Clinical trial NCT04964258: A Study of TAK-105 in Healthy Adults
Official title: A Randomized, Double-Blind, Sponsor-Open, Placebo-Controlled, Phase 1 Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of TAK-105 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: 2021-07-16
Enrollment: 80
Sex: ALL
Minimum age (years): 18
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 in the future, TAK-105 will be used to help treat people with nausea and vomiting. The main aims of this study are as follows:

* To check for side effects from TAK-105 in healthy adults.
* To learn how much TAK-105 they can receive without getting side effects from it.

Participants will receive either TAK-105 as TAK-105-a or TAK-105-b (depending upon the part they are enrolled in) or a placebo as an injection under the skin (sub-cutaneous injection). A placebo looks like TAK-105-a or TAK-105-b but will not have any medicine in it. Three times as many participants will receive TAK-105-a or TAK-105-b than placebo.

The study will have 6 parts. Each part will have several small groups of participants, called cohorts. Participants will only be in 1 cohort in 1 part of the study.

Part 1: Participants will check into the study clinic to receive a single dose of TAK-105-a or placebo and will stay in the clinic for about 10 days. Then, participants return to the clinic for follow-up visits up to about 60 days after the dose.

Part 2: Participants will check into the study clinic to receive TAK-105-a or placebo once a week for 4 weeks, and will stay in the clinic for about 26 days. Then, participants return to the clinic for follow-up visits up to about 60 days after last dose.

Part 3: Participants will check into the study clinic to receive 2, 3 or 4 weekly doses of TAK-105-a or placebo. Their clinic stay will be for 10 to 24 days depending which cohort they are in. Then, participants return to the clinic for follow-up visits up to about 28 days after last dose.

Part 4: Participants will check into the study clinic to receive 2 doses (once a week for 2 weeks) of TAK-105-a or placebo and will stay in the study clinic for about 12 days. They will return to the clinic later (in about 1-3 weeks) for another (third) dose and will stay for 2 days after the third dose. Then, participants return to the clinic for follow-up visits up to about 3 months after first dose.

Part 5a: Participants will check into the study clinic to receive a single dose of TAK-105-a or placebo and will stay in the clinic for about 10 days. Then, participants return to the clinic for follow-up visits up to about 60 days after the dose.

Part 5b: Participants will check into the study clinic to receive TAK-105-a or placebo once a week for 4 weeks, and will stay in the clinic for about 26 days. Then, participants return to the clinic for follow-up visits up to about 60 days after last dose. Part 5b will be optional, depending on the pharmacokinetic (PK) and safety data observed in Part 2.

Part 6: Participants will check into the study clinic to receive a single dose of TAK-105-b or placebo and will stay in the clinic for about 10 days. Then, participants return to the clinic for follow-up visits up to about 60 days after the dose.

Detailed description: The drug being tested in this study is called TAK-105. The study will look at the safety, tolerability, and PK of TAK-105-a and TAK-105-b in healthy participants.

Participants in each cohort will be randomized to receive treatment with TAK-105-a or TAK-105-b or matching placebo which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need). The study consists of 6 parts and up to 34 cohorts as mentioned below:

* Part 1 (SRD) will enroll healthy participants in up to 12 cohorts.
* Part 2 (MRD) will enroll healthy participants in up to 5 ascending cohorts.
* Part 3 (Dose titration) will enroll healthy participants in up to 6 multiple-dose cohorts.
* Part 4 (Redosing) will enroll healthy participants in up to 4 redosing cohorts.
* Part 5a (SRD) will enroll healthy Japanese participants in up to 3 cohorts.
* Part 5b (MRD) (optional) will enroll healthy Japanese participants in up to 2 cohorts. The MRD cohorts in Part 5b will be optional, depending on the PK and safety data observed in Part 2 (MRD).
* Part 6 (SRD) will enroll healthy participants in up to 2 cohorts.

Each cohort in all the parts will have 8 randomized participants with 6 participants receiving a single dose of TAK-105-a in Parts 1 to 5 or TAK-105-b in Part 6, and 2 receiving TAK-105-a matching placebo (Parts 1 to 5) or TAK-105-b matching placebo (Part 6) in a 3:1 ratio. This multi-center trial will be conducted in the United States. The overall duration of the study is approximately 18 months.

Eligibility criteria: Inclusion Criteria:

For All Cohorts

1. Must have a body mass index (BMI) greater than or equal to (\>=) 18.0 and less than or equal to (\<=) 30.0 kilogram per square meter (kg/m\^2).
2. Continuous nonsmoker who has not used nicotine and tobacco-containing products for at least 3 months prior to screening and through discharge.
3. Be judged to be in good health (example, no evidence of psychiatric, hepatic, renal, pulmonary, or cardiovascular disease) by the investigator, based on clinical evaluations including laboratory safety tests, medical history, physical examination, electrocardiogram (ECG), and vital sign measurements performed at the screening visit and before administration of the initial dose of study drug or invasive procedure.

   For Japanese participants in Part 5 (Cohorts 28 to 32 only):
4. Has 2 Japanese parents and 4 Japanese grandparents, as confirmed by interview.

Exclusion Criteria:

1. Participated in another investigational study within 4 weeks (or based on local regulations) or within 5 half-lives of the investigational product before the screening visit. The 4-week or 5 half-lives window will be derived from the date of the last dose and/or adverse event (AE) related to the study procedure in the previous study to the screening visit of the current study.
2. Has a history of significant multiple and/or severe allergies (example, food, drug, latex allergy) or has had an anaphylactic reaction or significant intolerance to prescription or nonprescription drugs or food.
3. Has a known hypersensitivity or contraindication to any component of TAK 105.
4. Has positive pregnancy test or is lactating or breastfeeding.
5. Has known or suspected current coronavirus disease 2019 (COVID-19) infection or is at risk of COVID-19 infection as assessed by the investigator.
6. Unable to refrain from or anticipates using all medications including herbal medicines beginning approximately 7 days before administration of the first dose of study drug, throughout the study until the last follow-up visit.
7. With history or presence of:

   * 3 or more incidences of syncope (example, vasovagal) within the last 5 years prior to screening;
   * A family history of unexplained sudden death or channelopathy;
   * Brugada syndrome (RBBB \[right bundle branch block\] pattern with ST-elevation in leads V1 V3);
   * CV or cerebrovascular disease, such as cardiac valvulopathy, myocardial infarction, stroke, sick sinus syndrome, pulmonary congestion, symptomatic or significant cardiac arrhythmia, supraventricular or ventricular tachycardia, second-degree atrioventricular (AV) block type 2, third degree AV block, prolonged QT interval with Fridericia correction method (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 QTcF (over 450 milli second \[msec\] or less than 360 msec), bifascicular block or QRS greater than equal to (\>=)120 msec or PR interval \> 200 msec at screening or Day 1 pre-Hour 0;
   * Has a documented history of sinus bradycardia less than (\<) 45 beats per minute \[bpm\]) based upon vital signs assessments, sinoatrial block as evidenced on ECG or sinus pause \>=3 seconds on ECG or predose telemetry.
8. Has an average semi recumbent blood pressure (BP) less than 90 (systolic) and 60 (diastolic) millimeter of mercury (mmHg) or greater than 140/90 mmHg from screening to predose, inclusive.
9. From screening to Day -2, participants with an average semirecumbent heart rate (HR) \<55 or \>100 beats per minute (bpm) should be excluded. From Day -2 to predose, enrollment of participants with an average HR \<55 or \>100 bpm will be left to the judgment of the investigator, unless HR is \<50 bpm, which must be discussed with the medical monitor for approval.
10. Has orthostatic hypotension defined as a decrease in systolic BP (SBP) \>=20 mmHg or a decrease in diastolic BP (DPB) \>=10 mmHg at approximately 2 minutes of standing when compared with BP from the semirecumbent position at screening to predose assessments, inclusive.
11. Has postural orthostatic tachycardia, defined as an increase of \>30 bpm or HR \>120 bpm at approximately 2 minutes of standing, at screening to predose assessments, inclusive.

