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

Phase 1

Completed

• Conditions: Renal Impairment; Healthy Volunteers
• Interventions: Drug: TAK-954

• Registration Number: NCT03296787
• Lead Sponsor: Takeda

Brief Summary

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.

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 Timeline

• Study First Submitted: 2017-09-25
• Study First Submitted QC: 2017-09-25
• Study First Posted: 2017-09-28
• Study Start: 2017-11-21
• Primary Completion: 2019-08-09
• Study Completion: 2019-08-09
• Status Verified: 2020-08
• Results First Submitted: 2020-08-06
• Results First Submitted QC: 2020-08-06
• Last Update Submitted: 2020-08-06
• Results First Posted: 2020-08-25
• Last Update Posted: 2020-08-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 32

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group A TAK-954 0.2 mg: Healthy Participants	TAK-954	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.
Group B TAK-954 0.2 mg: Mild Renal Impairment	TAK-954	Participants receive TAK-954 0.2 mg, infusion, intravenously in fasted state, once on Day 1 of a 6-day period.
Group C TAK-954 0.2 mg: Moderate Renal Impairment	TAK-954	Participants receive TAK-954 0.2 mg, infusion, intravenously in fasted state, once on Day 1 of a 6-day period.
Group D TAK-954 0.2 mg: Severe Renal Impairment	TAK-954	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.
Group E TAK-954 0.2 mg: End-stage Renal Disease (ESRD)	TAK-954	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.

Primary Outcome Measures

Name	Time	Method
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
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; CLR: Renal Clearance for TAK-954 in Period 1	Day 1 pre-infusion and at multiple time points (up to 24 hours) post-infusion
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; 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 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 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
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

Trial Locations

Locations (4)

PRA CZ, s.r.o; 🇨🇿 Praha 7, Praha, Czechia

Fakultni Nemocnice Hradec Kralove; 🇨🇿 Hradec Kralove, Czechia

PRA Magyarorszag Kft.; 🇭🇺 Budapest, Hungary

Szent Imre Egyetemi Oktatokorhaz Belgyogyazati Szakmak Matrix Intezet; 🇭🇺 Budapest, Hungary