A Study of TAK-105 in Healthy Adults

A Randomized, Double-Blind, Sponsor-Open, Placebo-Controlled, Phase 1 Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of TAK-105 in Healthy Subjects

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: TAK-105-a; Drug: TAK-105-a Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tempe, Arizona, United States, 85283
      • Celerion
  • Nevada
    • Las Vegas, Nevada, United States, 89113
      • PPD Development, LP
  • Texas
    • Austin, Texas, United States, 78744
      • PPD Development, LP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

11

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Part 1: Placebo; TAK-105-a matching-placebo, injection, subcutaneously, once on Day 1.	Drug: TAK-105-a Placebo; TAK-105-a placebo-matching solution.
Experimental: Part 1: TAK-105 Dose 1; TAK-105-a Dose 1, injection, subcutaneously, once on Day 1.	Drug: TAK-105-a; TAK-105-a subcutaneous solution.
Experimental: Part 1: TAK-105 Dose 2; TAK-105-a Dose 2, injection, subcutaneously, once on Day 1.	Drug: TAK-105-a; TAK-105-a subcutaneous solution.
Experimental: Part 1: TAK-105 Dose 3; TAK-105-a Dose 3, injection, subcutaneously, once on Day 1.	Drug: TAK-105-a; TAK-105-a subcutaneous solution.
Experimental: Part 1: TAK-105 Dose 4; TAK-105-a Dose 4, injection, subcutaneously, once on Day 1.	Drug: TAK-105-a; TAK-105-a subcutaneous solution.
Experimental: Part 1: TAK-105 Dose 5; TAK-105-a Dose 5, injection, subcutaneously, once on Day 1.	Drug: TAK-105-a; TAK-105-a subcutaneous solution.
Experimental: Part 1: TAK-105 Dose 6; TAK-105-a Dose 6, injection, subcutaneously, once on Day 1.	Drug: TAK-105-a; TAK-105-a subcutaneous solution.
Experimental: Part 1: TAK-105 Dose 7; TAK-105-a Dose 7, injection, subcutaneously, once on Day 1.	Drug: TAK-105-a; TAK-105-a subcutaneous solution.
Placebo Comparator: Part 2: Placebo; TAK-105-a matching-placebo, injection, subcutaneously, once weekly for 4 weeks.	Drug: TAK-105-a Placebo; TAK-105-a placebo-matching solution.
Experimental: Part 2: TAK-105 Dose 1A; TAK-105-a Dose 1A, injection, subcutaneously, once weekly for up to 4 weeks.	Drug: TAK-105-a; TAK-105-a subcutaneous solution.
Experimental: Part 2: TAK-105 Dose 2A; TAK-105-a Dose 2A, injection, subcutaneously, once weekly for 1 week.	Drug: TAK-105-a; TAK-105-a subcutaneous solution.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With At Least One Treatment-emergent Adverse Event (TEAEs)	An adverse event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A TEAE was defined as an AE that started or worsened after the first dose of the study treatment and last dose of study treatment.	Part 1: Baseline up to Day 60; Part 2: Baseline up to Day 82

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Based on Antidrug Antibody (ADA) Status	ADA included ADA-negative or transiently and persistently ADA-positive, and low or high ADA titer assessment. ADA negative was defined as participants who did not have a confirmed positive ADA status in any postbaseline assessment. Transiently ADA positive was defined as participants who had confirmed positive ADA status in 1 or 2 postbaseline assessments. Persistently ADA positive was defined as participants who had confirmed positive ADA status in more than 2 postbaseline assessments. For ADA positive (transiently ADA positive or persistently ADA positive) only, high ADA titer was defined as participant who has at least 1 postbaseline ADA titer greater than (>) 16; low ADA titer was defined as participant whose postbaseline ADA titers were all less than or equal to (<=) 16. ADA titer was assessed in ADA-positive participants.	Part 1: Baseline up to Day 60; Part 2: Baseline up to Day 82

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Parts 1, and 2, Cmax: Maximum Observed Plasma Concentration for TAK-105	Due to confidentiality reasons and chances of exposing the doses for TAK-105, the data for this pharmacokinetic outcome measure was not reported.	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
Part 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-105	Due to confidentiality reasons and chances of exposing the doses for TAK-105, the data for this pharmacokinetic outcome measure was not reported.	Part 1: Day 1 pre-dose and at multiple timepoints (up to Day 60) post-dose
Parts 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-105	Due to confidentiality reasons and chances of exposing the doses for TAK-105, the data for this pharmacokinetic outcome measure was not reported.	Part 1: Day 1 pre-dose and at multiple timepoints (up to Day 60) post-dose
Parts 1, and 2, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-105	Due to confidentiality reasons and chances of exposing the doses for TAK-105, the data for this pharmacokinetic outcome measure was not reported.	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
Parts 1, and 2, T1/2z: Terminal Disposition Phase Half-life for TAK-105	Due to confidentiality reasons and chances of exposing the doses for TAK-105, the data for this pharmacokinetic outcome measure was not reported.	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
Parts 1, and 2, CL/F: Apparent Clearance After Extravascular Administration for TAK-105	Due to confidentiality reasons and chances of exposing the doses for TAK-105, the data for this pharmacokinetic outcome measure was not reported.	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
Parts 1, and 2, Vz/F: Apparent Volume of Distribution During the Terminal Disposition Phase After Extravascular Administration for TAK-105	Due to confidentiality reasons and chances of exposing the doses for TAK-105, the data for this pharmacokinetic outcome measure was not reported.	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
Part 2, AUCτ: Area Under the Plasma Concentration-time Curve From Time 0 to Tau Over Dosing Interval for TAK-105	Due to confidentiality reasons and chances of exposing the doses for TAK-105, the data for this pharmacokinetic outcome measure was not reported.	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
Part 2, Ctrough: Observed Plasma Concentration at the End of a Dosing Interval at Steady State for TAK-105	Due to confidentiality reasons and chances of exposing the doses for TAK-105, the data for this pharmacokinetic outcome measure was not reported.	Part 2: Day 22 pre-dose and at multiple timepoints (up to Day 82) post-dose
Parts 1, and 2, Aet: Amount of Drug Excreted in Urine From Time 0 to Time t for TAK-105	Due to confidentiality reasons and chances of exposing the doses for TAK-105, the data for this pharmacokinetic outcome measure was not reported.	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
Parts 1, and 2, Aet1-t2: Amount of Drug Excreted in Urine From Time 1 to Time 2 for TAK-105	Due to confidentiality reasons and chances of exposing the doses for TAK-105, the data for this pharmacokinetic outcome measure was not reported.	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
Parts 1, and 2, Aeτ: Amount of Drug Excreted in Urine During a Dosing Interval (τ) at Steady State for TAK-105	Due to confidentiality reasons and chances of exposing the doses for TAK-105, the data for this pharmacokinetic outcome measure was not reported.	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
Parts 1, and 2, fe,t: Fraction of Administered Dose of Drug Excreted From Urine From Time 0 to Time t for TAK-105	Due to confidentiality reasons and chances of exposing the doses for TAK-105, the data for this pharmacokinetic outcome measure was not reported.	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
Parts 1, and 2, CLR: Renal Clearance for TAK-105	Due to confidentiality reasons and chances of exposing the doses for TAK-105, the data for this pharmacokinetic outcome measure was not reported.	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

Collaborators and Investigators

• Sponsor: Takeda
• Investigators: Study Director: Study Director, Takeda

Publications and helpful links

Helpful Links

• To obtain more information on the study, click on this link.

Study record dates

Study Major Dates

• Study Start (Actual): July 26, 2021
• Primary Completion (Actual): June 20, 2023
• Study Completion (Actual): June 20, 2023

Study Registration Dates

• First Submitted: July 7, 2021
• First Submitted That Met QC Criteria: July 7, 2021
• First Posted (Actual): July 16, 2021

Study Record Updates

• Last Update Posted (Actual): August 2, 2024
• Last Update Submitted That Met QC Criteria: February 23, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Drug Therapy
• Other Study ID Numbers: TAK-105-1001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
• IPD Sharing Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No