Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12624000083594
Ethics application status
Approved
Date submitted
1/12/2023
Date registered
30/01/2024
Date last updated
25/08/2024
Date data sharing statement initially provided
30/01/2024
Type of registration
Retrospectively registered

Titles & IDs
Public title
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
Scientific title
GS-US-611-6472 A Phase 1 Open-label, Parallel-Group, Single-Dose Study to Evaluate the Pharmacokinetics and Safety of Obeldesivir in Participants With Normal Renal Function and Renal Impairment
Secondary ID [1] 310791 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Renal Impairment 331765 0
Condition category
Condition code
Renal and Urogenital 328511 328511 0 0
Kidney disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Obeldesivir will be administered orally at the study site in the morning with 240 mL of water
following an overnight fast (no food or drinks, except water) for at least 10 hours. Additionally, participants will be restricted from water consumption 1 hour before until 2 hours after dosing, except for the 240 mL given with the study treatment. Participants will be allowed to consume clear liquids, such as broth or juices, following collection of the 2-hour post dose blood draw.
Approximately 60 unique participants will be enrolled to obtain at least 48 evaluable participants (8 per subcohort). Cohort 1 will enroll up to 20 participants (10 with moderate RI [Cohort 1a] and up to 10 matched controls [Cohort 1b]). Cohort 2 will enroll 20 participants (10 with severe RI [Cohort 2a] and 10 matched controls [Cohort 2b]). Cohort 3 will enroll up to 20 participants (10 with mild RI [Cohort 3a] and up to 10 matched controls [Cohort 3b]). Each participant with RI will have a matched control participant with normal renal function in the control subgroup.
Single oral dose of ODV 350 mg on Day 1 for mild and moderate RI and their matched controls; Single oral dose of ODV 175 mg on Day 1 for severe RI and their matched controls
ODV is administered as: Oral tablet
Each dose of study drug administered at the study site will be administered by qualified study site staff. The dose of study drug administered to participants will be done at the clinic under staff supervision and will be accurately recorded on source document and the study drug accountability form
Intervention code [1] 327205 0
Treatment: Drugs
Comparator / control treatment
Participants with normal renal functions will receive the same ODV dose as their matched renal impaired participant (ie, Cohort 1b and 3b to receive ODV 350 mg and Cohort 2b to receive ODV 175 mg).
Control group
Active

Outcomes
Primary outcome [1] 336335 0
To evaluate the single-dose pharmacokinetics (PK) of obeldesivir (ODV; GS-5245) in participants with renal impairment (RI) relative to matched control participants with normal renal function. Plasma PK Parameters to include Cmax, Clast, Tmax, Tlast, AUClast, AUCinf, %AUCexp, and t1/2.
Timepoint [1] 336335 0
To determine PK outcomes, blood samples will be collected on Day 1: predose (5 min before dose), 0.25, 0.5, 0.75, 1.5, 2, 3, 4, 6, 12 hours post dose; Day 2: 24 hours post dose; Day 3: 48 hours post dose; Day 4: 72 hours post dose, Day 5: 96 hours post dose; Day 6: 120 hours post dose, Day 7: 144 hours post dose, Day 8: 168 hours post dose; Day 9: 192 hours post dose; Day 10: 216 hours post dose and Day 11: 240 hours post dose.
Secondary outcome [1] 427891 0
This is a composite secondary outcome, which will be determined via the monitoring of adverse events, serious adverse events, concomitant medications, clinical laboratory analyses, vital signs measurements, electrocardiograms, and physical examinations
Timepoint [1] 427891 0
Adverse events and concomitant medications assessed daily to day 11 and at day 18 by telephone contact; vital signs taken daily to day 11; blood and urine samples for clinical laboratories taken on days 2, 5, 8 and 11; serum pregnancy test on day 11; 12-lead ECG conducted on days 5 and 11.

Eligibility
Key inclusion criteria
Criteria 1-8 apply to all cohorts including healthy participants:
1) 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.
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.
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:
9) 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 less than or equal to eGFRCKD-EPI,creatinine < 90 mL/min/1.73 m2 for mild disease (Cohort 3a) or
30 less than or equal to eGFRCKD-EPI,creatinine < 60 mL/min/1.73 m2 for moderate disease (Cohort 1a) or
15 less than or equal to 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]) less than or equal to 2 x upper limit of normal (ULN) at screening and at admission.
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:
12) Must have an eGFRCKD-EPI, creatinine of greater than or equal to 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.
Minimum age
18 Years
Maximum age
79 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1) Positive serum pregnancy test at screening and at admission. 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.
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
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 left ventricular ejection fraction less than or equal to 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 (greater than or equal to 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
12) Participants with RI requiring or anticipated to require dialysis within 6 months of dosing are not eligible.
13) 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, haematological, 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 1
Type of endpoint/s
Pharmacokinetics
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
31/01/2024
Actual
29/08/2023
Date of last participant enrolment
Anticipated
1/07/2024
Actual
28/05/2024
Date of last data collection
Anticipated
19/07/2024
Actual
14/06/2024
Sample size
Target
60
Accrual to date
Final
56
Recruitment outside Australia
Country [1] 25901 0
New Zealand
State/province [1] 25901 0
Country [2] 25903 0
United States of America
State/province [2] 25903 0
Country [3] 25904 0
Germany
State/province [3] 25904 0

Funding & Sponsors
Funding source category [1] 315026 0
Commercial sector/Industry
Name [1] 315026 0
Gilead Sciences
Country [1] 315026 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Gilead Sciences
Address
Level 28, 385 Bourke Street Melbourne VIC 3000
Country
Australia
Secondary sponsor category [1] 317050 0
None
Name [1] 317050 0
Address [1] 317050 0
Country [1] 317050 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 313992 0
Central Health and Disability Ethics Committee
Ethics committee address [1] 313992 0
Ethics committee country [1] 313992 0
New Zealand
Date submitted for ethics approval [1] 313992 0
11/10/2023
Approval date [1] 313992 0
06/11/2023
Ethics approval number [1] 313992 0
2023 FULL 18897

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 130046 0
Mr Nick Cross
Address 130046 0
New Zealand Clinical Research, Level 3/264 Antigua Street, Christchurch Central City, Christchurch 8011.
Country 130046 0
New Zealand
Phone 130046 0
+64 9 373 3474
Fax 130046 0
Email 130046 0
[email protected]
Contact person for public queries
Name 130047 0
Nick Cross
Address 130047 0
New Zealand Clinical Research, Level 3/264 Antigua Street, Christchurch Central City, Christchurch 8011.
Country 130047 0
New Zealand
Phone 130047 0
+64 9 373 3474
Fax 130047 0
Email 130047 0
[email protected]
Contact person for scientific queries
Name 130048 0
Nick Cross
Address 130048 0
New Zealand Clinical Research, Level 3/264 Antigua Street, Christchurch Central City, Christchurch 8011.
Country 130048 0
New Zealand
Phone 130048 0
+64 9 373 3474
Fax 130048 0
Email 130048 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Study is for supporting compound development only. (TBC)


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.