| Primary | Groups A, C and D; Cmax: Maximum Observed Plasma Concentration for TAK-954 (Total and Free) | | 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. | Posted | | Geometric Mean | Geometric Coefficient of Variation | nanogram per milliliter (ng/mL) | | Day 1 pre-infusion and at multiple time points (up to 120 hours) post-infusion | | | | ID | Title | Description |
|---|
| OG000 | 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. | | OG001 | 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. | | OG002 | 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. |
| | | Title | Denominators | Categories |
|---|
| TAK-954 (Total) | | | Title | Measurements |
|---|
| - OG0002.623± 12.8
- OG0012.536± 23.2
- OG0022.660± 17.6
|
| | TAK-954 (Free) |
| | Group IDs | Group Description | Statistical Method | Statistical Comment | P-Value | P-Value Comment | Parameter Type | Parameter Value | Dispersion Type | Dispersion Value | Confidence Interval Sides | Confidence Interval % | CI Lower Limit | CI Upper Limit | CI Lower Limit Comment | CI Upper Limit Comment | Estimate Comment | Tested Non-Inferiority | Non-Inferiority Type | Non-Inferiority Comment | Other Analysis Description |
|---|
| | ANOVA | | 0.7265 | | | | | | | | | | | | | | Superiority | TAK-954 (Total): An analysis of variance (ANOVA) were performed on log transformed Cmax (total TAK-954) to compare moderate renal impairment group with the normal renal function group. | | | | ANOVA |
|
| 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) | | 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. | Posted | | Geometric Mean | Geometric Coefficient of Variation | hour*nanogram per milliliter (h*ng/mL) | | Day 1 pre-infusion and at multiple time points (up to 72 hours) post-infusion | | | | ID | Title | Description |
|---|
| OG000 | 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. | | OG001 | 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. |
|
| 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) | | 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. | Posted | | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | | Day 1 pre-infusion and at multiple time points (up to 120 hours) post-infusion | | | | ID | Title | Description |
|---|
| OG000 | 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. | | OG001 | 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. |
|
| 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) | | 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. | Posted | | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | | Day 1 pre-infusion and at multiple time points (up to 120 hours) post-infusion | | | | ID | Title | Description |
|---|
| OG000 | 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. | | OG001 | 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. |
|
| Primary | Groups A, C and D; Ae: Amount of TAK-954 Excreted in Urine | | 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. | Posted | | Geometric Mean | Standard Deviation | milligram (mg) | | Day 1 pre-infusion and at multiple time points (up to 24 hours) post-infusion | | | | ID | Title | Description |
|---|
| OG000 | 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. | | OG001 | 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. | | OG002 | Group D: Severe Renal Impairment Not Requiring Dialysis |
|
| Primary | Group E; Ae: Amount of TAK-954 Excreted in Urine in Period 1 | | 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. | Posted | | Geometric Mean | Standard Deviation | mg | | Day 1 pre-infusion and at multiple time points (up to 24 hours) post-infusion | | | | ID | Title | Description |
|---|
| OG000 | 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. |
| |
| Primary | Group E; Ae: Amount of TAK-954 Excreted in Urine in Period 2 | | 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. | Posted | | Geometric Mean | Standard Deviation | mg | | Day 1 pre-infusion and at multiple time points (up to 24 hours) post-infusion | | | | ID | Title | Description |
|---|
| OG000 | 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. |
| |
| Primary | Groups A, C and D; Fe: Fraction of TAK-954 Excreted in Urine | | 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. | Posted | | Geometric Mean | Standard Deviation | percentage of TAK-954 dose | | Day 1 pre-infusion and at multiple time points (up to 24 hours) post-infusion | | | | ID | Title | Description |
|---|
| OG000 | 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. | | OG001 | 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. | | OG002 | Group D: Severe Renal Impairment Not Requiring Dialysis |
|
| Primary | Group E; Fe: Fraction of TAK-954 Excreted in Urine in Period 1 | | 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. | Posted | | Geometric Mean | Standard Deviation | percentage of TAK-954 dose | | Day 1 pre-infusion and at multiple time points (up to 24 hours) post-infusion | | | | ID | Title | Description |
|---|
| OG000 | 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. |
| |
| Primary | Group E; Fe: Fraction of TAK-954 Excreted in Urine in Period 2 | | 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. | Posted | | Geometric Mean | Standard Deviation | percentage of TAK-954 dose | | Day 1 pre-infusion and at multiple time points (up to 24 hours) post-infusion | | | | ID | Title | Description |
|---|
| OG000 | 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. |
| |
| Primary | Groups A, C and D; CLR: Renal Clearance for TAK-954 | | 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. | Posted | | Geometric Mean | Standard Deviation | liter per hour (L/h) | | Day 1 pre-infusion and at multiple time points (up to 24 hours) post-infusion | | | | ID | Title | Description |
|---|
| OG000 | 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. | | OG001 | 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. | | OG002 | Group D: Severe Renal Impairment Not Requiring Dialysis |
|
| Primary | Group E; CLR: Renal Clearance for TAK-954 in Period 1 | | 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. | Posted | | Geometric Mean | Standard Deviation | L/h | | Day 1 pre-infusion and at multiple time points (up to 24 hours) post-infusion | | | | ID | Title | Description |
|---|
| OG000 | 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. |
| |
| Primary | Group E; CLR: Renal Clearance for TAK-954 in Period 2 | | 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. | Posted | | Geometric Mean | Standard Deviation | L/h | | Day 1 pre-infusion and at multiple time points (up to 24 hours) post-infusion | | | | ID | Title | Description |
|---|
| OG000 | 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. |
| |
| Primary | Group E; CLD: Clearance of Dialysate for TAK-954 in Period 2 | | 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. | Posted | | Geometric Mean | Geometric Coefficient of Variation | L/h | | Day 1 pre-infusion and at multiple time points (up to 4 hours) post-infusion | | | | ID | Title | Description |
|---|
| OG000 | 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. |
| |