A Study of Danavorexton in Anesthetized Adults

A Randomized, Double-blind, Placebo-controlled, Phase 1 Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Danavorexton in Anesthetized Adults

The aims of the study are:

• to assess the safety profile of danavorexton when it is administered with anesthetics.
• to learn what effect danavorexton has on anesthetized adults.

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Danavorexton; Drug: Danavorexton Placebo; Drug: Propofol; Drug: Sevoflurane; Drug: Propofol

Detailed Description

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):

• Cohort A1: Danavorexton Low Dose
• Cohort A2: Danavorexton Middle Dose
• Cohort A3: Danavorexton High Dose
• Cohort P: Danavorexton TBD

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.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • San Antonio, Texas, United States, 78229-3818
      • Endeavor Clinical Trials

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Current non-smoker who has not used tobacco- or nicotine-containing products (example, nicotine patch) for at least 6 months before the administration of the study drug.
2. Has regular sleep-wake habits (example, routinely spends 6.5 to 9 hours in bed nightly).
3. Aged 18 to 55 years, inclusive, at the screening visit.
4. Has a body mass index (BMI) greater than or equal to (>=) 18 and less than or equal to (<=) 32 kilogram per square meter (kg/m^2) at the screening visit.
5. Must be American Society of Anesthesiologists (ASA) Classification I with a Mallampati score less than (<) III, and judged to be in good health based on results of safety laboratory tests (biochemistry, hematology, and urinalysis testing) performed at the screening visit and on medical history, physical examination, vital-sign measurements, and 12-lead electrocardiogram (ECG) performed at screening and Study Day 1 visits.
6. Not expected to have difficulty with the use of an laryngeal mask airway (LMA) as determined by the anesthesiologist or site staff.

Exclusion Criteria:

1. Received immunotherapy within the past year.
2. Has a history or family history of malignant hyperthermia or are known or suspected to have an allergy to inhalational anesthetics, propofol, neuromuscular blocking agents and/or other drugs used during general anesthesia.
3. Has facial hair that could interfere with the seal of a facemask per investigator or site staff and is unwilling to shave it off before check-in.
4. Has undergone major surgery or donated or lost 1 unit of blood (approximately 500 milliliter [mL]) within 4 weeks before the screening visit.
5. Has a risk of suicide according to endorsement of Item 4 or 5 of the Columbia-Suicide Severity Rating Scale (C-SSRS) at the screening/baseline visit or have made a suicide attempt in the previous 6 months.
6. Has a positive alcohol or drug screen at screening or Day 1 or has a history of alcohol consumption exceeding 2 standard drinks per day on average within the 12 months before screening. Participants who test positive for cannabis will be excluded.
7. Has caffeine consumption of more than 400 milligram per day (mg/day) for 2 weeks before screening (1 serving of coffee is approximately equivalent to 120 milligram [mg] of caffeine).
8. Has a screening ECG with a QT interval with Fridericia correction method (QTcF) greater than (>) 450 millisecond (ms) (men) or >470 ms (women).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A1: Danavorexton Low Dose; 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.	Drug: Danavorexton; Danavorexton intravenous infusion.; Other Names: TAK-925; Drug: Danavorexton Placebo; Danavorexton placebo-matching intravenous infusion.; Drug: Propofol; Propofol intravenous bolus.; Drug: Sevoflurane; Sevoflurane inhalation.; Drug: Propofol; Propofol intravenous infusion.
Experimental: Cohort A2: Danavorexton Middle Dose; 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.	Drug: Danavorexton; Danavorexton intravenous infusion.; Other Names: TAK-925; Drug: Danavorexton Placebo; Danavorexton placebo-matching intravenous infusion.; Drug: Propofol; Propofol intravenous bolus.; Drug: Sevoflurane; Sevoflurane inhalation.; Drug: Propofol; Propofol intravenous infusion.
Experimental: Cohort A3: Danavorexton High Dose; 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.	Drug: Danavorexton; Danavorexton intravenous infusion.; Other Names: TAK-925; Drug: Danavorexton Placebo; Danavorexton placebo-matching intravenous infusion.; Drug: Propofol; Propofol intravenous bolus.; Drug: Sevoflurane; Sevoflurane inhalation.; Drug: Propofol; Propofol intravenous infusion.
Experimental: Cohort P: Danavorexton TBD; 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.	Drug: Danavorexton; Danavorexton intravenous infusion.; Other Names: TAK-925; Drug: Danavorexton Placebo; Danavorexton placebo-matching intravenous infusion.; Drug: Propofol; Propofol intravenous bolus.; Drug: Propofol; Propofol intravenous infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants With at Least one Treatment-emergent Adverse Event (TEAE)	Up to Day 7

Secondary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Takeda

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): September 28, 2021
• Primary Completion (Actual): March 8, 2022
• Study Completion (Actual): March 8, 2022

Study Registration Dates

• First Submitted: August 26, 2021
• First Submitted That Met QC Criteria: August 26, 2021
• First Posted (Actual): August 27, 2021

Study Record Updates

• Last Update Posted (Actual): May 10, 2022
• Last Update Submitted That Met QC Criteria: May 6, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Drug Therapy
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Platelet Aggregation Inhibitors; Hypnotics and Sedatives; Anesthetics, Inhalation; Propofol; Sevoflurane
• Other Study ID Numbers: TAK-925-1019

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