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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT02509624




Registration number
NCT02509624
Ethics application status
Date submitted
16/07/2015
Date registered
28/07/2015
Date last updated
27/01/2021

Titles & IDs
Public title
Study to Evaluate the Pharmacokinetics of Selonsertib in Participants With Normal and Impaired Hepatic Function
Scientific title
A Phase 1, Open-Label, Parallel-Group, Single Dose Study to Evaluate the Pharmacokinetics of GS-4997 in Subjects With Normal and Impaired Hepatic Function
Secondary ID [1] 0 0
2015-002444-14
Secondary ID [2] 0 0
GS-US-223-1018
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diabetic Kidney Disease 0 0
Condition category
Condition code
Renal and Urogenital 0 0 0 0
Kidney disease
Metabolic and Endocrine 0 0 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Selonsertib

Experimental: Moderate hepatic impairment (Cohort 1) - Participants with moderate hepatic impairment and matched healthy controls will receive a single dose of selonsertib on Day 1.

Experimental: Severe hepatic impairment (Cohort 2) - Participants with severe hepatic impairment and matched healthy controls will receive a single dose of selonsertib on Day 1.

Experimental: Mild hepatic impairment (Cohort 3) - Participants with mild hepatic impairment and matched healthy controls will receive a single dose of selonsertib on Day 1.


Treatment: Drugs: Selonsertib
6 mg tablets administered orally in fed state
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Pharmacokinetic (PK) Parameter: AUCinf of Selonsertib and Its Metabolite GS-607509
Timepoint [1] 0 0
0 (predose), 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, and 120 hours postdose on Day 1. Additional PK samples were collected at the Day 10 and 14 follow-up visits approximately the same time as the Day 1 predose sample.
Primary outcome [2] 0 0
PK Parameter: AUClast of Selonsertib and Its Metabolite GS-607509
Timepoint [2] 0 0
0 (predose), 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, and 120 hours postdose on Day 1. Additional PK samples were collected at the Day 10 and 14 follow-up visits approximately the same time as the Day 1 predose sample.
Primary outcome [3] 0 0
PK Parameter: Cmax of Selonsertib and Its Metabolite GS-607509
Timepoint [3] 0 0
0 (predose), 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, and 120 hours postdose on Day 1. Additional PK samples were collected at the Day 10 and 14 follow-up visits approximately the same time as the Day 1 predose sample.
Secondary outcome [1] 0 0
Percentage of Participants Experiencing Treatment-Emergent Study Drug-related Adverse Events (AEs)
Timepoint [1] 0 0
Day 1 plus 30 days
Secondary outcome [2] 0 0
Percentage of Participants Experiencing Any Treatment-Emergent and Grade = 3 Laboratory Abnormalities
Timepoint [2] 0 0
Day 1 plus 30 days

Eligibility
Key inclusion criteria
Key

All participants:

- Body mass index (BMI) from 18 to 40 kg/m^2, inclusive at study screening

- Creatinine clearance (CrCl) = 60 mL/min (using the Cockcroft-Gault method) based on
serum creatinine and actual body weight as measured at screening

Participants with impaired hepatic function:

- Aside from hepatic insufficiency, participants must be sufficiently healthy for study
participation based upon screening evaluations.

- Must have diagnosis of chronic (> 6 months), stable hepatic impairment with no
clinically significant change in hepatic status within the 3 months (90 days) prior to
study drug administration (Day 1).

- Participants with severe hepatic impairment must have a score on the
Child-Pugh-Turcotte scale of 10-15 at screening.

- Participants with moderate hepatic impairment must have a score on the
Child-Pugh-Turcotte scale of 7-9 at screening.

- Participants with mild hepatic impairment must have a score on the Child-Pugh-Turcotte
scale of 5-6 at screening.

Healthy participants (matched control):

- Must be in good health based upon screening evaluations.

Key
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
All participants:

- Pregnant or lactating females

- Have received any investigational compound or device within 30 days prior to study
dosing

- Current alcohol or substance abuse

- A positive test result for human immunodeficiency virus (HIV-1/2) antibody

- Have poor venous access that limits phlebotomy

- Have been treated with systemic steroids, anti-HIV agents, immunosuppressant
therapies, or chemotherapeutic agents within 3 months prior to screening or expected
to receive these agents during the study (eg, corticosteroids, immunoglobulins, and
other immune- or cytokine-based therapies) that would be contraindicated for other
exclusion criteria.

