Opioid-induced respiratory depression
Conditions
Interventions
Subjects will receive sequentially single IV low and high dose danavorexton or
placebo on 2 separate occasions.
Sponsors
Takeda
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: 1. In the opinion of the investigator, the subject is capable of understanding and complying with protocol requirements. 2. The subject reviews, and signs and dates an informed (electronic) consent form, in addition to any required privacy authorization, before the initiation of any study procedure. 3. The subject is male and aged 18 to 55 years, inclusive, at the screening visit. 4. The subject is a current nonsmoker who has not used tobacco- or nicotine-containing products (eg, nicotine patch) for at least 6 months before the administration of the study drug. 5. The subject has regular sleep-wake habits (eg, routinely spends 6.5 to 9 hours in bed nightly) and regularly goes to bed between 9:00 PM and 1:00 AM, as determined by investigator interviews. 6. A male subject must meet the following birth control requirements: a) For a male subject who is sterile: no restrictions are required for a vasectomized male subject, provided the subject is at least 1-year postbilateral vasectomy procedure before the first dose of the study drug. If a vasectomy procedure was performed less than 1 year before the first dose of the study drug, the male subject must follow the same restrictions as a male that has not had a vasectomy/sterilization (below). Appropriate documentation of surgical procedures should be provided. b) For a male subject who is nonsterilized: if sexually active with a female partner of childbearing potential, the subject must agree to use an appropriate method of contraception, including a condom with or without spermicidal cream or jelly. These precautions will begin from the administration of the study drug until 5 half-lives plus 90 days after the administration of the study drug. c) Male subjects must agree to not donate sperm from the time of study drug administration until 5 half lives plus 90 days after the administration of the study drug. 7. The subject has a BMI >=18 and
Exclusion criteria
Exclusion criteria: - The subject has received treatment with another investigational drug within 3 months before screening, or the subject participated in more than 4 investigational drug studies within 1 year before screening. - The subject received immunotherapy within the past year. - The subject has facial hair that could interfere with the seal of a facemask (per investigator or site staff judgment), and is unwilling to shave it off before check-in. - The subject has a positive test result for hepatitis B surface antigen, HCV, HIV antibody/antigen, or syphilis serum reaction test at screening. Note: subjects with positive HBV or HCV serology may be enrolled if quantitative polymerase chain reaction for HBV or HCV viral RNA is negative. - The subject has a risk of suicide according to endorsement of Item 4 or 5 of the C-SSRS at the screening visit or has made a suicide attempt in the previous 6 months. - The subject has a positive alcohol or drug screen at screening or check-in, has a history of alcohol consumption exceeding 2 standard drinks per day on average within the 12 months before screening, or has a history of opioid abuse. - The subject has caffeine consumption of more than 400 mg/day for 2 weeks before screening (1 serving of coffee is approximately equivalent to 100 mg of caffeine). - The subject has a screening ECG with a QT interval with Fridericia correction method (QTcF) >450 ms.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety and tolerability will be assessed by number of subjects with at least 1 treatment-emergent adverse event (TEAE). | — |
Secondary
| Measure | Time frame |
|---|---|
| The following PK parameters of danavorexton will be estimated: • Observed plasma concentration at the end of infusion (Ceoi). • Area under the plasma concentration-time curve from time 0 to time of the last quantifiable concentration (AUClast). • Area under the plasma concentration-time curve from time 0 to infinity (AUC*). | — |
Countries
Netherlands
Outcome results
None listed