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

NCT03296787 | Completed Phase 1 Results FDA Drug

• 3 other identifiers: TAK-954-1007U1111-1196-92062017-000715-16
• Study Type: interventional
• Target: 32
• Locations: 2 countries
• Sites: 4

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.

Conditions

Renal Impairment; Healthy Volunteers

Keywords

Drug therapy

Outcome Measures

Primary Outcomes (14)

• 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

Study Arms (5)

Group A TAK-954 0.2 mg: Healthy Participants

EXPERIMENTAL

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

Group B TAK-954 0.2 mg: Mild Renal Impairment

EXPERIMENTAL

Participants receive TAK-954 0.2 mg, infusion, intravenously in fasted state, once on Day 1 of a 6-day period.

Drug: TAK-954

Group C TAK-954 0.2 mg: Moderate Renal Impairment

EXPERIMENTAL

Participants receive TAK-954 0.2 mg, infusion, intravenously in fasted state, once on Day 1 of a 6-day period.

Drug: TAK-954

Group D TAK-954 0.2 mg: Severe Renal Impairment

EXPERIMENTAL

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

Group E TAK-954 0.2 mg: End-stage Renal Disease (ESRD)

EXPERIMENTAL

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

Interventions

TAK-954 DRUG

TAK-954 intravenous infusion.

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; Group E TAK-954 0.2 mg: End-stage Renal Disease (ESRD)

Eligibility Criteria

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

You may qualify if:

• 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).
• 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.
• 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).
• 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.

You may not qualify if:

• 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.
• 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.
• 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.

Sponsors & Collaborators

• Takeda: lead

Study Sites (4)

PRA CZ, s.r.o

Prague, Prague, 170 00, Czechia

Location

Fakultni Nemocnice Hradec Kralove

Hradec Králové, 500 05, Czechia

Location

PRA Magyarorszag Kft.

Budapest, 1077, Hungary

Location

Szent Imre Egyetemi Oktatokorhaz Belgyogyazati Szakmak Matrix Intezet

Budapest, 1115, Hungary

Location

MeSH Terms

Conditions

Renal Insufficiency

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

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: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 25, 2017
• First Posted: September 28, 2017
• Study Start: November 21, 2017
• Primary Completion: August 9, 2019
• Study Completion: August 9, 2019
• Last Updated: August 25, 2020
• Results First Posted: August 25, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will share

Locations

HU (2); CZ (2)