NCT02509624

Study to Evaluate the Pharmacokinetics of Selonsertib in Participants With Normal and Impaired Hepatic Function

Completed Phase 1 Results posted Last updated 27 January 2021

What this trial tests

Phase 1 trial testing Selonsertib in Diabetic Kidney Disease in 52 participants. Completed in 15 December 2015.

Timeline

18 August 2015

Primary endpoint
15 December 2015

15 December 2015

Quick facts

Lead sponsor	Gilead Sciences
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	52
Start date	18 August 2015
Primary completion	15 December 2015
Estimated completion	15 December 2015
Sites	5 locations across United States

Drugs / interventions tested

• Selonsertib — full drug profile →

Conditions studied

• Diabetic Kidney Disease — all drugs for Diabetic Kidney Disease →

Sponsor

Gilead Sciences — full company profile →

Who can join

18 and older, any sex, with Diabetic Kidney Disease. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Pharmacokinetic (PK) Parameter: AUCinf of Selonsertib and Its Metabolite GS-607509 Primary · 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.

AUCinf is defined as the concentration of drug extrapolated to infinite time.

AUCinf of Selonsertib

Group	Value	95% CI
Cohort 1: Moderate Hepatic Impairment	3316.1	± 1734.11
Cohort 2: Severe Hepatic Impairment	3266.7	± 766.39
Cohort 3: Mild Hepatic Impairment	2962.1	± 901.12
Matched Healthy Control for Cohort 1	2835.3	± 499.58
Matched Healthy Control for Cohort 2	2277.9	± 490.96
Matched Healthy Control for Cohort 3	2711.6	± 919.83

AUCinf of GS-607509

Group	Value	95% CI
Cohort 1: Moderate Hepatic Impairment	5941.8	± 2286.80
Cohort 2: Severe Hepatic Impairment	5711.2	± 3401.94
Cohort 3: Mild Hepatic Impairment	10203.6	± 8689.39
Matched Healthy Control for Cohort 1	9993.3	± 4599.91
Matched Healthy Control for Cohort 2	9603.4	± 8057.84
Matched Healthy Control for Cohort 3	9846.6	± 8954.40

PK Parameter: AUClast of Selonsertib and Its Metabolite GS-607509 Primary · 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.

AUClast is defined as the concentration of drug from time zero to the last observable concentration.

AUClast of Selonsertib

Group	Value	95% CI
Cohort 1: Moderate Hepatic Impairment	2964.1	± 1493.69
Cohort 2: Severe Hepatic Impairment	3032.7	± 728.55
Cohort 3: Mild Hepatic Impairment	2790.8	± 847.18
Matched Healthy Control for Cohort 1	2679.9	± 486.23
Matched Healthy Control for Cohort 2	2129.7	± 493.83
Matched Healthy Control for Cohort 3	2530.9	± 902.55

AUClast of GS-607509

Group	Value	95% CI
Cohort 1: Moderate Hepatic Impairment	5405.2	± 2211.86
Cohort 2: Severe Hepatic Impairment	4868.0	± 3072.43
Cohort 3: Mild Hepatic Impairment	8475.8	± 7165.86
Matched Healthy Control for Cohort 1	9117.6	± 4127.22
Matched Healthy Control for Cohort 2	8157.5	± 6019.61
Matched Healthy Control for Cohort 3	8326.5	± 6604.26

PK Parameter: Cmax of Selonsertib and Its Metabolite GS-607509 Primary · 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.

Cmax is defined as the maximum concentration of drug.

