Healthy Volunteers
Conditions
Keywords
Drug Therapy
Brief summary
The purpose of this study is to evaluate the safety, tolerability, and PK of single ascending intravenous doses of TAK-954.
Detailed description
The drug being tested in this study is called TAK-954. This study will assess the safety, tolerability, PK and PD of single ascending TAK-954 higher intravenous doses than those previously studied. The study will enroll approximately 6 participants. Participants will be randomly assigned (By chance, like flipping a coin) to one of the three treatment sequences-which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need). In each treatment sequence, each participant will receive 2 doses of active drug out of 3 dose levels (TAK-954 0.5 mg, TAK-954 1 mg, or TAK-954 2 mg) and 1 dose of Placebo. Dose escalation will be based on the available safety/tolerability data from the previous period. This single center trial will be conducted in the United States. The overall time to participate in this study is approximately 73 days. Participants will make a final visit on Day 16 after receiving their last dose of study drug for a follow-up assessment.
Interventions
DRUGTAK-954
TAK-954 infusion administered intravenously.
DRUGTAK-954 Placebo
TAK-954 placebo-matching infusion intravenous.
Sponsors
Millennium Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Body mass index (BMI) greater than or equal to (\>=) 18 and less than or equal to (\<=) 32 kilogram per square meter (kg/m\^2), weighing \>=50 kilogram (kg) at screening. 2. Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs, orthostatic vital signs, or ECGs, as deemed by the Investigator or designee. 3. Continuous non-smoker who has not used nicotine-containing products for at least 3 months prior to the first dose and throughout the study, based on participant self-reporting.
Exclusion criteria
1. History or presence of alcoholism or drug abuse within the past 2 years prior to the first dosing. 2. Has infrequent bowel movements (less than approximately once per day) within 30 days prior to first dosing. 3. Recent history of abnormal bowel movements, such as diarrhea, loose stools, or constipation, within 2 weeks of first dosing.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| CLR: Renal Clearance for TAK-954 | Day 2 pre-dose and at multiple time points (up to 36 hours) post-dose |
| Fe: Fraction of TAK-954 Excreted in Urine on Day 2 up to 12 Hours Post-dose | Day 2 pre-dose and at multiple time points (up to 12 hours) post-dose |
| Fe: Fraction of TAK-954 Excreted in Urine on Day 2 up to 24 Hours Post-dose | Day 2 pre-dose and at multiple time points (up to 24 hours) post-dose |
| Fe: Fraction of TAK-954 Excreted in Urine on Day 2 up to 36 Hours Post-dose | Day 2 pre-dose and at multiple time points (up to 36 hours) post-dose |
| Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) for TAK-954 | Dosing on Day 2 in Period 1 up to 14 days after last dose of study drug on Day 2 of Period 3 (up to Day 52) |
| Number of Participants With Clinically Significant Change From Baseline in Vital Signs for TAK-954 | Dosing on Day 2 in Period 1 up to 14 days after last dose of study drug on Day 2 of Period 3 (up to Day 52) |
| Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiograms (ECG) for TAK-954 | Dosing on Day 2 in Period 1 up to 14 days after last dose of study drug on Day 2 of Period 3 (up to Day 52) |
| Number of Participants With Clinically Notable Shifts From Baseline to Abnormal Post-dose in Clinical Laboratory Values for TAK-954 | Dosing on Day 2 in Period 1 up to 14 days after last dose of study drug on Day 2 of Period 3 (up to Day 52) |
| AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-954 | Day 2 pre-dose and at multiple time points (up to 336 hours) post-dose |
| AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-954 | Day 2 pre-dose and at multiple time points (up to 336 hours) post-dose |
| Ceoi: Plasma Concentration Observed at the End of Infusion for TAK-954 | Day 2 pre-dose and at multiple time points (up to 336 hours) post-dose |
| CL: Total Clearance After Intravenous Administration for TAK-954 | Day 2 pre-dose and at multiple time points (up to 336 hours) post-dose |
| Vz: Volume of Distribution During the Terminal Disposition Phase After Intravenous Administration for TAK-954 | Day 2 pre-dose and at multiple time points (up to 336 hours) post-dose |
| Ae: Amount of Unchanged Drug Excreted in the Urine for TAK-954 on Day 2 up to 12 Hours Post-dose | Day 2 pre-dose and at multiple time points (up to 12 hours) post-dose |
| Ae: Amount of Unchanged Drug Excreted in the Urine for TAK-954 on Day 2 up to 24 Hours Post-dose | Day 2 pre-dose and at multiple time points (up to 24 hours) post-dose |
| Ae: Amount of Unchanged Drug Excreted in the Urine for TAK-954 on Day 2 up to 36 Hours Post-dose | Day 2 pre-dose and at multiple time points (up to 36 hours) post-dose |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Number of Stools of TAK-954 Within 36 Hours Post-dose on Day 2 | Day 2 dosing and at multiple time points (up to 36 hours) post-dose | — |
| Instances of Stool Type of TAK-954 Based on Bristol Stool Form Scale | Day 2 dosing and at multiple time points (up to 36 hours) post-dose | Number of occurrences for each stool type was reported based on their type assessed from Bristol Stool form scale. The Bristol Stool Form Scale was used to assess the stool shape using a 7-point scale. Where, Type 1 = separate hard lumps, like nuts (hard to pass), Type 2 = sausage-shaped but lumpy, Type 3 = like a sausage but with cracks on the surface, Type 4 = like a sausage or snake, smooth and soft, Type 5 = soft blobs with clear-cut edges (passed easily), Type 6 = fluffy pieces with ragged edges, a mushy stool, Type 7 = watery, no solid pieces; entirely liquid. A score of 1 or 2 indicates constipation and a score of 6 or 7 indicates diarrhea. |
| Number of Participants With First Stool of TAK-954 Within 36 Hours Post-dose on Day 2 | Day 2 dosing and at multiple time points (up to 36 hours) post-dose | — |
Countries
United States
Participant flow
Recruitment details
Participants took part in the study at 1 investigative site in the United States from 08 March 2019 to 16 May 2019.
Pre-assignment details
Healthy adult participants were enrolled in this 3-period cross-over study in 1 of the 3 treatment sequences to receive TAK-954 0.1 milligram (mg) or Placebo on Day 1 (Lead-in Dose), followed by TAK-954 (0.5 mg, 1 mg or 2 mg) or Placebo on Day 2 (Treatment Dose) of each study period.
Participants by arm
| Arm | Count |
|---|---|
| Sequence 1: Placebo + TAK-954 1 mg + TAK-954 2 mg Period 1: TAK-954 placebo-matching infusion, intravenously, once on Day 1 and Day 2.
Period 2: TAK-954 0.1 mg, infusion, intravenously, once on Day 1 and TAK-954 1 mg infusion, intravenously, once on Day 2.
Period 3: TAK-954 0.1 mg, infusion, intravenously, once on Day 1 and TAK-954 2 mg infusion, intravenously, once on Day 2.
A washout period of at least 16 days was maintained between each Treatment Period. | 2 |
| Sequence 2: TAK-954 0.5 mg + Placebo + TAK-954 2 mg Period 1: TAK-954 0.1 mg, infusion, intravenously, once on Day 1 and TAK-954 0.5 mg infusion, intravenously once on Day 2.
Period 2: TAK-954 placebo-matching infusion, intravenously, once on Day 1 and Day 2.
Period 3: TAK-954 0.1 mg, infusion, intravenously, once on Day 1 and TAK-954 2 mg, infusion, intravenously, once on Day 2.
A washout period of at least 16 days was maintained between each Treatment Period. | 2 |
| Sequence 3: TAK-954 0.5 mg + TAK-954 1 mg + Placebo Period 1: TAK-954 0.1 mg, infusion, intravenously, once on Day 1 and TAK-954 0.5 mg, infusion, intravenously once on Day 2.
