. It works by blocking neurokinin from sending signals to other parts of the body. There are treatments available for VMS, but these do not work for all people and may cause medical problems for some people.

The main purpose of this study is to help the researchers learn more about how elinzanetant moves into, through and out of the body in participants with kidneys that do not work as well as they should compared to healthy participants whose kidneys work normally. To do this, the doctors will take blood samples from the participants at different times during the study and measure the levels of elinzanetant in the blood. This will help the researchers learn more about whether elinzanetant could be given to treat VMS in people who also have kidneys that do not work as well as they should.

This study will include adult participants who have kidneys that do not work as well as they should and participants whose kidneys work normally. The participants who have kidneys that do not work as well as they should will be split into 2 groups based on how severe their kidney problems are. All of the participants will take elinzanetant once as a tablet by mouth.

The participants will be in the study for about 1 month and will stay at their study site for 7 days in a row. During this visit, the participants will:

* have their overall health checked
* have scans of their heart taken using an electrocardiogram
* have blood and urine samples taken
* answer questions about how they are feeling, what medications they are taking, and what adverse events they are having

The doctors will keep track of any adverse events. An adverse event is any medical problem that a participant has during a study. Doctors keep track of all adverse events that happen in studies, even if they do not think the adverse events might be related to the study treatments.


Eligibility criteria: Inclusion Criteria:

* Participant must be 18 to 79 years of age inclusive, at the time of signing the informed consent.
* Moderate or severe renal impairment as assessed by estimated glomerular filtration rate (eGFR) based on serum creatinine collected 2 to 10 days prior to dosing and calculated according to a modified Chronic Kidney Disease Epidemiology Collaboration formula (CKD-EPI). Moderately impaired renal function: eGFR: 30 up to 59 mL/min/1.73 m\^2 (inclusive); Severely impaired renal function: eGFR \< 30 mL/min/ 1.73 m\^2 (including at least 50% patients requiring hemodialysis).
* Stable renal disease, i.e. a serum creatinine value determined 3 or more months before screening (e.g. during routine diagnostics) should not differ by more than 25% from the serum creatinine value determined at screening.
* Normal renal function, as assessed by eGFR based on serum creatinine at screening according to the modified CKD-EPI formula: eGFR ≥90 mL/min/1.73 m\^2.
* Body mass index (BMI) within the range 18 - 32 kg/m\^2 (inclusive).
* Male or female.
* Study participants of reproductive potential must agree to use adequate contraception when sexually active. This applies for the time period from signing of the informed consent form (ICF) until the follow-up visit on Day 6. Use of adequate contraception should be consistent with local regulations.

Exclusion Criteria:

* Any relevant disease (other than those related to renal impairment for the renal impaired participants) within 4 weeks prior to study drug administration including infections and acute gastro-intestinal diseases (with vomiting, diarrhea, constipation, etc.) requiring medical treatment.
* Acute renal failure or acute nephritis within the past 2 years.
* Malignancy diagnosed or treated within the past 5 years (hepatocellular carcinoma within the past 2 years). This does not include adequately treated basal cell carcinoma or localized squamous cell carcinoma of the skin.
* Conditions associated with a risk of hypersensitivity reactions with study intervention (active substances, or excipients of the preparations) as judged by the investigator.
* Dialysis for acute renal failure within the previous 6 months prior to administration of study intervention.
* Use of drugs which may affect absorption (e.g. loperamide, metoclopramide),and systemic administration of any broad-spectrum antibiotic within 1 week before study drug administration, unless the drug is part of the mandatory dosing regimen for treatment of renal impairment or related conditions.
* Use of drugs which may affect absorption by increasing the gastro-intestinal pH e.g. proton pump inhibitors from 2 weeks before study drug administration until last day of blood sampling for PK after study drug administration.
* Use of anti-coagulant drugs other than 100 mg acetylsalicylic acid per day.
* Major change of any medication regimen less than 2 weeks prior to first study drug administration, including dose adjustments.
* Indication for immunosuppressants, receiving cytotoxic therapy, immunosuppressive therapy, or other immunotherapy within 6 months prior to administration of study intervention
* Women of childbearing potential with a positive pregnancy test at screening or on Day -1.

Primary outcomes:
measure: Area under the concentration vs. time curve in plasma from zero to infinity (AUCu) (unbound)
timeFrame: Predose up to 120 hours
measure: Maximum observed (unbound) drug concentration (Cmax,u)
timeFrame: Predose up to 120 hours
Secondary outcomes:
measure: Number of participants with treatment-emergent adverse events, categorized by severity
timeFrame: After administration of study intervention up to the follow-up visit on Day 6.
Other outcomes:
Locations:
city: Miami
country: United States
facility: Clinical Pharmacology of Miami, LLC
state: Florida
city: Orlando
country: United States
facility: Orlando Clinical Research Center
state: Florida
Study officials:
References: