A Study to Investigate the Safety, Tolerability, Pharmacokinetics (PK) and Pharmacodynamics (PD) of TAK-954 in Healthy Adult Participants

Sponsor
Millennium Pharmaceuticals, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT03870555
Collaborator
(none)
6
1
3
2.3
2.6

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

Study Type:
Interventional
Actual Enrollment :
6 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Other
Official Title:
A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose, 3-Period, Incomplete Block Design Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of TAK-954 in Healthy Adult Participants
Actual Study Start Date :
Mar 8, 2019
Actual Primary Completion Date :
May 16, 2019
Actual Study Completion Date :
May 16, 2019

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

  1. 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)]

  2. 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)]

  3. 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)]

  4. 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)]

  5. 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]

  6. 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]

  7. 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]

  8. CL: Total Clearance After Intravenous Administration for TAK-954 [Day 2 pre-dose and at multiple time points (up to 336 hours) post-dose]

  9. 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]

  10. 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]

  11. 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]

  12. 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]

  13. 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]

  14. 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]

  15. 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]

  16. CLR: Renal Clearance for TAK-954 [Day 2 pre-dose and at multiple time points (up to 36 hours) post-dose]

Secondary Outcome Measures

  1. 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]

  2. 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]

  3. 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

Ages Eligible for Study:
18 Years to 55 Years
Sexes Eligible for Study:
All
Accepts 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.

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.
Responsible Party:
Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT03870555
Other Study ID Numbers:
  • TAK-954-1009
  • U1111-1224-9803
First Posted:
Mar 12, 2019
Last Update Posted:
Jun 24, 2020
Last Verified:
Jun 1, 2020
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Millennium Pharmaceuticals, Inc.

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

1. Primary Outcome
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%
2. Primary Outcome
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%
3. Primary Outcome
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%
4. Primary Outcome
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%
5. Primary Outcome
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)
6. Primary Outcome
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)
7. Primary Outcome
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)
8. Primary Outcome
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)
9. Primary Outcome
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)
10. Primary Outcome
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)
11. Primary Outcome
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)
12. Primary Outcome
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)
13. Primary Outcome
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)
14. Primary Outcome
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)
15. Primary Outcome
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)
16. Primary Outcome
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)
17. Secondary Outcome
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%
18. Secondary Outcome
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)
19. Secondary Outcome
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

[Not Specified]

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
Email trialdisclosures@takeda.com
Responsible Party:
Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT03870555
Other Study ID Numbers:
  • TAK-954-1009
  • U1111-1224-9803
First Posted:
Mar 12, 2019
Last Update Posted:
Jun 24, 2020
Last Verified:
Jun 1, 2020