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

Healthy Volunteers Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03870555
• Other study ID #: TAK-954-1009
• Secondary ID: U1111-1224-9803
• Status: Completed
• Phase: Phase 1
• Start date: March 8, 2019
• Est. completion date: May 16, 2019

Study information

• Verified date: June 2020
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6
• Est. completion date: May 16, 2019
• Est. primary completion date: May 16, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• TAK-954
TAK-954 infusion administered intravenously.
• TAK-954 Placebo
TAK-954 placebo-matching infusion intravenous.

Locations

Country	Name	City	State
United States	Celerion	Tempe	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Millennium Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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
Primary	AUC8: 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
Primary	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
Primary	CL: Total Clearance After Intravenous Administration for TAK-954		Day 2 pre-dose and at multiple time points (up to 336 hours) post-dose
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	CLR: Renal Clearance for TAK-954		Day 2 pre-dose and at multiple time points (up to 36 hours) post-dose
Secondary	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
Secondary	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
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.	Day 2 dosing and at multiple time points (up to 36 hours) post-dose