Period 2: TAK-954 0.1 mg, infusion, intravenously, once on Day 1 and TAK-954 1 mg, infusion, intravenously, once on Day 2.
Period 3: TAK-954 placebo-matching infusion, intravenously, once on Day 1 and Day 2.
A washout period of at least 16 days was maintained between each Treatment Period. | 2 |
| Total | 6 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Period 3 (2 Days) | Adverse Event | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Sequence 2: TAK-954 0.5 mg + Placebo + TAK-954 2 mg | Total | Sequence 1: Placebo + TAK-954 1 mg + TAK-954 2 mg | Sequence 3: TAK-954 0.5 mg + TAK-954 1 mg + Placebo |
|---|---|---|---|---|
| Age, Continuous | 33.0 years STANDARD_DEVIATION 4.24 | 35.8 years STANDARD_DEVIATION 10.85 | 28.0 years STANDARD_DEVIATION 14.14 | 46.5 years STANDARD_DEVIATION 2.12 |
| Body Mass Index (BMI) | 24.375 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 2.5102 | 27.828 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 3.1252 | 29.655 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 1.9021 | 29.455 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 1.7607 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 6 Participants | 2 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Height | 167.0 centimeter (cm) STANDARD_DEVIATION 21.21 | 167.0 centimeter (cm) STANDARD_DEVIATION 10.43 | 168.5 centimeter (cm) STANDARD_DEVIATION 7.78 | 165.5 centimeter (cm) STANDARD_DEVIATION 4.95 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 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 |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 6 Participants | 2 Participants | 2 Participants |
| Region of Enrollment United States | 2 Participants | 6 Participants | 2 Participants | 2 Participants |
| Sex: Female, Male Female | 1 Participants | 4 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 1 Participants | 0 Participants |
| Weight | 67.60 kilogram STANDARD_DEVIATION 9.758 | 77.65 kilogram STANDARD_DEVIATION 10.858 | 84.80 kilogram STANDARD_DEVIATION 13.152 | 80.55 kilogram STANDARD_DEVIATION 0.495 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 4 | 0 / 4 | 0 / 3 | 0 / 6 |
| other Total, other adverse events | 5 / 6 | 1 / 6 | 4 / 4 | 3 / 4 | 0 / 3 | 0 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 4 | 0 / 4 | 0 / 3 | 0 / 6 |
Outcome results
Primary
Ae: Amount of Unchanged Drug Excreted in the Urine for TAK-954 on Day 2 up to 12 Hours Post-dose
Time frame: Day 2 pre-dose and at multiple time points (up to 12 hours) post-dose
Population: The PK set included all participants who complied sufficiently with the protocol and display an evaluable PK profile (example, exposure to treatment, availability of measurements and absence of major protocol violations).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment Dose: TAK-954 0.5 mg | Ae: Amount of Unchanged Drug Excreted in the Urine for TAK-954 on Day 2 up to 12 Hours Post-dose | 104300 nanogram | Geometric Coefficient of Variation 6.3 |
| Treatment Dose: TAK-954 1 mg | Ae: Amount of Unchanged Drug Excreted in the Urine for TAK-954 on Day 2 up to 12 Hours Post-dose | 226000 nanogram | Geometric Coefficient of Variation 16 |
| Treatment Dose: TAK-954 2 mg | Ae: Amount of Unchanged Drug Excreted in the Urine for TAK-954 on Day 2 up to 12 Hours Post-dose | 408900 nanogram | Geometric Coefficient of Variation 15.3 |
Primary
Ae: Amount of Unchanged Drug Excreted in the Urine for TAK-954 on Day 2 up to 24 Hours Post-dose
Time frame: Day 2 pre-dose and at multiple time points (up to 24 hours) post-dose
Population: The PK set included all participants who complied sufficiently with the protocol and display an evaluable PK profile (example, exposure to treatment, availability of measurements and absence of major protocol violations). PK-evaluable population where data at specified time points was available.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment Dose: TAK-954 0.5 mg | Ae: Amount of Unchanged Drug Excreted in the Urine for TAK-954 on Day 2 up to 24 Hours Post-dose | 53200 nanogram | Geometric Coefficient of Variation 27.3 |
| Treatment Dose: TAK-954 1 mg | Ae: Amount of Unchanged Drug Excreted in the Urine for TAK-954 on Day 2 up to 24 Hours Post-dose | 115300 nanogram | Geometric Coefficient of Variation 19.9 |
| Treatment Dose: TAK-954 2 mg | Ae: Amount of Unchanged Drug Excreted in the Urine for TAK-954 on Day 2 up to 24 Hours Post-dose | 190700 nanogram | Geometric Coefficient of Variation 23.7 |
Primary
Ae: Amount of Unchanged Drug Excreted in the Urine for TAK-954 on Day 2 up to 36 Hours Post-dose
Time frame: Day 2 pre-dose and at multiple time points (up to 36 hours) post-dose
Population: The PK set included all participants who complied sufficiently with the protocol and display an evaluable PK profile (example, exposure to treatment, availability of measurements and absence of major protocol violations).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment Dose: TAK-954 0.5 mg | Ae: Amount of Unchanged Drug Excreted in the Urine for TAK-954 on Day 2 up to 36 Hours Post-dose | 32420 nanogram | Geometric Coefficient of Variation 17.3 |
| Treatment Dose: TAK-954 1 mg | Ae: Amount of Unchanged Drug Excreted in the Urine for TAK-954 on Day 2 up to 36 Hours Post-dose | 66560 nanogram | Geometric Coefficient of Variation 5.3 |
| Treatment Dose: TAK-954 2 mg | Ae: Amount of Unchanged Drug Excreted in the Urine for TAK-954 on Day 2 up to 36 Hours Post-dose | 103600 nanogram | Geometric Coefficient of Variation 8.5 |
Primary
AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-954
Time frame: Day 2 pre-dose and at multiple time points (up to 336 hours) post-dose
Population: The PK set included all participants who complied sufficiently with the protocol and display an evaluable PK profile (example, exposure to treatment, availability of measurements and absence of major protocol violations).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment Dose: TAK-954 0.5 mg | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-954 | 89220 pg*hr/mL | Geometric Coefficient of Variation 22.8 |
| Treatment Dose: TAK-954 1 mg | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-954 | 163700 pg*hr/mL | Geometric Coefficient of Variation 12.8 |
| Treatment Dose: TAK-954 2 mg | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-954 | 299500 pg*hr/mL | Geometric Coefficient of Variation 29.6 |
Primary
AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-954
Time frame: Day 2 pre-dose and at multiple time points (up to 336 hours) post-dose
Population: The pharmacokinetic (PK) set included all participants who complied sufficiently with the protocol and display an evaluable PK profile (example, exposure to treatment, availability of measurements and absence of major protocol violations).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment Dose: TAK-954 0.5 mg | AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-954 | 88930 picogram*hour per milliliter (pg*hr/mL) | Geometric Coefficient of Variation 23 |
| Treatment Dose: TAK-954 1 mg | AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-954 | 163200 picogram*hour per milliliter (pg*hr/mL) | Geometric Coefficient of Variation 12.8 |
| Treatment Dose: TAK-954 2 mg | AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-954 | 298400 picogram*hour per milliliter (pg*hr/mL) | Geometric Coefficient of Variation 29.6 |
Primary
Ceoi: Plasma Concentration Observed at the End of Infusion for TAK-954
Time frame: Day 2 pre-dose and at multiple time points (up to 336 hours) post-dose
Population: The PK set included all participants who complied sufficiently with the protocol and display an evaluable PK profile (example, exposure to treatment, availability of measurements and absence of major protocol violations).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment Dose: TAK-954 0.5 mg | Ceoi: Plasma Concentration Observed at the End of Infusion for TAK-954 | 7502 picogram per milliliter (pg/mL) | Geometric Coefficient of Variation 24.1 |
| Treatment Dose: TAK-954 1 mg | Ceoi: Plasma Concentration Observed at the End of Infusion for TAK-954 | 15260 picogram per milliliter (pg/mL) | Geometric Coefficient of Variation 12.9 |
| Treatment Dose: TAK-954 2 mg | Ceoi: Plasma Concentration Observed at the End of Infusion for TAK-954 | 30270 picogram per milliliter (pg/mL) | Geometric Coefficient of Variation 28.5 |
Primary
CLR: Renal Clearance for TAK-954
Time frame: Day 2 pre-dose and at multiple time points (up to 36 hours) post-dose
Population: The PK set included all participants who complied sufficiently with the protocol and display an evaluable PK profile (example, exposure to treatment, availability of measurements and absence of major protocol violations).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment Dose: TAK-954 0.5 mg | CLR: Renal Clearance for TAK-954 | 3.457 L/hr | Geometric Coefficient of Variation 19.9 |
| Treatment Dose: TAK-954 1 mg | CLR: Renal Clearance for TAK-954 | 3.933 L/hr | Geometric Coefficient of Variation 8.9 |
| Treatment Dose: TAK-954 2 mg | CLR: Renal Clearance for TAK-954 | 3.624 L/hr | Geometric Coefficient of Variation 35 |
Primary
CL: Total Clearance After Intravenous Administration for TAK-954
Time frame: Day 2 pre-dose and at multiple time points (up to 336 hours) post-dose
Population: The PK set included all participants who complied sufficiently with the protocol and display an evaluable PK profile (example, exposure to treatment, availability of measurements and absence of major protocol violations).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment Dose: TAK-954 0.5 mg | CL: Total Clearance After Intravenous Administration for TAK-954 | 5.604 liter per hour (L/hr) | Geometric Coefficient of Variation 22.8 |
| Treatment Dose: TAK-954 1 mg | CL: Total Clearance After Intravenous Administration for TAK-954 | 6.110 liter per hour (L/hr) | Geometric Coefficient of Variation 12.8 |
| Treatment Dose: TAK-954 2 mg | CL: Total Clearance After Intravenous Administration for TAK-954 | 6.679 liter per hour (L/hr) | Geometric Coefficient of Variation 29.6 |
Primary
Fe: Fraction of TAK-954 Excreted in Urine on Day 2 up to 12 Hours Post-dose
Time frame: Day 2 pre-dose and at multiple time points (up to 12 hours) post-dose
Population: The PK set included all participants who complied sufficiently with the protocol and display an evaluable PK profile (example, exposure to treatment, availability of measurements and absence of major protocol violations). PK-evaluable population where data at specified time points was available.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment Dose: TAK-954 0.5 mg | Fe: Fraction of TAK-954 Excreted in Urine on Day 2 up to 12 Hours Post-dose | 20.86 percentage | Geometric Coefficient of Variation 6.3 |
| Treatment Dose: TAK-954 1 mg | Fe: Fraction of TAK-954 Excreted in Urine on Day 2 up to 12 Hours Post-dose | 22.60 percentage | Geometric Coefficient of Variation 16 |
| Treatment Dose: TAK-954 2 mg | Fe: Fraction of TAK-954 Excreted in Urine on Day 2 up to 12 Hours Post-dose | 20.45 percentage | Geometric Coefficient of Variation 15.3 |
Primary
Fe: Fraction of TAK-954 Excreted in Urine on Day 2 up to 24 Hours Post-dose
Time frame: Day 2 pre-dose and at multiple time points (up to 24 hours) post-dose
Population: The PK set included all participants who complied sufficiently with the protocol and display an evaluable PK profile (example, exposure to treatment, availability of measurements and absence of major protocol violations).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment Dose: TAK-954 0.5 mg | Fe: Fraction of TAK-954 Excreted in Urine on Day 2 up to 24 Hours Post-dose | 10.64 percentage | Geometric Coefficient of Variation 27.3 |
| Treatment Dose: TAK-954 1 mg | Fe: Fraction of TAK-954 Excreted in Urine on Day 2 up to 24 Hours Post-dose | 11.53 percentage | Geometric Coefficient of Variation 19.9 |
| Treatment Dose: TAK-954 2 mg | Fe: Fraction of TAK-954 Excreted in Urine on Day 2 up to 24 Hours Post-dose | 9.534 percentage | Geometric Coefficient of Variation 23.7 |
Primary
Fe: Fraction of TAK-954 Excreted in Urine on Day 2 up to 36 Hours Post-dose
Time frame: Day 2 pre-dose and at multiple time points (up to 36 hours) post-dose
Population: The PK set included all participants who complied sufficiently with the protocol and display an evaluable PK profile (example, exposure to treatment, availability of measurements and absence of major protocol violations).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment Dose: TAK-954 0.5 mg | Fe: Fraction of TAK-954 Excreted in Urine on Day 2 up to 36 Hours Post-dose | 6.484 percentage | Geometric Coefficient of Variation 17.3 |
| Treatment Dose: TAK-954 1 mg | Fe: Fraction of TAK-954 Excreted in Urine on Day 2 up to 36 Hours Post-dose | 6.656 percentage | Geometric Coefficient of Variation 5.3 |
| Treatment Dose: TAK-954 2 mg | Fe: Fraction of TAK-954 Excreted in Urine on Day 2 up to 36 Hours Post-dose | 5.181 percentage | Geometric Coefficient of Variation 8.5 |
Primary
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) for TAK-954
Time frame: Dosing on Day 2 in Period 1 up to 14 days after last dose of study drug on Day 2 of Period 3 (up to Day 52)
Population: The safety set included all participants who received at least one dose of the study drug (active or placebo).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Dose: TAK-954 0.5 mg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) for TAK-954 | 4 Participants |
| Treatment Dose: TAK-954 1 mg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) for TAK-954 | 3 Participants |
| Treatment Dose: TAK-954 2 mg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) for TAK-954 | 0 Participants |
Primary
Number of Participants With Clinically Notable Shifts From Baseline to Abnormal Post-dose in Clinical Laboratory Values for TAK-954
Time frame: Dosing on Day 2 in Period 1 up to 14 days after last dose of study drug on Day 2 of Period 3 (up to Day 52)
Population: The safety set included all participants who received at least one dose of the study drug (active or placebo).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Dose: TAK-954 0.5 mg | Number of Participants With Clinically Notable Shifts From Baseline to Abnormal Post-dose in Clinical Laboratory Values for TAK-954 | 0 Participants |
| Treatment Dose: TAK-954 1 mg | Number of Participants With Clinically Notable Shifts From Baseline to Abnormal Post-dose in Clinical Laboratory Values for TAK-954 | 0 Participants |
| Treatment Dose: TAK-954 2 mg | Number of Participants With Clinically Notable Shifts From Baseline to Abnormal Post-dose in Clinical Laboratory Values for TAK-954 | 0 Participants |
Primary
Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiograms (ECG) for TAK-954
Time frame: Dosing on Day 2 in Period 1 up to 14 days after last dose of study drug on Day 2 of Period 3 (up to Day 52)
Population: The safety set included all participants who received at least one dose of the study drug (active or placebo).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Dose: TAK-954 0.5 mg | Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiograms (ECG) for TAK-954 | 0 Participants |
| Treatment Dose: TAK-954 1 mg | Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiograms (ECG) for TAK-954 | 0 Participants |
| Treatment Dose: TAK-954 2 mg | Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiograms (ECG) for TAK-954 | 0 Participants |
Primary
Number of Participants With Clinically Significant Change From Baseline in Vital Signs for TAK-954
Time frame: Dosing on Day 2 in Period 1 up to 14 days after last dose of study drug on Day 2 of Period 3 (up to Day 52)
Population: The safety set included all participants who received at least one dose of the study drug (active or placebo).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Dose: TAK-954 0.5 mg | Number of Participants With Clinically Significant Change From Baseline in Vital Signs for TAK-954 | 0 Participants |
| Treatment Dose: TAK-954 1 mg | Number of Participants With Clinically Significant Change From Baseline in Vital Signs for TAK-954 | 0 Participants |
| Treatment Dose: TAK-954 2 mg | Number of Participants With Clinically Significant Change From Baseline in Vital Signs for TAK-954 | 0 Participants |
Primary
Vz: Volume of Distribution During the Terminal Disposition Phase After Intravenous Administration for TAK-954
Time frame: Day 2 pre-dose and at multiple time points (up to 336 hours) post-dose
Population: The PK set included all participants who complied sufficiently with the protocol and display an evaluable PK profile (example, exposure to treatment, availability of measurements and absence of major protocol violations).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment Dose: TAK-954 0.5 mg | Vz: Volume of Distribution During the Terminal Disposition Phase After Intravenous Administration for TAK-954 | 197.9 liter | Geometric Coefficient of Variation 13.7 |
| Treatment Dose: TAK-954 1 mg | Vz: Volume of Distribution During the Terminal Disposition Phase After Intravenous Administration for TAK-954 | 387.7 liter | Geometric Coefficient of Variation 45.6 |
| Treatment Dose: TAK-954 2 mg | Vz: Volume of Distribution During the Terminal Disposition Phase After Intravenous Administration for TAK-954 | 901.7 liter | Geometric Coefficient of Variation 61.7 |
Secondary
Instances of Stool Type of TAK-954 Based on Bristol Stool Form Scale
Number of occurrences for each stool type was reported based on their type assessed from Bristol Stool form scale. The Bristol Stool Form Scale was used to assess the stool shape using a 7-point scale. Where, Type 1 = separate hard lumps, like nuts (hard to pass), Type 2 = sausage-shaped but lumpy, Type 3 = like a sausage but with cracks on the surface, Type 4 = like a sausage or snake, smooth and soft, Type 5 = soft blobs with clear-cut edges (passed easily), Type 6 = fluffy pieces with ragged edges, a mushy stool, Type 7 = watery, no solid pieces; entirely liquid. A score of 1 or 2 indicates constipation and a score of 6 or 7 indicates diarrhea.
Time frame: Day 2 dosing and at multiple time points (up to 36 hours) post-dose
Population: The PD set included all participants who received at least one dose of the study drug (active or placebo) and had completed at least 1 PD sampling period and/or had at least 1 evaluable parameter.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment Dose: TAK-954 0.5 mg | Instances of Stool Type of TAK-954 Based on Bristol Stool Form Scale | Type 2 | 2 number of occurrences |
| Treatment Dose: TAK-954 0.5 mg | Instances of Stool Type of TAK-954 Based on Bristol Stool Form Scale | Type 5 | 3 number of occurrences |
| Treatment Dose: TAK-954 0.5 mg | Instances of Stool Type of TAK-954 Based on Bristol Stool Form Scale | Type 4 | 1 number of occurrences |
| Treatment Dose: TAK-954 0.5 mg | Instances of Stool Type of TAK-954 Based on Bristol Stool Form Scale | Type 1 | 0 number of occurrences |
| Treatment Dose: TAK-954 0.5 mg | Instances of Stool Type of TAK-954 Based on Bristol Stool Form Scale | Type 7 | 2 number of occurrences |
| Treatment Dose: TAK-954 0.5 mg | Instances of Stool Type of TAK-954 Based on Bristol Stool Form Scale | Type 6 | 5 number of occurrences |
| Treatment Dose: TAK-954 0.5 mg | Instances of Stool Type of TAK-954 Based on Bristol Stool Form Scale | Type 3 | 0 number of occurrences |
| Treatment Dose: TAK-954 1 mg | Instances of Stool Type of TAK-954 Based on Bristol Stool Form Scale | Type 4 | 2 number of occurrences |
| Treatment Dose: TAK-954 1 mg | Instances of Stool Type of TAK-954 Based on Bristol Stool Form Scale | Type 1 | 0 number of occurrences |
| Treatment Dose: TAK-954 1 mg | Instances of Stool Type of TAK-954 Based on Bristol Stool Form Scale | Type 2 | 3 number of occurrences |
| Treatment Dose: TAK-954 1 mg | Instances of Stool Type of TAK-954 Based on Bristol Stool Form Scale | Type 3 | 1 number of occurrences |
| Treatment Dose: TAK-954 1 mg | Instances of Stool Type of TAK-954 Based on Bristol Stool Form Scale | Type 5 | 1 number of occurrences |
| Treatment Dose: TAK-954 1 mg | Instances of Stool Type of TAK-954 Based on Bristol Stool Form Scale | Type 6 | 1 number of occurrences |
| Treatment Dose: TAK-954 1 mg | Instances of Stool Type of TAK-954 Based on Bristol Stool Form Scale | Type 7 | 0 number of occurrences |
| Treatment Dose: TAK-954 2 mg | Instances of Stool Type of TAK-954 Based on Bristol Stool Form Scale | Type 5 | 0 number of occurrences |
| Treatment Dose: TAK-954 2 mg | Instances of Stool Type of TAK-954 Based on Bristol Stool Form Scale | Type 2 | 2 number of occurrences |
| Treatment Dose: TAK-954 2 mg | Instances of Stool Type of TAK-954 Based on Bristol Stool Form Scale | Type 7 | 0 number of occurrences |
| Treatment Dose: TAK-954 2 mg | Instances of Stool Type of TAK-954 Based on Bristol Stool Form Scale | Type 6 | 0 number of occurrences |
| Treatment Dose: TAK-954 2 mg | Instances of Stool Type of TAK-954 Based on Bristol Stool Form Scale | Type 4 | 1 number of occurrences |
| Treatment Dose: TAK-954 2 mg | Instances of Stool Type of TAK-954 Based on Bristol Stool Form Scale | Type 3 | 0 number of occurrences |
| Treatment Dose: TAK-954 2 mg | Instances of Stool Type of TAK-954 Based on Bristol Stool Form Scale | Type 1 | 0 number of occurrences |
Secondary
Mean Number of Stools of TAK-954 Within 36 Hours Post-dose on Day 2
Time frame: Day 2 dosing and at multiple time points (up to 36 hours) post-dose
Population: The PD set included all participants who received at least one dose of the study drug (active or placebo) and had completed at least 1 PD sampling period and/or had at least 1 evaluable parameter.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Dose: TAK-954 0.5 mg | Mean Number of Stools of TAK-954 Within 36 Hours Post-dose on Day 2 | 3.3 stools | Standard Deviation 3.4 |
| Treatment Dose: TAK-954 1 mg | Mean Number of Stools of TAK-954 Within 36 Hours Post-dose on Day 2 | 2.0 stools | Standard Deviation 0.82 |
| Treatment Dose: TAK-954 2 mg | Mean Number of Stools of TAK-954 Within 36 Hours Post-dose on Day 2 | 1.0 stools | Standard Deviation 0 |
Secondary
Number of Participants With First Stool of TAK-954 Within 36 Hours Post-dose on Day 2
Time frame: Day 2 dosing and at multiple time points (up to 36 hours) post-dose
Population: The pharmacodynamic (PD) set included all participants who received at least one dose of the study drug (active or placebo) and had completed at least 1 PD sampling period and/or had at least 1 evaluable parameter.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Dose: TAK-954 0.5 mg | Number of Participants With First Stool of TAK-954 Within 36 Hours Post-dose on Day 2 | 3 Participants |
| Treatment Dose: TAK-954 1 mg | Number of Participants With First Stool of TAK-954 Within 36 Hours Post-dose on Day 2 | 4 Participants |
| Treatment Dose: TAK-954 2 mg | Number of Participants With First Stool of TAK-954 Within 36 Hours Post-dose on Day 2 | 3 Participants |