Renal ImpairmentPhase 1NCT04949438
A Study to Assess the Pharmacokinetics (Uptake of Drugs by the Body), Safety and Tolerability of AZD4831 in Participants With Severe Renal Impairment and Healthy Volunteers
A Phase 1 study testing AZD4831 in people with Renal Impairment, run by AstraZeneca at 1 site in Bulgaria.
Trial summary
This is a study to compare AZD4831 pharmacokinetic (PK) parameters between participants with severe renal impairment and matched healthy volunteers following a single dose administration. Read more about this study
- Who is it for?
- Ages 18 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Renal Impairment
- What is being tested?
- AZD4831
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteBulgaria
- Study dates
- 21 Jan 2022to 4 Mar 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- All participants must be 18 to 80 (inclusive) years of age, at the time of signing the informed consent.
- The age of participants in Cohort 2 (matched healthy volunteers) must not be lesser than 10 years below the lowest age in Cohort 1 (participants with severe renal impairment) or greater than 10 years above the highest age in Cohort 1.
- Healthy volunteers only (Cohort 2):
- Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring.
- An eGFR of ≥90 mL/min/1.73m^2 as determined at screening using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula.
- Participants with severe renal impairment only (Cohort 1):
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- An eGFR of ≥15 to <30 mL/min/1.73m^2 as determined at screening using the CKD-EPI formula.
- Stable renal function.
- If participants are on statin, ACEi/ARB, beta-blocker, diuretic or on any other cardiorenal relevant treatment, the dose should be stable at least 2 weeks prior to screening (Visit 1).
- Body weight of at least 50 kg and body mass index (BMI) within the range ≥18 to ≤35 kg/m^2.
- BMI of participants in Cohort 2 (healthy volunteers) must not be more than 20% below the lowest BMI in Cohort 1 (participants with severe renal impairment) or more than 20% above the highest BMI in Cohort 1.
- Male or female of non-childbearing potential.
- There should be an equal number of male and female participants in Cohort 2 (healthy volunteers) as in Cohort 1 (participants with severe renal impairment).
- Male participants: All male participants should use methods of contraception consistent with local regulations for those participating in clinical studies.
- Highly effective birth control methods are defined as those that can achieve a failure rate of less than 1% per year when used consistently and correctly
- Female participants: Must have a negative serum pregnancy test at screening and admission to the study centre (Day -1), must not be lactating and must be of non-childbearing potential confirmed at screening.
- Male participants should not donate sperm for the duration of the study and for at least 90 days after the last study follow-up visit.
- Provision of signed and dated written Optional Genetic Research Information informed consent prior to collection of samples for optional genetic research.
Who cannot join
- Any evidence of a clinically significant disease or disorder.
- Positive hepatitis C antibody, hepatitis B virus surface antigen, hepatitis B virus core antibody, or human immunodeficiency virus I or II at screening (Visit 1).
- History of drug or alcohol abuse within 1 year of screening or positive test for drugs of abuse and alcohol at screening and admission to the study centre.
- History of allergy/hypersensitivity to drugs with a similar chemical structure or class to AZD4831or any of the excipients of the product.
- Any of the following signs or confirmation of Corona Virus 2019 (COVID-19) infection
- Participant has a positive severe acute respiratory syndrome coronavirus 2 reverse transcription-polymerase chain reaction test result within 2 weeks before screening (Visit 1) or between screening and admission to study centre (Visit 2).
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- Clinical signs and symptoms consistent with COVID-19 (eg, fever, dry cough, dyspnoea, sore throat, fatigue) 2 weeks before screening (Visit 1) or between screening and admission to study centre (Visit 2).
- Participant has been previously hospitalised with COVID-19 infection within the last 3 months.
- Healthy volunteers only (Cohort 2):
- History or presence of gastrointestinal, hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
- Participants with severe renal impairment only (Cohort 1):
- Renal transplant participants or participants on dialysis.
- Use of concurrent medication, which affect creatinine clearance such as cephalosporin antibiotics, ascorbic acid, trimethoprim, cimetidine, or quinine within days of admission to the study centre (Day -1).
- Use of drugs with enzyme-inducing properties such as St John's Wort within 7 days or 5 half-lives (whichever is longer) prior to screening (Visit 1).
- Any concomitant medications known to be associated with Torsades de Pointes or strong cytochrome P450 3A4 (CYP3A4) inducers or inhibitors.
- Healthy volunteers only (Cohort 2):
- Use of any prescribed or non-prescribed medication including antacids, analgesics (other than paracetamol), herbal remedies, megadose vitamins and minerals within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) before the study intervention and until completion of the follow-up visits.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Single Dose, Non-Randomised, Open-Label, Parallel Group Study to Assess the Pharmacokinetics, Safety and Tolerability of AZD4831 in Participants With Severe Renal Impairment and Healthy Volunteers
This is a study to compare AZD4831 pharmacokinetic (PK) parameters between participants with severe renal impairment and matched healthy volunteers following a single dose administration.
Read the detailed description
All participants will receive a single oral dose of AZD4831 under fasted conditions and will be involved in the study approximately 2 weeks after dosing and up to approximately 38 days from screening.
Approximately 10 participants will be enrolled into each of the 2 cohorts parallelly and receive the study intervention to achieve 8 evaluable participants in each cohort.
- Cohort 1: 10 participants with severe renal impairment (Estimated glomerular filtration rate [eGFR] of ≥15 to <30 mL/min/1.73m^2)
- Cohort 2: 10 matched healthy volunteers with normal renal function (eGFR of ≥90 mL/min/1.73m^2).
The study will comprise of the following study periods:
- Screening period (21 days): participants will be screened for eligibility.
- Treatment period (3 days): participants will be admitted to the study centre in the evening of (Day -1) the day before administration of a single oral dose of AZD4831 (Day 1), and will be discharged after at least 24 h post-dose (Day 2).
- Follow-up period (13±2 days): participants will attend 5 visits at the study centre for PK sampling and safety assessments on Days 3, 5, 8, 11 and 15.
- Conditions
- Renal Impairment
- Being tested
- AZD4831
- Keywords
- AZD4831, Pharmacokinetics, Estimated glomerular filtration rate
- Medical subject headings
- Renal Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD4831Drug
Participants will receive a single dose of AZD4831 administered with 240 mL of water after an overnight fast of at least 10 hours.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1: Participants with severe renal impairment | Experimental | Participants with severe renal impairment will receive a single oral dose of AZD4831 on Day 1. Receives: Drug: AZD4831 |
| Cohort 2 :Healthy participants | Experimental | Healthy participants will receive a single oral dose of AZD4831 on Day 1. Receives: Drug: AZD4831 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum observed plasma concentration (Cmax)
Assessment of Cmax of a single oral dose of AZD4831 in participants with severe renal impairment compared with that in matched healthy volunteers.
Measured: From Day 1 to Day 15
Time to reach maximum observed plasma concentration (tmax)
Assessment of tmax of a single oral dose of AZD4831 in participants with severe renal impairment compared with that in matched healthy volunteers.
Measured: From Day 1 to Day 15
Half-life associated with terminal slope (λz) of a semi-logarithmic concentration-time curve (t½λz)
Assessment of t½λz of a single oral dose of AZD4831 in participants with severe renal impairment compared with that in matched healthy volunteers.
Measured: From Day 1 to Day 15
Apparent total body clearance of drug from plasma after extravascular administration (CL/F)
Assessment of CL/F of a single oral dose of AZD4831 in participants with severe renal impairment compared with that in matched healthy volunteers.
Measured: From Day 1 to Day 15
Apparent total non-renal body clearance of drug from plasma after extravascular administration (CLNR/F)
Assessment of CLNR/F of a single oral dose of AZD4831 in participants with severe renal impairment compared with that in matched healthy volunteers.
