A Study to Evaluate the Effect of Renal Impairment and Dialysis Treatment on the Pharmacokinetics (PK) of a Single Intravenous (IV) TAK-954

A Phase 1, Open-Label, Parallel Group Trial to Evaluate the Effect of Renal Impairment and Dialysis Treatment on the Pharmacokinetics of a Single Intravenous Dose of TAK-954

The purpose of this study is to evaluate the effect of varying degrees of renal function on the PK of TAK-954 following single-dose IV administration and to investigate the impact of hemodialysis on the PK of single IV doses of TAK-954.

Study Overview

• Status: Completed
• Conditions: Renal Impairment; Healthy Volunteers
• Intervention / Treatment: Drug: TAK-954

Detailed Description

The drug being tested in this study is called TAK-954. This study will evaluate the effect of varying degrees of renal function on the PK of TAK-954 following single-dose IV administration and to investigate the impact of hemodialysis on the PK of single IV doses of TAK-954.

The study will enroll approximately up to 40 participants. Participants will be enrolled in one of the 5 treatment groups based on their renal impairment which will be determined based on Cockcroft and Gault (CG) equation as follows:

• Group A TAK-954 0.2 mg: Healthy Participants
• Group B TAK-954 0.2 mg: Mild Renal Impairment
• Group C TAK-954 0.2 mg: Moderate Renal Impairment
• Group D TAK-954 0.2 mg: Severe Renal Impairment or End-stage Renal Disease (ESRD) Without Hemodialysis
• Group E TAK-954 0.2 mg: End-stage Renal Disease (ESRD) With Hemodialysis

All participants in groups A to D will receive a single dose of TAK-954 and two single doses in Group E.

Enrollment in Group B (Mild) and Group E (ESRD requiring dialysis) will be based on assessment of safety and available PK data from Group C and Group D respectively.

This multi-center trial will be conducted in Czech Republic and Hungary. The overall time to participate in this study is approximately 8 weeks. Participants in Groups A to D will remain confined to clinic for 3 days. For both treatments, participants in Group E requiring dialysis will remain confined to clinic for 3 days. All participants will make a final visit to the clinic 10-14 days after receiving their last dose for a follow-up assessment.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• Czechia
  • Hradec Kralove, Czechia, 500 05
    • Fakultni Nemocnice Hradec Kralove
  • Praha
    • Praha 7, Praha, Czechia, 170 00
      • PRA CZ, s.r.o
• Hungary
  • Budapest, Hungary, 1077
    • PRA Magyarország Kft.
  • Budapest, Hungary, 1115
    • Szent Imre Egyetemi Oktatokorhaz Belgyogyazati Szakmak Matrix Intezet

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. All participants: Male and female participants (non-childbearing potential) who are aged 18 to 75 years, inclusive, with a body mass index (BMI) between 18 to 35 kilogram per square meter (kg/m^2).
2. Group A: As much as possible, the healthy participants with normal renal function (creatinine clearance [CLcr] greater than or equal to [>=] 90 milliliter per minute [mL/min]) should be comparable to participants with renal impairment with respect to median age and weight (approximately 50 percent [%] of healthy participants on each side of the median age and weight of currently enrolled renally-impaired participants grouped together), sex, and race. This will be decided by the investigators in discussion with Takeda.

3. Groups B to E: Participants who have stable RI, defined as no clinically significant change in disease status, as documented by the participant's most recent CLcr assessment; serum creatinine must not vary more than approximately 30% from Screening to Day -1 to confirm stable disease. Participants should also be in good health commensurate with their renal status.

   • Group B: Participants with mild RI (CLcr 60 to less than [<] 90 mL/min).
   • Group C: Participants with moderate RI (CLcr 30 to <60 mL/min).
   • Group D: Participants with severe RI or ESRD but not requiring dialysis (CLcr <30 mL/min).
   • Group E: Participants with ESRD requiring dialysis (<15 mL/min requiring hemodialysis at least 3 times/week, and having been on the same dialysis treatment regimen for at least 1 month before trial entry).
4. Participants should be on a stable drug regimen defined as not starting a new drug or changing dosage within 7 days or 5 half-lives (whichever is longer) before dosing with TAK-954.

Exclusion Criteria:

1. All participants:

   • Are renal allograft recipients within 1 year of screening.
   • Have a history of gastrointestinal (GI) motility disorder or intestinal obstruction.
   • Have urinary incontinence without catheterization.
2. Group A: Participants who, in the discretion of the investigator, have a history of clinically significant endocrine, GI, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary, or major neurological (including stroke and chronic seizures) abnormalities or diseases will be excluded from the trial.

3. Groups B to E:

   • Receive dialysis other than intermittent dialysis (except Group E).
   • Have renal disease secondary to hepatic disease (hepatorenal syndrome).
   • At the discretion of the investigators, have any significant hepatic, cardiac, or pulmonary disease or participants who are clinically nephrotic.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A TAK-954 0.2 mg: Healthy Participants; Participants with normal renal function receive TAK-954 0.2 milligram (mg), infusion, intravenously in fasted state, once on Day 1 of a 6-day period.	Drug: TAK-954; TAK-954 intravenous infusion.
Experimental: Group B TAK-954 0.2 mg: Mild Renal Impairment; Participants receive TAK-954 0.2 mg, infusion, intravenously in fasted state, once on Day 1 of a 6-day period.	Drug: TAK-954; TAK-954 intravenous infusion.
Experimental: Group C TAK-954 0.2 mg: Moderate Renal Impairment; Participants receive TAK-954 0.2 mg, infusion, intravenously in fasted state, once on Day 1 of a 6-day period.	Drug: TAK-954; TAK-954 intravenous infusion.
Experimental: Group D TAK-954 0.2 mg: Severe Renal Impairment; Participants without hemodialysis or End-stage Renal Disease (ESRD) receive TAK-954 0.2 mg, infusion, intravenously in fasted state, once on Day 1 of a 6-day period.	Drug: TAK-954; TAK-954 intravenous infusion.
Experimental: Group E TAK-954 0.2 mg: End-stage Renal Disease (ESRD); Participants with hemodialysis receive TAK-954 0.2 mg, infusion, intravenously in fasted state, once on Day 1 of a 4-day period followed by a minimum 13-day washout period, further followed by TAK-954 0.2 mg, infusion, intravenously in fasted state, once on Day 1 of a 4-day period.	Drug: TAK-954; TAK-954 intravenous infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Groups A, C and D; Cmax: Maximum Observed Plasma Concentration for TAK-954 (Total and Free)	Day 1 pre-infusion and at multiple time points (up to 120 hours) post-infusion
Groups A, C and D; AUC(0-72): Area Under the Plasma Concentration-time Curve From Time 0 to 72 Hours Post-dose for TAK-954 (Free and Total)	Day 1 pre-infusion and at multiple time points (up to 72 hours) post-infusion
Groups A, C and D; AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-954 (Free and Total)	Day 1 pre-infusion and at multiple time points (up to 120 hours) post-infusion
Groups A, C and D; AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-954 (Free and Total)	Day 1 pre-infusion and at multiple time points (up to 120 hours) post-infusion
Groups A, C and D; Ae: Amount of TAK-954 Excreted in Urine	Day 1 pre-infusion and at multiple time points (up to 24 hours) post-infusion
Group E; Ae: Amount of TAK-954 Excreted in Urine in Period 1	Day 1 pre-infusion and at multiple time points (up to 24 hours) post-infusion
Group E; Ae: Amount of TAK-954 Excreted in Urine in Period 2	Day 1 pre-infusion and at multiple time points (up to 24 hours) post-infusion
Groups A, C and D; Fe: Fraction of TAK-954 Excreted in Urine	Day 1 pre-infusion and at multiple time points (up to 24 hours) post-infusion
Group E; Fe: Fraction of TAK-954 Excreted in Urine in Period 1	Day 1 pre-infusion and at multiple time points (up to 24 hours) post-infusion
Group E; Fe: Fraction of TAK-954 Excreted in Urine in Period 2	Day 1 pre-infusion and at multiple time points (up to 24 hours) post-infusion
Groups A, C and D; CLR: Renal Clearance for TAK-954	Day 1 pre-infusion and at multiple time points (up to 24 hours) post-infusion
Group E; CLR: Renal Clearance for TAK-954 in Period 1	Day 1 pre-infusion and at multiple time points (up to 24 hours) post-infusion
Group E; CLR: Renal Clearance for TAK-954 in Period 2	Day 1 pre-infusion and at multiple time points (up to 24 hours) post-infusion
Group E; CLD: Clearance of Dialysate for TAK-954 in Period 2	Day 1 pre-infusion and at multiple time points (up to 4 hours) post-infusion

Collaborators and Investigators

• Sponsor: Takeda

Study record dates

Study Major Dates

• Study Start (Actual): November 21, 2017
• Primary Completion (Actual): August 9, 2019
• Study Completion (Actual): August 9, 2019

Study Registration Dates

• First Submitted: September 25, 2017
• First Submitted That Met QC Criteria: September 25, 2017
• First Posted (Actual): September 28, 2017

Study Record Updates

• Last Update Posted (Actual): August 25, 2020
• Last Update Submitted That Met QC Criteria: August 6, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: Drug therapy
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency
• Other Study ID Numbers: TAK-954-1007; U1111-1196-9206 (Registry Identifier: WHO); 2017-000715-16 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Takeda makes patient-level, de-identified data sets and associated documents available for all interventional studies after applicable marketing approvals and commercial availability have been received (or program is completely terminated), an opportunity for the primary publication of the research and final report development has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No