NCT03277274

A Study to Evaluate the Effect of Hepatic Impairment on the Single Dose Pharmacokinetics (PK) of Intravenous TAK-954

Completed Phase 1 Results posted Last updated 25 September 2019

What this trial tests

Phase 1 trial testing TAK-954 in Hepatic Impairment in 25 participants. Completed in 10 September 2018.

Timeline

9 November 2017

Primary endpoint
1 September 2018

10 September 2018

Quick facts

Lead sponsor	Takeda
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	sequential
Masking	none
Primary purpose	other
Enrollment	25
Start date	9 November 2017
Primary completion	1 September 2018
Estimated completion	10 September 2018
Sites	2 locations across Slovakia, Czechia

Drugs / interventions tested

• TAK-954 — full drug profile →

Conditions studied

• Hepatic Impairment — all drugs for Hepatic Impairment →
• Healthy Volunteers — all drugs for Healthy Volunteers →

Sponsor

Takeda — full company profile →

Who can join

Adults 18 to 75, any sex, with Hepatic Impairment or Healthy Volunteers. 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.

Cmax: Maximum Observed Plasma Concentration for TAK-954 (Total and Free) Primary · Day 1 pre-infusion and at multiple time points (up to 96 hours) post-infusion

TAK-954 (Total)

Group	Value	95% CI
Healthy Participants: TAK-954 0.2 mg	2.629	± 19.1
Group B, Moderate Hepatic Impairment: TAK-954 0.2 mg	2.440	± 25.3
Group C, Severe Hepatic Impairment: TAK-954 0.2 mg	1.893	± 35.4

TAK-954 (Free)

Group	Value	95% CI
Healthy Participants: TAK-954 0.2 mg	0.1381	± 15.6
Group B, Moderate Hepatic Impairment: TAK-954 0.2 mg	0.1799	± 24.4
Group C, Severe Hepatic Impairment: TAK-954 0.2 mg	0.1778	± 23.1

AUClast: Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-954 (Total and Free) Primary · Day 1 pre-infusion and at multiple time points (up to 96 hours) post-infusion

TAK-954 (Total)

Group	Value	95% CI
Healthy Participants: TAK-954 0.2 mg	28.57	± 19.2
Group B, Moderate Hepatic Impairment: TAK-954 0.2 mg	23.57	± 26.2
Group C, Severe Hepatic Impairment: TAK-954 0.2 mg	20.19	± 32.7

TAK-954 (Free)

Group	Value	95% CI
Healthy Participants: TAK-954 0.2 mg	1.501	± 12.0
Group B, Moderate Hepatic Impairment: TAK-954 0.2 mg	1.737	± 23.0
Group C, Severe Hepatic Impairment: TAK-954 0.2 mg	1.898	± 19.3

AUC∞: Area Under the Concentration-time Curve From Time 0 to Infinity for TAK-954 (Total and Free) Primary · Day 1 pre-infusion and at multiple time points (up to 96 hours) post-infusion

TAK-954 (Total)

Group	Value	95% CI
Healthy Participants: TAK-954 0.2 mg	31.30	± 20.1
Group B, Moderate Hepatic Impairment: TAK-954 0.2 mg	25.44	± 27.1
Group C, Severe Hepatic Impairment: TAK-954 0.2 mg	22.60	± 34.3

TAK-954 (Free)

Group	Value	95% CI
Healthy Participants: TAK-954 0.2 mg	1.643	± 13.8
Group B, Moderate Hepatic Impairment: TAK-954 0.2 mg	1.875	± 24.0
Group C, Severe Hepatic Impairment: TAK-954 0.2 mg	2.122	± 21.8

Number of Participants With Clinically Significant Physical Examination Findings Secondary · Up to 14 days after the last dose of study drug (Day 15)

Group	Value	95% CI
Healthy Participants: TAK-954 0.2 mg	0
Group B, Moderate Hepatic Impairment: TAK-954 0.2 mg	0
Group C, Severe Hepatic Impairment: TAK-954 0.2 mg	0

Number of Participants With Markedly Abnormal Electrocardiograms (ECGs) Secondary · Up to 14 days after the last dose of study drug (Day 15)

Group	Value	95% CI
Healthy Participants: TAK-954 0.2 mg	0
Group B, Moderate Hepatic Impairment: TAK-954 0.2 mg	0
Group C, Severe Hepatic Impairment: TAK-954 0.2 mg	2

Number of Participants With Markedly Abnormal Values of Vital Signs Secondary · Up to 14 days after the last dose of study drug (Day 15)

Group	Value	95% CI
Healthy Participants: TAK-954 0.2 mg	0
Group B, Moderate Hepatic Impairment: TAK-954 0.2 mg	1
Group C, Severe Hepatic Impairment: TAK-954 0.2 mg	1

Number of Participants With Clinically Significant Change From Baseline in Clinical Laboratory Values Secondary · Up to 14 days after the last dose of study drug (Day 15)

Group	Value	95% CI
Healthy Participants: TAK-954 0.2 mg	0
Group B, Moderate Hepatic Impairment: TAK-954 0.2 mg	0
Group C, Severe Hepatic Impairment: TAK-954 0.2 mg	0

Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) Secondary · Baseline up to 30 days after last dose of study drug (Day 31)

Group	Value	95% CI
Healthy Participants: TAK-954 0.2 mg	2
Group B, Moderate Hepatic Impairment: TAK-954 0.2 mg	3
Group C, Severe Hepatic Impairment: TAK-954 0.2 mg	1

Adverse events — posted to ClinicalTrials.gov

Time frame: TEAEs are adverse events that started after the first dose of study drug and no more than 30 days (Day 31) after the last dose of study drug. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Healthy Participants: TAK-954 0.2 mg

Serious: 0/8 (0%)

Deaths: 0/8

Group B, Moderate Hepatic Impairment: TAK-954 0.2 mg

Serious: 0/10 (0%)

Deaths: 0/10

Group C, Severe Hepatic Impairment: TAK-954 0.2 mg

Serious: 0/7 (0%)

Deaths: 0/7

Other adverse events (3 terms — click to expand)

Reaction	System	Healthy Participants: TAK-…	Group B, Moderate Hepatic …	Group C, Severe Hepatic Im…
Diarrhoea	Gastrointestinal disorders	—	—	—
Flatulence	Gastrointestinal disorders	—	—	—
Headache	Nervous system disorders	—	—	—

Data from ClinicalTrials.gov NCT03277274 adverse events section.

Sponsor's own description

The purpose of this study is to evaluate the effect of varying degrees of hepatic function on the single dose PK of IV TAK-954.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. The Effect of Hepatic Impairment on the Pharmacokinetics of Intravenously Administered Felcisetrag (TAK-954).
   Czerniak R, Cieslarová B, Kupčová V, Rosario M, et al · · 2022 · cited 2× · PMID 35253917 · DOI 10.1002/jcph.2044