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

NCT03277274 | Completed Phase 1 Results

• 3 other identifiers: TAK-954-10062017-000714-37U1111-1196-9190
• Study Type: interventional
• Target: 25
• Locations: 2 countries
• Sites: 2

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.

Conditions

Hepatic Impairment; Healthy Volunteers

Keywords

Drug Therapy

Outcome Measures

Primary Outcomes (3)

• Cmax: Maximum Observed Plasma Concentration for TAK-954 (Total and Free)

  Day 1 pre-infusion and at multiple time points (up to 96 hours) post-infusion

• AUClast: Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-954 (Total and Free)

  Day 1 pre-infusion and at multiple time points (up to 96 hours) post-infusion

• AUC∞: Area Under the Concentration-time Curve From Time 0 to Infinity for TAK-954 (Total and Free)

  Day 1 pre-infusion and at multiple time points (up to 96 hours) post-infusion

Secondary Outcomes (5)

• Number of Participants With Clinically Significant Physical Examination Findings

  Up to 14 days after the last dose of study drug (Day 15)

• Number of Participants With Markedly Abnormal Electrocardiograms (ECGs)

  Up to 14 days after the last dose of study drug (Day 15)

• Number of Participants With Markedly Abnormal Values of Vital Signs

  Up to 14 days after the last dose of study drug (Day 15)

• Number of Participants With Clinically Significant Change From Baseline in Clinical Laboratory Values

  Up to 14 days after the last dose of study drug (Day 15)

• Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)

  Baseline up to 30 days after last dose of study drug (Day 31)

Study Arms (4)

Group 1 Mild Hepatic Impairment: TAK-954 0.2 mg

EXPERIMENTAL

TAK-954 0.2 milligram (mg), intravenous, administered as 60-minute infusion, once on Day 1.

Drug: TAK-954

Group 2 Moderate Hepatic Impairment: TAK-954 0.2 mg

EXPERIMENTAL

TAK-954 0.2 mg, intravenous, administered as 60-minute infusion, once on Day 1.

Drug: TAK-954

Group 3 Severe Hepatic Impairment: TAK-954 0.2 mg

EXPERIMENTAL

TAK-954 0.2 mg, intravenous, administered as 60-minute infusion, once on Day 1.

Drug: TAK-954

Group 4 Healthy Participants: TAK-954 0.2 mg

EXPERIMENTAL

TAK-954 0.2 mg, intravenous, administered as 60-minute infusion, once on Day 1.

Drug: TAK-954

Interventions

TAK-954 DRUG

TAK-954 intravenous infusion.

Group 1 Mild Hepatic Impairment: TAK-954 0.2 mg; Group 2 Moderate Hepatic Impairment: TAK-954 0.2 mg; Group 3 Severe Hepatic Impairment: TAK-954 0.2 mg; Group 4 Healthy Participants: TAK-954 0.2 mg

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• 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).
• Healthy participants (Group 4).

You may not qualify if:

• Participants who have:
• 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).
• Have severe hepatic encephalopathy (\[greater than\] \> Grade II Portal Systemic Encephalopathy Score) (Group 1 to 3).
• Surgical porto-systemic shunts, including transjugular intrahepatic portosystemic shunt (Group 1 to 3).
• A history of gastrointestinal hemorrhage due to esophageal varices or peptic ulcers less than 1 month prior to trial entry (Group 1 to 3).
• 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.
• Severe/advanced ascites and/or pleural effusion which requires emptying and albumin supplementation, as judged by the investigator (Group 1 to 3).
• 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).
• 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).

Sponsors & Collaborators

• Takeda: lead

Study Sites (2)

PRA CZ, s.r.o

Prague, Prague, 170 00, Czechia

Location

Summit Center of Clinical Research

Bratislava, 83101, Slovakia

Location

Results Point of Contact

• Title: Medical director
• Organization: Takeda

trialdisclosures@takeda.com

+1-877-825-3327

Study Officials

• Medical Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 7, 2017
• First Posted: September 11, 2017
• Study Start: November 9, 2017
• Primary Completion: September 1, 2018
• Study Completion: September 10, 2018
• Last Updated: September 25, 2019
• Results First Posted: September 25, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will share

Locations

CZ (1); SL (1)