Clinical trial NCT03277274: A Study to Evaluate the Effect of Hepatic Impairment on the Single Dose Pharmacokinetics (PK) of Intravenous TAK-954
Official title: A Phase 1, Non-Randomized, Open-Label Trial to Evaluate the Effect of Hepatic Impairment on the Single Dose Pharmacokinetics of Intravenous TAK-954
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatic Impairment
Healthy Volunteers
Keywords: Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2017-09-11
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: OTHER

Brief summary: 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.

Detailed description: The drug being tested in this study is called TAK-954. This study will evaluate the safety and tolerability of single intravenous doses of TAK-954 in participants with varying degrees of hepatic function.

The study will enroll approximately up to 32 participants. Participants will be enrolled in one of the 4 treatment groups based on their degree of hepatic impairment which will be determined based on Child-Pugh Score as follow:

* Group 1 TAK-954 0.2 mg: Mild Hepatic Impairment (Child Pugh Class A)
* Group 2 TAK-954 0.2 mg: Moderate Hepatic Impairment (Child Pugh Class B)
* Group 3 TAK-954 0.2 mg: Severe Hepatic Impairment (Child Pugh Class C)
* Group 4 TAK-954 0.2 mg: Healthy Participants

The Child-Pugh classification will assess the severity of 5 hepatic parameters (total serum bilirubin, serum albumin, prothrombin time, ascites and encephalopathy grade) on a scale of 1 (none) to 3 (moderate). Total hepatic impairment score ranges from 5 (mild) to 15 (severe) where higher score indicates more severity.

All participants will receive a single dose of TAK-954 0.2 mg on Day 1.

This study may have a full study design, where Group 1 to Group 4 will enroll approximately 8 participants in each group or a reduced study design, where no participants will be enrolled in Group 1 and approximately 8 participants will be enrolled in Group 2 to Group 4.

This multi-center trial will be conducted in Czech Republic and Slovakia. The overall time to participate in this study is approximately 7 weeks. Participants will remain confined to the clinic for 4 days, with 2 further out-patient visits, and will make a final visit to the clinic 10-14 days after receiving their last dose of TAK-954 for a follow-up assessment.

Eligibility criteria: Inclusion Criteria:

1. Male and female participants (non-childbearing potential), with a body mass index (BMI) between 18 to 35 kilogram per square meter (kg/m\^2) (All participants).
2. Participants with hepatic impairment who are medically stable as determined by the investigator, based on medical history and clinical evaluations including physical examinations, clinical laboratory tests, vital sign measurements, and 12-lead ECGs performed at the Screening Visit and at check-in on Day -1 (Group 1 to 3).
3. Healthy participants (Group 4).

Exclusion Criteria:

Participants who have:

1. A history of hepatic carcinoma, hepatorenal syndrome, or presence of a liver mass by ultrasound, CT or MRI, or acute liver disease caused by an infection or drug toxicity (Group 1 to 3).
2. Have severe hepatic encephalopathy (\[greater than\] \> Grade II Portal Systemic Encephalopathy Score) (Group 1 to 3).
3. Surgical porto-systemic shunts, including transjugular intrahepatic portosystemic shunt (Group 1 to 3).
4. A history of gastrointestinal hemorrhage due to esophageal varices or peptic ulcers less than 1 month prior to trial entry (Group 1 to 3).
5. Bilirubin levels above 5 times the upper limit of normal (ULN) at screening or Day -1 for Groups 1 and 2, there is no limit for Group 3.
6. Severe/advanced ascites and/or pleural effusion which requires emptying and albumin supplementation, as judged by the investigator (Group 1 to 3).
7. Renal creatinine clearance (CLcr) less than or equal to (\<=) 50 milliliter per minute (mL/min), calculated using the Cockcroft-Gault equation from the serum creatinine measurement taken at screening (Group 1 to 3).
8. Who have a history of clinically significant endocrine, gastrointestinal (GI) (including motility disorder and intestinal obstruction), cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary, or major neurological (including stroke and chronic seizures) abnormalities or diseases will be excluded from the trial (Group 4).

Primary outcomes:
measure: Cmax: Maximum Observed Plasma Concentration for TAK-954 (Total and Free)
timeFrame: Day 1 pre-infusion and at multiple time points (up to 96 hours) post-infusion
measure: AUClast: Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-954 (Total and Free)
timeFrame: Day 1 pre-infusion and at multiple time points (up to 96 hours) post-infusion
measure: AUC∞: Area Under the Concentration-time Curve From Time 0 to Infinity for TAK-954 (Total and Free)
timeFrame: Day 1 pre-infusion and at multiple time points (up to 96 hours) post-infusion
Secondary outcomes:
measure: Number of Participants With Clinically Significant Physical Examination Findings
timeFrame: Up to 14 days after the last dose of study drug (Day 15)
measure: Number of Participants With Markedly Abnormal Electrocardiograms (ECGs)
timeFrame: Up to 14 days after the last dose of study drug (Day 15)
measure: Number of Participants With Markedly Abnormal Values of Vital Signs
timeFrame: Up to 14 days after the last dose of study drug (Day 15)
measure: Number of Participants With Clinically Significant Change From Baseline in Clinical Laboratory Values
timeFrame: Up to 14 days after the last dose of study drug (Day 15)
measure: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)
timeFrame: Baseline up to 30 days after last dose of study drug (Day 31)
Other outcomes:
Locations:
city: Praha 7
country: Czechia
facility: PRA CZ, s.r.o
state: Praha
city: Bratislava
country: Slovakia
facility: Summit Center of Clinical Research
Study officials:
affiliation: Takeda
name: Medical Director
role: STUDY_DIRECTOR
References: