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The aims of the study are:
On Day 1, participants will receive a single intravenous (IV) infusion of danavorexton or a placebo after participants have been anesthetized for about 40 minutes. Clinic doctors will arrange a follow-up visit by phone or video on Day 7.
The drug being tested in this study is called danavorexton or TAK-925. Danavorexton is being tested to evaluate safety, tolerability, PK, and pharmacodynamics (PD) in healthy participants.
The study will enroll approximately 28 participants. This study consists of 4 cohorts: Cohorts A1, A2, A3 and P (healthy participants aged 18 to 55 years). In each of the 4 cohorts, participants will be randomly assigned (by chance) to receive danavorexton or danavorexton placebo-matching -which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need):
Additional optional cohorts may be added to the study based on the outcomes from the mandatory cohorts described above.
This trial will be conducted in the United States. The overall time to participate in this study is 37 days including screening period, residential period, and safety follow up period. A follow-up visit by phone or video will be conducted on Day 7.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort A1: Danavorexton Low Dose | Experimental | Danavorexton low dose or danavorexton placebo-matching infusion, once, intravenously on Day 1 in healthy adult participants with intravenous propofol as induction anesthetic and inhaled sevoflurane as the primary maintenance anesthetic. |
|
| Cohort A2: Danavorexton Middle Dose | Experimental | Danavorexton middle dose or danavorexton placebo-matching infusion, once, intravenously on Day 1 in healthy adult participants with intravenous propofol as induction anesthetic and inhaled sevoflurane as the primary maintenance anesthetic. |
|
| Cohort A3: Danavorexton High Dose | Experimental | Danavorexton high dose or danavorexton placebo-matching infusion, single, intravenously on Day 1 in healthy adult participants with intravenous propofol as induction anesthetic and inhaled sevoflurane as the primary maintenance anesthetic. |
|
| Cohort P: Danavorexton TBD | Experimental | Danavorexton dose to be decided (TBD) or danavorexton placebo-matching infusion, once, intravenously on Day 1 in healthy adult participants with intravenous propofol as induction and primary maintenance anesthetic. Dose of danavorexton will be based on the review of observed safety and tolerability data and pharmacokinetic (PK) data of previous cohorts. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Danavorexton | Drug | Danavorexton intravenous infusion. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With at Least one Treatment-emergent Adverse Event (TEAE) | Up to Day 7 |
| Measure | Description | Time Frame |
|---|---|---|
| Ceoi: Observed Plasma Concentration at the end of Infusion for Danavorexton | Day 1: Pre-anesthesia, pre-infusion and at multiple timepoints (up to 24 hours) post-infusion | |
| AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Danavorexton |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Study Director | Takeda | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Endeavor Clinical Trials | San Antonio | Texas | 78229-3818 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38296753 | Derived | Suzuki M, Shiraishi E, Cronican J, Kimura H. Effects of the orexin receptor 2 agonist danavorexton on emergence from general anaesthesia and opioid-induced sedation, respiratory depression, and analgesia in rats and monkeys. Br J Anaesth. 2024 Mar;132(3):541-552. doi: 10.1016/j.bja.2023.12.032. Epub 2024 Feb 1. |
| 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.
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| ID | Term |
|---|---|
| C000729607 | TAK-925 |
| D015742 | Propofol |
| D000077149 | Sevoflurane |
| ID | Term |
|---|---|
| D010636 | Phenols |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
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|
|
| Danavorexton Placebo | Drug | Danavorexton placebo-matching intravenous infusion. |
|
| Propofol | Drug | Propofol intravenous bolus. |
|
| Sevoflurane | Drug | Sevoflurane inhalation. |
|
| Propofol | Drug | Propofol intravenous infusion. |
|
| Day 1: Pre-anesthesia, pre-infusion and at multiple timepoints (up to 24 hours) post-infusion |
| AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Danavorexton | Day 1: Pre-anesthesia, pre-infusion and at multiple timepoints (up to 24 hours) post-infusion |
| D006838 |
| Hydrocarbons |
| D009930 | Organic Chemicals |
| D008738 | Methyl Ethers |
| D004987 | Ethers |
| D006845 | Hydrocarbons, Fluorinated |
| D006846 | Hydrocarbons, Halogenated |