Study in Participants With Normal Kidney Function and Reduced Kidney Function to Test How Kidney Function Can Change What Happens to Obeldesivir in the Body

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Gilead Sciences Inc.

Participant type

Healthy volunteers

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02]

Trial duration

19 Mar 2024 → 15 Jun 2024

Decision date (initial)

2024-01-15

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic

To evaluate the single-dose pharmacokinetic of Obeldesivir in participants with renal impairment relative to matched control participants with normal renal function

Secondary objectives 2

1. To evaluate the safety and tolerability of administration of a single dose of ODV in participants with RI relative to matched control participants with normal renal function.
2. To evaluate the urine PK of ODV in participants with RI relative to matched control participants with normal renal function.

Conditions and MedDRA coding

Renal Impairment

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-236621-PIP20-23

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

1. All Participants Have the ability to understand and sign a written informed consent form (ICF), which must be obtained prior to initiation of study procedures.
2. Be aged 18 through 79 years, inclusive, at screening and at admission.
3. Have a calculated BMI of at least 18.0 and no greater than 38.0 kg/m2 at screening.
4. Participants assigned male at birth and participants assigned female at birth and of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified methods of contraception as described in Appendix 11.4.
5. Have not donated blood within 56 days of study entry or plasma within 7 days of study entry and must refrain from blood donation from clinic admission, throughout the study period, and continuing for at least 30 days following study drug administration.
6. Laboratory evaluations and 12-lead ECG evaluations at screening and admission must be without clinically significant abnormalities as assessed by the investigator.
7. Must be willing and able to comply with all study requirements.
8. Must, in the opinion of the investigator, be in good health (with the exception of renal function in the mild, moderate, and severe RI groups) based upon medical history and physical examination (PE), including vital signs.
9. Participants With Impaired Renal Function In addition to the criteria listed above, participants with RI must also meet the following additional inclusion criteria to be eligible for participation in this study: Must have an unchanged RI classification during the 3 months prior to screening and no evidence of worsening of clinical and/or laboratory signs of RI within the screening period.
10. Must have an eGFRCKD-EPI,creatinine at screening of: 60 ≤ eGFRCKD-EPI,creatinine < 90 mL/min/1.73 m2 for mild disease (Cohort 3a) or 30 ≤ eGFRCKD-EPI,creatinine < 60 mL/min/1.73 m2 for moderate disease (Cohort 1a) or 15 ≤ eGFRCKD-EPI,creatinine < 30 mL/min/1.73 m2 for severe disease (Cohort 2a).
11. Have hepatic transaminase (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) ≤ 2 x upper limit of normal (ULN) at screening and at admission.
12. Matched Control Participants In addition to the criteria listed above, matched control participants must also meet the following additional inclusion criteria to be eligible for participation in this study: Must have an eGFRCKD-EPI,creatinine of ≥ 90 mL/min/1.73 m2 at screening.
13. Must match in gender, age (± 10 years), and BMI (± 20%) with the respective participant in the RI group (Cohorts 1a, 2a, and 3a). Note: Participants with normal renal function can serve as a control for both mild and moderate RI cohorts, as long as the matching criteria are met, but may only serve as a matched control to one renal impaired participant within a cohort.
14. Have ALT and AST at or below the ULN at screening and at admission.

Exclusion criteria 14

1. All Participants Positive serum pregnancy test at screening and at admission (Appendix 11.4). Admission urine pregnancy test can be performed in addition to, but not in place of, admission serum pregnancy test when expedited serum pregnancy test results are unavailable.
2. Breastfeeding participant.
3. Participants who plan to donate sperm from clinic admission (ie, Day −1) throughout the study period, and through the required contraception period as described in Appendix 11.4.
4. Have received any study drug within 30 days prior to study dosing.
5. Have current alcohol or substance abuse judged by the investigator to potentially interfere with participant compliance or participant safety, or a positive drug or alcohol test at screening or admission.
6. Have a positive test result for HIV-1 or HIV-2 antibodies, hepatitis B virus (HBV) surface antigen, or hepatitis C virus (HCV) antibody at screening.
7. Have poor venous access that limits phlebotomy.
8. Have been treated with systemic steroids, immunosuppressant therapies, or chemotherapeutic agents within 3 months prior to screening or is expected to receive these agents during the study (eg, corticosteroids, immunoglobulins, other immune- or cytokine-based therapies).
9. Have any psychiatric illness (including depression) that, in the opinion of the investigator, would interfere with participant treatment, assessment, or compliance with the protocol.
10. Have a history of any of the following: a) Significant serious skin disease, such as but not limited to rash, food allergy, eczema, psoriasis, or urticaria. b) Significant drug sensitivity or drug allergy (such as anaphylaxis or hepatotoxicity). c) Known hypersensitivity to the study drug, its metabolites, or to formulation excipients (see Section 5). d) Significant cardiac disease (including history of myocardial infarction based on ECG and/or clinical history, any history of ventricular tachycardia, congestive heart failure, or dilated cardiomyopathy with lef+C12t ventricular ejection fraction ≤ 40%); or a family history of long QT syndrome, or unexplained death in an otherwise healthy individual between the ages of 1 and 30 years. e) Syncope, palpitations, or unexplained dizziness. f) Implanted defibrillator or pacemaker. g) Liver disease, including Gilbert syndrome. h) Severe peptic ulcer disease, gastroesophageal reflux disease, or other gastric acid hypersecretory conditions requiring prolonged (≥ 6 months) medical treatment. i) Medical or surgical treatment that permanently altered gastric absorption (eg, gastric or intestinal surgery). A history of cholecystectomy is not exclusionary.
11. Requirement for ongoing therapy with or prior use of any prohibited medications listed in Section 5.6.1.
12. Participants With Impaired Renal Function: Participants with RI requiring or anticipated to require dialysis within 6 months of dosing are not eligible.
13. Matched Control Participants: Have taken any prescription medications or over-the-counter medications, including herbal products, within 28 days prior to study drug administration, with the exception of vitamins, and/or acetaminophen and/or ibuprofen and/or hormonal contraceptive medications.
14. Have any serious or active medical illness that, in the opinion of the investigator, would interfere with participant treatment, assessment, or compliance with the protocol. This would include cardiac, hematological, hepatic, pulmonary (including chronic asthma), endocrine (including diabetes), central nervous, gastrointestinal (including an ulcer), vascular, metabolic (thyroid disorders, adrenal disease), and immunodeficiency disorders, active infection, or malignancy that are clinically significant or requiring treatment.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Plasma PK parameters Cmax, AUClast, and AUCinf of GS-441524 (ODV metabolite)

Secondary endpoints 2

1. Incidence of AEs and laboratory abnormalities.
2. Urine concentrations of GS-441524 (ODV metabolite) and its urine PK parameters (Ae, CLr, and %Fe).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Gilead Sciences Inc.

Sponsor organisation

Gilead Sciences Inc.

Address

333 Lakeside Drive

City

Foster City

Postcode

94404-1147

Country

United States

Scientific contact point

Organisation

Gilead Sciences Inc.

Contact name

EU CT Support

Public contact point

Organisation

Gilead Sciences Inc.

Contact name

EU CT Support

Third parties 4

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 2 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications