Clinical trial NCT05567393: A Study of TAK-951 in Healthy Adults
Official title: A Randomized, Double-blind, Placebo-Controlled, Three-part Phase 1 Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of TAK-951 in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2022-10-05
Enrollment: 128
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a study of TAK-951 for people with symptoms of nausea and vomiting. The main aims of this study in healthy adults 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.
* To check how much TAK-951 stays in the blood over time to work out the best dose.

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 evaluated the safety, tolerability and pharmacokinetics (PK) of TAK-951 in healthy participants.

The study enrolled 128 healthy participants and consisted of 2 parts: Single-rising Dose (SRD) part (13 cohorts) of sequential panel design, and Multiple-rising Dose (MRD) part (5 cohorts) of sequential panel design. Participants in each cohort were randomized to receive treatment with TAK-951 or matching placebo using SC injection, once daily on Day 1 (for SRD part) and twice daily (BID) on Days 1 through 5 (for MRD part) following a minimum fast of 8 hours.

This single center trial was conducted in the United States. The overall time to participate in this study was approximately 155 days.

Eligibility criteria: Inclusion Criteria:

1. Have a body mass index (BMI) ≥18 and ≤30.0 (kg/m\^2) at the Screening Visit.

Exclusion Criteria:

1. The participant has a positive test result for hepatitis B surface antigen, hepatitis C virus antibody, or human immunodeficiency antibody/antigen, at the Screening Visit. Note: Participants with positive hepatitis B virus or hepatitis C virus serology may be enrolled if quantitative polymerase chain reaction for hepatitis B virus or hepatitis C virus ribonucleic acid is negative.
2. The participant had major surgery or donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks before the Screening Visit.
3. Heavy consumption of alcohol within 3 months before screening (\>7 drinks/week for women, \>14 drinks/week for men, where 1 drink = 5 ounces \[150 mL\] of wine or 12 ounces \[360 mL\] of beer or 1.5 ounces \[45 mL\] of hard liquor) or use of soft drugs (such as marijuana) within 3 months before screening, or hard drugs (such as cocaine and phencyclidine) within 1 year before Screening.
4. The participant has used nicotine-containing products (including, but not limited to, cigarettes, pipes, cigars, chewing tobacco, nicotine patch, or nicotine gum) within 28 days before check-in (Day -1) or cotinine test is positive at Screening or Day -1.
5. The participant has had 3 incidences of vasovagal syncope within the last 5 years.
6. The participant has Brugada syndrome (right bundle branch block \[RBBB\] pattern with ST-elevation in leads V1-V3).
7. The participant has an average semirecumbent systolic blood pressure \<90 millimeters of mercury (mm Hg) or diastolic blood pressure \<60 mm Hg at Screening or admission.
8. The participant has an average heart rate (HR) \<60 or \>100 beats per minute (bpm) \[at Screening, at Day -1, or at predose\]; athletic participants with an average HR \<60 bpm can be enrolled only with medical monitor approval.
9. The participant has orthostatic hypotension defined as a decrease in systolic blood pressure ≥20 mm Hg or a decrease in diastolic blood pressure ≥10 mm Hg after 2 minutes of standing when compared with blood pressure from the sitting position at Screening, and at Day -1. Participants with postural orthostatic tachycardia, defined as HR \>120 bpm standing, will also be excluded.

Primary outcomes:
measure: Parts 1 and 3: Percentage of Participants With Clinically Significant Physical Examination Findings
timeFrame: From the first dose of study drug up to follow-up or early termination (Up to approximately 32 days)
measure: Parts 1 and 3: Percentage of Participants With Markedly Abnormal Values of Vital Signs Parameters
timeFrame: From the first dose of study drug up to follow-up or early termination (Up to approximately 32 days)
measure: Parts 1 and 3: Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters
timeFrame: From the first dose of study drug up to follow-up or early termination (Up to approximately 32 days)
measure: Parts 1 and 3: Percentage of Participants With Markedly Abnormal Values of Laboratory Parameters
timeFrame: From the first dose of study drug up to follow-up or early termination (Up to approximately 32 days)
measure: Parts 1 and 3: Percentage of Participants With Treatment-Emergent Adverse Events
timeFrame: From the first dose of study drug up to follow-up or early termination (Up to approximately 32 days)
measure: Parts 1 and 3: Percentage of Participants With Positive Immunogenicity (ADA) Status
timeFrame: From the first dose of study drug up to follow-up or early termination (Up to approximately 32 days)
Secondary outcomes:
measure: Part 1: Cmax: Maximum Observed Plasma Concentration for TAK-951
timeFrame: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose in Part 1
measure: Part 1: 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 48 hours) post-dose in Part 1
measure: Part 3: Cmax: Maximum Observed Plasma Concentration for TAK-951 on Day 1
timeFrame: Pre-dose and at multiple time points (up to 24 hours) post-dose on Day 1 in Part 3
measure: Part 3: AUCτ: Area Under the Plasma Concentration-time Curve During a Dosing Interval Tau (τ), From Time of First Daily Dose to 8 Hours for TAK-951 on Day 1
timeFrame: Pre-dose and at multiple time points (up to 24 hours) post-dose on Day 1 in Part 3
Other outcomes:
Locations:
city: Glendale
country: United States
facility: California Clinical Trials Medical Group
state: California
Study officials:
affiliation: Takeda
name: Medical Director
role: STUDY_DIRECTOR
References: