Clinical trial NCT05025397: A Study of Danavorexton in Anesthetized Adults
Official title: A Randomized, Double-blind, Placebo-controlled, Phase 1 Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Danavorexton in Anesthetized Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2021-08-27
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: OTHER

Brief summary: 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.

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.

Eligibility criteria: 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).

Primary outcomes:
measure: Number of Participants With at Least one Treatment-emergent Adverse Event (TEAE)
timeFrame: Up to Day 7
Secondary outcomes:
measure: Ceoi: Observed Plasma Concentration at the end of Infusion for Danavorexton
timeFrame: Day 1: Pre-anesthesia, pre-infusion and at multiple timepoints (up to 24 hours) post-infusion
measure: AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Danavorexton
timeFrame: Day 1: Pre-anesthesia, pre-infusion and at multiple timepoints (up to 24 hours) post-infusion
measure: AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Danavorexton
timeFrame: Day 1: Pre-anesthesia, pre-infusion and at multiple timepoints (up to 24 hours) post-infusion
Other outcomes:
Locations:
city: San Antonio
country: United States
facility: Endeavor Clinical Trials
state: Texas
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: