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| ID | Type | Description | Link |
|---|---|---|---|
| U1111-1251-9214 | Registry Identifier | WHO |
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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:
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.
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):
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1 (Low Dose): TAK-951 20 mcg Infusion Over 60 Minutes | Experimental | TAK-951 20 microgram (mcg) or TAK-951 placebo-matching, infusion, intravenously, over a period of 60 minutes on Day 1. |
|
| Cohort 2 (High Dose): TAK-951 1 mg Infusion Over 60 Minutes | Experimental | TAK-951 1 milligram (mg) or TAK-951 placebo-matching, infusion, intravenously, over a period of 60 minutes on Day 1. Dose level will be determined based on safety, tolerability and PK data from previous cohorts. |
|
| Cohort 3: TAK-951 1 mg Infusion Over 120 Minutes | Experimental | TAK-951 1 mg or TAK-951 placebo-matching, infusion, intravenously, over a period of 120 minutes on Day 1. Dose level will be determined based on safety, tolerability and PK data from previous cohorts. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| TAK-951 | Drug | TAK-951 intravenous infusion. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants Who Reported One or More Treatment-emergent Adverse Events (TEAEs) | Baseline up to Day 29 | |
| Number of Participants With Clinically Significant Change From Baseline in Vital Sign Values | Baseline up to Day 2 | |
| Number of Participants With Clinically Significant Change From Baseline in 12- Lead Electrocardiogram (ECG) Values | Baseline up to Day 2 | |
| Number of Participants With Clinically Significant Change From Baseline in Laboratory Values | Baseline up to Day 2 | |
| Number of Participants With Clinically Significant Change From Baseline in Physical Examination Values | Baseline up to Day 29 |
| Measure | Description | Time Frame |
|---|---|---|
| AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-951 | Day 1 pre-dose and at multiple time points (up to 30 hours) post-dose | |
| Ceoi: Plasma Concentration at the End of Infusion for TAK-951 | Day 1: at the end of infusion (at 30 hours post-infusion) |
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Inclusion Criteria:
Exclusion Criteria:
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.
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.
Have any tattoos, scars or skin issue at planned IV infusion site which could interfere with dosing.
History or presence of:
Semi-recumbent blood pressure (average of duplicate) is less than 90/60 millimeter of mercury (mmHg) or greater than 140/90 mmHg at screening.
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.
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.
Has postural orthostatic tachycardia, defined as an increase of 30 bpm or heart rate >120 bpm after standing for 2 minutes.
Positive urine drug or alcohol results at screening or check-in.
Positive urine cotinine at screening or check-in.
Positive results at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV).
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.
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.
Donation of blood or significant blood loss within 56 days prior to dosing.
Plasma donation within 7 days prior to dosing.
Has positive results for Coronavirus disease 2019 (COVID-19) testing at screening or check-in.
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| Name | Affiliation | Role |
|---|---|---|
| Study Director | Takeda | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Celerion | Lincoln | Nebraska | 68502 | United States |
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| Label | URL |
|---|---|
| To obtain more information on the study, click here/on this link | View source |
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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.
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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.
Healthy participants were randomized and treated sequentially in Cohorts: 1, 2, 3 and 4 to receive intravenous infusion of TAK-951 20 microgram (mcg), TAK-951 1.0 milligram (mg) or TAK-951 matching placebo (normal saline).
Participants took part in the study at 1 investigative site in the United States from 07 July 2020 to 27 May 2021.
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| ID | Title | Description |
|---|---|---|
| FG000 | Cohorts 1 to 2, Treatment P1: Placebo Pooled | TAK-951 placebo-matching (0.2 milliliter [ml] normal saline), infusion, intravenously over 60 minutes in fasted condition once on Day 1 in healthy participants. |
| FG001 | Cohort 3, Treatment P2: Placebo | TAK-951 placebo-matching (1 ml normal saline), infusion, intravenously over 120 minutes in fasted condition once on Day 1 in healthy participants. |
| FG002 | Cohort 4, Treatment P3: Placebo | TAK-951 placebo-matching (1 ml normal saline), infusion, intravenously over 180 minutes in fasted condition once on Day 1 in healthy participants. |
| FG003 | Cohort 1, Treatment A: TAK-951 20 mcg | TAK-951 20 mcg, infusion, intravenously over 60 minutes in fasted condition once on Day 1 in healthy participants. |
| FG004 | Cohort 2, Treatment B: TAK-951 1.0 mg | TAK-951 1.0 mg, infusion, intravenously over 60 minutes in fasted condition once on Day 1 in healthy participants. |
| FG005 | Cohort 3, Treatment C: TAK-951 1.0 mg | TAK-951 1.0 mg, infusion, intravenously over 120 minutes in fasted condition once on Day 1 in healthy participants. |
| FG006 | Cohort 4, Treatment D: TAK-951 1.0 mg | TAK-951 1.0 mg, infusion, intravenously over 180 minutes in fasted condition once on Day 1 in healthy participants. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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|
The safety analysis set consisted of all participants who were enrolled and received the full or partial dose of study drug or placebo.
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| ID | Title | Description |
|---|---|---|
| BG000 | Cohorts 1 to 2, Treatment P1: Placebo Pooled | TAK-951 placebo-matching (0.2 ml normal saline), infusion, intravenously over 60 minutes in fasted condition once on Day 1 in healthy participants. |
| BG001 | Cohort 3, Treatment P2: Placebo |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants Who Reported One or More Treatment-emergent Adverse Events (TEAEs) | The safety analysis set consisted of all participants who were enrolled and received the full or partial dose of study drug or placebo. | Posted | Count of Participants | Participants | Baseline up to Day 29 |
|
TEAEs were adverse events that started after the first dose of study drug (Baseline) up to Day 29
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Cohorts 1 to 2, Treatment P1: Placebo Pooled | TAK-951 placebo-matching (0.2 ml normal saline), infusion, intravenously over 60 minutes in fasted condition once on Day 1 in healthy participants. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 23 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Takeda | +1-877-825-3327 | TrialDisclosures@takeda.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jan 8, 2021 | May 4, 2022 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | May 13, 2021 | May 4, 2022 | SAP_001.pdf |
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| TAK-951 Placebo | Drug | TAK-951 placebo-matching intravenous infusion. |
|
| AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-951 | Day 1 pre-dose and at multiple time points (up to 30 hours) post-dose |
| T1/2z: Terminal Disposition Phase Half-life for TAK-951 | Day 1 pre-dose and at multiple time points (up to 30 hours) post-dose |
| λz: Terminal Disposition Phase Rate Constant for TAK-951 | Day 1 pre-dose and at multiple time points (up to 30 hours) post-dose |
| Number of Participants With Positive Anti-drug Antibodies (ADA) in Serum | ADA positive was defined as a sample that was evaluated as positive in both the ADA screening and confirmatory assays. ADA positive participants was defined as participants who had at least 1 positive ADA result. | Baseline up to Day 29 |
TAK-951 placebo-matching (1 ml normal saline), infusion, intravenously over 120 minutes in fasted condition once on Day 1 in healthy participants. |
| BG002 | Cohort 4, Treatment P3: Placebo | TAK-951 placebo-matching (1 ml normal saline), infusion, intravenously over 180 minutes in fasted condition once on Day 1 in healthy participants. |
| BG003 | Cohort 1, Treatment A: TAK-951 20 mcg | TAK-951 20 mcg, infusion, intravenously over 60 minutes in fasted condition once on Day 1 in healthy participants. |
| BG004 | Cohort 2, Treatment B: TAK-951 1.0 mg | TAK-951 1.0 mg, infusion, intravenously over 60 minutes in fasted condition once on Day 1 in healthy participants. |
| BG005 | Cohort 3, Treatment C: TAK-951 1.0 mg | TAK-951 1.0 mg, infusion, intravenously over 120 minutes in fasted condition once on Day 1 in healthy participants. |
| BG006 | Cohort 4, Treatment D: TAK-951 1.0 mg | TAK-951 1.0 mg, infusion, intravenously over 180 minutes in fasted condition once on Day 1 in healthy participants. |
| BG007 | Total | Total of all reporting groups |
| Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants |
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| OG002 | Cohort 4, Treatment P3: Placebo | TAK-951 placebo-matching (1 ml normal saline), infusion, intravenously over 180 minutes in fasted condition once on Day 1 in healthy participants. |
| OG003 | Cohort 1, Treatment A: TAK-951 20 mcg | TAK-951 20 mcg, infusion, intravenously over 60 minutes in fasted condition once on Day 1 in healthy participants. |
| OG004 | Cohort 2, Treatment B: TAK-951 1.0 mg | TAK-951 1.0 mg, infusion, intravenously over 60 minutes in fasted condition once on Day 1 in healthy participants. |
| OG005 | Cohort 3, Treatment C: TAK-951 1.0 mg | TAK-951 1.0 mg, infusion, intravenously over 120 minutes in fasted condition once on Day 1 in healthy participants. |
| OG006 | Cohort 4, Treatment D: TAK-951 1.0 mg | TAK-951 1.0 mg, infusion, intravenously over 180 minutes in fasted condition once on Day 1 in healthy participants. |
|
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| Primary | Number of Participants With Clinically Significant Change From Baseline in Vital Sign Values | The safety analysis set consisted of all participants who were enrolled and received the full or partial dose of study drug or placebo. | Posted | Count of Participants | Participants | Baseline up to Day 2 |
|
|
|
| Primary | Number of Participants With Clinically Significant Change From Baseline in 12- Lead Electrocardiogram (ECG) Values | The safety analysis set consisted of all participants who were enrolled and received the full or partial dose of study drug or placebo. | Posted | Count of Participants | Participants | No | Baseline up to Day 2 |
|
|
|
| Primary | Number of Participants With Clinically Significant Change From Baseline in Laboratory Values | The safety analysis set consisted of all participants who were enrolled and received the full or partial dose of study drug or placebo. | Posted | Count of Participants | Participants | Baseline up to Day 2 |
|
|
|
| Primary | Number of Participants With Clinically Significant Change From Baseline in Physical Examination Values | The safety analysis set consisted of all participants who were enrolled and received the full or partial dose of study drug or placebo. | Posted | Count of Participants | Participants | Baseline up to Day 29 |
|
|
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| Secondary | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-951 | The pharmacokinetic (PK) analysis set consisted of all participants who received the active study drug and had at least one measurable plasma concentration of TAK-951. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram*hour per milliliter (ng*hr/mL) | Day 1 pre-dose and at multiple time points (up to 30 hours) post-dose |
|
|
|
| Secondary | Ceoi: Plasma Concentration at the End of Infusion for TAK-951 | The PK analysis set consisted of all participants who received the active study drug and had at least one measurable plasma concentration of TAK-951. Here "overall number of participants" analyzed are those who were evaluable for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram per milliliter (ng/mL) | Day 1: at the end of infusion (at 30 hours post-infusion) |
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| Secondary | AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-951 | The PK analysis set consisted of all participants who received the active study drug and had at least one measurable plasma concentration of TAK-951. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | Day 1 pre-dose and at multiple time points (up to 30 hours) post-dose |
|
|
|
| Secondary | T1/2z: Terminal Disposition Phase Half-life for TAK-951 | The PK analysis set consisted of all participants who received the active study drug and had at least one measurable plasma concentration of TAK-951. | Posted | Mean | Standard Deviation | hour | Day 1 pre-dose and at multiple time points (up to 30 hours) post-dose |
|
|
|
| Secondary | λz: Terminal Disposition Phase Rate Constant for TAK-951 | The PK analysis set consisted of all participants who received the active study drug and had at least one measurable plasma concentration of TAK-951. | Posted | Mean | Standard Deviation | per hour (1/hour) | Day 1 pre-dose and at multiple time points (up to 30 hours) post-dose |
|
|
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| Secondary | Number of Participants With Positive Anti-drug Antibodies (ADA) in Serum | ADA positive was defined as a sample that was evaluated as positive in both the ADA screening and confirmatory assays. ADA positive participants was defined as participants who had at least 1 positive ADA result. | The immunogenicity analysis set included those participants from the safety analysis set who had a baseline and at least 1 post-dose immunogenicity sample assessment. | Posted | Count of Participants | Participants | No | Baseline up to Day 29 |
|
|
|
| 0 |
| 4 |
| 0 |
| 4 |
| 1 |
| 4 |
| EG001 | Cohort 3, Treatment P2: Placebo | TAK-951 placebo-matching (1 ml normal saline), infusion, intravenously over 120 minutes in fasted condition once on Day 1 in healthy participants. | 0 | 2 | 0 | 2 | 0 | 2 |
| EG002 | Cohort 4, Treatment P3: Placebo | TAK-951 placebo-matching (1 ml normal saline), infusion, intravenously over 180 minutes in fasted condition once on Day 1 in healthy participants. | 0 | 2 | 0 | 2 | 1 | 2 |
| EG003 | Cohort 1, Treatment A: TAK-951 20 mcg | TAK-951 20 mcg, infusion, intravenously over 60 minutes in fasted condition once on Day 1 in healthy participants. | 0 | 6 | 0 | 6 | 3 | 6 |
| EG004 | Cohort 2, Treatment B: TAK-951 1.0 mg | TAK-951 1.0 mg, infusion, intravenously over 60 minutes in fasted condition once on Day 1 in healthy participants. | 0 | 6 | 0 | 6 | 1 | 6 |
| EG005 | Cohort 3, Treatment C: TAK-951 1.0 mg | TAK-951 1.0 mg, infusion, intravenously over 120 minutes in fasted condition once on Day 1 in healthy participants. | 0 | 6 | 0 | 6 | 3 | 6 |
| EG006 | Cohort 4, Treatment D: TAK-951 1.0 mg | TAK-951 1.0 mg, infusion, intravenously over 180 minutes in fasted condition once on Day 1 in healthy participants. | 0 | 6 | 0 | 6 | 1 | 6 |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 23 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 23 | Systematic Assessment |
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| Heart rate increased | Investigations | MedDRA 23 | Systematic Assessment |
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| Joint swelling | Musculoskeletal and connective tissue disorders | MedDRA 23 | Systematic Assessment |
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| Medical device site reaction | General disorders | MedDRA 23 | Systematic Assessment |
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| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 23 | Systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 23 | Systematic Assessment |
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| Orthostatic heart rate response increased | Investigations | MedDRA 23 | Systematic Assessment |
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| Palpitations | Cardiac disorders | MedDRA 23 | Systematic Assessment |
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| Paraesthesia | Nervous system disorders | MedDRA 23 | Systematic Assessment |
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| Respiratory tract congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 23 | Systematic Assessment |
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| Vessel puncture site bruise | General disorders | MedDRA 23 | Systematic Assessment |
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| Vessel puncture site pain | General disorders | MedDRA 23 | Systematic Assessment |
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Research Organization shall not publish any articles or papers nor make any presentations, nor assist any other person in publishing any articles or papers or in making any presentations relating or referring to the Study or any results, data or insights from or any data, information or materials obtained or generated in the performance of its obligations without the prior written consent of Takeda, which consent may be granted or withheld in Takeda's sole discretion.