Primary outcomes:
measure: Number of Participants With At Least One Treatment-emergent Adverse Event (TEAEs)
timeFrame: Part 1: Baseline up to Day 60; Part 2: Baseline up to Day 82
Secondary outcomes:
measure: Number of Participants Based on Antidrug Antibody (ADA) Status
timeFrame: Part 1: Baseline up to Day 60; Part 2: Baseline up to Day 82
Other outcomes:
measure: Parts 1, and 2, Cmax: Maximum Observed Plasma Concentration for TAK-105
timeFrame: Part 1: Day 1 pre-dose and at multiple timepoints (up to Day 60) post-dose; Part 2: Day 1 pre-dose and at multiple timepoints (up to Day 6) post-dose; Part 2: Day 22 pre-dose and at multiple timepoints (up to Day 82) post-dose
measure: Part 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-105
timeFrame: Part 1: Day 1 pre-dose and at multiple timepoints (up to Day 60) post-dose
measure: Parts 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-105
timeFrame: Part 1: Day 1 pre-dose and at multiple timepoints (up to Day 60) post-dose
measure: Parts 1, and 2, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-105
timeFrame: Part 1: Day 1 pre-dose and at multiple timepoints (up to Day 60) post-dose; Part 2: Day 1 pre-dose and at multiple timepoints (up to Day 6) post-dose; Part 2: Day 22 pre-dose and at multiple timepoints (up to Day 82) post-dose
measure: Parts 1, and 2, T1/2z: Terminal Disposition Phase Half-life for TAK-105
timeFrame: Part 1: Day 1 pre-dose and at multiple timepoints (up to Day 60) post-dose; Part 2: Day 1 pre-dose and at multiple timepoints (up to Day 6) post-dose; Part 2: Day 22 pre-dose and at multiple timepoints (up to Day 82) post-dose
measure: Parts 1, and 2, CL/F: Apparent Clearance After Extravascular Administration for TAK-105
timeFrame: Part 1: Day 1 pre-dose and at multiple timepoints (up to Day 60) post-dose; Part 2: Day 22 pre-dose and at multiple timepoints (up to Day 82) post-dose
measure: Parts 1, and 2, Vz/F: Apparent Volume of Distribution During the Terminal Disposition Phase After Extravascular Administration for TAK-105
timeFrame: Part 1: Day 1 pre-dose and at multiple timepoints (up to Day 60) post-dose; Part 2: Day 22 pre-dose and at multiple timepoints (up to Day 82) post-dose
measure: Part 2, AUCτ: Area Under the Plasma Concentration-time Curve From Time 0 to Tau Over Dosing Interval for TAK-105
timeFrame: Part 2: Day 1 pre-dose and at multiple timepoints (up to Day 6) post-dose; Day 22 pre-dose and at multiple timepoints (up to Day 82) post-dose
measure: Part 2, Ctrough: Observed Plasma Concentration at the End of a Dosing Interval at Steady State for TAK-105
timeFrame: Part 2: Day 22 pre-dose and at multiple timepoints (up to Day 82) post-dose
measure: Parts 1, and 2, Aet: Amount of Drug Excreted in Urine From Time 0 to Time t for TAK-105
timeFrame: Parts 1 and 2: Day 1 pre-dose and at multiple time points (up to Day 8) post-dose; Part 2: Day 22 pre-dose and at multiple time points (up to 48 hours) post-dose
measure: Parts 1, and 2, Aet1-t2: Amount of Drug Excreted in Urine From Time 1 to Time 2 for TAK-105
timeFrame: Parts 1 and 2: Day 1 pre-dose and at multiple time points (up to Day 8) post-dose; Part 2: Day 22 pre-dose and at multiple time points (up to 48 hours) post-dose
measure: Parts 1, and 2, Aeτ: Amount of Drug Excreted in Urine During a Dosing Interval (τ) at Steady State for TAK-105
timeFrame: Parts 1 and 2: Day 1 pre-dose and at multiple time points (up to Day 8) post-dose; Part 2: Day 22 pre-dose and at multiple time points (up to 48 hours) post-dose
measure: Parts 1, and 2, fe,t: Fraction of Administered Dose of Drug Excreted From Urine From Time 0 to Time t for TAK-105
timeFrame: Parts 1 and 2: Day 1 pre-dose and at multiple time points (up to Day 8) post-dose; Part 2: Day 22 pre-dose and at multiple time points (up to 48 hours) post-dose
measure: Parts 1, and 2, CLR: Renal Clearance for TAK-105
timeFrame: Parts 1 and 2: Day 1 pre-dose and at multiple time points (up to Day 8) post-dose; Part 2: Day 22 pre-dose and at multiple time points (up to 48 hours) post-dose
Locations:
city: Tempe
country: United States
facility: Celerion
state: Arizona
city: Las Vegas
country: United States
facility: PPD Development, LP
state: Nevada
city: Austin
country: United States
facility: PPD Development, LP
state: Texas
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: