Clinical trial NCT03870555: A Study to Investigate the Safety, Tolerability, Pharmacokinetics (PK) and Pharmacodynamics (PD) of TAK-954 in Healthy Adult Participants
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2019-03-12
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

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

Detailed description: The drug being tested in this study is called TAK-954. This study will assess the safety, tolerability, PK and PD of single ascending TAK-954 higher intravenous doses than those previously studied.

The study will enroll approximately 6 participants. Participants will be randomly assigned (By chance, like flipping a coin) to one of the three treatment sequences-which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need).

In each treatment sequence, each participant will receive 2 doses of active drug out of 3 dose levels (TAK-954 0.5 mg, TAK-954 1 mg, or TAK-954 2 mg) and 1 dose of Placebo. Dose escalation will be based on the available safety/tolerability data from the previous period.

This single center trial will be conducted in the United States. The overall time to participate in this study is approximately 73 days. Participants will make a final visit on Day 16 after receiving their last dose of study drug for a follow-up assessment.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) for TAK-954
timeFrame: 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)
measure: Number of Participants With Clinically Significant Change From Baseline in Vital Signs for TAK-954
timeFrame: 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)
measure: Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiograms (ECG) for TAK-954
timeFrame: 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)
measure: Number of Participants With Clinically Notable Shifts From Baseline to Abnormal Post-dose in Clinical Laboratory Values for TAK-954
timeFrame: 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)
measure: AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-954
timeFrame: Day 2 pre-dose and at multiple time points (up to 336 hours) post-dose
measure: AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-954
timeFrame: Day 2 pre-dose and at multiple time points (up to 336 hours) post-dose
measure: Ceoi: Plasma Concentration Observed at the End of Infusion for TAK-954
timeFrame: Day 2 pre-dose and at multiple time points (up to 336 hours) post-dose
measure: CL: Total Clearance After Intravenous Administration for TAK-954
timeFrame: Day 2 pre-dose and at multiple time points (up to 336 hours) post-dose
measure: Vz: Volume of Distribution During the Terminal Disposition Phase After Intravenous Administration for TAK-954
timeFrame: Day 2 pre-dose and at multiple time points (up to 336 hours) post-dose
measure: Ae: Amount of Unchanged Drug Excreted in the Urine for TAK-954 on Day 2 up to 12 Hours Post-dose
timeFrame: Day 2 pre-dose and at multiple time points (up to 12 hours) post-dose
measure: Ae: Amount of Unchanged Drug Excreted in the Urine for TAK-954 on Day 2 up to 24 Hours Post-dose
timeFrame: Day 2 pre-dose and at multiple time points (up to 24 hours) post-dose
measure: Ae: Amount of Unchanged Drug Excreted in the Urine for TAK-954 on Day 2 up to 36 Hours Post-dose
timeFrame: Day 2 pre-dose and at multiple time points (up to 36 hours) post-dose
measure: Fe: Fraction of TAK-954 Excreted in Urine on Day 2 up to 12 Hours Post-dose
timeFrame: Day 2 pre-dose and at multiple time points (up to 12 hours) post-dose
measure: Fe: Fraction of TAK-954 Excreted in Urine on Day 2 up to 24 Hours Post-dose
timeFrame: Day 2 pre-dose and at multiple time points (up to 24 hours) post-dose
measure: Fe: Fraction of TAK-954 Excreted in Urine on Day 2 up to 36 Hours Post-dose
timeFrame: Day 2 pre-dose and at multiple time points (up to 36 hours) post-dose
measure: CLR: Renal Clearance for TAK-954
timeFrame: Day 2 pre-dose and at multiple time points (up to 36 hours) post-dose
Secondary outcomes:
measure: Number of Participants With First Stool of TAK-954 Within 36 Hours Post-dose on Day 2
timeFrame: Day 2 dosing and at multiple time points (up to 36 hours) post-dose
measure: Mean Number of Stools of TAK-954 Within 36 Hours Post-dose on Day 2
timeFrame: Day 2 dosing and at multiple time points (up to 36 hours) post-dose
measure: Instances of Stool Type of TAK-954 Based on Bristol Stool Form Scale
timeFrame: Day 2 dosing and at multiple time points (up to 36 hours) post-dose
Other outcomes:
Locations:
city: Tempe
country: United States
facility: Celerion
state: Arizona
Study officials:
affiliation: Millennium Pharmaceuticals, Inc.
name: Medical Director
role: STUDY_DIRECTOR
References: