RECRUITING

A Phase I Study to Investigate the Effects of Renal Impairment on the Pharmacokinetics, Safety, and Tolerability of Opemalirsen (AZD2373)

Conditions

Renal Impairment AZD2373 Pharmacokinetics Severe Mild Moderate Matched Healthy Controls opemalirsen

Quick Navigation

Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This study is being conducted to investigate the PK, safety, and tolerability of opemalirsen in participants with renal impairment, compared to participants with normal renal function.

Official Title

A Single-Dose, Non-Randomised, Open-Label, Parallel-Group Study to Investigate the Effects of Renal Impairment on the Pharmacokinetics, Safety, and Tolerability of Opemalirsen (AZD2373)

Quick Facts

Study Start:2025-08-18

Study Completion:2025-12-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT07154901

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 80 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:Yes

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Participants are eligible to be included in the study only if all of the following criteria apply: 1. Participant must be 18 to 80 years of age, inclusive, at the time of signing the informed consent. Type of Participant and Disease Characteristics For all participants, BSA-adjusted eGFR will be determined by the local laboratory, calculated based on serum creatinine using the CKD-EPI equation (see Section 4.1). 2. Participant must be medically healthy with no clinically significant medical history, physical examination, clinical laboratory profiles, vital signs, or 12-lead ECGs, as deemed by the investigator at screening and Day -1. 3. Have an eGFR of ≥ 90 mL/min determined at screening. 1. Group 2: have severe renal impairment (eGFR \< 30 mL/min), not requiring dialysis. 2. Group 3 (optional): have moderate renal impairment (eGFR ≥ 30 to \< 60 mL/min) 3. Group 4 (optional): have mild renal impairment (eGFR ≥ 60 to \< 90 mL/min) 6 Participants on angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, beta-blocker, diuretics, or on any other cardiorenal relevant treatment should be on a stable dose for at least 2 weeks prior to screening. Weight 7 Body weight of at least 50 kg and body mass index (BMI) within the range 18 to 40 kg/m2 (inclusive). Sex and Contraceptive/Barrier Requirements 8 Male and/or female, assigned at birth, inclusive of all gender identities. 9 Contraceptive use by participants should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. * Females \< 50 years old would be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatment and follicle stimulating hormone levels in the postmenopausal range. * Females ≥ 50 years old would be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of all exogenous hormonal treatment. (i) Female participants should be stable on the chosen method of contraception for a minimum of 3 months before entering the study. (ii) Female participants of childbearing potential must use one highly effective form of birth control. A highly effective method of contraception is defined as one that can achieve a failure rate of less than 1% per year when used consistently and correctly. Females of childbearing potential who are sexually active with a non-sterilised male partner must agree to use one highly effective method of birth control, as defined below, throughout the study and until at least 3 months after discharge. Cessation of contraception after this point should be discussed with a responsible physician. Note: contraception is not required for female participants of non-childbearing potential. * Highly effective birth control methods include: * Non-hormonal • Total sexual abstinence provided it is the usual lifestyle of the participant (defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments) • a vasectomised partner (confirmed absence of sperm in semen) • bilateral tubal occlusion * Hormonal contraceptives associated with inhibition of ovulation levonorgestrel intrauterine system • medroxyprogesterone injections • combined Oral or transdermal contraceptives (ethinyl estradiol plus progestin) • intravaginal device (eg, EE and etonogestrel) The following are not acceptable methods of contraception: female condom, periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhoea.	* Medical Conditions 1. History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity, as judged by the investigator, at screening or Day -1, or history of hypersensitivity to drugs with a similar chemical structure or class to opemalirsen. 2. History of any major surgical procedure within 30 days prior to study intervention. 3. Judgement by the investigator that the participant should not participate in the study if they have any ongoing or recent (ie, during the screening period) minor medical complaints that may interfere with the interpretation of study data or if they are considered unlikely to comply with study procedures, restrictions, and requirements. 4. Liver disease (non-alcoholic and alcoholic steatohepatitis; drug-induced, viral, or autoimmune hepatitis; primary biliary cirrhosis; primary sclerosing cholangitis; hemochromatosis; alpha-1 antitrypsin deficiency; Wilson's disease) including positive results for hepatitis B surface antigen, hepatitis B core antibody or hepatitis C virus antibody. 5. History of cirrhosis and/or hepatic decompensation, including ascites, hepatic encephalopathy, or variceal bleeding. 6. QTcF \> 470 ms in participants without bundle branch block and \> 480 ms in participants with bundle branch block. 7. Any of the following out of range laboratory values: 1. ALT or AST \> 1.5 × ULN 2. TBL \> ULN (an isolated increase in TBL in participants with Gilbert syndrome is not a reason for exclusion) 3. INR \> 1.2, unless related to therapeutic anticoagulation 4. APTT ≥ 1.3 × normal, unless related to therapeutic anticoagulation 5. HbA1c ≥ 10% 8. Positive test for human immunodeficiency virus at screening. 9. Known history of drug or alcohol abuse within 1 year of screening. 10. Any clinically significant disease or disorder (eg, cardiovascular, pulmonary, gastrointestinal, liver, renal, neurological, musculoskeletal including bone fractures, endocrine including adrenal insufficiency, metabolic, malignant, psychiatric, major physical impairment) which, in the opinion of the investigator, may put the participant at risk because of participation in the study, influence the results of the study, or affect the participant's ability to participate in the study. 11. Abnormal resting vital signs (after resting for 10 minutes) of supine BP \> 150 mmHg or \< 90 mmHg systolic or \> 95 mmHg or \< 50 mmHg diastolic or supine pulse rate ≥ 100 bpm or ≤ 45 bpm. Note: the blood pressure values will be based on the average of the 3 measurements. 12. Evidence of rapidly deteriorating renal function. 13. Presence of unstable medical (eg, diabetes) or psychological conditions which, in the opinion of the investigator, would compromise the participant's safety or successful participation in this study. 14. Renal transplant patients, that is, participants that have received a kidney transplant or participants waiting for organ transplant scheduled to occur during the study, and those with a history of acute kidney injury occurring within 3 months prior to screening. 15. Abnormal resting vital signs (after resting for 10 minutes) of supine BP \> 180 mmHg or \< 110 mmHg systolic or \> 110 mmHg or \< 60 mmHg diastolic or supine pulse rate ≥ 100 bpm or ≤ 40 bpm. Note: the blood pressure values will be based on the average of the 3 measurements. 16. Use of any prescription or non-prescription drugs (including vitamins, recreational drugs, and dietary or herbal supplements) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) before study intervention, unless, in the opinion of the investigator and sponsor, the medication will not interfere with the study. 17. Use of concurrent medication, which affect creatinine clearance such as cephalosporin antibiotics, ascorbic acid, trimethoprim, cimetidine, quinine within 7 days prior to Day -1. 18. Has received another new chemical entity (defined as a compound which has not been approved for marketing) within 30 days of study intervention in this study or, if known, 5 half-lives from last dose in the previous study to study intervention in this study, whichever is longest. 19. Previous enrolment in the present study. Note: participants consented and screened, but not receiving study intervention in this study or a previous Phase I study, are not excluded. Other Exclusions 20. Positive screen for drugs of abuse (unless participant has renal impairment and positive screen is due to medication\[s\] prescribed by physician) and/or alcohol test at screening or Day -1; a positive result for tetrahydrocannabinol and/or cannabinoids is not considered exclusionary. 21. Receipt of blood products within 2 months prior to Day -1, plasma or platelets donation within 1 month prior to Day -1, or any blood donation/blood loss \> 500 mL within

Inclusion Criteria

Exclusion Criteria

* Participants are eligible to be included in the study only if all of the following criteria apply:
1. Participant must be 18 to 80 years of age, inclusive, at the time of signing the informed consent. Type of Participant and Disease Characteristics For all participants, BSA-adjusted eGFR will be determined by the local laboratory, calculated based on serum creatinine using the CKD-EPI equation (see Section 4.1).
2. Participant must be medically healthy with no clinically significant medical history, physical examination, clinical laboratory profiles, vital signs, or 12-lead ECGs, as deemed by the investigator at screening and Day -1.
3. Have an eGFR of ≥ 90 mL/min determined at screening.
1. Group 2: have severe renal impairment (eGFR \< 30 mL/min), not requiring dialysis.
2. Group 3 (optional): have moderate renal impairment (eGFR ≥ 30 to \< 60 mL/min)
3. Group 4 (optional): have mild renal impairment (eGFR ≥ 60 to \< 90 mL/min) 6 Participants on angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, beta-blocker, diuretics, or on any other cardiorenal relevant treatment should be on a stable dose for at least 2 weeks prior to screening. Weight 7 Body weight of at least 50 kg and body mass index (BMI) within the range 18 to 40 kg/m2 (inclusive). Sex and Contraceptive/Barrier Requirements 8 Male and/or female, assigned at birth, inclusive of all gender identities. 9 Contraceptive use by participants should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
* Females \< 50 years old would be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatment and follicle stimulating hormone levels in the postmenopausal range.
* Females ≥ 50 years old would be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of all exogenous hormonal treatment. (i) Female participants should be stable on the chosen method of contraception for a minimum of 3 months before entering the study. (ii) Female participants of childbearing potential must use one highly effective form of birth control. A highly effective method of contraception is defined as one that can achieve a failure rate of less than 1% per year when used consistently and correctly. Females of childbearing potential who are sexually active with a non-sterilised male partner must agree to use one highly effective method of birth control, as defined below, throughout the study and until at least 3 months after discharge. Cessation of contraception after this point should be discussed with a responsible physician. Note: contraception is not required for female participants of non-childbearing potential.
* Highly effective birth control methods include:
* Non-hormonal • Total sexual abstinence provided it is the usual lifestyle of the participant (defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments) • a vasectomised partner (confirmed absence of sperm in semen) • bilateral tubal occlusion
* Hormonal contraceptives associated with inhibition of ovulation levonorgestrel intrauterine system • medroxyprogesterone injections • combined Oral or transdermal contraceptives (ethinyl estradiol plus progestin) • intravaginal device (eg, EE and etonogestrel) The following are not acceptable methods of contraception: female condom, periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhoea.

* Medical Conditions
1. History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity, as judged by the investigator, at screening or Day -1, or history of hypersensitivity to drugs with a similar chemical structure or class to opemalirsen.
2. History of any major surgical procedure within 30 days prior to study intervention.
3. Judgement by the investigator that the participant should not participate in the study if they have any ongoing or recent (ie, during the screening period) minor medical complaints that may interfere with the interpretation of study data or if they are considered unlikely to comply with study procedures, restrictions, and requirements.
4. Liver disease (non-alcoholic and alcoholic steatohepatitis; drug-induced, viral, or autoimmune hepatitis; primary biliary cirrhosis; primary sclerosing cholangitis; hemochromatosis; alpha-1 antitrypsin deficiency; Wilson's disease) including positive results for hepatitis B surface antigen, hepatitis B core antibody or hepatitis C virus antibody.
5. History of cirrhosis and/or hepatic decompensation, including ascites, hepatic encephalopathy, or variceal bleeding.
6. QTcF \> 470 ms in participants without bundle branch block and \> 480 ms in participants with bundle branch block.
7. Any of the following out of range laboratory values:
1. ALT or AST \> 1.5 × ULN
2. TBL \> ULN (an isolated increase in TBL in participants with Gilbert syndrome is not a reason for exclusion)
3. INR \> 1.2, unless related to therapeutic anticoagulation
4. APTT ≥ 1.3 × normal, unless related to therapeutic anticoagulation
5. HbA1c ≥ 10%
8. Positive test for human immunodeficiency virus at screening.
9. Known history of drug or alcohol abuse within 1 year of screening.
10. Any clinically significant disease or disorder (eg, cardiovascular, pulmonary, gastrointestinal, liver, renal, neurological, musculoskeletal including bone fractures, endocrine including adrenal insufficiency, metabolic, malignant, psychiatric, major physical impairment) which, in the opinion of the investigator, may put the participant at risk because of participation in the study, influence the results of the study, or affect the participant's ability to participate in the study.
11. Abnormal resting vital signs (after resting for 10 minutes) of supine BP \> 150 mmHg or \< 90 mmHg systolic or \> 95 mmHg or \< 50 mmHg diastolic or supine pulse rate ≥ 100 bpm or ≤ 45 bpm. Note: the blood pressure values will be based on the average of the 3 measurements.
12. Evidence of rapidly deteriorating renal function.
13. Presence of unstable medical (eg, diabetes) or psychological conditions which, in the opinion of the investigator, would compromise the participant's safety or successful participation in this study.
14. Renal transplant patients, that is, participants that have received a kidney transplant or participants waiting for organ transplant scheduled to occur during the study, and those with a history of acute kidney injury occurring within 3 months prior to screening.
15. Abnormal resting vital signs (after resting for 10 minutes) of supine BP \> 180 mmHg or \< 110 mmHg systolic or \> 110 mmHg or \< 60 mmHg diastolic or supine pulse rate ≥ 100 bpm or ≤ 40 bpm. Note: the blood pressure values will be based on the average of the 3 measurements.
16. Use of any prescription or non-prescription drugs (including vitamins, recreational drugs, and dietary or herbal supplements) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) before study intervention, unless, in the opinion of the investigator and sponsor, the medication will not interfere with the study.
17. Use of concurrent medication, which affect creatinine clearance such as cephalosporin antibiotics, ascorbic acid, trimethoprim, cimetidine, quinine within 7 days prior to Day -1.
18. Has received another new chemical entity (defined as a compound which has not been approved for marketing) within 30 days of study intervention in this study or, if known, 5 half-lives from last dose in the previous study to study intervention in this study, whichever is longest.
19. Previous enrolment in the present study. Note: participants consented and screened, but not receiving study intervention in this study or a previous Phase I study, are not excluded. Other Exclusions
20. Positive screen for drugs of abuse (unless participant has renal impairment and positive screen is due to medication\[s\] prescribed by physician) and/or alcohol test at screening or Day -1; a positive result for tetrahydrocannabinol and/or cannabinoids is not considered exclusionary.
21. Receipt of blood products within 2 months prior to Day -1, plasma or platelets donation within 1 month prior to Day -1, or any blood donation/blood loss \> 500 mL within

Contacts and Locations

Study Contact

AstraZeneca Clinical Study Information Center

CONTACT

1-877-240-9479

information.center@astrazeneca.com

Study Locations (Sites)

Research Site

Miami, Florida, 33172

United States

Research Site

Orlando, Florida, 32808

United States

Collaborators and Investigators

Sponsor: AstraZeneca

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-08-18

Study Completion Date2025-12-31

Study Record Updates

Study Start Date2025-08-18

Study Completion Date2025-12-31

Terms related to this study

Keywords Provided by Researchers

Renal impairment
AZD2373
Pharmacokinetics
Severe
Mild
Moderate
Matched Healthy Controls
opemalirsen

Additional Relevant MeSH Terms

Renal Impairment