A Study of TAK-105 in Healthy Adults
Study Details
Study Description
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:
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To check for side effects from TAK-105 in healthy adults.
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To learn how much TAK-105 they can receive without getting side effects from it.
Participants will receive either TAK-105 or a placebo as an injection under the skin (sub-cutaneous injection). A placebo looks like TAK-105 but will not have any medicine in it. Three times as many participants will receive TAK-105 than placebo.
The study will have 4 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 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 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 or placebo. Their clinic stay will be from 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 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
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 in healthy participants.
Participants in each cohort will be randomized to receive treatment with TAK-105 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 4 parts and up to 27 cohorts as mentioned below:
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Part 1 (SRD) will enroll healthy participants in up to 12 cohorts.
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Part 2 (MRD) will enroll healthy participants in up to 5 ascending cohorts.
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Part 3 (Dose titration) will enroll healthy participants in up to 6 multiple-dose cohorts.
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Part 4 (Redosing) will enroll healthy participants in up to 4 redosing cohorts.
Each cohort in all the parts will have 8 randomized participants with 6 participants receiving a single dose of TAK-105, and 2 receiving TAK-105 matching placebo 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 Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Part 1: TAK-105 TAK-105 at starting dose of 30 microgram (mcg) or placebo-matching solution, subcutaneously, once on Day 1. Staggered dosing will be done in the first cohort of Part 1 (Cohort 1). Staggered dosing in subsequent Cohorts (Cohorts 2-12) may be used. After the pre-specified first dose, subsequent doses will be determined in the dose escalation meeting based on emerging safety, tolerability, and PK data from the study. |
Drug: TAK-105
TAK-105 subcutaneous solution.
Drug: TAK-105 Placebo
TAK-105 placebo-matching solution.
|
| Experimental: Part 2: TAK-105 TAK-105 dose to be decided (TBD) or TAK-105 matching-placebo, subcutaneously, once weekly for 4 weeks. Dose of multiple rising dose (MRD) Cohorts (Cohorts 13-17) of Part 2 will be determined based on emerging safety, immunogenicity, tolerability, and PK data from Part 1 (SRD) determined in the dose escalation meeting. |
Drug: TAK-105
TAK-105 subcutaneous solution.
Drug: TAK-105 Placebo
TAK-105 placebo-matching solution.
|
| Experimental: Part 3: TAK-105 TAK-105 dose TBD or placebo-matching solution, subcutaneously, once weekly for 2-4 weeks. Dose for the first 2 Cohorts (Cohorts 18-19) of Part 3 will be based on emerging safety, tolerability, and available PK data from Part 1 single rising dose (SRD) and Part 2 (MRD) as determined in the dose escalation meeting. The data from Cohorts 18-19 will further determine additional enrollment of Cohorts 20, 21, 22 and 23. Part 3 will evaluate whether dose titration result in different tolerability in relation with CV observations. |
Drug: TAK-105
TAK-105 subcutaneous solution.
Drug: TAK-105 Placebo
TAK-105 placebo-matching solution.
|
| Experimental: Part 4: TAK-105 TAK-105 dose TBD or placebo-matching solution, subcutaneously, once a week for 2 weeks, followed by a period of withholding drug and then redosing with a third dose. Part 4 (Cohorts 24 to 27) will provide an exploratory evaluation to assess the safety and CV tolerability profile of redosing with TAK 105. |
Drug: TAK-105
TAK-105 subcutaneous solution.
Drug: TAK-105 Placebo
TAK-105 placebo-matching solution.
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With At Least one Adverse Event [Baseline up to Month 18]
Secondary Outcome Measures
- Parts 1 and 2, Cmax: Maximum Observed Plasma Concentration for TAK-105 [Day 1 (Part 1): pre-dose and at multiple time points (up to Day 60) post-dose; Day 1 (Part 2): pre-dose and at multiple time-points (up to Day 6) post-dose; Day 22 (Part 2): pre-dose and multiple time points (up to Day 82) post-dose]
- Part 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-105 [Day 1: pre-dose and at multiple time points (up to Day 60) post-dose]
- Part 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-105 [Day 1: pre-dose and at multiple time points (up to Day 60) post-dose]
- Parts 1 and 2, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-105 [Day 1 (Part 1): pre-dose and at multiple time points (up to Day 60) post-dose; Day 1 (Part 2): pre-dose and at multiple time-points (up to Day 6) post-dose; Day 22 (Part 2): pre-dose and multiple time points (up to Day 82) post-dose]
- Parts 1 and 2, T1/2z: Terminal Disposition Phase Half-life for TAK-105 [Day 1 (Part 1): pre-dose and at multiple time points (up to 60 days) post-dose; Day 22 (Part 2): pre-dose and multiple time points (up to Day 82) post-dose]
- Parts 1 and 2, CL/F: Apparent Clearance After Extravascular Administration for TAK-105 [Day 1 (Part 1): pre-dose and at multiple time points (up to 60 days) post-dose; Day 22 (Part 2): pre-dose and multiple time points (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 [Day 1 (Part 1): pre-dose and at multiple time points (up to 60 days) post-dose; Day 22 (Part 2): pre-dose and multiple time points (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 [Day 1 (Part 2): pre-dose and at multiple time points (up to Day 6) post-dose; Day 22 (Part 2): pre-dose and multiple time points (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 [Day 22 (Part 2): pre-dose and multiple time points (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 [Day 1 (Part 1): pre-dose and at multiple time points (up to Day 8) post-dose; Day 1 (Part 2): pre-dose and at multiple time points (up to Day 7) post-dose; Day 22 (Part 2): 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 [Day 1 (Part 1): pre-dose and at multiple time points (up to Day 8) post-dose; Day 1 (Part 2): pre-dose and at multiple time points (up to Day 7) post-dose; Day 22 (Part 2): 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 [Day 1 (Part 1): pre-dose and at multiple time points (up to Day 8) post-dose; Day 1 (Part 2): pre-dose and at multiple time points (up to Day 7) post-dose; Day 22 (Part 2): 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 [Day 1 (Part 1): pre-dose and at multiple time points (up to Day 8) post-dose; Day 1 (Part 2): pre-dose and at multiple time points (up to Day 7) post-dose; Day 22 (Part 2): pre-dose and at multiple time points (up to 48 hours) post-dose]
- Parts 1 and 2, CLR: Renal clearance for TAK-105 [Day 1 (Part 1): pre-dose and at multiple time points (up to Day 8) post-dose; Day 1 (Part 2): pre-dose and at multiple time points (up to Day 7) post-dose; Day 22 (Parts 2): pre-dose and at multiple time points (up to 48 hours) post-dose]
- Number of Participants Based on Antidrug Antibody (ADA) Levels in Serum [Baseline up to Month 18]
The number participants in each category of the immunogenicity status (ADA-negative or ADA-positive) will be determined in this study. A 3-tiered ADA testing strategy will be used in this study. A Sample will initially be screened for ADA by the ADA screening assay. Any positive sample in the screening assay is considered a potential positive, which will be confirmed for true positivity by the confirmatory assay. If a sample is confirmed as an ADA true positive, ADA titer will be assessed.
Eligibility Criteria
Criteria
Inclusion Criteria:
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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).
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Continuous nonsmoker who has not used nicotine and tobacco-containing products for at least 3 months prior to screening and through discharge.
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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.
Exclusion Criteria:
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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.
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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.
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Has a known hypersensitivity or contraindication to any component of TAK 105.
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Has positive pregnancy test or is lactating or breastfeeding.
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Has known or suspected current coronavirus disease 2019 (COVID-19) infection or is at risk of COVID-19 infection as assessed by the investigator.
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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.
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With history or presence of:
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3 or more incidences of vasovagal syncope within the last 5 years prior to screening;
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A family history of unexplained sudden death or channelopathy;
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Brugada syndrome (RBBB [right bundle branch block] pattern with ST-elevation in leads V1 V3);
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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;
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Risk factors for Torsade de Pointes (example, heart failure, cardiomyopathy, or family history of Long QT Syndrome);
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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;
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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.
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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.
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Has an average heart rate (HR) <55 or >100 beats per minute (bpm) from screening to predose, inclusive.
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Has orthostatic hypotension defined as a decrease in systolic BP (SBP) >=20 mmHg or a decrease in diastolic BP (DPB) >=10 mmHg at approximately 3 minutes of standing when compared with BP from the semirecumbent position at screening to predose assessments, inclusive.
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Has postural orthostatic tachycardia, defined as an increase of >30 bpm or HR >120 bpm at approximately 3 minutes of standing, at screening to predose assessments, inclusive.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Celerion | Tempe | Arizona | United States | 85283 |
| 2 | PPD Development, LP | Las Vegas | Nevada | United States | 89113 |
| 3 | PPD Development, LP | Austin | Texas | United States | 78744 |
Sponsors and Collaborators
- Takeda
Investigators
- Study Director: Study Director, Takeda
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- TAK-105-1001