Clinical trial NCT04486950: A Study of TAK-951 in Healthy Adults
Official title: A Randomized, Double-Blind, Placebo-Controlled, Phase 1 Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of TAK-951 in Healthy Subjects Following Intravenous Administration
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteer
Keywords: Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2020-07-27
Enrollment: 32
Sex: ALL
Minimum age (years): 19
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: OTHER

Brief summary: It is hoped that a medicine called TAK-951 will eventually be used to treat nausea and vomiting. Before then, the sponsor needs to understand how the body processes TAK-951 in healthy adults.

The main aims of this study are as follows:

* To check for side effects from TAK-951 when given at a slow and fast infusion rate.
* To learn how much TAK-951 participants can receive without getting side effects from it.

Participants will receive a single infusion of either TAK-951 or placebo. In this study, a placebo looks like TAK-951 but does not have any medicine in it. Participants will receive either a low dose or high dose of TAK-951. The infusion will take from 1-3 hours.

Participants will stay in the study clinic for about 4 days to receive the study medicine (TAK-951 or placebo) and check for side effects. They will have follow-up visits at the clinic about 2 weeks and 4 weeks after treatment.

Detailed description: The drug being tested in this study is called TAK-951. The study will evaluate the safety, tolerability and PK of TAK-951 in healthy participants.

The study will enroll approximately 40 healthy participants. Each cohort will have 8 participants to be randomized and a minimum of 3 cohorts will be evaluated. Participants will be randomly assigned (by chance, like flipping a coin) to receive TAK-951 or placebo in a 6:2 ratio in one of the following 3 cohorts, which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need):

* Cohort 1 (Low Dose): TAK-951 20 mcg Infusion Over 60 Minutes
* Cohort 2 (High Dose): TAK-951 1 mg Infusion Over 60 Minutes
* Cohort 3: TAK-951 1 mg Infusion over 120 Minutes

Sentinel dosing will be done in first 2 participants in each cohort. The dosing in rest of the cohort will done if there are no significant safety or tolerability concerns. Additional 2 cohorts, each cohort with 8 participants may be added in study to evaluate additional intravenous dosing regimen after clinical data analysis of first 3 cohorts. Dosing of the subsequent cohort will be based on the analysis of the previous cohort's data.

This single-center trial will be conducted in the United States. The overall time to participate in this study is up to 57 days. All participants will return to clinic after 14 and 28 days after the last visit to the clinic for a follow-up assessment.

Eligibility criteria: Inclusion Criteria:

1. Continuous non-smoker who has not used nicotine- and tobacco-containing products and/or cannabis products for at least 3 months prior to dosing and throughout the study.
2. Body mass index (BMI) greater than or equal to (\>=) 18.0 and less than or equal to (\<=) 32.0 kilogram per square meter (kg/m\^2) at screening.
3. Female must be of non-childbearing potential.

Exclusion Criteria:

1. Is mentally or legally incapacitated or has significant emotional problems at the time of the screening visit or expected during the conduct of the study.
2. Drink alcohol in excess of 21 glasses/units per week for males or 14 glasses/units per week for females, with one unit equal to (=) 150 milliliter (mL) of wine or 360 mL of beer or 45 mL of 45 percent (%) alcohol.
3. Have any tattoos, scars or skin issue at planned IV infusion site which could interfere with dosing.
4. History or presence of:

   * Three (3) or more incidences of vasovagal syncope within the last 5 years prior to screening.
   * Family history of unexplained sudden death or channelopathy.
   * Brugada syndrome (that is, right bundle branch block (RBBB) pattern with ST-elevation in leads V1-V3).
   * Cardiovascular or cerebrovascular disease, such as cardiac valvulopathy, myocardial infarction, stroke, sick sinus syndrome, pulmonary congestion, symptomatic or significant cardiac arrhythmia, second-degree AV block type 2, third-degree AV block, prolonged corrected QT interval by Fredericia (QTcF) interval, hypokalemia, hypomagnesemia, or conduction abnormalities;
   * Risk factors for Torsade de Pointes (example, heart failure, cardiomyopathy, or family history of Long QT Syndrome);
   * Any clinically significant ECG findings or medical history including: long or short QT interval with QTcF (over 450 msec or less than 360 msec), bifascicular block or QRS \>=120 msec or PR interval greater than (\>) 200 msec at screening or Day -1 pre-Hour 0.
   * Documented history of sinoatrial block or sinus pause \>=3 seconds.
5. Semi-recumbent blood pressure (average of duplicate) is less than 90/60 millimeter of mercury (mmHg) or greater than 140/90 mmHg at screening.
6. Has an average semi-recumbent heart rate \<60 or \>100 beats per minute (bpm) (at screening, at Day -1 pre-Hour 0, or at pre-dose Day 1); athletic participants with an average semi-recumbent heart rate \<60 bpm can be enrolled only with medical monitor approval. If participant has heart rate \<60 bpm Investigator should obtain medical approval from Sponsor.
7. Has orthostatic hypotension defined as a decrease in systolic blood pressure \>=20 mmHg or a decrease in diastolic blood pressure \>=10 mmHg after 2 minutes of standing when compared with blood pressure from the semi-recumbent position at screening and at Day -1 pre-Hour 0. The semi-recumbent blood pressure will be an average of duplicate measurements.
8. Has postural orthostatic tachycardia, defined as an increase of 30 bpm or heart rate \>120 bpm after standing for 2 minutes.
9. Positive urine drug or alcohol results at screening or check-in.
10. Positive urine cotinine at screening or check-in.
11. Positive results at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV).
12. Unable to refrain from or anticipates the use of any drug, including prescription and non-prescription medications, herbal remedies, or vitamin supplements beginning 14 days prior to dosing and throughout the study. Thyroid hormone replacement medication may be permitted if the participant has been on same stable dose for the last 3 months prior to study drug administration. After dosing, acetaminophen (up to 2 g per 24 hours) may be administered at the discretion of the Investigator or designee. Hormone replacement therapy will also be allowed.
13. Has been on a diet incompatible with the on-study diet, in the opinion of the Investigator or designee, within the 30 days prior to dosing and throughout the study.
14. Donation of blood or significant blood loss within 56 days prior to dosing.
15. Plasma donation within 7 days prior to dosing.
16. Has positive results for Coronavirus disease 2019 (COVID-19) testing at screening or check-in.

Primary outcomes:
measure: Number of Participants Who Reported One or More Treatment-emergent Adverse Events (TEAEs)
timeFrame: Baseline up to Day 29
measure: Number of Participants With Clinically Significant Change From Baseline in Vital Sign Values
timeFrame: Baseline up to Day 2
measure: Number of Participants With Clinically Significant Change From Baseline in 12- Lead Electrocardiogram (ECG) Values
timeFrame: Baseline up to Day 2
measure: Number of Participants With Clinically Significant Change From Baseline in Laboratory Values
timeFrame: Baseline up to Day 2
measure: Number of Participants With Clinically Significant Change From Baseline in Physical Examination Values
timeFrame: Baseline up to Day 29
Secondary outcomes:
measure: AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-951
timeFrame: Day 1 pre-dose and at multiple time points (up to 30 hours) post-dose
measure: Ceoi: Plasma Concentration at the End of Infusion for TAK-951
timeFrame: Day 1: at the end of infusion (at 30 hours post-infusion)
measure: AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-951
timeFrame: Day 1 pre-dose and at multiple time points (up to 30 hours) post-dose
measure: T1/2z: Terminal Disposition Phase Half-life for TAK-951
timeFrame: Day 1 pre-dose and at multiple time points (up to 30 hours) post-dose
measure: λz: Terminal Disposition Phase Rate Constant for TAK-951
timeFrame: Day 1 pre-dose and at multiple time points (up to 30 hours) post-dose
measure: Number of Participants With Positive Anti-drug Antibodies (ADA) in Serum
timeFrame: Baseline up to Day 29
Other outcomes:
Locations:
city: Lincoln
country: United States
facility: Celerion
state: Nebraska
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: