Danavorexton in healthy volunteers receiving an opioid
- Conditions
- Opioid-induced respiratory depressionRespiratory
- Registration Number
- ISRCTN63027076
- Lead Sponsor
- Takeda (United States)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Male
- Target Recruitment
- 13
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 (e.g., nicotine patch) for at least 6 months before the administration of the study drug.
5. The subject has regular sleep-wake habits (e.g., 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:
6.1. 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.
6.2. 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.
6.3. 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 =32 kg/m² at the screening visit
8. The subject must be judged to be in good health based on the 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 ECG performed at screening and baseline assessments.
9. The subject has no history of hypertension or use of antihypertensive medication. BP must be <140 mmHg (systolic) and <90 mmHg (diastolic); subjects will have a heart rate within the range of 50 to 90 beats per minute at the screening visit. BP will be averaged over three readings that are done 10 minutes apart.
10. The subject agrees to refrain from taking excluded medications, vitamins, supplements or dietary products listed in the protocol during the study
1. The subject has received treatment with another investigational drug within 3 months before screening, or the subject participated in more than four investigational drug studies within 1 year before screening
2. The subject received immunotherapy within the past year
3. 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
4. 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
5. The subject 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 visit or has made a suicide attempt in the previous 6 months
6. 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
7. The subject has caffeine consumption of more than 400 mg/day for 2 weeks before screening (one serving of coffee is approximately equivalent to 100 mg of caffeine).
8. The subject has a screening ECG with a QT interval with Fridericia correction method (QTcF) >450 ms
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Safety and tolerability will be assessed by the number of subjects with at least one treatment-emergent adverse event (TEAE) at any timepoint during the study
- Secondary Outcome Measures
Name Time Method <br> Plasma concentrations of danavorexton are measured using high-performance liquid chromatography tandem mass spectrometry (HPLC-MS-MS) at 15 different timepoints after infusion until 9 hours after the start of the infusion. The following PK parameters of danavorexton will be estimated:<br> 1. Observed plasma concentration at the end of infusion (Ceoi)<br> 2. Area under the plasma concentration-time curve from time 0 to time of the last quantifiable concentration (AUClast)<br> 3. Area under the plasma concentration-time curve from time 0 to infinity (AUC8)<br>