Healthy Volunteers, Renal Impairment
Conditions
Keywords
Drug therapy
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.
Interventions
DRUGTAK-954
TAK-954 intravenous infusion.
Sponsors
Takeda
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 |
| 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 |
Countries
Czechia, Hungary
Participant flow
Recruitment details
Participants took part in the study at 4 investigative sites in Czech Republic and Hungary from 21 November 2017 to 09 August 2019.
Pre-assignment details
Participants with normal renal function and renal impairment were enrolled in 1 of the 4 groups: A (healthy), C (moderate), D (severe), and E (end-stage renal disease \[ESRD\]) to receive TAK-954 0.2 milligram (mg). Based on available safety and pharmacokinetics (PK) data from Group C, participants were not enrolled in Group B (mild).
Participants by arm
| Arm | Count |
|---|---|
| Group A: Healthy Participants TAK-954 0.2 mg, infusion, intravenously in fasted state, once on Day 1 of a 6-day period (Treatment 1), followed by a minimum 13-day washout period, further followed by probe cocktail of different cytochrome P-450 (CYP) substrates (caffeine 100 mg, oral \[CYP1A2\] + midazolam 0.025 milligram per kilogram \[mg/kg\], intravenously \[CYP3A4\]), once on Day 1 of a 4-day period (Treatment 2) in participants with normal renal function. | 8 |
| Group C: Moderate Renal Impairment TAK-954 0.2 mg, infusion, intravenously in fasted state, once on Day 1 of a 6-day period (Treatment 1), followed by a minimum 13-day washout period, further followed by probe cocktail of different CYP substrates (caffeine 100 mg, oral \[CYP1A2\] + midazolam 0.025 mg/kg, intravenously \[CYP3A4\]), once on Day 1 of a 4-day period (Treatment 2) in participants with moderate renal impairment. | 8 |
| Group D: Severe Renal Impairment Not Requiring Dialysis TAK-954 0.2 mg, infusion, intravenously in fasted state, once on Day 1 of a 6-day period (Treatment 1) in participants with severe renal impairment or ESRD without dialysis. | 9 |
| Group E: ESRD Requiring Dialysis TAK-954 0.2 mg, infusion, intravenously in fasted state, 1 hour after the end of dialysis, once on Day 1 of a 6-day Period 1, followed by a minimum 13-day washout period, further followed by TAK-954 0.2 mg, infusion, intravenously in fasted state, 2 hours before the start of dialysis, once on Day 1 of a 4-day Period 2 in participants with ESRD requiring dialysis. | 7 |
| Total | 32 |
Baseline characteristics
| Characteristic | Group A: Healthy Participants | Group C: Moderate Renal Impairment | Group D: Severe Renal Impairment Not Requiring Dialysis | Group E: ESRD Requiring Dialysis | Total |
|---|---|---|---|---|---|
| Age, Continuous | 57.0 years STANDARD_DEVIATION 15.62 | 70.6 years STANDARD_DEVIATION 3.5 | 62.2 years STANDARD_DEVIATION 11.03 | 52.6 years STANDARD_DEVIATION 10.06 | 60.9 years STANDARD_DEVIATION 12.38 |
| Body Mass Index (BMI) | 26.88 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 4.051 | 26.25 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 4.166 | 27.33 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 4.272 | 28.14 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 2.673 | 27.13 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 3.765 |
| Creatine Clearance | 107.11 milliliter per minute (mL/min) STANDARD_DEVIATION 23.417 | 46.20 milliliter per minute (mL/min) STANDARD_DEVIATION 10.767 | 23.20 milliliter per minute (mL/min) STANDARD_DEVIATION 6.385 | 10.54 milliliter per minute (mL/min) STANDARD_DEVIATION 2.504 | 47.16 milliliter per minute (mL/min) STANDARD_DEVIATION 39.484 |
| Estimated Glomerular Filtration Rate (eGFR) | 89.93 milliliter per minute/1.73 square meter STANDARD_DEVIATION 13.779 | 41.68 milliliter per minute/1.73 square meter STANDARD_DEVIATION 11.527 | 18.13 milliliter per minute/1.73 square meter STANDARD_DEVIATION 8.648 | 6.93 milliliter per minute/1.73 square meter STANDARD_DEVIATION 2.757 | 39.52 milliliter per minute/1.73 square meter STANDARD_DEVIATION 33.514 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 8 Participants | 9 Participants | 7 Participants | 32 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Height | 173.25 centimeter (cm) STANDARD_DEVIATION 9.706 | 170.25 centimeter (cm) STANDARD_DEVIATION 9.543 | 166.89 centimeter (cm) STANDARD_DEVIATION 9.519 | 171.00 centimeter (cm) STANDARD_DEVIATION 6.976 | 170.22 centimeter (cm) STANDARD_DEVIATION 8.965 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 8 Participants | 9 Participants | 7 Participants | 32 Participants |
| Region of Enrollment Czech Republic | 6 Participants | 6 Participants | 5 Participants | 3 Participants | 20 Participants |
| Region of Enrollment Hungary | 2 Participants | 2 Participants | 4 Participants | 4 Participants | 12 Participants |
| Sex: Female, Male Female | 3 Participants | 4 Participants | 4 Participants | 0 Participants | 11 Participants |
| Sex: Female, Male Male | 5 Participants | 4 Participants | 5 Participants | 7 Participants | 21 Participants |
| Weight | 79.95 kilogram (kg) STANDARD_DEVIATION 7.773 | 75.95 kilogram (kg) STANDARD_DEVIATION 13.035 | 76.22 kilogram (kg) STANDARD_DEVIATION 14.457 | 82.39 kilogram (kg) STANDARD_DEVIATION 7.006 | 78.43 kilogram (kg) STANDARD_DEVIATION 11.072 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 8 | 0 / 9 | 0 / 7 | 0 / 7 |
| other Total, other adverse events | 1 / 8 | 2 / 8 | 2 / 9 | 1 / 7 | 2 / 7 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 | 0 / 9 | 0 / 7 | 0 / 7 |
Outcome results
Primary
Group E; Ae: Amount of TAK-954 Excreted in Urine in Period 1
Time frame: Day 1 pre-infusion and at multiple time points (up to 24 hours) post-infusion
Population: The PK set consisted of all participants who were enrolled and received at least 1 dose of trial drug and had at least 1 measurable TAK-954 plasma concentration. Here, overall number of participants analyzed are the participants who were evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group A: Healthy Participants | Group E; Ae: Amount of TAK-954 Excreted in Urine in Period 1 | 0.0003489 mg | Standard Deviation 0.00021788 |
Primary
Group E; Ae: Amount of TAK-954 Excreted in Urine in Period 2
Time frame: Day 1 pre-infusion and at multiple time points (up to 24 hours) post-infusion
Population: The PK set consisted of all participants who were enrolled and received at least 1 dose of trial drug and had at least 1 measurable TAK-954 plasma concentration. Here, overall number of participants analyzed are the participants who were evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group A: Healthy Participants | Group E; Ae: Amount of TAK-954 Excreted in Urine in Period 2 | 0.001240 mg | Standard Deviation 0.00062 |
Primary
Group E; CLD: Clearance of Dialysate for TAK-954 in Period 2
Time frame: Day 1 pre-infusion and at multiple time points (up to 4 hours) post-infusion
Population: The PK set consisted of all participants who were enrolled and received at least 1 dose of trial drug and had at least 1 measurable TAK-954 plasma concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group A: Healthy Participants | Group E; CLD: Clearance of Dialysate for TAK-954 in Period 2 | 1.368 L/h | Geometric Coefficient of Variation 30 |
Primary
Group E; CLR: Renal Clearance for TAK-954 in Period 1
Time frame: Day 1 pre-infusion and at multiple time points (up to 24 hours) post-infusion
Population: The PK set consisted of all participants who were enrolled and received at least 1 dose of trial drug and had at least 1 measurable TAK-954 plasma concentration. Here, overall number of participants analyzed are the participants who were evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group A: Healthy Participants | Group E; CLR: Renal Clearance for TAK-954 in Period 1 | 0.03192 L/h | Standard Deviation 0.01767 |