- Significant serious skin disease, such as but not limited to rash, food allergy,
eczema, psoriasis, or urticaria

- Significant drug sensitivity or drug allergy (such as anaphylaxis or hepatoxicity)

- Unstable cardiac disease, including history of myocardial infarction within 1 year of
screening, recurrent episodes of ventricular tachycardia despite appropriate medical
therapy, decompensated congestive heart failure, or dilated cardiomyopathy with left
ventricular ejection fraction < 40%, or a family history of Long QT Syndrome, or
unexplained death in an otherwise healthy participants between the ages of 1 and 30
years.

- Syncope, palpitations, or unexplained dizziness

- Implanted defibrillator or pacemaker

- Severe peptic ulcer disease, severe gastroesophageal reflux disease, or other severe
gastric acid hypersecretory conditions

- Medical or surgical treatment that permanently alters gastric absorption (eg, gastric
or intestinal surgery). A history of cholecystectomy is not exclusionary.

- History of prior allogeneic bone marrow progenitor cell or solid organ
transplantation.

- Currently registered on an organ transplantation list.

- History of bleeding from esophageal varices within 90 days prior to Admission (Day
-1).

- Use of strong cytochrome P3A4 (CYP3A4) inhibitors (eg, indinavir, nelfinavir,
ritonavir, clarithromycin, itraconazole, ketoconazole, nefazodone, saquinavir,
suboxone, telithromycin, atazanavir) and strong CYP3A4 inducers (eg, carbamazepine,
rifampin, phenytoin and St. John's wort), within 28 days prior to study drug
administration (Day 1).

- Consumption of grapefruit juice, grapefruits, and Seville orange juice within 2 weeks
prior to study drug administration (Day 1).

- Recent significant changes in the use of nicotine or nicotine containing products

Participants with impaired hepatic function:

- Aside from hepatic insufficiency, serious or active medical or psychiatric illness
that, in the opinion of the investigator, would interfere with treatment, assessment,
or compliance with the protocol.

- Chronic hepatitis B virus (HBV) infection, defined as a positive test for hepatitis B
surface antigen (HBsAg), unless the participant has been treated with a nucleos(t)ide
analog (eg, tenofovir or entecavir) for at least 6 months and the HBV deoxyribonucleic
acid (DNA) by polymerase chain reaction (PCR) assay has been persistently undetectable
for at least 6 months.

- Positive test for drugs of abuse, including alcohol at screening or on Day
-1/check-in, with the exception of opioids and tetrahydrocannabinol (THC, marijuana)
under prescription and investigator verification for pain management. Participants who
screen positive for benzodiazepines may be allowed if prescribed under the care of a
physician and after review by investigator and Sponsor.

- Requires paracentesis > 1 time per month.

- Participants with hepatic impairment with co-morbid diseases not associated with
hepatic impairment requiring medication(s) must be taking the medication(s) without a
change in dose for > 3 months prior to screening.

- Changes in concomitant medications or dosage used to treat symptoms of hepatic
impairment or associated co-morbid conditions that could lead to clinically
significant changes in medical conditions during the course of the study that would
affect the ability to interpret potential drug-drug interactions within 28 days prior
to dosing.

Healthy participants (matched control):

- A positive test result for hepatitis C virus (HCV) antibody, hepatitis B surface
antigen (HBsAg), or hepatitis B core antibody (anti-HBc)

- Positive test for drugs of abuse, including alcohol at screening or on Day
-1/check-in.

- Have any serious or active medical or psychiatric illness (including depression)
which, in the opinion of the investigator, would interfere with treatment, assessment,
or compliance with the protocol.

- History of liver disease.

- Have taken any prescription medications or over-the-counter medications including
herbal products within 28 days of commencing study drug dosing with the exception of
vitamins, acetaminophen, ibuprofen, and hormonal contraceptive medications.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

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
Open (masking not used)
Who is / are masked / blinded?



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

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
18/08/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
15/12/2015
Sample size
Target
Accrual to date
Final
52
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Colorado
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Minnesota
Country [4] 0 0
United States of America
State/province [4] 0 0
Texas

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Gilead Sciences
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The primary objective of this study is to evaluate the pharmacokinetics (PK) of selonsertib
in participants with impaired hepatic function relative to matched, healthy controls.
Trial website
https://clinicaltrials.gov/ct2/show/NCT02509624
Trial related presentations / publications
Public notes
This record is viewable in the ANZCTR as it had previously listed Australia and/or New Zealand as a recruitment site, however these sites have since been removed

Contacts
Principal investigator
Name 0 0
Gilead Study Director
Address 0 0
Gilead Sciences
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries