A Study to Investigate the Safety, Tolerability, Pharmacokinetics (PK) and Pharmacodynamics (PD) of TAK-954 in Healthy Adult Participants
Study Details
Study Description
Brief Summary
The purpose of this study is to evaluate the safety, tolerability, and PK of single ascending intravenous doses of TAK-954.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 1 |
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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Sequence 1 Period 1: TAK-954 placebo-matching infusion, administered intravenously over 60-minutes, once on Day 1 and Day 2. Period 2: TAK-954 0.1 milligram (mg), infusion, administered intravenously over 60-minutes, once on Day 1, TAK-954 1 mg infusion, administered intravenously over 60-minutes, once on Day 2. Period 3: TAK-954 0.1 mg, infusion, administered intravenously over 60-minutes, once on Day 1, TAK-954 2 mg infusion, administered intravenously over 60-minutes, once on Day 2. A washout period of at least 16 days will be maintained between each Treatment Period. |
Drug: TAK-954
TAK-954 infusion administered intravenously.
Drug: TAK-954 Placebo
TAK-954 placebo-matching infusion intravenous.
|
Experimental: Sequence 2 Period 1: TAK-954 0.1 mg, infusion, administered intravenously over 60-minutes, once on Day 1, TAK-954 0.5 mg infusion, administered intravenously over 60-minutes once on Day 2. Period 2: TAK-954 placebo-matching infusion, administered intravenously over 60-minutes, once on Day 1 and Day 2. Period 3: TAK-954 0.1 mg, infusion, administered intravenously over 60-minutes, once on Day 1, TAK-954 2 mg, infusion, administered intravenously over 60-minutes, once on Day 2. A washout period of at least 16 days will be maintained between each Treatment Period. |
Drug: TAK-954
TAK-954 infusion administered intravenously.
Drug: TAK-954 Placebo
TAK-954 placebo-matching infusion intravenous.
|
Experimental: Sequence 3 Period 1: TAK-954 0.1 mg, infusion, administered intravenously over 60-minutes, once on Day 1, TAK-954 0.5 mg, infusion, administered intravenously over 60-minutes once on Day 2. Period 2: TAK-954 0.1 mg, infusion, administered intravenously over 60-minutes, once on Day 1, TAK-954 1 mg, infusion, administered intravenously over 60-minutes, once on Day 2. Period 3: TAK-954 placebo-matching infusion, administered intravenously over 60-minutes, once on Day 1 and Day 2. A washout period of at least 16 days will be maintained between each Treatment Period. |
Drug: TAK-954
TAK-954 infusion administered intravenously.
Drug: TAK-954 Placebo
TAK-954 placebo-matching infusion intravenous.
|
Outcome Measures
Primary Outcome Measures
- 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]
- 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]
- CLR: Renal Clearance for TAK-954 [Day 2 pre-dose and at multiple time points (up to 36 hours) post-dose]
Secondary Outcome Measures
- 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]
- 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.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
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.
-
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.
-
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:
-
History or presence of alcoholism or drug abuse within the past 2 years prior to the first dosing.
-
Has infrequent bowel movements (less than approximately once per day) within 30 days prior to first dosing.
-
Recent history of abnormal bowel movements, such as diarrhea, loose stools, or constipation, within 2 weeks of first dosing.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Celerion | Tempe | Arizona | United States | 85283 |
Sponsors and Collaborators
- Millennium Pharmaceuticals, Inc.
Investigators
- Study Director: Medical Director, Millennium Pharmaceuticals, Inc.
Study Documents (Full-Text)
More Information
Publications
None provided.- TAK-954-1009
- U1111-1224-9803
Study Results
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 Detail | 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. |
Arm/Group Title | Sequence 1: Placebo + TAK-954 1 mg + TAK-954 2 mg | Sequence 2: TAK-954 0.5 mg + Placebo + TAK-954 2 mg | Sequence 3: TAK-954 0.5 mg + TAK-954 1 mg + Placebo |
---|---|---|---|
Arm/Group Description | 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. | 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. | 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. |
Period Title: Period 1 (2 Days) | |||
STARTED | 2 | 2 | 2 |
COMPLETED | 2 | 2 | 2 |
NOT COMPLETED | 0 | 0 | 0 |
Period Title: Period 1 (2 Days) | |||
STARTED | 2 | 2 | 2 |
COMPLETED | 2 | 2 | 2 |
NOT COMPLETED | 0 | 0 | 0 |
Period Title: Period 1 (2 Days) | |||
STARTED | 2 | 2 | 2 |
COMPLETED | 2 | 2 | 2 |
NOT COMPLETED | 0 | 0 | 0 |
Period Title: Period 1 (2 Days) | |||
STARTED | 2 | 2 | 2 |
COMPLETED | 2 | 2 | 2 |
NOT COMPLETED | 0 | 0 | 0 |
Period Title: Period 1 (2 Days) | |||
STARTED | 2 | 2 | 2 |
COMPLETED | 1 | 2 | 2 |
NOT COMPLETED | 1 | 0 | 0 |
Baseline Characteristics
Arm/Group Title | Sequence 1: Placebo + TAK-954 1 mg + TAK-954 2 mg | Sequence 2: TAK-954 0.5 mg + Placebo + TAK-954 2 mg | Sequence 3: TAK-954 0.5 mg + TAK-954 1 mg + Placebo | Total |
---|---|---|---|---|
Arm/Group Description | 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. | 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. | 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. | Total of all reporting groups |
Overall Participants | 2 | 2 | 2 | 6 |
Age (years) [Mean (Standard Deviation) ] | ||||
Mean (Standard Deviation) [years] |
28.0
(14.14)
|
33.0
(4.24)
|
46.5
(2.12)
|
35.8
(10.85)
|
Sex: Female, Male (Count of Participants) | ||||
Female |
1
50%
|
1
50%
|
2
100%
|
4
66.7%
|
Male |
1
50%
|
1
50%
|
0
0%
|
2
33.3%
|
Ethnicity (NIH/OMB) (Count of Participants) | ||||
Hispanic or Latino |
2
100%
|
2
100%
|
2
100%
|
6
100%
|
Not Hispanic or Latino |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Race (NIH/OMB) (Count of Participants) | ||||
American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Asian |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Black or African American |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
White |
2
100%
|
2
100%
|
2
100%
|
6
100%
|
More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Region of Enrollment (Count of Participants) | ||||
United States |
2
100%
|
2
100%
|
2
100%
|
6
100%
|
Weight (kilogram) [Mean (Standard Deviation) ] | ||||
Mean (Standard Deviation) [kilogram] |
84.80
(13.152)
|
67.60
(9.758)
|
80.55
(0.495)
|
77.65
(10.858)
|
Height (centimeter (cm)) [Mean (Standard Deviation) ] | ||||
Mean (Standard Deviation) [centimeter (cm)] |
168.5
(7.78)
|
167.0
(21.21)
|
165.5
(4.95)
|
167.0
(10.43)
|
Body Mass Index (BMI) (kilogram per square meter (kg/m^2)) [Mean (Standard Deviation) ] | ||||
Mean (Standard Deviation) [kilogram per square meter (kg/m^2)] |
29.655
(1.9021)
|
24.375
(2.5102)
|
29.455
(1.7607)
|
27.828
(3.1252)
|
Outcome Measures
Title | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) for TAK-954 |
---|---|
Description | |
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) |
Outcome Measure Data
Analysis Population Description |
---|
The safety set included all participants who received at least one dose of the study drug (active or placebo). |
Arm/Group Title | Treatment Dose: TAK-954 0.5 mg | Treatment Dose: TAK-954 1 mg | Treatment Dose: TAK-954 2 mg |
---|---|---|---|
Arm/Group Description | TAK-954 0.5 mg, infusion, intravenously, once on Day 2 of Period 1 in Sequence 2 or 3. | TAK-954 1 mg, infusion, intravenously, once on Day 2 of Period 2 in Sequence 1 or 3. | TAK-954 2 mg, infusion, intravenously, once on Day 2 of Period 3 in Sequence 1 or 2. |
Measure Participants | 4 | 4 | 3 |
Count of Participants [Participants] |
4
200%
|
3
150%
|
0
0%
|
Title | Number of Participants With Clinically Significant Change From Baseline in Vital Signs for TAK-954 |
---|---|
Description | |
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) |
Outcome Measure Data
Analysis Population Description |
---|
The safety set included all participants who received at least one dose of the study drug (active or placebo). |
Arm/Group Title | Treatment Dose: TAK-954 0.5 mg | Treatment Dose: TAK-954 1 mg | Treatment Dose: TAK-954 2 mg |
---|---|---|---|
Arm/Group Description | TAK-954 0.5 mg, infusion, intravenously, once on Day 2 of Period 1 in Sequence 2 or 3. | TAK-954 1 mg, infusion, intravenously, once on Day 2 of Period 2 in Sequence 1 or 3. | TAK-954 2 mg, infusion, intravenously, once on Day 2 of Period 3 in Sequence 1 or 2. |
Measure Participants | 4 | 4 | 3 |
Count of Participants [Participants] |
0
0%
|
0
0%
|
0
0%
|
Title | Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiograms (ECG) for TAK-954 |
---|---|
Description | |
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) |
Outcome Measure Data
Analysis Population Description |
---|
The safety set included all participants who received at least one dose of the study drug (active or placebo). |
Arm/Group Title | Treatment Dose: TAK-954 0.5 mg | Treatment Dose: TAK-954 1 mg | Treatment Dose: TAK-954 2 mg |
---|---|---|---|
Arm/Group Description | TAK-954 0.5 mg, infusion, intravenously, once on Day 2 of Period 1 in Sequence 2 or 3. | TAK-954 1 mg, infusion, intravenously, once on Day 2 of Period 2 in Sequence 1 or 3. | TAK-954 2 mg, infusion, intravenously, once on Day 2 of Period 3 in Sequence 1 or 2. |
Measure Participants | 4 | 4 | 3 |
Count of Participants [Participants] |
0
0%
|
0
0%
|
0
0%
|
Title | Number of Participants With Clinically Notable Shifts From Baseline to Abnormal Post-dose in Clinical Laboratory Values for TAK-954 |
---|---|
Description | |
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) |
Outcome Measure Data
Analysis Population Description |
---|
The safety set included all participants who received at least one dose of the study drug (active or placebo). |
Arm/Group Title | Treatment Dose: TAK-954 0.5 mg | Treatment Dose: TAK-954 1 mg | Treatment Dose: TAK-954 2 mg |
---|---|---|---|
Arm/Group Description | TAK-954 0.5 mg, infusion, intravenously, once on Day 2 of Period 1 in Sequence 2 or 3. | TAK-954 1 mg, infusion, intravenously, once on Day 2 of Period 2 in Sequence 1 or 3. | TAK-954 2 mg, infusion, intravenously, once on Day 2 of Period 3 in Sequence 1 or 2. |
Measure Participants | 4 | 4 | 3 |
Count of Participants [Participants] |
0
0%
|
0
0%
|
0
0%
|
Title | AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-954 |
---|---|
Description | |
Time Frame | Day 2 pre-dose and at multiple time points (up to 336 hours) post-dose |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Treatment Dose: TAK-954 0.5 mg | Treatment Dose: TAK-954 1 mg | Treatment Dose: TAK-954 2 mg |
---|---|---|---|
Arm/Group Description | TAK-954 0.5 mg, infusion, intravenously, once on Day 2 of Period 1 in Sequence 2 or 3. | TAK-954 1 mg, infusion, intravenously, once on Day 2 of Period 2 in Sequence 1 or 3. | TAK-954 2 mg, infusion, intravenously, once on Day 2 of Period 3 in Sequence 1 or 2. |
Measure Participants | 4 | 4 | 3 |
Geometric Mean (Geometric Coefficient of Variation) [picogram*hour per milliliter (pg*hr/mL)] |
88930
(23.0)
|
163200
(12.8)
|
298400
(29.6)
|
Title | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-954 |
---|---|
Description | |
Time Frame | Day 2 pre-dose and at multiple time points (up to 336 hours) post-dose |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Treatment Dose: TAK-954 0.5 mg | Treatment Dose: TAK-954 1 mg | Treatment Dose: TAK-954 2 mg |
---|---|---|---|
Arm/Group Description | TAK-954 0.5 mg, infusion, intravenously, once on Day 2 of Period 1 in Sequence 2 or 3. | TAK-954 1 mg, infusion, intravenously, once on Day 2 of Period 2 in Sequence 1 or 3. | TAK-954 2 mg, infusion, intravenously, once on Day 2 of Period 3 in Sequence 1 or 2. |
Measure Participants | 4 | 4 | 3 |
Geometric Mean (Geometric Coefficient of Variation) [pg*hr/mL] |
89220
(22.8)
|
163700
(12.8)
|
299500
(29.6)
|
Title | Ceoi: Plasma Concentration Observed at the End of Infusion for TAK-954 |
---|---|
Description | |
Time Frame | Day 2 pre-dose and at multiple time points (up to 336 hours) post-dose |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Treatment Dose: TAK-954 0.5 mg | Treatment Dose: TAK-954 1 mg | Treatment Dose: TAK-954 2 mg |
---|---|---|---|
Arm/Group Description | TAK-954 0.5 mg, infusion, intravenously, once on Day 2 of Period 1 in Sequence 2 or 3. | TAK-954 1 mg, infusion, intravenously, once on Day 2 of Period 2 in Sequence 1 or 3. | TAK-954 2 mg, infusion, intravenously, once on Day 2 of Period 3 in Sequence 1 or 2. |
Measure Participants | 4 | 4 | 3 |
Geometric Mean (Geometric Coefficient of Variation) [picogram per milliliter (pg/mL)] |
7502
(24.1)
|
15260
(12.9)
|
30270
(28.5)
|
Title | CL: Total Clearance After Intravenous Administration for TAK-954 |
---|---|
Description | |
Time Frame | Day 2 pre-dose and at multiple time points (up to 336 hours) post-dose |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Treatment Dose: TAK-954 0.5 mg | Treatment Dose: TAK-954 1 mg | Treatment Dose: TAK-954 2 mg |
---|---|---|---|
Arm/Group Description | TAK-954 0.5 mg, infusion, intravenously, once on Day 2 of Period 1 in Sequence 2 or 3. | TAK-954 1 mg, infusion, intravenously, once on Day 2 of Period 2 in Sequence 1 or 3. | TAK-954 2 mg, infusion, intravenously, once on Day 2 of Period 3 in Sequence 1 or 2. |
Measure Participants | 4 | 4 | 3 |
Geometric Mean (Geometric Coefficient of Variation) [liter per hour (L/hr)] |
5.604
(22.8)
|
6.110
(12.8)
|
6.679
(29.6)
|
Title | Vz: Volume of Distribution During the Terminal Disposition Phase After Intravenous Administration for TAK-954 |
---|---|
Description | |
Time Frame | Day 2 pre-dose and at multiple time points (up to 336 hours) post-dose |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Treatment Dose: TAK-954 0.5 mg | Treatment Dose: TAK-954 1 mg | Treatment Dose: TAK-954 2 mg |
---|---|---|---|
Arm/Group Description | TAK-954 0.5 mg, infusion, intravenously, once on Day 2 of Period 1 in Sequence 2 or 3. | TAK-954 1 mg, infusion, intravenously, once on Day 2 of Period 2 in Sequence 1 or 3. | TAK-954 2 mg, infusion, intravenously, once on Day 2 of Period 3 in Sequence 1 or 2. |
Measure Participants | 4 | 4 | 3 |
Geometric Mean (Geometric Coefficient of Variation) [liter] |
197.9
(13.7)
|
387.7
(45.6)
|
901.7
(61.7)
|
Title | Ae: Amount of Unchanged Drug Excreted in the Urine for TAK-954 on Day 2 up to 12 Hours Post-dose |
---|---|
Description | |
Time Frame | Day 2 pre-dose and at multiple time points (up to 12 hours) post-dose |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Treatment Dose: TAK-954 0.5 mg | Treatment Dose: TAK-954 1 mg | Treatment Dose: TAK-954 2 mg |
---|---|---|---|
Arm/Group Description | TAK-954 0.5 mg, infusion, intravenously, once on Day 2 of Period 1 in Sequence 2 or 3. | TAK-954 1 mg, infusion, intravenously, once on Day 2 of Period 2 in Sequence 1 or 3. | TAK-954 2 mg, infusion, intravenously, once on Day 2 of Period 3 in Sequence 1 or 2. |
Measure Participants | 4 | 4 | 3 |
Geometric Mean (Geometric Coefficient of Variation) [nanogram] |
104300
(6.3)
|
226000
(16.0)
|
408900
(15.3)
|
Title | Ae: Amount of Unchanged Drug Excreted in the Urine for TAK-954 on Day 2 up to 24 Hours Post-dose |
---|---|
Description | |
Time Frame | Day 2 pre-dose and at multiple time points (up to 24 hours) post-dose |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Treatment Dose: TAK-954 0.5 mg | Treatment Dose: TAK-954 1 mg | Treatment Dose: TAK-954 2 mg |
---|---|---|---|
Arm/Group Description | TAK-954 0.5 mg, infusion, intravenously, once on Day 2 of Period 1 in Sequence 2 or 3. | TAK-954 1 mg, infusion, intravenously, once on Day 2 of Period 2 in Sequence 1 or 3. | TAK-954 2 mg, infusion, intravenously, once on Day 2 of Period 3 in Sequence 1 or 2. |
Measure Participants | 4 | 4 | 3 |
Geometric Mean (Geometric Coefficient of Variation) [nanogram] |
53200
(27.3)
|
115300
(19.9)
|
190700
(23.7)
|
Title | Ae: Amount of Unchanged Drug Excreted in the Urine for TAK-954 on Day 2 up to 36 Hours Post-dose |
---|---|
Description | |
Time Frame | Day 2 pre-dose and at multiple time points (up to 36 hours) post-dose |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Treatment Dose: TAK-954 0.5 mg | Treatment Dose: TAK-954 1 mg | Treatment Dose: TAK-954 2 mg |
---|---|---|---|
Arm/Group Description | TAK-954 0.5 mg, infusion, intravenously, once on Day 2 of Period 1 in Sequence 2 or 3. | TAK-954 1 mg, infusion, intravenously, once on Day 2 of Period 2 in Sequence 1 or 3. | TAK-954 2 mg, infusion, intravenously, once on Day 2 of Period 3 in Sequence 1 or 2. |
Measure Participants | 4 | 4 | 3 |
Geometric Mean (Geometric Coefficient of Variation) [nanogram] |
32420
(17.3)
|
66560
(5.3)
|
103600
(8.5)
|
Title | Fe: Fraction of TAK-954 Excreted in Urine on Day 2 up to 12 Hours Post-dose |
---|---|
Description | |
Time Frame | Day 2 pre-dose and at multiple time points (up to 12 hours) post-dose |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Treatment Dose: TAK-954 0.5 mg | Treatment Dose: TAK-954 1 mg | Treatment Dose: TAK-954 2 mg |
---|---|---|---|
Arm/Group Description | TAK-954 0.5 mg, infusion, intravenously, once on Day 2 of Period 1 in Sequence 2 or 3. | TAK-954 1 mg, infusion, intravenously, once on Day 2 of Period 2 in Sequence 1 or 3. | TAK-954 2 mg, infusion, intravenously, once on Day 2 of Period 3 in Sequence 1 or 2. |
Measure Participants | 4 | 4 | 3 |
Geometric Mean (Geometric Coefficient of Variation) [percentage] |
20.86
(6.3)
|
22.60
(16.0)
|
20.45
(15.3)
|
Title | Fe: Fraction of TAK-954 Excreted in Urine on Day 2 up to 24 Hours Post-dose |
---|---|
Description | |
Time Frame | Day 2 pre-dose and at multiple time points (up to 24 hours) post-dose |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Treatment Dose: TAK-954 0.5 mg | Treatment Dose: TAK-954 1 mg | Treatment Dose: TAK-954 2 mg |
---|---|---|---|
Arm/Group Description | TAK-954 0.5 mg, infusion, intravenously, once on Day 2 of Period 1 in Sequence 2 or 3. | TAK-954 1 mg, infusion, intravenously, once on Day 2 of Period 2 in Sequence 1 or 3. | TAK-954 2 mg, infusion, intravenously, once on Day 2 of Period 3 in Sequence 1 or 2. |
Measure Participants | 4 | 4 | 3 |
Geometric Mean (Geometric Coefficient of Variation) [percentage] |
10.64
(27.3)
|
11.53
(19.9)
|
9.534
(23.7)
|
Title | Fe: Fraction of TAK-954 Excreted in Urine on Day 2 up to 36 Hours Post-dose |
---|---|
Description | |
Time Frame | Day 2 pre-dose and at multiple time points (up to 36 hours) post-dose |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Treatment Dose: TAK-954 0.5 mg | Treatment Dose: TAK-954 1 mg | Treatment Dose: TAK-954 2 mg |
---|---|---|---|
Arm/Group Description | TAK-954 0.5 mg, infusion, intravenously, once on Day 2 of Period 1 in Sequence 2 or 3. | TAK-954 1 mg, infusion, intravenously, once on Day 2 of Period 2 in Sequence 1 or 3. | TAK-954 2 mg, infusion, intravenously, once on Day 2 of Period 3 in Sequence 1 or 2. |
Measure Participants | 4 | 4 | 3 |
Geometric Mean (Geometric Coefficient of Variation) [percentage] |
6.484
(17.3)
|
6.656
(5.3)
|
5.181
(8.5)
|
Title | CLR: Renal Clearance for TAK-954 |
---|---|
Description | |
Time Frame | Day 2 pre-dose and at multiple time points (up to 36 hours) post-dose |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Treatment Dose: TAK-954 0.5 mg | Treatment Dose: TAK-954 1 mg | Treatment Dose: TAK-954 2 mg |
---|---|---|---|
Arm/Group Description | TAK-954 0.5 mg, infusion, intravenously, once on Day 2 of Period 1 in Sequence 2 or 3. | TAK-954 1 mg, infusion, intravenously, once on Day 2 of Period 2 in Sequence 1 or 3. | TAK-954 2 mg, infusion, intravenously, once on Day 2 of Period 3 in Sequence 1 or 2. |
Measure Participants | 3 | 4 | 3 |
Geometric Mean (Geometric Coefficient of Variation) [L/hr] |
3.457
(19.9)
|
3.933
(8.9)
|
3.624
(35.0)
|
Title | Number of Participants With First Stool of TAK-954 Within 36 Hours Post-dose on Day 2 |
---|---|
Description | |
Time Frame | Day 2 dosing and at multiple time points (up to 36 hours) post-dose |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Treatment Dose: TAK-954 0.5 mg | Treatment Dose: TAK-954 1 mg | Treatment Dose: TAK-954 2 mg |
---|---|---|---|
Arm/Group Description | TAK-954 0.5 mg, infusion, intravenously, once on Day 2 of Period 1 in Sequence 2 or 3. | TAK-954 1 mg, infusion, intravenously, once on Day 2 of Period 2 in Sequence 1 or 3. | TAK-954 2 mg, infusion, intravenously, once on Day 2 of Period 3 in Sequence 1 or 2. |
Measure Participants | 4 | 4 | 3 |
Count of Participants [Participants] |
3
150%
|
4
200%
|
3
150%
|
Title | Mean Number of Stools of TAK-954 Within 36 Hours Post-dose on Day 2 |
---|---|
Description | |
Time Frame | Day 2 dosing and at multiple time points (up to 36 hours) post-dose |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Treatment Dose: TAK-954 0.5 mg | Treatment Dose: TAK-954 1 mg | Treatment Dose: TAK-954 2 mg |
---|---|---|---|
Arm/Group Description | TAK-954 0.5 mg, infusion, intravenously, once on Day 2 of Period 1 in Sequence 2 or 3. | TAK-954 1 mg, infusion, intravenously, once on Day 2 of Period 2 in Sequence 1 or 3. | TAK-954 2 mg, infusion, intravenously, once on Day 2 of Period 3 in Sequence 1 or 2. |
Measure Participants | 4 | 4 | 3 |
Mean (Standard Deviation) [stools] |
3.3
(3.40)
|
2.0
(0.82)
|
1.0
(0.00)
|
Title | Instances of Stool Type of TAK-954 Based on Bristol Stool Form Scale |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Treatment Dose: TAK-954 0.5 mg | Treatment Dose: TAK-954 1 mg | Treatment Dose: TAK-954 2 mg |
---|---|---|---|
Arm/Group Description | TAK-954 0.5 mg, infusion, intravenously, once on Day 2 of Period 1 in Sequence 2 or 3. | TAK-954 1 mg, infusion, intravenously, once on Day 2 of Period 2 in Sequence 1 or 3. | TAK-954 2 mg, infusion, intravenously, once on Day 2 of Period 3 in Sequence 1 or 2. |
Measure Participants | 4 | 4 | 3 |
Type 1 |
0
|
0
|
0
|
Type 2 |
2
|
3
|
2
|
Type 3 |
0
|
1
|
0
|
Type 4 |
1
|
2
|
1
|
Type 5 |
3
|
1
|
0
|
Type 6 |
5
|
1
|
0
|
Type 7 |
2
|
0
|
0
|
Adverse Events
Time Frame | Lead-in Dose: Day 1 of Period 1, 2, and 3; Treatment Dose: 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) | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Adverse Event Reporting Description | At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. | |||||||||||
Arm/Group Title | Lead-in Dose: TAK-954 0.1 mg | Lead-in Dose: Placebo | Treatment Dose: TAK-954 0.5 mg | Treatment Dose: TAK-954 1 mg | Treatment Dose: TAK-954 2 mg | Treatment Dose: Placebo | ||||||
Arm/Group Description | TAK-954 0.1 mg, infusion, intravenously, once on Day 1 of Period 1, 2 or 3 in Sequence 1, 2, or 3. | TAK-954 placebo-matching, infusion, intravenously, once on Day 1 of Period 1, 2, or 3 in Sequence 1, 2, or 3. | TAK-954 0.5 mg, infusion, intravenously, once on Day 2 of Period 1 in Sequence 2 or 3. | TAK-954 1 mg, infusion, intravenously, once on Day 2 of Period 2 in Sequence 1 or 3. | TAK-954 2 mg, infusion, intravenously, once on Day 2 of Period 3 in Sequence 1 or 2. | TAK-954 placebo-matching, infusion, intravenously once on Day 2 of Period 1, 2 and 3. | ||||||
All Cause Mortality |
||||||||||||
Lead-in Dose: TAK-954 0.1 mg | Lead-in Dose: Placebo | Treatment Dose: TAK-954 0.5 mg | Treatment Dose: TAK-954 1 mg | Treatment Dose: TAK-954 2 mg | Treatment Dose: Placebo | |||||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/6 (0%) | 0/6 (0%) | 0/4 (0%) | 0/4 (0%) | 0/3 (0%) | 0/6 (0%) | ||||||
Serious Adverse Events |
||||||||||||
Lead-in Dose: TAK-954 0.1 mg | Lead-in Dose: Placebo | Treatment Dose: TAK-954 0.5 mg | Treatment Dose: TAK-954 1 mg | Treatment Dose: TAK-954 2 mg | Treatment Dose: Placebo | |||||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/6 (0%) | 0/6 (0%) | 0/4 (0%) | 0/4 (0%) | 0/3 (0%) | 0/6 (0%) | ||||||
Other (Not Including Serious) Adverse Events |
||||||||||||
Lead-in Dose: TAK-954 0.1 mg | Lead-in Dose: Placebo | Treatment Dose: TAK-954 0.5 mg | Treatment Dose: TAK-954 1 mg | Treatment Dose: TAK-954 2 mg | Treatment Dose: Placebo | |||||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 5/6 (83.3%) | 1/6 (16.7%) | 4/4 (100%) | 3/4 (75%) | 0/3 (0%) | 0/6 (0%) | ||||||
Gastrointestinal disorders | ||||||||||||
Abdominal pain | 0/6 (0%) | 1/6 (16.7%) | 0/4 (0%) | 0/4 (0%) | 0/3 (0%) | 0/6 (0%) | ||||||
Abdominal pain upper | 1/6 (16.7%) | 0/6 (0%) | 0/4 (0%) | 0/4 (0%) | 0/3 (0%) | 0/6 (0%) | ||||||
Anorectal discomfort | 1/6 (16.7%) | 0/6 (0%) | 0/4 (0%) | 0/4 (0%) | 0/3 (0%) | 0/6 (0%) | ||||||
Diarrhoea | 2/6 (33.3%) | 0/6 (0%) | 1/4 (25%) | 1/4 (25%) | 0/3 (0%) | 0/6 (0%) | ||||||
Flatulence | 1/6 (16.7%) | 0/6 (0%) | 0/4 (0%) | 0/4 (0%) | 0/3 (0%) | 0/6 (0%) | ||||||
Nausea | 4/6 (66.7%) | 0/6 (0%) | 2/4 (50%) | 1/4 (25%) | 0/3 (0%) | 0/6 (0%) | ||||||
Vomiting | 1/6 (16.7%) | 0/6 (0%) | 1/4 (25%) | 0/4 (0%) | 0/3 (0%) | 0/6 (0%) | ||||||
General disorders | ||||||||||||
Catheter site pain | 1/6 (16.7%) | 0/6 (0%) | 0/4 (0%) | 0/4 (0%) | 0/3 (0%) | 0/6 (0%) | ||||||
Chills | 0/6 (0%) | 0/6 (0%) | 1/4 (25%) | 0/4 (0%) | 0/3 (0%) | 0/6 (0%) | ||||||
Fatigue | 1/6 (16.7%) | 0/6 (0%) | 0/4 (0%) | 0/4 (0%) | 0/3 (0%) | 0/6 (0%) | ||||||
Feeling hot | 1/6 (16.7%) | 0/6 (0%) | 0/4 (0%) | 0/4 (0%) | 0/3 (0%) | 0/6 (0%) | ||||||
Thirst | 1/6 (16.7%) | 0/6 (0%) | 0/4 (0%) | 0/4 (0%) | 0/3 (0%) | 0/6 (0%) | ||||||
Infections and infestations | ||||||||||||
Upper respiratory tract infection | 0/6 (0%) | 0/6 (0%) | 1/4 (25%) | 0/4 (0%) | 0/3 (0%) | 0/6 (0%) | ||||||
Metabolism and nutrition disorders | ||||||||||||
Increased appetite | 1/6 (16.7%) | 0/6 (0%) | 0/4 (0%) | 0/4 (0%) | 0/3 (0%) | 0/6 (0%) | ||||||
Nervous system disorders | ||||||||||||
Dizziness | 0/6 (0%) | 0/6 (0%) | 1/4 (25%) | 0/4 (0%) | 0/3 (0%) | 0/6 (0%) | ||||||
Dysgeusia | 2/6 (33.3%) | 0/6 (0%) | 1/4 (25%) | 0/4 (0%) | 0/3 (0%) | 0/6 (0%) | ||||||
Headache | 3/6 (50%) | 0/6 (0%) | 1/4 (25%) | 0/4 (0%) | 0/3 (0%) | 0/6 (0%) | ||||||
Respiratory, thoracic and mediastinal disorders | ||||||||||||
Cough | 0/6 (0%) | 0/6 (0%) | 0/4 (0%) | 1/4 (25%) | 0/3 (0%) | 0/6 (0%) | ||||||
Nasal congestion | 0/6 (0%) | 0/6 (0%) | 0/4 (0%) | 2/4 (50%) | 0/3 (0%) | 0/6 (0%) | ||||||
Skin and subcutaneous tissue disorders | ||||||||||||
Erythema | 1/6 (16.7%) | 0/6 (0%) | 0/4 (0%) | 0/4 (0%) | 0/3 (0%) | 0/6 (0%) |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Research Organization shall not publish any articles or papers nor make any presentations, nor assist any other person in publishing any articles or papers or in making any presentations relating or referring to the Study or any results, data or insights from or any data, information or materials obtained or generated in the performance of its obligations without the prior written consent of Takeda, which consent may be granted or withheld in Takeda's sole discretion.
Results Point of Contact
Name/Title | Medical Director |
---|---|
Organization | Takeda |
Phone | +1-877-825-3327 |
trialdisclosures@takeda.com |
- TAK-954-1009
- U1111-1224-9803