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

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

The purpose of this study is to evaluate the safety, tolerability, and PK of single ascending intravenous doses of TAK-954.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: TAK-954; Drug: TAK-954 Placebo

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 Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tempe, Arizona, United States, 85283
      • Celerion

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Measure Description	Time Frame
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	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.	Day 2 dosing and at multiple time points (up to 36 hours) post-dose

Collaborators and Investigators

• Sponsor: Millennium Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): March 8, 2019
• Primary Completion (Actual): May 16, 2019
• Study Completion (Actual): May 16, 2019

Study Registration Dates

• First Submitted: March 4, 2019
• First Submitted That Met QC Criteria: March 8, 2019
• First Posted (Actual): March 12, 2019

Study Record Updates

• Last Update Posted (Actual): June 24, 2020
• Last Update Submitted That Met QC Criteria: June 11, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: Drug Therapy
• Other Study ID Numbers: TAK-954-1009; U1111-1224-9803 (Registry Identifier: WHO)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Takeda makes patient-level, de-identified data sets and associated documents available for all interventional studies after applicable marketing approvals and commercial availability have been received (or program is completely terminated), an opportunity for the primary publication of the research and final report development has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No