Measured: From Day 1 to Day 15
Apparent volume of distribution during the terminal phase after extravascular administration (Vz/F)
Assessment of Vz/F of a single oral dose of AZD4831 in participants with severe renal impairment compared with that in matched healthy volunteers.
Measured: From Day 1 to Day 15
Area under the plasma concentration-curve from time zero to time of last quantifiable concentration (AUClast)
Assessment of AUClast of a single oral dose of AZD4831 in participants with severe renal impairment compared with that in matched healthy volunteers.
Measured: From Day 1 to Day 15
Area under plasma concentration-time curve from time zero to infinity (AUCinf)
Assessment of AUCinf of a single oral dose of AZD4831 in participants with severe renal impairment compared with that in matched healthy volunteers.
Measured: From Day 1 to Day 15
Renal clearance of drug from plasma (CLR)
Assessment of CLR of a single oral dose of AZD4831 in participants with severe renal impairment compared with that in matched healthy volunteers.
Measured: Days 1 and 2
Secondary outcomes (1)
Number of participants with adverse events
Assessment of the safety and tolerability of a single oral dose administration of AZD4831 in participants with severe renal impairment and their matched healthy volunteers.
Measured: From Screening (Day -21 to Day -1) until Day 15 or Early Termination Visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jul 2021
- Study start21 Jan 2022
- Primary completion4 Mar 2022
- Study completion4 Mar 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Renal ImpairmentStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Parexel
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04949438
- Sponsor's protocol ID
- D6580C00009
- Status last verified
- Mar 2022
- First submitted
- 25 Jun 2021
- Last updated
- 5 Apr 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
Study at a glance
From the registry record, last updated by the sponsor on 5 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single Dose, Non-Randomised, Open-Label, Parallel Group Study to Assess the Pharmacokinetics, Safety and Tolerability of AZD4831 in Participants With Severe Renal Impairment and Healthy Volunteers
- ClinicalTrials.gov ID
- NCT04949438
- Acronym / sponsor ID
- D6580C00009
- Conditions
- Renal Impairment
- Keywords
- AZD4831, Pharmacokinetics, Estimated glomerular filtration rate
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Collaborators
- Parexel
- Study start
- 21 Jan 2022 (actual)
- Primary completion
- 4 Mar 2022 (actual)
- Study completion
- 4 Mar 2022 (actual)
- First posted
- 2 Jul 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a study to compare AZD4831 pharmacokinetic (PK) parameters between participants with severe renal impairment and matched healthy volunteers following a single dose administration.
Detailed description
All participants will receive a single oral dose of AZD4831 under fasted conditions and will be involved in the study approximately 2 weeks after dosing and up to approximately 38 days from screening.
Approximately 10 participants will be enrolled into each of the 2 cohorts parallelly and receive the study intervention to achieve 8 evaluable participants in each cohort.
- Cohort 1: 10 participants with severe renal impairment (Estimated glomerular filtration rate [eGFR] of ≥15 to <30 mL/min/1.73m^2)
- Cohort 2: 10 matched healthy volunteers with normal renal function (eGFR of ≥90 mL/min/1.73m^2).
The study will comprise of the following study periods:
- Screening period (21 days): participants will be screened for eligibility.
- Treatment period (3 days): participants will be admitted to the study centre in the evening of (Day -1) the day before administration of a single oral dose of AZD4831 (Day 1), and will be discharged after at least 24 h post-dose (Day 2).
- Follow-up period (13±2 days): participants will attend 5 visits at the study centre for PK sampling and safety assessments on Days 3, 5, 8, 11 and 15.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort 1: Participants with severe renal impairment | Experimental | Drug: AZD4831Participants with severe renal impairment will receive a single oral dose of AZD4831 on Day 1. |
| Cohort 2 :Healthy participants | Experimental | Drug: AZD4831Healthy participants will receive a single oral dose of AZD4831 on Day 1. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- All participants must be 18 to 80 (inclusive) years of age, at the time of signing the informed consent.
- The age of participants in Cohort 2 (matched healthy volunteers) must not be lesser than 10 years below the lowest age in Cohort 1 (participants with severe renal impairment) or greater than 10 years above the highest age in Cohort 1.
- Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring.
- An eGFR of ≥90 mL/min/1.73m^2 as determined at screening using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula.
- An eGFR of ≥15 to <30 mL/min/1.73m^2 as determined at screening using the CKD-EPI formula.
Key exclusion criteria (17 listed)
- Any evidence of a clinically significant disease or disorder.
- Positive hepatitis C antibody, hepatitis B virus surface antigen, hepatitis B virus core antibody, or human immunodeficiency virus I or II at screening (Visit 1).
- History of drug or alcohol abuse within 1 year of screening or positive test for drugs of abuse and alcohol at screening and admission to the study centre.
- History of allergy/hypersensitivity to drugs with a similar chemical structure or class to AZD4831or any of the excipients of the product.
- Any of the following signs or confirmation of Corona Virus 2019 (COVID-19) infection
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AZD4831Participants will receive a single dose of AZD4831 administered with 240 mL of water after an overnight fast of at least 10 hours. | Drug | Cohort 1: Participants with severe renal impairment, Cohort 2 :Healthy participants |
Primary outcome
Maximum observed plasma concentration (Cmax)
Time frame: From Day 1 to Day 15
Assessment of Cmax of a single oral dose of AZD4831 in participants with severe renal impairment compared with that in matched healthy volunteers.
Time to reach maximum observed plasma concentration (tmax)
Time frame: From Day 1 to Day 15
Assessment of tmax of a single oral dose of AZD4831 in participants with severe renal impairment compared with that in matched healthy volunteers.
Half-life associated with terminal slope (λz) of a semi-logarithmic concentration-time curve (t½λz)
Time frame: From Day 1 to Day 15
Assessment of t½λz of a single oral dose of AZD4831 in participants with severe renal impairment compared with that in matched healthy volunteers.
Apparent total body clearance of drug from plasma after extravascular administration (CL/F)
Time frame: From Day 1 to Day 15
Assessment of CL/F of a single oral dose of AZD4831 in participants with severe renal impairment compared with that in matched healthy volunteers.
Apparent total non-renal body clearance of drug from plasma after extravascular administration (CLNR/F)
Time frame: From Day 1 to Day 15
Assessment of CLNR/F of a single oral dose of AZD4831 in participants with severe renal impairment compared with that in matched healthy volunteers.
Apparent volume of distribution during the terminal phase after extravascular administration (Vz/F)
Time frame: From Day 1 to Day 15
Assessment of Vz/F of a single oral dose of AZD4831 in participants with severe renal impairment compared with that in matched healthy volunteers.
Area under the plasma concentration-curve from time zero to time of last quantifiable concentration (AUClast)
Time frame: From Day 1 to Day 15
Assessment of AUClast of a single oral dose of AZD4831 in participants with severe renal impairment compared with that in matched healthy volunteers.
Area under plasma concentration-time curve from time zero to infinity (AUCinf)
Time frame: From Day 1 to Day 15
Assessment of AUCinf of a single oral dose of AZD4831 in participants with severe renal impairment compared with that in matched healthy volunteers.
Renal clearance of drug from plasma (CLR)
Time frame: Days 1 and 2
Assessment of CLR of a single oral dose of AZD4831 in participants with severe renal impairment compared with that in matched healthy volunteers.
1 secondary outcome
Number of participants with adverse events
Time frame: From Screening (Day -21 to Day -1) until Day 15 or Early Termination Visit
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Apr 2022.
- Individual participant dataSharing planned: Yes. Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AZD4831 in people with Renal Impairment, run by AstraZeneca at 1 site in Bulgaria.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Bulgaria. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum observed plasma concentration (Cmax) (time frame: From Day 1 to Day 15). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Apr 2022.