Primary
Group E; CLR: Renal Clearance for TAK-954 in Period 2
Time frame: Day 1 pre-infusion and at multiple time points (up to 24 hours) post-infusion
Population: The PK set consisted of all participants who were enrolled and received at least 1 dose of trial drug and had at least 1 measurable TAK-954 plasma concentration. Here, overall number of participants analyzed are the participants who were evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group A: Healthy Participants | Group E; CLR: Renal Clearance for TAK-954 in Period 2 | 0.08330 L/h | Standard Deviation 0.04165 |
Primary
Group E; Fe: Fraction of TAK-954 Excreted in Urine in Period 1
Time frame: Day 1 pre-infusion and at multiple time points (up to 24 hours) post-infusion
Population: The PK set consisted of all participants who were enrolled and received at least 1 dose of trial drug and had at least 1 measurable TAK-954 plasma concentration. Here, overall number of participants analyzed are the participants who were evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group A: Healthy Participants | Group E; Fe: Fraction of TAK-954 Excreted in Urine in Period 1 | 0.1739 percentage of TAK-954 dose | Standard Deviation 0.10869 |
Primary
Group E; Fe: Fraction of TAK-954 Excreted in Urine in Period 2
Time frame: Day 1 pre-infusion and at multiple time points (up to 24 hours) post-infusion
Population: The PK set consisted of all participants who were enrolled and received at least 1 dose of trial drug and had at least 1 measurable TAK-954 plasma concentration. Here, overall number of participants analyzed are the participants who were evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group A: Healthy Participants | Group E; Fe: Fraction of TAK-954 Excreted in Urine in Period 2 | 0.6190 percentage of TAK-954 dose | Standard Deviation 0.3095 |
Primary
Groups A, C and D; Ae: Amount of TAK-954 Excreted in Urine
Time frame: Day 1 pre-infusion and at multiple time points (up to 24 hours) post-infusion
Population: The PK set consisted of all participants who were enrolled and received at least 1 dose of trial drug and had at least 1 measurable TAK-954 plasma concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group A: Healthy Participants | Groups A, C and D; Ae: Amount of TAK-954 Excreted in Urine | 0.03797 milligram (mg) | Standard Deviation 0.011633 |
| Group C: Moderate Renal Impairment | Groups A, C and D; Ae: Amount of TAK-954 Excreted in Urine | 0.01763 milligram (mg) | Standard Deviation 0.0087713 |
| Group D: Severe Renal Impairment Not Requiring Dialysis | Groups A, C and D; Ae: Amount of TAK-954 Excreted in Urine | 0.01190 milligram (mg) | Standard Deviation 0.0091124 |
Primary
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)
Time frame: Day 1 pre-infusion and at multiple time points (up to 72 hours) post-infusion
Population: The PK set consisted of all participants who were enrolled and received at least 1 dose of trial drug and had at least 1 measurable TAK-954 plasma concentration. The OM was planned to be assessed for the groups where blood samples were collected before the start of TAK-954 infusion and through 120 hours post-infusion.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Group A: Healthy Participants | 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) | TAK-954 (Total) | 22.25 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 19.1 |
| Group A: Healthy Participants | 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) | TAK-954 (Free) | 1.078 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 25.7 |
| Group C: Moderate Renal Impairment | 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) | TAK-954 (Total) | 24.91 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 22.9 |
| Group C: Moderate Renal Impairment | 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) | TAK-954 (Free) | 1.259 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 25.1 |
| Group D: Severe Renal Impairment Not Requiring Dialysis | 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) | TAK-954 (Total) | 28.62 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 18.1 |
| Group D: Severe Renal Impairment Not Requiring Dialysis | 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) | TAK-954 (Free) | 1.690 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 25.9 |
p-value: 0.2686ANOVA
p-value: 0.0059ANOVA
p-value: 0.36ANOVA
p-value: 0.0816ANOVA
Primary
Groups A, C and D; AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-954 (Free and Total)
Time frame: Day 1 pre-infusion and at multiple time points (up to 120 hours) post-infusion
Population: PK set:participants who enrolled and received at least 1 dose of trial drug and had at least 1 measurable TAK-954 plasma concentration. Here,overall number of participants analyzed: participants who were evaluable for this OM. OM was planned to be assessed in groups where blood samples collected pre-TAK-954 infusion up to 120 hours post-infusion.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Group A: Healthy Participants | Groups A, C and D; AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-954 (Free and Total) | TAK-954 (Total) | 25.43 h*ng/mL | Geometric Coefficient of Variation 16.8 |
| Group A: Healthy Participants | Groups A, C and D; AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-954 (Free and Total) | TAK-954 (Free) | 1.234 h*ng/mL | Geometric Coefficient of Variation 28.4 |
| Group C: Moderate Renal Impairment | Groups A, C and D; AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-954 (Free and Total) | TAK-954 (Total) | 34.90 h*ng/mL | Geometric Coefficient of Variation 16.2 |
| Group C: Moderate Renal Impairment | Groups A, C and D; AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-954 (Free and Total) | TAK-954 (Free) | 1.749 h*ng/mL | Geometric Coefficient of Variation 24.8 |
| Group D: Severe Renal Impairment Not Requiring Dialysis | Groups A, C and D; AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-954 (Free and Total) | TAK-954 (Total) | 38.59 h*ng/mL | Geometric Coefficient of Variation 23.9 |
| Group D: Severe Renal Impairment Not Requiring Dialysis | Groups A, C and D; AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-954 (Free and Total) | TAK-954 (Free) | 2.320 h*ng/mL | Geometric Coefficient of Variation 29.7 |
p-value: 0.0038ANOVA
p-value: 0.0004ANOVA
p-value: 0.0389ANOVA
p-value: 0.0011ANOVA
Primary
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)
Time frame: Day 1 pre-infusion and at multiple time points (up to 120 hours) post-infusion
Population: The PK set consisted of all participants who were enrolled and received at least 1 dose of trial drug and had at least 1 measurable TAK-954 plasma concentration. The OM was planned to be assessed for the groups where blood samples were collected before the start of TAK-954 infusion and through 120 hours post-infusion.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Group A: Healthy Participants | 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) | TAK-954 (Total) | 24.39 h*ng/mL | Geometric Coefficient of Variation 17.7 |
| Group A: Healthy Participants | 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) | TAK-954 (Free) | 1.184 h*ng/mL | Geometric Coefficient of Variation 26.8 |
| Group C: Moderate Renal Impairment | 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) | TAK-954 (Total) | 30.00 h*ng/mL | Geometric Coefficient of Variation 20 |
| Group C: Moderate Renal Impairment | 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) | TAK-954 (Free) | 1.516 h*ng/mL | Geometric Coefficient of Variation 24.3 |
| Group D: Severe Renal Impairment Not Requiring Dialysis | 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) | TAK-954 (Total) | 34.28 h*ng/mL | Geometric Coefficient of Variation 19.3 |
| Group D: Severe Renal Impairment Not Requiring Dialysis | 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) | TAK-954 (Free) | 2.025 h*ng/mL | Geometric Coefficient of Variation 26.7 |
p-value: 0.0998ANOVA
p-value: 0.0155ANOVA
p-value: 0.0916ANOVA
p-value: 0.0014ANOVA
Primary
Groups A, C and D; CLR: Renal Clearance for TAK-954
Time frame: Day 1 pre-infusion and at multiple time points (up to 24 hours) post-infusion
Population: The PK set consisted of all participants who were enrolled and received at least 1 dose of study drug and had at least 1 measurable TAK-954 plasma concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group A: Healthy Participants | Groups A, C and D; CLR: Renal Clearance for TAK-954 | 2.629 liter per hour (L/h) | Standard Deviation 0.78762 |
| Group C: Moderate Renal Impairment | Groups A, C and D; CLR: Renal Clearance for TAK-954 | 1.255 liter per hour (L/h) | Standard Deviation 0.51478 |
| Group D: Severe Renal Impairment Not Requiring Dialysis | Groups A, C and D; CLR: Renal Clearance for TAK-954 | 0.6836 liter per hour (L/h) | Standard Deviation 0.56141 |
Primary
Groups A, C and D; Cmax: Maximum Observed Plasma Concentration for TAK-954 (Total and Free)
Time frame: Day 1 pre-infusion and at multiple time points (up to 120 hours) post-infusion
Population: The PK set consisted of all participants who were enrolled and received at least 1 dose of trial drug and had at least 1 measurable TAK-954 plasma concentration. The outcome measure (OM) was planned to be assessed for the groups where blood samples were collected before the start of TAK-954 infusion and through 120 hours post-infusion.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Group A: Healthy Participants | Groups A, C and D; Cmax: Maximum Observed Plasma Concentration for TAK-954 (Total and Free) | TAK-954 (Total) | 2.623 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 12.8 |
| Group A: Healthy Participants | Groups A, C and D; Cmax: Maximum Observed Plasma Concentration for TAK-954 (Total and Free) | TAK-954 (Free) | 0.1270 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 29.2 |
| Group C: Moderate Renal Impairment | Groups A, C and D; Cmax: Maximum Observed Plasma Concentration for TAK-954 (Total and Free) | TAK-954 (Total) | 2.536 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 23.2 |
| Group C: Moderate Renal Impairment | Groups A, C and D; Cmax: Maximum Observed Plasma Concentration for TAK-954 (Total and Free) | TAK-954 (Free) | 0.1282 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 22.5 |
| Group D: Severe Renal Impairment Not Requiring Dialysis | Groups A, C and D; Cmax: Maximum Observed Plasma Concentration for TAK-954 (Total and Free) | TAK-954 (Total) | 2.660 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 17.6 |
| Group D: Severe Renal Impairment Not Requiring Dialysis | Groups A, C and D; Cmax: Maximum Observed Plasma Concentration for TAK-954 (Total and Free) | TAK-954 (Free) | 0.1572 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 21.7 |
p-value: 0.7265ANOVA
p-value: 0.9839ANOVA
p-value: 0.9393ANOVA
p-value: 0.1321ANOVA
Primary
Groups A, C and D; Fe: Fraction of TAK-954 Excreted in Urine
Time frame: Day 1 pre-infusion and at multiple time points (up to 24 hours) post-infusion
Population: The PK set consisted of all participants who were enrolled and received at least 1 dose of trial drug and had at least 1 measurable TAK-954 plasma concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group A: Healthy Participants | Groups A, C and D; Fe: Fraction of TAK-954 Excreted in Urine | 19.00 percentage of TAK-954 dose | Standard Deviation 5.8075 |
| Group C: Moderate Renal Impairment | Groups A, C and D; Fe: Fraction of TAK-954 Excreted in Urine | 8.808 percentage of TAK-954 dose | Standard Deviation 4.3746 |
| Group D: Severe Renal Impairment Not Requiring Dialysis | Groups A, C and D; Fe: Fraction of TAK-954 Excreted in Urine | 5.953 percentage of TAK-954 dose | Standard Deviation 4.5595 |