Cmax of Selonsertib

Group	Value	95% CI
Cohort 1: Moderate Hepatic Impairment	93.7	± 20.66
Cohort 2: Severe Hepatic Impairment	82.4	± 10.63
Cohort 3: Mild Hepatic Impairment	110.6	± 24.77
Matched Healthy Control for Cohort 1	105.4	± 22.13
Matched Healthy Control for Cohort 2	91.9	± 22.01
Matched Healthy Control for Cohort 3	110.3	± 23.40

Cmax of GS-607509

Group	Value	95% CI
Cohort 1: Moderate Hepatic Impairment	44.1	± 15.01
Cohort 2: Severe Hepatic Impairment	31.2	± 15.34
Cohort 3: Mild Hepatic Impairment	63.5	± 31.42
Matched Healthy Control for Cohort 1	62.3	± 23.44
Matched Healthy Control for Cohort 2	63.2	± 27.03
Matched Healthy Control for Cohort 3	64.2	± 21.99

Percentage of Participants Experiencing Treatment-Emergent Study Drug-related Adverse Events (AEs) Secondary · Day 1 plus 30 days

An AE was any untoward medical occurrence in a clinical study participant which did not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and/or unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Treatment-emergent AEs were defined as events that met one of the following criteria: 1) Any AEs with an onset date of on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug; or 2) Any AEs leading

Group	Value	95% CI
Cohort 1: Moderate Hepatic Impairment	20.0
Cohort 2: Severe Hepatic Impairment	0
Cohort 3: Mild Hepatic Impairment	10.0
Healthy Control	13.6

Percentage of Participants Experiencing Any Treatment-Emergent and Grade ≥ 3 Laboratory Abnormalities Secondary · Day 1 plus 30 days

Treatment-emergent laboratory abnormalities were defined as values that increased at least 1 toxicity grade from predose at any postdose visit, up to and including the date of last dose of study drug plus 30 days for participants who permanently discontinued study drug. If the relevant baseline laboratory value was missing, then any abnormality of at least Grade 1 observed within the time frame specified above was considered treatment-emergent. Severity grades were defined based on modified Common Terminology Criteria for Adverse Events (CTCAE) Laboratory Abnormality and Adverse Event Severity

Any Treatment-Emergent Laboratory Abnormalities

Group	Value	95% CI
Cohort 1: Moderate Hepatic Impairment	90.0
Cohort 2: Severe Hepatic Impairment	90.0
Cohort 3: Mild Hepatic Impairment	70.0
Healthy Control	59.1

Grade ≥ 3 Laboratory Abnormalities

Group	Value	95% CI
Cohort 1: Moderate Hepatic Impairment	20.0
Cohort 2: Severe Hepatic Impairment	40.0
Cohort 3: Mild Hepatic Impairment	10.0
Healthy Control	4.5

Adverse events — posted to ClinicalTrials.gov

Time frame: Day 1 plus 30 days. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Cohort 1: Moderate Hepatic Impairment

Serious: 0/10 (0%)

Deaths: —

Cohort 2: Severe Hepatic Impairment

Serious: 0/10 (0%)

Deaths: —

Cohort 3: Mild Hepatic Impairment

Serious: 0/10 (0%)

Deaths: —

Healthy Control

Serious: 0/22 (0%)

Deaths: —

Other adverse events (4 terms — click to expand)

Reaction	System	Cohort 1: Moderate Hepatic…	Cohort 2: Severe Hepatic I…	Cohort 3: Mild Hepatic Imp…	Healthy Control
Headache	Nervous system disorders	—	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—	—
Dry mouth	Gastrointestinal disorders	—	—	—	—
Arthropod bite	Injury, poisoning and procedural complications	—	—	—	—

Data from ClinicalTrials.gov NCT02509624 adverse events section.

Sponsor's own description

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.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

1. Targeting protein modifications in metabolic diseases: molecular mechanisms and targeted therapies.
   Wu X, Xu M, Geng M, Chen S, et al · · 2023 · cited 161× · PMID 37244925 · DOI 10.1038/s41392-023-01439-y
2. Clinical Advancements in the Targeted Therapies against Liver Fibrosis.
   Bansal R, Nagórniewicz B, Prakash J. · · 2016 · cited 72× · PMID 27999454 · DOI 10.1155/2016/7629724
3. ASK1 Inhibitor in Chronic Kidney Disease Therapy: From Bench to Bedside.
   Wen L, Wei Q. · · 2022 · cited 5× · PMID 35919531 · DOI 10.34067/kid.0002562022